Cervical interlaminar epidural steroid injection for neck pain and cervical radiculopathy: effect and prognostic factors

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1 Skeletal Radiol (2007) 36: DOI /s SCIENTIFIC ARTICLE Cervical interlaminar epidural steroid injection for neck pain and cervical radiculopathy: effect and prognostic factors Jong Won Kwon & Joon Woo Lee & Sung Hyun Kim & Ja-Young Choi & Jin-Sup Yeom & Hyun-Jib Kim & Kyu-Sung Kwack & Sung Gyu Moon & Woo Sun Jun & Heung Sik Kang Received: 19 April 2006 /Revised: 14 August 2006 /Accepted: 15 January 2007 / Published online: 6 March 2007 # ISS 2007 Abstract Objective To verify the usefulness of a fluoroscopy guided cervical interlaminar epidural steroid injection (CIESI) in patients with neck pain and cervical radiculopathy and to evaluate outcome predictors. Design We retrospectively analyzed 91 patients from July 2004 to June 2005 in whom CIESI was initially performed for neck pain and cervical radiculopathy. Therapeutic effects were evaluated 2 weeks after the administration of CIESI, and CIESI effectiveness was graded using a fivepoint scale, namely, whether the pain had disappeared, was much improved, slightly improved, the same, or aggravated. We also used a visual analog scale (VAS) for the clinical J. W. Kwon : J. W. Lee (*) : S. H. Kim : K.-S. Kwack : H. S. Kang Department of Radiology, Seoul National University Bundang Hospital, 300 Gumidong, Bundang-Gu, Seongnam-si, Gyeonggi-do , South Korea joonwoo@radiol.snu.ac.kr J.-Y. Choi : S. G. Moon : W. S. Jun : H. S. Kang Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea J.-S. Yeom Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Gyeongi-Do, South Korea H.-J. Kim Department of Neurosurgery, Seoul National University Bundang Hospital, Gyeongi-Do, South Korea evaluation. According to documentation and follow-up charts, we categorized treatments as effective or ineffective. Possible outcome predictors, namely, diagnosis (spinal stenosis vs herniated disc), primary symptoms (neck pain vs radiculopathy vs both), age, gender, and duration of pain (more or less than 6 months) were also analyzed. Fisher s exact test, the chi-square test, and multiple logistic regression analysis were used for the statistical analysis. Patients After their medical records had been reviewed, 76 patients were included in this study. Inclusion criteria were: the availability of a cross-sectional image, such as a CT scan or an MR image, and a follow-up record after injection. Results and conclusions The medical records of 76 patients (male:female=41 : 35) of mean age 53.1 years (range 32 years to 82 years) were reviewed. Two weeks after injection, 55 patients (72.4%) had experienced effective pain relief. Patients with herniated discs had significantly better results than patients with spinal stenosis (86.1% vs 60.0%) (P<0.05). Other non-significant predictors of an improved outcome included: a symptom duration of <6 months, a young age, and the presence of cervical radiculopathy. Multiple regression analysis showed that the only factor that was significantly associated with outcome was the cause of the pain, i.e., herniated disc or spinal stenosis. Fluoroscopy guided CIESI is a safe and effective means of treating patients with neck pain and cervical radiculopathy. The most important outcome predictor was cause of pain, and patients with herniated disc experienced better pain relief than those with spinal stenosis. Keywords Interventional procedure. Spine, interventional procedure. Spine, intervertebral disc. Spinal canal, stenosis

2 432 Skeletal Radiol (2007) 36: Cervical interlaminar epidural steroid injections (CIESIs) are being used for the conservative management of neck pain or cervical radiculopathy [1 4]. These injections are often performed in a blind manner, i.e., without fluoroscopic guidance. Fluoroscopy and epidurography can improve the accuracy of needle placement and medication delivery to targeted areas and reduce procedure-related complications [5, 6]. Thus, recently, CIESI has been performed mainly under fluoroscopic guidance [4 7]. The patients that have been treated by CIESI tend to doubt the short- and long-term effects of the procedure. Several reports have been issued on the long-term effects of repeated CIESIs [1, 2], but no report is available on its short-term effects. Knowledge of the short-term effects of this procedure would improve rapport with patients and enable us to predict long-term effects. To our knowledge, this is the first report about the short-term effects of single CIESI administration for the treatment of neck pain or cervical radiculopathy. Moreover, little is available in the literature to indicate which types of pathological conditions respond best to CIESI. The purpose of this study was to investigate short-term response to fluoroscopically guided single CIESI in patients with neck pain and cervical radiculopathy and to identify factors that are predictive of therapeutic outcome after CIESI. Materials and methods Patients Consecutive patients referred for CIESI were considered for entry into the study. From July 2004 to June 2005, 91 patients were treated by CIESI administration in our department of radiology. This investigation was based on medical records, MRI or CT scans, and sets of anteroposterior and lateral radiographs obtained using a biplane fluoroscopy unit during CIESI. Inclusion criteria were: (a) the presence of axial cervical pain or cervical radiculopathy, (b) initial session of CIESI, (c) no previous (3 month) spinal steroid injection or surgery, (d) a cross-sectional imaging study (CT or MR) of the cervical spine. By definition, axial pain consisted of generalized neck symptoms, occipital headache, and/or interscapular pain. Cervical radiculopathy consisted of shoulder pain, arm pain, or both, with radicular distribution, and the patients with radiculopathy showed positive Spurling s sign, which is used for evaluation of cervical nerve root compression. All patients who had undergone CIESI revisited our clinic for the evaluation of the effect of CIESI 2 weeks later. To check the effect of CIESI, all patients were recommended not to take any drugs or participate in physical therapy to control pain throughout the 2-week period after CIESI. The institutional review board of Seoul National University Bundang Hospital approved this study and did not require informed consent. Injection technique All CIESIs were conducted under biplane fluoroscopic guidance by two musculoskeletal radiologists (J.W.K. and J.W.L.) experienced in spinal intervention. The procedures were performed under fluoroscopic guidance on an outpatient basis. We used Integris Allura 12 & 12 Biplane (Philips, The Netherlands) fluoroscopic equipment. Informed consent was obtained from all patients. With the patient in a prone position, the following procedure was performed at the C6 7 disc level, because the epidural space of C6 7 level is the widest in the C-spine. In cases where the C6 7 level overlapped with the shoulders on lateral view, we approached at C5 6 disc level. After skin disinfection, a local anesthetic was administered with a 26- gauge needle. A 22-gauge 12 cm spinal needle was then advanced to the epidural space with a midline approach. Test injections of contrast material [Omnipaque 300 (iohexol, 300 mg of iodine per milliliter); Amersham Health, Princeton, NJ, USA] were administered while the needle was being advanced. If the needle did not puncture the ligamentum flavum, the needle was carefully advanced so as not to puncture the dura. When the contrast material in the needle was spreading in epidural space, we stopped advancing the needle and confirmed the needle tip in the epidural space with a test injection of contrast agent (Fig. 1c and d). If the epidural space was not found, regardless of enough advancement, we advanced by twirling the needle and opening the ligamentum flavum. An epidurogram was obtained to document the needle position and evaluate the extent of opacification. We injected 40 mg (1 ml) of triamcinolone acetonide suspension (Tamcelon; Hanall, Seoul) and 1.5 ml of a normal saline mixture. After CIESI, follow-up was usually done at our department 2 weeks later. A 2-week follow-up has been previously proposed and relates to the duration of the therapeutic effect of corticosteroids [8, 9]. When the dura was punctured and the subarachnoid space was entered, we changed the approach level and tried again. Image analysis Image analysis was performed by consensus between two radiologists. Diagnoses were made based on predominant MRI or CT findings, without recourse to clinical data, as

3 Skeletal Radiol (2007) 36: Fig. 1 A 35-year-old female patient with posterior neck pain of 8 months duration. a T2-weighted sagittal MRI showing intervertebral disc herniation at the C5 6 level. b Axial image showing an intervertebral disc herniation of the central zone. c, d Anteroposterior and lateral epidurogram showing proper needle location (in the follows: disc herniation (Fig. 1a and b) vs spinal stenosis (Fig. 2a and b, including central canal stenosis and neural foraminal stenosis). We defined disc herniation as localized displacement of disc material beyond the normal margins of the intervertebral disc space. Localized displacement means less than 50% of the circumference of the disc. Central canal stenosis was diagnosed when the dural sac was impinged upon by a diffuse bulging disc, ligamentum flavum thickening and osteophyte. The same two radiologists also checked procedure-related problems, such as dural puncture, on sets of anteroposterior and lateral spot radiographs obtained during CIESI. Review of clinical data Retrospective reviews of patients charts were performed by another radiologist (S.H.K.) who was not involved in the image analysis. In the present study we followed patients up to the 2-week follow-up interview only. The midline position) and spread of contrast media. Contrast material (large arrow) before puncture of the ligamentum flavum (white arrow) and epidural spreading of contrast material (small arrows) after membrane puncture. This patient had much reduced pain with only mild discomfort on the posterior neck 2 weeks after CIESI patients were brought back to our clinic 2 weeks after receiving their injections. A pain questionnaire was used before and at the follow-up interview, and these included a visual analog scale (VAS), which used a 100 mm line to represent the pain scale. The distance between the left end of this line and the position representing a patient s pain level was expressed in millimeters. We also adopted the five-point outcome scale as follows: 0 (aggravated), 1 (stationary), 2 (improved), 3 (much improved), and 4 (no residual symptoms). A successful outcome was defined as an outcome scale score of 3 or more and a VAS score reduction of more than 50% after CIESI. Demographic variables, such as age and gender, were available from the initial pretreatment clinical evaluation. For statistical analysis, we classified patients ages into five age groups, i.e., 30~39 years, 40~49 years, 50~59 years, 60~69 years, over 70 years. Primary symptoms were classified as neck pain, radiculopathy, or both. Details of pretreatment pain duration were also available, and patients were classified as having durations of <6 months Fig. 2 A 62-year-old male patient with neck and bilateral shoulder pain of 2 years duration. a, b T2-weighted sagittal and axial MR images showing central canal and bilateral neural foraminal stenoses at the C5 6 and C6 7 levels due to diffuse bulging discs and ligamentum flavum hypertrophy. Two weeks after CIESI his state was much improved, with mild residual pain in the left fourth and fifth fingers

4 434 Skeletal Radiol (2007) 36: or 6 months [10]. Procedure-related complications were also reviewed. Statistical analysis Predictors for treatment effectiveness (effective or not) were searched for. The potential predictors assessed were: types of symptoms (neck pain or cervical radiculopathy), cause of pain on MRI or CT (spinal stenosis or herniated disc), age group and gender, pain duration (< or 6 months). Fisher s exact test was used to examine associations between the above and outcome; except for age group. The chi-square test was used to examine this association by age group. Using all six variables mentioned above, we also performed multiple logistic regression analysis to rule out the effect of confounders. SPSS (version 10.0.; SPSS, Chicago, Ill, USA) software was used throughout, and P values of <0.05 were considered statistically significant. Results Seventy-six patients (35 women, 41 men; ages years; mean age 53.1 years) who met all enrollment criteria were consecutively included in this study. Fifteen patients were excluded from analysis for the following reasons: loss to follow-up in ten, pain from other causes in three (two metastases and one vascular insufficiency), lack of crosssectional imaging study in one, and recent operation of cervical spine in one. Overall, 55 patients (72.4%) had experienced effective pain relief, and 21 patients (27.6%) had not, 2 weeks after CIESI. Outcome predictors are summarized in Table 1. Thirty-one (86.1%) of 36 patients with herniated discs had effective pain relief, and 24 (60.0%) of 40 patients with spinal stenosis had effective pain relief (P<0.05). No other significant outcome predictors were identified. Multiple regression analysis showed that the only factor significantly associated with outcome was cause of pain, i.e., herniated disc versus spinal stenosis. In two patients, dural punctures were detected by epidurography, and thus, CIESI was performed after change of level; no complication developed. No serious complication requiring hospitalization occurred during the study. Discussion Of our patients, 72% reported no pain or much improved pain relief after a single injection. Patients tend to worry about effects of CIESI before the procedure. However, based on the results of this analysis, physicians performing CIESI can offer rapid pain relief to patients with neck pain or cervical radiculopathy. The time protocol for epidural delivery was suggested in 1999 and is now used by most practitioners in the USA [11]. It calls for the repeated epidural injection of steroids every 2 weeks, if only partial improvement in radicular signs and symptoms is observed. If there is no improvement, other therapies should be considered. We followed-up the patients at 2 weeks and evaluated the effect of CIESI. On reviewing 100 patients who underwent cervical epidural steroid injections, Ferrante et al. [2] concluded that patients with radicular symptoms and signs experienced better pain relief than those with neck pain. There is also a trend that shows that the effect of CIESI on radiculopathy was superior to its effect on neck pain in our study. In this study, we classified the symptoms as neck pain, radiculopathy and neck pain with radiculopathy, and we found that CIESI for neck pain with radiculopathy was least effective. However, the difference was not statistically significant. A previous report [12] showed that patients with lumbar spinal stenoses had poorer responses to epidural steroid Table 1 Statistical relationship between treatment outcome and the variables examined (HIVD herniated intervertebral disc) a Analyzed by logistic regression Parameter No effect (%) Effect (%) P a Gender Female 10 (28.6) 25 (71.4) Male 11 (26.8) 30 (73.2) Primary symptom Radiculopathy 7 (21.2) 26 (78.8) Neck pain 4 (30.8) 9 (69.2) Both pain 10 (33.3) 20 (66.7) Duration Less than 6 months 9 (19.6) 37 (80.4) More than 6 months 12 (40.0) 18 (60.0) Cause HIVD 5 (13.9) 31 (86.1) Spinal stenosis 16 (40.0) 24 (60.0) Age group (years) (10.0) 9 (90.0) (27.3) 16 (72.7) (38.9) 11 (61.1) (31.8) 15 (68.2) 70 4 (100.0)

5 Skeletal Radiol (2007) 36: injections than patients with herniated discs, and the present study produced a similar result, which is probably due to the characteristics of the steroid used. Much research supports the rationale for the use of steroid injections for the management of sciatica [13 17]. Painful symptoms of herniated disc diseases are commonly thought to be due to inflammatory changes compressing a nerve root or inflammation of the longitudinal ligaments of the spine [18 20]. The beneficial effect of steroid is due to a reduction in this inflammation [21], and we think that steroid injections are less effective in the mechanical compression of nerve root or dural sac of spinal stenosis. We performed CIESI via a midline interlaminar approach, which is relatively easy. The transforaminal approach offers another route to the epidural space, but this is considered technically difficult. In our experience, epidural steroid injection through a transforaminal approach occasionally causes nerve root puncture and pain provocation. Moreover, the risk of intravascular penetration in cervical transforaminal epidural steroid injection is higher than that for lumbosacral transforaminal epidural steroid injections [22 25]. However, no study has compared the clinical effects of the interlaminar and transforaminal approaches. The complications of CIESI are infrequent and minor [1]. In our series no serious complication occurred during or after treatment. The minor complications of CIESI include increased neck pain, transient headaches, insomnia, facial flushing, dural puncture, and vasovagal reaction. The major complications are direct cord injury due to needle trauma, spinal cord infarction, and epidural hematoma or abscess. The best way to avoid cord injury is to know exactly where the needle is at all times. Infections are rare but may occur and can be difficult to recognize [26]. Although complications have been reported, only a few studies have quantified complication rates. Botwin et al. found no major complications in 157 patients after fluoroscopically guided CIESI [4]. Many CIESIs have been performed without imaging guidance. However, fluoroscopy guided techniques increase the procedure precision and help confirm correct needle placement. Because fluoroscopy guided techniques should lead to better results and reduce complication rates, they are now becoming more popular [7]. The loss of resistance technique may be inadequate for ensuring accurate needle placement during unguided cervical epidural injections. Moreover, the use of epidurography can improve the accuracy of needle placement and medication delivery to targeted areas [5, 6]. Although a multimodality approach is absolutely necessary for the treatment of patients with chronic pain, we have found that a cervical epidural injection of corticosteroids is useful in patient with cervical pain. The procedure is easily accomplished in an outpatient setting and appears to be reasonably safe, and when performed as an outpatient procedure, has low associated costs. The limitations of this study are as follows. This is a report about the short-term effects of CIESI. We think, however, that the short-term effects are as important as long-term effects for cervical pain management. Another limitation of this study is the relatively limited number of patients. However, 76 cases were enough to evaluate the effects of CIESI statistically. In conclusion, the present study demonstrates that fluoroscopy guided CIESI is a safe and effective method of treating patients with neck pain and cervical radiculopathy. The most important predictor of therapeutic outcome was identified as the cause of the pain. Moreover, the effect of CIESI in cases of herniated disc was superior to that in cases of spinal stenosis. References 1. Cicala RS, Thoni K, Angel JJ. Long-term results of cervical epidural steroid injections. Clin J Pain 1989;5: Ferrante FM, Wilson SP, Iacobo C, Orav EJ, Rocco AG, Lipson S. Clinical classification as a predictor of therapeutic outcome after cervical epidural steroid injection. Spine 1993;18: Rowlingson JC, Kirschenbaum LP. Epidural analgesic techniques in the management of cervical pain. Anesth Analg 1986;65: Botwin KP, Castellanos R, Rao S et al. Complications of fluoroscopically guided interlaminar cervical epidural injections. Arch Phys Med Rehabil 2003;84: Stojanovic MP, Vu TN, Caneris O, Slezak J, Cohen SP, Sang CN. The role of fluoroscopy in cervical epidural steroid injections: an analysis of contrast dispersal patterns. Spine 2002;27: Johnson BA, Schellhas KP, Pollei SR. Epidurography and therapeutic epidural injections: technical considerations and experience with 5334 cases. AJNR Am J Neuroradiol 1999;20: Silbergleit R, Mehta BA, Sanders WP, Talati SJ. Imaging-guided injection techniques with fluoroscopy and CT for spinal pain management. Radiographics 2001;21: Pfirrmann CW, Oberholzer PA, Zanetti M et al. Selective nerve root blocks for the treatment of sciatica: evaluation of injection site and effectiveness a study with patients and cadavers. Radiology 2001;221: Jamison RN, VadeBoncouer T, Ferrante FM. Low back pain patients unresponsive to an epidural steroid injection: identifying predictive factors. Clin J Pain 1991;7: Sontag MJ. A theoretical overview of the diagnosis and management of low back pain: acute vs chronic pain and the mind/body continuum. In: Cole AJ, Herring SA, editors. The low back pain handbook: a guide for the practicing clinician. 2nd ed. Philadelphia, PA: Hanley & Belfus; 1993; Abram SE. Treatment of lumbosacral radiculopathy with epidural steroids. Anesthesiology 1999;91: Rivest C, Katz JN, Ferrante FM, Jamison RN. Effects of epidural steroid injection on pain due to lumbar spinal stenosis or herniated disks: a prospective study. Arthritis Care Res 1998; 11: Gooding MR. Pathogenesis of myelopathy in cervical spondylosis. Lancet 1974;2: Johansson A, Hao J, Sjolund B. Local corticosteroid application blocks transmission in normal nociceptive C-fibres. Acta Anaesthesiol Scand 1990;34:

6 436 Skeletal Radiol (2007) 36: Olmarker K, Rydevik B, Nordborg C. Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 1993;18: Olmarker K, Byrod G, Cornefjord M, Nordborg C, Rydevik B. Effects of methylprednisolone on nucleus pulposus-induced nerve root injury. Spine 1994;19: Saal JA, Saal JS, Herzog RJ. The natural history of lumbar intervertebral disc extrusions treated nonoperatively. Spine 1990;15: Sizer PS, Phelps V, Matthijs O. Pain generators of the lumbar spine. Pain Pract 2001;3: Bogduk N. Clinical anatomy of the lumbar spine and sacrum. New York: Churchill Livingstone, Scuderi GJ, Brusovamik VG, Greg Anderson D et al. Cytokine assay of the epidural space lavage in patients with lumbar intervertebral disk herniation and radiculopathy. J Spinal Disord Tech 2006;19: Winnie AP, Hartman JT, Meyers HL et al. Pain clinic II: intradural and extradural corticosteroids for sciatica. Anesth Analg 1972;51: Ludwig MA, Burns SP. Spinal cord infarction following cervical transforaminal epidural injection: a case report. Spine 2005;30: E266 E Rathmell JP, Aprill C, Bogduk N. Cervical transforaminal injection of steroids. Anesthesiology 2004;100: Furman MB, Giovanniello MT, O Brien EM. Incidence of intravascular penetration in transforaminal cervical epidural steroid injections. Spine 2003;28: Tiso RL, Cutler T, Catania JA, Whalen K. Adverse central nervous system sequelae after selective transforaminal block: the role of corticosteroids. Spine J 2004;4: Huang RC, Shapiro GS, Lim M, Sandhu HS, Lutz GE, Herzog RJ. Cervical epidural abscess after epidural steroid injection. Spine 2004;29: E7 E9.

7 Curr Rev Musculoskelet Med (2009) 2:30 42 DOI /s Cervical epidural steroid injections in the management of cervical radiculitis: interlaminar versus transforaminal. A review Christopher W. Huston Published online: 7 January 2009 Ó The Author(s) This article is published with open access at Springerlink.com Abstract There has been recent concern regarding the safety of cervical epidural steroid injections. The decision to proceed with treatment requires balancing the risk and benefits. This article is an in depth review of the efficacy, complications, and technique of both interlaminar and transforaminal cervical epidural steroid injections in the management of cervical radiculitis. Keywords Cervical epidural steroid injections Transforaminal Interlaminar Introduction Cervical radiculitis affects approximately 83 per 100,000 population per year [1]. The most common causes of cervical radiculitis in this study were herniated disk in 21.9% and spondylosis in 68.4%. The majority of those affected did not undergo surgery. Outcomes are favorable in both surgical and non-surgically treated groups without reproducible significant outcome differences of one treatment over the other [1 3]. The favorable outcome from cervical radiculitis from herniated disk may be due in part to the natural regression of disk herniation over time [4, 5]. However, well-designed randomized trials of surgical outcome and non-surgical outcome for specific diagnostic entities have not been performed. Current treatment strategies typically involve a gradual progression in the C. W. Huston (&) The Orthopedic Clinic Association, 2222 E. Highland Avenue, Suite 300, Phoenix, AZ 85016, USA cwhuston@cox.net aggressiveness of intervention, progressing from less to more invasive interventions only in refractory cases. Initial treatment usually consists of activity modification, NSAID s, and physical therapy. Narcotic analgesics and analgesic adjuvants may be needed when pain is not adequately controlled. A cervical orthosis may provide comfort for some patients in the acute phase. If there is no improvement in 3 4 weeks of conservative treatment, cervical epidural steroid injections may be performed. The rationale for corticosteroid instillation is the antiinflammatory affect. Cervical herniated disk specimens have demonstrated increased levels of matrix metalloproteinase activity, nitric oxide, prostaglandin E2, and interleukin-6 [6, 7]. Phospholipase A2 also plays a role in the inflammation of the nerve root and can be neurotoxic [8 10]. Epidural steroids have been shown to inhibit phospholipase A2 activity, thus reducing symptoms [10]. Corticosteroid mitigates nerve conduction slowing due to inflammation [11]. Corticosteroids also affect cell-mediated activity and cytokines, which may be involved in the pathogenesis of radicular pain [12]. Corticosteroids have actions other than anti-inflammatory. Corticosteroids stabilize nerve membranes inhibiting ectopic impulses [13], inhibits ion conductance [14], hyperpolarizes spinal neurons [15], and inhibits C fiber transmission [16]. These latter properties of corticosteroids can explain relief of symptoms in non-inflammatory states. Local anesthetic mixed with the corticosteroid may have additional benefits beyond the direct anesthetic affects. Lidocaine has been shown to have anti-inflammatory effect on nucleus pulposus induced nerve injury [17]. Lidocaine has been demonstrated to increase intra-radicular blood flow in an animal compressed nerve root model [18]. This may improve intra-neural metabolism and reduce inflammatory mediators.

8 Curr Rev Musculoskelet Med (2009) 2: The efficacy, complications, side-effects, and technique for interlaminar and transforaminal cervical epidural steroid injections are reviewed. Because of the paucity of studies, blinded interlaminar cervical epidural steroid injections are included in the review. However, the author does not condone the use of blinded interlaminar injections, which should become evident to the reader upon completion of this review. Efficacy Cervical epidural steroid injections (CESI) have been utilized for decades in the treatment of radicular pain. Over time the techniques in delivering corticosteroid into the epidural space has changed. Initial injections were performed blind without fluoroscopy. Table 1 summarizes the following studies. Blind interlaminar CESI Rowlingson and Kirschenbaum [19] retrospectively present their results on 25 subjects with cervical radiculopathy who underwent 45 blind interlaminar CESI at C6-7 or C7-T1. Advanced imaging with CT and/or Myelography was performed in only 12 of the subjects. A compressive lesion was found in nine. Whether the compressive lesion correlated with the subject s symptoms was not stated. Average follow-up was 8.9 months. Excellent response defined as complete resolution of symptoms occurred in 24%. Symptom improvement of greater than 75% occurred in 40%. Three subjects had no improvement. Mangar and Thomas [20] briefly report their results for 40 subjects who underwent 117 blind interlaminar CESI for cervical radiculitis. Greater than 70% pain relief and more than 50% relief were reported in 38% and 7%, respectively. No relief occurred in 32%. However, 75% of subjects with Table 1 Summary of CESI outcomes. Under diagnosis, mixed indicates inclusion of subjects with neck pain only and neck and arm pain. Under type of CESI, blind refers to interlaminar injections performed without fluoroscopic guidance. TF indicates fluoroscopically guided transforaminal injection. IL indicates fluoroscopically guided interlaminar injection. See text for further descriptions of studies Investigators Study design N Diagnosis CESI type F/U Outcome Rowlings and Kirschenbaum Retrospective 25 Non-specific Blind 8.9 months 24% excellent 40% [75% relief Mangar and Thomas Observational 40 HNP Spondylosis Blind Not stated 38% [70% relief 7% [50% relief 32% no relief Ferrante Retrospective 100 Mixed Blind 13.5 months 62% with radiculitis with [50% relief Stav Randomized 60 Mixed Blind 1 year [50% decrease VAS ESI: 68% T.P. 11.8% Castagnera Randomized 24 Chemical radiculitis Blind 3 months VAS 87% decrease Steroid:lidocaine = Steroid:morphine Grenier Prospective 29 Chemical radiculitis Blind 2 years 83% Success Bush and Hillier Prospective 68 HNP spondylosis Plexus TF IL 39 months 76% Relief of arm pain 84% Full work capacity Bush Prospective 13 HNP Blind TF IL 12 months 12 Complete relief & resolution of HNP Vallee Prospective 32 HNP spondylosis TF 6 months 56% [50% relief Cyteval Observational 30 HNP spondylosis TF-CT guided 6 months 18/30 VAS decreased from 6.3 to 0.7 Slipman Retrospective 22 Chemical radiculitis after MVA TF 33.3 months 14% Good to excellent VAS: 73.3 to 50.7 Slipman Retrospective 15 Spondylosis with trauma TF 20.7 months 20% Good to excellent Slipman Retrospective 20 Spondylosis no trauma TF 21.2 months 60% Good to excellent VAS: 6.9 to 2.0 Lin Retrospective 70 HNP TF 13 months 65.3% Good to excellent Anderberg Randomized 40 Spondylosis TF 3 weeks Carbocaine with steroid vs. saline No difference

9 32 Curr Rev Musculoskelet Med (2009) 2:30 42 herniated disk had improvement. Time from treatment to analysis was not reported in this retrospective review. Ferrante et al. [21] retrospectively analyzed records of 100 subjects who underwent 235 blind midline interlaminar CESI for radicular or axial pain. Of those with radiculopathy, 62% had greater than or equal to 50% pain relief. Of those with cervical radiculitis with structural abnormality on imaging, only 35% had 50% or better pain relief. Stav et al. [22] performed a prospective, randomized trial of blind interlaminar CESI (group A), posterior muscle trigger point with steroid:anesthetic mixture (group B), and intra-muscular lidocaine injection (group C). Group C consisted of 10 subjects who were later divided equally into groups A and B. Groups A and B initially consisted of 25 subjects each, but 8 in group B were later excluded secondary to litigation. Inclusion was neck and neck with radicular pain from cervical disk disease or spondylosis that failed physical therapy and medications. Groups A and B received 3 injections performed every 2 weeks. Outcome was considered very good for 75% decrease and good for 50 74% decrease in VAS. At 1 year, very good or good relief was 68% and 11.8% for groups A and B, respectively. Group C had poor results in all subjects at 3 4 week follow-up. The results suggest benefit from CESI. The observational studies suggest a success rate of 40 62% for blind, interlaminar CESI for cervical radiculopathy. The one prospective, randomized trial demonstrated superiority of blind, interlaminar CESI over trigger point injection for radicular pain. However, the actual diagnosis of subjects in these studies is elusive. Treatment outcomes will be dependent upon a specific diagnosis. Mangar and Thomas [20] support this premise noting 75% of subjects with a herniated disk had improvement, while overall success rate in their study was only 45%. For blind, interlaminar CESI only two studies were performed for a specific diagnostic group. Chemical radiculitis is defined as radicular pain in the absence of nerve root compression on imaging studies [23]. Castagnera et al. [24] randomized 24 subjects suffering from cervical chemical radiculitis treated with blind interlaminar CESI with steroid/lidocaine combination versus interlaminar CESI with steroid/morphine sulfate combination. At 3 months, there was no difference between groups with mean VAS decrease of 87% for both groups. The authors concluded there is no advantage to the addition of morphine to CESI. Grenier et al. [25] prospectively report on 29 subjects who underwent one blind interlaminar CESI at C7-T1 for chemical radiculitis with 83% success rate at 3 month follow-up that remained for 2 years. Blind, interlaminar CESI may be misplaced 53% of the time utilizing the loss of resistance technique [26]. Hence, studies performed with blind, interlaminar CESI have been criticized for probably underestimating efficacy. Fluoroscopy with conformation utilizing non-ionic contrast agent has been advocated to improve accuracy of interlaminar CESI s [26]. Fluoroscopically guided interlaminar and transforaminal CESI Bush and Hillier [27] prospectively evaluated with an independent review of 68 consecutive subjects suffering from cervical radiculopathy. Cervical spondylosis was present in 30% and herniated disk in 70% of subjects. Subjects received a cervical brachial plexus block. If no relief the subjects progressed to fluoroscopically guided transforaminal CESI and lastly, fluoroscopically guided interlaminar CESI. Twenty-nine percent had relief with brachial plexus injection, 62% with transforaminal CESI, and 16% interlaminar CESI. At mean follow-up of 39 months (range 4 112), 76% had complete relief of arm pain and 24% had average pain score of 2. Prior to treatment 75% had weakness. At follow-up 73% no longer experienced weakness. Eighty-four percent did not feel their symptoms interfered with their capacity to work. Bush et al. [5] prospectively reported on 13 subjects with cervical radiculopathy from HNP that received either a blind injection, fluoroscopically guided transforaminal CESI or interlaminar CESI. An average follow-up of 12 months (range, 4 31 months) underwent telephone interview and repeat MRI. Twelve of thirteen had resolution of the herniated nucleus pulposus. The one subject with persistent herniated nucleus pulposus on MRI had residual neck pain. While the above studies suggest CESI s are beneficial in the management of cervical radicular pain from a herniated disk, the lack of a control group does not exclude the improvement being secondary to the favorable natural history of cervical disk herniation. Saal et al. [28] experienced an 83% success rate for non-operative management of radiculopathy from a cervical disk herniation in 26 subjects. Treatment consisted of relative rest, modalities, hard cervical collar, medications, and physical therapy. Nine subjects with persistent symptoms underwent either fluoroscopically guided interlaminar or transforaminal CESI. Follow-up was over 1 year in all subjects. Fluoroscopically guided transforaminal CESI Fluoroscopy allowed the development of transforaminal CESI s. Transforaminal epidural injections have the advantage of being able to place medication directly around the dorsal root ganglion pathologically involved in causing a patient s radicular pain. Medication in the epidural space will tend to flow in the direction of least

10 Curr Rev Musculoskelet Med (2009) 2: resistance. With interlaminar paramedian cervical epidural injections, the medication tends to spread unilateral in 51% and ventral in only 28% [26]. The authors utilized a 2-ml volume stating larger volumes could result in dilution of corticosteroid at the site of pathology. In a separate study with a midline approach, ventral flow occurred in 44.6% of epidural injections with volumes ranging from 2 to 4 ml [29]. Foraminal and entrance zone disk herniations, cervical spondylotic foraminal stenosis, and epidural fibrosis can potentially block the flow of medication from an interlaminar epidural injection to the involved dorsal root ganglion. Hence, interventionalists seeking to improve efficacy began to perform transforaminal epidural steroid injections to put medication at the site of pathology. Anderberg et al. [30] performed a prospective, randomized study of radicular pain from cervical spondylosis with positive MRI finding and 50% or greater relief with diagnostic selective nerve root injection. Subjects were randomized to receive either 0.5 ml Carbocain and 1 ml steroid (40 mg methylprednisolone) or 0.5 ml Carbocain and 1 ml saline transforaminal cervical epidural injection with fluoroscopic guidance. Follow-up was performed at 3 weeks. Twenty subjects were in each group with subjective improvement in pain occurred in 8 in the steroid group and 7 in the saline group. There was no statistical significance between groups. Vallee et al. [31] prospectively evaluated transforaminal CESI performed on 32 consecutive subjects with radicular pain from foraminal stenosis either from spondylosis or disk herniation. At 6 months follow-up greater than 50% relief occurred in 56% who also resumed full activities. Cyteval et al. [32] report on 30 subjects with cervical radiculopathy from either spondylotic foraminal stenosis (16 subjects) or foraminal disk protrusion (14 subjects). All subjects had persistent symptoms despite 1 month of physical therapy and medication management. Subjects underwent one CT-guided transforaminal CESI. Eighteen subjects had good to excellent pain relief at 2 weeks with average VAS decreasing from 6.3 to 1.2. At 6 months these 18 subjects had mean VAS of 0.7. For the 12 subjects with fair or poor results at 2 weeks, 3 had a second CT-guided transforaminal CESI. At 2 weeks from the second injection 2 subjects had greater than 75% relief (excellent) and 1 with less than 25% relief (poor). Slipman et al. [33] retrospectively evaluated 22 subjects with radicular pain without a compressive lesion on imaging studies following a motor vehicle accident. All subjects had at least 80% pain reduction from a diagnostic cervical selective nerve root injection. Additionally, all subjects had greater arm than neck pain. Mean follow-up was 33.3 months (range 4 65 months). An average of 2.1 injections was performed. A steroid effect occurred in 59%. Only 14% had a good to excellent outcome, based upon VAS, Oswestry, work status, and medication usage. Average Oswestry score at presentation and follow-up was 45.5 and 40.7, respectively. Average VAS score at presentation and follow-up was 73.3 and 50.7, respectively. However, high functioning at time of presentation had a more favorable outcome statistically with 48.9% improvement in pain and continued high functional status. The authors concluded transforaminal CESI was not indicated in this group except for possibly higher functioning individuals at presentation. Slipman et al. [34] retrospectively report only 20% with good to excellent outcome with mean follow-up of 20.7 month for transforaminal CESI in 15 subjects for traumatically induced cervical spondylotic radicular pain. In these subjects with cervical spondylotic foraminal stenosis, symptoms occurred following a traumatic incident. Motor vehicle accident accounted for 46.7%, fall 13.3%, lifting injury 20%, and sport injury 20%. The authors concluded the use of transforaminal CESI is not supported in this group. Slipman et al. [35] retrospectively present 20 subjects that underwent transforaminal CESI for radicular pain due to non-traumatic cervical spondylotic foraminal stenosis. Follow-up was done at an average of 21.2 months (range, months) with subjects receiving an average of 2.2 injections. Sixty percent had good to excellent results. Pain decreased from VAS score 6.9 to verbal numeric scale score of 2.0. There was no significant change in employment status but significant decrease of medication usage. Lin et al. [36] retrospectively reported on 70 consecutive subjects that underwent transforaminal CESI for radicular pain from a herniated cervical disk. All patients had been offered surgical treatment but given the option of a transforaminal CESI. Mean follow-up was 13 months (range, 6 months to 4 years) with 65.3% good to excellent relief with Odom criteria and avoidance of surgery. The authors found more favorable result in those over age 50 and symptom duration less than 100 days. The above observational studies with cervical transforaminal ESI suggest benefit for radicular pain due to non-traumatic spondylotic stenosis and herniated disk [31, 35, 36]. However the lack of a control group does not exclude a favorable natural history. The studies also suggested transforaminal CESI is not beneficial in those with chemical radiculitis or cervical spondylotic foraminal stenosis following a motor vehicle accident [33, 34]. The one randomized, prospective study was poorly designed [30]. A validated outcome measure was not utilized. For pain relief, any pain improvement at the 3 week follow-up was included. A subject with only 10% relief would be included in the same group as one with 90% relief. Only short-term outcome was measured. Also, local anesthetic has antiinflammatory effect and improves radicular flow both

11 34 Curr Rev Musculoskelet Med (2009) 2:30 42 therapeutic benefits. Clinically, patients may receive from one to four therapeutic injections in a treatment regimen not just one. Nevertheless, prospective, randomized controlled trials are needed to determine the effectiveness of CESI in the management of radicular pain from herniated disk and spondylotic foraminal stenosis. A randomized controlled trial of perineural injection was found to be superior to inter-laminar epidural injection in radiculitis from herniated lumbar disk [37]. A retrospective study also found lumbar transforaminal epidural steroid injections had superior pain reduction than interlaminar epidural steroid injections at short term and less surgical interventions at 1 year review [38]. These studies support the benefits of target-specific injection. However, studies of the lumbar spine cannot necessarily be extrapolated to the cervical spine. There are currently no prospective studies in the English literature comparing the effectiveness of transforaminal versus interlaminar CESI for specific diagnostic groups. Complications and side-effects The decision to proceed with any intervention not only requires understanding of the benefits but also the risks. Complications reported with interlaminar cervical epidural steroid injections include dural puncture, bloating, nausea and vomiting, vasovagal reaction, facial flushing, fever, nerve root injury, pneumocephalus, epidural hematoma, subdural hematoma, stiff neck, Cushing s syndrome, transient paresthesias, hypotension, respiratory insufficiency, transient blindness, epidural abscess, paralysis, cord injury, and death [39 51]. Complications reported with transforaminal cervical epidural steroid injections include neck pain, transient increased radicular pain, nausea, vasovagal reaction, dural puncture, non-specific headache, transient lightheadedness, dyspepsia, fluid retention, transient global amnesia, vertebral artery injury, paralysis, cord infarction and cerebellar infarction, and death [52 57]. Blinded and fluoroscopically guided interlaminar CESI Waldman [58] prospectively reported upon complications with blind interlaminar C5-6 or C6-7 epidural steroid injections utilizing loss of resistance technique on 215 subjects receiving 790 injections. Complications were recorded immediately at 6 weeks by the pain management physician or nurse. Two individuals suffered dural puncture with headache requiring blood patching. There were 3 vasovagal reactions and one superficial infection. Botwin et al. [59] retrospectively reported complications with fluoroscopically guided C6-7 or C7-T1 interlaminar epidural steroid injections on 157 subjects receiving 345 injections. Data were obtained at 24 h from the ambulatory surgical center questionnaire and 3 week physician followup. There was 6.7% neck pain, 4.6% non-positional headache, 1.7% insomnia, 1.7% vasovagal reaction, 1.5% facial flushing, 0.3% fever, and 0.3% dural puncture incidence. The overall rate of complications was 16.8%. Fluoroscopically guided transforaminal CESI Ma et al. [52] reviewed records of 1,036 cervical transforaminal epidural steroid injections in 844 subjects. Immediate complications were recorded by the radiologist performing the procedure. If any complications occurred after discharge, the subjects were told to contact their referring physician. Hence, complications that occurred after discharge are at risk of being underreported. The authors report complications occurred in 14 subjects (1.66%). These included headache/dizziness (0.59%), transient pain or weakness (0.71%), hypersensitivity reaction (0.12%), transient global amnesia (0.12%), vasovagal reaction (0.12%), and wrong site injection (0.36%). Huston et al. [53] performed a prospective, controlled study with independent interviewer of lumbar and cervical selective nerve root injections on 151 subjects who received 306 injections. The control group was 60 subjects with similar demographics and spinal complaints that did not undergo an intervention at time of interview. Procedural complications were recorded by the interventionalist. Immediate, 1 week and 3 month complications were recorded by an independent interviewer. Of the cervical group, there were 89 cervical selective nerve root injections performed on 37 subjects. There were no major complications. There was one dural puncture but the subject did not develop a headache and no treatment was needed. In the cervical group immediate complications were increased pain at injection site 22.7%, increased radicular pain 18.2%, lightheadedness 13.6%, increased spine pain 9.1%, non-specific headache 4.5%, and nausea 3.4%. One week follow-up compared to the control group had significance for increased pain at injection site (P =.001), non-specific headache (P =.019), and nonspinal headache (P =.002). At 3 months follow-up 2 subjects complained of increased neck pain. One would repeat the injections again. The other subject would not repeat the injection. This subject did have complete resolution of radicular pain from a herniated disk but was not satisfied because of persistent neck pain. Interlaminar versus transforaminal CESI Incidence of dural puncture with interlaminar CESI ranges from 0.25% to 2.00% [21, 58, 60] and transforaminal CESI

12 Curr Rev Musculoskelet Med (2009) 2: % [53]. With dural puncture the procedure is discontinued to avoid subarachnoid instillation of local anesthetic or corticosteroid. Instillation of local anesthesia could result in spinal anesthesia with respiratory depression, hypotension, and syncope [61]. Additionally, subarachnoid corticosteroid injection has been hypothesized to cause arachnoiditis [62, 63]. Celestone Chronodose has been evaluated in sheep and found to result in arachnoiditis at suprapharmacologic levels [64]. Epidural injections of triamcinolone and methyprednisolone in animal studies did not result in arachnoiditis or nerve root injury [65, 66]. After dural puncture, there is still the concern of spinal headache. However, dural puncture does not always result in a spinal headache [53, 58, 60, 61]. If a headache does occur, treatment may consist of strict bed rest, hydration, analgesics, and caffeine [67]. For severe or persistent headache interlaminar or transforaminal blood patching may be performed [58, 68]. The risk of dural puncture may be higher with an interlaminar than a transforaminal approach. Cryomicrotome studies of the cervical epidural space report absence of the posterior epidural space above C7-T1. In another study, the posterior epidural space at C5 has been reported at mm [69]. Furthermore, there is an absence of the interspinous ligament in the cervical spine [69] along with half of specimens being deficient in the midline of the ligamentum flavum. Hence, blind injections utilizing loss of resistance technique may inadvertently puncture the dura. With transforaminal CESI, utilizing multi-planar imaging should avoid inadvertent dural puncture. On the AP view, the needle should not be advanced beyond the 6 o clock (midline) position of the lateral mass. Dural puncture typically occurs by advancing the needle too far in the oblique plane. The technique section will discuss the need for frequent multi-planar imaging while advancing the spinal needle. Non-positional headaches occurred with cervical selective nerve root injections in 4.5% and was found to be statistical significant when compared to a control population [53]. For fluoroscopically guided interlaminar CESI, non-positional headache occurred in 4.6%. The rate is comparable between the two techniques. These headaches have been attributed to alterations in CSF pressure which is related to rapid injection and/or higher volumes [70, 71]. These headaches are typically transient and respond to oral analgesics. These headaches can be minimized by injecting slowly and the use of lower volumes. Transient blindness after epidural steroid injection has been reported primarily with lumbar interlaminar and caudal injections. However, Kao [47] reported a case of impaired visual acuity following a C6-7 interlaminar ESI with 4 ml lidocaine and 2 ml triamcinolone. Five days after the second CESI, the patient developed headache, vomiting, neck stiffness, and decreased left visual acuity. A serous retinal detachment was found. The detachment resolved after 4 weeks but still with impaired vision. By 4 months, the patient reported normal vision. The cause of the retinal detachment is unknown. The author hypothesizes the following possibilities: (1) stress during the injection resulted in neuroendocrine alteration, (2) corticosteroid may have damaged the choroicapillaris with altered permeability, and (3) the corticosteroids may have elevated cathecholamine levels resulting in constriction of choroids vessels. If due to the steroids, then any utilization of corticosteroid whether oral, intra-muscular, or epidural with systemic absorption could potentially result in retinal detachment. Another possibility is increased CSF pressures which could explain the headache and vomiting the patient experienced. While the volume was 6 ml, rapid instillation could increase CSF pressures. Bilateral retinal hemorrhages with transient blindness after caudal and lumbar ESI has been reported [72 75]. The retinal hemorrhages were felt to be related to increased CSF pressure created by rapid instillation and large volumes of medication injected with ESI [72, 73]. Volumes of 20 ml can increase CSF pressures [72]. Volumes of lidocaine and bupivicaine have ranged from 2 to 20 ml with cervical interlaminar ESI [21, 58, 76]. Larger volume CESI s with rapid instillation should be avoided. Cushing s syndrome has been reported after interlaminar CESI with 60 mg of methylprednisolone [45]. The syndrome resolved after 12 months. Cushing s syndrome has also been reported after lumbar ESI. While Cushing s syndrome has not been reported with transforaminal ESI, the occurrence is probably related to the systemic absorption of the corticosteroid as opposed to the technique of delivery. Additionally, systemic affects of corticosteroids can result in hyperglycemia in diabetics and needs to be closely monitored. Infection is always a risk whenever the skin is punctured. Huang et al. [51] present a case of epidural abscess following CESI. The patient initially presented with increased neck pain and chills. The patient subsequently developed left arm pain, paresthesia, and weakness but was neurologically intact in the lower extremities. An epidural abscess from C4 to C6 was seen on gadolinium-enhanced MRI. The patient underwent surgical decompression, irrigation, and debridement. The patient was placed on intravenous antibiotics. By 7 months post-operative, the patient regained baseline neurologic function [51]. Whether one technique is more predisposed is unknown. The procedure should be done with sterile technique. Additionally, the interventionalist should not touch the spinal needle tip. Both techniques are at risk for infection. Nerve root injury and transient paresthesias have been reported after interlaminar CESI [46, 60]. After a blind

13 36 Curr Rev Musculoskelet Med (2009) 2:30 42 interlaminar C5-6 ESI, nerve root injury was postulated as the initial injury resulting in complex regional pain syndrome [50]. For cervical selective nerve root injections transient increased radicular pain occurred in 18.2% but with no episodes of nerve root injury [53]. Paralysis: interlaminar and transforaminal CESI Epidural hematoma after fluoroscopically guided C5-6 interlaminar CESI requiring surgical evacuation has been reported [42]. The patient had near full recovery of paralysis. Another case occurred within half and hour after painful paresthesia with the introduction to a Touhy needle at the C6-7 interspace [43]. The patient had incomplete recovery prior to surgery with high-dose intravenous methylprednisolone. The patient also required immediate surgical evacuation of the hematoma. Puncturing of the epidural venous plexus is the probable etiology. Whether the risk of epidural hematoma and subsequent quadriplegia is greater with interlaminar versus transforaminal CESI is unknown. However, with tranforaminal injections the needle is not placed directly into the spinal canal. Puncturing a radicular vein or artery within the foramen may be less likely to result in thrombosis formation with cord compression as the needle is not within the spinal canal. However, there may be other serious consequences of vascular puncture with transforaminal injections. Brouwers [54] reported a case of tetraplegia following a right C6 transforaminal ESI with bupivicaine/triamcinolone mixture. The paralysis was consistent with anterior spinal artery syndrome. Another case was reported of cord infarction after left C6 transforaminal ESI with the patient suffering incomplete tetraplegia [56]. In another case, digital subtraction revealed puncture of a radicular artery terminating with several branches in the region of the spinal cord despite correct technique with a transforaminal cervical epidural injection [77]. The procedure was done with live fluoroscopy when injecting contrast. Fortunately, the procedure was abandoned without sequelae after noting the vascular flow. Tiso et al. [57] reported a case of cerebellar infarction after a C6 transforaminal CESI with bupivicaine/triamcinolone mixture. Intra-vascular injection of particulate steroid resulting in embolic occlusion through the vertebral artery with subsequent infarction was postulated as the cause. Pathology revealed bilateral cerebellar and occipital cortex infarction, thromboembolism of the leptomeningeal artery. Light microscopy of steroid particulate size found up to 50 lm particle size for methylprednisolone, triamcinolone, betamethasone sodium phosphate and acetate, dexamethasone, and betamethasone sodium phosphate [57]. Only betamethasone sodium phosphate had no particles greater than 50 lm. Less than 5% of particles were greater than 50 lm for methylprednisolone, betamethasone sodium phosphate and acetate, and dexamethasone. Methylprednisolone and triamcinolone had a tendency to coalesce into large aggregates of greater than 100 lm, which could result in sludging [57]. Particle and aggregate size is relevant when one considers the diameter of the artery system: artery [50 lm, metarteriole lm, arteriole lm, and capillary 5 8 lm. Based upon dimensions, methylprednisolone and triamcinolone sludge could block smaller arteries and arterioles and result in ischemia [57]. Dexamethasone and betamethasone sodium phosphate would be better choices to avoid vascular occlusion. However, betamethasone sodium phosphate is not available commercially. While betamethasone sodium phosphate can be obtained through a compounding pharmacy, it is not recommended. Meningitis with subsequent death has been linked to compounding pharmacies making betamethasone sodium phosphate [78]. Hence, at this time, the corticosteroid recommended for transforaminal CESI is commercially available dexamethasone [57]. Furthermore, there was no statistical significance difference between outcomes with dexamethasone versus triamcinolone for cervical radicular pain [79]. Temporary paralysis was reported after a diagnostic C7 transforaminal injection with 0.8 ml 2% lidocaine [80]. Sixty-seconds after injection the patient felt unwell. In the next 2 3 min the patient developed quadraparesis that resolved after 20 min. The neurologic deficits were consistent with anterior spinal artery syndrome. The authors recommend injecting local anesthetic first and separate from the steroid [80]. The current hypothesis of tetraplegia following transforaminal epidural steroid injection relates to arterial injection of corticosteroid into a radiculomedullary artery with subsequent occlusion. The radiculomedullary arteries are major feeders to the anterior spinal artery. These arteries can arise anywhere from C3 to C8. Occlusion of a radiculomedullary artery can result in spinal cord infarction anterior spinal artery syndrome. While vertebral artery puncture should be avoided by adhering to correct technique, Baker et al. [77] demonstrated a correct technique which can still result in injection into a radicular artery. When performing a transforaminal CESI, the following are modified recommendations to minimize the chance of radicular artery injection of corticosteroid [77]: (1) once the needle is in place, tubing should be connected to the spinal needle hub and syringe. This is to prevent inadvertent needle movement when attaching different syringes of injectate. (2) Injection of contrast under live fluoroscopy evaluating for any vascular flow. Digital subtraction imaging may be of benefit. [3] If no vascular flow with contrast, then proceed to injection of local anesthetic under live fluoroscopy. The patient is then

14 Curr Rev Musculoskelet Med (2009) 2: monitored for at least 90 s. This is based upon the case report of Karasek and Bogduk [80] in which initial symptoms of radicular artery injection of local anesthetic occurred at 1 min and paralysis in 2 min. After the time interval expires, the patient should be asked about a metallic taste, peri-oral numbness, auditory changes, agitation suggesting local anesthetic toxicity. Additionally pin-prick is tested in the hands and lower extremities along with movement of the hands and feet. If no signs are present to suggest anterior spinal artery syndrome or intraarterial injection, then proceed to step 4. (4) Before injecting dexamethasone, confirm needle placement has not changed utilizing fluoroscopy. Then slowly inject dexamethasone. The occurrence of tetraplegia has opened the debate of whether transforaminal or interlaminar CESI should be performed. However, tetraplegia has occurred after interlaminar CESI. Cord injury following two cases of fluoroscopically guided interlaminar C5-6 ESI occurred in sedated patients [81]. The authors suggested the sedation did not allow the patients to respond to cord penetration by the needle. However, needle penetration of the cord in alert patients can be without pain or paresthesias [82]. While cord puncture may not be painful, injection of contrast agent into the cord produced pain [83]. Tetraplegia followed a fluoroscopically guided C6-7 interlaminar ESI [84]. While the cause is unknown, the authors hypothesized ischemic injury to the cord [84]. Bromage and Benumof reported a case of paralysis consistent with anterior artery syndrome in an individual undergoing spinal epidural anesthesia at T12 [85]. While the cause was unknown, the case report raised caution in epidural injections performed above the termination of the cord [85]. The cord is at risk of puncture with interlaminar CESI. The ligamentum flavum in the cervical region was found to be deficient in the midline in half of specimens [69]. Furthermore, the interspinous ligament is absent in the cervical spine [69]. When utilizing a loss of resistance technique, lack of resistance from absence of the interspinous ligament and unfused ligamentum flavum could lead to inadvertent dural and cord puncture. Performing the procedure under fluoroscopic guidance should help avoid inadvertent cord penetration. Both interlaminar and transforaminal CESI s have case reports of catastrophic neurologic complications and death. The incidence of these complications while felt to be rare is unknown. Derby et al. [86] surveyed instructors of the International Spine Intervention Society. While not scientific, the survey revealed no major complication, no paralysis or death, in 4,389 interlaminar and 1,579 transforaminal injections. A national databank of complications would be helpful in determining the incidence of rare complications. This would be helpful in developing safer techniques and in appropriate consenting of patients undergoing CESI s. This system would be beneficial for the continuous improvement of patient care. Unfortunately, the current medical malpractice legal climate in the United States creates challenges in developing such a system. Technique Advanced imaging with magnetic resonance imaging (MRI) or at least multi-planar computed tomography should be obtained before proceeding with spinal interventions, including cervical epidural injections. Cervical spine MRI can determine the cause of radicular pain herniated disk or cervical foraminal stenosis. If not diagnostic, further testing may be required electrodiagnostic studies, diagnostic selective nerve root injections, brachial plexus MRI [87]. Knowing the cause of radicular pain will help determine the benefit of a cervical epidural injection. This is important in obtaining informed consent from the patient. Furthermore, one can plan the procedure noting any anatomic variances that may affect the procedure. The vertebral artery path can be followed to evaluate for a tortuous vertebral artery overlying a foramen that may interfere with a transforaminal injection. A tortuous vertebral artery in the C4-5 foramen compressing the C5 nerve root resulting in radicular symptoms has been reported [88]. Magnetic resonance angiogram (MRA) identified the tortuous artery [88]. Obviously, attempt at a transforaminal CESI in that case could have potentially resulted in cerebral vascular accident and death [55]. Central stenosis or posterior displacement of the cord reducing or obliterating the posterior epidural space at the level of a planned interlaminar cervical epidural injection places the cord at risk of puncture. If a patient develops complications post-injection, a preprocedure MRI is very helpful to compare to a new MRI for any changes. Is the cystic structure seen on MRI a synovial cyst or abscess? Are the endplate changes Modic type I degenerative endplate changes or suggestions of osteomyelitis with marrow edema? A pre-procedure MRI would easily answer these questions. Anatomy Understanding cervical spine anatomy is imperative to the interventionalist performing cervical spine procedures. The epidural space is a triangular space extending from the foramen magnum to the sacral hiatus. The inner border is the thecal sac dura mater. The outer border is the bony spinal canal and the covering periosteum. The anterior border is the posterior longitudinal ligament. The posterior border is the lamina and ligamentum flavum. The lateral

15 38 Curr Rev Musculoskelet Med (2009) 2:30 42 border is the pedicle and intervertebral foramen. The epidural space contains loose areolar tissue, venous plexus, spinal nerve roots, radicular arteries, superficial and deep cervical arteries, arachnoid granules, and lymphatics. Above C7-T1 no posterior epidural space was evident on study [69]. The ligamentum flavum is unfused in the midline in approximately half of individuals and the interspinous ligament is absent [69]. Rootlets arise from the cord to form ventral and dorsal nerve roots which exit with the thecal sac covered with dura the root sleeve. The dura ends at the proximal margin of the dorsal root ganglion. The ventral and dorsal roots coalesce to form the spinal nerve that exits from the foramen. The dura extends as the epiradicular sheath covering the dorsal root ganglion and spinal nerve. The spinal nerve is located in the inferior aspect of the foramen. The foramen is formed by the superior and inferior pedicle. The superior articular process of the zygapophyseal joint forms the posterior wall. The anterior wall is superior vertebral endplate and disk. The spinal nerve is posterior to the vertebral artery [89]. The vertebral artery arises from the subclavian and enters the costotransverse foramen at C6 and exits at C1 but can enter at C5 [90]. The vertebral artery crosses posterior to C1 arch before entering the skull through the foramen magnum. Branches from the vertebral artery descend forming the anterior spinal artery. The anterior spinal artery is divided into cervical, thoracic, and lumbar segments [89]. Spinal arteries arising from the vertebral, subclavian, and ascending cervical and deep cervical arteries enter through the foramen and divide into the anterior and posterior cervical radicular arteries [90]. Most radicular arteries supply the nerve root. A variable number of anterior radicular arteries supply the anterior spinal artery. These radicullomedullary arteries are larger and may ascend and descend within the thecal sac supplying the anterior spinal artery. In the cervical region a variable number of radicullomedullary arteries are present and may enter anywhere from C3 to C8 [91, 92] The radicular arteries and radicullomedullary arteries may be located posterior to the spinal nerve in the posterior-inferior aspect of the foramen, close to the target zone of transforaminal injections [90]. Interlaminar CESI The patient is placed in a prone position on the fluoroscopy table with arms at the side. A blanket is placed under the chest. The neck is flexed with the head resting on a folded towel or blanket. To help prevent movement the head may be held in place with a Velcro strap though not all practitioners do this. The neck is prepped and draped in the usual sterile manner and sterile technique is utilized throughout the procedure. AP view is obtained to ensure the C7-T1 interspace located and the patient is correctly positioned in a true AP view. A skin wheal is raised with a 10:1 mixture of 1% lidocaine and 8.4% bicarbonate. A gauge Touhy needle is directed in the midline with a tunnel view parallel to the trajectory of the spinous processes. Once purchase of the needle in the paraspinal muscles occurs, a lateral view is obtained. A syringe containing normal saline is attached to the Touhy needle. Maintaining the same trajectory, the needle is advanced in the lateral plane checking for loss of resistance. The needle should not be advanced beyond the spinolaminar line. Advancing beyond this line risks dural and cord puncture. Additionally, loss of resistance may not occur despite entering the epidural space [93]. If the patient develops pain or paresthesias suggesting cord puncture or nerve root puncture, the needle should be withdrawn and the procedure abandoned. Contrast should not be injected as intra-cord instillation could be catastrophic [81]. More specifically, if cord puncture occurred, then dural puncture also occurred. Once loss of resistance occurs or the needle tip is at the spinolaminar line, needle advancement should stop. Position of the needle is checked in both the AP and lateral plane to ensure the needle is midline and at or only slightly beyond the spinolaminar line. A syringe contained non-ionic contrast (Isovue or Omnipaque) is attached to low volume extension tubing and flushed. Prior to attaching the extension tubing, a drop of contrast is placed in the Touhy needle to flush out any air. Then under live fluoroscopy contrast is injected evaluating for epidural flow and ensuring no vascular pattern. If a venous pattern occurs, the needle is withdrawn and repositioned. If an arterial pattern occurs, the procedure should be abandoned. If a myelographic pattern is obtained indicating subarachnoid injection, the procedure is abandoned [93]. Contrast should flow epidurally along the spinolaminar line creating a dorsal stripe [94]. Then under live fluoroscopy 2 cc of 1% lidocaine and 2 cc Dexamethasone is slowly infused. While the risk of radicular artery cannulation is probably lower for interlaminar injection, one may err on the side of caution and inject local anesthetic and steroid separately. Transforaminal CESI The patient is placed in the supine-oblique position on the fluoroscopy table. A towel or blanket is placed under the head to keep the neck parallel to the table. The patient is rolled into the correct position with the foramen perpendicular to the radiographic imager. A bolster is then placed behind the patient to support this position. The patient is prepped and draped in a sterile fashion and sterile technique is utilized throughout the procedure. Before starting, the interventionalist should review the image to visualize the target and path of the needle. One should visualize the path of the vertebral artery on the fluoroscopic image. If the

16 Curr Rev Musculoskelet Med (2009) 2: patient s position is too oblique, the vertebral artery may be in the path of the needle. If too lateral, attempts to advance the needle into the foramen will result in anterior placement of the needle, risking vertebral artery puncture. Proper patient positioning is paramount. Once correctly positioned, a skin wheal is raised with 10:1 mixture of 1% lidocaine and 8.4% bicarbonate. A 22 gauge inch spinal needle is advanced parallel to the radiographic beam to abut upon the mid-portion near the anterior edge of the superior articular process to gauge depth. The needle is slightly withdrawn and then redirected into the posterior aspect of the foramen 1 2 mm. The position is checked in the AP plane, the needle tip should be slightly beyond the lateral border of the cervical pillar. The needle is then advanced 1 2 mm in the AP plane. If nerve is contacted, the patient typically experiences pain or paresthesia into the scapula or upper extremity. The needle should be slightly withdrawn off the nerve. The needle should not be advanced beyond the mid-sagittal line of the lateral mass. Oblique and lateral views are checked to ensure the needle is in the posterior aspect of the foramen [52]. A 1 cc syringe containing non-ionic contrast (Isovue or Omnipaque) is connected to low volume extension tubing and flushed with contrast. The extension tubing is then connected to the spinal needle hub after first providing a drop of contrast into the spinal needle to flush out any air. The extension tubing minimizes the chance of needle movement with attaching and detaching the various syringes. Furthermore, the tubing keeps the interventionalist s hand away from the fluoroscopic beam. Contrast cc is then infused under live fluoroscopy carefully evaluating not only for outline of the nerve root but also for any vascular flow. If arterial flow is obtained the procedure is abandoned. If a myelographic pattern is obtained dural puncture with subarachnoid injection the procedure is abandoned. If venous flow is obtained, the needle is withdrawn back upon the superior articular process. The needle is then redirected into a different region of the foramen keeping the needle in the posterior half of the foramen away from the vertebral artery. Multi-planar fluoroscopic imaging of needle placement is performed before infusion of contrast. Contrast should outline the nerve root with epidural flow and no vascular pattern. Digital subtraction imaging has been recommended but not required [77]. Preservative free 1% xylocaine cc is then instilled under live fluoroscopy carefully watching for any vascular flow. After 90 s, the patient is queried about peri-oral numbness, metallic taste, tinnitus, light-headedness, shortness of breath, and agitation. The patient is asked to move the fingers and toes, and pin-prick is tested on the hands and lower legs or feet. If there are no untoward effects, cc dexamethasone may then be infused slowly. Before injecting, imaging is performed to ensure the needle position has not changed. Sedation Most patients do not require any sedation. For those who are very anxious, needle-phobic, vasovagal tendency, poor tolerance to pain or the procedure; intravenous minimal to moderate sedation may be performed. However, the patient still needs to be responsive to voice commands and have their protective mechanisms intact. More specifically, the patient should be able to respond with pain to needle touching nerve root or cord. As previously mentioned cord penetration may be asymptomatic. However, cord injection can be painful and the patient should be awake enough to respond to such an occurrence. The goal of moderate sedation is allow the patient to tolerate the procedure such that the procedure can be performed safely and without endangering the patient. Conclusion Cervical epidural steroid injections are frequently utilized in the treatment of cervical radicular pain. Pathophysiologic studies of cervical disk herniation support the utilization of corticosteroids. Observational studies are also supportive of cervical epidural injections in the management of cervical disk herniation and atraumatic cervical spondylotic foraminal stenosis. However, prospective, randomized controlled studies are needed. Transforaminal CESI s have been postulated to be more effective than interlaminar CESI s based upon accurate delivery of medication to the site of pathology. However, prospective studies are needed to compare the techniques. Both procedures have the potential for catastrophic complications. Whether one technique is safer than another is unknown. By utilizing impeccable technique complications can be minimized. Both procedures should be performed under fluoroscopy to reduce risk of serious complications and to ensure appropriate delivery of medication into the epidural space. The change to live fluoroscopy, separate injections of anesthetic and steroid, and the change to dexamethasone will hopefully minimize or eliminate the cases of anterior spinal artery syndrome following transforaminal CESI. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Radhakrishnan K, Litchy WJ, O Fallon WM, Kurland LT. Epidemiology of cervical radiculopathy: a population-based study of Rochester, Minnesota, Brain. 1994;117:

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21 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 1 North American Spine Society Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders NASS Evidence-Based Guideline Development Committee Christopher M. Bono, MD, Committee Chair Gary Ghiselli, MD, Outcome Measures Chair Thomas J. Gilbert, MD, Diagnosis/Imaging Chair D. Scott Kreiner, MD, Medical/Interventional Chair Charles Reitman, MD, Surgical Treatment Chair Jeffrey Summers, MD, Natural History Chair Jamie Baisden, MD John Easa, MD Robert Fernand, MD Tim Lamer, MD Paul Matz, MD Dan Mazanec, MD Daniel K. Resnick, MD William O. Shaffer, MD Anil Sharma, MD Reuben Timmons, MD John Toton, MD

22 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 2 Financial Statement This clinical guideline was developed and funded in its entirety by the North American Spine Society (NASS). All participating authors have submitted a disclosure form relative to potential conflicts of interest which is kept on file at NASS. Comments Comments regarding the guideline may be submitted to the North American Spine Society and will be considered in development of future revisions of the work. North American Spine Society Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Copyright 2010 North American Spine Society 7075 Veterans Boulevard Burr Ridge, IL ISBN:

23 3 Table of Contents I. Introduction II. Guideline Development Methodology III. Natural History of Cervical Radiculopathy from Degenerative Disorders...9 IV. Recommendations for Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders A. Diagnosis/Imaging B. Outcome Measures for Treatment C. Medical and Interventional Treatment D. Surgical Treatment V. Appendices A. Acronyms B. Levels of Evidence for Primary Research Questions C. Grades of Recommendations for Summaries or Reviews of Studies D. Protocol for NASS Literature Searches E. Literature Search Parameters F. Evidentiary Tables VI. References...168

24 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 4 I. Introduction Objective The objective of the North American Spine Society (NASS) Clinical Guideline for the Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders is to provide evidence-based recommendations to address key clinical questions surrounding the diagnosis and treatment of cervical radiculopathy from degenerative disorders. The guideline is intended to reflect contemporary treatment concepts for cervical radiculopathy from degenerative disorders as reflected in the highest quality clinical literature available on this subject as of May The goals of the guideline recommendations are to assist in delivering optimum, efficacious treatment and functional recovery from this spinal disorder. Scope, Purpose and Intended User This document was developed by the North American Spine Society Evidence-Based Guideline Development Committee as an educational tool to assist practitioners who treat patients with cervical radiculopathy from degenerative disorders. The goal is to provide a tool that assists practitioners in improving the quality and efficiency of care delivered to patients with cervical radiculopathy from degenerative disorders. The NASS Clinical Guideline for the Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders provides a definition and explanation of the natural history of cervical radiculopathy from degenerative disorders, outlines a reasonable evaluation of patients suspected to have cervical radiculopathy from degenerative disorders and outlines treatment options for adult patients with a diagnosis of cervical radiculopathy from degenerative disorders. THIS GUIDELINE DOES NOT REPRESENT A STANDARD OF CARE, nor is it intended as a fixed treatment protocol. It is anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases, treatment falling outside this guideline will sometimes be necessary. This guideline should not be seen as prescribing the type, frequency or duration of intervention. Treatment should be based on the individual patient s need and physician s professional judgment. This document is designed to function as a guideline and should not be used as the sole reason for denial of treatment and services. This guideline is not intended to expand or restrict a health care provider s scope of practice or to supersede applicable ethical standards or provisions of law. Patient Population The patient population for this guideline encompasses adults (18 years or older) with a chief complaint of pain in a radicular pattern in one or both upper extremities related to compression and/or irritation of one or more cervical nerve roots.

25 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 5 II. Guideline Development Methodology Through objective evaluation of the evidence and transparency in the process of making recommendations, it is NASS goal to develop evidence-based clinical practice guidelines for the diagnosis and treatment of adult patients with various spinal conditions. These guidelines are developed for educational purposes to assist practitioners in their clinical decision-making processes. It is anticipated that where evidence is very strong in support of recommendations, these recommendations will be operationalized into performance measures. Multidisciplinary Collaboration With the goal of ensuring the best possible care for adult patients suffering with spinal disorders, NASS is committed to multidisciplinary involvement in the process of guideline and performance measure development. To this end, NASS has ensured that representatives from medical, interventional and surgical spine specialties have participated in the development and review of all NASS guidelines. It is also important that primary care providers and musculoskeletal specialists who care for patients with spinal complaints are represented in the development and review of guidelines that address treatment by first contact physicians, and NASS has involved these providers in the development process as well. To ensure broad-based representation, NASS has invited and welcomes input from other societies and specialties. Evidence Analysis Training of All NASS Guideline Developers NASS has initiated, in conjunction with the University of Alberta s Centre for Health Evidence, an online training program geared toward educating guideline developers about evidence analysis and guideline development. All participants in guideline development for NASS have completed the training prior to participating in the guideline development program at NASS. This training includes a series of readings and exercises, or interactivities, to prepare guideline developers for systematically evaluating literature and developing evidence-based guidelines. The online course takes approximately hours to complete, and participants have been awarded CME credit upon completion of the course. Disclosure of Potential Conflicts of Interest All participants involved in guideline development have disclosed their relationships with other entities and potential conflicts of interest to their colleagues and their potential conflicts have been documented for future reference. They will not be published in any guideline, but kept on file for reference, if needed. Participants have been asked to update their disclosures regularly throughout the guideline development process. Levels of Evidence and Grades of Recommendation NASS has adopted standardized levels of evidence (Appendix B) and grades of recommendation (Appendix C) to assist practitioners in easily understanding the strength of the evidence and recommendations within the guidelines. The levels of evidence range from Level I (high quality randomized controlled trial) to Level V (expert consensus). Grades of recommendation indicate the strength of the recommendations made in the guideline based on the quality of the literature. Grades of Recommendation: A: Good evidence (Level I studies with consistent findings) for or against recommending intervention. B: Fair evidence (Level II or III studies with consistent findings) for or against recommending intervention.

26 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 6 C: Poor quality evidence (Level IV or V studies) for or against recommending intervention. I: Insufficient or conflicting evidence not allowing a recommendation for or against intervention. Guideline recommendations are written utilizing a standard language that indicates the strength of the recommendation. A recommendations indicate a test or intervention is recommended ; B recommendations suggest a test or intervention and C recommendations indicate a test or intervention may be considered or is an option. I or Insufficient Evidence statements clearly indicate that there is insufficient evidence to make a recommendation for or against a test or intervention. Work group consensus statements clearly state that in the absence of reliable evidence, it is the work group s opinion that a test or intervention may be appropriate. The levels of evidence and grades of recommendation implemented in this guideline have also been adopted by the Journal of Bone and Joint Surgery, the American Academy of Orthopaedic Surgeons, Clinical Orthopaedics and Related Research, the journal Spine and the Pediatric Orthopaedic Society of North America. In evaluating studies as to levels of evidence for this guideline, the study design was interpreted as establishing only a potential level of evidence. As an example, a therapeutic study designed as a randomized controlled trial would be considered a potential Level I study. The study would then be further analyzed as to how well the study design was implemented and significant short comings in the execution of the study would be used to downgrade the levels of evidence for the study s conclusions. In the example cited previously, reasons to downgrade the results of a potential Level I randomized controlled trial to a Level II study would include, among other possibilities: an underpowered study (patient sample too small, variance too high), inadequate randomization or masking of the group assignments and lack of validated outcome measures. In addition, a number of studies were reviewed several times in answering different questions within this guideline. How a given question was asked might influence how a study was evaluated and interpreted as to its level of evidence in answering that particular question. For example, a randomized control trial reviewed to evaluate the differences between the outcomes of surgically treated versus untreated patients with lumbar spinal stenosis might be a well designed and implemented Level I therapeutic study. This same study, however, might be classified as giving Level II prognostic evidence if the data for the untreated controls were extracted and evaluated prognostically. Guideline Development Process Step 1: Identification of Clinical Questions Trained guideline participants were asked to submit a list of clinical questions that the guideline should address. The lists were compiled into a master list, which was then circulated to each member with a request that they independently rank the questions in order of importance for consideration in the guideline. The most highly ranked questions, as determined by the participants, served to focus the guideline. Step 2: Identification of Work Groups Multidisciplinary teams were assigned to work groups and assigned specific clinical questions to address. Because NASS is comprised of surgical, medical and interventional specialists, it is imperative to the guideline development process that a crosssection of NASS membership is represented on each group. This also helps to ensure that the potential for inadvertent biases in evaluating the literature and formulating recommendations is minimized. Step 3: Identification of Search Terms and Parameters One of the most crucial elements of evidence analysis to support development of recommendations for appropriate clinical care is the comprehensive litera-

27 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 7 ture search. Thorough assessment of the literature is the basis for the review of existing evidence and the formulation of evidence-based recommendations. In order to ensure a thorough literature search, NASS has instituted a Literature Search Protocol (Appendix D) which has been followed to identify literature for evaluation in guideline development. In keeping with the Literature Search Protocol, work group members have identified appropriate search terms and parameters to direct the literature search. Specific search strategies, including search terms, parameters and databases searched, are documented in the appendices (Appendix E). Step 4: Completion of the Literature Search Once each work group identified search terms/parameters, the literature search was implemented by a medical/research librarian, consistent with the Literature Search Protocol. Following these protocols ensures that NASS recommendations (1) are based on a thorough review of relevant literature; (2) are truly based on a uniform, comprehensive search strategy; and (3) represent the current best research evidence available. NASS maintains a search history in Endnote, for future use or reference. Step 5: Review of Search Results/ Identification of Literature to Review Work group members reviewed all abstracts yielded from the literature search and identified the literature they will review in order to address the clinical questions, in accordance with the Literature Search Protocol. Members have identified the best research evidence available to answer the targeted clinical questions. That is, if Level I, II and or III literature is available to answer specific questions, the work group was not required to review Level IV or V studies. Work group members reviewed the evidence on the topic of cervical radiculopathy, and studies eligible for review were required to address radiculopathy alone or include a subgroup analysis of patients with radiculopathy. Many of the studies considered for potential inclusion in this guideline included groups of patients with myelopathy, without appropriate subgroup analyses of those patients with cervical radiculopathy alone. For this reason, in the absence of subgroup analyses, a large number of studies were excluded from consideration in addressing the questions and formulating recommendations. These studies, having been reviewed, are included in the reference sections. Step 6: Evidence Analysis Members have independently developed evidentiary tables summarizing study conclusions, identifying strengths and weaknesses and assigning levels of evidence. In order to systematically control for potential biases, at least two work group members have reviewed each article selected and independently assigned levels of evidence to the literature using the NASS levels of evidence. Any discrepancies in scoring have been addressed by two or more reviewers. The consensus level (the level upon which two-thirds of reviewers were in agreement) was then assigned to the article. As a final step in the evidence analysis process, members have identified and documented gaps in the evidence to educate guideline readers about where evidence is lacking and help guide further needed research by NASS and other societies. Step 7: Formulation of Evidence-Based Recommendations and Incorporation of Expert Consensus Work groups held webcasts to discuss the evidencebased answers to the clinical questions, the grades of recommendations and the incorporation of expert consensus. Expert consensus has been incorporated only where Level I-IV evidence is insufficient and the work group has deemed that a recommendation is warranted. Transparency in the incorporation of consensus is crucial, and all consensus-based rec-

28 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 8 ommendations made in this guideline very clearly indicate that Level I-IV evidence is insufficient to support a recommendation and that the recommendation is based only on expert consensus. Consensus Development Process Voting on guideline recommendations was conducted using a modification of the nominal group technique in which each work group member independently and anonymously ranked a recommendation on a scale ranging from 1 ( extremely inappropriate ) to 9 ( extremely appropriate ). Consensus was obtained when at least 80% of work group members ranked the recommendation as 7, 8 or 9. When the 80% threshold was not attained, up to three rounds of discussion and voting were held to resolve disagreements. If disagreements were not resolved after these rounds, no recommendation was adopted. After the recommendations were established, work group members developed the guideline content, addressing the literature which supports the recommendations. Step 8: Submission of the Draft Guidelines for Review/Comment Guidelines were submitted to the full Evidence- Based Guideline Development Committee and the Research Council Director for review and comment. Revisions to recommendations were considered for incorporation only when substantiated by a preponderance of appropriate level evidence. Step 9: Submission for Board Approval Once any evidence-based revisions were incorporated, the drafts were prepared for NASS Board review and approval. Edits and revisions to recommendations and any other content were considered for incorporation only when substantiated by a preponderance of appropriate level evidence. Step 10: Submission for Endorsement, Publication and National Guideline Clearinghouse (NGC) Inclusion Following NASS Board approval, the guidelines have been slated for publication, submitted for endorsement to all appropriate societies and submitted for inclusion in the National Guidelines Clearinghouse (NGC). No revisions were made at this point in the process, but comments have been and will be saved for the next iteration. Step 11: Identification and Development of Performance Measures The recommendations will be reviewed by a group experienced in performance measure development (eg, the AMA Physician s Consortium for Performance Improvement) to identify those recommendations rigorous enough for measure development. All relevant medical specialties involved in the guideline development and at the Consortium will be invited to collaborate in the development of evidence-based performance measures related to spine care. Step 12: Review and Revision Process The guideline recommendations will be reviewed every three years by an EBM-trained multidisciplinary team and revised as appropriate based on a thorough review and assessment of relevant literature published since the development of this version of the guideline. Use of Acronyms Throughout the guideline, readers will see many acronyms with which they may not be familiar. A glossary of acronyms is available in Appendix A. Nomenclature for Medical/Interventional Treatment Throughout the guideline, readers will see that what has traditionally been referred to as nonoperative, nonsurgical or conservative care is now referred to as medical/interventional care. The term medical/interventional is meant to encompass pharmacological treatment, physical therapy, exercise therapy, manipulative therapy, modalities, various types of external stimulators and injections.

29 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 9 III. Definition and Natural History of Cervical Radiculopathy from Degenerative Disorders What is the best working definition of cervical radiculopathy from degenerative disorders? Cervical radiculopathy from degenerative disorders can be defined as pain in a radicular pattern in one or both upper extremities related to compression and/or irritation of one or more cervical nerve roots. Frequent signs and symptoms include varying degrees of sensory, motor and reflex changes as well as dysesthesias and paresthesias related to nerve root(s) without evidence of spinal cord dysfunction (myelopathy). Work Group Consensus Statement What is the natural history of cervical radiculopathy from degenerative disorders? To address the natural history of cervical radiculopathy from degenerative disorders, the work group performed a comprehensive literature search and analysis. The group reviewed 31 articles that were selected from a search of MEDLINE (PubMed), Cochrane Register of Controlled Trials, Web of Science and EMBASE Drugs & Pharmacology. However, all identified studies failed to meet the guideline s inclusion criteria because they did not ade-quately present data about the natural history of cervical radiculopathy. The plurality of studies did not report results of untreated patients, thus limiting conclusions about natural history. This includes works that have been frequently cited as so-called natural history studies but are in fact reports of the results of one or more medical/interventional treatment measures. 5,12,18,22,28 In other investigations, data were reported for untreated and conservatively-treated patients together without an analysis specific to the untreated group. Other commonly cited studies did not report subgroup analyses of patients with cervical radiculopathy alone and thereby presented generalized natural history data regarding a heterogeneous cohort of patients with isolated neck pain, cervical radiculopathy or cervical myelopathy. Because of the limitations of available literature, the work group was unable to definitively answer the question posed related to the natural history of cervical radiculopathy from degenerative disorders. In lieu of an evidence-based answer, the work group did reach consensus on the following statement addressing natural history. It is likely that for most patients with cervical radiculopathy from degenerative disorders signs and symptoms will be self-limited and will resolve spontaneously over a variable length of time without specific treatment. Work Group Consensus Statement Future Directions for Research The work group identified the following potential studies, which could generate meaningful evidence to assist in further defining the natural history of cervical radiculopathy from degenerative disorders. Recommendation #1: A prospective study of patients with cervical radiculopathy from degenerative disorders without treatment, notwithstanding nonprescription analgesics, would provide Level I evidence regarding the natural history of this disorder. Recommendation #2: A systematic study of patients with untreated cer-

30 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 10 vical radiculopathy from degenerative disorders would provide evidence regarding the natural history of the disease in this patient population. Natural History References 1. Anderberg L, Annertz M, Persson L, Brandt L, Saveland H. Transforaminal steroid injections for the treatment of cervical radiculopathy: a prospective and randomised study. Eur Spine J. Mar 2007;16(3): Carette S, Fehlings MG. Clinical practice. Cervical radiculopathy. N Engl J Med. Jul ;353(4): Garvey TA, Eismont FJ. Diagnosis and treatment of cervical radiculopathy and myelopathy. Orthop Rev. Jul 1991;20(7): Gore DR, Carrera GF, Glaeser ST. Smoking and degenerative changes of the cervical spine: a roentgenographic study. Spine J. Sep-Oct 2006;6(5): Gore DR, Sepic SB, Gardner GM, Murray MP. Neck pain: a long-term follow-up of 205 patients. Spine. Jan-Feb 1987;12(1): Hamalainen O, Toivakka-Hamalainen SK, Kuronen P. +Gz associated stenosis of the cervical spinal canal in fighter pilots. Aviat Space Environ Med. Apr 1999;70(4): Harrop JS, Hanna A, Silva MT, Sharan A. Neurological manifestations of cervical spondylosis: an overview of signs, symptoms, and pathophysiology. Neurosurgery. Jan 2007;60(1 Supp1 1):S Healy JF, Healy BB, Wong WH, Olson EM. Cervical and lumbar MRI in asymptomatic older male lifelong athletes: frequency of degenerative findings. J Comput Assist Tomogr. Jan-Feb 1996;20(1): Hendriksen IJ, Holewijn M. Degenerative changes of the spine of fighter pilots of the Royal Netherlands Air Force (RNLAF). Aviat Space Environ Med. Nov 1999;70(11): Humphreys SC, Hodges SD, Patwardhan A, Eck JC, Covington LA, Sartori M. The natural history of the cervical foramen in symptomatic and asymptomatic individuals aged years as measured by magnetic resonance imaging. A descriptive approach. Spine. Oct ;23(20): Kang JD, Stefanovic-Racic M, McIntyre LA, Georgescu HI, Evans CH. Toward a biochemical understanding of human intervertebral disc degeneration and herniation. Contributions of nitric oxide, interleukins, prostaglandin E2, and matrix metalloproteinases. Spine. May ;22(10): Lees F, Turner JW. Natural history and prognosis of cervical spondylosis. Br Med J. Dec ;2(5373): Murphey F, Simmons JC, Brunson B. Chapter 2. Ruptured cervical discs, 1939 to Clin Neurosurg. 1973;20: Murphy DR, Hurwitz EL, Gregory A, Clary R. A nonsurgical approach to the management of patients with cervical radiculopathy: A prospective observational cohort study. J Manipulative Physiol Ther. May 2006;29(4): Peng B, Hao J, Hou S, et al. Possible pathogenesis of painful intervertebral disc degeneration. Spine. Mar ;31(5): Petren-Mallmin M, Linder J. Cervical spine degeneration in fighter pilots and controls: a 5-yr follow-up study. Aviat Space Environ Med. May 2001;72(5): Petren-Mallmin M, Linder J. MRI cervical spine findings in asymptomatic fighter pilots. Aviat Space Environ Med. Dec 1999;70(12): Radhakrishnan K, Litchy WJ, O Fallon WM, Kurland LT. Epidemiology of cervical radiculopathy. A populationbased study from Rochester, Minnesota, 1976 through Brain. Apr 1994;117 ( Pt 2): Rao R. Neck pain, cervical radiculopathy, and cervical myelopathy: pathophysiology, natural history, and clinical evaluation. J Bone Joint Surg Am. Oct 2002;84-A(10): Ross JS, Modic MT, Masaryk TJ, Carter J, Marcus RE, Bohlman H. Assessment of extradural degenerative disease with Gd-DTPA-enhanced MR imaging: correlation with surgical and pathologic findings. AJR Am J Roentgenol. Jan 1990;154(1): Rubin D. Cervical radiculitis: diagnosis and treatment. Arch Phys Med Rehabil. Dec 1960;41: Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine. Aug 1996;21(16): Sambrook PN, MacGregor AJ, Spector TD. Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum. Feb 1999;42(2): Sampath P, Bendebba M, Davis JD, Ducker T. Outcome in patients with cervical radiculopathy. Prospective, multicenter study with independent clinical review. Spine. Mar ;24(6): Swezey RL. Conservative treatment of cervical radiculopathy. J Clin Rheumatol. Apr 1999;5(2): Teresi LM, Lufkin RB, Reicher MA, et al. Asymptomatic degenerative disk disease and spondylosis of the cervical spine: MR imaging. Radiology. Jul 1987;164(1): Van Zundert J, Harney D, Joosten EA, et al. The role of the dorsal root ganglion in cervical radicular pain: diagnosis, pathophysiology, and rationale for treatment. Reg Anesth Pain Med. Mar-Apr 2006;31(2): Wainner RS, Gill H. Diagnosis and nonoperative management of cervical radiculopathy. J Orthop Sports Phys Ther. Dec 2000;30(12): Yoo K, Origitano TC. Familial cervical spondylosis. Case report. J Neurosurg. Jul 1998;89(1): Yoshida M, Tamaki T, Kawakami M, Hayashi N, Ando M.

31 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 11 Indication and clinical results of laminoplasty for cervical myelopathy caused by disc herniation with developmental canal stenosis. Spine. Nov 1998;23(22): Zejda JE, Stasiow B. Cervical spine degenerative changes (narrowed intervertebral disc spaces and osteophytes) in coal miners. Int J Occup Med Environ Health. 2003;16(1):49-53.

32 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 12 IV. Recommendations for Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders A. Diagnosis and Imaging What history and physical examination findings best support a diagnosis of cervical radiculopathy from degenerative disorders? RECOMMENDATION: It is suggested that the diagnosis of cervical radiculopathy be considered in patients with arm pain, neck pain, scapular or periscapular pain, and paresthesias, numbness and sensory changes, weakness, or abnormal deep tendon reflexes in the arm. These are the most common clinical findings seen in patients with cervical radiculopathy. Grade of Recommendation: B Henderson et al 30 presented findings of a retrospective observational study reporting results of PLF in the treatment of 736 patients with cervical radiculopathy. Patients included in the study reported the following symptoms: arm pain (99.4%), neck pain (79.7%), scapular pain (52.5%), anterior chest pain (17.8%) and headache (9.7%). Eleven patients presented with only left chest and arm pain ( cervical angina ). Pain or paresthesia in a dermatomal pattern was reported by 53.9% of patients, while 45.5% experienced pain or paresthesia in a diffuse or nondermatomal pattern. No pain or paresthesia was reported by 0.6% of patients. Of patients included in the study, 85.2% reported a sensory change to pinprick, 68% had a specific motor deficit and 71.2% had a specific decrease in a DTR. One nerve root level was thought to be primarily responsible for symptoms in 87.3% of patients and two levels were felt to be equally involved for the remaining 12.7%. The correlation between pain/paresthesia, motor deficit, DTR change and the primary operative level was 73.8%, 84.8% and 83.5%, respectively. There was a 71.5% incidence of correlation between preoperative clinical findings and operative findings. Good or excellent results were reported by 91.5% of patients. Good or excellent relief of arm pain was found in 95.5% of patients, neck pain in 88.8%, scapular pain in 95.9%, chest pain in 95.4% and headache in 89.8%. Resolution of DTR abnormalities was reported in 96.9%. Residual sensory deficit was found in 20.9% of patients and motor deficit in 2.3%. In a large group of patients with cervical radiculopathy, this study elucidates the common clinical findings of pain, paresthesia, motor deficit and decreased DTRs, along with their respective frequencies. These data present evidence that the surgical site can be accurately predicted on the basis of clinical findings 71.5% of the time. In critique, no validated outcome measures were used in the study. Thus, it provides Level II evidence that 71.5% of the time, the surgical site can be accurately predicted on the basis of clinical findings. Jenis et al 31 described a retrospective case series reporting the results of surgical intervention in 11 cervical radiculopathy patients with neck pain from C4 radiculopathy. Pain was localized to the posterior aspect of the neck and lateralized to the side with C4 root involvement. Pain was also reported in trapezial areas and upper extremities depending on the presence of more caudal radiculopathies. Neck pain was exacerbated by flexion and extension in all patients. Decreased sensation in the C4 dermatome was present in all patients. MRI was obtained in all patients and CT scan in three patients prior to surgery. Excluding a single myelopathic patient, four patients were treated with anterior cervical discectomy and fusion (ACDF) and seven with posterior

33 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 13 foraminotomy (PLF). Evaluating fusion status, pain relief and level of activity based on Odom s criteria, good or excellent results were obtained in 10 of the 11 patients. The authors concluded that patients with neck pain should be evaluated for C4 radiculopathy, the examination should include C4 sensory testing, and neck pain from C4 radiculopathy can respond to surgical decompression unlike neck pain arising from degenerative disc disease. In critique, no validated outcome measures were used and the sample size was small. This study provides Level IV evidence that neck pain with or without upper extremity clinical findings should prompt evaluation for a C4 radiculopathy and that this evaluation should include C4 sensory testing. Post et al 38 reported a retrospective case series reviewing experience with the surgical management of a series of 10 patients with C7-T1 herniations. Symptoms included shoulder pain radiating into the lateral aspect of the hand, hand weakness and weakness in finger flexion, finger extension and intrinsic hand muscles. Sensation and DTRs were unremarkable. MRI on each patient revealed a soft disc compressing the C8 nerve root. Recovery of hand strength was noted in each patient; however, recovery was incomplete in two patients with symptoms greater than four months. In critique, no validated outcome measures were used and the sample size was small. This study provides Level IV evidence that C8 radiculopathy usually presents as weakness of the hand and pain radiating to shoulder, scapular area, and to the fourth and fifth fingers. Physical exam may reveal normal sensation and DTRs. Motor examination may show weakness of finger flexion and extension and weakness of the intrinsic muscles of the hand. Tanaka et al 48 described a prospective observational study examining whether or not pain in the neck or scapular regions in 50 consecutive patients with cervical radiculopathy originated from a compressed nerve root, and whether the site of pain is useful for identifying the level involved. Patients underwent single level nerve root decompression using a posterior open foraminotomy. The surgical level was determined by correlation of symptoms and imaging, with selective nerve root block (SNRB) in five patients. Cervical disc herniation (CDH) was found in 20 patients and stenosis in 30. Neck or scapular pain preceeded the arm/finger symptoms in 35 patients (70%) and was relieved early in 46 (92%). When the pain was suprascapular, C5 or C6 radiculopathy was frequent; when interscapular, C7 or C8 radiculopathy was frequent; and when scapular, C8 was frequent. Arm and finger symptoms improved significantly in all groups after decompression. Sixty-one painful sites were noted before surgery: one in 39 patients and two in 11 patients. One month after surgery, 27 patients reported complete pain relief, 23 complained of pain in 24 subregions, seven of which were the same as before surgery. Seventeen pain sites were new since surgery. All but one new site were nuchal and suprascapular. At one year follow-up, 45 patients reported no pain, five patients had pain in six sites, three of which were the same as before surgery. The authors concluded that pain in the suprascapular, interscapular or scapular regions can orginate from a compressed cervical nerve root and is valuable for determing the nerve root involved. This study provides Level I evidence that cervical radiculopathy at C5, C6, C7 and C8 frequently causes pain in suprascapular, interscapular and scapular areas and is useful in determining the level of nerve root involvement. Pain in the suprascapular region suggests C5 or C6 radiculopathy, pain in the interscapular region suggests C7 or C8 radiculopathy, and pain in the scapular region suggests C8 radiculopathy. Yoss et al 55 conducted a retrospective observational study of 100 patients to correlate clinical findings with surgical findings when a single cervical nerve root (C5, C6, C7, C8) is compressed by a disc herniation. Symptoms included pain in the neck, shoulder,

34 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 14 scapular or interscapular regions, arm, forearm or hand; paresthesias in forearm, and hand; and weakness of upper extremity. Signs included diminution of triceps, biceps and brachioradialis reflexes, muscle weakness and sensory loss. Pain or paresthesia in the neck, shoulder, scapular or interscapular region were present in cases of C5, C6, C7 or C8 compression. The presence of pain in the arm corresponded to the site compression in 23% of cases. The presence of pain or paresthesia in the forearm corresponded to a single root or one of two roots in 32% and 66%, respectively. Hand pain and paresthesia corresponded to a single root or one of two roots in 70% and 27%, respectively. Subjective weakness corresponded to a single level in 22/34 (79%) cases. When a diminution of DTR was present, the lesion could be correctly localized to a single level or one of two levels in 11% and 82%, respectively. Objective muscle weakness corresponded to a single root or one of two roots in 77% and 12%, respectively. In all cases in which the C5 and C8 nerve root was involved and objective weakness was present, the level was correctly localized. Sensory loss corresponded to a single root or one of two roots in 65% and 35%, respectively. The authors concluded that clinical findings related to the fingers are the most accurate for localizing a CDH to a single level. A single level CDH may produce signs and symptoms that correspond to overlapping dermatomal levels. This study provides Level II evidence that clinical findings related to the fingers are the most accurate for localizing a CDH to a single level. Single level CDH may produce signs and symptoms that correspond to overlapping dermatomal levels. RECOMMENDATION: It is suggested that the diagnosis of cervical radiculopathy be considered in patients with atypical findings such as deltoid weakness, scapular winging, weakness of the intrinsic muscles of the hand, chest or deep breast pain, and headaches. Atypical symptoms and signs are often present in patients with cervical radiculopathy, and can improve with treatment. Grade of Recommendation: B Henderson et al 30 presented findings of a retrospective observational study reporting results of PLF in the treatment of 736 patients with cervical radiculopathy. Patients included in the study reported the following symptoms: arm pain (99.4%), neck pain (79.7%), scapular pain (52.5%), anterior chest pain (17.8%) and headache (9.7%). Eleven patients presented with only left chest and arm pain ( cervical angina ). Pain or paresthesia in a dermatomal pattern was reported by 53.9% of patients, while 45.5% experienced pain or paresthesia in a diffuse or nondermatomal pattern. No pain or paresthesia was reported by 0.6% of patients. Of patients included in the study, 85.2% reported a sensory change to pinprick, 68% had a specific motor deficit and 71.2% had a specific decrease in a DTR. One nerve root level was thought to be primarily responsible for symptoms in 87.3% of patients and two levels were felt to be equally involved for the remaining 12.7%. The correlation between pain/paresthesia, motor deficit, DTR change and the primary surgical level was 73.8%, 84.8% and 83.5%, respectively. There was a 71.5% incidence of correlation between presurgical clinical findings and surgical findings. Good or excellent results were reported by 91.5% of patients. Good or excellent relief of arm pain was found in 95.5% of patients, neck pain in 88.8%, scapular pain in 95.9%, chest pain in 95.4% and headache in 89.8%. Resolution of DTR abnormalities was reported in 96.9%. Residual sensory deficit was found in 20.9% of patients and motor deficit in 2.3%. In a large group of patients with cervical radiculopathy, this study elucidates the common clinical findings of pain, paresthesia, motor deficit, and decreased DTRs, along with their respective frequencies. These data present evidence that the operative site can be accurately predicted on the basis of clinical findings 71.5% of the time.

35 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 15 In critique, no validated outcome measures were used in the study. Thus, it provides Level II evidence that 71.5% of the time, the operative site can be accurately predicted on the basis of clinical findings. Chang et al 13 described a retrospective case series identifying the characteristics of cervical radiculopathy causing deltoid paralysis, and reporting on the surgical outcomes of ACDF for the treatment of deltoid paralysis. All 14 patients had pain radiating to the scapula, shoulder or arm, with weakness of shoulder abduction due to paralysis of deltoid (graded 0-5). Severity of radicular pain was graded on a visual analog scale (VAS) from zero to 10. Plain radiographs and MRI were correlated with clinical findings. Surgery was performed on patients with single level CDH or cervical spondylotic radiculopathy (CSR). Patients with multilevel disease were excluded. The following lists the single levels implicated in deltoid paralysis and their respective frequencies: 1-C3-4 CDH (central), 4-C4-5 CDH, 1-C5-6 CDH, 3-C4-5 CSR, 5-C5-6 CSR. Both radiculopathy and deltoid paralysis improved significantly with surgery. The authors found that a painful cervical radiculopathy with deltoid paralysis arose from the C4-5, C5-6 and C3-4 levels in 50%, 43% and 7% of the cases, respectively. This small study provides Level IV evidence that a painful cervical radiculopathy with deltoid paralysis can arise from compressive disease at the C4-5, C5-6 or C3-4 levels. Makin et al 34 reported a retrospective case series of six patients with scapular winging as a finding with C7 radiculopathy. Scapular winging from serratus anterior weakness was detected by pushing forward against a wall with the hands at shoulder level or with the hands at waist level. The latter method places the serratus anterior muscle at a mechanical disadvantage and reveals partial paralysis. Each case of C7 compression was confirmed by surgical findings or by CT myelography. The authors concluded that scapular winging may be a component of C7 radiculopathy and when present serves to exclude lesions of the brachial plexus or radial nerve. This small study provides Level IV evidence that scapular winging can be a feature of C7 radiculopathy. Ozgur et al 35 described a retrospective case series of the presenting symptomatology of 241 consecutive patients following C6-7 discectomy. Of the patients, 83% had typical C7 radicular signs while 17% had atypical symptoms, 12% reporting isolated subscapular pain and 5% deep breast or chest pain. The authors reported that patients presenting with atypical symptoms had correlative pathology confirmed by surgical findings, 93% of whom experienced symptom relief. This study provides Level IV evidence that a substantial percentage of patients may present with atypical symptoms associated with C7 nerve root compression Persson et al 37 conducted a prospective observational study to describe the frequency of headaches in patients with lower level cervical radiculopathy and its response to a selective nerve root block (SNRB). Of 275 patients, 161 suffered from daily or recurrent headaches, most often ipsilateral to the patients radiculopathy. All patients underwent clinical exam and MRI. Patients with significantly compressed nerve roots underwent SNRB. All patients with headaches had tender points in the neck/shoulder region ipsilateral to the radiculopathy. Patients with headache had significantly more limitations in daily activities and higher pain in the neck/shoulder. Immediately before the injections, 161 (59%) of patients experienced a headache exceeding 15 on the VAS. Of these 161 patients, 101 (63%) experienced >25% headache reduction following SNRB, 93 (58%) reported greater than 50% headache reduction, and 66 experienced 100% relief (C4 3%, C5 11%, C6 52%, C7 29%, C8 5%). A significant correlation was found between reduced headache and decreased pain in the neck and shoulder region. The authors concluded that cervical nerve root compression from degenerative disease in the lower cervical spine producing radiculopathy can also result in headache. Thus, headache assessment together with muscle palpation should be part of the clinical exam for patients with cervical radiculopathy.

36 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 16 In critique, the study had a low (50%) threshold and lack of specificity for the injection. Because of these limitations, this potential Level II study provides Level III evidence that complaint of a headache can be a symptom with C4-C8 nerve root compression. SNRB can reduce headache in a substantial percentage of patients and may be a useful diagnostic tool. Post et al 38 reported a retrospective case series reviewing experience with the surgical management of a series of 10 patients with C7-T1 herniations. Symptoms included shoulder pain radiating into the lateral aspect of the hand, hand weakness and weakness in finger flexion, finger extension and intrinsic hand muscles. Sensation and DTRs were unremarkable. MRI on each patient revealed a soft disc compressing the C8 nerve. Recovery of hand strength was noted in each patient; however, recovery was incomplete in two patients with symptoms greater than four months. In critique, no validated outcome measures were used and the sample size was small. This study provides Level IV evidence that C8 radiculopathy can present with weakness of the hand, and pain radiating to the shoulder, scapular area, and fourth and fifth fingers. RECOMMENDATION: Provocative tests including the shoulder abduction and Spurling s tests may be considered in evaluating patients with clinical signs and symptoms consistent with the diagnosis of cervical radiculopathy. Grade of Recommendation: C Davidson et al 16 described observations from a retrospective case series of 22 patients with cervical monoradiculopathy caused by compressive disease in whom clinical signs included relief of pain with abduction of the shoulder. Twenty-two patients with arm pain had cervical extradural myelographic defects. Of the 22 patients, 15 experienced relief from their pain with shoulder abduction. Motor weakness was present in 15, paresthesias in 11 and reflex changes in nine patients. Of the 15 patients with a positive shoulder abduction sign, 13 required surgery and all achieved good results. Two of the 15 had pain relief with conservative therapy. Of the seven patients with negative shoulder abduction signs, five required surgery and two were successfully treated with traction. Of the five surgical patients, three had surgery for a central lesion and improved after surgery, two had surgery for a lateral disc fragment and only one had good results. The authors concluded that the shoulder abduction test is a reliable indicator of significant cervical extradural compressive radicular disease. In critique, no validated outcome measures were used and the sample size was small. This study provides Level III evidence that relief from arm pain with shoulder abduction is an indicator of cervical extradural compressive radiculopathy. Shah et al 45 conducted a prospective observational study to determine the sensitivity and specificity of the Spurling s test in predicting the diagnosis of a soft lateral CDH in 50 patients with neck and arm pain. Spurling s test with cervical extension, lateral flexion to the side of pain, and downward pressure on the head was performed on all patients. Twentyfive patients underwent surgery (Group 1) and 25 were managed conservatively (Group 2). Spurling s test was correlated with surgical findings in Group 1 and with MRI findings in Group 2. Patients with their first episode of radicular pain and minimal or no neurologic deficits, and those who refused surgery were managed conservatively. In Group 1, of the 18 patients with a positive Spurling s test, all had surgically confirmed soft disc herniations. Of seven patients with a negative Spurling s test, two had a soft disc herniation and five had a hard disc. In Group 2, of the 10 patients with a positive Spurling s test, nine had a soft disc herniation, one had a hard disc. Of the 15 patients with a negative Spurling s test, a hard disc was seen in eight, and MRI was normal in seven. The Spurling s test had a sensitivity of 92%, a specificity of 95%, a positive predictive value (PPV) of 96.4% and a negative predictive power (NPP) of 90.9% for a soft disc herniation. The authors concluded that

37 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 17 the high PPV of the test can be used to improve the yield of postivie MRI examinations in patients with cervical radiculopathy. This study provides Level II evidence that a positive Spurling s test improves the clinician s ability to diagnose compressive disease in patients with cervical radiculopathy. Tong et al 49 performed a prospective comparative study to determine the sensitivity and specificity of the Spurling test for 255 patients referred for electrodiagnosis of upper extremity nerve disorders. The Spurling test was performed on all patients before electromyography (EMG). The test was scored as positive if it resulted in pain or tingling starting in the shoulder and radiating distally to the elbow. A differential diagnosis based on the history and physical exam was made prior to EMG. EMG was performed and each diagnosis in the differential was scored relative to the likelihood of its occurrence. Of the 255 patients presented, 31 had missing data, leaving 224 patients for inclusion. Of 20 patients with a positive EMG for cervical radiculopathy, the Spurling s test was positive in seven, for a sensitivity of 7/20 or 30%. Of 172 patients with no EMG evidence for radiculopathy, the Spurling s test was negative in 160, for a specificity of 160/172 or 93%. The Spurling s test was positive in 16.6% of patients with a normal EMG, in 3.4% of patients with an EMG diagnosis of a nerve problem other than radiculopathy, and in 15% of patients with nonspecific EMG findings. The odds ratio of a positive Spurling s test in a patient with a positive EMG for cervical radiculopathy is The authors concluded that the Spurling s test is not sensitive but is specific for cervical radiculopathy as diagnosed by EMG. Although not useful as a screening test, it may be useful to confirm the diagnosis. In critique, the study uses a poor reference standard (EMG). This study provides Level IV evidence that the Spurling s test is not sensitive but is specific for cervical radiculopathy as diagnosed by EMG. Thus, a positive Spurling s test is clinically useful in helping confirm the presence of cervical radiculopathy. Wainner et al 51 described a prospective comparative study assessing the reliability and accuracy of individual clinical exam items and self reported instruments for the diagnosis of cervical radiculopathy in 82 patients with a goal of identifying and assessing the accuracy of an optimal cluster of test items. Consecutive patients were referred for EMG for the evaluation of cervical radiculopathy or carpal tunnel syndrome. Only patients judged by one of seven laboratory providers to have signs and symptoms compatible with CR or CTS were eligible to participate. Patients with Class 5 or 6 cervical radiculopathy findings were further classified according to the severity of their EMG findings. Self-reported items included the VAS and NDI. A standardized clinical exam was performed by two of nine physical therapists and contained 34 items. History contained six questions asked by two physical therapists. Neurological exam included strength, DTRs and sensation. Provocative tests included Spurling s test, shoulder abduction test, Valsalva maneuver, neck distraction test and the upper limb tension test (ULTT). Cervical range of motion was also measured. Fifteen patients had an EMG diagnosis of cervical radiculopathy, and five patients were diagnosed with cervical radiculopathy and carpal tunnel sydrome, one with concomitant ulnar neuropathy. One patient with combined findings dropped out of the study. Of the 19 patients reported, 13 had mild symptoms and six had moderate symptoms. Reliability of different clinical items was reported including the Spurling s A/B 0.6/0.62, shoulder abduction 0.2, valsalva 0.69, distraction 0.88, ULTT A/B 0.76/0.83. Sensitivity/ specificity: Spurling s A/B 0.6/0.62, shoulder abduction 0.2, valsalva 0.69, distraction 0.88, ULTT A/B 0.76/0.83. Sensitivity/Specificity of different clinical items was reported including the Spurling s A/B - 0.5/ ; shoulder abduction /0.92; valsalva -.22/.94; distraction /0.9; ULTT A/B / ; Cluster of ULTT A, cervical rotation <60degrees, distraction, and Spurling s A /0.99. The authors concluded that many items were found to have at least a fair level of reliability

38 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 18 and to have acceptable diagnostic properties. The test item cluster identified was found to be the most useful. In critique, the small study utilized EMG as a gold standard with an apparent test selection bias. Because of these limitations, this potential Level III study provides Level IV evidence that provocative tests, including the Spurling s test, shoulder abduction test, Valsalva and distraction test had a low sensitivity but high specificity for cervical radiculopathy as diagnosed by EMG. Bertilson et al 11 reported a prospective case series analyzing the reliability of clinical tests, including provocative maneuvers, in the assessment of neck and arm pain in 100 primary care patients. Reliability of clinical tests was poor to fair in several test categories. Only a bimanual sensitivity test reached good values. However, when the examiner knows the clinical history, the prevalence of positive findings increased in 80% of test categories. Bias was apparent in all test categories except for sensitivity. The authors concluded that sensitivity testing was the most reliable and was exempt from bias. Knowledge of the patient s history had no impact on reliability, however it increased the incidence of positive findings. In critique, patients were not enrolled at the same point in their disease and there were only two reviewers. Because of these limitations, this potential Level I study provides Level II evidence that history and physical findings are not definitive, that the incidence of positive findings can increase with known history, and that several categories may be susceptable to bias with a suggestive clinical history. RECOMMENDATION: Because dermatomal arm pain alone is not specific in identifying the pathologic level in patients with cervical radiculopathy, further evaluation including CT, CT myelography, or MRI is suggested prior to surgical decompression. Grade of Recommendation: B Henderson et al 30 presented findings of a retrospective observational study reporting results of PLF in the treatment of 736 patients with cervical radiculopathy. Patients included in the study reported the following symptoms: arm pain (99.4%), neck pain (79.7%), scapular pain (52.5%), anterior chest pain (17.8%) and headache (9.7%). Eleven patients presented with only left chest and arm pain ( cervical angina ). Pain or paresthesia in a dermatomal pattern was reported by 53.9% of patients, while 45.5% experienced pain or paresthesia in a diffuse or nondermatomal pattern. No pain or paresthesia was reported by 0.6% of patients. Of patients included in the study, 85.2% reported a sensory change to pinprick, 68% had a specific motor deficit and 71.2% had a specific decrease in a DTR. One nerve root level was thought to be primarily responsible for symptoms in 87.3% of patients and two levels were felt to be equally involved for the remaining 12.7%. The correlation between pain/paresthesia, motor deficit, DTR change and the primary operative level was 73.8%, 84.8% and 83.5%, respectively. There was a 71.5% incidence of correlation between preoperative clinical findings and operative findings. Good or excellent results were reported by 91.5% of patients. Good or excellent relief of arm pain was found in 95.5% of patients, neck pain in 88.8%, scapular pain in 95.9%, chest pain in 95.4% and headache in 89.8%. Resolution of DTR abnormalities was reported in 96.9%. Residual sensory deficit was found in 20.9% of patients and motor deficit in 2.3%. In a large group of patients with cervical radiculopathy, this study elucidates the common clinical findings of pain, paresthesia, motor deficit, and decreased DTRs, along with their respective frequencies. These data present evidence that the surgical site can be accurately predicted on the basis of clinical findings 71.5% of the time. In critique, no validated outcome measures were used in the study. Thus, it provides Level II evidence that 71.5% of the time, the operative site can be accurately predicted on the basis of clinical findings.

39 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 19 Slipman et al 46 described a prospective observational study evaluating the distribution of pain and paresthesias that result from the stimulation of specific cervical nerve roots in 87 patients with 134 selective nerve root stimulations. Mechanical stimulation of nerve roots was carried out: four at C4, 14 at C5; 43 at C6; 52 at C7; and 21 at C8. An independent observer recorded the location of provoked symptoms on a pain diagram. Visual data was compiled using a 793 body sector bit map with 43 body regions identified. Although the distribution of symptom provocation resembled the classic dermatomal maps, symptoms were frequently provoked outside the classic descriptions. The authors concluded that there was a distinct difference between the dynatomal and dermatomal maps. This study provides Level I evidence that distribution of pain and paresthesias in the arm from nerve root stimulation can be different from traditional dermatomal maps in a substantial percentage of patients making it difficult to identify the level based on pain distribution. Yoss et al 55 conducted a retrospective observational study of 100 patients to correlate clinical findings with surgical findings when a single cervical nerve root (C5, C6, C7, C8) is compressed by a disc herniation. Symptoms included pain in the neck, shoulder, scapular or interscapular region, arm, forearm or hand; paresthesias in forearm, and hand; and weakness of upper extremity. Signs included diminution of triceps, biceps and brachioradialis reflexes, muscle weakness and sensory loss. Pain or paresthesia in the neck, shoulder, scapular or interscapular region were present in cases of C5, C6, C7, or C8 compression. The presence of pain in the arm corresponded to the site compression in 23% of cases. The presence of pain or paresthesia in the forearm corresponded to a single root or one of two roots in 32% and 66%, respectively. Hand pain and paresthesia corresponded to a single root or one of two roots in 70% and 27%, respectively. Subjective weakness corresponded to a single level in 22/34 (79%) cases. When a diminution of DTR was present, the lesion could be correctly localized to a single level or one of two levels in 11% and 82%, respectively. Objective muscle weakness corresponded to a single root or one of two roots in 77% and 12%, respectively. In all cases in which C5 or C8 radiculopathy was accompanied by weakness, the level was correctly localized. Sensory loss corresponded to a single root or one of two roots in 65% and 35%, respectively. The authors concluded that clinical findings related to the fingers are the most accurate for localizing a CDH to a single level. A single level CDH may produce signs and symptoms that correspond to overlapping dermatomal levels. This study provides Level II evidence that clinical findings related to the fingers are the most accurate for localizing a CDH to a single level. Single level CDH may produce signs and symptoms that correspond to overlapping dermatomal levels. Future Directions for Research Further studies are needed to demonstrate the PPV of specific symptoms and physical exam findings in patients with confirmed cervical radiculopathy to demonstrate their usefulness in predicting a good outcome with conservative or surgical treatment. History and Physical Exam Findings References 1. Abbed KM, Coumans JV. Cervical radiculopathy: pathophysiology, presentation, and clinical evaluation. Neurosurgery. Jan 2007;60(1 Supp1 1):S Al-Hami S. Cervical monosegmental interbody fusion using titanium implants in degenerative, intervertebral disc disease. Minim Invasive Neurosurg. Mar 1999;42(1): An HS. Cervical root entrapment. Hand Clin. Nov 1996;12(4): Anderberg L, Annertz M, Brandt L, Saveland H. Selective diagnostic cervical nerve root block--correlation with clinical symptoms and MRI-pathology. Acta Neurochir (Wien). Jun 2004;146(6): ; discussion Anderberg L, Annertz M, Rydholm U, Brandt L, Saveland H. Selective diagnostic nerve root block for the evaluation of radicular pain in the multilevel degenerated cervical spine. Eur Spine J. Jun 2006;15(6): Anderson PA, Subach BR, Riew KD. Predictors of outcome after anterior cervical discectomy and fusion: a multivariate analysis. Spine. Jan ;34(2):

40 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Bartleson JD. Spine Disorder Case Studies. Neurologic Clinics. May 2006;24(2): Beatty RM, Fowler FD, Hanson EJ, Jr. The abducted arm as a sign of ruptured cervical disc. Neurosurgery. Nov 1987;21(5): Bell GR. The anterior approach to the cervical spine. Neuroimaging Clin N Am. 1995;5(3): Bertalanffy H, Eggert HR. Clinical long-term results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. A follow-up of 164 cases. Acta Neurochirurgica (Wien). 1988;90(3-4): Bertilson BC, Grunnesjo M, Strender LE. Reliability of clinical tests in the assessment of patients with neck/shoulder problems-impact of history. Spine (Phila Pa 1976). Oct ;28(19): Bucciero A. Myeloradicular damage in traumatic cervical disc herniation. J Neurosurg Sci. 1998;42(4): Chang H, Park JB, Hwang JY, Song KJ. Clinical analysis of cervical radiculopathy causing deltoid paralysis. Eur Spine J. Oct 2003;12(5): Chen TY. The clinical presentation of uppermost cervical disc protrusion. Spine ;25(4): Connell MD, Wiesel SW. Natural history and pathogenesis of cervical disk disease. Orthop Clin North Am. 1992;23(3): Davidson RI, Dunn EJ, Metzmaker JN. The shoulder abduction test in the diagnosis of radicular pain in cervical extradural compressive monoradiculopathies. Spine (Phila Pa 1976). Sep-Oct 1981;6(5): Deshmukh VR, Rekate HL, Sonntag VKH. High cervical disc herniation presenting with C-2 radiculopathy: Case report and review of the literature. J Neurosurg. Mar 2004;100(3 SUPPL.): Devereaux M. Neck Pain. Med Clin North Am. March 2009;93(2): Dubuisson A, Lenelle J, Stevenaert A. Soft cervical disc herniation: A retrospective study of 100 cases. Acta Neurochir (Wien). 1993;125(1-4): Ellenberg MR, Honet JC, Treanor WJ. Cervical radiculopathy. Arch Phys Med Rehabil. Mar 1994;75(3): Farmer JC, Wisneski RJ. Cervical spine nerve root compression: An analysis of neuroforaminal pressures with varying head and arm positions. Spine. 1994;19(16): Garvey TA, Eismont FJ. Diagnosis and treatment of cervical radiculopathy and myelopathy. Orthop Rev. Jul 1991;20(7): Gifford L. Acute low cervical nerve root conditions: symptom presentations and pathobiological reasoning. Man Ther. May 2001;6(2): Goldstein B. Anatomic issues related to cervical and lumbosacral radiculopathy. Phys Med Rehabil Clin N Am. Aug 2002;13(3): Grisoli F, Graziani N, Fabrizi AP, Peragut JC, Vincentelli F, Diaz-Vasquez P. Anterior discectomy without fusion for treatment of cervical lateral soft disc extrusion: A followup of 120 cases. Neurosurgery. 1989;24(6): Hardin JG, Halla JT. Cervical spine and radicular pain syndromes. Curr Opin Rheumatol. Mar 1995;7(2): Heckmann JG, Lang CJG, Zobelein I, Laumer R, Druschky A, Neundorfer B. Herniated cervical intervertebral discs with radiculopathy: An outcome study of conservatively or surgically treated patients. J Spinal Disord. 1999;12(5): Heidecke V, Rainov NG, Marx T, Burkert W. Outcome in Cloward anterior fusion for degenerative cervical spinal disease. Acta Neurochir (Wien). 2000;142(3): Heller JG. The syndromes of degenerative cervical disease. Orthop Clin North Am. 1992;23(3): Henderson CM, Hennessy RG, Shuey HM, Jr., Shackelford EG. Posterior-lateral foraminotomy as an exclusive operative technique for cervical radiculopathy: a review of 846 consecutively operated cases. Neurosurgery. Nov 1983;13(5): Jenis LG, An HS. Neck pain secondary to radiculopathy of the fourth cervical root: an analysis of 12 surgically treated patients. J Spinal Disord. Aug 2000;13(4): Kuijper B, Tans JTJ, Schimsheimer RJ, et al. Degenerative cervical radiculopathy: Diagnosis and conservative treatment. A review. Eur J Neurol. January 2009;16(1): Lauder TD. Physical examination signs, clinical symptoms, and their relationship to electrodiagnostic findings and the presence of radiculopathy. Phys Med Rehabil Clin N Am. Aug 2002;13(3): Makin GJ, Brown WF, Ebers GC. C7 radiculopathy: importance of scapular winging in clinical diagnosis. J Neurol Neurosurg Psychiatry. Jun 1986;49(6): Ozgur BM, Marshall LF. Atypical presentation of C-7 radiculopathy. J Neurosurg. Sep 2003;99(2 Suppl): Peolsson A, Peolsson M. Predictive factors for long-term outcome of anterior cervical decompression and fusion: a multivariate data analysis. Eur Spine J. Mar 2008;17(3): Persson LCG, Carlsson JY, Anderberg L. Headache in patients with cervical radiculopathy: A prospective study with selective nerve root blocks in 275 patients. Euro Spine J. Jul 2007;16(7): Post NH, Cooper PR, Frempong-Boadu AK, Costa ME. Unique features of herniated discs at the cervicothoracic junction: Clinical presentation, imaging, operative management, and outcome after anterior decompressive operation in 10 patients. Neurosurgery. Mar 2006;58(3): Rao R. Neck pain, cervical radiculopathy, and cervical myelopathy: Pathophysiology, natural history, and clinical evaluation. J Bone Joint Surg - Series A ;84(10):1872-

41 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Rao R. Neck pain, cervical radiculopathy, and cervical myelopathy: pathophysiology, natural history, and clinical evaluation. Instr Course Lect. 2003;52: Rao RD, Currier BL, Albert TJ, et al. Degenerative cervical spondylosis: clinical syndromes, pathogenesis, and management. J Bone Joint Surg Am. Jun 2007;89(6): Rechtine GR, Bolesta MJ. Cervical radiculopathy. Semin Spine Surgery. 1999;11(4): Rubinstein SM, Pool JJM, van Tulder MW, Riphagen I, de Vet HCW. A systematic review of the diagnostic accuracy of provocative tests of the neck for diagnosing cervical radiculopathy. Euro Spine J. Mar 2007;16(3): Ruggieri PM. Cervical radiculopathy. Neuroimaging Clin N Am. 1995;5(3): Shah KC, Rajshekhar V. Reliability of diagnosis of soft cervical disc prolapse using Spurling s test. Br J Neurosurg. Oct 2004;18(5): Slipman CW, Plastaras CT, Palmitier RA, Huston CW, Sterenfeld EB. Symptom provocation of fluoroscopically guided cervical nerve root stimulation. Are dynatomal maps identical to dermatomal maps? Spine (Phila Pa 1976). Oct ;23(20): Tanaka Y, Kokubun S, Sato T. Mini-symposium: Cervical spine: (i) Cervical radiculopathy and its unsolved problems. Curr Orthop. Jan 1998;12(1): Tanaka Y, Kokubun S, Sato T, Ozawa H. Cervical roots as origin of pain in the neck or scapular regions. Spine. Aug ;31(17):E Tong HC, Haig AJ, Yamakawa K. The Spurling test and cervical radiculopathy. Spine (Phila Pa 1976). Jan ;27(2): Viikari-Juntura E, Porras M, Laasonen EM. Validity of clinical tests in the diagnosis of root compression in cervical disc disease. Spine (Phila Pa 1976). Mar 1989;14(3): Wainner RS, Fritz JM, Irrgang JJ, Boninger ML, Delitto A, Allison S. Reliability and diagnostic accuracy of the clinical examination and patient self-report measures for cervical radiculopathy. Spine (Phila Pa 1976). Jan ;28(1): Wainner RS, Gill H. Diagnosis and nonoperative management of cervical radiculopathy. J Orthop Sports Phys Ther. Dec 2000;30(12): Waldrop MA. Diagnosis and treatment of cervical radiculopathy using a clinical prediction rule and a multimodal intervention approach: a case series. J Orthop Sports Phys Ther. Mar 2006;36(3): Witzmann A, Hejazi N, Krasznai L. Posterior cervical foraminotomy. A follow-up study of 67 surgically treated patients with compressive radiculopathy. Neurosurg Rev. Dec 2000;23(4): Yoss RE, Corbin KB, Maccarty CS, Love JG. Significance of symptoms and signs in localization of involved root in cervical disk protrusion. Neurology. Oct 1957;7(10): What are the most appropriate diagnostic tests (including imaging and electrodiagnostics), and when are these tests indicated in the evaluation and treatment of cervical radiculopathy from degenerative disorders? RECOMMENDATION: MRI is suggested for the confirmation of correlative compressive lesions (disc herniation and spondylosis) in cervical spine patients who have failed a course of conservative therapy and who may be candidates for interventional or surgical treatment. Grade of Recommendation: B Bartlett et al 9 conducted a prospective study comparing the accuracy of gadolinium (Gd) enhanced MRI with 3D gradient recalled echo (3D GRE) images in the evaluation of cervical radiculopathy in 30 consecutive patients. The 3D GRE images had an accuracy of 87% for the diagnosis of foraminal encroachment. CTM had an accuracy of 90%. MRI with Gd conferred no additional benefit. Oblique reconstructions were less accurate than axial images. The authors concluded that MRI with 3D GRE images is an acceptable technique for the primary evaluation of cervical radiculopathy. CTM remains indicated for patients with symptoms that are incongruent with MRI findings. This study provides Level II diagnostic evidence that MRI with 3D T2 technique has an accuracy approaching that of CT myelography for the diagnosis of a compressive lesion in patients with cervical radiculopathy. Hedberg et al 22 described a retrospective comparative study assessing the accuracy of MRI with limited flip angle (LFA) GRE technique in patients with

42 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 22 cervical radiculopathy. MRI was performed in 130 patients, myelography in 30, CTM in 16 and CT in five. Pathologic confirmation was obtained in 13 surgically treated patients. MRI was normal in 31 cases and neither myelography nor surgery were performed. Extradural defects were detected on MRI in 99/130 patients (52 central, 26 dorsolateral osteophyte, 4 dorsolateral disc, 17 dorsolateral disc/ osteophyte). Myelography/CTM and nonenhanced CT confirmed the abnormalities in 20 and five patients, respectively. Surgical findings from 13 patients and 30 sites showed correlation with MRI on 3/3 herniations and 26/27 degenerative abnormalities. The authors concluded that MRI is sufficient for the evaluation of cervical radiculopathy and may obviate the need for more invasive tests such as myelography or CTM. In critique, since surgical confirmation of cervical radiculopathy was obtained for only 13 patients, the relevant sample size was small. Also, the study utilized an older technique. This study provides Level III diagnostic evidence that MRI is accurate in the diagnosis of disc herniation and degenerative abnormalities in the spine. Modic et al 34 conducted a prospective study comparing the accuracy of MRI, CTM and myelography in the evaluation of cervical radiculopathy. Of the 63 patients enrolled in the study, 52 underwent MRI, myelography and CTM, and 28 underwent surgery. Findings confirmed in surgery identified diagnostic accuracy rates of 74% for MRI, 85% for CTM, and 67% for myelography. Diagnostic agreement with surgical findings was obtained in 90% of patients when MR and CTM were used jointly, 92% when CTM and myelography were used jointly. The authors concluded that MRI is a viable alternative to myelography, and together with CT if needed, provides a thorough exam of the c-spine. MRI is as sensitive, but less specific, for type of disease. CTM is better at distinguishing bone from disc. In critique, patients were not consecutively assigned in this small study. This study provides Level III diagnostic evidence that MRI is a viable alternative to myelography, and together with CT if needed, provides a thorough exam for cervical nerve root compression. Van de Kelft et al 54 performed a prospective comparative study describing the value of MRI on a 0.5 T system plus plain radiography in the evaluation of patients with cervical radiculopathy. One hundred patients with cervical radiculopathy and failed conservative therapy were scheduled for surgery. Of these patients, 18 with myelopathy, history of surgery and history of trauma were referred for CTM instead of MRI; 23 with spondylosis, major spurs, or instability on plain radiography were also referred for CTM. This excluded 41 from the potential study. In the 59 patients that underwent MRI, CDH was found in 55, the location corresponding to the patients symptoms. Four patients without CDH were referred for CTM; a foraminal herniation was found in one. Of the 55 patients with CDH, 50 underwent surgery. In two patients, foraminal spurs were found, not seen on MRI. MRI correlated with surgery at a rate of 94%. The authors concluded that MRI combined with plain radiography is an accurate noninvasive technique in the evaluation of patients with cervical radiculopathy. In critique, the patients included in this study were not consecutively assigned. This study provides Level III diagnostic evidence that early MRI techniques are reasonably accurate in diagnosing CDH in patients with radiculopathy. This emphasizes that noninvasive MRI with plain radiography can diagnose specific CDH, stenosis and nerve root compression with a high degree of useful accuracy. Wilson et al 61 described a retrospective comparative study evaluating the accuracy of MRI in the detection of compressive lesions in patients with cervical radiculopathy. Surgical diagnoses were disc herniation in 32, spondylosis in two, and a combination of the two in six patients. MRI identified the surgical lesion in 37/40 patients (92%). Two independent reading radiologists knew surgery was performed,

43 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 23 but were blinded to the diagnosis and the level. MRI diagnosed an HNP at the correct location in 32/38 patients and spondylosis in two. In the six cases, in which HNP was missed, the MRI was interpreted as spondylosis. In three patients MRI did not diagnose the surgical lesion. CTM was performed in 13 patients, and in five of these patients CTM was felt to add additional information. There was complete recovery in 31/40 patients, and incomplete recovery in 8/40. One patient was lost to follow-up. The authors concluded that MRI is the only preoperative test necessary in most cases of cervical radiculopathy. The authors added that CTM might be useful in patients with a negative MRI, positive EMG and neurologic deficits. In critique, the patients included in this study were not consecutively assigned and there was a significant dropout rate. Due to these limitations, this potential Level II study provides Level III diagnostic evidence that MRI is an accurate tool in the initial preoperative evaluation of patients with cervical radiculopathy. RECOMMENDATION: In the absence of reliable evidence, it is the work group s opinion that CT may be considered as the initial study to confirm a correlative compressive lesion (disc herniation or spondylosis) in cervical spine patients who have failed a course of conservative therapy, who may be candidates for interventional or surgical treatment and who have a contraindication to MRI. Work Group Consensus Statement An article by Ilkko et al 26 examined the accuracy of CT, myelography and MR imaging in 120 patients. Gold standard was surgery in 37 patients. The sensitivities of CT, myelography, and MRI were 66%, 84%, and 86% however MRI was only available in 8 patients. The accuracy of CT was degraded by beam hardening artifact from the shoulders in the lower cervical spine. The authors concluded that CT was a usable alternative to MRI in selected patients. This article was excluded from the formal analysis, however, because it included patients with both radiculopathy and myelopathy without sufficient subgroup analysis. RECOMMENDATION: CT myelography is suggested for the evaluation of patients with clinical symptoms or signs that are discordant with MRI findings (eg, foraminal compression that may not be identified on MRI). CT myelography is also suggested in patients who have a contraindication to MRI. Grade of Recommendation: B Bartlett et al 9 conducted a prospective study comparing the accuracy of Gd-enhanced MRI with 3D GRE images in the evaluation of cervical radiculopathy in 30 consecutive patients. 3D GRE images had an accuracy of 87% for the diagnosis of foraminal encroachment. CTM had an accuracy of 90%. MRI with Gd conferred no additional benefit. Oblique reconstructions were less accurate than axial images. The authors concluded that MRI with 3D GRE images is an acceptable technique for the primary evaluation of cervical radiculopathy. CTM remains indicated for patients with incongruent symptoms and MRI results. This study provides Level II diagnostic evidence that MRI with 3D T2 technique has an accuracy approaching that of CT myelography for the diagnosis of a compressive lesion in patients with cervical radiculopathy. Houser et al 24 reported a retrospective case series correlating the findings on CTM with surgical and path proven cervical herniations. Over three years, 734 patients underwent CTM for cervical disc disease. At surgery, CDH was noted in 297 patients. Of the 297 patients, 280 had a diagnosis of radiculopathy and 17 of myelopathy. Surgical reports noted one or more prolapsed discs in 258, a prolapsed disc and spur in 38 and a prolapsed disc with a fracture in one. CTM corresponded to surgical findings in 260 of the 280 patients with radiculopathy and in all 17 patients with myelopathy. Surgery was performed in 22 patients on the basis of clinical symptoms alone.

44 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 24 Of these 22 patients, 19 had herniations not seen on CTM and three had no herniations based upon surgical findings and CTM. A soft tissue extradural deformity appeared to be present on CTM in seven patients who had no cervical abnormalities on surgical exploration. The authors concluded that imaging of CDHs continues to be difficult and the results are not always specific. CTM is the most sensitive imaging examination. In critique, patients were not consecutively assigned. This study provides Level III diagnostic evidence that CT myelography can identify 90% of cervical extruded disc herniations confirmed by surgery. Houser et al 25 presented a retrospective case series reviewing the surgical and CTM findings in 95 patients with foraminal stenosis. CTM showed stenosis at the entrance in 70 (52%), within the canal itself in 37 (28%) and site not definitively identified in 27 (20%). At the entrance to the foramen, stenosis secondary to a cartilaginous cap was identified in 10 patients (8%), osteophyte in 17 (13%), synovial cyst in one and a combination of bone and cartilaginous cap in 42 (31%). Within the canal, small bone spurs arising from the uncovertebral process contributed to stenosis in 29 instances and from the facet joint in eight. Diagnosis on the basis of CTM was difficult because stenosis was evident as a bone spur in only 13% of cases, could not be distinguished from a disc herniation in 39%, had to be distinguished from a congenitally narrowed foramen in 27% and was missed in 20%. The authors concluded that the diagnosis of foraminal stenosis on CTM is difficult. In critique, patients included in this study were not consecutively assigned. This study provides Level III diagnostic evidence that there is limited correlation between CT myelography and foraminal stenosis as confirmed by surgical exploration. Modic et al 34 conducted a prospective study comparing the accuracy of MRI, CTM and myelography in the evaluation of cervical radiculopathy. Of the 63 patients enrolled in the study, 52 underwent MRI, myelography and CTM, and 28 underwent surgery. Findings confirmed in surgery identified diagnostic accuracy rates of 74% for MRI, 85% for CTM and 67% for myelography. Diagnostic agreement with surgical findings was obtained in 90% of patients when MR and CTM were used jointly, 92% when CTM and myelography were used jointly. The authors concluded that MRI is a viable alternative to myelography, and together with CT if needed, provides a thorough exam of the c-spine. MRI is as sensitive, but less specific, for type of disease. CTM is better at distinguishing bone from disc. In critique, patients were not consecutively assigned in this small study. This study provides Level III diagnostic evidence that MRI is a viable alternative to myelography, and together with CT if needed, provides a thorough exam of the cervical spine. Russell et al 45 reported on a retrospective comparative study assessing the value of CT with IV contrast in the evaluation of patients with cervical radiculopathy. Ventral epidural and intervertebral veins were consistently well visualized with CT enhanced with IV contrast. Disc protrusions were diagnosed in nine of 30 patients. A clear and definitive marginal ring blush between the disc protrusion and the enhanced venous system was seen in eight of these patients. Surgical confirmation was obtained in only five of these eight patients since only five of the eight came to surgery. Visualization of posterior displacement of the enhance epidural veins and epidural enhancement surrounding extruded disc fragments provided excellent delineation of disc extrusion and in some cases allowed demarcation of multiple discrete disc fragments. The authors concluded that although routine CT is usually diagnostic, the addition of IV contrast improves anatomic information and diagnostic certainty and may obviate the need for myelography in some patients. In critique, patients included in this small study were not consecutively assigned. Of the nine cases that reported abnormal findings, only five went on to surgery and obtained surgical confirmation. This study provides Level III diagnostic evidence that the

45 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 25 technique of high dose contrast infusion with CT provides useful venous enhancement with improved visualization of the disc/epidural vein interface and improved visualization of disc herniations. Myelography for cervical discs may be unnecessary unless further spinal column delineation is required. Van de Kelft et al 54 performed a prospective comparative study describing the value of MRI on a 0.5 T system plus plain radiography in the evaluation of patients with cervical radiculopathy. The study included 100 patients with cervical radiculopathy and failed conservative therapy scheduled for surgery. All patients underwent plain radiography. Patients with myelopathy, history of previous surgery and history of trauma (18), and patients with spondylosis, major spurs or instability on plain radiography (23) were referred for CTM. The remaining 59 patients underwent MRI. On MRI, a soft disc herniation (CDH) was found in 55 patients, the location corresponding to the patients symptoms. The four patients without CDH were referred for CTM, and a foraminal herniation was found in one. Of the 55 patients with CDH, 50 underwent surgery. Findings on MRI correlated with surgical findings in 94%. In two patients, foraminal spurs were found, not seen on MRI. The authors concluded that MRI combined with plain radiography is an accurate noninvasive technique in the evaluation of patients with cervical radiculopathy. In critique, the patients included in this study were not consecutively assigned. This study provides Level III diagnostic evidence that early MRI techniques are reasonably accurate in diagnosing CDH in patients with radiculopathy. This emphasizes that noninvasive MRI with plain radiography can diagnose CDHs and nerve root compression with a high degree of useful accuracy. Wilson et al 61 described a retrospective comparative study evaluating the accuracy of MRI in the detection of compressive lesions in patients with cervical radiculopathy. Surgical diagnoses were disc herniation in 32, spondylosis in two and a combination of the two in six patients. MRI identified the surgical lesion in 37/40 patients (92%). Two independent reading radiologists knew surgery was performed, but were blinded to the diagnosis and the level. MRI diagnosed an HNP at the correct location in 32/38 patients and spondylosis in two. In the six cases in which HNP was missed, the MRI was interpreted as spondylosis. In three patients MRI did not diagnose the surgical lesion. CTM was performed in 13 patients, and in five of these patients, CTM was felt to add additional information. There was complete recovery in 31/40 patients and incomplete recovery in 8/40. One patient was lost to follow-up. The authors concluded that MRI is the only preoperative test necessary in most cases of cervical radiculopathy. The author added that CTM may be useful in patients with a negative MRI, positive EMG and neurologic deficits. In critique, the patients included in this study were not consecutively assigned and there was a significant dropout rate. Due to these limitations, this potential Level II study provides Level III diagnostic evidence that MRI is an accurate tool in the initial preoperative evaluation of patients with cervical radiculopathy. RECOMMENDATION: The evidence is insufficient to make a recommendation for or against the use of EMG for patients in whom the diagnosis of cervical radiculopathy is unclear after clinical exam and MRI. Grade of Recommendation: I (Insufficient Evidence) Alrawi et al 2 reported a prospective case series investigating whether preoperative EMG can help identify those most likely to benefit from intervention. The study included 20 patients with clinical manifestations of cervical radiculopathy and an MRI showing disc bulges associated with narrowing of the exiting foramina. Preoperatively, patients were divided into two groups on the basis of EMG findings. Group A consisted of eight patients with denervation changes

46 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 26 in the distribution of a least one cervical nerve root. Group B had 12 patients with no EMG evidence of cervical radiculopathy. Patients in Group A had better clinical outcomes and patient satisfaction from their ACDF at least 12 months postoperatively than patients in Group B. The authors concluded that preoperative neurophysiologic studies (NPS) can help identify which patients are more likely to benefit from surgery for cervical radiculopathy. In critique, patients were not consecutively assigned to the study. This study provides Level III diagnostic evidence that patients with cervical radiculopathy and an MRI showing a disc bulge with narrowing of the exiting foramina have better clinical outcomes and patient satisfaction from ACDF if a preoperative EMG shows denervation changes. Ashkan et al 6 reported on a retrospective case series assessing whether NPS added significant information to high resolution MRI in the evaluation of cervical radiculopathy. Of the 45 patients included in the study, three experienced bilateral symptoms. Radicular arm pain was present in all cases, parasthesias in 28, numbness in 22 and subjective weakness in 14. Following surgery, 36 patients had complete resolution of symptoms and seven experienced significant improvement in symptoms. Of patients who improved following surgery, 16 (37%) had a positive MRI and NPS; 24 (56%) had a positive MRI and negative NPS; two (5%) had a negative MRI and positive NPS; and one (2%) had negative MRI and NPS studies. In the three cases with a negative MRI, surgical plans were based on the NPS in one case and on CTM in two. In five patients with foraminal stenosis on MRI the patients did not improve. Of these five patients, four were operated on at the level indicated by MRI. Sensitivity for diagnosing cervical radiculopathy was 93% for MRI and 42% for NPS; with PPVs at 91% for MRI and 86% for NPS. NPPs were 25% for MRI and 7% for NPS. The authors concluded that in patients with clinical and MRI evidence of cervical radiculopathy, NPS has limited additional diagnostic value. In critique, the patients included in the study were not consecutive. This study provides Level III diagnostic evidence that MRI is more accurate and more sensitive than NPS in the preoperative evaluation of patients with cervical radiculopathy. RECOMMENDATION: Selective nerve root block with specific dosing and technique protocols may be considered in the evaluation of patients with cervical radiculopathy and compressive lesions identified at multiple levels on MRI or CT myelography to discern the symptomatic level(s). Selective nerve root block may also be considered to confirm a symptomatic level in patients with discordant clinical symptoms and MRI or CT myelography findings. Grade of Recommendation: C Anderberg et al 4 described a prospective case series assessing the use of transforaminal SNRB in patients with cervical radiculopathy and MRI findings at two levels ipsilateral to the patient s symptoms. The study included 30 consecutive patients with cervicobrachialgia, 22 with neurologic deficits. Degenerative changes on MRI were found in close relation to nerve roots. Neuroforaminal narrowing was graded as slight, moderate or severe, without further analysis. Clinical findings were correlated with MRI findings and root block levels were determined. No analgesics were administered within 12 hours prior to the procedure, and there was no mention if sedation was given prior to the procedure. Contrast was administered to confirm perineural needle position within the foramen prior to SNRB. SNRB with 0.5 ml solution of 5 mg of Mepivacaine was administered. VAS outcomes were assessed 30 minutes and four hours after SNRB. VAS reduction of at least 50% was required to determine that the SNRB was positive; however, the authors did not indicate if this measure referred to the VAS score at 30 minutes or four hours after the SNRB, or both. In 18 patients with positive SNRB at a single level, the SNRB correlated with the

47 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 27 level of more marked pathology in 12, to the level determined by the neurologic deficits in eight and to the level corresponding to the sensory dermatome in seven. Eleven patients had a positive SNRB at two levels. Of 13 patients treated at one level, nine (67%) had good or excellent results. Of nine patients treated at two levels, 100% had good or excellent results. The authors concluded that clinical symptoms and signs in isolation or in combination with MRI findings are not always reliable indicators of the paingenerating nerve root. SNRB may be useful in treatment planning in patients with radiculopathy and degenerative changes at two levels ipsilateral to the patient s symptoms. In critique, this small study did not utilize a consistently applied gold standard and surgical treatment or epidural steroid injection was performed in only 22 or the 30 patients. This study provides Level III diagnostic evidence that SNRB may be useful in the preoperative evaluation of patients with radiculopathy and findings of compressive lesion at multiple levels on MRI. Anderberg et al 5 reviewed a prospective case series of nine patients studying the selectivity of cervical transforaminal injections and the distributions of a range of injection volumes in patients with cervical radiculopathy. Three groups of three patients received one of the following: 0.6, 1.1 or 1.7 ml of injectate via the transforaminal root technique used by Kikuchi. The groups injected with 0.6 and 1.1 ml received local anesthetic and contrast. The group injected with 1.7 ml received local anesthetic, corticosteroid and contrast. Contrast distribution was determined by a post injection CT scan. An injection was considered a successful SNRB if the contrast media surrounded an adjacent nerve root by less than half of its circumference. In all three patients receiving 0.6 ml of injectate the injections were considered selective. In 2 of 3 of patients given 1.1 ml of injectate, the injections were considered selective. None of the three patients receiving 1.7 ml of injectate were considered selective. The perineural distribution length averaged 36 mm, with no correlation to injectate volume. The authors concluded that only 0.6 ml injections should be used for SNRBs. This small case series provides Level II diagnostic evidence that transforaminal injectate volumes of 0.6 ml consistently meet the criteria for a SNRB. Future Directions for Research The work group identified the following recommendations that would assist in generating meaningful evidence to assist in further defining the appropriate diagnostic tests for cervical radiculopathy from degenerative disorders. Studies should assess a set of diagnostic criteria established a priori. Recommendation #1: Studies evaluating the accuracy of MRI, CT and CT myelography in detecting and characterizing compressive lesions in the cervical spine in patients with cervical radiculopathy should be repeated using state of the art equipment and imaging techniques and should implement surgical findings and outcomes as gold standards. Recommendation #2: Further studies should be done to evaluate the contribution of EMG to the evaluation of cervical radiculopathy patients with discordant MRI findings and clinical findings using surgical findings and outcomes as gold standards. Recommendation #3: Further studies should be done evaluating the contribution of SNRB to the evaluation of cervical radiculopathy patients with discordant MRI findings and clinical findings, and to the evaluation of cervical radiculopathy patients with findings on MRI at multiple levels ipsilateral to the patient s symptoms using surgical findings and outcomes as gold standards. Recommendation #4: Studies should be done evaluating the contribution of dynamic upright cervical spine MRI to the evaluation of and long term outcome of patients undergoing surgical decompression for cervical radiculopa-

48 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 28 thy with attention to the following question: Does the presence of dynamic central canal stenosis at an adjacent level affect the long term outcome of patients undergoing surgical decompression using an anterior approach with fusion versus a motion preserving posterior approach? Imaging References 1. Ahmed M, Modic MT. Neck and Low Back Pain: Neuroimaging. Neurologic Clin. May 2007;25(2): Alrawi MF, Khalil NM, Mitchell P, Hughes SP. The value of neurophysiological and imaging studies in predicting outcome in the surgical treatment of cervical radiculopathy. Eur Spine J. Apr 2007;16(4): Anderberg L, Annertz M, Brandt L, Saveland H. Selective diagnostic cervical nerve root block--correlation with clinical symptoms and MRI-pathology. Acta Neurochir (Wien). Jun 2004;146(6): ; discussion Anderberg L, Annertz M, Rydholm U, Brandt L, Saveland H. Selective diagnostic nerve root block for the evaluation of radicular pain in the multilevel degenerated cervical spine. Eur Spine J. Jun 2006;15(6): Anderberg L, Saveland H, Annertz M. Distribution patterns of transforaminal injections in the cervical spine evaluated by multi-slice computed tomography. Euro Spine J. Oct 2006;15(10): Ashkan K, Johnston P, Moore AJ. A comparison of magnetic resonance imaging and neurophysiological studies in the assessment of cervical radiculopathy. Br J Neurosurg. Apr 2002;16(2): Baron EM, Loftus CM, Ducker TB, Nakagawa H. Dynamic computed tomography myelography for the investigation of cervical degenerative disease: Commentary. Neurol Med Chir (Tokyo). 2006;46(4): Bartlett RJ, Hill CA, Devlin R, Gardiner ED. Two-dimensional MRI at 1.5 and 0.5 T versus CT myelography in the diagnosis of cervical radiculopathy. Neuroradiology. Feb 1996;38(2): Bartlett RJV, Hill CR, Gardiner E. A comparison of T₂ and gadolinium enhanced MRI with CT myelography in cervical radiculopathy. Br J Radiol. Jan 1998;71(JAN.): Bell GR. The anterior approach to the cervical spine. Neuroimag Clin N Am. 1995;5(3): Bell GR, Ross JS. Diagnosis of nerve root compression: Myelography, computed tomography, and MRI. Orthop Clin North Am. 1992;23(3): Ben-Eliyahu DJ. Thermographic imaging of pathoneurophysiology due to cervical disc herniation. J Manipulative and Physiol Ther. 1989;12(6): Birchall D, Connelly D, Walker L, Hall K. Evaluation of magnetic resonance myelography in the investigation of cervical spondylotic radiculopathy. Br J Radiol. Aug 2003;76(908): Boden SD, McCowin PR, Davis DO, Dina TS, Mark AS, Wiesel S. Abnormal magnetic-resonance scans of the cervical spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am. Sep 1990;72(8): Brown BM, Schwartz RH, Frank E, Blank NK. Preoperative evaluation of cervical radiculopathy and myelopathy by surface-coil MR imaging. AJR Am J Roentgenol. Dec 1988;151(6): Daniels DL, Grogan JP, Johansen JG. Cervical radiculopathy: Computed tomography and myelography compared. Radiology. 1984;151(1): Daniels DL, Grogan JP, Johansen JG, Meyer GA, Williams AL, Haughton VM. Cervical radiculopathy: computed tomography and myelography compared. Radiology. Apr 1984;151(1): Fish DE, Kobayashi HW, Chang TL, Pham Q. MRI prediction of therapeutic response to epidural steroid injection in patients with cervical radiculopathy. Am J Phys Med Rehabil. March 2009;88(3): Fisher MA. Electrophysiology of radiculopathies. Clin Neurophysiol. Mar 2002;113(3): Gore DR, Sepic SB, Gardner GM. Roentgenographic findings of the cervical spine in asymptomatic people. Spine (Phila Pa 1976). Jul-Aug 1986;11(6): Grundy CR, Fritts HM. Magnetic resonance imaging of the musculoskeletal system.8. The spine, section 1. Clin Orthop Relat Res. May 1997(338): Hedberg MC, Drayer BP, Flom RA, Hodak JA, Bird CR. Gradient echo (GRASS) MR imaging in cervical radiculopathy. AJR Am J Roentgenol. Mar 1988;150(3): Hitselberger WE, Witten RM. Abnormal myelograms in asymptomatic patients. J Neurosurg. Mar 1968;28(3): Houser OW, Onofrio BM, Miller GM, Folger WN, Smith PL. Cervical Disk Prolapse. Mayo Clinic Proceedings. Oct 1995;70(10): Houser OW, Onofrio BM, Miller GM, Folger WN, Smith PL, Kallman DA. Cervical Neural Foraminal Canal Stenosis - Computerized Tomographic Myelography Diagnosis. J Neurosurg. Jul 1993;79(1): Ilkko E, Lahde S, Heiskari M. Thin-section CT in the examination of cervical disc herniation. A prospective study with 1-mm axial and helical images. Acta Radiol. Mar 1996;37(2): Kaech DL, Elsig JPJ. Functional magnetic resonance imaging of the spine. Rivista Medica. Sep 2006;12(3-4): Kaiser JA, Holland BA. Imaging of the cervical spine. Spine (Phila Pa 1976). Dec ;23(24): Kent DL, Haynor DR, Longstreth WT, Larson EB. Clinical Efficacy of Magnetic-Resonance-Imaging in Neuroimaging. Ann Intern Med. May 1994;120(10):

49 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Kuijper B, Tans JTJ, Schimsheimer RJ, et al. Degenerative cervical radiculopathy: Diagnosis and conservative treatment. A review. Euro J Neurol. January 2009;16(1): Larsson EM, Holtas S, Cronqvist S, Brandt L. Comparison of myelography, CT myelography and magnetic resonance imaging in cervical spondylosis and disk herniation. Pre- and postoperative findings. Acta Radiol. May-Jun 1989;30(3): Leblhuber F, Reisecker F. Diagnostic efficacy of DSER in patients with spine pain and radiculopathy in the cervical and lumbar region. Clin Electroencephalogr. Jan 1990;21(1):VII-IX. 33. Manchikanti L, Pampati V, Damron KS, et al. The effect of sedation on diagnostic validity of facet joint nerve blocks: an evaluation to assess similarities in population with involvement in cervical and lumbar regions (ISRCTNo: ). Pain Physician. Jan 2006;9(1): Modic MT, Masaryk TJ, Mulopulos GP. 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Cervical disk herniation: CT demonstration after contrast enhancement. Radiology. 1984;152(3): Sabbahi MA, Khalil M. Segmental H-reflex studies in upper and lower limbs of patient with radiculopathy. Arch Phys Med Rehabil. 1990;71(3): Scotti G, Scialfa G, Pieralli S, Boccardi E, Valsecchi F, Tonon C. Myelopathy and radiculopathy due to cervical spondylosis: myelographic-ct correlations. AJNR Am J Neuroradiol. May-Jun 1983;4(3): Shafaie FF, Wippold FJ, 2nd, Gado M, Pilgram TK, Riew KD. Comparison of computed tomography myelography and magnetic resonance imaging in the evaluation of cervical spondylotic myelopathy and radiculopathy. Spine. Sep ;24(17): Siivola SM, Levoska S, Tervonen O, Ilkko E, Vanharanta H, Keinanen-Kiukaanniemi S. MRI changes of cervical spine in asymptomatic and symptomatic young adults. Eur Spine J. Aug 2002;11(4): Strobel K, Pfirrmann CW, Schmid M, Hodler J, Boos N, Zanetti M. Cervical nerve root blocks: indications and role of MR imaging. Radiology. 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51 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 31 B. Outcome Measures for Medical/Interventional and Surgical Treatment What are the most appropriate outcome measures to evaluate the treatment of cervical radiculopathy from degenerative disorders? Asking this question about the treatment of cervical radiculopathy from degenerative disorders is intrinsically valuable. Our review of the literature on cervical radiculopathy from degenerative disorders confirmed that outcome studies are valuable in determining the course of treatment. When evaluating studies in terms of the use of outcome measures, the work group evaluated this literature as prognostic in nature. Prognostic studies investigate the effect of a patient characteristic on the outcome of a disease. Studies investigating outcome measures, by their design, are prognostic studies. An appropriate clinical outcome measure must be validated. Further, the validated outcome measure must be used in a high quality, prospective outcome trial in order to be useful. The literature review yielded no validated outcome measures utilized for the subset of patients with cervical radiculopathy from degenerative disorders. RECOMMENDATION: The Neck Disability Index (NDI), SF-36, SF-12 and VAS are recommended outcome measures for assessing treatment of cervical radiculopathy from degenerative disorders. Grade of Recommendation: A Anderberg et al 2 described a prospective observational study examining the correlation between SNRB and MRI findings and clinical symptoms. Of the twenty consecutively assigned patients included in the study, all received SNRB with mepivicaine and their arm and neck pain were assessed 30 minutes following the procedure using VAS. The authors reported an 86% mean reduction in VAS arm pain scores and 65% mean reduction in VAS neck pain scores, and concluded that the VAS can be used to document response to the anesthetic phase of SNRB for arm and neck pain. In critique, this study had a very small sample size and the patients included were not enrolled at the same point in their disease, with duration of symptoms ranging from one to 60 months. This study provides Level II prognostic evidence that the VAS pain scale can be used to document the immediate anesthetic response to SNRB for radicular arm pain. Fernandez-Fairen et al 19 reported a prospective, randomized controlled trial assessing the effectiveness and safety of a tantalum implant in achieving anterior cervical fusion following single level discectomy as treatment for degenerative cervical disc disease with radiculopathy. Of the 61 patients included in the study, 28 were treated with ACDF with interbody implant of tantalum and 33 received ACDF with autologous iliac bone graft and plating. At 24 months, clinical outcomes, as assessed by the NDI, VAS pain scale (arm), Odom s criteria and Zung Depression Scale were similar for both treatment groups without significant difference. The authors concluded that clinical outcome as assessed by the VAS, NDI and ZDS demonstrated that tantalum implant was equivalent to autogenous graft and anterior plate. This study provides Level I prognostic evidence that the NDI and VAS pain scale (arm) are instruments that can be used to assess the outcome of surgical intervention for cervical radiculopathy from degenerative disorders. Additionally, patient satisfaction as measured by Odom s criteria and depression as assessed by the ZDS appear useful. Foley et al 22 conducted a prospective randomized controlled trial to determine the efficacy and safety

52 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 32 of pulsed electromagnetic field stimulation as an adjunct to arthrodesis after ACDF in patients with potential risk factors for nonunion. Of the 323 consecutively assigned patients, 163 received PEMF in addition to the ACDF. Clinical outcomes as assessed by the NDI, VAS (arm) and SF-12 demonstrated that there were no significant differences between the two treatments. Because less than 80% of patients were available at 12 month follow-up, this study provides Level II evidence NDI, VAS (arm) and SF-12 can be used to assess outcome after surgical intervention for cervical radiculopathy from degenerative disorders. Hacker et al 25 described a randomized controlled trial to report clinical results with maximum 24 month follow-up of fusions performed with the BAK/C fusion cage. Of the 344 patients available at 12 month follow-up, 245 had been assigned to the BAK/C fusion cage groups and 105 were assigned to the control group. Clinical outcome as assessed with the VAS and SF-36 showed that there were similar outcomes between the ACDF group and the BAK/C group at 12 months and 24 months. The authors concluded that clinical outcomes after a cervical fusion with a threaded cage are the same as those of a conventional uninstrumented bone-only ACDF. This study provides Level I evidence that the VAS and SF-36 can be used to assess outcome following surgery for cervical radiculopathy from degenerative disorders. Kumar et al 38 reported on a retrospective observational study designed to highlight the effectiveness and safety of cervical selective nerve root block (SNRB) using a two needle technique for treatment of radiculopathy. Although the 33 patients included in the study were followed for two years, clinical outcomes were reported only for the first year. Statistical improvements in VAS and NDI scores were seen at six weeks and 12 months following the procedure. The authors concluded that the VAS and NDI can be used to show that the two needle technique of cervical foraminal SNRB produces improved outcomes at six weeks and 12 months. This study provides Level II evidence that NDI, VAS and SF-36 can be used to assess outcome of interventional treatment of cervical radiculopathy from degenerative disorders. Lofgren et al 41 conducted a prospective observational study to compare the clinical outcome after surgery for cervical radiculopathy from degenerative disorders to conservative treatment. Forty-three surgical patients were studied prospectively and received ACDF (Cloward, single level). Their outcomes were compared with a control group of 39 patients (two did have surgery) who were treated conservatively. The conservative treatment protocol was not described. Outcomes were assessed at three months, six months, nine months and two years. Pain reduction measured with the VAS (arm) was more pronounced among the surgically treated patients at the final follow-up for maximal neck pain (p=0.03) and at three months and nine months, respectively, for average neck pain (p=0.02, both). Initially there was no statistically significant difference in pain intensity between the surgically and conservatively treated groups. Sickness Impact Profile showed that patients scheduled for surgery had higher sickness impact in the overall index. The authors concluded that surgically treated patinets demonstrated an improvement in VAS (arm) pain and SIP scores, as well as at the clinical examination, all indicating a true improvement, although only partially maintained. This study provides Level I evidence that VAS (arm) may be a useful surgical outcome measure for patients with cervical radiculopathy from degenerative disorders. Mummaneni et al 43 reported findings of a prospective randomized controlled trial comparing the results of cervical disc arthroplasty to ACDF. Of the 541 patients included in the study, 276 received a Prestige disc and 265 were treated with ACDF and plating. Outcomes were assessed at 1.5 months, three months, six months, 12 months and 24 months. Neck pain, arm pain and NDI scores were improved in the Prestige disc group, with statistically superior success rates at 12 and 24 months compared with

53 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 33 the control group. Neck pain improved in both treatment groups, but statistically significant improvements were noted in the Prestige group at six weeks, three months and 12 months. No significant intergroup differences in arm pain or return to work were noted at 24 months. The NDI score was statistically significantly higher only at three months, but tended to have higher scores than the control group. The authors concluded that the Prestige ST-cervical disc system maintained physiological segmental motion at 24 months after implanation and was associated with improved neurologic success, improved clinical outcomes (SF-36) and reduced rate of secondary surgeries compared to ACDF. In critique, this study had a 75% follow-up in the control group and provides Level II evidence that NDI and SF-36 can be used to assess the outcomes of cervical radiculpathy treated by discectomy and articifial disc replacement or fusion. Murrey et al 45 described a prospective randomized controlled trial comparing the safety and efficacy of C-TDR with ProDisc-C to ACDF for the treatment of a symptomatic cervical disc at one level between C3 and C7. Of the 209 patients included in the study, 103 received ProDisc-C TDR and 106 were treated with single level ACDF. Outcomes were assessed at three months, six months, 12 months, 18 months and 24 months. NDI and SF-36 improved in both groups as compared to preoperative scores (ρ<0.0001). VAS neck and arm pain intensity and frequency were statistically lower at all follow-up time points compared with preoperatively (ρ<0.0001) but were no different between treatment groups. Authors concluded that neurologic success (improvement or maintenance) as determined by NDI, SF-36 and VAS neck and arm pain scores was seen in 90.9% of ProDisc-C and 88% of fusion patients (ρ=0.638) at 24 months. Fusion patients had a higher secondary surgery rate and higher medication usage postoperatively. This study provides Level I evidence that NDI, SF-36 and VAS are outcome tools that can be used to assess cervical disc disease, including cervical radiculopathy, following surgery. Nunley et al 46 conducted a prospective randomized controlled trial comparing the clinical and radiographic outcomes of patients treated with onelevel or multiple level ACDF using cervical plates of dynamic/slotted vs. static/fixed hole design. Of the 66 patients included in the study and treated with ACDF, 33 received static plates and 33 received dynamic plates. VAS and NDI score were lower in patients with dynamic plates than static plates. At mean follow-up of 16 months, 49 patients (73.7%) had clinical success and 56 (85%) showed radiographic fusion. In single-level fusion, no statistical difference of outcome was observed between the two groups, but multilevel fusions with dynamic plate showed significantly lower VAS and NDI scores than those with static plates (ρ=0.050). The authors concluded that SF-36 and NDI scores were better in patients with dynamic plates as compared to those with static plates. They stated that clinical improvement is a good predictor of successful ACDF and that radiologic evidence of fusion alone is not reliable as a parameter of success. Plate design for single-level fusion does not affect outcomes, but outcome studies indicate that multilevel fusions may have better clinical outcomes when dynamic/slotted plates are used. This study provides Level I evidence that NDI and VAS are outcome measures that can be used to assess cervical radiculopathy from degenerative disorders. Park et al 49 described a retrospective case control study comparing the clinical and radiographic outcomes of CDR-Mobi-C to ADV-Solis cage. Of the 53 patients included in the study, 21 were treated with CDR-Mobi-C and 32 received ADF-Solis-cage. Outcomes were assessed at six weeks, three months, six months and 12 months. Mean hospital stay and interval between surgery and return to work were significantly shorter in the arthroplasty group than the fusion group. Mean NDI and extremity VAS score improved after 12 months in both groups. Although it was not significant, segmental range of motion (ROM) at adjacent levels was higher in the fusion group than the arthroplasty group. Segmental mo-

54 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 34 tion at the operative level in the arthroplasty group maintained more motion than preoperative values at final follow-up. The authors concluded that clinical outcomes were similar in both groups. Mean NDI and extremity VAS scores improved after 12 months in both groups. In critique, this study had a small sample size and the authors did not adequately explain how assignments to the two treatment groups were made. The two groups were not appropriately matched; the fusion group had more males, iliac crest graft was only performed in the fusion group and the fusion group had cervical orthosis for two months. Due to these limitations, this potential Level II study provides Level III evidence that NDI and VAS may be appropriate outcome measures to assess cervical radiculopathy from degenerative disorders. Peolsson et al 51 conducted a prospective randomized controlled trial to determine the predictive factors for short-term and long-term outcome of ACDF using VAS and NDI multivariate analysis. Of the 103 consecutively assigned patients included in the study, 95 proceeded with surgical treatment. Of the 95 surgically treated patients, 52 received a cervical intervertebral fusion cage and 51 received a Cloward procedure. Outcomes were assessed at 12 months and 24 months and compared with preoperative data. Using multivariate analysis, the variables influence on projection showed that the most important preoperative variables for predicting short-term NDI and pain intensity were: NDI, horizontal active range of motion (AROM), pain intensity, smoking, right hand strength, gender and kyphosis. Radiological finding and surgical technique except preoperative kyphosis were insignificant as predictors of both short- and long-term outcome. The authors concluded that a preoperative low neck specific disability, low pain intensity, nonsmoking status, male gender, good preoperative hand strength and neck AROM were significant predictors for a good longterm outcome of pain intensity and NDI after ACDF. Short-term outcome measures of NDI and pain intensity were better predictors of the long-term outcome than were baseline values. NDI was not only overall the most important factor in explaining short- and long-term outcomes, but also was the factor with the highest impact explaining the total prediction model. NDI may be regarded as an important outcome measurement in evaluation of ACDF. This study provides Level I evidence that NDI and VAS are good outcome measures to assess cervical radiculopathy from degenerative disorders. Xie et al 65 performed a prospective randomized controlled trial to determine the clinical outcome of ACD, ACDF and anterior cervical discectomy and fusion with instrumentation (ACDFI). Of the 45 patients included in the study, 15 were assigned to each treatment group. Outcomes were asessed at three weeks, six weeks, three months, six months, one year and two years. SF-36 scores demonstrated a dynamic postoperative improvement followed by further gradual improvement in both physical and mental components as well as other subscale scores in all groups during the follow-up period (ρ<0.05). The amount of pain demonstrated by the McGill pain rating index scores significantly decreased for all three groups immediately after surgery and continued to decline, plateauing at about one year. The authors concluded that SF-36 scores improved in all three groups during the follow-up period, and McGill pain scores markedly improved immediately after surgery and continued to improve until the one year follow-up evaluation before plateauing. In critique, neither patients nor reviewers were masked to treatment group and the sample size was small. Three of the 45 patients were lost to follow-up. Patients included in the study were enrolled at different points in their disease and received surgery at single and multiple levels. Due to these limitations, this potential Level I study provides Level II evidence that SF-36 may be an appropriate outcome tool for cervical radiculopathy from degenerative disorders treated with surgery. Zoega et al 65 described a prospective observational study of patients undergoing ACDF or ACDFI at

55 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 35 single or multiple levels to determine the usefulness of outcome scores in the treatment of degenerative disc disease. Of the 46 patients included in the study, 12 received single-level ACDF, 10 received two-level ACDF, 15 received single-level ACDFI and 9 received two-level ACDFI. At two years, 81% of patients were satisfied with the outcome of surgery. All scores improved in the group operated on at two-levels. VAS arm and neck pain decreased in both groups. The improvement in arm pain was significantly more pronounced in patients operated with a plate at twolevels compared to those who were operated without a plate. At two year follow-up, patients with an excellent or good result according to Odom s criteria had a lower Million Index (ρ<0.0005), Oswestry Index (ρ<0.0005) and Zung Depression Scale (ρ=0.024) score than the group classified as fair or poor. There was a significant correlation (ρ<0.0001) for all scores between the test and retest. The authors concluded that Modified Million Index and Oswestry Index are clinically useful tools in the evaluation of outcome after degenerative cervical disc disease surgery. The outcome after surgery measured with the Oswestry Index, Modified Million Index, and VAS neck and arm pain seem to correlate well with the classification of outcome by Odom. This study provides Level II evidence that VAS may be an appropriate outcome measure for cervical radiculopathy from degenerative disorders treated with surgery. RECOMMENDATION: The Modified Prolo, Patient Specific Functional Scale (PSFS), Health Status Questionnaire, Sickness Impact Profile, Modified Million Index, McGill Pain Scores and Modified Oswestry Disability Index are suggested outcome measures for assessing treatment of cervical radiculopathy from degenerative disorders. GRADE OF RECOMMENDATION: B Alrawi et al 1 reported the findings of a prospective observational study examining the utility of neurophysiological EMG to predict outcome after ACDF. Of the 20 patients included in the study, eight showed EMG evidence of nerve root involvement, while 12 did not. Patient outcomes at minimum of 12 months as measured with a modified Prolo scale were better predicted by EMG. The authors concluded that EMG can better predict outcomes as measured by a modified Prolo scale. In critique, this study had a very small sample size of nonrandomized patients who were enrolled at different points of their disease. Patients still received an operation even if they had a negative EMG. Due to these limitations, this study provides Level III evidence that the modified Prolo scale can be used to assess patient outcome after ACDF. Cleland et al 15 described a prospective observational study examining the test-retest reliability, construct validity and minimum levels of detectable and clinically important change for the NDI and PSFS in a cohort of patients with cervical radiculopathy. All 38 patients included in the study received physical therapy and were assessed at a mean of 21.5 days. Test-retest reliability was moderate for the NDI and high for the PSFS. The PSFS was more responsive to change than the NDI. The minimal detectable change for the NDI was 10.2 and for the PSFS was 2.1. The authors concluded that the PSFS exhibits superior reliability, construct validity, and responsiveness in this cohort of patients with cervical radiculopathy compared with the NDI. This study provides Level I evidence that the PSFS may be better than the NDI for the assessment of outcomes in patients with cervical radiculopathy. Davis et al 17 conducted a retrospective observational study assessing the outcome of posterior decompression for cervical radiculopathy. Of the 170 patients included in the study, patients who had sedentary occupations and housewives had significantly higher Prolo scores (p<0.001) than those who did strenuous work. In 86% of patients, outcome was good (defined as a Prolo score of 8 in 5%, 9 in 38% and 10 in 43%). The authors concluded that although outcome studies must have subjective criteria, the Prolo scale is more objective and quantitative than

56 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 36 currently used methods. This study provides Level II evidence that the author s modified Prolo scale may be reasonable to assess outcomes for cervical radiculopathy from degenerative disorders. Klein et al 34 reported results from a prospective observational study assessing patient outcomes using the Health Status Questionnaire after one- or twolevel ACDF. In the 28 patients included in the study, statistically significant improvements were found in postoperative scores for bodily pain (p<0.001), vitality (p=0.003), physical function (p=0.01), role function/physical (p=0.0003) and social function (p=0.0004). No significant differences were found for three health scales: general health, mental health and role function associated with emotional limitations. Authors concluded that the HSQ may be a good disease specific outcome tool for one- and two-level ACDF. This small study provides Level II evidence that the HSQ may be a good outcome measure for assessing treatment of cervical radiculopathy from degenerative disorders. Lofgren et al 41 conducted a prospective observational study to follow the clinical outcome after surgery for cervical radiculopathy from degenerative disorders and to compare it with the outcome after conservative treatment. Forty-three surgical patients were studied prospectively and received ACDF (Cloward-single level). Their outcomes were compared with a control group of 39 patients (two did have surgery) who were treated conservatively. The conservative treatment protocol was not described. Outcomes were assessed at three months, six months, nine months and two years. Pain reduction measured with the VAS (arm) was more pronounced among the surgically treated patients at the final follow-up for maximal neck pain (p=0.03) and at three months and nine months, respectively, for average neck pain (p=0.02, both). Initially there was no statistically significant difference in pain intensity between the surgically and conservatively treated groups. Sickness Impact Profile showed that patients scheduled for surgery had higher sickness impact in the overall index. The authors concluded that surgically treated patients demonstrated an improvement in VAS (arm) pain and SIP scores, as well as at the clinical examination, all indicating a true improvement, although only partially maintained. This study provides Level I evidence that SIP may be a useful surgical outcome measure for patients with cervical radiculopathy from degenerative disorders. Witzmann et al 64 described a retrospective observational study designed to determine the clinical and economic outcome of patients undergoing posterior cervical foraminotomy for the treatment of compressive radiculopathy. At mean follow-up of 3.1 years, VAS scores indicated 93% of the 67 patients included in the study were improved. Prolo scores indicated 90% of patients had an excellent economic outcome and 79% of patients returned to their prior employment. In critique, patients were enrolled at different points in their disease with 57 single-level surgeries and 10 multiple level surgeries. Less than 80% of patients were available for follow-up. Due to these limitations, this potential Level II study provides Level III evidence that the Prolo scale may be an appropriate outcome measure to assess surgical treatment results for cervical radiculopathy from degenerative disorders. Xie et al 65 performed a prospective randomized controlled trial to determine the clinical outcome of ACD, ACDF and ACDFI. Of the 45 patients included in the study, 15 were assigned to each treatment group. Outcomes were asessed at three weeks, six weeks, three months, six months, one year and two years. SF-36 scores demonstrated a dynamic postoperative improvement followed by further gradual improvement in both physical and mental components as well as other subscale scores in all groups during the follow-up period (ρ<0.05). The amount of pain demonstrated by the McGill pain scores significantly decreased for all three groups immediately after surgery and continued to decline, plateauing at about one year. The authors concluded that SF- 36 scores improved in all three groups during the

57 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 37 follow-up period. McGill pain scores markedly improved immediately after surgery and continued to improve until the one year follow-up evaluation before plateauing. In critique, neither patients nor reviewers were masked to treatment group and the sample size was small. Three of the 45 patients were lost to follow-up. Patients included in the study were enrolled at different points in their disease and received surgery at single and multiple levels. Due to these limitations, this potential Level I study provides Level II evidence that the McGill pain scores may be an appropriate outcome tool for cervical radiculopathy from degenerative disorders treated with surgery. Zoega et al 65 described a prospective observational study of patients undergoing ACDF or ACDFI at single or multiple levels to determine the usefulness of outcome scores in the treatment of degenerative disc disease. Of the 46 patients included in the study, 12 received single-level ACDF, 10 received two-level ACDF, 15 received single-level ACDFI and 9 received two-level ACDFI. At two years, 81% of patients were satisfied with the outcome of surgery. All scores improved in the group operated on at two-levels. VAS arm and neck pain decreased in both groups. The improvement in arm pain was significantly more pronounced in patients operated with a plate at twolevels compared to those who were operated without a plate. At two year follow-up, patients with an excellent or good result according to Odom s criteria had a lower Million Index (ρ<0.0005), Oswestry Index (ρ<0.0005) and Zung Depression Scale (ρ=0.024) score than the group classified as fair or poor. There was a significant correlation (ρ<0.0001) for all scores between the test and retest. The authors concluded that Modified Million Index and Oswestry Index are clinically useful tools in the evaluation of outcome after degenerative cervical disc disease surgery. The outcome after surgery measured with the Oswestry Index, Modified Million Index, and VAS neck and arm pain seem to correlate well with the classification of outcome by Odom. This study provides Level II evidence that the Modified Million Index and Modified Oswestry Disability Index may be appropriate outcome measures for cervical radiculopathy from degenerative disorders treated with surgery. Future Directions for Research Disease specific outcome measures like the PSFS and the HSQ have been developed and seem to be useful in assessing outcome for the treatment of cervical radiculopathy from degenerative disorders. These measures are limited in that they have not been widely used or accepted. Outcome measures such as these need to be incorporated into Level I studies to confirm their validity and to establish themselves as acceptable research tools to quantitate outcome after cervical radiculopathy from degenerative disorders. References 1. Alrawi MF, Khalil NM, Mitchell P, Hughes SP. The value of neurophysiological and imaging studies in predicting outcome in the surgical treatment of cervical radiculopathy. Eur Spine J. Apr 2007;16(4): Anderberg L, Annertz M, Brandt L, Saveland H. Selective diagnostic cervical nerve root block--correlation with clinical symptoms and MRI-pathology. Acta Neurochir (Wien). Jun 2004;146(6): ; discussion Anderson PA, Subach BR, Riew KD. Predictors of outcome after anterior cervical discectomy and fusion: a multivariate analysis. Spine. Jan ;34(2): Andrews NB, Lawson HL, Odjidja TL. Elective non-instrumented anterior cervical diskectomy and fusion in Ghana: a preliminary report. West Afr J Med. Jun 2003;22(2): Arnold P, Boswell S, McMahon J. Threaded interbody fusion cage for adjacent segment degenerative disease after previous anterior cervical fusion. Surg Neurol. Oct 2008;70(4): Balasubramanian C, Price R, Brydon H. Anterior cervical microforaminotomy for cervical radiculopathy--results and review. Minim Invasive Neurosurg. Oct 2008;51(5): Boehm H, Greiner-Perth R, El-Saghir H, Allam Y. A new minimally invasive posterior approach for the treatment of cervical radiculopathy and myelopathy: surgical technique and preliminary results. Eur Spine J. Jun 2003;12(3): Bolton JE, Humphreys BK. The Bournemouth Questionnaire: a short-form comprehensive outcome measure. II. Psychometric properties in neck pain patients. J Manipulative Physiol Ther. Mar-Apr 2002;25(3):

58 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Bommireddy R, Kamat A, Smith ET, et al. Magnetic resonance image findings in the early post-operative period after anterior cervical discectomy. Eur Spine J. Jan 2007;16(1): Caroli E, Orlando ER, D Andrea G, Ferrante L. Anterior cervical fusion with interbody titanium cage containing surgical bone site graft: our institution s experience in 103 consecutive cases of degenerative spondylosis. J Spinal Disord Tech. May 2007;20(3): Cauthen JC, Kinard RE, Vogler JB, et al. Outcome analysis of noninstrumented anterior cervical discectomy and interbody fusion in 348 patients. Spine (Phila Pa 1976). Jan ;23(2): Chiba K, Ogawa Y, Ishii K, et al. Long-term results of expansive open-door laminoplasty for cervical myelopathy - Average 14-year follow-up study. Spine. Dec 2006;31(26): Chiles BW, Leonard MA, Choudhri HF, Cooper PR. Cervical spondylotic myelopathy: Patterns of neurological deficit and recovery after anterior cervical decompression. Neurosurgery. Apr 1999;44(4): Cho DY, Lee WY, Sheu PC. Treatment of multilevel cervical fusion with cages. Surgical Neurology. Nov 2004;62(5): Cleland JA, Fritz JM, Whitman JM, Palmer JA. The reliability and construct validity of the Neck Disability Index and patient specific functional scale in patients with cervical radiculopathy. Spine (Phila Pa 1976). Mar ;31(5): Dai LY, Jiang LS. Anterior cervical fusion with interbody cage containing beta-tricalcium phosphate augmented with plate fixation: a prospective randomized study with 2-year follow-up. Eur Spine J. May 2008;17(5): Davis RA. A long-term outcome study of 170 surgically treated patients with compressive cervical radiculopathy. Surg Neurol. Dec 1996;46(6): ; discussion Duggal N, Pickett GE, Mitsis DK, Keller JL. Early clinical and biomechanical results following cervical arthroplasty. Neurosurg Focus. Sep ;17(3):E Fernandez-Fairen M, Sala P, Dufoo M, Jr., Ballester J, Murcia A, Merzthal L. Anterior cervical fusion with tantalum implant: a prospective randomized controlled study. Spine. Mar ;33(5): Fessler RG, Khoo LT. Minimally invasive cervical microendoscopic foraminotomy: an initial clinical experience. Neurosurgery. Nov 2002;51(5 Suppl):S Fish DE, Kobayashi HW, Chang TL, Pham Q. MRI Prediction of Therapeutic Response to Epidural Steroid Injection in Patients with Cervical Radiculopathy. Am J Phys Med Rehabil. Mar 2009;88(3): Foley KT, Mroz TE, Arnold PM, et al. Randomized, prospective, and controlled clinical trial of pulsed electromagnetic field stimulation for cervical fusion. Spine J. May 2008;8(3): Goffin J, Van Calenbergh F, van Loon J, et al. Intermediate follow-up after treatment of degenerative disc disease with the Bryan Cervical Disc Prosthesis: single-level and bi-level. Spine (Phila Pa 1976). Dec ;28(24): Goldberg EJ, Singh K, Van U, Garretson R, An HS. Comparing outcomes of anterior cervical discectomy and fusion in workman s versus non-workman s compensation population. Spine J. Nov-Dec 2002;2(6): Hacker RJ, Cauthen JC, Gilbert TJ, Griffith SL. A prospective randomized multicenter clinical evaluation of an anterior cervical fusion cage. Spine. Oct ;25(20): ; discussion Herkowitz HN, Kurz LT, Overholt DP. Surgical management of cervical soft disc herniation. A comparison between the anterior and posterior approach. Spine (Phila Pa 1976). Oct 1990;15(10): Hida K, Iwasaki Y, Yano S, Akino M, Seki T. Long-term follow-up results in patients with cervical disk disease treated by cervical anterior fusion using titanium cage implants. Neurol Med Chir (Tokyo). Oct 2008;48(10): ; discussion Jagannathan J, Shaffrey CI, Oskouian RJ, et al. Radiographic and clinical outcomes following single-level anterior cervical discectomy and allograft fusion without plate placement or cervical collar. J Neurosurg Spine. May 2008;8(5): Jho HD, Jho DH. Ventral uncoforaminotomy. J Neurosurg Spine. Nov 2007;7(5): Jho HD, Kim WK, Kim MH. Anterior microforaminotomy for treatment of cervical radiculopathy: part 1--disc-preserving functional cervical disc surgery. Neurosurgery. Nov 2002;51(5 Suppl):S Kadoya S, Iizuka H, Nakamura T. Long-term outcome for surgically treated cervical spondylotic radiculopathy and myelopathy. Neurol Med Chir (Tokyo). May 2003;43(5): ; discussion Kim SH, Shin HC, Shin DA, Kim KN, Yoon do H. Early clinical experience with the mobi-c disc prosthesis. Yonsei Med J. Jun ;48(3): Kim SW, Limson MA, Kim SB, et al. Comparison of radiographic changes after ACDF versus Bryan disc arthroplasty in single and bi-level cases. Euro Spine J. Feb 2009;18(2): Klein GR, Vaccaro AR, Albert TJ. Health outcome assessment before and after anterior cervical discectomy and fusion for radiculopathy: a prospective analysis. Spine. Apr ;25(7): Koc RK, Menku A, Tucer B, Gocmez C, Akdemir H. Anterior cervical foraminotomy for unilateral spondylotic radiculopathy. Minim Invasive Neurosurg. Jun 2004;47(3):

59 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Kolstad F, Leivseth G, Nygaard OP. Transforaminal steroid injections in the treatment of cervical radiculopathy. A prospective outcome study. Acta Neurochir (Wien). Oct 2005;147(10): ; discussion Kotil K, Bilge T. Prospective study of anterior cervical microforaminotomy for cervical radiculopathy. J Clin Neurosci. Jul 2008;15(7): Kumar N, Gowda V. Cervical foraminal selective nerve root block: a two-needle technique with results. Eur Spine J. Apr 2008;17(4): Li J, Yan DL, Zhang ZH. Percutaneous cervical nucleoplasty in the treatment of cervical disc herniation. Eur Spine J. Dec 2008;17(12): Lin HL, Cho DY, Liu YF, Lee WY, Lee HC, Chen CC. Change of cervical balance following single to multi-level interbody fusion with cage. Br J Neurosurg. Dec 2008;22(6): Lofgren H, Johansen F, Skogar O, Levander B. Reduced pain after surgery for cervical disc protrusion/stenosis: a 2 year clinical follow-up. Disabil Rehabil. Sep ;25(18): Matsumoto M, Chiba K, Ishikawa M, Maruiwa H, Fujimura Y, Toyama Y. Relationships between outcomes of conservative treatment and magnetic resonance imaging findings in patients with mild cervical myelopathy caused by soft disc herniations. Spine. Jul ;26(14): Mummaneni PV, Burkus JK, Haid RW, Traynelis VC, Zdeblick TA. Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. J Neurosurg Spine. Mar 2007;6(3): Murphy DR, Hurwitz EL, Gregory A, Clary R. A nonsurgical approach to the management of patients with cervical radiculopathy: A prospective observational cohort study. J Manipulative Physiol Ther. May 2006;29(4): Murrey D, Janssen M, Delamarter R, et al. Results of the prospective, randomized, controlled multicenter Food and Drug Administration investigational device exemption study of the ProDisc-C total disc replacement versus anterior discectomy and fusion for the treatment of 1-level symptomatic cervical disc disease. Spine J. Apr 2009;9(4): Nunley PD, Jawahar A, Kerr EJ, 3rd, Cavanaugh DA, Howard C, Brandao SM. Choice of plate may affect outcomes for single versus multilevel ACDF: results of a prospective randomized single-blind trial. Spine J. Feb 2009;9(2): Odom GL, Finney W, Woodhall B. Cervical disk lesions. J Am Med Assoc. 1958;166(1): Oktenoglu T, Cosar M, Ozer AF, et al. Anterior cervical microdiscectomy with or without fusion. J Spinal Disord Tech. Jul 2007;20(5): Park JH, Roh KH, Cho JY, Ra YS, Rhim SC, Noh SW. Comparative analysis of cervical arthroplasty using Mobi-C and anterior cervical discectomy and husion using the Solis-cage. Journal of Korean Neurosurgical Society. 2008;44(4): Pechlivanis I, Brenke C, Scholz M, Engelhardt M, Harders A, Schmieder K. Treatment of degenerative cervical disc disease with uncoforaminotomy--intermediate clinical outcome. Minim Invasive Neurosurg. Aug 2008;51(4): Peolsson A, Peolsson M. Predictive factors for long-term outcome of anterior cervical decompression and fusion: a multivariate data analysis. Eur Spine J. Mar 2008;17(3): Pimenta L, McAfee PC, Cappuccino A, Cunningham BW, Diaz R, Coutinho E. Superiority of multilevel cervical arthroplasty outcomes versus single-level outcomes: 229 consecutive PCM prostheses. Spine. May ;32(12): Rao RD, Currier BL, Albert TJ, et al. Degenerative cervical spondylosis: clinical syndromes, pathogenesis, and management. J Bone Joint Surg Am. Jun 2007;89(6): Rocchi G, Caroli E, Salvati M, Delfini R. Multilevel oblique corpectomy without fusion: our experience in 48 patients. Spine. Sep ;30(17): Sasso RC, Smucker JD, Hacker RJ, Heller JG. Artificial disc versus fusion: a prospective, randomized study with 2-year follow-up on 99 patients. Spine. Dec ;32(26): ; discussion Scheufler KM, Kirsch E. Percutaneous multilevel decompressive laminectomy, foraminotomy, and instrumented fusion for cervical spondylotic radiculopathy and myelopathy: assessment of feasibility and surgical technique. J Neurosurg Spine. Nov 2007;7(5): Schoggl A, Reddy M, Saringer W, Ungersbock K. Social and economic outcome after posterior microforaminotomy for cervical spondylotic radiculopathy. Wien Klin Wochenschr. Mar ;114(5-6): Shad A, Leach JC, Teddy PJ, Cadoux-Hudson TA. Use of the Solis cage and local autologous bone graft for anterior cervical discectomy and fusion: early technical experience. J Neurosurg Spine. Feb 2005;2(2): Suetsuna F, Yokoyama T, Kenuka E, Harata S. Anterior cervical fusion using porous hydroxyapatite ceramics for cervical disc herniation. a two-year follow-up. Spine J. Sep- Oct 2001;1(5): Tan J, Zheng Y, Gong L, Liu X, Li J, Du W. Anterior cervical discectomy and interbody fusion by endoscopic approach: a preliminary report. J Neurosurg Spine. Jan 2008;8(1): Waldrop MA. Diagnosis and treatment of cervical radiculopathy using a clinical prediction rule and a multimodal intervention approach: a case series. J Orthop Sports Phys Ther. Mar 2006;36(3):

60 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Wang MY, Liu CY. Resorbable polylactic acid interbody spacers with vertebral autograft for anterior cervical discectomy and fusion. Neurosurgery. Jul 2005;57(1): ; discussion Wirth FP, Dowd GC, Sanders HF, Wirth C. Cervical discectomy. A prospective analysis of three operative techniques. Surg Neurol. Apr 2000;53(4): ; discussion Witzmann A, Hejazi N, Krasznai L. Posterior cervical foraminotomy. A follow-up study of 67 surgically treated patients with compressive radiculopathy. Neurosurg Rev. Dec 2000;23(4): Xie JC, Hurlbert RJ. Discectomy versus discectomy with fusion versus discectomy with fusion and instrumentation: a prospective randomized study. Neurosurgery. Jul 2007;61(1): ; discussion Zoega B, Karrholm J, Lind B. Outcome scores in degenerative cervical disc surgery. Euro Spine J. Apr 2000;9(2):

61 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 41 C. Medical and Interventional Treatment What is the role of pharmacological treatment in the management of cervical radiculopathy from degenerative disorders? A systematic review of the literature yielded no studies to adequately address the role of pharmacological treatment in the management of cervical radiculopathy from degenerative disorders. Future Directions for Research The work group identified the following suggestions for future studies which would generate meaningful evidence to assist in further defining the role of pharmacological treatment in the management of cervical radiculopathy from degenerative disorders. Recommendation #1: Future studies of the effects of pharmacological treatment in the management of cervical radiculopathy from degenerative disorders should include an untreated control group when ethically possible. Recommendation #2: Future outcome studies including patients with cervical radiculopathy from degenerative disorders treated only with pharmacological treatment should include subgroup analysis for this patient population. Pharmacological Treatment References 1. Peloso Paul Michael J, Gross A, Haines T, et al. Medicinal and injection therapies for mechanical neck disorders. Cochrane Database of Systematic Reviews Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine. Aug ;21(16): Verbiest H. Chapter 23. The management of cervical spondylosis. Clin Neurosurg. 1973;20: What is the role of physical therapy/exercise in the treatment of cervical radiculopathy from degenerative disorders? A systematic review of the literature yielded no studies to adequately address the role of physical therapy/exercise in the management of cervical radiculopathy from degenerative disorders. RECOMMENDATION: Emotional and cognitive factors (eg, job dissatisfaction) should be considered when addressing surgical or medical/interventional treatment for patients with cervical radiculopathy from degenerative disorders. GRADE OF RECOMMENDATION: I (Insufficient Evidence) Persson et al 6 conducted a prospective randomized controlled trial comparing coping strategies, pain and emotional relationships of patients with cervical radiculopathy of at least three months duration randomly assigned to one of three treatment groups. Of the 81 patients included in the study, 27 were assigned to cervical bracing, 27 to physical therapy and 27 to ACDF (Cloward technique). Three patients assigned to the surgical group refused the procedure and were handled in intent to treat analysis. In the surgical group, eight patients had a second operation: six on adjacent level, one infection and one plexus exploration. Eleven patients in the surgery group also received physical therapy. One patient in the physical therapy group and five in the collar group had surgery with Cloward technique. Chronic symptoms influenced both function and mental well being such as emotional state, level of anxiety, depression, sleep and coping behavior. Pain was the most important primary stressor. Surgery reduced the pain faster, but no difference was seen

62 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 42 after 12 months. Reoperation rate was 29%, mostly for adjacent segment disease. The low positive mood state (MACL score) did not improve over time. Patients who still had pain after treatment were more socially withdrawn and ceased to express their emotions. The Hospital Anxiety and Depression (HAD) anxiety score was especially high in patients before and after treatment. In patients with high pain intensity, low function, high depression and anxiety were seen. The group treated with surgery showed more anxiety and depression if pain continued, implying higher expectations and more disappointment if it failed. The strongest correlation between depression and pain was seen in the collar group, possibly because they received less attention overall. In general, coping strategies changed. Active coping (cognitive reappraisal and problem solving) was common before treatment, but disappeared after treatment, especially in the surgical group. Coping with pain was changed in general into a more passive/escape focused strategy. It appeared that with intervention, especially surgery, healthy active coping strategies tended to be replaced by passive coping strategies as patients allowed themselves to become more dependent on the intervention. This also implied that the ability for active coping was present before intervention, and thus cognitive behavioral treatment started concurrently with other interventions may be particularly successful for maintaining better coping patterns. Function was significantly related to pain intensity. About 40% had anxiety only partially connected to pain. Prior to treatment, 30% of patients were depressed. After 12 months, 20% suffered from depression. The authors concluded that cognitive and behavioral therapy is important to include in multidisciplinary rehabilitation. Patients need to improve coping strategies, self image and mood. In critique, neither patients nor reviewers were masked to treatment group, the sample size was small and duration of follow-up was short. Due to these limitations, this potential Level I study provides Level II evidence that there is a high incidence of behavioral and emotional dysfunction in cervical radiculopathy patients. Medical/interventional and surgical treatment must include a cognitive, behavioral component for either method to be successful. Future Directions for Research The work group identified the following suggestions for future studies which would generate meaningful evidence to assist in further defining the role of physical therapy/exercise in the management of cervical radiculopathy from degenerative disorders. Recommendation #1: Future studies of the effects of physical therapy/exercise in the management of cervical radiculopathy from degenerative disorders should include an untreated control group when ethically possible. Recommendation #2: Future outcome studies including patients with cervical radiculopathy from degenerative disorders treated only with physical therapy/exercise should include subgroup analysis for this patient population. Recommendation #3: Future studies evaluating the effects of emotional, cognitive and work-related issues would add to our understanding of how these factors affect outcomes in patients with cervical radiculopathy from degenerative disorders. Physical Therapy/Exercise References 1. Lipetz JS, Misra N, Silber JS. Resolution of pronounced painless weakness arising from radiculopathy and disk extrusion. Am J Phys Med Rehabil. Jul 2005;84(7): McClure P. The degenerative cervical spine: pathogenesis and rehabilitation concepts. J Hand Ther. Apr-Jun 2000;13(2): McCormack BM, Weinstein PR. Cervical spondylosis. An update. West J Med. Jul-Aug 1996;165(1-2): Murphy DR, Beres JL. Is treatment in extension contraindicated in the presence of cervical spinal cord compression without myelopathy? A case report. Man Ther. Oct 2008;13(5): Murphy DR, Hurwitz EL, Gregory A, Clary R. A nonsurgical approach to the management of patients with cervical

63 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 43 radiculopathy: A prospective observational cohort study. J Manipulative Physiol Ther. May 2006;29(4): Persson LC, Lilja A. Pain, coping, emotional state and physical function in patients with chronic radicular neck pain. A comparison between patients treated with surgery, physiotherapy or neck collar--a blinded, prospective randomized study. Disabil Rehabil. May ;23(8): Rosomoff HL, Fishbain D, Rosomoff RS. Chronic cervical pain: radiculopathy or brachialgia. Noninterventional treatment. Spine. Oct 1992;17(10 Suppl):S Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine. Aug ;21(16): Waldrop MA. Diagnosis and treatment of cervical radiculopathy using a clinical prediction rule and a multimodal intervention approach: a case series. J Orthop Sports Phys Ther. Mar 2006;36(3): What is the role of manipulation/ chiropractics in the treatment of cervical radiculopathy from degenerative disorders? A systematic review of the literature yielded no studies to adequately address the role of manipulation/ chiropractics in the management of cervical radiculopathy from degenerative disorders. The review did identify several case reports and series describing serious vascular and nonvascular complications and adverse outcomes associated with manipulation including radiculopathy, myelopathy, disc herniation and vertebral artery compression. 9,13,14,17 The true incidence of such complications is unknown and estimates vary widely. Some complications have occurred in patients with previously unrecognized spinal metastatic disease who did not have premanipulation imaging. Most patients with serious complications of manipulation require emergent surgical treatment. RECOMMENDATION: As the efficacy of manipulation in the treatment of cervical radiculopathy from degenerative disorders is unknown, careful consideration should be given to evidence suggesting that manipulation may lead to worsened symptoms or significant complications when considering this therapy. Premanipulation imaging may reduce the risk of complications. Work Group Consensus Statement Future Directions for Research The work group identified the following suggestions for future studies which would generate meaningful evidence to assist in further defining the role of manipulation/chiropractics in the management of cervical radiculopathy from degenerative disorders. Recommendation #1: Future studies of the effects of manipulation/chiropractics in the management of cervical radiculopathy from degenerative disorders should include an untreated control group when ethically possible. Recommendation #2: Future outcome studies including patients with cervical radiculopathy from degenerative disorders treated only with manipulation/chiropractics should include subgroup analysis for this patient population. Recommendation #3: Future studies of the effects of manipulation/chiropractics in the management of cervical radiculopathy from degenerative disorders should include data and discussion about any complications associated with treatment. Manipulation/Chiropractics References 1. Brouillette DL, Gurske DT. Chiropractic treatment of cervical radiculopathy caused by a herniated cervical disc. J Manipulative Physiol Ther. Feb 1994;17(2): Eriksen K. Management of cervical disc herniation with upper cervical chiropractic care. J Manipulative Physiol Ther. Jan 1998;21(1): Gudavalli S, Kruse RA. Foraminal stenosis with radiculopathy from a cervical disc herniation in a 33-year-old man treated with flexion distraction decompression manipulation. J Manipulative Physiol Ther. Jun 2008;31(5):

64 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Haneline MT, Lewkovich G. Malone D G, Baldwin N G, Tomecek F J, et al: Complications of cervical spine manipulation therapy: 5-year retrospective study in a single-group practice. Neurosurg Focus. 13(6):Clinical Pearl, Neurosurg Focus. Mar ;14(3):e10; author reply e Heckmann JG, Lang CJ, Zobelein I, Laumer R, Druschky A, Neundorfer B. Herniated cervical intervertebral discs with radiculopathy: an outcome study of conservatively or surgically treated patients. J Spinal Disord. Oct 1999;12(5): Herzog J. Use of cervical spine manipulation under anesthesia for management of cervical disk herniation, cervical radiculopathy, and associated cervicogenic headache syndrome. J Manipulative Physiol Ther. Mar-Apr 1999;22(3): Hubka MJ, Phelan SP, Delaney PM, Robertson VL. Rotary manipulation for cervical radiculopathy: observations on the importance of the direction of the thrust. J Manipulative Physiol Ther. Nov-Dec 1997;20(9): Kruse RA, Imbarlina F, De Bono VF. Treatment of cervical radiculopathy with flexion distraction. J Manipulative Physiol Ther. Mar-Apr 2001;24(3): Malone DG, Baldwin NG, Tomecek FJ, et al. Complications of cervical spine manipulation therapy: 5-year retrospective study in a single-group practice. Neurosurg Focus. Dec ;13(6):ecp Murphy DR. Herniated disc with radiculopathy following cervical manipulation: nonsurgical management. Spine J. Jul-Aug 2006;6(4): Murphy DR, Beres JL. Cervical myelopathy: a case report of a near-miss complication to cervical manipulation. J Manipulative Physiol Ther. Sep 2008;31(7): Murphy DR, Beres JL. Is treatment in extension contraindicated in the presence of cervical spinal cord compression without myelopathy? A case report. Man Ther. Oct 2008;13(5): Oppenheim JS, Spitzer DE, Segal DH. Nonvascular complications following spinal manipulation. Spine J. Nov 2005;5(6): Padua L, Padua R, LoMonaco M, Tonali PA. Radiculomedullary complications of cervical spinal manipulation. Spinal Cord. Aug 1996;34(8): Pollard H, Tuchin P. Cervical radiculopathy: a case for ancillary therapies? J Manipulative Physiol Ther. May 1995;18(4): Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine. Aug ;21(16): Tseng SH, Lin SM, Chen Y, Wang CH. Ruptured cervical disc after spinal manipulation therapy: report of two cases. Spine. Feb ;27(3):E Waldrop MA. Diagnosis and treatment of cervical radiculopathy using a clinical prediction rule and a multimodal intervention approach: a case series. J Orthop Sports Phys Ther. Mar 2006;36(3): What is the role of epidural steroid injections for the treatment of cervical radiculopathy from degenerative disorders? A systematic review of the literature revealed limited high quality studies to address this question. There is Level IV data indicating that transforaminal epidural steroid injections may provide relief for 60% of patients, and about 25% of patients referred with clear surgical indications may obtain at least shortterm pain relief negating the need for surgery. Interestingly, there is limited Level II evidence that suggests that the addition of steroid to local anesthetic does not improve pain relief in these patients at three weeks post-injection. All of the studies that qualified as at least Level IV data used transforaminal epidural injections under fluoroscopic or CT guidance as the method of treatment. For this reason, the work group was unable to make recommendations regarding the safety or efficacy of interlaminar epidural steroid injections for the treatment of cervical radiculopathy. The literature search yielded a number of publications demonstrating that transforaminal epidural steroid injections are not without risk and the potential complications, including spinal cord injury and death, need to be considered before performing this procedure. 20,25 RECOMMENDATION: Transforaminal epidural steroid injections using fluoroscopic or CT guidance may be considered when developing a medical/interventional treatment plan for patients with cervical radiculopathy from degenerative disorders. Due consideration should be given to the potential complications. GRADE OF RECOMMENDATION: C

65 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 45 Cyteval et al 10 described a prospective case series of 30 patients treated with transforaminal epidural steroid injections under CT guidance. At six month follow-up 60% of patients obtained good or excellent pain relief. In critique of this study, this is a nonrandomized, nonconsecutive case series with a small sample size and fairly short term follow-up. This study provides Level IV evidence that 60% of patients can obtain good or excellent pain relief at up to six months following transforaminal epidural steroid injections. Kim et al 14 retrospectively reviewed 19 patients who underwent cervical transforaminal epidural steroid injections under CT guidance. At 16 week follow-up patients noted an average 50% reduction in pain. In critique of this study, it is retrospective and excluded any patients with neurologic deficits. Further limiting the relevance of this study is the small sample size and relatively short term follow-up. This study provides Level IV evidence that, on average, patients will experience a 50% reduction in pain 16 weeks following transforaminal epidural steroid injections. Kolstad et al 15 described a prospective case series of 21 patients with cervical radiculopathy awaiting cervical disc surgery. Two cervical transforaminal epidural steroid injections under fluoroscopic guidance were performed two weeks apart. Patients were followed for four months with approximately 25% opting to cancel surgery because of clinical improvement. In critique of this study, the sample size is small. It is difficult to make any outcome statements regarding these patients other than they opted out of surgery at four months following this treatment. This study provides Level IV evidence that 25% of patients awaiting cervical disc surgery can obtain enough pain relief at four months following two cervical transforaminal epidural steroid injections to cancel surgery. Lin et al 17 described a retrospective case series of 70 patients considered potential surgical candidates for cervical radiculopathy. Patients underwent cervical transforaminal epidural steroid injections and were followed until they obtained satisfactory relief or underwent surgical management. Of these patients, 65% (45/70) reported good or excellent results with regard to pain relief and 63% (44/70) opted not to have surgery. In critique of this study, no validated outcome measures were used, though avoiding surgery could be considered a valid endpoint. This study provides Level IV evidence that 65% of patients with cervical radiculopathy can obtain pain relief to the level necessary to avoid surgery. Anderberg et al 3 described a prospective randomized controlled trial of 40 patients with cervical radiculopathy. They were randomized into one group that received transforaminal epidural steroid injections and a control group that received transforaminal injections of local anesthetic. At three week follow-up, 40% (8/20) of the patients in the steroid injection group, and 35% (7/20) of the patients in the control group noted improvement in their pain on a VAS. This difference was not statistically significant. In critique of this study, no validated outcome measures were used and the sample size was very small. This potential Level I study was downgraded to a Level II study because of these shortcomings. This study provides Level II evidence that the addition of steroid to local anesthetic in transforaminal epidural injections provides no additional therapeutic benefit at three weeks post-injection. Future Directions for Research The work group identified the following suggestions for future studies which would generate meaningful evidence to assist in further defining the role of epidural steroid injections in the management of cervical radiculopathy from degenerative disorders. Recommendation #1: Future studies of the effects of epidural steroid injections in the management of cervical radiculopathy from degenerative disorders should include an untreated control group when ethically possible.

66 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 46 Recommendation #2: Future outcome studies including patients with cervical radiculopathy from degenerative disorders treated only with epidural steroid injections should include subgroup analysis for this patient population. Recommendation #3: Future studies of the effects of epidural steroid injections in the management of cervical radiculopathy from degenerative disorders should include data and discussion about any complications associated with treatment. Epidural Steroid Injection References 1. Alexandre A, Coro L, Azuelos A, et al. Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations. Acta Neurochir Suppl. 2005;92: Anderberg L, Annertz M, Brandt L, Saveland H. Selective diagnostic cervical nerve root block--correlation with clinical symptoms and MRI-pathology. Acta Neurochir (Wien). Jun 2004;146(6): ; discussion Anderberg L, Annertz M, Persson L, Brandt L, Saveland H. Transforaminal steroid injections for the treatment of cervical radiculopathy: a prospective and randomised study. Eur Spine J. Mar 2007;16(3): Anderberg L, Saveland H, Annertz M. Distribution patterns of transforaminal injections in the cervical spine evaluated by multi-slice computed tomography. Eur Spine J. Oct 2006;15(10): Benyamin R, Singh V, Parr AT, Conn A, Diwan S, Abdi S. Systematic Review of the Effectiveness of Cervical Epidurals in the Management of Chronic Neck Pain. Pain Physician. Jan-Feb 2009;12(1): Boswell MV, Hansen HC, Trescot AM, Hirsch JA. Epidural steroids in the management of chronic spinal pain and radiculopathy. Pain Physician. Jul 2003;6(3): Bush K, Hillier S. Outcome of cervical radiculopathy treated with periradicular/epidural corticosteroid injections: a prospective study with independent clinical review. Eur Spine J. 1996;5(5): Carragee EJ, Hurwitz EL, Cheng I, et al. Treatment of neck pain - Injections and surgical interventions: Results of the bone and joint decade task force on neck pain and its associated disorders. Spine. Feb 2008;33(4):S153- S Castagnera L, Maurette P, Pointillart V, Vital JM, Erny P, Senegas J. Long-term results of cervical epidural steroid injection with and without morphine in chronic cervical radicular pain. Pain. Aug 1994;58(2): Cyteval C, Thomas E, Decoux E, et al. Cervical radiculopathy: open study on percutaneous periradicular foraminal steroid infiltration performed under CT control in 30 patients. AJNR Am J Neuroradiol. Mar 2004;25(3): Ellenberg MR, Honet JC, Treanor WJ. Cervical radiculopathy. Arch Phys Med Rehabil. Mar 1994;75(3): Fish DE, Kobayashi HW, Chang TL, Pham Q. MRI prediction of therapeutic response to epidural steroid injection in patients with cervical radiculopathy. Am J Phys Med Rehabil. March 2009;88(3): Heckmann JG, Lang CJ, Zobelein I, Laumer R, Druschky A, Neundorfer B. Herniated cervical intervertebral discs with radiculopathy: an outcome study of conservatively or surgically treated patients. J Spinal Disord. Oct 1999;12(5): Kim H, Lee SH, Kim MH. Multislice CT fluoroscopy-assisted cervical transforaminal injection of steroids: technical note. J Spinal Disord Tech. Aug 2007;20(6): Kolstad F, Leivseth G, Nygaard OP. Transforaminal steroid injections in the treatment of cervical radiculopathy. A prospective outcome study. Acta Neurochir (Wien). Oct 2005;147(10): ; discussion Kwon JW, Lee JW, Kim SH, et al. Cervical interlaminar epidural steroid injection for neck pain and cervical radiculopathy: Effect and prognostic factors. Skeletal Radiology. May 2007;36(5): Lin EL, Lieu V, Halevi L, Shamie AN, Wang JC. Cervical epidural steroid injections for symptomatic disc herniations. J Spinal Disord Tech. May 2006;19(3): Pawl RP, Matz M, Wissinger JP, Vacca DF, Goldfarb RP. Epidural steroids for cervical and lumbar radiculopathy. Surg Neurol. Nov 1996;46(5): Peloso Paul Michael J, Gross A, Haines T, et al. Medicinal and injection therapies for mechanical neck disorders. Cochrane Database of Systematic Reviews Rosenkranz M, Grzyska U, Niesen W, et al. Anterior spinal artery syndrome following periradicular cervical nerve root therapy. J Neurol. Feb 2004;251(2): Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine. Aug ;21(16): Slipman CW, Chow DW. Therapeutic spinal corticosteroid injections for the management of radiculopathies. Phys Med Rehabil Clin N Am. Aug 2002;13(3): Strobel K, Pfirrmann CW, Schmid M, Hodler J, Boos N, Zanetti M. Cervical nerve root blocks: indications and role of MR imaging. Radiology. Oct 2004;233(1): Strub WM, Brown TA, Ying J, Hoffmann M, Ernst RJ, Bulas RV. Translaminar cervical epidural steroid injection: short-term results and factors influencing outcome. J Vasc Interv Radiol. Sep 2007;18(9): Tiso RL, Cutler T, Catania JA, Whalen K. Adverse central nervous system sequelae after selective transforaminal block: the role of corticosteroids. Spine J. Jul-Aug 2004;4(4):

67 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 47 What is the role of ancillary treatments such as bracing, traction, electrical stimulation, acupuncture and transcutaneous electrical stimulation in the treatment of cervical radiculopathy from degenerative disorders? RECOMMENDATION: Ozone injections, cervical halter traction and combinations of medications, physical therapy, injections and traction have been associated with improvements in patient reported pain in uncontrolled case series. Such modalities may be considered recognizing that no improvement relative to the natural history of cervical radiculopathy has been demonstrated. Work Group Consensus Statement Alexandre et al 1 reported results of a retrospective case series investigating the effects of intervertebral disc and paravertebral injections of ozone and oxygen in patients with CDH. The authors reported that 80% of the 252 patients experienced some degree symptom relief at some point following the injections. In critique, this case series did not utilize any validated outcome measures, report specific data or delineate a specific follow-up period. No comparison to the natural history was made. Due to these weaknesses, this potential Level IV study provides Level V evidence suggesting that approximately 80% of patients will report symptomatic relief from cervical radiculopathy at some point following ozone and oxygen injection into the intervertebral disc and paravertebral musculature. Olivero et al 6 discussed a retrospective case series evaluating the use of halter traction and collar in patients with mild cervical radiculopathy. The authors reported that of the 81 patients included in the study, 75% of patients with mild cervical radiculopathy of approximately six weeks reported some degree of pain relief with halter traction. In critique, this case series did not utilize any validated outcome measures and had a very short follow-up period. Due to these weaknesses, this potential Level IV study provides Level V evidence suggesting that 75% of patients with mild radiculopathy may improve with traction over a six week time frame. Saal et al 8 presented a retrospective case series evaluating the use of a multifaceted medical/interventional treatment program for 26 patients with cervical radiculopathy. Of the 26 patients who completed the program, 24 were available for follow-up at three months, with 89% (22/24) of patients reporting a good treatment outcome. In critique, this study did not utilize any validated outcome measures. This study provides Level IV evidence that a multifaceted medical/interventional treatment program is associated with good outcomes in many patients with cervical radiculopathy. RECOMMENDATION: Emotional and cognitive factors (eg, job dissatisfaction) should be considered when addressing surgical or medical/interventional treatment for patients with cervical radiculopathy from degenerative disorders. GRADE OF RECOMMENDATION: I (Insufficient Evidence) Persson et al 7 conducted a prospective randomized controlled trial comparing coping strategies, pain and emotional relationships of patients with cervical radiculopathy of at least three months duration randomly assigned to one of three treatment groups. Of the 81 patients included in the study, 27 were assigned to cervical bracing, 27 to physical therapy and 27 to ACDF (Cloward technique). Three patients assigned to the surgical group refused the procedure and were handled in intent to treat analysis. In the surgical group, eight patients had a second operation: six on adjacent level, one infection and one plexus exploration. Eleven patients in the surgery group also received physical therapy. One patient

68 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 48 in the physical therapy group and five in the collar group had surgery with Cloward technique. Chronic symptoms influenced both function and mental well being such as emotional state, level of anxiety, depression, sleep and coping behavior. Pain was the most important primary stressor. Surgery reduced the pain faster, but no difference was seen after 12 months. Reoperation rate was 29%, mostly for adjacent segment disease. The low positive mood state (MACL score) did not improve over time. Patients who still had pain after treatment were more socially withdrawn and ceased to express their emotions. The Hospital Anxiety and Depression (HAD) anxiety score was especially high in patients before and after treatment. In patients with high pain intensity, low function, high depression and anxiety were seen. The group treated with surgery showed more anxiety and depression if pain continued, implying higher expectations and more disappointment if it failed. The strongest correlation between depression and pain was seen in the collar group, possibly because they received less attention overall. In general, coping strategies changed. Active coping (cognitive reappraisal and problem solving) was common before treatment, but disappeared after treatment, especially in the surgical group. Coping with pain was changed in general into a more passive/escape focused strategy. It appeared that with intervention, especially surgery, healthy active coping strategies tended to be replaced by passive coping strategies as patients allowed themselves to become more dependent on the intervention. This also implied that the ability for active coping was present before intervention, and thus cognitive behavioral treatment started concurrently with other interventions may be particularly successful for maintaining better coping patterns. Function was significantly related to pain intensity. About 40% had anxiety only partially connected to pain. Prior to treatment, 30% of patients were depressed. After 12 months, 20% suffered from depression. The authors concluded that cognitive and behavioral therapy is important to include in multidisciplinary rehabilitation. Patients need to improve coping strategies, self image and mood. In critique, neither patients nor reviewers were masked to treatment group, the sample size was small and duration of follow-up was short. Due to these limitations, this potential Level I study provides Level II evidence that there is a high incidence of behavioral and emotional dysfunction in cervical radiculopathy patients. Medical/interventional and surgical treatment must include a cognitive, behavioral component for either method to be successful. Future Directions for Research The work group identified the following suggestions for future studies which would generate meaningful evidence to assist in further defining the role of ancillary treatments in the management of cervical radiculopathy from degenerative disorders. Recommendation #1: Future studies of the effects of ancillary treatments in the management of cervical radiculopathy from degenerative disorders should include an untreated control group when ethically possible. Recommendation #2: Future outcome studies including patients with cervical radiculopathy from degenerative disorders treated only with ancillary treatments should include subgroup analysis for this patient population. Recommendation #3: Future studies evaluating the effects of emotional, cognitive and work-related issues would add to our understanding of how these factors affect outcomes in patients with cervical radiculopathy from degenerative disorders. Ancillary Treatment References 1. Alexandre A, Coro L, Azuelos A, et al. Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations. Acta Neurochir Suppl. 2005;92: Constantoyannis C, Konstantinou D, Kourtopoulos H, Papadakis N. Intermittent cervical traction for cervical radiculopathy caused by large-volume herniated disks. J Manipulative Physiol Ther. Mar-Apr 2002;25(3):

69 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Ellenberg MR, Honet JC, Treanor WJ. Cervical radiculopathy. Arch Phys Med Rehabil. Mar 1994;75(3): LaBan MM, Macy JA, Meerschaert JR. Intermittent cervical traction: a progenitor of lumbar radicular pain. Arch Phys Med Rehabil. Mar 1992;73(3): Matsumoto M, Chiba K, Ishikawa M, Maruiwa H, Fujimura Y, Toyama Y. Relationships between outcomes of conservative treatment and magnetic resonance imaging findings in patients with mild cervical myelopathy caused by soft disc herniations. Spine. Jul ;26(14): Olivero WC, Dulebohn SC. Results of halter cervical traction for the treatment of cervical radiculopathy: retrospective review of 81 patients. Neurosurg Focus. Feb ;12(2):ECP1. 7. Persson LC, Lilja A. Pain, coping, emotional state and physical function in patients with chronic radicular neck pain. A comparison between patients treated with surgery, physiotherapy or neck collar--a blinded, prospective randomized study. Disabil Rehabil. May ;23(8): Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine. Aug ;21(16): Verbiest H. Chapter 23. The management of cervical spondylosis. Clin Neurosurg. 1973;20: Waldrop MA. Diagnosis and treatment of cervical radiculopathy using a clinical prediction rule and a multimodal intervention approach: a case series. J Orthop Sports Phys Ther. Mar 2006;36(3):

70 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 50 D. Surgical Treatment Does surgical treatment (with or without preoperative medical/interventional treatment) result in better outcomes than medical/interventional treatment for cervical radiculopathy from degenerative disorders? RECOMMENDATION: Surgical intervention is suggested for the rapid relief of symptoms of cervical radiculopathy from degenerative disorders when compared to medical/interventional treatment. GRADE OF RECOMMENDATION: B Persson et al 48 described a prospective randomized controlled trial comparing outcomes in pain, strength and sensation in three treatment groups of patients with cervical radiculopathy of a minimum of three months duration. Of the 81 patients included in the study, 27 were assigned to cervical bracing, 27 to physical therapy and 27 to ACDF (Cloward technique). Three surgical patients refused the procedure and were handled in intent to treat analysis. In the surgical group, eight patients had a second operation: six on adjacent level, one infection and one plexus exploration. Eleven patients in the surgery group also received physical therapy. One patient in the physical therapy group and five in the collar group had surgery with Cloward technique. Strength measurements were all performed by one physical therapist with standard protocol. Physical therapy was done for 15 visits and was not standardized. Several different collars were used and worn for three months. At four month follow-up, pain was improved in the surgical and physical therapy groups and improvement in pain scores in the surgical group was significantly better than in the collar group. After another year, the pain was about the same across groups. The surgical group improved strength a little faster, but at final follow-up strength improvement was equal across groups. At final follow-up, there was no difference between groups on the sensory exam. The authors concluded that there was no difference in outcomes after one year between patients treated with a collar, physical therapy or surgery. In critique, neither patients nor reviewers were masked to treatment group, the sample size was small and duration of follow-up was short. Due to these limitations, this potential Level I study provides Level II evidence that at one year, outcomes are similar for medical/interventional treatment and surgical treatment of patients with cervical radiculopathy from degenerative disorders. Due to the small sample size, one may not expect to see a difference between the groups on a statistical basis. Surgical treatment resulted in improved outcomes earlier in the postoperative treatment period when compared with the medical/interventional treatment group. Sampath et al 53 reported results of a prospective, multicenter comparative study evaluating clinical outcomes in patients with cervical radiculopathy. Medical/interventional treatment was nonstandardized in this multicenter trial and included medications, steroids, bed rest, exercise, traction, bracing, injections, chiropractic care, acupuncture and homeopathic medicine. Surgery included foraminotomy, ACD and ACDF. Of the 246 patients with radiculopathy, 160 were nonrandomized to medical treatment and 86 received surgical treatment. Of the 246 patients, only 155 reported data at final followup. Of the 155 patients, 104 were medically/interventionally treated and 51 had surgery.

71 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 51 In general, pain scores were worse in the surgical group preoperatively than in the medical/interventional treatment group. Both groups improved significantly, with greater improvement seen in the surgical group. Patient satisfaction, neurological improvement and functional improvement were seen in both groups, with greater improvement reported in the surgical group. There was significant improvement in activities of daily living (ADL) in the surgical group. Although there was improvement, there was still significant pain in about 26% of surgical patients. The number returning to work did not differ before and after intervention in either group despite improved functional ability, implying that the most important factor for return to work was work status prior to treatment. The authors concluded that surgery appears to have more success than medical/interventional treatment, although both help. Despite this, a substantial percentage of patients continue to have severe pain, neurologic symptoms and no work activity. In critique, this was a nonrandomized study which did not utilize validated outcome measures. There was a high attrition rate to follow-up and the length of follow-up was short. Both medical/interventional and surgical treatment protocols were nonstandardized. Due to these limitations, this potential Level II study provides Level III evidence that surgical treatment results in improved outcomes when compared with medical/interventional treatment on short term follow-up. RECOMMENDATION: Emotional and cognitive factors (eg, job dissatisfaction) should be considered when addressing surgical or medical/interventional treatment for patients with cervical radiculopathy from degenerative disorders. GRADE OF RECOMMENDATION: I (Insufficient Evidence) Persson et al 47 conducted a prospective randomized controlled trial comparing coping strategies, pain and emotional relationships of patients with cervical radiculopathy of at least three months duration randomly assigned to one of three treatment groups. Of the 81 patients included in the study, 27 were assigned to cervical bracing, 27 to physical therapy and 27 to ACDF (Cloward technique). Three patients assigned to the surgical group refused the procedure and were handled in intent to treat analysis. In the surgical group, eight patients had a second operation: six on adjacent level, one infection and one plexus exploration. Eleven patients in the surgery group also received physical therapy. One patient in the physical therapy group and five in the collar group had surgery with Cloward technique. Chronic symptoms influenced both function and mental well being such as emotional state, level of anxiety, depression, sleep and coping behavior. Pain was the most important primary stressor. Surgery reduced the pain faster, but no difference was seen after 12 months. Reoperation rate was 29%, mostly for adjacent segment disease. The low positive mood state (MACL score) did not improve over time. Patients who still had pain after treatment were more socially withdrawn and ceased to express their emotions. The Hospital Anxiety and Depression (HAD) anxiety score was especially high in patients before and after treatment. In patients with high pain intensity, low function, high depression and anxiety were seen. The group treated with surgery showed more anxiety and depression if pain continued, implying higher expectations and more disappointment if it failed. The strongest correlation between depression and pain was seen in the collar group, possibly because they received less attention overall. In general, coping strategies changed. Active coping (cognitive reappraisal and problem solving) was common before treatment, but disappeared after treatment, especially in the surgical group. Coping with pain was changed in general into a more passive/escape focused strategy. It appeared that with intervention, especially surgery, healthy active coping strategies tended to be replaced by passive coping strategies as patients allowed themselves to become more dependent on the intervention. This also implied that the ability for active coping was present before in-

72 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 52 tervention, and thus cognitive behavioral treatment started concurrently with other interventions may be particularly successful for maintaining better coping patterns. Function was significantly related to pain intensity. About 40% had anxiety only partially connected to pain. Prior to treatment, 30% of patients were depressed. After 12 months, 20% suffered from depression. The authors concluded that cognitive and behavioral therapy is important to include in multidisciplinary rehabilitation. Patients need to improve coping strategies, self image and mood. In critique, neither patients nor reviewers were masked to treatment group, the sample size was small and duration of follow-up was short. Due to these limitations, this potential Level I study provides Level II evidence that there is a high incidence of behavioral and emotional dysfunction in cervical radiculopathy patients. Medical/interventional and surgical treatment must include a cognitive, behavioral component for either method to be successful. Future Directions for Research The work group identified the following suggestions for future studies which would generate meaningful evidence to assist in further defining the role of medical/interventional and surgical treatment in the management of cervical radiculopathy from degenerative disorders. Recommendation #1: A prospective, multicenter randomized controlled trial (RCT) with minimum two year follow-up comparing surgical to medical/interventional treatment for the treatment of cervical radiculopathy from degenerative disorders would yield invaluable information regarding the relative outcomes of these two treatment options. Recommendation #2: Future studies evaluating the effects of emotional, cognitive and work-related issues would add to our understanding of how these factors affect outcomes in patients with cervical radiculopathy from degenerative disorders. References 1. Anderson PA, Sasso RC, Riew KD. Comparison of adverse events between the Bryan artificial cervical disc and anterior cervical arthrodesis. Spine. 2008: Arnasson O, Carlsson CA, Pellettieri L. Surgical and conservative treatment of cervical spondylotic radiculopathy and myelopathy. Acta Neurochir (Wien). 1987;84(1-2): Bartels RH, Donk R, van der Wilt GJ, Grotenhuis JA, Venderink D. Design of the PROCON trial: a prospective, randomized multi-center study comparing cervical anterior discectomy without fusion, with fusion or with arthroplasty. BMC Musculoskelet Disord. 2006;7: Bartels RH, Verbeek AL, Grotenhuis JA. Design of Lamifuse: a randomised, multi-centre controlled trial comparing laminectomy without or with dorsal fusion for cervical myeloradiculopathy. BMC Musculoskelet Disord. 2007;8: Bertalanffy H, Eggert HR. Clinical long-term results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. A follow-up of 164 cases. Acta Neurochir (Wien). 1988;90(3-4): Boswell MV, Hansen HC, Trescot AM, Hirsch JA. Epidural steroids in the management of chronic spinal pain and radiculopathy. Pain Physician. Jul 2003;6(3): Brodke DS, Zdeblick TA. Modified Smith-Robinson procedure for anterior cervical discectomy and fusion. Spine. Oct 1992;17(10 Suppl):S Bruneau M, Nisolle JF, Gilliard C, Gustin T. Anterior cervical interbody fusion with hydroxyapatite graft and plate system. Neurosurg Focus. 2001;10(4):E8. 9. Bucciero A, Vizioli L, Cerillo A. Soft cervical disc herniation. An analysis of 187 cases. J Neurosurg Sci. Sep 1998;42(3): Caglar YS, Bozkurt M, Kahilogullari G, et al. Keyhole approach for posterior cervical discectomy: experience on 84 patients. Minim Invasive Neurosurg. Feb 2007;50(1): Carragee EJ, Hurwitz EL, Cheng I, et al. Treatment of neck pain - Injections and surgical interventions: Results of the bone and joint decade task force on neck pain and its associated disorders. Spine. Feb 2008;33(4):S153- S Cornelius JF, Bruneau M, George B. Microsurgical cervical nerve root decompression via an anterolateral approach: Clinical outcome of patients treated for spondylotic radiculopathy. Neurosurgery. Nov 2007;61(5): Dai LY, Jiang LS. Anterior cervical fusion with interbody cage containing beta-tricalcium phosphate augmented with plate fixation: a prospective randomized study with

73 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 53 2-year follow-up. Eur Spine J. May 2008;17(5): Davis RA. A long-term outcome study of 170 surgically treated patients with compressive cervical radiculopathy. Surg Neurol. Dec 1996;46(6): ; discussion Fernandez-Fairen M, Sala P, Dufoo M, Jr., Ballester J, Murcia A, Merzthal L. Anterior cervical fusion with tantalum implant: a prospective randomized controlled study. Spine. Mar ;33(5): Fessler RG, Khoo LT. Minimally invasive cervical microendoscopic foraminotomy: an initial clinical experience. Neurosurgery. Nov 2002;51(5 Suppl):S Fouyas IP, Sandercock PA, Statham PF, Lynch C. WITH- DRAWN: Surgery for cervical radiculomyelopathy. Cochrane Database Syst Rev. 2006(2):CD Frederic S, Benedict R, Payer M. Implantation of an empty carbon fiber cage or a tricortical iliac crest autograft after cervical discectomy for single-level disc herniation: a prospective comparative study. J Neurosurg Spine. Apr 2006;4(4): Gaetani P, Tancioni F, Spanu G, Rodriguez y Baena R. Anterior cervical discectomy: an analysis on clinical long-term results in 153 cases. J Neurosurg Sci. Dec 1995;39(4): Hacker RJ. A randomized prospective study of an anterior cervical interbody fusion device with a minimum of 2 years of follow-up results. J Neurosurg. Oct 2000;93(2 Suppl): Hacker RJ. Cervical disc arthroplasty: a controlled randomized prospective study with intermediate follow-up results. J Neurosurg Spine. Dec 2005;3(6): Hacker RJ, Cauthen JC, Gilbert TJ, Griffith SL. A prospective randomized multicenter clinical evaluation of an anterior cervical fusion cage. Spine. Oct ;25(20): ; discussion Hamburger C, Festenberg FV, Uhl E. Ventral discectomy with pmma interbody fusion for cervical disc disease: longterm results in 249 patients. Spine. Feb ;26(3): Harrop JS, Silva MT, Sharan AD, Dante SJ, Simeone FA. Cervicothoracic radiculopathy treated using posterior cervical foraminotomy/discectomy. J Neurosurg ;98(2 supp.): Hauerberg J, Kosteljanetz M, Boge-Rasmussen T, et al. Anterior cervical discectomy with or without fusion with ray titanium cage: a prospective randomized clinical study. Spine. Mar ;33(5): Heckmann JG, Lang CJ, Zobelein I, Laumer R, Druschky A, Neundorfer B. Herniated cervical intervertebral discs with radiculopathy: an outcome study of conservatively or surgically treated patients. J Spinal Disord. Oct 1999;12(5): Heidecke V, Burkert W, Brucke M, Rainov NG. Intervertebral disc replacement for cervical degenerative disease-- clinical results and functional outcome at two years in patients implanted with the Bryan cervical disc prosthesis. Acta Neurochir (Wien). May 2008;150(5): ; discussion Heidecke V, Rainov NG, Marx T, Burkert W. Outcome in Cloward anterior fusion for degenerative cervical spinal disease. Acta Neurochir (Wien). 2000;142(3): Herkowitz HN, Kurz LT, Overholt DP. Surgical management of cervical soft disc herniation. A comparison between the anterior and posterior approach. Spine. Oct 1990;15(10): Hida K, Iwasaki Y, Yano S, Akino M, Seki T. Long-term follow-up results in patients with cervical disk disease treated by cervical anterior fusion using titanium cage implants. Neurol Med Chir (Tokyo). Oct 2008;48(10): ; discussion Hwang SL, Hwang YF, Lieu AS, et al. Outcome analyses of interbody titanium cage fusion used in the anterior discectomy for cervical degenerative disc disease. J Spinal Disord Tech. Aug 2005;18(4): Jagannathan J, Sherman JH, Szabo T, Shaffrey CI, Jane JA. The posterior cervical foraminotomy in the treatment of cervical disc/osteophyte disease: a single-surgeon experience with a minimum of 5 years clinical and radiographic follow-up Clinical article. J Neurosurg Spine. Apr 2009;10(4): Kadoya S, Iizuka H, Nakamura T. Long-term outcome for surgically treated cervical spondylotic radiculopathy and myelopathy. Neurol Med Chir (Tokyo). May 2003;43(5): ; discussion Klein GR, Vaccaro AR, Albert TJ. Health outcome assessment before and after anterior cervical discectomy and fusion for radiculopathy: a prospective analysis. Spine. Apr ;25(7): Korinth MC, Kruger A, Oertel MF, Gilsbach JM. Posterior foraminotomy or anterior discectomy with polymethyl methacrylate interbody stabilization for cervical soft disc disease: results in 292 patients with monoradiculopathy. Spine. May ;31(11): ; discussion Kotil K, Bilge T. Prospective study of anterior cervical microforaminotomy for cervical radiculopathy. J Clin Neurosci. Jul 2008;15(7): Krupp W, Schattke H, Muke R. Clinical-Results of the Foraminotomy as Described by Frykholm for the Treatment of Lateral Cervical Disk Herniation. Acta Neurochir (Wien). 1990;107(1-2): Kumar GRV, Maurice-Williams RS, Bradford R. Cervical foraminotomy: an effective treatment for cervical spondylotic radiculopathy. Br J Neurosurg. Dec 1998;12(6): Matge G. Cervical cage fusion with 5 different implants: 250 cases. Acta Neurochir (Wien). Jun 2002;144(6):539-

74 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders ; discussion Matge G, Leclercq TA. Rationale for interbody fusion with threaded titanium cages at cervical and lumbar levels. Results on 357 cases. Acta Neurochir (Wien). 2000;142(4): Mobbs RJ, Rao P, Chandran NK. Anterior cervical discectomy and fusion: analysis of surgical outcome with and without plating. J Clin Neurosci. Jul 2007;14(7): Mummaneni PV, Burkus JK, Haid RW, Traynelis VC, Zdeblick TA. Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. J Neurosurg Spine. Mar 2007;6(3): Murrey D, Janssen M, Delamarter R, et al. Results of the prospective, randomized, controlled multicenter Food and Drug Administration investigational device exemption study of the ProDisc-C total disc replacement versus anterior discectomy and fusion for the treatment of 1-level symptomatic cervical disc disease. Spine J. Apr 2009;9(4): Nabhan A, Ahlhelm F, Pitzen T, et al. Disc replacement using Pro-Disc C versus fusion: a prospective randomised and controlled radiographic and clinical study. Euro Spine J. Mar 2007;16(3): Nabhan A, Ahlhelm F, Shariat K, et al. The ProDisc-C prothesis - Clinical and radiological experience 1 year after surgery. Spine. Aug 2007;32(18): Nunley PD, Jawahar A, Kerr EJ, 3rd, Cavanaugh DA, Howard C, Brandao SM. Choice of plate may affect outcomes for single versus multilevel ACDF: results of a prospective randomized single-blind trial. Spine J. Feb 2009;9(2): Persson LC, Lilja A. Pain, coping, emotional state and physical function in patients with chronic radicular neck pain. A comparison between patients treated with surgery, physiotherapy or neck collar--a blinded, prospective randomized study. Disabil Rehabil. May ;23(8): Persson LC, Moritz U, Brandt L, Carlsson CA. Cervical radiculopathy: pain, muscle weakness and sensory loss in patients with cervical radiculopathy treated with surgery, physiotherapy or cervical collar. A prospective, controlled study. Eur Spine J. 1997;6(4): Pimenta L, McAfee PC, Cappuccino A, Cunningham BW, Diaz R, Coutinho E. Superiority of multilevel cervical arthroplasty outcomes versus single-level outcomes: 229 consecutive PCM prostheses. Spine. May ;32(12): Pointillart V, Cernier A, Vital JM, Senegas J. Anterior discectomy without interbody fusion for cervical disc herniation. Eur Spine J. 1995;4(1): Romner B, Due-Tonnessen BJ, Egge A, Anke IM, Trumpy JH. Modified Robinson-Smith procedure for the treatment of cervical radiculopathy. Acta Neurol Scand. Sep 1994;90(3): Ruetten S, Komp M, Merk H, Godolias G. A new full-endoscopic technique for cervical posterior foraminotomy in the treatment of lateral disc herniations using 6.9-mm endoscopes: prospective 2-year results of 87 patients. Minim Invasive Neurosurg. Aug 2007;50(4): Sampath P, Bendebba M, Davis JD, Ducker T. Outcome in patients with cervical radiculopathy. Prospective, multicenter study with independent clinical review. Spine. Mar ;24(6): Sasso RC, Smucker JD, Hacker RJ, Heller JG. Artificial disc versus fusion: a prospective, randomized study with 2-year follow-up on 99 patients. Spine. Dec ;32(26): ; discussion Schneeberger AG, Boos N, Schwarzenbach O, Aebi M. Anterior cervical interbody fusion with plate fixation for chronic spondylotic radiculopathy: a 2- to 8-year followup. J Spinal Disord. Jun 1999;12(3): ; discussion Schoggl A, Reddy M, Saringer W, Ungersbock K. Social and economic outcome after posterior microforaminotomy for cervical spondylotic radiculopathy. Wien Klin Wochenschr. Mar ;114(5-6): Shen FH, Samartzis D, Khanna N, Goldberg EJ, An HS. Comparison of clinical and radiographic outcome in instrumented anterior cervical discectomy and fusion with or without direct uncovertebral joint decompression. Spine J. Nov 2004;4(6): Sugawara T, Itoh Y, Hirano Y, Higashiyama N, Mizoi K. Long term outcome and adjacent disc degeneration after anterior cervical discectomy and fusion with titanium cylindrical cages. Acta Neurochir (Wien). Apr 2009;151(4): Tegos S, Rizos K, Papathanasiu A, Kyriakopulos K. Results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. Eur Spine J. 1994;3(2): Topuz K, Colak A, Kaya S, et al. Two-level contiguous cervical disc disease treated with peek cages packed with demineralized bone matrix: results of 3-year follow-up. Eur Spine J. Feb 2009;18(2): Wirth FP, Dowd GC, Sanders HF, Wirth C. Cervical discectomy. A prospective analysis of three operative techniques. Surg Neurol. Apr 2000;53(4): ; discussion Xie JC, Hurlbert RJ. Discectomy versus discectomy with fusion versus discectomy with fusion and instrumentation: a prospective randomized study. Neurosurgery. 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75 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Zeidman SM, Ducker TB. Posterior cervical laminoforaminotomy for radiculopathy: review of 172 cases. Neurosurgery. Sep 1993;33(3): Zoega B, Karrholm J, Lind B. Outcome scores in degenerative cervical disc surgery. Eur Spine J. Apr 2000;9(2): Does ACDF result in better outcomes (clinical or radiographic) than ACD alone? RECOMMENDATION: Both ACD and ACDF are suggested as comparable treatment strategies, producing similar clinical outcomes, in the treatment of single level cervical radiculopathy from degenerative disorders. GRADE OF RECOMMENDATION: B Barlocher et al 3 conducted a prospective randomized controlled trial comparing outcomes of ACD to three different types of ACDF: iliac crest bone graft (ICBG), polymethylmethacrylate (PMMA) and titanium cages. All patients had single level degenerative disease. Of the 125 patients included in the study, 33 were assigned to the ACD group, 30 to ICBG, 26 to PMMA and 36 to titanium cages. At one year follow-up, 123 patients were available. The functional outcomes were grouped by good and excellent to poor and fair, with good/excellent results reported for 75% of the ACDF group, 80% for ICBG, 87% for PMMA and 94% for cage. Average reported kyphosis for ACD patients was 24 degrees, with one patient requiring revision surgery (31 degrees); 12 degrees for PMMA and about three degrees for the ICBG and cage groups. Twelve month fusion results based on flexion and extension radiographs were reported as 93% for the ACD patients, 93% for ICBG and 97% for cage. Fusion rate was faster in the cage group as well with 86% achieving fusion at six months compared with 61% in the ACD group and 65% in the ICBG group. The authors concluded that ACDF with cage did significantly better with faster and better recovery and less kyphotic deformity than ACD. ACD compared to ICBG had similar outcomes but more kyphotic deformity at medium length follow-up. In critique, neither reviewers nor patients were masked to treatment group and the randomization process was not described. No validated outcome measures were utilized, the sample size was small and length of follow-up was short. Use of PMMA as a spacer is not standard practice. Due to these limitations, this potential Level II RCT provides Level III evidence that suggests that there are variable outcomes when comparing ACD to ACDF for the treatment of cervical radiculopathy due to single level degenerative disease. In one cohort comparing ACD to fusion with ICBG, outcomes were equivalent, while another cohort showed superiority of interbody fusion with a titanium cage and allograft versus ACD. Validity of conclusions is weakened by small sample size and short follow-up. Hauerberg et al 9 reported results of a prospective randomized controlled trial comparing radiographic and clinical outcomes of ACD with ACDF using a titanium cage. Of the 86 patients included in the study, 46 were randomized to the ACD group and 40 to ACDF. One patient withdrew in each group. Two year follow-up data were available for 36 cage and 43 ACD patients. Early outcomes, though not statistically significant, favored ACD. At two years 63% of ACD patients and 78% of cage patients reported good outcomes (not statistically significant). Reoperation rates at the same level were reported as follows: at three months, three reoperations in ACD group, two in cage group; at one year, an additional reoperation in each group; at two years, an additional three in the ACD group. There were some additional procedures at adjacent levels that were equivalent for both groups over two years. In total, for the ACD group, 17/46 were investigated, seven had the same level reoperation and two had adjacent level operations. In the cage group, 15/40 were investigated with three having same level reoperation and three having adjacent level operations. There were no statistically significant differences reported in kyphosis

76 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 56 or fusion rate. The authors concluded that there was no difference in outcome at two years between ACD and ACDF with cage and local autograft bone. In critique, the reviewers were not masked to treatment group, no validated outcome measures were used and the sample size was small. Due to these limitations, this potential Level I RCT provides Level II evidence that for cervical radiculopathy due to single level degenerative disease, clinical outcomes are similar at two years for patients undergoing ACD and ACDF with threaded titanium cage and local autograft. Fusion rates and symptomatic adjacent segment disease were also similar between the two groups. Oktenoglu et al 16 described a prospective randomized controlled trial comparing radiographic and clinical outcomes of ACD and ACDF with plate. Of the 20 patients included in the study, 11 were assigned to the ACD group and nine to the ACDF group. Inclusion criteria required only two weeks of failed medical/interventional treatment. VAS upper extremity pain scores (dominant complaint) improved significantly in both groups, from mean 8 to 3. Although less severe initially than arm pain, VAS neck pain scores had less improvement overall, but statistically significant improvement was noted in the ACDF group. CT follow-up at one year showed disc space collapse in both groups, but significantly more in the ACD group. There was some subsidence of the graft over the first year. Final foraminal dimensions were slightly larger in ACDF group, but not significant. Reported fusion rates were 100% in the ACDF group and 45% (5/11) in the ACD group. The authors concluded that ACD alone provides satisfactory clinical outcomes when compared to ACDF with semirigid plate. In critique, patients were not masked to treatment group and duration of symptoms for study inclusion was short. Randomization was accomplished by coin flip and the sample size was small. No validated outcome measures were utilized and follow-up was short. Due to these limitations, this potential Level II study provides Level III evidence that for cervical radiculopathy due to single level degenerative disease, ACD alone provides satisfactory clinical outcomes when compared to ACDF with allograft ICBG and semirigid plate. Radiographically, disc height is maintained significantly better with plate and fusion although the clinical significance is unknown. The validity of the conclusions is uncertain due to small sample size. Savolainen et al 19 reported results of a prospective randomized controlled trial comparing clinical results of ACD to ACDF with or without plate. Of the 91 patients included in the study, follow-up data were reported for 88 patients. Good/excellent results were reported in 76% of ACD patients, 82% ACDF and 73% ACDFP. Of the 88 patients, 71 had long term radiographic follow-up, with slight kyphosis in 62% of ACD, 41% ACDF, 44% ACDFP and fusion achieved in 100% of ACDF and 90% of ACD patients. Complication rates were similar for all groups, with the exception of short term ICBG pain which was severe in 80% of both ACDF groups. The authors concluded that because outcomes were similar for the three groups, ACD is recommended as the procedure of choice for ease of surgery and reduced complications. In critique, neither patients nor reviewers were masked to treatment group. The randomization process was not specified. No validated outcome measures were used and the sample size was small. Patients were seen up to six months following surgery, and then final follow-up at four years was conducted via telephone interview. Due to these limitations, this potential Level II study provides Level III evidence that for patients with cervical radiculopathy due to single level degenerative disease, ACD yields results equivalent to ACDF with or without a plate. The validity of the conclusion is uncertain due to small sample size.

77 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 57 Wirth et al 24 conducted a prospective randomized controlled trial comparing clinical outcomes of ACD, ACDF and posterior cervical foraminotomy for single level HNP with radiculopathy. Of the 72 consecutively assigned patients included in the study, 22 were assigned to foraminotomy, 25 to ACD and 25 to ACDF. For immediate postoperative results, surgical time, hospital stay and cost were slightly better for the ACD group. Postoperative pain was worse in the foraminotomy group. At two months, according to the non validated grading scheme implemented, all three groups were about the same. Reoperations were greater at the operative site for foraminotomy and adjacent sites for ACDF patients. Long-term follow-up was accomplished via phone interview at 53 months for the foraminotomy group (14/22 patients), 56 months for the ACD group (13/25 patients) and 69 months for the ACDF group (16/25 patients), with a loss of about 40% of patients to follow-up. Within the limits of their study design and patient capture, pain improvement remained high for all groups. Return to work was 79% for the foraminotomy group, 92% for ACD and 81% for ACDF (not statistically significant). Of the patients available at final follow-up, 100% were satisfied and would have the surgery again. The authors concluded that for single level HNP, all procedures are efficacious. In critique, neither patients nor reviewers were masked to the treatment group and the randomization method was poor. No validated outcome measures were utilized to assess this small patient sample. Approximately 40% of patients were lost to follow-up. Because of these limitations, this potential Level II study provides Level III evidence that for single level HNP causing cervical radiculopathy, outcomes for ACD are equivalent to ACDF. Xie et al 25 reported results of a prospective randomized controlled trial comparing clinical and radiographic outcomes of ACD, ACDF, and anterior cervical discectomy with instrumented fusion (ACDFI) for single level cervical radiculopathy. Of the 45 patients included in the study, 15 were randomly assigned to each treatment group. Three patients in the ACD group were lost to follow-up. No graft site pain was reported at two years. In general, clinical results improved to one year then plateaued. Arm pain was completely absent in 92% of ACD patients, 93% of ACDF patients and 100% of ACDFI patients. Neck pain was absent in 83%, 80% and 73%, respectively. All had significant and similar improvements in McGill Pain Questionnaire and SF-36. At two years, fusion rate on radiograph was 67%, 93%, and 100% respectively. Of patients treated with ACD, 75% had kyphosis at two years. The authors concluded that patient selection is the key to surgical success. Any of these surgeries are suitable for cervical radiculopathy due to nerve root compression. Because the long term effects of kyphosis are unknown, the potential consequences of ACD remain uncertain. In critique, neither the patients nor reviewers were masked to treatment group, and the sample size was small. Due to these limitations, this potential Level I study provides Level II evidence that clinical outcomes for treatment of cervical radiculopathy due to single level degenerative disease are similar when comparing ACD to ACDF, with or without plating. Radiographic outcomes were worse with ACD, resulting in a significant loss of lordosis, although the clinical consequences of this are unknown. The validity of the conclusions may be compromised by a very small sample size. RECOMMENDATION: The addition of an interbody graft for fusion is suggested to improve sagittal alignment following ACD. GRADE OF RECOMMENDATION: B Barlocher et al 3 conducted a prospective randomized controlled trial comparing outcomes of ACD to three different types of ACDF: ICBG, PMMA and titanium cages. All patients had one level disease. Of the 125 patients included in the study, 33 were assigned to the ACD group, 30 to ICBG, 26 to PMMA

78 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 58 and 36 to titanium cages. At one year follow-up, 123 patients were available. The functional outcomes were grouped by good and excellent to poor and fair, with good/excellent results reported for 75% of the ACDF group, 80% for ICBG, 87% for PMMA and 94% for cage. Average reported kyphosis for ACD patients was 24 degrees, with one patient requiring revision surgery (31 degrees); 12 degrees for PMMA and about three degrees for the ICBG and cage groups. Twelve month fusion results were reported as 93% for the ACD patients, 93% for ICBG and 97% for cage. Fusion rate was faster in the cage group as well with 86% achieving fusion at six months compared with 61% in the ACD group and 65% in the ICBG group. The authors concluded that ACDF with cage did significantly better with faster and better recovery and less kyphotic deformity than ACD. ACD compared to ICBG had similar outcomes at medium length follow-up. In critique, neither reviewers nor patients were masked to treatment group and the randomization process was not described. No validated outcome measures were utilized, the sample size was small and length of follow-up was short. Use of PMMA as a spacer is not standard practice. Due to these limitations, this potential Level II RCT provides Level III evidence that suggests that there are variable outcomes when comparing ACD to ACDF for the treatment of cervical radiculopathy due to single level degenerative disease. While not the primary outcome measure, radiographic sagittal alignment was clearly better with ACDF compared to ACD. Validity of conclusions are weakened by small sample size and short follow-up. Xie et al 25 reported results of a prospective randomized controlled trial comparing clinical and radiographic outcomes of ACD, ACDF, and anterior cervical discectomy with instrumented fusion (ACDFI) for single level cervical radiculopathy. Of the 45 patients included in the study, 15 were randomly assigned to each treatment group. Three patients in the ACD group were lost to follow-up. No graft site pain was reported at two years. In general, clinical results improved to one year then plateaued. Arm pain was completely absent in 92% of ACD patients, 93% of ACDF patients and 100% of ACDFI patients. Neck pain was absent in 83%, 80% and 73%, respectively. All had significant and similar improvements in McGill Pain Questionnaire and SF-36. At two years, fusion rate on radiograph was 67%, 93%, and 100% respectively. Of patients treated with ACD, 75% had kyphosis at two years. Approximately 25% had kyphosis between 5 and 15 degrees, while the other 50% were between 0 and 5 degrees. It should be noted that 15% of the patients had some measure of preoperative kyphosis. In both the ACDF and ACDFI groups, less than 5% of patients had a kyphosis of 5 to 15 degrees at final follow up. There was 0 to 5 degrees of kyphosis in approximately 30% and 20% of the ACDF and ACDFI groups respectively. Pre operative kyphosis was noted in 20% and 30% respectively. Looking at the data more closely, there was a clear loss of kyphosis in the ACD group. In the ACDF group, alignment tended to remain close to the pre operative condition in general, with slight subsidence and minimal loss of kyphosis in a small percent of patients such that at final follow up pre and post operative sagittal alignment were generally similar. If these patients exhibited pre operative segmental kyphosis, they tended to stay that way, as did those with pre operative lordosis. In the ACDFI group, there was a trend towards improved sagittal alignment when comparing pre and post operative lordosis. The authors concluded that patient selection is the key to surgical success. Any of these surgeries are suitable for cervical radiculopathy due to nerve root compression. There was a clear advantage for maintaining sagittal alignment with either ACDF or ACDFI. Because the long term effects of kyphosis are unknown, the potential consequences of ACD remain uncertain. In critique, neither the patients nor reviewers were masked to treatment group, and the sample size was small. Due to these limitations, this potential Level I study provides Level II evidence that clinical out-

79 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 59 comes for treatment of cervical radiculopathy due to single level degenerative disease are similar when comparing ACD to ACDF, with or without plating. Radiographic outcomes were worse with ACD, resulting in a significant loss of lordosis, although the clinical consequences of this are unknown. The validity of the conclusions may be compromised by a very small sample size. Future Directions for Research The work group identified the following suggestions for future studies which would generate meaningful evidence to assist in further defining the role of fusion with ACD in the surgical treatment of cervical radiculopathy from degenerative disorders. Prospective, blinded, RCT comparing clinical outcomes and radiographic alignment of patients treated for cervical radiculopathy due to single level degenerative disease with ACD compared with ACDF with a uniform surgical technique would generate important information about the relative value of preserving normal alignment. References 1. Abd-Alrahman N, Dokmak AS, Abou-Madawi A. Anterior cervical discectomy (ACD) versus anterior cervical fusion (ACF), clinical and radiological outcome study. Acta Neurochir (Wien). 1999;141(10): Alvarez JA, Hardy RW. Anterior cervical discectomy for one- and two-level cervical disc disease: the controversy surrounding the question of whether to fuse, plate, or both. Crit Rev Neurosurg. Jul 1999;9(4): Barlocher CB, Barth A, Krauss JK, Binggeli R, Seiler RW. Comparative evaluation of microdiscectomy only, autograft fusion, polymethylmethacrylate interposition, and threaded titanium cage fusion for treatment of single-level cervical disc disease: a prospective randomized study in 125 patients. Neurosurg Focus. Jan ;12(1):E4. 4. Bartels RH, Donk R, van der Wilt GJ, Grotenhuis JA, Venderink D. Design of the PROCON trial: a prospective, randomized multi-center study comparing cervical anterior discectomy without fusion, with fusion or with arthroplasty. BMC Musculoskelet Disord. 2006;7: Bertalanffy H, Eggert HR. Clinical long-term results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. A follow-up of 164 cases. Acta Neurochir (Wien). 1988;90(3-4): Donaldson JW, Nelson PB. Anterior cervical discectomy without interbody fusion. Surg Neurol. Apr 2002;57(4): ; discussion Dowd GC, Wirth FP. Anterior cervical discectomy: is fusion necessary? J Neurosurg. Jan 1999;90(1 Suppl): Gaetani P, Tancioni F, Spanu G, Rodriguez y Baena R. Anterior cervical discectomy: an analysis on clinical long-term results in 153 cases. J Neurosurg Sci. Dec 1995;39(4): Hauerberg J, Kosteljanetz M, Boge-Rasmussen T, et al. Anterior cervical discectomy with or without fusion with ray titanium cage: a prospective randomized clinical study. Spine. Mar ;33(5): Husag L, Costabile G, Vanloffeld W, Keller RJD, Landolt H. Anterior cervical discectomy without fusion: A comparison with Cloward s procedure. J Clin Neurosci. Jul 1997;4(3): Jacobs WC, Anderson PG, Limbeek J, Willems PC, Pavlov P. Single or double-level anterior interbody fusion techniques for cervical degenerative disc disease. Cochrane Database Syst Rev. 2004(4):CD Klaiber RD, Vonammon K, Sarioglu AC. Anterior Microsurgical Approach for Degenerative Cervical Disk Disease. Acta Neurochir (Wien). 1992;114(1-2): Maurice-Williams RS, Elsmore A. Extended anterior cervical decompression without fusion: a long-term follow-up study. Br J Neurosurg. Oct 1999;13(5): Murphy MA, Trimble MB, Piedmonte MR, Kalfas IH. Changes in the cervical foraminal area after anterior discectomy with and without a graft. Neurosurgery. Jan 1994;34(1): Naderi S, Ozgen S, Ozek MM, Pamir MN. Cervical disc herniations: When to fuse? Neuro-Orthopedics. 2000;28(1): Oktenoglu T, Cosar M, Ozer AF, et al. Anterior cervical microdiscectomy with or without fusion. J Spinal Disord Tech. Jul 2007;20(5): Pointillart V, Cernier A, Vital JM, Senegas J. Anterior discectomy without interbody fusion for cervical disc herniation. Eur Spine J. 1995;4(1): Rao PJ, Christie JG, Ghahreman A, Cartwright CA, Ferch RD. Clinical and functional outcomes of anterior cervical discectomy without fusion. J Clin Neurosci. December 2008;15(12): Savolainen S, Rinne J, Hernesniemi J. A prospective randomized study of anterior single-level cervical disc operations with long-term follow-up: surgical fusion is unnecessary. Neurosurgery. Jul 1998;43(1): Tegos S, Rizos K, Papathanasiu A, Kyriakopulos K. Results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. Eur Spine J. 1994;3(2): Thorell W, Cooper J, Hellbusch L, Leibrock L. The long-

80 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 60 term clinical outcome of patients undergoing anterior cervical discectomy with and without intervertebral bone graft placement. Neurosurgery. Aug 1998;43(2): ; discussion Watters WC, 3rd, Levinthal R. Anterior cervical discectomy with and without fusion. Results, complications, and longterm follow-up. Spine. Oct ;19(20): White BD, Fitzgerald JJ. To graft or not to graft: rationalizing choice in anterior cervical discectomy. Br J Neurosurg. Apr 2005;19(2): Wirth FP, Dowd GC, Sanders HF, Wirth C. Cervical discectomy. A prospective analysis of three operative techniques. Surg neurol. 2000: ; discussion Xie JC, Hurlbert RJ. Discectomy versus discectomy with fusion versus discectomy with fusion and instrumentation: a prospective randomized study. Neurosurgery. Jul 2007;61(1): ; discussion Yamamoto I, Ikeda A, Shibuya N, Tsugane R, Sato O. Clinical long-term results of anterior discectomy without interbody fusion for cervical disc disease. Spine. Mar 1991;16(3): Does ACDF with instrumentation result in better outcomes (clinical or radiographic) than ACDF without instrumentation? RECOMMENDATION: Both ACDF with and without a plate are suggested as comparable treatment strategies, producing similar clinical outcomes and fusion rates, in the treatment of single level cervical radiculopathy from degenerative disorders. GRADE OF RECOMMENDATION: B Grob et al 5 conducted a prospective randomized controlled trial comparing clinical and radiographic outcomes of ACDF and ACDFP. Of the 50 patients available at follow-up, 24 were randomized to ACD- FP and 26 to ACDF. Both groups had a statistically significant decrease in VAS pain scores and improvement in cervical spine range of motion postoperatively, but there was no significant difference between groups for either of these outcome measures. Radiographically, there was no difference in the frequency of pseudoarthrosis/nonunion. The authors defined inferior graft quality as ventral graft dislocation greater than 2mm and/or loss of disc height by more than 2mm. Based upon these criteria, the plate group had significantly better results (p=.04). The authors concluded that addition of an anterior cervical plate did not lead to an improved clinical outcome for patients treated for cervical radiculopathy with a one or two level anterior procedure. In critique, patients were not masked to treatment group and no validated outcome measures were utilized to assess this small sample of patients. The authors did not indicate that the patients were consecutively assigned and utilized a questionable randomization method. Due to these limitations, this potential Level I study provides Level II evidence that the addition of a plate does not improve outcomes following ACDF for cervical radiculopathy from degenerative disorders at an average of 34 months follow up, although it does appear to improve sagittal alignment. Mobbs et al 8 described a retrospective comparative study comparing clinical and radiographic outcomes of ACDF with ACDFP in patients with cervical radiculopathy. Of the 212 radiculopathy patients included in the study, 116 received ACDF and 96 were treated with ACDFP. Using Odom s criteria, there was no significant difference in good to excellent outcomes between the two groups (87% of the ACDF patient group and 92% of the ACDFP). On the other hand, the noninstrumented group had a statistically significantly higher frequency of poor outcomes at 7% (8/116) compared to the ACDFP group at 1% (1/96). Poor outcomes were considered to be postoperative kyphosis and nonunion. The authors concluded that excellent results were similar for both groups. There was a significantly higher rate of poor outcomes in the uninstrumented group and this lead to higher rate of second surgery.

81 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 61 In critique, no validated outcome measures were used and the length of follow-up was short. This study provides Level III evidence that addition of an anterior locking plate may not lead to an increased likelihood of a satisfactory clinical outcome, but it may lower the likelihood of a poor outcome and need for reoperation. Zoega et al 16 reported results of a prospective randomized controlled trial evaluating whether the addition of a plate to a single level cervical fusion for degenerative disc disease enhances fusion rate and contributes to maintaining alignment. Of the 27patients included in the study, 15 were assigned to the ACDFP group and 12 to the ACDF group. There was a statistically significant increase in the frequency of postoperative kyphosis in the nonplated group at one year follow-up (p=.04). At two years statistical significance was lost (p=>06). There was one nonunion in the plate group; none in the ACDF group. Clinical scores were the same for both groups. The authors concluded that the plate maintains alignment, but provides no advantage for healing or for clinical outcomes In critique, neither patients nor reviewers were masked to treatment group. No validated outcome measures were utilized in this small sample of patients. Due to these limitations, this potential Level I study provides Level II evidence that the addition of a plate to ACDF maintains alignment. RECOMMENDATION: The addition of a cervical plate is suggested to improve sagittal alignment following ACDF. GRADE OF RECOMMENDATION: B Grob et al 5 conducted a prospective randomized controlled trial comparing clinical and radiographic outcomes of ACDF and ACDFP. Of the 50 patients available at follow-up, 24 were randomized to ACD- FP and 26 to ACDF. Both groups had a statistically significant decrease in VAS pain scores and improvement in cervical spine range of motion postoperatively, but there was no significant difference between groups for either of these outcome measures. Radiographically, there was no difference in the frequency of pseudoarthrosis/nonunion. The authors defined inferior graft quality as ventral graft dislocation greater than 2mm and/or loss of disc height by more than 2mm. Based upon these criteria, the plate group had significantly better results (p=.04). The authors concluded that addition of an anterior cervical plate did not lead to an improved clinical outcome for patients treated for cervical radiculopathy with a one or two level anterior procedure. In critique, patients were not masked to treatment group and no validated outcome measures were utilized to assess this small sample of patients. The authors did not indicate that the patients were consecutively assigned and utilized a questionable randomization method. Due to these limitations, this potential Level I study provides Level II evidence that the addition of a plate does not improve outcomes following ACDF for cervical radiculopathy from degenerative disorders at an average of 34 months follow up, although it does appear to improve sagittal alignment. Mobbs et al 8 described a retrospective comparative study comparing clinical and radiographic outcomes of ACDF with ACDFP in patients with cervical radiculopathy. Of the 212 radiculopathy patients included in the study, 116 received ACDF and 96 were treated with ACDFP. Using Odom s criteria, there was no significant difference in good to excellent outcomes between the two groups (87% of the ACDF patient group and 92% of the ACDFP). On the other hand, the uninstrumented group had a statistically significantly higher frequency of poor outcomes at 7% (8/116) compared to the ACDFP group at 1% (1/96). Poor outcomes were considered to be postoperative kyphosis and nonunion. The authors concluded that excellent results were similar for both groups. There was a significantly higher rate of poor outcomes in the uninstrumented group and this lead to higher rate of second surgery.

82 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 62 In critique, no validated outcome measures were used and the length of follow-up was short. This study provides Level III evidence that addition of an anterior locking plate may not lead to an increased likelihood of a satisfactory clinical outcome, but it may lower the likelihood of a poor outcome and need for reoperation. Zoega et al 16 reported results of a prospective randomized controlled trial evaluating whether the addition of a plate to a single level cervical fusion for degenerative disc disease enhances fusion rate and contributes to maintaining alignment. Of the 27patients included in the study, 15 were assigned to the ACDFP group and 12 to the ACDF group. There was a statistically significant increase in the frequency of postoperative kyphosis in the nonplated group at one year follow-up (p=.04). At two years statistical significance was lost (p=>06). There was one nonunion in the plate group; none in the ACDF group. Clinical scores were the same for both groups. The authors concluded that the plate maintains alignment, but provides no advantage for healing or for clinical outcomes. In critique, neither patients nor reviewers were masked to treatment group. No validated outcome measures were utilized in this small sample of patients. Due to these limitations, this potential Level I study provides Level II evidence that the addition of a plate to ACDF maintains alignment. RECOMMENDATION: While plate stabilization may be indicated in some patients undergoing multilevel ACDF, there is insufficient evidence that this practice results in significant improvement in clinical outcomes for degenerative cervical radiculopathy. Work Group Consensus Statement A systematic review of the literature yielded no studies to adequately compare outcomes for ACDF with and without a plate for multilevel surgeries. Future Directions for Research The work group identified the following suggestion for a future study which would generate meaningful evidence to assist in further defining the role of instrumentation in addition to ACDF in the surgical treatment of cervical radiculopathy from degenerative disorders. A well designed, prospective RCT to compare radiographic and clinical outcomes following ACDF with or without a plate for degenerative cervical radiculopathy would generate meaningful data regarding the potential long term benefits of preserving or restoring sagittal alignment. There should be two cohorts, one with single level disease, and one with multilevel disease. References 1. Alvarez JA, Hardy RW. Anterior cervical discectomy for one- and two-level cervical disc disease: the controversy surrounding the question of whether to fuse, plate, or both. Crit Rev Neurosurg. Jul 1999;9(4): Bolesta MJ, Rechtine GR, 2nd, Chrin AM. One- and twolevel anterior cervical discectomy and fusion: the effect of plate fixation. Spine J. May-Jun 2002;2(3): Caspar W, Geisler FH, Pitzen T, Johnson TA. Anterior cervical plate stabilization in one- and two-level degenerative disease: overtreatment or benefit? J Spinal Disord. Feb 1998;11(1): Connolly PJ, Esses SI, Kostuik JP. Anterior cervical fusion: outcome analysis of patients fused with and without anterior cervical plates. J Spinal Disord. Jun 1996;9(3): Grob D, Peyer JV, Dvorak J. The use of plate fixation in anterior surgery of the degenerative cervical spine: a comparative prospective clinical study. Eur Spine J. Oct 2001;10(5): Kaiser MG, Haid RW, Jr., Subach BR, Barnes B, Rodts GE, Jr. Anterior cervical plating enhances arthrodesis after discectomy and fusion with cortical allograft. Neurosurgery. Feb 2002;50(2): ; discussion McLaughlin MR, Purighalla V, Pizzi FJ. Cost advantages of two-level anterior cervical fusion with rigid internal fixation for radiculopathy and degenerative disease. Surg Neurol. Dec 1997;48(6): Mobbs RJ, Rao P, Chandran NK. Anterior cervical discectomy and fusion: analysis of surgical outcome with and without plating. J Clin Neurosci. Jul 2007;14(7): Nabhan A, Pape D, Pitzen T, et al. Radiographic analysis of fusion progression following one-level cervical fusion with or without plate fixation. Zentralbl Neurochir. Aug 2007;68(3):

83 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Resnick DK, Trost GR. Use of ventral plates for cervical arthrodesis. Neurosurgery. Jan 2007;60(1 Supp1 1):S Samartzis D, Shen FH, Lyon C, Phillips M, Goldberg EJ, An HS. Does rigid instrumentation increase the fusion rate in one-level anterior cervical discectomy and fusion? Spine J. Nov-Dec 2004;4(6): Troyanovich SJ, Stroink AR, Kattner KA, Dornan WA, Gubina I. Does anterior plating maintain cervical lordosis versus conventional fusion techniques? A retrospective analysis of patients receiving single-level fusions. J Spinal Disord Tech. Feb 2002;15(1): Wang JC, McDonough PW, Endow K, Kanim LE, Delamarter RB. The effect of cervical plating on single-level anterior cervical discectomy and fusion. J Spinal Disord. Dec 1999;12(6): Wang JC, McDonough PW, Endow KK, Delamarter RB. Increased fusion rates with cervical plating for two-level anterior cervical discectomy and fusion. Spine. Jan 2000;25(1): Wang JC, McDonough PW, Kanim LE, Endow KK, Delamarter RB. Increased fusion rates with cervical plating for three-level anterior cervical discectomy and fusion. Spine. Mar ;26(6): ; discussion Zoega B, Karrholm J, Lind B. One-level cervical spine fusion. A randomized study, with or without plate fixation, using radiostereometry in 27 patients. Acta Orthop Scand. Aug 1998;69(4): Zoega B, Karrholm J, Lind B. Plate fixation adds stability to two-level anterior fusion in the cervical spine: a randomized study using radiostereometry. Eur Spine J. 1998;7(4): Does anterior surgery result in better outcomes (clinical or radiographic) than posterior surgery in the treatment of cervical radiculopathy from degenerative disorders? RECOMMENDATION: Either ACDF or PLF are suggested for the treatment of single level degenerative cervical radiculopathy secondary to foraminal soft disc herniation to achieve comparably successful clinical outcomes. GRADE OF RECOMMENDATION: B Herkowitz et al 7 reported results of a prospective study comparing ACDF to posterior laminoforaminotomy (PLF). Of the 33 radiculopathy patients included in the study, 17 were treated with ACDF and 16 with PLF. The average age of the patients assigned to the ACDF group was 43, while the average age of the patients assigned to the PLF group was 39. Of the ACDF patients, 94% reported good (5/17) or excellent (11/17) results. Of the PLF patients, 75% reported good (6/16) or excellent (6/16) results. ACDF was not significantly better (p<0.175). Osteophytic changes were seen in 9/17 ACDF patients and 8/16 PLF patients. The authors concluded that both surgical procedures are effective, but ACDF tends to be better over the long term. In critique, neither patients nor reviewers were masked to treatment group and the randomization technique employed was questionable. No validated outcome measures were utilized to assess this small patient sample. Due to these limitations, this potential Level II study provides Level III evidence that ACD with fusion and posterior laminoforaminotomy appear equally effective in improving pain and weakness. Korinth et al 8 described a retrospective comparative study comparing clinical results of anterior and posterior surgery for cervical radiculopathy due to soft disc herniation. Of the 363 patients included in the study, 154 were treated with ACDF using PMMA for median or paramedian discs and 209 received PLF for posterolateral or foraminal discs, and 80% (292/363: 124/154 ACDF, 168/209 PLF) were available for long term follow-up via clinical outpatient examination (14.7%), questionnaire (64.4%), and/or a telephone interview (20.9%). Complication rates, primarily related to hoarseness and dysphagia, were reported in 6.5 % of ACDF patients and 1.8% of PLF patients. Reoperation rates were reported as 2.4% for the ACDF group and 7.1% for the PLF group. Mean operating time in the ACDF

84 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 64 group was 112 minutes and 94.1 minutes for the PLF group ( p<0.000). Of the patients in the ACDF group, 93.6% (116/124) reported good (36.3%) or excellent (59.5%) results according to Odom s criteria and 0.8% reported poor results (p<0.05). Of the patients in the PLF group, 85.1% (142/168) reported good (25.6%) or excellent (59.5%) results according to Odom s criteria and 7.2% reported poor results (p<0.05). In the ACDF group, a pure soft disc was removed in 60 cases (48.4%) and a mixture of both hard and soft disc elements was removed in 64 (51.6%). In the PLF group, a pure soft disc was removed in 148 cases (88.1%) and a mixture of both hard and soft disc elements was removed in 20 cases (11.9%) (p<0.000). Soft disc herniations did not have significantly better outcomes than the mixture of soft and hard disc, although there appeared to be a trend. In general, shorter duration of preoperative symptoms correlated with improved outcomes. The authors concluded that anterior surgery yielded statistically superior outcomes, but both were effective. The findings show a higher success rate with anterior microdiscectomy with PMMA interbody stabilization for treatment of degenerative cervical monoradiculopathy compared with PLF. In critique, no validated outcome measures were utilized and there was a tendency for patient selection to posterior procedure for more lateral disc herniations, whereas for paramedian and central herniations, there was an anterior bias. This study excluded patients with pure hard discs and pure foraminal stenosis. This study provides Level III evidence that patients improve with both PLF and ACDF, but ACDF results in statistically significantly better outcomes. However, ACDF is associated with a higher risk of complications, primarily related to dysphagia/hoarseness. PLF is associated with a higher reoperation rate. Wirth et al 12 reported results of a prospective randomized controlled trial comparing clinical outcomes for surgery for unilateral disc herniation causing radiculopathy. Of the 72 patients included in the study, 22 were assigned to the PLF group, 25 to ACD and 25 to ACDF. Age, gender and duration of symptoms were similar for all groups. Although not specifically stated, follow-up was inclusive. Anesthesia time, hospital stay, charges and analgesics were similar. Pain improvement was reported by more than 96% of patients in all groups. It appears that all groups had similar outcomes. Return-towork was reported as greater than 88% in all groups and there was similar incidence of new weakness and new numbness across all groups. Reoperation rate were reported as 27% for the PLF group, 12% for ACD and 28% for ACDF. The authors concluded that although the numbers in this study were small, none of the procedures could be considered superior to the others. This study suggests that the selection of surgical procedure may reasonably be based on the preference of the surgeon and tailored to the individual patient. In critique, neither patients nor reviewers were masked to the treatment group and no validated outcome measures were utilized. The functional outcome tools were broad and subjective. The initial clinical visit occurred at two months; the 60 month follow-up was poorly coordinated and varied. Numbers were small with poor statistical analysis. Due to these limitations, this potential Level II study provides Level III evidence that ACD, ACDF and PLF result in comparable clinical outcomes in the treatment of cervical radiculopathy from unilateral disc herniation. RECOMMENDATION: Compared to PLF, ACDF is suggested for the treatment of single level degenerative cervical radiculopathy from central and paracentral nerve root compression and spondylotic disease. Work Group Consensus Statement Future Directions for Research The work group identified the following suggestion for a future study which would generate meaningful evidence to assist in further defining the roles of PLF and ACDF in the surgical treatment of cervical

85 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 65 radiculopathy from degenerative disorders. Prospective, RCT with long term follow up to evaluate clinical outcomes, perioperative complications, and long term success including need for revision surgery following treatment of degenerative cervical radiculopathy with PLF versus ACDF. The study group would consist of foraminal stenosis only and should include two separate cohorts, including soft disc herniation and hard disc or spondylotic disease. References 1. An HS, Ahn NU. Posterior decompressive procedures for the cervical spine. Instr Course Lect. 2003;52: Caglar YS, Bozkurt M, Kahilogullari G, et al. Keyhole approach for posterior cervical discectomy: experience on 84 patients. Minim Invasive Neurosurg. Feb 2007;50(1): Chesnut RM, Abitbol JJ, Garfin SR. Surgical management of cervical radiculopathy. Indication, techniques, and results. Orthop Clin North Am. Jul 1992;23(3): Davis RA. A long-term outcome study of 170 surgically treated patients with compressive cervical radiculopathy. Surg Neurol. Dec 1996;46(6): ; discussion Dubuisson A, Lenelle J, Stevenaert A. Soft cervical disc herniation: a retrospective study of 100 cases. Acta Neurochir (Wien). 1993;125(1-4): Grieve JP, Kitchen ND, Moore AJ, Marsh HT. Results of posterior cervical foraminotomy for treatment of cervical spondylitic radiculopathy. Br J Neurosurg. Feb 2000;14(1): Herkowitz HN, Kurz LT, Overholt DP. Surgical management of cervical soft disc herniation. A comparison between the anterior and posterior approach. Spine. Oct 1990;15(10): Korinth MC, Kruger A, Oertel MF, Gilsbach JM. Posterior foraminotomy or anterior discectomy with polymethyl methacrylate interbody stabilization for cervical soft disc disease: results in 292 patients with monoradiculopathy. Spine. May ;31(11): ; discussion Riew KD, Cheng I, Pimenta L, Taylor B. Posterior cervical spine surgery for radiculopathy. Neurosurgery. Jan 2007;60(1 Supp1 1):S Rodrigues MA, Hanel RA, Prevedello DM, Antoniuk A, Araujo JC. Posterior approach for soft cervical disc herniation: a neglected technique? Surg Neurol. Jan 2001;55(1):17-22; discussion Ruetten S, Komp M, Merk H, Godolias G. A new fullendoscopic technique for cervical posterior foraminotomy in the treatment of lateral disc herniations using 6.9-mm endoscopes: prospective 2-year results of 87 patients. Minim Invasive Neurosurg. Aug 2007;50(4): Wirth FP, Dowd GC, Sanders HF, Wirth C. Cervical discectomy. A prospective analysis of three operative techniques. Surg Neurol. Apr 2000;53(4): ; discussion Witzmann A, Hejazi N, Krasznai L. Posterior cervical foraminotomy. A follow-up study of 67 surgically treated patients with compressive radiculopathy. Neurosurg Rev. Dec 2000;23(4): Zeidman SM, Ducker TB. Posterior cervical laminoforaminotomy for radiculopathy: review of 172 cases. Neurosurgery. Sep 1993;33(3): Does posterior decompression with fusion result in better outcomes (clinical or radiographic) than posterior decompression alone in the treatment of cervical radiculopathy from degenerative disorders? A systematic review of the literature yielded no studies to adequately compare the outcomes of posterior decompression with posterior decompression with fusion in the treatment of cervical radiculopathy from degenerative disorders. Most decompression and fusion appears to be indicated for multilevel stenosis resulting in myelopathy or for instability due to trauma, tumor, or inflammatory disease. Due to limited indications and thus limited sample size, there is likely little to gain and a low probability of generating meaningful data to compare effects of posterior decompression alone to posterior decompression and fusion for degenerative disease resulting in cervical radiculopathy. Future Directions for Research The study of posterior decompression and fusion for radiculopathy appears inappropriate. While this procedure may be indicated occasionally, there will not be enough data to study results effectively, and it would not be an appropriate arm of a randomized

86 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 66 study. Thus the workgroup would not recommend further pursuit of this question. References 1. Epstein NE. Technical note: unilateral posterior resection of cervical disc and spondylostenosis with contralateral fusion for instability. Surg Neurol. Oct 2001;56(4): Rhee JM, Yoon T, Riew KD. Cervical radiculopathy. J Am Acad Orthop Surg. Aug 2007;15(8): Scheufler KM, Kirsch E. Percutaneous multilevel decompressive laminectomy, foraminotomy, and instrumented fusion for cervical spondylotic radiculopathy and myelopathy: assessment of feasibility and surgical technique. J Neurosurg Spine. Nov 2007;7(5): Does ACD and reconstruction with total disc replacement result in better outcomes (clinical or radiographic) than ACDF in the treatment of cervical radiculopathy from degenerative disorders? RECOMMENDATION: ACDF and total disc arthroplasty (TDA) are suggested as comparable treatments, resulting in similarly successful short term outcomes, for single level degenerative cervical radiculopathy. GRADE OF RECOMMENDATION: B Murrey et al 6 conducted a prospective randomized controlled trial comparing safety and efficacy of TDA to ACDF for single level symptomatic cervical disc disease with radiculopathy. Of the 209 patients included in the study, 106 were assigned to the ACDF group and 103 to TDA. There was no difference in demographics between the TDA and ACDF groups. Follow-up rates were 98% for TDA and 94% for ACDF. ACDF had statistically significantly lower smaller blood loss and operative time (although differences small). Neurological improvement was better for TDA than ACDF at six months (p<0.05), but no significant difference was seen at 24 months (p=0.638). NDI improved from baseline for each group (p<0.0001); however, between groups there was a significant difference at three months for TDA (p<0.05) but not at 24 months (p=1.0000). This was also true for aggregate patients who had greater than a 15 point improvement. Secondary surgical procedures were performed in 1.9% of TDA patients and 8.5% of ACDF patients. Implant revision was required in 4.7% of the ACDF patients, with 2.8% of the ACDF patients requiring supplemental fixation, while no TDA patients required revision. VAS neck pain, arm pain frequency and intensity were similar for TDA and ACDF patients at 24 months. Success, as defined by greater than 20% improvement in VAS scores, was reported for 87.9% of TDA patients and 86.9% of ACDF patients at 24 months. At 24 months, 80.8% of TDA patients and 74.4% of ACDF patients had successful outcomes as assessed by the SF-36 physical component summary. The SF- 36 mental component summary showed 71.8% of TDA and 68.9% of ACDF patients were successful. Patient satisfaction, narcotic use and adverse events were similar for both groups. The authors concluded that TDA for single level disease is safe and effective and at least as good as ACDF. In critique, neither patients nor reviewers were masked to treatment group. This study provides Level I evidence that TDA shows equivalent outcomes to ACDF at two years for treatment of cervical radiculopathy due to single level disease. Nabhan et al 7 reported results of a prospective randomized controlled trial comparing radiographic and clinical results of TDA to ACDF. Of the 49 patients included in the study, 25 were assigned to TDA and 24 to ACDF; however, only 20 TDA and 21 ACDF patients could be measured due to artifact. Range of motion decreased in both groups. In the TDA group, average motion decreased from 2.3 at one week to 0.8 at 52 weeks; in ACDF, it decreased from 0.6 at one week to 0.1 at 52 weeks. Comparison between

87 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 67 groups showed that the motion was significantly less in the ACDF group for all time points except three weeks. Preoperatively, there was no statistical difference in symptoms between both groups (P=0.1), as measured by the VAS. Both groups showed the same pattern of pain relief in arm pain at all examination times without a statistically significant difference (P=0.13). The ACDF group showed a higher postsurgical resolving ratio in neck pain relief at three weeks, although without any statistically significant differences (P=0.09). The authors concluded that disc motion was maintained by TDA at one year and was greater than ACDF, with similar clinical results to ACDF. In critique, neither patients nor reviewers were masked to treatment group. No validated outcome measures were used and the sample size was small. The study utilized a good radiographic analysis tool, but investigators chose neutral and extreme extension and lateral rotation for their motion analysis. Clinical evaluation was limited and was not the emphasis. Follow-up was only one year. Also the authors concluded that motion was maintained with TDA; however, the data demonstrate that it was not. Range of motion was decreased, but significantly greater than with ACDF. Due to these limitations, this potential Level I study provides Level II evidence that compared with ACDF, patients treated with TDA have statistically significantly greater range of motion. Clinical outcomes are similar for both groups. There were several additional studies reviewed, some of them of high quality, that could not be included in this guideline due to confounding of myelopathy grouped with radiculopathy. Due to lack of subgroup analyses in these studies, no conclusions could be reached in regards to outcomes in patients with cervical radiculopathy from degenerative disorders. Future Directions for Research The work group identified the following suggestions for future studies which would generate meaningful evidence to assist in comparing outcomes of ACDF and TDA in the treatment of cervical radiculopathy from degenerative disorders. Recommendation #1: Continued long term follow-up of patients currently enrolled in previously reported RCTs is necessary to determine if purported advantages of TDA compared with ACDF can be validated, with particular focus on validated clinical outcomes, revision surgery and adjacent segment disease. Subgroup analysis should include soft disc compared with hard disc and foraminal compared with paracentral pathology for cervical radiculopathy patients. Recommendation #2: Additional independent, masked, prospective RCTs comparing ACDF to TDA for the treatment of cervical radiculopathy from degenerative disorders would add substantial unbiased validation to the results of the investigational device exemption (IDE) studies. References 1. Anderson PA, Sasso RC, Riew KD. Comparison of adverse events between the Bryan artificial cervical disc and anterior cervical arthrodesis. Spine. 2008: Bartels RH, Donk R, van der Wilt GJ, Grotenhuis JA, Venderink D. Design of the PROCON trial: a prospective, randomized multi-center study comparing cervical anterior discectomy without fusion, with fusion or with arthroplasty. BMC Musculoskelet Disord. 2006;7: Heidecke V, Burkert W, Brucke M, Rainov NG. Intervertebral disc replacement for cervical degenerative disease-- clinical results and functional outcome at two years in patients implanted with the Bryan cervical disc prosthesis. Acta Neurochir (Wien). May 2008;150(5): ; discussion Kim SW, Limson MA, Kim SB, et al. Comparison of radiographic changes after ACDF versus Bryan disc arthroplasty in single and bi-level cases. Euro Spine J. Feb 2009;18(2): Mummaneni PV, Burkus JK, Haid RW, Traynelis VC, Zdeblick TA. Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. J Neurosurg Spine. Mar 2007;6(3): Murrey D, Janssen M, Delamarter R, et al. Results of the prospective, randomized, controlled multicenter Food and Drug Administration investigational device exemp-

88 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 68 tion study of the ProDisc-C total disc replacement versus anterior discectomy and fusion for the treatment of 1-level symptomatic cervical disc disease. Spine J. Apr 2009;9(4): Nabhan A, Ahlhelm F, Shariat K, et al. The ProDisc-C prothesis - Clinical and radiological experience 1 year after surgery. Spine. Aug 2007;32(18): Sasso RC, Smucker JD, Hacker RJ, Heller JG. Artificial disc versus fusion: a prospective, randomized study with 2-year follow-up on 99 patients. Spine. Dec ;32(26): ; discussion What is the long-term result (four+ years) of surgical management of cervical radiculopathy from degenerative disorders? RECOMMENDATION: Surgery is an option for the treatment of single level degenerative radiculopathy to produce and maintain favorable long term (greater than four year) outcomes. GRADE OF RECOMMENDATION: C Hamburger et al 7 described a retrospective case series reviewing results of ACD with PMMA. Of the 319 cervical radiculopathy patients included in the study, 249 were available for final follow-up at a mean of 12.2 years. Of the 249 patients available for final follow-up, 246 had single level and 3 had two level surgery. Good or excellent results were reported by 87% of patients. Lumbar symptoms and high occupational stress were correlated with clinical failure. Patients with soft disc herniations reported the best results. Relatively worse outcomes were reported when patients had unclear preoperative findings. The authors concluded that ACD with PMMA is a safe and reliable method for treating monosegmental radiculopathy with outcomes and complication rates similar to other published studies. In critique, no validated outcome measures were used. This study provides Level IV evidence that for the treatment of cervical radiculopathy due to single level disease, ACD with PMMA interbody spacer results in 77% of patients reporting satisfactory clinical outcomes at 10 to 15 years following surgery. Heidecke et al 8 reported a case series reviewing outcomes of Cloward-type fusion at mean follow-up of 6.5 years. Of the 28 radiculopathy patients included, long term outcome was reported as good for 93% and fair for 7%. No poor results were reported. Adverse events were dominated by graft site complications. The authors concluded that Cloward ACDF is a reliable and safe procedure for single level disease. In critique, no validated outcome measures were used in the study including a small sample of radiculopathy patients. This study provides Level IV evidence that for treatment of cervical radiculopathy due to degenerative disease, ACDF with Cloward technique results in 93% satisfactory results with long term (4-10 year) follow-up. Jagannathan et al 11 presented findings from a retrospective case series reviewing results of PLF for treatment of single level cervical radiculopathy. Of the 212 cervical radiculopathy patients included in the study, long term outcomes were reported at a mean of 78 months for the 162 patients. While NDI improved in 93% of patients, 20% developed kyphosis. Patients who developed kyphosis reported worse results overall. During the follow-up period, 3.1% (5/162) required additional procedures; two had progression of disease at the index level, two developed stenosis and one developed instability. The authors concluded that PLF is highly successful for treating cervical radiculopathy. This study provides Level IV evidence that posterior laminoforaminotomy for the treatment of cervical radiculopathy due to degenerative disease results in significant improvement in 93% of cases at 5-15 year follow-up. There may be a trend for patients older than 60 years with initial lordosis of less than 10 degrees to be more vulnerable to development of postoperative cervical kyphosis or translational deformity, though the clinical significance of this is uncertain.

89 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 69 Wirth et al 21 reported results of a prospective randomized controlled trial comparing clinical outcomes for surgery for unilateral disc herniation causing radiculopathy. Of the 72 patients included in the study, 22 were assigned to the PLF group, 25 to ACD and 25 to ACDF. Age, gender and duration of symptoms were similar for all groups. Although not specifically stated, follow-up was inclusive. Anesthesia time, hospital stay, charges and analgesics were similar. Pain improvement was reported by more than 96% of patients in all groups. It appears that all groups had similar outcomes. Return-towork was reported as greater than 88% in all groups and there was similar incidence of new weakness and new numbness across all groups. Reoperation rates were reported as 27% for the PLF group, 12% for ACD and 28% for ACDF. Of the 72 patients included in the study, 60% [13/25 (52%) for ACD, 16/25 (64%) for ACDF, and 14/22 (64%) for PLF] were available for final follow-up at a mean of 60 months via telephone interview or clinic visit. The authors concluded that ACD, ACDF or PLF are reasonable surgical choices for cervical radiculopathy due to unilateral disc herniation. In critique, neither patients nor reviewers were masked to the treatment group and no validated outcome measures were utilized. The functional outcome tools were broad and subjective. The initial clinical visit occurred at two months; the 60 month follow-up was poorly coordinated and varied. Numbers were small with poor statistical analysis and 40% were lost to follow-up. Due to these limitations, this potential Level II study provides Level III evidence that for unilateral radiculopathy caused by CDH, ACD, ACDF or PLF result in satisfactory outcomes at five year follow-up. Future Directions for Research The work group identified the following suggestion for future studies which would generate meaningful evidence to assist in comparing long term outcomes of various surgical procedures to assist in defining their role in the treatment of cervical radiculopathy from degenerative disorders. An adequately powered, prospective, comparative study of patients treated with ACDF, ACD, TDA and PLF followed for greater than four years and assessed with validated outcome measures would yield useful information about the long term outcomes of surgery for cervical radiculopathy from degenerative disorders. References 1. Bertalanffy H, Eggert HR. Clinical long-term results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. A follow-up of 164 cases. Acta Neurochir (Wien). 1988;90(3-4): Cornelius JF, Bruneau M, George B. Microsurgical cervical nerve root decompression via an anterolateral approach: Clinical outcome of patients treated for spondylotic radiculopathy. Neurosurgery. Nov 2007;61(5): Davis RA. A long-term outcome study of 170 surgically treated patients with compressive cervical radiculopathy. Surg Neurol. Dec 1996;46(6): ; discussion Gaetani P, Tancioni F, Spanu G, Rodriguez y Baena R. Anterior cervical discectomy: an analysis on clinical long-term results in 153 cases. J Neurosurg Sci. Dec 1995;39(4): Goffin J, Geusens E, Vantomme N, et al. Long-term followup after interbody fusion of the cervical spine. J Spinal Disord Tech. Apr 2004;17(2): Goldberg EJ, Singh K, Van U, Garretson R, An HS. Comparing outcomes of anterior cervical discectomy and fusion in workman s versus non-workman s compensation population. Spine J. Nov-Dec 2002;2(6): Hamburger C, Festenberg FV, Uhl E. Ventral discectomy with pmma interbody fusion for cervical disc disease: longterm results in 249 patients. Spine. Feb ;26(3): Heidecke V, Rainov NG, Marx T, Burkert W. Outcome in Cloward anterior fusion for degenerative cervical spinal disease. Acta Neurochir (Wien). 2000;142(3): Hida K, Iwasaki Y, Yano S, Akino M, Seki T. Long-term follow-up results in patients with cervical disk disease treated by cervical anterior fusion using titanium cage implants. Neurol Med Chir (Tokyo). Oct 2008;48(10): ; discussion Hilibrand AS, Carlson GD, Palumbo MA, Jones PK, Bohlman HH. Radiculopathy and myelopathy at segments adjacent to the site of a previous anterior cervical arthrodesis. J Bone Joint Surg Am. Apr 1999;81(4): Jagannathan J, Sherman JH, Szabo T, Shaffrey CI, Jane JA. The posterior cervical foraminotomy in the treatment of cervical disc/osteophyte disease: a single-surgeon experience with a minimum of 5 years clinical and radiographic

90 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 70 follow-up. J Neurosurg Spine. Apr 2009;10(4): Kadoya S, Iizuka H, Nakamura T. Long-term outcome for surgically treated cervical spondylotic radiculopathy and myelopathy. Neurol Med Chir (Tokyo). May 2003;43(5): ; discussion Korinth MC, Kruger A, Oertel MF, Gilsbach JM. Posterior foraminotomy or anterior discectomy with polymethyl methacrylate interbody stabilization for cervical soft disc disease: results in 292 patients with monoradiculopathy. Spine. May ;31(11): ; discussion Matge G, Leclercq TA. Rationale for interbody fusion with threaded titanium cages at cervical and lumbar levels. Results on 357 cases. Acta Neurochir (Wien). 2000;142(4): Peolsson A, Peolsson M. Predictive factors for long-term outcome of anterior cervical decompression and fusion: a multivariate data analysis. Eur Spine J. Mar 2008;17(3): Ramzi N, Ribeiro-Vaz G, Fomekong E, Lecouvet FE, Raftopoulos C. Long term outcome of anterior cervical discectomy and fusion using coral grafts. Acta Neurochir (Wien). Dec 2008;150(12): ; discussion Rao PJ, Christie JG, Ghahreman A, Cartwright CA, Ferch RD. Clinical and functional outcomes of anterior cervical discectomy without fusion. J Clin Neurosci. December 2008;15(12): Schneeberger AG, Boos N, Schwarzenbach O, Aebi M. Anterior cervical interbody fusion with plate fixation for chronic spondylotic radiculopathy: a 2- to 8-year followup. J Spinal Disord. Jun 1999;12(3): ; discussion Shapiro S, Connolly P, Donnaldson J, Abel T. Cadaveric fibula, locking plate, and allogeneic bone matrix for anterior cervical fusions after cervical discectomy for radiculopathy or myelopathy. J Neurosurg. Jul 2001;95(1 Suppl): Sugawara T, Itoh Y, Hirano Y, Higashiyama N, Mizoi K. Long term outcome and adjacent disc degeneration after anterior cervical discectomy and fusion with titanium cylindrical cages. Acta Neurochir (Wien). Apr 2009;151(4): Wirth FP, Dowd GC, Sanders HF, Wirth C. Cervical discectomy. A prospective analysis of three operative techniques. Surg Neurol. Apr 2000;53(4): ; discussion Yamamoto I, Ikeda A, Shibuya N, Tsugane R, Sato O. Clinical long-term results of anterior discectomy without interbody fusion for cervical disc disease. Spine. Mar 1991;16(3): Zeidman SM, Ducker TB. Posterior cervical laminoforaminotomy for radiculopathy: review of 172 cases. Neurosurgery. Sep 1993;33(3): How do long-term results of singlelevel compare with multilevel surgical decompression for cervical radiculopathy from degenerative disorders? A systematic review of the literature yielded no studies to adequately address the comparison of long term results of single-level compared with multilevel surgical decompression in the management of cervical radiculopathy from degenerative disorders. After this review, it is clear that most patients with true radiculopathy suffer from one level and occasionally two level disease. The incidence of multilevel disease without the additional presence of myelopathy is rare. Thus, there is likely little to gain and a low probability of generating meaningful data to answer this question. Future Directions for Research The work group would not recommend further pursuit of this question, but suggests limiting efforts to collecting long term data in primarily single level disease. References 1. Bertalanffy H, Eggert HR. Clinical long-term results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. A follow-up of 164 cases. Acta Neurochir (Wien). 1988;90(3-4): Cornelius JF, Bruneau M, George B. Microsurgical cervical nerve root decompression via an anterolateral approach: Clinical outcome of patients treated for spondylotic radiculopathy. Neurosurgery. Nov 2007;61(5): Gaetani P, Tancioni F, Spanu G, Rodriguez y Baena R. Anterior cervical discectomy: an analysis on clinical long-term results in 153 cases. J Neurosurg Sci. Dec 1995;39(4): Goffin J, Geusens E, Vantomme N, et al. Long-term followup after interbody fusion of the cervical spine. J Spinal Disord Tech. Apr 2004;17(2): Hamburger C, Festenberg FV, Uhl E. Ventral discectomy with pmma interbody fusion for cervical disc disease: longterm results in 249 patients. Spine. Feb ;26(3):

91 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Heidecke V, Rainov NG, Marx T, Burkert W. Outcome in Cloward anterior fusion for degenerative cervical spinal disease. Acta Neurochir (Wien). 2000;142(3): Kadoya S, Iizuka H, Nakamura T. Long-term outcome for surgically treated cervical spondylotic radiculopathy and myelopathy. Neurol Med Chir (Tokyo). May 2003;43(5): ; discussion Korinth MC, Kruger A, Oertel MF, Gilsbach JM. Posterior foraminotomy or anterior discectomy with polymethyl methacrylate interbody stabilization for cervical soft disc disease: results in 292 patients with monoradiculopathy. Spine. May ;31(11): ; discussion Peolsson A, Peolsson M. Predictive factors for long-term outcome of anterior cervical decompression and fusion: a multivariate data analysis. Eur Spine J. Mar 2008;17(3): Ramzi N, Ribeiro-Vaz G, Fomekong E, Lecouvet FE, Raftopoulos C. Long term outcome of anterior cervical discectomy and fusion using coral grafts. Acta Neurochir (Wien). Dec 2008;150(12): ; discussion Rao PJ, Christie JG, Ghahreman A, Cartwright CA, Ferch RD. Clinical and functional outcomes of anterior cervical discectomy without fusion. J Clin Neurosci. December 2008;15(12): Shapiro S, Connolly P, Donnaldson J, Abel T. Cadaveric fibula, locking plate, and allogeneic bone matrix for anterior cervical fusions after cervical discectomy for radiculopathy or myelopathy. J Neurosurg. Jul 2001;95(1 Suppl): Sugawara T, Itoh Y, Hirano Y, Higashiyama N, Mizoi K. Long term outcome and adjacent disc degeneration after anterior cervical discectomy and fusion with titanium cylindrical cages. Acta Neurochir (Wien). Apr 2009;151(4): Yamamoto I, Ikeda A, Shibuya N, Tsugane R, Sato O. Clinical long-term results of anterior discectomy without interbody fusion for cervical disc disease. Spine. Mar 1991;16(3): Zeidman SM, Ducker TB. Posterior cervical laminoforaminotomy for radiculopathy: review of 172 cases. Neurosurgery. Sep 1993;33(3):

92 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 72 V. Appendices Appendix A: Acronyms ACD ACDF ACDFI ACDFP ADL AROM C-TDR CDH CR CSR CT CTM CTS DTR EBM EMG GRE HAD HNP HSQ ICBG LFA anterior cervical discectomy/ decompression anterior cervical discectomy/ decompression and fusion anterior cervical discectomy/ decompression and instrumented fusion anterior cervical discectomy/ decompression and fusion plus plate activities of daily living active range of motion cervical total disc replacement cervical disc herniation cervical radiculopathy cervical spondylotic radiculopathy computed tomography computed tomography myelography carpal tunnel syndrome deep tendon reflex evidence-based medicine electromyography gradient recall echo Hospital Anxiety and Depression herniated nucleus pulposus Health Status Questionnaire iliac crest bone graft limited flip angle MMI Modified Million Index MR magnetic resonance MRI magnetic resonance imaging NASS North American Spine Society NDI Neck Disability Index NPS neurophysiologic studies NPP negative predictive power NSAIDs nonsteroidal anti-inflammatory drugs ODI Oswestry Disability Index PEMF pulsed electromagnetic field PLF posterior laminoforaminotomy PMMA polymethylmethacrylate PPV positive predictive value PSFS Patient Specific Functional Scale RCT randomized clinical trial ROM range of motion SF Item Short Form Health Survey SF Item Short Form Health Survey SIP Sickness Impact Profile SNRB selective nerve root block TDA total disc arthroplasty TENS transcutaneous electrical nerve stimulation ULTT Upper Limb Tension Test VAS Visual Analog Scale ZDS Zung Depression Scale

93 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 73 Appendix B: Levels of Evidence For Primary Research Question 1 Level 1 Therapeutic Studies Investigating the results of treatment High quality randomized trial with statistically significant difference or no statistically significant difference but narrow confidence intervals Systematic review 2 of Level I RCTs (and study results were homogenous 3 ) Types of Studies Prognostic Studies Investigating the effect of a patient characteristic on the outcome of disease High quality prospective study 4 (all patients were enrolled at the same point in their disease with 80% follow-up of enrolled patients) Systematic review 2 of Level I studies Diagnostic Studies Investigating a diagnostic test Testing of previously developed diagnostic criteria on consecutive patients (with universally applied reference gold standard) Systematic review 2 of Level I studies Economic and Decision Analyses Developing an economic or decision model Sensible costs and alternatives; values obtained from many studies; with multiway sensitivity analyses Systematic review 2 of Level I studies Level II Lesser quality RCT (eg, < 80% follow-up, no blinding, or improper randomization) Prospective 4 comparative study 5 Systematic review 2 of Level II studies or Level 1 studies with inconsistent results Retrospective 6 study Untreated controls from an RCT Lesser quality prospective study (eg, patients enrolled at different points in their disease or <80% follow-up) Systematic review 2 of Level II studies Development of diagnostic criteria on consecutive patients (with universally applied reference gold standard) Systematic review 2 of Level II studies Sensible costs and alternatives; values obtained from limited studies; with multiway sensitivity analyses Systematic review 2 of Level II studies Level III Case control study 7 Retrospective 6 comparative study 5 Systematic review 2 of Level III studies Case control study 7 Study of nonconsecutive patients; without consistently applied reference gold standard Systematic review 2 of Level III studies Analyses based on limited alternatives and costs; and poor estimates Systematic review 2 of Level III studies Level IV Case series 8 Case series Case-control study Poor reference standard Analyses with no sensitivity analyses Level V Expert opinion Expert opinion Expert opinion Expert opinion 1. A complete assessment of quality of individual studies requires critical appraisal of all aspects of the study design. 2. A combination of results from two or more prior studies. 3. Studies provided consistent results. 4. Study was started before the first patient enrolled. 5. Patients treated one way (eg, cemented hip arthroplasty) compared with a group of patients treated in another way (eg, uncemented hip arthroplasty) at the same institution. 6. The study was started after the first patient enrolled. 7. Patients identified for the study based on their outcome, called cases (eg, failed total arthroplasty) are compared to those who did not have outcome, called controls (eg, successful total hip arthroplasty). 8. Patients treated one way with no comparison group of patients treated in another way.

94 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 74 Appendix C: Grades of Recommendation for Summaries or Reviews of Studies A: Good evidence (Level I Studies with consistent findings) for or against recommending intervention. B: Fair evidence (Level II or III Studies with consistent findings) for or against recommending intervention. C: Poor quality evidence (Level IV or V Studies) for or against recommending intervention. I: Insufficient or conflicting evidence not allowing a recommendation for or against intervention.

95 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 75 Appendix D: Protocol for NASS Literature Searches One of the most crucial elements of evidence analysis to support development of recommendations for appropriate clinical care or use of new technologies is the comprehensive literature search. Thorough assessment of the literature is the basis for the review of existing evidence, which will be instrumental to these activities. Background It has become apparent that the number of literature searches being conducted at NASS is increasing and that they are not necessarily conducted in a consistent manner between committees/projects. Because the quality of a literature search directly affects the quality of recommendations made, a comparative literature search was undertaken to help NASS refine the process and make recommendations about how to conduct future literature searches on a NASS-wide basis. In November-December 2004, NASS conducted a trial run at new technology assessment. As part of the analysis of that pilot process, the same literature searches were conducted by both an experienced NASS member and a medical librarian for comparison purposes. After reviewing the results of that experiment and the different strategies employed for both searches, it was the recommendation of NASS Research Staff that a protocol be developed to ensure that all future NASS searches be conducted consistently to yield the most comprehensive results. While it is recognized that some searches occur outside the Research and Clinical Care Councils, it is important that all searches conducted at NASS employ a solid search strategy, regardless of the source of the request. To this end, this protocol has been developed and NASS-wide implementation is recommended. Protocol for NASS Literature Searches The NASS Research Department has a relationship with Northwestern University s Galter Health Sciences Library. When it is determined that a literature search is needed, NASS research staff will work with the requesting parties and Galter to run a comprehensive search employing at a minimum the following search techniques: 1. A preliminary search of the evidence will be conducted using the following clearly defined search parameters (as determined by the content experts). The following parameters are to be provided to research staff to facilitate this search. Time frames for search Foreign and/or English language Order of results (chronological, by journal, etc.) Key search terms and connectors, with or without MeSH terms to be employed Age range Answers to the following questions: Should duplicates be eliminated between searches? Should searches be separated by term or as one large package? Should human studies, animal studies or cadaver studies be included? This preliminary search should encompass a search of the Cochrane database when access is available. 2. Search results with abstracts will be compiled by Galter in Endnote software. Galter typically responds to requests and completes the searches within two to five days. Results will be forwarded to the research staff, who will share it with the appropriate NASS staff member or requesting party(ies). (Research staff hasve access to EndNote software and will maintain a database of search results for future use/documentation.)

96 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders NASS staff shares the search results with an appropriate content expert (NASS Committee member or other) to assess relevance of articles and identify appropriate articles to review and on which to run a related articles search. 4. Based on content expert s review, NASS research staff will then coordinate with the Galter medical librarian the second level searching to identify relevant related articles. 5. Galter will forward results to Research Staff to share with appropriate NASS staff. 6. NASS staff share related articles search results with an appropriate content expert (NASS Committee member or other) to assess relevance of this second set of articles, and identify appropriate articles to review and on which to run a second related articles search. 7. NASS research staff will work with Galter library to obtain the 2nd related articles search results and any necessary full-text articles for review. 8. NASS members reviewing full-text articles should also review the references at the end of each article to identify additional articles which should be reviewed, but may have been missed in the search. Protocol for Expedited Searches At a minimum, numbers 1, 2 and 3 should be followed for any necessary expedited search. Following #3, depending on the time frame allowed, deeper searching may be conducted as described by the full protocol or request of full-text articles may occur. If full-text articles are requested, #8 should also be included. Use of the expedited protocol or any deviation from the full protocol should be documented with explanation. Following these protocols will help ensure that NASS recommendations are (1) based on a thorough review of relevant literature; (2) are truly based on a uniform, comprehensive search strategy; and (3) represent the current best research evidence available. Research staff will maintain a search history in EndNote for future use or reference.

97 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 77 Appendix E: Literature Search Parameters Natural History of Cervical Radiculopathy from Degenerative Disorders Search Strategies Search Strategies by Clinical Question: 1. What is the best working definition of cervical radiculopathy from degenerative disorders? Reviewed book chapters (see reference section). 2. What is the natural history of cervical radiculopathy from degenerative disoders? ((("Radiculopathy"[Mesh] OR "Polyradiculopathy"[Mesh] OR "Intervertebral Disk Displacement"[Mesh]) AND cervical[all Fields]) OR ("cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields] OR "cervical disc herniation"[all Fields])) AND degenerative[all Fields] AND ("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang] Databases Searched: MEDLINE (PubMed) EMBASE Web of Science Cochrane Database of Systematic reviews Cochrane Central Register of Controlled Trials

98 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 78 Diagnosis/Imaging of Cervical Radiculopathy from Degenerative Disorders Search Strategies Search Strategies by Clinical Question: 1. What are the most appropriate historical and physical exam findings consistent with the diagnosis of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Radiculopathy/diagnosis"[Mesh] OR "Diagnosis"[Mesh:noexp] OR "Diagnosis, Differential"[Mesh] OR "Signs and Symptoms"[Mesh]) 2. What are the most appropriate diagnostic tests for cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Radiculopathy/diagnosis"[Mesh] OR "Diagnosis"[Mesh] OR "Signs and Symptoms"[Mesh]) AND (accuracy[all Fields] OR reliability[all Fields] OR validity[all Fields] OR "sensitivity and specificity"[all Fields] OR "predictive value of tests"[all Fields]) Databases Searched: MEDLINE (PubMed) EMBASE Web of Science Cochrane Database of Systematic reviews Cochrane Central Register of Controlled Trials

99 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 79 Outcome Measures for Cervical Radiculopathy from Degenerative Disorders Search Strategies Search Strategies by Clinical Question: 1. What are the appropriate outcome measures for the treatment of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("outcome assessment (health care)"[mesh Terms] OR ("outcome"[all Fields] AND "assessment"[all Fields] AND "(health"[all Fields] AND "care)"[all Fields]) OR "outcome assessment (health care)"[all Fields] OR ("outcome"[all Fields] AND "measure"[all Fields]) OR "outcome measure"[all Fields]) OR ("outcome assessment (health care)"[mesh Terms] OR ("outcome"[all Fields] AND "assessment"[all Fields] AND "(health"[all Fields] AND "care)"[all Fields]) OR "outcome assessment (health care)"[all Fields] OR ("outcome"[all Fields] AND "measures"[all Fields]) OR "outcome measures"[all Fields])) Databases Searched: MEDLINE (PubMed) EMBASE Web of Science Cochrane Database of Systematic reviews Cochrane Central Register of Controlled Trials

100 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 80 Medical/Interventional Treatment of Cervical Radiculopathy from Degenerative Disorders Search Strategies Search Strategies by Clinical Question: 1. What is the role of pharmacological treatment in the management of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("Drug Therapy"[Mesh] OR "drug therapy "[Subheading] OR ("pharmacology"[mesh Terms] OR "pharmacology"[all Fields] OR "pharmacological"[all Fields]) OR ("pharmaceutical preparations"[mesh Terms] OR ("pharmaceutical"[all Fields] AND "preparations"[all Fields]) OR "pharmaceutical preparations"[all Fields] OR "medication"[all Fields])) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang]) 2. What is the role of physical therapy/exercise in the treatment of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Physical Therapy Modalities"[Mesh] OR "Exercise"[Mesh] OR "Physical Exertion"[Mesh] OR "Physical Fitness"[Mesh] OR "Rehabilitation"[Mesh] OR "rehabilitation "[Subheading] OR exercise[title] OR physical therapy[title] OR rehabilitation[title] AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang]))

101 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders What is the role of manipulation/chiropractics in the treatment of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Manipulation, Chiropractic"[Mesh] OR "Manipulation, Spinal"[Mesh] OR "Manipulation, Orthopedic"[Mesh] OR "Musculoskeletal Manipulations"[Mesh] OR "Chiropractic"[Mesh] OR manipulation[all Fields] OR ("chiropractic"[mesh Terms] OR "chiropractic"[all Fields])) 4. What is the role of epidural steroid injections for the treatment of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Injections"[Mesh] OR injections[title] OR injection[title]) 5. What is the role of ancillary treatments such as bracing, traction, electrical stimulation, acupuncture and transcutaneous electrical stimulation (TENS) in the treatment of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Braces"[Mesh] OR "Traction"[Mesh] OR "Electric Stimulation"[Mesh] OR "Transcutaneous Electric Nerve Stimulation"[Mesh] OR "Acupuncture Therapy"[Mesh] OR "Acupuncture"[Mesh] OR bracing[all Fields] OR ("braces"[mesh Terms] OR "braces"[all Fields] OR "brace"[all Fields]) OR ("braces"[mesh Terms] OR "braces"[all Fields]) OR ("traction"[mesh Terms] OR "traction"[all Fields]) OR "electrical stimulation"[all Fields] OR ("transcutaneous electric nerve stimulation"[mesh Terms] OR ("transcutaneous"[all Fields] AND "electric"[all Fields] AND "nerve"[all Fields] AND "stimulation"[all Fields]) OR "transcutaneous electric nerve stimulation"[all Fields] OR "tens"[all Fields]))

102 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 82 Databases Searched: MEDLINE (PubMed) EMBASE Web of Science Cochrane Database of Systematic reviews Cochrane Central Register of Controlled Trials Surgical Treatment of Cervical Radiculopathy from Degenerative Disorders Search Strategies Search Strategies by Clinical Question 1. Does surgical treatment (with or without preoperative medical/interventional treatment) result in better outcomes than medical/interventional treatment for cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Surgical Procedures, Operative"[Mesh] OR "surgery "[Subheading] OR surgery[title] OR surgical[title] OR operative[title] OR operation[title] AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang]) 2. Does anterior cervical decompression with fusion result in better outcomes (clinical or radiographic) than anterior cervical decompression alone? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("Decompression, Surgical"[Mesh] AND anterior[all Fields] AND cervical[all Fields]) OR (anterior[all Fields] AND cervical[all Fields] AND ("decompression"[mesh Terms] OR "decompression"[all Fields]) OR (anterior[all Fields] AND cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields] OR "discectomy"[all Fields]))) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang]) AND (("Nucl Eng Des/Fusion"[Journal] OR "fusion"[all Fields]) OR ("arthrodesis"[mesh Terms] OR "arthrodesis"[all Fields]))

103 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Does anterior cervical decompression and fusion with instrumentation result in better outcomes (clinical or radiographic) than anterior cervical decompression and fusion without instrumentation? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("Decompression, Surgical"[Mesh] AND anterior[all Fields] AND cervical[all Fields]) OR (anterior[all Fields] AND cervical[all Fields] AND ("decompression"[mesh Terms] OR "decompression"[all Fields]) OR ((anterior[all Fields] AND cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields] OR "discectomy"[all Fields])) OR (anterior[all Fields] AND cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields]))) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang]) AND (("Nucl Eng Des/Fusion"[Journal] OR "fusion"[all Fields]) OR ("arthrodesis"[mesh Terms] OR "arthrodesis"[all Fields]))) AND ("instrumentation "[Subheading] OR "Bone Plates"[Mesh] OR ("bone plates"[mesh Terms] OR ("bone"[all Fields] AND "plates"[all Fields]) OR "bone plates"[all Fields] OR "plate"[all Fields]) OR plates[all Fields] OR plating[all Fields] OR instrumentation[title] OR ("computers"[mesh Terms] OR "computers"[all Fields] OR "hardware"[all Fields])) 4. Does anterior surgery result in better outcomes (clinical or radiographic) than posterior surgery in the treatment of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("Decompression, Surgical"[Mesh] OR "Laminectomy"[Mesh] OR "cervical decompression"[all Fields] OR "laminectomy"[title] OR "laminotomy"[title] OR foraminotomy[title] OR laminoplasty[title] OR (cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields] OR "discectomy"[all Fields])) OR (cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields]))) AND (anterior[all Fields] AND posterior[all Fields])) 5. Does posterior decompression with fusion result in better outcomes (clinical or radiographic) than posterior decompression alone in the treatment of cervical radiculopathy from degenerative disorders?

104 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 84 ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Decompression, Surgical"[Mesh] OR "Laminectomy"[Mesh] OR "cervical decompression"[all Fields] OR "laminectomy"[title] OR "laminotomy"[title] OR foraminotomy[title] OR laminoplasty[title] OR (cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields] OR "discectomy"[all Fields])) OR (cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields]))) AND posterior[all Fields] AND (("Nucl Eng Des/Fusion"[Journal] OR "fusion"[all Fields]) OR ("arthrodesis"[mesh Terms] OR "arthrodesis"[all Fields])) 6. Does anterior cervical decompression and reconstruction with total disc replacement result in better outcomes (clinical or radiographic) than anterior cervical decompression and fusion in the treatment of cervical radiculopathy from degenerative disorders? ((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("Arthroplasty"[Mesh] AND disc[all Fields]) OR disc arthroplasty[all Fields] OR disk arthroplasty[all Fields] OR disc replacement[all Fields] OR disk replacement[all Fields] AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("Nucl Eng Des/Fusion"[Journal] OR "fusion"[all Fields]) OR ("arthrodesis"[mesh Terms] OR "arthrodesis"[all Fields])) AND (("Decompression, Surgical"[Mesh] AND anterior[all Fields] AND cervical[all Fields]) OR (anterior[all Fields] AND cervical[all Fields] AND ("decompression"[mesh Terms] OR "decompression"[all Fields]) OR (anterior[all Fields] AND cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields] OR "discectomy"[all Fields]))) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) 7. What is the long-term result (four+ years) of surgical management of cervical radiculopathy from degenerative disorders? ("Longitudinal Studies"[Mesh:noexp] OR (long[all Fields] AND term[all Fields]) OR long-term[all Fields] AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields]

105 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 85 OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Surgical Procedures, Operative"[Mesh] OR "surgery "[Subheading] OR surgery[title] OR surgical[title] OR operative[title] OR operation[title] AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang]) 8. How do long-term results of single-level compare with multilevel surgical decompression for cervical radiculopathy from degenerative disorders? (((("Radiculopathy"[All Fields] AND cervical[all Fields]) OR "cervical radiculopathy"[all Fields] OR "cervical radiculitis"[all Fields]) AND ("Intervertebral Disk Displacement"[Mesh] OR foraminal stenosis[all Fields] OR ("intervertebral disk degeneration"[mesh Terms] OR ("intervertebral"[all Fields] AND "disk"[all Fields] AND "degeneration"[all Fields]) OR "intervertebral disk degeneration"[all Fields] OR ("disc"[all Fields] AND "degeneration"[all Fields]) OR "disc degeneration"[all Fields]) OR disk degeneration[all Fields] OR disk herniation[all Fields] OR disc herniation[all Fields] OR degenerative[all Fields]) AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) AND ("Decompression, Surgical"[Mesh] OR "Laminectomy"[Mesh] OR "cervical decompression"[all Fields] OR "laminectomy"[all Fields] OR "laminotomy"[all Fields] OR foraminotomy[all Fields] OR laminoplasty[all Fields] OR (cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields] OR "discectomy"[all Fields])) OR (cervical[all Fields] AND ("diskectomy"[mesh Terms] OR "diskectomy"[all Fields])))) AND ("Longitudinal Studies"[Mesh:noexp] OR (long[all Fields] AND term[all Fields]) OR long-term[all Fields] AND (("1966"[PDAT] : "3000"[PDAT]) AND "humans"[mesh Terms] AND English[lang])) Databases Searched: MEDLINE (PubMed) EMBASE Web of Science Cochrane Database of Systematic reviews Cochrane Central Register of Controlled Trials

106 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 86 Appendix F: Evidentiary Tables Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Diagnosis/Imaging What history and physical examination findings best support a diagnosis of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Bertilson BC, Grunnesjo M, Strender LE. Reliability of clinical tests in the assessment of patients with neck/shoulder problems-impact of history. Spine (Phila Pa 1976). Oct ;28(19): Level of evidence Description of study Conclusion Level II Type of evidence: diagnostic Prospective Retrospective Study design: case series Stated objective of study: To analyze the reliability of clinical tests in the assessment of neck and arm pain in primary care patients. Number of patients: 100 patients Physical examination/diagnostic test description: 66 clinical tests divided into nine categories Results/subgroup analysis (relevant to question): Reliability of clinical tests was poor to fair. Only a bimanual sensitivity test reached good values. With known clinical history, the prevalence of positive findings increased in all test categories. Sensitivity tests remained diagnostically useful. Usually helpful tests were not as diagnostically predictable, but also had increased positive findings when history was prerecorded before an exam was performed, as opposed to exam first before history was obtained. Shoulder abduction test k w/o - with history , Spurling's , traction relieves.63-.8, Author conclusions (relative to question): Sensitivity tests were the most reliable and were exempt from bias. History had no impact on reliability, however, it had an impact on the incidence of positive findings. Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: only two reviewers Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that:history and physical findings are not definitive, and may be susceptable to bias with a suggestive clinical history. Chang H, Park JB, Hwang JY, Song KJ. Clinical analysis of cervical radiculopathy Level IV Type of evidence: prognostic Prospective Retrospective Study design: case series Stated objective of study: To investigate the characteristics of cervical radiculopathy causing Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used:

107 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 87 causing deltoid paralysis. Eur Spine J. Oct 2003;12(5): Davidson RI, Dunn EJ, Metzmaker JN. The shoulder abduction test in the diagnosis of radicular pain in cervical extradural compressive monoradiculopat hies. Spine (Phila Pa 1976). Sep-Oct 1981;6(5): Level III Type of evidence: diagnostic deltoid paralysis, and to report on the surgical outcomes of anterior cervical decompression with fusion (ACDF) for the treatment of deltoid paralysis. Number of patients: 14 Physical examination/diagnostic test description: All patients had radiating pain to scapula, shoulder or arm, with weakness of shoulder abduction due to paralysis of deltoid (graded 0-5). Severity of radiculopathy graded on VAS Plain radiographs and MRI were correlated with clinical findings. Surgery performed on patients with single level cervical disc herniation (CDH) or cervical spondylotic radiculopathy (CSR). Patients with multilevel disease were excluded. Results/subgroup analysis (relevant to question): Paralysis of the deltoid with ipsilateral scapular, shoulder or arm pain may be the result of a single level CDH or CSR. Following are the single levels implicated and their respective frequencies: 1-C3-4 CDH (central), 4-C4-5 CDH, 1-C5-6 CDH, 3-C4-5 CSR, 5-C5-6 CSR. Both radiculopathy and deltoid paralysis improved significantly with surgery. Author conclusions (relative to question): A painful cervical radiculopathy with deltoid paralysis emanates from the C4-5, C5-6 and C3-4 levels: 50%, 43% and 7% of the time respectively. Prospective Retrospective Study design: case series Stated objective of study: To report observations on a series of patients with cervical monoradiculopathy due to compressive disease in whom clinical signs included relief of pain with abduction of the shoulder. Number of patients: 22 Physical examination/diagnostic test description: Twenty-two patients with arm pain had cervical extradural myelographic defects. 15/22 patients had relief from their pain with shoulder abduction (SAR). The 15 patients in the SAR group all had extradural defects consistent with their clinical findings. Motor weakness was present in 15, Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:a painful cervical radiculopathy with deltoid paralysis arose from compressive disease at the C4-5, C5-6 and C3-4 levels: 50%, 43% and 7% of the time respectively. Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question: This paper provides evidence that:relief from arm pain with

108 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 88 paresthesias in 11 and reflex changes in 9 patients. Results/subgroup analysis (relevant to question): Of the 15 patients with a positive shoulder abduction sign, 13 required surgery and all achieved good results. Two of the 15 had pain relief with conservative therapy. Of the seven patients with negative shoulder abduction signs, five required surgery and two were successfully treated with traction. Of the five surgical patients, three had surgery for a central lesion and improved after surgery, two had surgery for a lateral disc fragment and only one had good results. shoulder abduction is an indicator of cervical extradural compressive radiculopathy. Henderson CM, Hennessy RG, Shuey HM, Jr., Shackelford EG. Posterior-lateral foraminotomy as an exclusive operative technique for cervical radiculopathy: a review of 846 consecutively operated cases. Neurosurgery. Nov 1983;13(5): Level II Type of evidence: prognostic Author conclusions (relative to question): The shoulder abduction test is a reliable indicator of significant cervical extradural compressive radicular disease. Prospective Retrospective Study design: observational Stated objective of study: Report the results of posterior foraminotomy in the treatment of cervical radiculopathy. Number of patients: 736 patients underwent one or more posterior-lateral foraminotomies for simple cervical radiculopathy. Physical examination/diagnostic test description: The following symptoms were present: arm pain 99.4%, neck pain 79.7%, scapular pain 52.5%, anterior chest pain 17.8%, and headache 9.7%. Eleven patients presented with only left chest and arm pain ("cervical angina"). 53.9% of patients had pain or paresthesia in a dermatomal pattern. In 45.5%, the pain or paresthesia was diffuse or nondermatomal. No pain or parasthesia was reported by 0.6% of patients. 85.2% of patients reported a sensory change to pinprick, 68% had a specific motor deficit, and 71.2% had a specific decrease in a deep tendon reflex (DTR). Results/subgroup analysis (relevant to question): One level was thought to be primary 87.3% of the time and two levels were felt to be equally involved 12.7% of the time. The correlation between pain/paresthesia, motor deficit, DTR change, and Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Work group conclusions: Potential level: II Downgraded level: II Conclusions relative to question: This paper provides evidence that: 71.5% of the time, the operative site can be accurately predicted on the basis of clinical findings.

109 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 89 the primary operative space was 73.8%, 84.8% and 83.5%, respectively. There was a 71.5% incidence of correlation between preoperative clinical findings and operative findings. Good or excellent results were reported by 91.5% of patients. Good or excellent relief of arm pain was found in 95.5% of patients, neck pain in 88.8%, scapular pain in 95.9%, chest pain in 95.4% and headache in 89.8%. Resolution of DTRs were reported by 96.9%. Residual sensory deficit was found in 20.9% of patients, and motor deficit in 2.3%. Author conclusions (relative to question): In a large group of patients with cervical radiculopathy, the study elucidates the common clinical findings of pain, paresthesia, motor deficit, and decreased deep tendon reflexes, along with their respective frequencies. It presents evidence that the operative site can be accurately predicted on the basis of clinical findings 71.5% of the time. Jenis LG, An HS. Neck pain secondary to radiculopathy of the fourth cervical root: an analysis of 12 surgically treated patients. J Spinal Disord. Aug 2000;13(4): Level IV Type of evidence: prognostic Prospective Retrospective Study design: case series Stated objective of study: To report the results of surgical intervention in a series of patients with neck pain from C4 radiculopathy. Number of patients: 12 (11 with cervical radiculopathy without myelopathy) Physical examination/diagnostic test description: Pain localized to the posterior aspect of the neck, lateralized to the side with more involvement of the C4 root. Pain also reported in trapezial areas and upper extremities depending on the presence of more caudal radiculopathies. Neck pain was exacerbated by flexion and extension in all patients. Decreased sensation in the C4 dermatome was uniformily present. MRI in all patients and CT scan in three patients were performed prior to surgery. Excluding the myelopathic patient, four patients were treated with ACDF and seven patients were treated with PLF including 3/7 PSF. Evaluation of surgical results was determined by status of fusion, pain relief and level of activity based on Odom's criteria. Follow-up data was obtain at months. Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:neck pain with or without upper extremity clinical findings should include evaluation for a C4 radiculopathy. The examination should include C4 sensory testing.

110 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 90 Results/subgroup analysis (relevant to question): Excluding the myelopathic patient, excellent, good and satisfactory relief was obtained in five, five and one patient, respectively. The three patients with isolated C4 radiculopathy had excellent results. Author conclusions (relative to question): Neck pain with or without upper extremity clinical findings should include evaluation for a C4 radiculopathy. The examination should include C4 sensory testing. Makin GJ, Brown WF, Ebers GC. C7 radiculopathy: importance of scapular winging in clinical diagnosis. J Neurol Neurosurg Psychiatry. Jun 1986;49(6): Level IV Type of evidence: prognostic Prospective Retrospective Study design: case series Stated objective of study: Report on six cases with scapular winging as a finding in some patients with C7 radiculopathy Number of patients: 6 Physical examination/diagnostic test description: Scapular winging was detected with the hands at shoulder level. In the remainder scapular winging was only evident when pushing against the wall with the hands at waist level. This latter method places the serratus anterior muscle at a mechanical disadvantage and reveals partial paralysis. Results/subgroup analysis (relevant to question): Each case confirmed by surgery or by CTM Author conclusions (relative to question): Scapular winging may be a component of C7 radiculopathy and when present serves to exclude lesions of the brachial plexus or radial nerve. Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that: scapular winging may be a feature of C7 radiculopathy in some patients and should not be misleading when present. Ozgur BM, Marshall LF. Atypical presentation of C-7 radiculopathy. J Neurosurg. Sep 2003;99(2 Suppl): Level IV Type of evidence: prognostic Prospective Retrospective Study design: case series Stated objective of study: review 241 consecutive C6-7 discectomy patients for "presenting symptomatology" Number of patients: 241 Physical examination/diagnostic test description: clinical evaluation of presenting signs and Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other:

111 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 91 symptoms for usual and unusual findings Results/subgroup analysis (relevant to question): Most patients had usual C7 traditional radicular signs (dermatomal distribution), with 12% reporting sole complaint of subscapular pain, 5% having deep breast or chest pain. None of these 17% had the "typical" C7 presenting symptoms. Author conclusions (relative to question): Patients presenting with unusual symptoms had their complaints validated by surgical findings and 93% experienced symptom relief Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:a significant percentage of patients may present with atypical symptoms, in addition to or without standard symptoms (eg, scapular pain only). These patients responded well to surgical treatment. Persson LCG, Carlsson JY, Anderberg L. Headache in patients with cervical radiculopathy: A prospective study with selective nerve root blocks in 275 patients. European Spine Journal. Jul 2007;16(7): Level III Type of evidence: prognostic Prospective Retrospective Study design: observational Stated objective of study: To describe the frequency of headaches in patients with lower level cervical radiculopathy and its response to a selective nerve root block (SNRB). Number of patients: Of 275 total patients, 161 complained of headaches in addition to other symptoms. These are the ones studied. Physical examination/diagnostic test description: Of 275 patients, 161 suffered from daily or recurrent headaches, most often ipsilateral to the patients' radiculopathy. All patients underwent clinical exam and MRI. Patients with significantly compressed nerve root underwent SNRB. Effect on headache was evaluated with VAS. Results/subgroup analysis (relevant to question): All patients with headaches had tender points in the neck/shoulder region ipsilateral to the radiculopathy. Patients with headache had significantly more limitations in daily activites and higher pain in the neck/shoulder. Immediately before the injections, 161 (59%) of patients experienced a headache exceeding 15 on the VAS. Of the 161 patients, 101 (63%) experienced >25% headache reduction following SNRB, 93 (58%) reported greater than 50% headache reduction, 66 experienced 100% relief. (C4 3%, C5 11%, C6 52%, C7 29%, C8 5%) A significant correlation was found between reduced headache and decreased pain in the neck and shoulder region. Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: 50% threshold and lack of specificity of the injection Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that:complaint of headache is also a common symptom with C4 and lower nerve compression problems. SNRB can reduce headaches in a significant percentage of patients, and this was considered significant as a diagnostic tool.

112 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 92 Author conclusions (relative to question): Cervical nerve root compression from degenerative disease in the lower cervical spine producing radiculopathy can also result in headache. The neck pain seems to restrict the patient's activity. Headache classification and assessment together with muscle palpation should be part of the neck exam for patients with cervical radiculopathy. Post NH, Cooper PR, Frempong- Boadu AK, Costa ME. Unique features of herniated discs at the cervicothoracic junction: Clinical presentation, imaging, operative management, and outcome after anterior decompressive operation in 10 patients. Neurosurgery. Mar 2006;58(3): Level IV Type of evidence: prognostic Prospective Retrospective Study design: case series Stated objective of study: Review their experience with the operative management of a series of patients with C7-T1 herniations. Number of patients: 10 Physical examination/diagnostic test description: Symptoms included shoulder pain radiating into the lateral aspect of the hand, hand weakness and weakness in finger flexion, finger extension, and intrinsic hand muscles. Sensation and DTRs were unremarkable. Results/subgroup analysis (relevant to question): MRI on each patient revealed a soft disc compressing the C8 nerve. Recovery of hand strength was noted in each patient, however, recovery was incomplete in two patients with symptoms greater than four months. Author conclusions (relative to question): None stated Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:c8 radiculopathy usually presents as weakness of the hand, and pain radiating to shoulder, scapular area, and to the fourth and fifth fingers. Physical exam may reveal normal sensory and DTR's. Motor examination may show weakness of flexors and extensors of the fingers and also weakness of intrinsic muscles of the hand. Shah KC, Rajshekhar V. Reliability of diagnosis of soft cervical disc prolapse using Spurling's test. Br J Neurosurg. Oct 2004;18(5): Level II Type of evidence: diagnostic Prospective Retrospective Study design: observational Stated objective of study: To determine the sensitivity and specificity of the Spurling's test in predicting the diagnosis of a soft lateral cervical disc herniation in patients with neck and arm pain. Number of patients: 50 Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other:

113 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 93 Physical examination/diagnostic test description: Spurling's test with cervical extension, lateral flexion to the side of pain, and downward pressure on the head was performed on all patients. Twenty-five patients underwent surgery (Group 1) and 25 were managed conservatively (Group 2). Spurling's test correlated with surgical findings in Group 1, and with MRI findings in Group 2. Patients with minimal or no neurologic deficits with the first episode of radicular pain and those who refused surgery were managed conservatively. Results/subgroup analysis (relevant to question): Group 1 (25 patients): 18/18 with a positive Spurling's test had a soft disc herniation. Of seven patients with a negative Spurling's test, two had a soft disc herniation and five had a hard disc. Group 2 (25 patients): Of the 10 patients with a positive Spurling's test, nine had a soft disc herniation, one had a hard disc. Of the 15 patients with a negative Spurling's test, a hard disc was seen in eight, and MRI was normal in seven. The Spurling's test had a sensitivity of 92%, a specificity of 95%, a positive predictive value (PPV) of 96.4% and a negative predictive value (NPP) of 90.9% for a soft disc herniation. Work group conclusions: Potential level: II Downgraded level: II Conclusions relative to question: This paper provides evidence that:a positive Spurling's test can increase the incidence of compressive disease in patients undergoing evaluation for cervical radiculopathy. Author conclusions (relative to question): The high PPV indicates that the Spurling's test can be used to increase the incidence of disease in patients undergoing MRI for cervical radiculopathy. Slipman CW, Plastaras CT, Palmitier RA, Huston CW, Sterenfeld EB. Symptom provocation of fluoroscopically guided cervical nerve root stimulation. Are dynatomal maps identical to dermatomal maps? Spine (Phila Pa 1976). Oct ;23(20): Level I Type of evidence: prognostic Prospective Retrospective Study design: observational Stated objective of study: To study the distribution of pain and parasthesias that result from the stimulation of specific cervical nerve roots. Number of patients: 87 patients, 134 selective nerve root stimulations Physical examination/diagnostic test description: Mechanical stimulation of nerve roots were carried out: 4 at C4, 14 at C5; 43 at C6; 52 at C7; and 21 at C8. An independent observer recorded the location of provoked symptoms on a pain diagram. Visual data was compiled using a 793 body sector bit map with 43 body regions identified. Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Work group conclusions: Potential level: I Downgraded level: I Conclusions relative to question: This paper provides evidence that:distribution of pain and

114 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 94 Tanaka Y, Kokubun S, Sato T, Ozawa H. Cervical roots as origin of pain in the neck or scapular regions. Spine. Aug ;31(17):E Level I Type of evidence: prognostic Results/subgroup analysis (relevant to question): Although the distribution of symptom provocation resembled the classic dermatomal maps, symptoms were frequently provoked outside the classic descriptions. Author conclusions (relative to question): There was a distinct difference between the dynatomal and dermatomal maps. Prospective Retrospective Study design: observational Stated objective of study: To determine if pain in the neck or scapular regions in patients with cervical radiculopathy originates from the compressed nerve root and whether the site of pain is useful for identifying the level involved. Number of patients: 50 consecutive Physical examination/diagnostic test description: Patients who experienced pain with arm and finger symptoms underwent single level decompression. The level was determined based on correlation of symptoms and imaging, and SNRB in five patients. Cervical disc herniation was found in 20 patients and stenosis in 30. Patients underwent posterior open foraminotomy with follow-up at one month and one year after surgery. Results/subgroup analysis (relevant to question): Pain preceeded the arm/finger symptoms in 35 patients (70%) and was relieved early in 46 (92%). When the pain was suprascapular, C5 or C6 radiculopathy was frequent. When it was interscapular, C7 or C8 radiculopathy was frequent. When scapular, C8 was frequent. Arm and finger symptoms improved significantly in all groups after decompression. Sixty-one painful sites were noted before surgery: one in 39 patients, and two in 11 patients. Following surgery, 27 patients reported complete pain relief, 23 had pain in 24 regions and seven reported no change with surgery. Seventeen pain sites were new since surgery. All but one new site were nuchal and suprascapular. At one year follow-up, 45 patients reported no pain, five patients had pain in six sites, three of which were the same as before surgery. C5 pain localized to the nuchal, scapula, and paresthesias in the arm from nerve root stimulation can be different than dermatomal maps in a significant percentage of patients, making it difficult to identify the level based on pain distribution. In some patients it explains the nondermatomal distribution of pain. Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Work group conclusions: Potential level: I Downgraded level: I Conclusions relative to question: This paper provides evidence that:cervical radiculopathy at C5, C6, C7 and C8 frequently causes pain in suprascapular, interscapular and scapular areas and is useful in determining the level of nerve root involvement. Pain in the suprascapular region indicates C5 or C6 radiculopathy, the pain in the interscapular region indicates C7 or C8 radiculopathy, and pain in the scapular region indicates C8 radiculopathy.

115 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 95 suprascapular areas; C6, suprascapular pain was significant; C7, interscapular pain was frequent; and C8, interscapular pain and scapular pain was frequent. Author conclusions (relative to question): Pain in the suprascapular, interscapular or scapular regions can orginate directly in the compressed root and is valuable for determing the nerve root involved. Tong HC, Haig AJ, Yamakawa K. The Spurling test and cervical radiculopathy. Spine (Phila Pa 1976). Jan ;27(2): Level IV Type of evidence: diagnostic Prospective Retrospective Study design: comparative Stated objective of study: To determine the sensitivity and specificity of the Spurling test for cervical radiculopathy. Number of patients: 255 patients were referred for electrodiagnosis of upper extremity nerve disorders. Physical examination/diagnostic test description: The Spurling test was performed on all patients before EMG. The test was scored as positive if it resulted in pain or tingling starting in the shoulder and radiating distal to the elbow. A differential diagnosis based on the history and physical exam was made prior to EMG. EMG was performed and each diagnosis in the differential was scored relative to the likelihood of its occurrence. Results/subgroup analysis (relevant to question): Of the 255 patients presented, 31 had missing data, leaving 224 patients for inclusion. Of 20 patients with a positive EMG for cervical radiculopathy, the Spurling's test was positive in seven, for a sensitivity of 7/20 or 30%. Of 172 patients with no EMG evidence for radiculopathy, the Spurling's test was negative in 160, for a specificity of 160/172 or 93%. The Spurling's test was positive in 16.6% of patients with a normal EMG, in 3.4% of patients with an EMG diagnosis of a nerve problem other than radiculopathy, and in 15% of patients with nonspecific EMG findings. The odds ratio of a positive Spurling's test for a positive EMG for cervical radiculopathy is Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: poor reference standard. Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:the Spurling's test is not sensitive, but is specific for cervical radiculopathy as diagnosed by EMG. A positive test increases the incidence of radiculopathy in patients undergoing EMG for upper extremity nerve disorders. Author conclusions (relative to question): Spurling's test is not sensitive, but is specific for

116 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 96 cervical radiculopathy as diagnosed by EMG. Not useful as a screening test, but may be useful to confirm the diagnosis. Wainner RS, Fritz JM, Irrgang JJ, Boninger ML, Delitto A, Allison S. Reliability and diagnostic accuracy of the clinical examination and patient selfreport measures for cervical radiculopathy. Spine (Phila Pa 1976). Jan ;28(1): Level IV Type of evidence: diagnostic Prospective Retrospective Study design: comparative Stated objective of study: To assess the reliability and accuracy of individual clinical exam items and self reported instruments for the diagnosis of cervical radiculopathy, and to identify and assess the accuracy of an optimal cluster of test items. Number of patients: 82 Physical examination/diagnostic test description: Consecutive patients referred for EMG for the evaluation of cervical radiculopathy (CR) or carpal tunnel syndrome (CTS). Only patients judged by the laboratory provider (seven different providers) to have signs and symptoms compatible with CR or CTS were eligible to participate. Patients with Class 5 or 6 cervical radiculopathy findings were further classified according to the severity of their EMG findings. Self-reported items included the VAS and NDI. Standardized clinical exam was performed by two of nine physical therapists and contained 34 items. History contained six questions asked by two physical therapists. Neurological exam included strength, DTRs and sensation. Provocative tests included Spurling's test, shoulder abduction test, Valsalva maneuver, neck distraction test and the upper limb tension test. Cervical range of motion measured. Results/subgroup analysis (relevant to question): Fifteen patients had an EMG diagnosis of cervical radiculopathy (CR), five patients with CR and concomitant ulnar neuropathy and CTS. One patient with combined findings dropped out of the study. Of the 19 patients reported, 13 had mild symptoms and six had moderate symptoms. Reliability of different clinical items were reported including the Spurlings A/B.6/.62, shoulder abduction.2, valsalva.69, distraction.88, Upper Limb Tension Test (ULTT) A/B.76/.83. Sensitivity/specificity: Spurlings A/B.6/.62, shoulder abduction.2, valsalva.69, distraction.88, ULTT A/B.76/ patients with CR (13 mild, 6 moderate). Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: EMG gold standard, also test selection bias. Work group conclusions: Potential level: III Downgraded level: IV Conclusions relative to question: This paper provides evidence that:provocative tests, including the Spurling's test, shoulder abduction test, Valsalva and distraction test had a low sensitivity and high specificity for cervical radiculopathy as diagnosed by EMG.

117 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 97 Sensitivity/Specificity: Spurling's A/B - 0.5/ ; shoulder abduction /0.92; valsalva -.22/.94; distraction /0.9; ULTT A/B / Cluster of ULTTA, cervical rotation <60degrees, distraction, and Spurling's A /0.99 Author conclusions (relative to question): Many items were found to have at least a fair level of reliability, and to have acceptable diagnostic properties. The test item cluster identified was found to be the most useful. Yoss RE, Corbin KB, Maccarty CS, Love JG. Significance of symptoms and signs in localization of involved root in cervical disk protrusion. Neurology. Oct 1957;7(10): Level II Type of evidence: prognostic Prospective Retrospective Study design: observational Stated objective of study: To correlate clinical findings with operative findings when a single cervical nerve root (C5,C6,C7,C8) is compressed by a CDH. Number of patients: 100 Physical examination/diagnostic test description: Symptoms included pain in the neck, shoulder, scapular or interscapular region, arm, forearm or hand; paresthesias in forearm, and hand; and weakness of upper extremity. Signs included diminution of triceps, biceps and brachioradialis reflexes, muscle weakness and sensory loss. Surgically verified nerve root compression, sufficient information to support the surgeons preoperative impression, relief of symptoms following surgery. Results/subgroup analysis (relevant to question): The presence of pain or paresthesia in the neck, shoulder, scapular or interscapular region was present in cases of C5, C6, C7, C8 compression. The presence of pain in the arm corresponded to the site compression in 23% of cases. The presence of pain or paresthesia in the forearm corresponded to a single root or one of two roots in 32% and 66%, respectively. Hand pain and paresthesia corresponded to a single root or one of two roots in 70% and 27%, respectively. Subjective weakness corresponded to a single level in 22/34 (79%) cases. When a diminution of DTR was present, the lesion could be correctly localized to a single level or one Critique of methodology: Patients not enrolled at same point in their disease <80% follow-up No Validated outcome measures used: Tests not uniformly applied across patients Small sample size Lacked subgroup analysis Other: Marked testing bias Work group conclusions: Potential level: II Downgraded level: II Conclusions relative to question: This paper provides evidence that:clinical findings related to the fingers are the most accurate for localizing a CDH to a single level. Single level CDH may produce signs and symptoms that correspond to overlapping dermatomal levels.

118 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 98 of two levels in 11% and 82%, respectively. Objective muscle weakness corresponded to a single root or one of two roots in 77% and 12%, respectively. All cases of objective weakness in which root C5 or C8 was involved, the level was correctly localized. Sensory loss corresponded to a single root or one of two roots in 65% and 35%, respectively. Author conclusions (relative to question): Clinical findings related to the fingers are the most accurate for localizing a CDH to a single level. A single level CDH may produce signs and symptoms that correspond to overlapping dermatomal levels.

119 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 99 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Diagnosis/Imaging What are the most appropriate diagnostic tests (including imaging and electrodiagnostics), and when are these tests indicated in the evaluation and treatment of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Level of evidence Description of study Conclusion Alrawi MF, Khalil NM, Mitchell P, Hughes SP. The value of neurophysiologi cal and imaging studies in predicting outcome in the surgical treatment of cervical radiculopathy. Eur Spine J. Apr 2007;16(4): Level III Type of evidence: diagnostic Prospective Retrospective Study design: case series Stated objective of study: Investigate whether preoperative electromyography (EMG) can help select those most likely to benefit from intervention. Diagnostic test(s) studied: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Compared to: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Gold standard? Yes No If Yes, please specify: surgical outcome Number of patients: 20 Critique of methodology: Nonconsecutive patients Small sample size No consistently applied gold standard Poor reference standard/no gold standard applied Lacked subgroup analysis Other: Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question: This paper provides evidence that:patients with cervical radiculopathy and an MRI showing a disc bulge with narrowing of the exit foramina have better clinical outcomes and patient satisfaction from their anterior cervical decompression with fusion (ACDF) if a preoperative EMG shows denervation changes. Consecutively assigned? No Results/subgroup analysis (relevant to question): Study of 20 patients with clinical manifestations of cervical

120 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 100 radiculopathy and an magnetic resonance imaging (MRI) showing disc bulges associated with narrowing of the exit foramina. The operative level was unclear in all patients. Preoperatively patients were divided into groups A and B on the basis of an EMG. Group A had eight patients with denervation changes in the distribution of a least one cervical nerve root. Group B had 12 patients with no EMG evidence of cervical radiculopathy. Patients in group A had better clinical outcomes and patient satisfaction from their ACDF at least 12 months postoperatively than patients in group B. Author conclusions (relative to question): Preoperative neurophysiological studies (NPS) can help identify which patients are likely to benefit from surgery for cervical radiculopathy. Anderberg L, Annertz M, Rydholm U, Brandt L, Saveland H. Selective diagnostic nerve root block for the evaluation of radicular pain in the multilevel degenerated cervical spine. Eur Spine J. Jun 2006;15(6): Level III Type of evidence: diagnostic Prospective Retrospective Study design: case series Stated objective of study: Assess the ability of transforaminal selective nerve root blocks (SNRB) to correlate clinical symptoms with MRI findings in patients with cervical radiculopathy and two level MRI degeneration ipsilateral to the radicular pain. Diagnostic test(s) studied: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: SNRB Compared to: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Critique of methodology: Nonconsecutive patients Small sample size No consistently applied gold standard Poor reference standard/no gold standard applied Lacked subgroup analysis Other: surgical treatment or transforminal epidural steroid injection (ESI) treatment performed in only 22/30 Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question: This paper provides evidence that:snrb may be useful in the preoperative evaluation of patients with radiculopathy and findings of compressive lesion at multiple levels on MRI.

121 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 101 Other: Gold standard? Yes No If Yes, please specify: surgical outcomes Number of patients: 30 Consecutively assigned? Yes Results/subgroup analysis (relevant to question): Of 30 patients, 22 had neurologic deficits that occurred with cervical radiculopathy. Degenerative changes on MRI were found in close relation to nerve roots. Neuroforaminal narrowing was graded as slight, moderate or severe, without further analysis. Clinical findings were correlated with MRI findings and root block levels were determined. No analgesics were administered within 12 hours prior to the procedure, and there was no mention if sedation was given prior to the procedure. An unspecified volume of contrast was administered to confirm perineural needle position within the foramen prior to SNRB. SNRB with 0.5 ml solution of 5 mg of Mepivacaine was administered. VAS outcomes were assessed 30 minutes and four hours after SNRB. VAS reduction of at least 50% was required to determine that the SNRB was positive; no indication if VAS score occurred 30 minutes or 4 hours after the SNRB. In 18 patients with positive SNRB at a single level, the SNRB correlated with the level of more marked pathology in 12, to the level determined by the neurologic deficits in eight, and to the level corresponding to the sensory dermatone in seven. In 11 patients with positive SNRB at two levels, these levels corresponded to findings on MRI in 6. Of 13 patients treated at one level, 9 (67%) had good or excellent results. Of nine patients treated at two levels, 100% had good or excellent results. Author conclusions (relative to question): Clinical symptoms and signs in isolation or in combination with MRI findings are

122 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 102 not always reliable indicators of the pain generating nerve root. SNRB may be useful in treatment planning in patients with radiculopathy and degenerative changes at two levels ipsilateral to the patient's symptoms Anderberg L, Saveland H, Annertz M. Distribution patterns of transforaminal injections in the cervical spine evaluated by multi-slice computed tomography. European Spine Journal. Oct 2006;15(10): Level II Type of evidence: diagnostic Prospective Retrospective Study design: case series Stated objective of study: Study the selectivity of cervical transforaminal injections and the distributions of a range of injection volumes in patients with cervical radiculopathy. Diagnostic test(s) studied: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: SNRB Compared to: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Critique of methodology: Nonconsecutive patients Small sample size No consistently applied gold standard Poor reference standard/no gold standard applied Lacked subgroup analysis Other: Work group conclusions: Potential level: II Downgraded level: II Conclusions relative to question: This paper provides evidence that:transforaminal injectate volumes of 0.6 ml consistently meet the criteria for SNRB. Gold standard? Yes No If Yes, please specify: CT Number of patients: 9 Consecutively assigned? Yes Results/subgroup analysis (relevant to question): Three groups of three patients received either 0.6, 1.1 and 1.7 ml of injectate via the transforaminal root technique used by Kikuchi. The groups injected with 0.6 and 1.1 ml received local anesthetic and contrast. The group injected with 1.7 ml received local anesthetic, corticosteroid and contrast.

123 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 103 Contrast distribution was determined by a postinjection CT scan. An injection was considered a SNRB if the contrast media surrounded an adjacent nerve root by less than half of its circumference. In all three patients receiving 0.6 ml of injectate, the injections were considered SNRB. In 1/3 of patients the contrast was noted in an intraspinal/epidural distribution. In 2/3 of patients given 1.1 ml of injectate the injections were considered SNRB. In both of these SNRB injections, there was spread of contrast around less than onehalf the circumference of adjacent nerve roots. None of the three patients receiving 1.7 ml of injectate had a SNRB. The perineural distribution length averaged 36 mm, with no correlation to injectate volume. Author conclusions (relative to question): Only 0.6 ml injections should be accepted as SNRB. Ashkan K, Johnston P, Moore AJ. A comparison of magnetic resonance imaging and neurophysiologi cal studies in the assessment of cervical radiculopathy. Br J Neurosurg. Apr 2002;16(2): Level III Type of evidence: diagnostic Prospective Retrospective Study design: comparative Stated objective of study: To assess whether neurophysiologic studies (NPS) added significant information to high resolution MRI in the evaluation of cervical radiculopathy. Diagnostic test(s) studied: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: nerve conduction studies Compared to: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Critique of methodology: Nonconsecutive patients Small sample size No consistently applied gold standard Poor reference standard/no gold standard applied Lacked subgroup analysis Other: Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question: This paper provides evidence that:mri is mlore accurate and more sensitive than NPS in the preoperative evaluation of patients with cervical radiculopathy.

124 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 104 Gold standard? Yes No If Yes, please specify: surgical outcomes Number of patients: 45 Consecutively assigned? No Bartlett RJV, Hill CR, Gardiner E. A comparison of T₂ and gadolinium enhanced MRI with CT Level II Type of evidence: diagnostic Results/subgroup analysis (relevant to question): Of the 45 patients, three experienced bilateral symptoms. Radicular arm pain was present in all cases, parasthesias in 28, numbness in 22 and subjective weakness in 14. Following surgery, 36 patients had complete resolution of symptoms and seven experienced significant improvement in symptoms. Of patients who improved following surgery, 16 (37%) had a positive MRI and NPS; 24 (56%) had a positive MRI and negative NPS; two (5%) had a negative MRI and positive NPS; and one (2%) had negative MRI and NPS studies. In the three cases with a negative MRI, surgical plans were based on the NPS in one case and on CTM in two. In five patients with foraminal stenosis on MRI the patients did not improve. Of these five patients, four were operated on at the level indicated by MRI. Sensitivity for diagnosing cervical radiculopathy was 93% for MRI and 42% for NPS; with positive predictive values at 91% for MRI and 86% for NPS. Negative predictive values were 25% for MRI, and 7% for NPS. Author conclusions (relative to question): In patients with clinical and MRI evidence of cervical radiculopathy, NPS has limited additional diagnostic value. Prospective Retrospective Study design: comparative Stated objective of study: To compare the accuracy of gadolinium (Gd) enhanced MRI with 3D gradient recalled echo (3D GRE) images in the evaluation of cervical Critique of methodology: Nonconsecutive patients Small sample size No consistently applied gold standard Poor reference standard/no gold standard applied Lacked subgroup analysis

125 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 105 myelography in cervical radiculopathy. British Journal of Radiology. Jan 1998;71(JAN.): radiculopathy. Diagnostic test(s) studied: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Compared to: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Gold standard? Yes No If Yes, please specify: best diagnosis reviewing all the studies Number of patients: 20 Other: Work group conclusions: Potential level: II Downgraded level: II Conclusions relative to question: This paper provides evidence that:mri with 3D T2 technique has an accuracy approaching that of CT myelography for the diagnosis of a compressive lesion in patients with cervical radiculopathy. Consecutively assigned? Yes Results/subgroup analysis (relevant to question): 3D GRE images had an accuracy of 87% for the diagnosis of foraminal encroachment. CTM had an accuracy of 90%. MRI with Gd conferred no additional benefit. Oblique reconstructions were less accurate than axial images. Author conclusions (relative to question): MRI with 3D GRE images is an acceptable technique for the primary evaluation of cervical radiculopathy. CTM remains indicated for patients with incongruent symptoms and MRI results. Hedberg MC, Drayer BP, Flom RA, Hodak JA, Bird CR. Gradient echo (GRASS) MR imaging in Level III Type of evidence: diagnostic Prospective Retrospective Study design: comparative Stated objective of study: To determine the accuracy of MRI with limited flip angle (LFA) GRE technique in patients with Critique of methodology: Nonconsecutive patients Small sample size No consistently applied gold standard Poor reference standard/no gold standard applied

126 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 106 cervical radiculopathy. AJR Am J Roentgenol. Mar 1988;150(3): cervical radiculopathy. Diagnostic test(s) studied: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Compared to: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Gold standard? Yes No If Yes, please specify: surgical findings Number of patients: 13/130 Lacked subgroup analysis Other: older technique Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question: This paper provides evidence that:mri is accurate in the diagnosis of disc herniation and degenerative abnormalities in the spine. Consecutively assigned? Yes Results/subgroup analysis (relevant to question): MRI was performed in 130 patients, myelography in 30, CTM in 16 and CT in five. Pathologic confirmation was obtained in 13 surgically treated patients. Of the studies, 31 were normal and neither myelography nor surgery were performed. Extradural defects were detected in 99/130 patients (52 central, 26 dorsolateral osteophyte, 4 dorsolateral disc, 17 dorsolateral disc/osteophyte). Myelography/CTM and nonenhanced CT confirmed the abnormalities in 20 and five patients, respectively. Surgical findings from 13 patients and 30 sites showed correlation with MRI on 3/3 herniations and 26/27 degenerative abnormalities. Author conclusions (relative to question): MRI is sufficient for the evaluation of cervical radiculopathy and may obviate the need for more invasive myelography and CT.

127 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 107 Houser OW, Onofrio BM, Miller GM, Folger WN, Smith PL. Cervical Disk Prolapse. Mayo Clinic Proceedings. Oct 1995;70(10): Level III Type of evidence: diagnostic Prospective Retrospective Study design: case series Stated objective of study: To correlate the findings on CTM with surgical and path proven cervical herniations. Diagnostic test(s) studied: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Compared to: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Gold standard? Yes No If Yes, please specify: surgical findings/pathology Number of patients: 297 Critique of methodology: Nonconsecutive patients Small sample size No consistently applied gold standard Poor reference standard/no gold standard applied Lacked subgroup analysis Other: Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question: This paper provides evidence that:ct myelography can identify 90% of cervical extruded disc herniations confirmed by surgery. Consecutively assigned? No Results/subgroup analysis (relevant to question): Over three years, 734 patients underwent CTM for cervical disc disease. CTM findings identified cervical disc hernations (CDH) in 297 patients. Of the 297 patients, 280 were diagnosed with radiculopathy and 17 with myelopathy. At surgery, cervical disc hernations (CDH) were noted in 297 patients. In the 297 patients, surgical reports noted one or more prolapsed discs in 258, a prolapsed disk and spur in 38, and a prolapsed disk with a fractue in 1. CTM corresponded to surgical findings in than 260/280 patients with radiculopathy and in 17/17 patients with myelopathy. Surgery was performed in 22 patients on the basis of clinical

128 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 108 symptoms alone. Of these 22 patients, 19 had herniations not seen on CTM and three had no herniations based upon surgical findings and CTM. A soft tissue extradural deformity appeared to be present on CTM in seven patients who had no cervical abnormalities on surgical exploration. The authors concluded that imaging of cervical disc prolapse continues to be difficult and the results are not always specific. CTM is the most sensitive imaging examination. In critique, patients were not consecutively assigned. This study provides Level III evidence that CT myelography can identify 90% of cervical extruded disc herniations confirmed by surgery. Author conclusions (relative to question): Imaging of cervical disc prolapse continues to be difficult and the results are not always specific. CTM is the most sensitive imaging examination, but the number of MRI studies were insufficient to allow a direct comparison Houser OW, Onofrio BM, Miller GM, Folger WN, Smith PL, Kallman DA. Cervical Neural Foraminal Canal Stenosis - Computerized Tomographic Myelography Diagnosis. Journal of Neurosurgery. Jul 1993;79(1): Level III Type of evidence: diagnostic Prospective Retrospective Study design: case series Stated objective of study: To review the surgical and CTM findings in patients with foraminal stenosis. Diagnostic test(s) studied: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Compared to: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: surgical findings Critique of methodology: Nonconsecutive patients Small sample size No consistently applied gold standard Poor reference standard/no gold standard applied Lacked subgroup analysis Other: Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question: This paper provides evidence that:during surgical exploration, there was limited correlation between CT myelography and foraminal stenosis.

129 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 109 Gold standard? Yes No If Yes, please specify: surgical findings Number of patients: 95, 134 stenotic foramina Consecutively assigned? No Results/subgroup analysis (relevant to question): CTM showed stenosis at the entrance in 70 (52%), within the canal itself in 37 (28%), and site not definitively identified in 27 (20%). At the entrance to the foramen, stenosis secondary to a cartilagenous cap was identified in 10 patients (8%), osteophyte in 17 (13%), synovial cyst in one, and a combination of bone and cartilagenous cap in 42 (31%). Within the canal, small bone spurs arising from the uncovertebral process contributed to stenosis in 29 instances, and from the facet joint in 8. Diagnosis on the basis of CTM was difficult because stenosis was evident as a bone spur in only 13% of cases, could not be distinguished from a disc prolapse in 39%, had to be distinguished from a congenitally narrowed foramen in 27% and was missed in 20%. Author conclusions (relative to question): The diagnosis of foraminal stenosis on CTM is difficult.

130 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 110 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Outcome Measures What are the most appropriate outcome measures to evaluate the treatment of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Level of evidence Description of study Conclusion Alrawi MF, Khalil NM, Mitchell P, Hughes SP. The value of neurophysiologi cal and imaging studies in predicting outcome in the surgical treatment of cervical radiculopathy. Eur Spine J. Apr 2007;16(4): Level III Type of evidence: prognostic Prospective Retrospective Study design: observational Stated objective of study: To use neurophysiological electromyography (EMG) to predict outcome after ACDF. Type of treatment(s): ACDF with a cage Total number of patients: 20 Number of patients in relevant subgroup(s): 12 with no evidence of nerve root involvement/8 with evidence of nerve root involvement Consecutively assigned? Yes Duration/intervals of follow-up: minimum 12 months Outcome measure(s) implemented Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: Prolo (modified), patient satisfaction grade Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Patients still received an operation even if they had a negative EMG. Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that:the modified Prolo scale can be used to assess patient outcome after ACDF

131 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 111 Results/subgroup analysis (relevant to question): Patients' outcome as measured with a modified Prolo scale was better predicted by EMG. Author conclusions (relative to question): EMG can better predict outcomes as measured by a modified Prolo scale. Anderberg L, Annertz M, Brandt L, Saveland H. Selective diagnostic cervical nerve root block-- correlation with clinical symptoms and MRI-pathology. Acta Neurochir (Wien). Jun 2004;146(6): ; discussion 565. Level II Type of evidence: prognostic Prospective Retrospective Study design: observational Stated objective of study: To correlate selective nerve root block (SNRB) with MRI findings and clinical symptoms. Type of treatment(s): SNRB with Mepivacaine Total number of patients: 20 Number of patients in relevant subgroup(s): 20 Consecutively assigned? Yes Duration/intervals of follow-up: immediate-30 minutes Outcome measure(s) implemented: Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: Results/subgroup analysis (relevant to question): 86% mean reduction in VAS arm scores; 65% mean reduction in VAS neck scores. Author conclusions (relative to question): Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Duration of symptoms 1-60 months Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that:vas pain scale can be used to document the immediate anesthetic response to SNRB for radicular arm pain.

132 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 112 The VAS can be used to document response to anesthetic phase of SNRB for arm (and neck) pain. Cleland JA, Fritz JM, Whitman JM, Palmer JA. The reliability and construct validity of the Neck Disability Index and patient specific functional scale in patients with cervical radiculopathy. Spine (Phila Pa 1976). Mar ;31(5): Level I Type of evidence: prognostic Prospective Retrospective Study design: observational Stated objective of study: Examine the test-retest reliability, construct validity and minimum levels of detectable and clinically important change for the Neck Disability Index (NDI) and Patient Specific Functional Scale (PSFS) in a cohort of patients with cervical radiculopathy. Type of treatment(s): Physical therapy Total number of patients: 38 Number of patients in relevant subgroup(s): 38 Consecutively assigned? Yes Duration/intervals of follow-up: days. Mean 21.5 days Outcome measure(s) implemented Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Work group conclusions: Potential level: I Downgraded level: I Conclusions relative to question: This paper provides evidence that:psfs may be better than the NDI for the assessment of outcomes in patients with cervical radiculopathy. Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: PSFS Results/subgroup analysis (relevant to question): Test-retest reliability was moderate for the NDI and high for the PSFS. The PSFS was more responsive to change than the NDI. The minimal detectable change for the NDI was 10.2 and for the PSFS was 2.1.

133 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 113 Author conclusions (relative to question): The PSFS exhibits superior reliability, construct validity, and responsiveness in this cohort of patients with cervical radiculopathy compared with the NDI. Davis RA. A long-term outcome study of 170 surgically treated patients with compressive cervical radiculopathy. Surg Neurol. Dec 1996;46(6): ; discussion Level II Type of evidence: prognostic ~~~~~ Notes: Prospective Retrospective Study design: observational Stated objective of study: To assess the outcome of posterior decompression for cervical radiculopathy. Type of treatment(s): Posterior decompression Total number of patients: 170 Number of patients in relevant subgroup(s): 170 Consecutively assigned? No Duration/intervals of follow-up: not stated Outcome measure(s) implemented Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: Prolo (modified) Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Work group conclusions: Potential level: II Downgraded level: II Conclusions relative to question: This paper provides evidence that:the author's modified Prolo scale may be reasonable to assess outcomes for cervical radiculopathy from degenerative disorders. Results/subgroup analysis (relevant to question): Patients who had sedentary occupations and housewives had significantly higher Prolo scores (p<0.001) than those who did strenuous work. In 86% of patients, outcome was good (defined as a Prolo score of 8 in 5%, 9 in 38% and 10 in 43%).

134 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 114 Author conclusions (relative to question): Although outcome studies must have subjective criteria, the Prolo scale is more objective and quantitative than currently used methods. Fernandez- Fairen M, Sala P, Dufoo M, Jr., Ballester J, Murcia A, Merzthal L. Anterior cervical fusion with tantalum implant: a prospective randomized controlled study. Spine. Mar ;33(5): Level I Type of evidence: prognostic Prospective Study design: RCT Retrospective Stated objective of study: To determine the effectiveness and safety of a tantalum implant in achieving anterior cervical fusion following 1-level discectomy as treatment of degenerative cervical disc disease with radiculopathy. Type of treatment(s): Anterior cervical discectomy and fusion with interbody implant of tantalum (n=28) or by means of autologous iliac bone graft and plating (n=33). Total number of patients: 61 Number of patients in relevant subgroup(s): 28/33 Consecutively assigned? Yes Duration/intervals of follow-up: 24 months Outcome measure(s) implemented Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Work group conclusions: Potential level: I Downgraded level: I Conclusions relative to question: This paper provides evidence that:ndi, VAS (arm) are instruments that can be used to assess the outcome of surgical intervention for cervical radiculopathy from degenerative disorders. Additionally, patient satisfaction as measured by Odom's criteria and depression as measured by the ZDS appears useful. Results/subgroup analysis (relevant to question): At 24 months, radiologic and

135 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 115 clinical outcomes were similar for both treatments without significant difference. The safety of fusion with tantalum implant was documented Author conclusions (relative to question): Clinical outcome using the VAS, NDI and Zung Depression Scale (ZDS) showed that tantalum implant is equivalent to autogenous graft and anterior plate. Foley KT, Mroz TE, Arnold PM, et al. Randomized, prospective, and controlled clinical trial of pulsed electromagnetic field stimulation for cervical fusion. Spine Journal. May 2008;8(3): Level II Type of evidence: prognostic Prospective Study design: RCT Retrospective Stated objective of study: To determine the efficacy and safety of pulsed electromagnetic field (PEMF) stimulation as an adjunct to arthrodesis after ACDF in patients with potential risk factors for nonunion. Type of treatment(s): ACDF with PEMF Total number of patients: 323 Number of patients in relevant subgroup(s): 163/160 Consecutively assigned? Yes Duration/intervals of follow-up: 12 months Outcome measure(s) implemented Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: SF-12 Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Work group conclusions: Potential level: II Downgraded level: II Conclusions relative to question: This paper provides evidence that:ndi, VAS (arm) and SF-12 can be used to assess outcome after surgical intervention for cervical radiculopathy from degenerative disorders. Results/subgroup analysis (relevant to question): Clinical outcome as measured

136 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 116 with the NDI, VAS (arm) and SF-12 showed that PEMF and control groups had no significant differences in outcome. Author conclusions (relative to question): Clinical outcome as measured with the NDI, VAS (arm) and SF-12 showed that PEMF and control groups had no significant differences in outcome. Hacker RJ, Cauthen JC, Gilbert TJ, Griffith SL. A prospective randomized multicenter clinical evaluation of an anterior cervical fusion cage. Spine. Oct ;25(20): ; discussion Level I Type of evidence: prognostic Prospective Study design: RCT Retrospective Stated objective of study: To report clinical results with maximum 24-month follow-up of fusions performed with the BAK/C fusion cage. Type of treatment(s): ACDF with BAK/C cage Total number of patients: 344 Number of patients in relevant subgroup(s): 239/105 Consecutively assigned? Yes Duration/intervals of follow-up: 344 at one year, 180 at 2 years Outcome measure(s) implemented Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Work group conclusions: Potential level: I Downgraded level: I Conclusions relative to question: This paper provides evidence that:vas and SF-36 can be used to assess outcome following surgery for cervical radiculopathy. Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: Results/subgroup analysis (relevant to question): Clinical outcome as assessed with the VAS and SF-36 showed that

137 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 117 with the NDI, VAS (arm) and SF-12 showed that PEMF and control groups had no significant differences in outcome. Author conclusions (relative to question): Clinical outcome as measured with the NDI, VAS (arm) and SF-12 showed that PEMF and control groups had no significant differences in outcome. Hacker RJ, Cauthen JC, Gilbert TJ, Griffith SL. A prospective randomized multicenter clinical evaluation of an anterior cervical fusion cage. Spine. Oct ;25(20): ; discussion Level I Type of evidence: prognostic Prospective Study design: RCT Retrospective Stated objective of study: To report clinical results with maximum 24-month follow-up of fusions performed with the BAK/C fusion cage. Type of treatment(s): ACDF with BAK/C cage Total number of patients: 344 Number of patients in relevant subgroup(s): 239/105 Consecutively assigned? Yes Duration/intervals of follow-up: 344 at one year, 180 at 2 years Outcome measure(s) implemented Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Work group conclusions: Potential level: I Downgraded level: I Conclusions relative to question: This paper provides evidence that:vas and SF-36 can be used to assess outcome following surgery for cervical radiculopathy. Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: Results/subgroup analysis (relevant to question): Clinical outcome as assessed with the VAS and SF-36 showed that

138 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 118 Results/subgroup analysis (relevant to question): Statistically significant improvements were found in postoperative scores for bodily pain (p<0.001), vitality (p=0.003), physical function (p=0.01), role function/physical (p=0.0003) and social function (p=0.0004). No significant differences were found for three health scales: general health, mental health and role function associated with emotional limitations. Author conclusions (relative to question): HSQ may be a good disease specific outcome tool for one and two level ACDF. Kumar N, Gowda V. Cervical foraminal selective nerve root block: a 'two-needle technique' with results. Eur Spine J. Apr 2008;17(4): Level II Type of evidence: prognostic Prospective Retrospective Study design: observational Stated objective of study: To highlight the effectiveness and safety of cervical selective nerve root block using a two needle technique for treatment of radiculopathy. Type of treatment(s): SNRB Total number of patients: 33 Number of patients in relevant subgroup(s): 33 Consecutively assigned? No Duration/intervals of follow-up: 2 years, but only one year follow-up data on outcomes Outcome measure(s) implemented Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Work group conclusions: Potential level: II Downgraded level: II Conclusions relative to question: This paper provides evidence that:ndi, VAS and SF-36 can be used to assess outcome of cervical radiculopathy from degenerative disorders. Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up

139 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 119 Device Success Adverse Event Occurrence Return to Work Other: Results/subgroup analysis (relevant to question): Statistical improvements in VAS score and NDI score were seen at 6 weeks and 12 months after the procedure. Author conclusions (relative to question): The VAS score and NDI can be used to show that the two-needle technique of cervical foraminal SNRB produces improved outcomes at 6 weeks and 12 months. Lofgren H, Johansen F, Skogar O, Levander B. Reduced pain after surgery for cervical disc protrusion/sten osis: a 2 year clinical followup. Disabil Rehabil. Sep ;25(18): Level I Type of evidence: prognostic Prospective Retrospective Study design: observational Stated objective of study: To follow the clinical outcome after surgery for cervical radiculopathy caused by cervical DDD and to compare it with the outcome after conservative treatment Type of treatment(s): ACDF (Clowardsingle level), conservative treatment Total number of patients: 43 Number of patients in relevant subgroup(s): 43 ACDF-Cloward, 39 Conservative controls (2 did have surgery) Consecutively assigned? Yes Duration/intervals of follow-up: 2 year duration with follow-up at 3, 9 and 24 months Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: question of selection bias in group selection; conservative treatment not stated Work group conclusions: Potential level: I Downgraded level: I Conclusions relative to question: This paper provides evidence that:sip and VAS (arm) may be useful surgical outcome measures for patients with cervical radiculopathy. Outcome measure(s) implemented Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria

140 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 120 Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: Sickness Impact Profile (SIP) Results/subgroup analysis (relevant to question): Pain reduction measured with VAS was more pronounced among the operated patients at the final follow-up for maximal neck pain (ρ=0.03) and at 3 months and 9 months, respectively for average neck pain (ρ=0.02, both). Initially, there was no statistically significant difference in pain intensity between the surgically and conservatively treated groups. SIP scheduled for surgery had higher sickness impact in the overall index. Author conclusions (relative to question): Operated patients demonstrated an improvement in pain (VAS) and in SIP, as well as at the clinical examination, all indicating a true improvement, although it was only partially maintained. Mummaneni PV, Burkus JK, Haid RW, Traynelis VC, Zdeblick TA. Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. J Neurosurg Spine. Mar 2007;6(3): Level II Type of evidence: prognostic Prospective Study design: RCT Retrospective Stated objective of study: To compare the results of cervical disc arthroplasty to ACDF Type of treatment(s): Prestige Artificial Cervical Disc Replacement Total number of patients: 541 Number of patients in relevant subgroup(s): Prestige disc, ACDF & Plating Consecutively assigned? No Duration/intervals of follow-up: 2 year duration with follow-up at 1.5, 3, 6, 12 and 24 months Critique of methodology: Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size <80% follow-up Patients enrolled at different points in their disease Lacked subgroup analysis Other: Use of arthrosis in ACDF&P group, <80%follow-up: 80%in Prestige treatment group, and 75% in ACDF&P control group Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question:

141 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 121 Outcome measure(s) implemented: Neck Disability Index (NDI) SF-36 Visual Analog Scale (VAS), Pain Visual Analog Scale (VAS), Satisfaction Odom s Criteria Zung Depression Scale Sickness Impact Profile (SIP) Neurologic Exam Radiographic Follow-Up Device Success Adverse Event Occurrence Return to Work Other: Neck and arm pain numeric rating(vas) This paper provides evidence that:ndi and SF-36 can be used to assess the outcomes of cervical radiculopathy treated by discectomy and artifical disc replacement or fusion. Results/subgroup analysis (relevant to question): Neck pain, arm pain and NDI scores were improved in the Prestige disc group. Success rates at 12 and 24 months for Prestige were statistically superior to control group. Neck pain improved in both treatment groups, but statistically significant in Prestige group at 6 weeks, 3 months and 12 months. No significant intergroup differences in arm pain or return to work at 24 months. NDI score was statistically significantly higher only at 3 months, but tended to have higher score than control. Author conclusions (relative to question): The Prestige ST-cervical disc system maintained physiological segmental motion at 24 months after implantation and was associated with improved neurologic success, improved clinical outcomes (SF-36) and reduced rate of secondary surgeries Compared to: ACDF.

142 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 122 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Medical/Interventional Treatment What is the role of physical therapy/exercise in the treatment of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Level of evidence Description of study Conclusion Persson LC, Lilja A. Pain, coping, emotional state and physical function in patients with chronic radicular neck pain. A comparison between patients treated with surgery, physiotherapy or neck collar-- a blinded, prospective randomized study. Disabil Rehabil. May ;23(8): Level II Type of evidence: therapeutic Prospective Study design: RCT Retrospective Stated objective of study: To compare coping strategies, pain and emotional relationships of patients with cervical radiculopathy of at least three months duration randomly assigned to one of three treatment groups. Type of treatment(s): Cervical brace, physical therapy (PT), and anterior cervical decompression and fusion (ACDF) Total number of patients: 81 Number of patients in relevant subgroup(s): 27 in each group Consecutively assigned? Yes Duration of follow-up: 16 months Validated outcome measures used: VAS pain score, Hospital Anxiety and Depression scale (HAD), Mood Adjective Check List (MACL), general coping questionnaire, and Disability Rating Index (DRI). Nonvalidated outcome measures used: Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that: there is a high incidence of behavioral and emotional dysfunction in cervical radiculopathy patients. Medical/interventional and surgical treatment must include a cognitive, behavioral component for either method to be successful.

143 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 123 Myelogram MRI CT CT/Myelogram Other: behavioral and functional outcomes Results/subgroup analysis (relevant to question): Three patients assigned to the surgical group refused the procedure and were handled in intent to treat analysis. In the surgical group, eight patients had a second operation: six on adjacent level, one infection and one plexus exploration. Eleven patients in the surgery group also received physical therapy. One patient in the physical therapy group and five in the collar group had surgery with Cloward technique. Chronic symptoms influenced both function and mental well being such as emotional state, level of anxiety, depression, sleep and coping behavior. Pain was the most important primary stressor. Surgery reduced the pain faster, but no difference was seen after 12 months. Reoperation rate was 29%, mostly for adjacent segment disease. The low positive mood state (MACL score) did not improve over time. Patients who still had pain after treatment were more socially withdrawn and ceased to express their emotions. The Hospital Anxiety and Depression (HAD) anxiety score was especially high in patients before and after treatment. In patients with high pain intensity, low function, high depression and anxiety were seen. The group treated with surgery showed more anxiety and depression if pain continued, implying higher expectations and more disappointment if it failed. The strongest correlation between depression and pain was seen in the collar group, possibly because they received less attention overall. In general, coping strategies changed. Active coping was common before treatment, but disappeared after treatment, especially in the surgical group. Coping with pain was changed in general into a more passive/escape focused strategy. Also used less alcohol.

144 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 124 Function was significantly related to pain intensity. About 40% had anxiety only partially connected to pain. Prior to treatment, 30% of patients were depressed. After 12 months, 20% suffered from depression. Author conclusions (relative to question): Cognitive and behavioral therapy is important to include in multidisciplinaryy rehabilitation. Patients need to improve coping strategies, self image and mood.

145 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 125 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Medical/Interventional Treatment What is the role of epidural steroid injections for the treatment of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Anderberg L, Annertz M, Persson L, Brandt L, Saveland H. Transforaminal steroid injections for the treatment of cervical radiculopathy: a prospective and randomised study. Eur Spine J. Mar 2007;16(3): Level of evidence Description of study Conclusion Level II Type of evidence: therapeutic Prospective Study design: RCT Retrospective Stated objective of study: Evaluate role of transforaminal epidural steroid injections for pain relief following successful SNRB Type of treatment(s): transforaminal epidural injection with steroid/local anesthetic or saline/local anesthetic (control) Total number of patients: 40 Number of patients in relevant subgroup(s): 20 Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: II Consecutively assigned? Yes Duration of follow-up: 3 weeks Validated outcome measures used: VAS Conclusions relative to question: This paper provides evidence that:the addition of steroids to a local anesthetic injection provides no additional therapeutic benefit at 3 weeks post-procedure. Nonvalidated outcome measures used: Follow-up questionairre Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: selective nerve root block Results/subgroup analysis (relevant to question):

146 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 126 Cyteval C, Thomas E, Decoux E, et al. Cervical radiculopathy: open study on percutaneous periradicular foraminal steroid infiltration performed under CT control in 30 patients. AJNR Am J Neuroradiol. Mar 2004;25(3): Level IV Type of evidence: therapeutic Author conclusions (relative to question): Prospective Retrospective Study design: case series Stated objective of study: To evaluate the feasability, tolerance, and efficacy of transforaminal periganglionic steroid infiltration under CT control Type of treatment(s): transforaminal epidural steroid injection Total number of patients: 30 Number of patients in relevant subgroup(s): Consecutively assigned? Yes Duration of follow-up: 6 months Validated outcome measures used: used a modified VAS (excellent/good/fair/poor) Nonvalidated outcome measures used: Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Results/subgroup analysis (relevant to question): 60% of patients obtain good or excellent pain relief following a transforaminal epidural steroid injection under CT guidance Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:60% of patients obtain good or excellent pain relief following a transforaminal epidural steroid injection under CT guidance Kim H, Lee SH, Kim MH. Author conclusions (relative to question): CT guided transforaminal ESI provided sustained relief regardless of the cause of radiculopathy Level IV Prospective Retrospective Critique of methodology: Nonconsecutive patients

147 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 127 Multislice CT fluoroscopyassisted cervical transforaminal injection of steroids: technical note. J Spinal Disord Tech. Aug 2007;20(6): Type of evidence: therapeutic Study design: case series Stated objective of study: To evaluate the feasibility and the outcome of cervical transforaminal epidural steroid injection guided by multislice CT Type of treatment(s): transforaminal epidural steroid injection Total number of patients: 19 Number of patients in relevant subgroup(s): 19 Consecutively assigned? Yes Duration of follow-up: 4 months Validated outcome measures used: VAS Nonvalidated outcome measures used: Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: excluded patients with neurologic deficit Results/subgroup analysis (relevant to question): No patient required more than 2 injections. Significant improvement in VAS at 2, 4, 8, 16 weeks. No serious complications. Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:cervical transforaminal steroid injections provide approximately a 50% reduction in pain which lasts for 16 weeks. Kolstad F, Leivseth G, Nygaard OP. Transforaminal steroid injections in the treatment of Level IV Type of evidence: therapeutic Author conclusions (relative to question): CT guided cervical transforaminal epidural steroid injections are safe and effective. Prospective Retrospective Study design: case series Stated objective of study: To determine if transforaminal steroid injections applied to a cohort of patients waiting Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used:

148 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 128 cervical radiculopathy. A prospective outcome study. Acta Neurochir (Wien). Oct 2005;147(10): ; discussion for cervical disc surgery, reduce the pain of cervical radiculopathy and hence reduce the need for surgical intervention. Type of treatment(s): 2 cervical transforaminal steroid injections, 2 weeks apart Total number of patients: 21 Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: IV Downgraded level: IV Number of patients in relevant subgroup(s): Consecutively assigned? Duration of follow-up: 4 months Validated outcome measures used: VAS Conclusions relative to question: This paper provides evidence that:about 1/4 of patients who could be considered for surgery could potentially achieve short term pain relief with 2 cervical transforaminal epidural steroid injections two weeks apart. Nonvalidated outcome measures used: Odom's criteria, operative indications Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Results/subgroup analysis (relative to question): Lin EL, Lieu V, Halevi L, Shamie AN, Wang JC. Cervical epidural steroid injections for symptomatic disc herniations. Journal of Spinal Level IV Type of evidence: therapeutic Author conclusions (relative to question): Prospective Retrospective Study design: case series Stated objective of study: To examine the efficacy of cervical epidural steroid injections for the treatment of symptomatic herniated cervical discs in patients considered potential surgical candidates. Type of treatment(s): cervical Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated

149 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 129 Disorders and Techniques. May 2006;19(3): transforaminal epidural steroid injections using fluoroscopic guidance Total number of patients: 70 Number of patients in relevant subgroup(s): Consecutively assigned? Yes Duration of follow-up: 1 year Validated outcome measures used: main outcome measure was whether or not surgery was performed Nonvalidated outcome measures used: Odom's Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Results/subgroup analysis (relevant to question): older patients and those with shorter duration of symptoms did better with ESI Author conclusions (relative to question): Patients considering surgery may improve with a trial of ESI and avoid surgery Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:approximately 60% of patients who are considered surgical candidates may obtain pain relief from cervical epidural steroid injections.

150 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 130 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Medical/Interventional Treatment What is the role of ancillary treatments such as bracing, traction, electrical stimulation, acupuncture and transcutaneous electrical stimulation (TENS) in the treatment of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Alexandre A, Coro L, Azuelos A, et al. Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations. Acta Neurochir Suppl. 2005;92: Level of evidence Description of study Conclusion Level V Type of evidence: therapeutic Prospective Retrospective Study design: case series Stated objective of study: Report the effects of intervertebral disc and paravertebral injections of ozone & oxygen in patients with cervical disc herniations Type of treatment(s): Intervertebral disc and five paravertebral injections of ozone & oxygen Total number of patients: 252 Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: No specified duration of follow-up, no data tables or speed of recovery noted. Number of patients in relevant subgroup(s): Consecutively assigned? No Duration of follow-up: possibly 7 months Validated outcome measures used: Nonvalidated outcome measures used: pain improvement, sensory dysfunction, strength improvement Work group conclusions: Potential level: IV Downgraded level: V Conclusions relative to question: This paper provides evidence that:approximately 80% of patients will report symptomatic relief from cervical radiculopathy at some point following ozone and oxygen injection into the intervertebral disc and paravertebral musculature. Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other:

151 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 131 Results/subgroup analysis (relevant to question): Author conclusions (relative to question): Approximately 80% of patients reported relief of symptoms at some point following the injection procedure. Olivero WC, Dulebohn SC. Results of halter cervical traction for the treatment of cervical radiculopathy: retrospective review of 81 patients. Neurosurg Focus. Feb ;12(2):EC P1. Level V Type of evidence: therapeutic Prospective Retrospective Study design: case series Stated objective of study: Evaluate the use of halter traction and collar in patients with cervical radiculopathy Type of treatment(s): traction for 6 weeks - additional traction if improving; (8-12 lbs, TID for 15 minutes) cervical collar. Patients with severe symptoms excluded from study. Total number of patients: 81 Number of patients in relevant subgroup(s): Consecutively assigned? No Duration of follow-up: 6-12 weeks Validated outcome measures used: none Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: IV Downgraded level: V Conclusions relative to question: This paper provides evidence that:75% of patients with mild radiculopathy may improve with traction over a six week time frame. Nonvalidated outcome measures used: patient report of pain relief Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Results/subgroup analysis (relevant to question): 63 (78%) of patients responded to traction

152 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders patients who initially responded relapsed Persson LC, Lilja A. Pain, coping, emotional state and physical function in patients with chronic radicular neck pain. A comparison between patients treated with surgery, physiotherapy or neck collar-- a blinded, prospective randomized study. Disabil Rehabil. May ;23(8): Level II Type of evidence: therapeutic Author conclusions (relative to question): 75% of patients with mild cervical radiculopathy of approximately 6 weeks duration may improve with halter traction Prospective Retrospective Study design: RCT Stated objective of study: To compare coping strategies, pain and emotional relationships of patients with cervical radiculopathy of at least three months duration randomly assigned to one of three treatment groups. Type of treatment(s): Cervical brace, physical therapy (PT), and anterior cervical decompression and fusion (ACDF) Total number of patients: 81 Number of patients in relevant subgroup(s): 27 in each group Consecutively assigned? Yes Duration of follow-up: 16 months Validated outcome measures used: VAS pain score, Hospital Anxiety and Depression scale (HAD), Mood Adjective Check List (MACL), general coping questionnaire, and Disability Rating Index (DRI). Nonvalidated outcome measures used: Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: behavioral and functional Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that: there is a high incidence of behavioral and emotional dysfunction in cervical radiculopathy patients. Medical/interventional and surgical treatment must include a cognitive, behavioral component for either method to be successful.

153 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 133 outcomes Results/subgroup analysis (relevant to question): Three patients assigned to the surgical group refused the procedure and were handled in intent to treat analysis. In the surgical group, eight patients had a second operation: six on adjacent level, one infection and one plexus exploration. Eleven patients in the surgery group also received physical therapy. One patient in the physical therapy group and five in the collar group had surgery with Cloward technique. Chronic symptoms influenced both function and mental well being such as emotional state, level of anxiety, depression, sleep and coping behavior. Pain was the most important primary stressor. Surgery reduced the pain faster, but no difference was seen after 12 months. Reoperation rate was 29%, mostly for adjacent segment disease. The low positive mood state (MACL score) did not improve over time. Patients who still had pain after treatment were more socially withdrawn and ceased to express their emotions. The Hospital Anxiety and Depression (HAD) anxiety score was especially high in patients before and after treatment. In patients with high pain intensity, low function, high depression and anxiety were seen. The group treated with surgery showed more anxiety and depression if pain continued, implying higher expectations and more disappointment if it failed. The strongest correlation between depression and pain was seen in the collar group, possibly because they received less attention overall. In general, coping strategies changed. Active coping was common before treatment, but disappeared after treatment, especially in the surgical group. Coping with pain was changed in general into a more passive/escape focused strategy. Also used less alcohol. Function was significantly related to pain intensity. About 40%

154 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 134 had anxiety only partially connected to pain. Prior to treatment, 30% of patients were depressed. After 12 months, 20% suffered from depression. Author conclusions (relative to question): Cognitive and behavioral therapy is important to include in multidisciplinaryy rehabilitation. Patients need to improve coping strategies, self image and mood. Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine. Aug ;21(16): Level IV Type of evidence: therapeutic Prospective Retrospective Study design: case series Stated objective of study: report success of a conservative management program for cervical radiculopathy Type of treatment(s): PT, NSAIDs, po steroids, ESI, exercise, postural training, collar, acupuncture, TENS Total number of patients: 26; 24/26 completed program Number of patients in relevant subgroup(s): Consecutively assigned? Yes Duration of follow-up: 3 months Validated outcome measures used: none Nonvalidated outcome measures used: patient questionaire, return to work Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:a multifaceted medical/interventional treatment program is associated with good outcomes in many patients with cervical radiculopathy.

155 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 135 Results/subgroup analysis (relevant to question): 24 completed program 22/24 returned to work 89% had good/excellent response Author conclusions (relative to question): Comprehensive nonoperative treatment program was associated with favorable results in treating cervical radiculopathy

156 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 136 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Surgical Treatment Does surgical treatment (with or without preoperative medical/interventional treatment) result in better outcomes than medical/interventional treatment for cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Level of evidence Description of study Conclusion Persson LC, Lilja A. Pain, coping, emotional state and physical function in patients with chronic radicular neck pain. A comparison between patients treated with surgery, physiotherapy or neck collar-- a blinded, prospective randomized study. Disabil Rehabil. May ;23(8): Level II Type of evidence: therapeutic Prospective Study design: RCT Retrospective Stated objective of study: To compare coping strategies, pain and emotional relationships of patients with cervical radiculopathy of at least three months duration randomly assigned to one of three treatment groups. Type of treatment(s): Cervical brace, physical therapy (PT), and anterior cervical decompression and fusion (ACDF) Total number of patients: 81 Number of patients in relevant subgroup(s): 27 in each group Consecutively assigned? Yes Duration of follow-up: 16 months Validated outcome measures used: VAS pain score, Hospital Anxiety and Depression scale (HAD), Mood Adjective Check List (MACL), general coping questionnaire, and Disability Rating Index (DRI). Nonvalidated outcome measures used: Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that: there is a high incidence of behavioral and emotional dysfunction in cervical radiculopathy patients. Medical/interventional and surgical treatment must include a cognitive, behavioral component for either method to be successful.

157 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 137 MRI CT CT/Myelogram Other: behavioral and functional outcomes Results/subgroup analysis (relevant to question): Three patients assigned to the surgical group refused the procedure and were handled in intent to treat analysis. In the surgical group, eight patients had a second operation: six on adjacent level, one infection and one plexus exploration. Eleven patients in the surgery group also received physical therapy. One patient in the physical therapy group and five in the collar group had surgery with Cloward technique. Chronic symptoms influenced both function and mental well being such as emotional state, level of anxiety, depression, sleep and coping behavior. Pain was the most important primary stressor. Surgery reduced the pain faster, but no difference was seen after 12 months. Reoperation rate was 29%, mostly for adjacent segment disease. The low positive mood state (MACL score) did not improve over time. Patients who still had pain after treatment were more socially withdrawn and ceased to express their emotions. The Hospital Anxiety and Depression (HAD) anxiety score was especially high in patients before and after treatment. In patients with high pain intensity, low function, high depression and anxiety were seen. The group treated with surgery showed more anxiety and depression if pain continued, implying higher expectations and more disappointment if it failed. The strongest correlation between depression and pain was seen in the collar group, possibly because they received less attention overall. In general, coping strategies changed. Active coping was common before treatment, but disappeared after treatment, especially in the surgical group. Coping with pain was changed in general into a more passive/escape focused strategy. Also used less alcohol. Function was significantly related to pain

158 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 138 intensity. About 40% had anxiety only partially connected to pain. Prior to treatment, 30% of patients were depressed. After 12 months, 20% suffered from depression. Author conclusions (relative to question): Cognitive and behavioral therapy is important to include in multidisciplinaryy rehabilitation. Patients need to improve coping strategies, self image and mood. Persson LC, Moritz U, Brandt L, Carlsson CA. Cervical radiculopathy: pain, muscle weakness and sensory loss in patients with cervical radiculopathy treated with surgery, physiotherapy or cervical collar. A prospective, controlled study. Eur Spine J. 1997;6(4): Level II Type of evidence: therapeutic Prospective Study design: RCT Retrospective Stated objective of study: To compare outcomes in pain, strength and sensation in three treatment groups of patients with cervical radiculopathy of a minimum of three months duration Type of treatment(s): Cervical brace, physical therapy (PT), and anterior cervical decompression and fusion (ACDF) (Cloward technique) Total number of patients: 81 Number of patients in relevant subgroup(s): 27 in each group. Consecutively assigned? Yes Duration of follow-up: 16 months Validated outcome measures used: VAS pain scale, muscle strength assessed by a handheld dynamometer, vigorometer and pinchometer. Sensory loss recorded Nonvalidated outcome measures used: Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that:at one year, outcomes are similar for medical/interventional treatment and surgical treatment of patients with cervical radiculopathy from degenerative disorders. Due to the small sample size, one may not expect to see a difference between the groups on a statistical basis. Surgical treatment resulted in improved outcomes earlier in the postoperative treatment period when compared with the medical/interventional treatment group.

159 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 139 Results/subgroup analysis (relevant to question): Three surgical patients refused the procedure and were handled in intent to treat analysis. In the surgical group, eight patients had a second operation: six on adjacent level, one infection and one plexus exploration. Eleven patients in the surgery group also received physical therapy. One patient in the physical therapy group and five in the collar group had surgery with Cloward technique. Strength measurements were all performed by one physical therapist with standard protocol. Physical therapy was done for 15 visits and was not standardized. Several different collars were used and worn for three months. At four month follow-up, pain was improved in the surgical and physical therapy groups, and improvement in pain scores in the surgical group was significantly better than in the collar group. After another year, the pain was about the same across groups. The surgical group improved strength a little faster, but at final follow-up strength improvement was equal across groups. At final follow-up, there was no difference between groups on the sensory exam. Author conclusions (relative to question): No difference in outcomes after one year between patients treated with a collar, physical therapy or surgery. Sampath P, Bendebba M, Davis JD, Ducker T. Outcome in patients with cervical radiculopathy. Prospective, multicenter study with independent clinical review. Spine. Mar ;24(6):591- Level III Type of evidence: therapeutic Prospective Retrospective Study design: comparative Stated objective of study: Evaluated clinical outcomes in patients with cervical radiculopathy Type of treatment(s): Medical/interventional treatment was nonstandardized in this multicenter trial, and included medications, steroids, bed rest, exercise, traction, bracing, injections, chiropractic care, acupuncture and homeopathic medicine. Surgery included Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: high attrition rate, medical/interventional and surgical treatment protocols were

160 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders foraminotomy, anterior cervical decompression (ACD), and anterior cervical decompression and fusion (ACDF). Total number of patients: 503 Number of patients in relevant subgroup(s): 246, 160 medical, 86 surgical. Nonrandomized from 41 different surgeons. Consecutively assigned? No nonstandardized/variable. Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that:surgical treatment results in improved outcomes when compared with medical/interventional treatment on short term follow-up. Duration of follow-up: Mean 11 months (range: 8 to 13 months) Validated outcome measures used: Nonvalidated outcome measures used: Pain scale, satisfaction scale, neurologic score, functional scale, activities of daily living (ADL) scale. Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Imaging not stated Results/subgroup analysis (relevant to question): Of the 246 patients, only 155 reported data at final follow-up. Of the 155 patients, 104 were medically/interventionally treated and 51 had surgery. In general, pain scores were worse in the surgical group preoperatively than in the medical/interventional treatment group. Both groups improved significantly, with greater improvement seen in the surgical group. Patient satisfaction, neurological improvement and functional improvement were seen in both groups, with greater improvement reported in the surgical group. There was significant improvement in activities of daily living (ADL) in the surgical group. Although there was improvement, there

161 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 141 was still significant pain in about 26% of surgical patients. The number returning to work did not differ before and after intervention in either group despite improved functional ability, implying that the most important factor for return to work was work status prior to treatment. Author conclusions (relative to question): Surgery appears to have more success than medical/interventional treatment, although both help. Despite this, a substantial percentage of patients continue to have severe pain, neurologic symptoms and no work activity.

162 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 142 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Surgical Treatment Does anterior cervical decompression with fusion result in better outcomes (clinical or radiographic) than anterior cervical decompression alone? Article (Alpha by Author) Barlocher CB, Barth A, Krauss JK, Binggeli R, Seiler RW. Comparative evaluation of microdiscectom y only, autograft fusion, polymethylmeth acrylate interposition, and threaded titanium cage fusion for treatment of single-level cervical disc disease: a prospective randomized study in 125 patients. Neurosurg Focus. Jan ;12(1):E4. Level of evidence Description of study Conclusion Level III Type of evidence: therapeutic Prospective Study design: RCT Retrospective Stated objective of study: Compare outcomes of anterior cervical decompression (ACD) to three different types of anterior cervical decompression and fusion (ACDF): iliac crest bone graft (ICBG), polymethylmethacrylate (PMMA) and titanium cages. Type of treatment(s): ACD vs ACDF Total number of patients: 125 Number of patients in relevant subgroup(s): 33 ACD, 30 ICBG, 26 PMMA, and 36 cages Consecutively assigned? Yes Duration of follow-up: 12 months Validated outcome measures used: Nonvalidated outcome measures used: Odom Criteria, VAS pain scale Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Used imaging; not specified Results/subgroup analysis (relevant to question): Of the 125 patients, 123 were Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Single level disease only, PMMA as spacer is not standard practice, randomization process is not described Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that:suggests that there are variable outcomes when comparing ACD to ACDF for the treatment of cervical radiculopathy due to single level degenerative disease. In one cohort comparing ACD to fusion with ICBG, outcomes were equivalent, while another cohort showed superiority of interbody fusion with a titanium cage and allograft versus ACD. Validity of conclusions are weakened by small sample size and short follow-up.

163 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 143 available for follow-up. The functional outcomes were grouped by good and excellent to poor and fair, with good/excellent results reported for 75% of the ACDF group, 80% for ICBG, 87% for PMMA and 94% for cage. Average reported kyphosis for ACD patients was 24 degrees, with one patient requiring revision surgery (31 degrees); 12 degrees for PMMA and about three degrees for the ICBG and cage groups. Twelve month fusion results were reported as 93% for the ACD patients, 93% for ICBG and 97% for cage. Fusion rate was faster in the cage group as well with 86% achieving fusion at six months compared with 61% in the ACD group and 65% in the ICBG group. Hauerberg J, Kosteljanetz M, Boge- Rasmussen T, et al. Anterior cervical discectomy with or without fusion with ray titanium cage: a prospective randomized clinical study. Spine. Mar ;33(5): Level II Type of evidence: therapeutic Author conclusions (relative to question): Concluded that ACDF with cage did significantly better with faster and better recovery and less kyphotic deformity than ACD. ACD Compared to: ICBG had similar outcomes at medium length followup. Prospective Retrospective Study design: RCT Stated objective of study: Compare radiographic and clinical outcomes of ACD with ACDF using a titanium cage. Type of treatment(s): anterior cervical discectomy (ACD), anterior cervical discectomy with fusion ( ACDF) at one level only in subaxial cervical spine Total number of patients: 86 Number of patients in relevant subgroup(s): 46 ACD and 40 ACDF Consecutively assigned? Yes Duration of follow-up: minimum two years Validated outcome measures used: none Nonvalidated outcome measures used: Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that: for cervical radiculopathy due to single level degenerative disease, clinical outcomes are similar at two years for patients undergoing ACD and ACDF with threaded titanium cage and local

164 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 144 four point scale, converted to dichotomized scale of good/excellent vs. unchanged/worse, numerical pain score, and return to work autograft. Fusion rates and symptomatic adjacent segment disease were also similar between the two groups. Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Imaging; not specified Results/subgroup analysis (relevant to question): One patient withdrew in each group. Two year follow-up data were available for 36 cage and 43 ACD patients. Early outcomes, though not statistically significant, favored ACD. At two years 63% of ACD patients and 78% of cage patients reported good outcomes (not statistically significant). Reoperation rates at the same level were reported as follows: at three months, three reoperations in ACD group, two in cage group; at one year, an additional reoperation in each group; at two years, an additional three in the ACD group. There were some additional procedures at adjacent levels that were equivalent for both groups over two years. In total, for the ACD group, 17/46 were investigated, seven had the same level reoperation and two had adjacent level operations. In the cage group, 15/40 were investigated with three having same level reoperation and three having adjacent level operations. There were no statistically significant differences reported in kyphosis or fusion rate. Oktenoglu T, Cosar M, Ozer AF, et al. Anterior Level III Type of evidence: Author conclusions (relative to question): No difference in outcome between ACD and ACDF with cage and local autograft bone. Prospective Retrospective Study design: RCT Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers

165 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 145 cervical microdiscectom y with or without fusion. J Spinal Disord Tech. Jul 2007;20(5): therapeutic Stated objective of study: Compare radiographic and clinical outcomes Type of treatment(s): anterior cervical decompression with fusion and plate (ACDFP) vs. anterior cervical decompression (ACD) Total number of patients: 20 Number of patients in relevant subgroup(s): 11 ACD and 9 ACDF Consecutively assigned? Yes Duration of follow-up: 12 to 18 months, mean 14 months Validated outcome measures used: Nonvalidated outcome measures used: VAS Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Results/subgroup analysis (relevant to question): Inclusion criteria required only two weeks of failed medical/interventional treatment. VAS upper extremity pain scores (dominant complaint) improved significantly in both groups, from mean 8 to 3. Although less severe initially than arm pain, VAS neck pain scores had less improvement overall, but statistically significant improvement was noted in the ACDF group. CT follow-up at one year showed disc space collapse in both groups, but significantly more in the ACD group. There was some subsidence of the graft over the first year. Final foraminal dimensions were slightly larger in ACDF group, but not significant. Reported fusion rates were 100% in the ACDF group and 45% (5/11) in the ACD group. Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: coin flip randomization; short duration of symptoms for inclusion criteria Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that:for cervical radiculopathy due to single level degenerative disease, ACD alone provides satisfactory clinical outcomes when Compared to: ACDF with allograft ICBG and semirigid plate. Radiographically, disc height is maintained significantly better with plate and fusion although the clinical significance is unknown. The validity of the conclusions is uncertain due to small sample size.

166 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 146 Author conclusions (relative to question): ACD alone provides satisfactory clinical outcomes when Compared to: ACDF with semirigid plate. Savolainen S, Rinne J, Hernesniemi J. A prospective randomized study of anterior singlelevel cervical disc operations with long-term follow-up: surgical fusion is unnecessary. Neurosurgery. Jul 1998;43(1): Level III Type of evidence: therapeutic Prospective Study design: RCT Retrospective Stated objective of study: Compare clinical results of anterior cervical decompression (ACD) to anterior cervical decompression and fusion (ACDF) with or without plate Type of treatment(s): ACD, ACDF, ACDFP with plate for one level disease, using autograft ICBG. Total number of patients: 91 Number of patients in relevant subgroup(s): 91; specific number in each group were not reported Consecutively assigned? Yes Duration of follow-up: 3.2 to 4.8 years, mean four years Validated outcome measures used: Nonvalidated outcome measures used: four point scale Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Radiologic studies, not specified Results/subgroup analysis (relevant to question): Follow-up data were reported for 88/91 patients. Good/excellent results were reported in 76% of ACD patients, 82% ACDF, and 73% ACDFP. Of the 88 patients, 71 had long term radiographic Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: randomization process not specified; phone follow-up at four years Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that:for patients with cervical radiculopathy due to single level degenerative disease, ACD yields results equivalent to ACDF with or without a plate. The validity of the conclusions is uncertain due to small sample size.

167 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 147 follow-up, with slight kyphosis in 62% of ACD, 41% ACDF, 44% ACDFP and fusion achieved in 100% of ACDF and 90% of ACD patients. Complication rates were similar for all groups, with the exception of short term ICBG pain which was severe in 80% of both ACDF groups. Wirth FP, Dowd GC, Sanders HF, Wirth C. Cervical discectomy. A prospective analysis of three operative techniques. Surgical neurology; 2000: ; discussion Level III Type of evidence: therapeutic Author conclusions (relative to question): Because outcomes were similar for the three groups, ACD is recommended as procedure of choice for ease of surgery and reduced complications. Prospective Retrospective Study design: RCT Stated objective of study: Compare clinical outcomes of anterior cervical discectomy (ACD), anterior cervical discectomy with fusion ( ACDF) and posterior cervical foraminomtomy for single level HNP with radiculopathy Type of treatment(s): ACD, ACDF, foraminotomy Total number of patients: 72 Number of patients in relevant subgroup(s): 22 foraminotomy, 25 ACD, 25 ACDF Consecutively assigned? Yes Duration of follow-up: Mean 60 months Validated outcome measures used: Nonvalidated outcome measures used: grading scheme incorporating length of hospitalization, radicular pain improvement, and return to work Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Poor randomization; high attrition rate for long term follow-up Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that: for single level HNP causing cervical radiculopathy, outcomes for ACD are equivalent to ACDF.

168 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 148 Other: Imaging; not specified Results/subgroup analysis (relevant to question): In immediate postoperative results, surgical time, hospital stay and cost were slightly better for the ACD group. Postoperative pain was worse in the foraminotomy group. At two months, according to the grading scheme implemented, all three groups were about the same. Reoperations were greater at the operative site for foraminotomy and adjacent sites for ACDF patients. Longterm follow-up was accomplished via phone interview at 53 months for the foraminotomy group (14/22 patients), 56 months for the ACD group (13/25 patients) and 69 months for the ACDF group (16/25 patients), with a loss of about 40% of patients to follow-up. Within the limits of their study design and patient capture, pain improvement remained high for all groups. Return to work for was 79% for the foraminotomy group, 92% for ACD and 81% for ACDF (not statisically significant). Of the patients available at final follow-up, 100% were satisfied and would have the surgery again. Xie JC, Hurlbert RJ. Discectomy versus discectomy with fusion versus discectomy with fusion and instrumentation: a prospective randomized study. Neurosurgery. Jul 2007;61(1): ; discussion Level II Type of evidence: therapeutic Author conclusions (relative to question): For single level HNP, all procedures are efficacious. Prospective Retrospective Study design: RCT Stated objective of study: Compare clinical and radiographic outcomes of anterior cervical discectomy (ACD), anterior cervical discectomy with fusion (ACDF), and anterior cervical discectomy with instrumented fusion (ACDFI) for single level cervical radiculopathy Type of treatment(s): ACD, ACDF, ACDFI; graft was autograft iliac crest bone graft (ICBG) Total number of patients: 45 Number of patients in relevant subgroup(s): 15 ACD, 15 ADCF, 15 Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question:

169 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 149 ACDFI Consecutively assigned? Yes Duration of follow-up: two years Validated outcome measures used: McGill Pain Questionnaire (MPQ), SF-36, General Health Outcome Measure Nonvalidated outcome measures used: Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: This paper provides evidence that:clinical outcomes for treatment of cervical radiculopathy due to single level degenerative disease are similar when comparing ACD to ACDF, with or without plating. Radiographic outcomes were worse with ACD, resulting in a significant loss of lordosis, although the clinical consequences of this are unknown.the validity of the conclusions may be compromised by a very small sample size. Results/subgroup analysis (relevant to question): Three patients in the ACD group lost to follow-up. No graft site pain was reported at two years. In general, clinical results improved to one year then plateaued. Arm pain was completely absent in 92% of ACD patients, 93% of ACDF patients and 100% of ACDFI patients. Neck pain was absent in 83%, 80% and 73%, respectively. All had significant and similar improvements in MPQ and SF-36. At two years, fusion rate on radiograph was 67%, 93%, and 100% respectively. Of patients treated with ACD, 75% had kyphosis at two years. Author conclusions (relative to question): Patient selection is the key to surgical success. Any of these surgeries are suitable for cervical radiculopathy due to nerve root compression. Because the long term effects of kyphosis are unknown, we cannot be certain about the potential consequences of ACD.

170 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 150 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Surgical Treatment Does anterior cervical decompression and fusion with instrumentation result in better outcomes (clinical or radiographic) than anterior cervical decompression and fusion without instrumentation? Article (Alpha by Author) Level of evidence Description of study Conclusion Grob D, Peyer JV, Dvorak J. The use of plate fixation in anterior surgery of the degenerative cervical spine: a comparative prospective clinical study. Eur Spine J. Oct 2001;10(5): Level II Type of evidence: therapeutic Prospective Study design: RCT Retrospective Stated objective of study: compare clinical and radiographic outcomes of anterior cervical decompression and fusion (ACDF) and anterior cervical decompression and fusion plus plate (ACDFP) Type of treatment(s): ACDF, ACDFP Total number of patients: 54, 50 available for follow-up Number of patients in relevant subgroup(s): 50: 24 ACDFP, 26 ACDF Consecutively assigned? No Duration of follow-up: 22 to 46 months, average 34 months. Validated outcome measures used: Nonvalidated outcome measures used: Visual Analog Scale (VAS) - pain, neurological exam, functional (ROM) assessment, and radiographic evidence of fusion Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Not sure if patients were consecutively assigned. Questionable randomization method used. Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that:use of plate in addition to anterior cervical decompression and fusion is not supported for the treatment of cervical radiculopathy from degenerative disorders.

171 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 151 CT/Myelogram Other: Results/subgroup analysis (relevant to question): Both groups had a statistically significant decrease in VAS pain scores and improvement in cervical spine range of motion postoperatively, but there was no significant difference between groups for either of these outcome measures. Radiographically, there was no difference in the frequency of pseudoarthrosis/nonunion. The authors defined inferior graft quality as ventral graft dislocation greater than 2mm and/or loss of disc height by more than 2mm. Based upon these criteria, the plate group had significantly better results (p=.04). Mobbs RJ, Rao P, Chandran NK. Anterior cervical discectomy and fusion: analysis of surgical outcome with and without plating. J Clin Neurosci. Jul 2007;14(7): Level III Type of evidence: therapeutic Author conclusions (relative to question): Addition of an anterior cervical plate did not lead to an improved clinical outcome for patients treated for cervical radiculopathy with a one or two level anterior procedure. Prospective Retrospective Study design: comparative Stated objective of study: compare clinical and radiographic outcomes of anterior cervical decompression and fusion (ACDF) vs anterior cervical decompression and fusion with plate (ACDFP) in patients with cervical radiculopathy Type of treatment(s): ACDF, ACDFP Total number of patients: 242; 212 radiculopathy Number of patients in relevant subgroup(s): 212: 116 ACDF, 96 ACDFP Consecutively assigned? No Duration of follow-up: one year Validated outcome measures used: Nonvalidated outcome measures used: Odoms criteria, radiographic fusion Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question: This paper provides evidence that:addition of an anterior locking plate may not lead to an increased likelihood of a satisfactory clinical outcome, but it may lower the likelihood of a poor outcome and need for reoperation.

172 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 152 Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Imaging; not specified Results/subgroup analysis (relevant to question): Using Odom s criteria, there was no significant difference in good to excellent outcomes between the two groups (87% of the ACDF patient group and 92% of the ACDFP). On the other hand, the noninstrumented group had a statistically significantly higher frequency of poor outcomes at 7% (8/116) Compared to: the ACDFP group at 1% (1/96. Poor outcomes were considered to be postoperative kyphosis and nonunion. Zoega B, Karrholm J, Lind B. Onelevel cervical spine fusion. A randomized study, with or without plate fixation, using radiostereometr y in 27 patients. Acta Orthop Scand. Aug 1998;69(4): Level II Type of evidence: therapeutic Author conclusions (relative to question): Excellent results were similar for both groups. There was a significantly higher rate of poor outcomes in the uninstrumented group and this lead to higher rate of second surgery. Prospective Retrospective Study design: RCT Stated objective of study: to evaluate whether addition of a plate to a single level cervical fusion for DDD enhances fusion rate and contributes to maintaining alignment Type of treatment(s): anterior cervical discectomy and fusion (ACDF), anterior cervical discectomy and fusion plus plate (ACDFP) Total number of patients: 27 Number of patients in relevant subgroup(s): 15 ACDFP, 12 ACDF Consecutively assigned? Yes Duration of follow-up: 24 months Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that:plate maintains alignment.

173 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 153 Validated outcome measures used: radiostereometry (RSA) Nonvalidated outcome measures used: VAS pain scale Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Results/subgroup analysis (relevant to question): There was a statistically significant increase in the frequency of postoperative kyphosis in the nonplated group at one year follow-up (p=.04). At two years statistical significance was lost (p=>06). There was one nonunion in the plate group; none in the ACDF group. Clinical scores were the same for both groups. Author conclusions (relative to question): Plate maintains alignment, but provides no advantage for healing or for clinical outcomes

174 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 154 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Surgical Treatment Does anterior surgery result in better outcomes (clinical or radiographic) than posterior surgery in the treatment of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Level of evidence Description of study Conclusion Herkowitz HN, Kurz LT, Overholt DP. Surgical management of cervical soft disc herniation. A comparison between the anterior and posterior approach. Spine. Oct 1990;15(10): Level III Type of evidence: therapeutic Prospective Retrospective Study design: comparative Stated objective of study: compare anterior cervical decompression and fusion (ACDF) to posterior laminoforaminotomy (PLF) Type of treatment(s): ACDF, PLF Total number of patients: 44: Type II central herniations with myelopathy (n=11), Type I lateral herniations with radiculopathy (n=17 ACDF, n = 16 PLF) Number of patients in relevant subgroup(s): 33: 17 ACDF, 16 PLF Consecutively assigned? Yes Duration of follow-up: 1.6 to 8.2 years, mean 4.2 years Validated outcome measures used: Nonvalidated outcome measures used: Odom's type criteria [Excellent (complete relief of pain and weakness), good (improvement of pain and weakness), fair, poor] Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Improper randomization technique -- Randomization: Type I herniations alternated between ACDF and PLF (it did not state how the randomization was completed or how allocation was concealed). It simply states "alternated" and does not state "randomized." Uncertain how, or if, allocation was concealed from outcome observers. Also, it was uncertain if follow-up was at a similar times. Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that: anterior cervical decompression with fusion and posterior laminoforaminotomy appear equally effective in improving pain and weakness.

175 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 155 Other: Results/subgroup analysis (relevant to question): The average age of the 17 patients assigned to the ACDF group was 43, while the average age of the 16 patients assigned to the PLF group was 39. Of the 17 ACDF patients, 94% reported good (5/17) or excellent (11/17) results. Of the 16 PLF patients, 75% reported good (6/16) or excellent (6/16) results. ACDF was not significantly better (p<0.175). Osteophytic changes were seen in 9/17 ACDF patients and 8/16 PLF patients. Korinth MC, Kruger A, Oertel MF, Gilsbach JM. Posterior foraminotomy or anterior discectomy with polymethyl methacrylate interbody stabilization for cervical soft disc disease: results in 292 patients with monoradiculopa thy. Spine. May ;31(11): ; discussion Level III Type of evidence: therapeutic Author conclusions (relative to question): Both surgical procedures are effective, but ACDF tends to be better over long term. Prospective Retrospective Study design: comparative Stated objective of study: compare clinical results of anterior vs. posterior surgery for cervical radiculopathy due to soft disc herniation Type of treatment(s): anterior cervical decompression with fusion (ACDF) using PMMA for median or paramedian discs, posterior laminoforaminotomy (PLF) for posterolateral or foraminal discs Total number of patients: 363 Number of patients in relevant subgroup(s): 363: 154 ACDF, 209 PLF Consecutively assigned? No Duration of follow-up: mean 72 months, minimum 30 months Validated outcome measures used: Nonvalidated outcome measures used: Odoms criteria Diagnosis of cervical radiculopathy made by: Clinical exam/history Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Tendency for patient selection to more lateral disc herniations for posterior procedure, whereas anterior for paramedian and central introduced bias. This study excluded patients with pure hard discs and pure foraminal stenosis (so not consecutively assigned). Work group conclusions: Potential level: III Downgraded level: III Conclusions relative to question:this paper provides evidence that:acdf results in statistically significantly better outcomes than PLF; however, ACDF is associated with a higher risk

176 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 156 Electromyography Myelogram MRI CT CT/Myelogram Other: of complications, primarily related to dysphagia/hoarseness. PLF is associated with a higher reoperation rate. Results/subgroup analysis (relevant to question): Of the 363 patients included in the study, 80% (292/363: 124/154 ACDF, 168/209 PLF) were available for long term follow-up via clinical outpatient examination (14.7%), questionnaire (64.4%), and/or a telephone interview (20.9%). Complication rates, primarily related to hoarseness and dysphagia, were reported in 6.5 % of ACDF patients and 1.8% of PLF patients. Reoperation rates were reported as 2.4% for the ACDF group and 7.1% for the PLF group. Mean operating time in the ACDF group was 112 minutes 94.1 minutes for the PLF group ( p<0.000). Of the patients in the ACDF group, 93.6% (116/124) reported good (36.3%) or excellent (59.5%) results according to Odom's criteria and 0.8% reported poor results (p<0.05). Of the patients in the PLF group, 85.1% (142/168) reported good (25.6%) or excellent (59.5%) results according to Odom's criteria and 7.2% reported poor results (p<0.05). In the ACDF group, a pure soft disc was removed in 60 cases (48.4%) and a mixture of both hard and soft disc elements was removed in 64 (51.6%). In the PLF group, a pure soft disc was removed in 148 cases (88.1%) and a mixture of both hard and soft disc elements was removed in 20 (11.9%) (p<0.000). Soft disc herniations did not have significantly better outcomes than the mixture of soft and hard disc, although there appeared to be a trend. In general, shorter duration of preoperative symptoms correlated with improved outcomes. Author conclusions (relative to question): Anterior surgery yielded statistically superior outcomes, but both were effective. The findings show a higher

177 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 157 Wirth FP, Dowd GC, Sanders HF, Wirth C. Cervical discectomy. A prospective analysis of three operative techniques. Surg Neurol. Apr 2000;53(4): ; discussion Level III Type of evidence: therapeutic success rate with anterior microdiscectomy with PMMA interbody stabilization for treatment of degenerative cervical monoradiculopathy compared with posterior foraminotomy. Prospective Retrospective Study design: RCT Stated objective of study: compare clinical outcomes for surgery for unilateral disc herniation causing radiculopathy Type of treatment(s): anterior cervical decompression (ACD), anterior cervical decompression with fusion (ACDF), posterior laminoforaminotomy (PLF) Total number of patients: 72 Number of patients in relevant subgroup(s): 22 PLF, 25 ACD, 25 ACDF Consecutively assigned? Yes Duration of follow-up: 2 months scheduled visit, mean 60 months by phone or clinic visit Validated outcome measures used: Nonvalidated outcome measures used: Satisfaction; pain; perioperative demographics; complications; scoring scale for outcomes based on return to work, hospital stay, and pain relief Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Imaging; not specified Results/subgroup analysis (relevant to question): Age, gender and duration of symptoms were similar for all groups. Although not specifically stated, follow-up was inclusive. Anesthesia time, hospital Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Functional outcome tools were too broad and subjective. The initial clinical visit occurred at two months; the 60 month follow-up was poorly coordinated and varied. Numbers were small with poor statistical analysis. Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that:acd, ACDF and PLF result in comparable clinical outcomes in the treatment of cervical radiculopathy from unilateral disc herniation.

178 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 158 stay, charges and analgesics were similar. Pain improvement was reported by more than 96% of patients in all groups. It appears that all groups had similar outcomes. Return-to-work was reported as greater than 88% in all groups. Similar incidence of new weakness and new numbness across all groups. Reoperation rate were reported as 27% for the PLF group, 12% for ACD and 28% for ACDF. Author conclusions (relative to question): Although the numbers in this study were small, none of the procedures could be considered superior to the others. This study suggests that the selection of surgical procedure may reasonably be based on the preference of the surgeon and tailored to the individual patient.

179 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 159 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Surgical Treatment Does anterior cervical decompression and reconstruction with total disc replacement result in better outcomes (clinical or radiographic) than anterior cervical decompression and fusion in the treatment of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Murrey D, Janssen M, Delamarter R, et al. Results of the prospective, randomized, controlled multicenter Food and Drug Administration investigational device exemption study of the ProDisc-C total disc replacement versus anterior discectomy and fusion for the treatment of 1- level symptomatic cervical disc disease. Spine J. Apr 2009;9(4): Level of evidence Description of study Conclusion Level I Type of evidence: therapeutic Prospective Study design: RCT Retrospective Stated objective of study: compare safety and efficacy of total disc arthroplasty (TDA) to anterior cervical decompression with fusion (ACDF) for single level symptomatic cervical disc disease with radiculopathy Type of treatment(s): ProDisc TDA, ACDF with allograft and plate Total number of patients: 209 Number of patients in relevant subgroup(s): 106 ACDF, 103 TDA Consecutively assigned? Yes Duration of follow-up: 2 years with followup intervals at 6 weeks, 3 months, 6 months, 12 months and 2 years Validated outcome measures used: Neck Disability Index (NDI), SF-36, Visual Analog Scale (VAS) pain scores Nonvalidated outcome measures used: Neurological exam, VAS satisfaction Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: I Downgraded level: I Conclusions relative to question: This paper provides evidence that:tda shows equivalent outcomes to ACDF at two years for treatment of cervical radiculopathy.

180 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 160 Other: Results/subgroup analysis (relevant to question): There was no difference in demographics between the TDA and ACDF groups. Follow-up rates were 98% for TDA and 94% for ACDF. ACDF had statistically significantly lower smaller blood loss and operative time (although differences small). Neurological improvement was better for TDA than ACDF at six months (p<0.05), but no significant difference was seen 24 months (p=0.638). NDI improved from baseline for each group (p<0.0001); however, between groups there was a significant difference at three months for TDA (p<0.05) but not at 24 months (p=1.0000). This was also true for aggregate patients who had greater than 15 point improvement. Secondary surgical procedure were performed in 1.9% of TDA patients and 8.5% of ACDF patients. Implant revision was required in no TDA patients, but 4.7% of the ACDF patients, with 2.8% of the ACDF patients requiring supplemental fixaton. VAS neck pain, arm pain frequency and intensity was similar for TDA and ACDF patients at 24 months. Success, as defined by greater than 20% improvement in VAS scores, was reported for 87.9% of TDA patients and 86.9% of ACDF patients at 24 months. At 24 months, 80.8% of TDA patients and 74.4% of ACDF patients had successful outcomes as assessed by the SF-36 physical component summary. The SF-36 mental component summary showed 71.8% of TDA and 68.9% of ACDF patients were successful. Patient satisfaction, narcotic use and adverse events were similar for both groups. Nabhan A, Ahlhelm F, Shariat K, et al. The ProDisc-C Level II Type of evidence: Author conclusions (relative to question): TDA with ProDisc is safe and effective and at least as good as ACDF. Prospective Retrospective Study design: RCT Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers

181 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 161 prothesis - Clinical and radiological experience 1 year after surgery. Spine. Aug 2007;32(18): therapeutic Stated objective of study: compare radiographic and clinical results of total disc arthroplasty (TDA) to anterior cervical decompression with fusion ( ACDF) Type of treatment(s): ProDIsc TDA, ACDF with PEEK cage and plate Total number of patients: 49 Number of patients in relevant subgroup(s): 25 TDA and 24 ACDF, all with radiculopathy; however, only 20 TDA and 21 ACDF patients could be measured due to artifact. Consecutively assigned? Yes Duration of follow-up: One year Validated outcome measures used: RSA for dynamic radiographic evaluation Nonvalidated outcome measures used: VAS pain score Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Imaging; not specified Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: They used a good radiographic analysis tool, but chose neutral and extreme extension and lateral rotation for their motion analysis. Clinical evaluation was limited and was not their emphasis. Follow-up of only one year. Also they conclude motion was maintained with TDA; however, it was not. Range of motion was decreased, but significantly greater than with ACDF. Work group conclusions: Potential level: I Downgraded level: II Conclusions relative to question: This paper provides evidence that:compared with ACDF, patients treated with TDA have statistically significantly greater range of motion. Clinical outcomes are similar for both groups. Results/subgroup analysis (relevant to question): Range of motion decreased in both groups. In the TDA group, average motion decreased from 2.3 at one week to 0.8 at 52 weeks; in ACDF, it decreased from 0.6 at one week to 0.1 at 52 weeks. Comparison between groups showed that the motion was significantly less in the ACDF group for all time points except three weeks. Preoperatively, there was no statistical difference in symptoms between both groups (P=0.1), as measured by the VAS. Both groups showed the same pattern of pain relief in arm pain at all examination times without statically significant difference (P=0.13).

182 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 162 The ACDF group showed a higher postsurgical resolving ratio in neck pain relief at three weeks, although without any statistically significant differences (P=0.09). Author conclusions (relative to question): Disc motion was maintained by TDA at one year and was greater than ACDF, with similar clinical results to ACDF.

183 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 163 Evidentiary Table Cervical Radiculopathy from Degenerative Disorders, Surgical Treatment What is the long-term result (four+ years) of surgical management of cervical radiculopathy from degenerative disorders? Article (Alpha by Author) Level of evidence Description of study Conclusion Hamburger C, Festenberg FV, Uhl E. Ventral discectomy with pmma interbody fusion for cervical disc disease: longterm results in 249 patients. Spine. Feb ;26(3): Level IV Type of evidence: therapeutic Prospective Retrospective Study design: case series Stated objective of study: review results of anterior cervical decompression (ACD) with polymethylmethacralate (PMMA) Type of treatment(s): ACD with PMMA Total number of patients: 351 Number of patients in relevant subgroup(s): 319:; 249/319 available for final follow-up Consecutively assigned? No Duration of follow-up: 10 to 15 years, mean 12.2 years Validated outcome measures used: Nonvalidated outcome measures used: Odoms criteria Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: radiograph Results/subgroup analysis (relevant to question): Of the 249 patients available for final follow-up, 246 had single level Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:for the treatment of cervical radiculopathy due to single level disease, ACD with PMMA interbody spacer results in 77% of patients reporting satisfactory clinical outcomes at 10 to 15 years following surgery.

184 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 164 and 3 had two level surgery. Good or excellent results were reported by 87% of patients. Lumbar symptoms and high occupational stress were correlated with clinical failure. Patients with soft disc herniations reported the best results. Relatively worse outcomes were reported when "patients had unclear preoperative findings." Heidecke V, Rainov NG, Marx T, Burkert W. Outcome in Cloward anterior fusion for degenerative cervical spinal disease. Acta Neurochir (Wien). 2000;142(3): Level IV Type of evidence: therapeutic Author conclusions (relative to question): ACD with PMMA is a safe and reliable method for treating monosegmental radiculopathy with outcomes and complication rates similar to other published studies. Prospective Retrospective Study design: case series Stated objective of study: to review outcomes of Cloward type fusion Type of treatment(s): anterior cervical decompression with fusion (ACDF) using Cloward technique and iliac crest bone graft (ICBG) Total number of patients: 156 Number of patients in relevant subgroup(s): 28 patients with radiculopathy only Consecutively assigned? No Duration of follow-up: 4 to 10.5 years, mean 6.5 years Validated outcome measures used: Nonvalidated outcome measures used: three point scale of good, fair and poor; radiographic analysis; neurological exam. Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:for treatment of cervical radiculopathy due to degenerative disease, ACDF with Cloward technique results in 93% satisfactory results with long term (4-10 year) follow-up. Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT

185 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 165 CT/Myelogram Other: Results/subgroup analysis (relevant to question): Of the 28 radiculopathy patients included, long term outcome was reported as good for 93% and fair for 7%. No poor results were reported. Adverse events were dominated by graft site complications. Jagannathan J, Sherman JH, Szabo T, Shaffrey CI, Jane JA. The posterior cervical foraminotomy in the treatment of cervical disc/osteophyte disease: a single-surgeon experience with a minimum of 5 years' clinical and radiographic follow-up. J Neurosurg Spine. Apr 2009;10(4): Level IV Type of evidence: therapeutic Author conclusions (relative to question): Cloward ACDF is a reliable and safe procedure for single level disease. Prospective Retrospective Study design: case series Stated objective of study: review results of posterior foraminotomy (PLF) for treatment of single level cervical radiculopathy Type of treatment(s): PLF Total number of patients: 973 Number of patients in relevant subgroup(s): 212 Consecutively assigned? Yes Duration of follow-up: 5 to 15 years, mean 78 months Validated outcome measures used: Neck Disability Index (NDI) Nonvalidated outcome measures used: Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI CT CT/Myelogram Other: Results/subgroup analysis (relevant to question): Follow-up was reported for Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Work group conclusions: Potential level: IV Downgraded level: IV Conclusions relative to question: This paper provides evidence that:posterior laminoforaminotomy for the treatment of cervical radiculopathy due to degenerative disease results in significant improvement in 93% of cases at 5-15 year follow-up. There may be a trend for patients older than 60 years with initial lordosis of less than 10 degrees to be more vulnerable to development of postoperative cervical kyphosis or translational deformity, though the clinical significance of this is uncertain.

186 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders /212 patients. While NDI improved in 93% of patients, 20% developed kyphosis. Patients who developed kyphosis reported worse results overall. During the follow-up period, 3.1% (5/162) required additional procedures; two had progression of disease at the index level, two developed stenosis and one developed "instability." Wirth FP, Dowd GC, Sanders HF, Wirth C. Cervical discectomy. A prospective analysis of three operative techniques. Surg Neurol. Apr 2000;53(4): ; discussion Level III Type of evidence: therapeutic Author conclusions (relative to question): PLF is highly successful for treating cervical radiculopathy. Prospective Retrospective Study design: RCT Stated objective of study: compare clinical outcomes for surgery for unilateral disc herniation causing radiculopathy Type of treatment(s): anterior cervical discectomy ACD), anterior cervical discectomy with fusion (ACDF), posterior foraminotomy Total number of patients: 72 Number of patients in relevant subgroup(s): 22 PLF, 25 ACD, 25 ACDF Consecutively assigned? Yes Duration of follow-up: 2 months scheduled visit, mean 60 months by phone or clinic visit Validated outcome measures used: Nonvalidated outcome measures used: satisfaction; pain; perioperative demographics; complications; scoring scale for outcomes based on return to work, hospital stay, and pain relief Diagnosis of cervical radiculopathy made by: Clinical exam/history Electromyography Myelogram MRI Critique of methodology: Nonconsecutive patients Nonrandomized Nonmasked reviewers Nonmasked patients No Validated outcome measures used: Small sample size Inadequate length of follow-up <80% follow-up Lacked subgroup analysis Diagnostic method not stated Other: Functional outcome tools were too broad and subjective. The initial clinical visit occurred at two months; the 60 month follow-up was poorly coordinated and varied. Numbers were small with poor statistical analysis. 40% lost to followup. Work group conclusions: Potential level: II Downgraded level: III Conclusions relative to question: This paper provides evidence that:for unilateral radiculopathy caused by cervical disc herniation, ACD, ACDF or posterior foraminotomy result in satisfactory outcomes at five year follow-up.

187 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders 167 CT CT/Myelogram Other: Imaging not stated Results/subgroup analysis (relevant to question): Age, gender and duration of symptoms were similar for all groups. Although not specifically stated, follow-up was inclusive. Anesthesia time, hospital stay, charges and analgesics were similar. Pain improvement was reported by more than 96% of patients in all groups. It appears that all groups had similar outcomes. Return-to-work was reported as greater than 88% in all groups. Similar incidence of new weakness and new numbness across all groups. Reoperation rate were reported as 27% for the PLF group, 12% for ACD and 28% for ACDF. Of the 72 patients included in the study, 60% (43/72) were available at final follow-up [13/25 (52%) for ACD, 16/25 (64%) for ACDF, and 14/22 (64%) for posterior foraminotomy]. Author conclusions (relative to question): ACD, ACDF or posterior foraminotomy are reasonable surgical choices for cervical radiculopathy due to unilateral disc herniation.

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Prospective, multicenter study with independent clinical review. Spine. Mar ;24(6): Sasso RC, Smucker JD, Hacker RJ, Heller JG. Artificial disc versus fusion: a prospective, randomized study with 2-year follow-up on 99 patients. Spine. Dec ;32(26): ; discussion Savolainen S, Rinne J, Hernesniemi J. A prospective randomized study of anterior single-level cervical disc operations with long-term follow-up: surgical fusion is unnecessary. Neurosurgery. Jul 1998;43(1): Scheufler KM, Kirsch E. Percutaneous multilevel decompressive laminectomy, foraminotomy, and instrumented fusion for cervical spondylotic radiculopathy and myelopathy: assessment of feasibility and surgical technique. J Neurosurg Spine. Nov 2007;7(5): Schneeberger AG, Boos N, Schwarzenbach O, Aebi M. Anterior cervical interbody fusion with plate fixation for chronic spondylotic radiculopathy: a 2- to 8-year followup. J Spinal Disord. Jun 1999;12(3): ; discussion Schoggl A, Reddy M, Saringer W, Ungersbock K. 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197 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Scotti G, Scialfa G, Pieralli S, Boccardi E, Valsecchi F, Tonon C. Myelopathy and radiculopathy due to cervical spondylosis: myelographic-ct correlations. AJNR Am J Neuroradiol. May-Jun 1983;4(3): Shad A, Leach JC, Teddy PJ, Cadoux-Hudson TA. Use of the Solis cage and local autologous bone graft for anterior cervical discectomy and fusion: early technical experience. J Neurosurg Spine. Feb 2005;2(2): Shafaie FF, Wippold FJ, 2nd, Gado M, Pilgram TK, Riew KD. Comparison of computed tomography myelography and magnetic resonance imaging in the evaluation of cervical spondylotic myelopathy and radiculopathy. Spine. Sep ;24(17): Shah KC, Rajshekhar V. Reliability of diagnosis of soft cervical disc prolapse using Spurling's test. Br J Neurosurg. Oct 2004;18(5): Shapiro S, Connolly P, Donnaldson J, Abel T. Cadaveric fibula, locking plate, and allogeneic bone matrix for anterior cervical fusions after cervical discectomy for radiculopathy or myelopathy. J Neurosurg. Jul 2001;95(1 Suppl): Shen FH, Samartzis D, Khanna N, Goldberg EJ, An HS. Comparison of clinical and radiographic outcome in instrumented anterior cervical discectomy and fusion with or without direct uncovertebral joint decompression. Spine J. Nov 2004;4(6): Siivola SM, Levoska S, Tervonen O, Ilkko E, Vanharanta H, Keinanen-Kiukaanniemi S. MRI changes of cervical spine in asymptomatic and symptomatic young adults. Eur Spine J. Aug 2002;11(4): Slipman CW, Chow DW. Therapeutic spinal corticosteroid injections for the management of radiculopathies. Phys Med Rehabil Clin N Am. Aug 2002;13(3): Slipman CW, Plastaras CT, Palmitier RA, Huston CW, Sterenfeld EB. Symptom provocation of fluoroscopically guided cervical nerve root stimulation. Are dynatomal maps identical to dermatomal maps? Spine (Phila Pa 1976). Oct ;23(20): Strobel K, Pfirrmann CW, Schmid M, Hodler J, Boos N, Zanetti M. Cervical nerve root blocks: indications and role of MR imaging. Radiology. Oct 2004;233(1): Strub WM, Brown TA, Ying J, Hoffmann M, Ernst RJ, Bulas RV. Translaminar cervical epidural steroid injection: short-term results and factors influencing outcome. J Vasc Interv Radiol. Sep 2007;18(9): Suetsuna F, Yokoyama T, Kenuka E, Harata S. Anterior cervical fusion using porous hydroxyapatite ceramics for cervical disc herniation. a two-year follow-up. Spine J. Sep- Oct 2001;1(5): Sugawara T, Itoh Y, Hirano Y, Higashiyama N, Mizoi K. Long term outcome and adjacent disc degeneration after anterior cervical discectomy and fusion with titanium cylindrical cages. Acta Neurochir (Wien). Apr 2009;151(4): Swezey RL. Conservative treatment of cervical radiculopathy. J Clin Rheumatol. Apr 1999;5(2): Tan J, Zheng Y, Gong L, Liu X, Li J, Du W. Anterior cervical discectomy and interbody fusion by endoscopic approach: a preliminary report. J Neurosurg Spine. Jan 2008;8(1): Tanaka Y, Kokubun S, Sato T. Mini-symposium: Cervical spine: (i) Cervical radiculopathy and its unsolved problems. Curr Orthop. Jan 1998;12(1): Tanaka Y, Kokubun S, Sato T, Ozawa H. Cervical roots as origin of pain in the neck or scapular regions. Spine. Aug ;31(17):E Tegos S, Rizos K, Papathanasiu A, Kyriakopulos K. Results of anterior discectomy without fusion for treatment of cervical radiculopathy and myelopathy. Eur Spine J. 1994;3(2): Teresi LM, Lufkin RB, Reicher MA, et al. Asymptomatic degenerative disk disease and spondylosis of the cervical spine: MR imaging. Radiology. Jul 1987;164(1): Thorell W, Cooper J, Hellbusch L, Leibrock L. The longterm clinical outcome of patients undergoing anterior cervical discectomy with and without intervertebral bone graft placement. Neurosurgery. Aug 1998;43(2): ; discussion Tiso RL, Cutler T, Catania JA, Whalen K. Adverse central nervous system sequelae after selective transforaminal block: the role of corticosteroids. Spine J. Jul-Aug 2004;4(4): Tong HC, Haig AJ, Yamakawa K. The Spurling test and cervical radiculopathy. Spine (Phila Pa 1976). Jan ;27(2): Topuz K, Colak A, Kaya S, et al. Two-level contiguous cervical disc disease treated with peek cages packed with demineralized bone matrix: results of 3-year follow-up. Eur Spine J. Feb 2009;18(2): Troyanovich SJ, Stroink AR, Kattner KA, Dornan WA, Gubina I. Does anterior plating maintain cervical lordosis versus conventional fusion techniques? A retrospective analysis of patients receiving single-level fusions. J Spinal Disord Tech. Feb 2002;15(1): Truumees E, Herkowitz HN. Cervical spondylotic myelopathy and radiculopathy. Instr Course Lect. 2000;49: Tsao B. The Electrodiagnosis of Cervical and Lumbosacral Radiculopathy. Neurologic Clinics. May 2007;25(2): Tseng SH, Lin SM, Chen Y, Wang CH. Ruptured cervical disc after spinal manipulation therapy: report of two cases. Spine. Feb ;27(3):E Van de Kelft E, van Vyve M. Diagnostic imaging algorithm for cervical soft disc herniation. J Neurol Neurosurg Psychiatry. Jun 1994;57(6):

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199 NASS Clinical Guidelines Diagnosis and Treatment of Cervical Radiculopathy from Degenerative Disorders Zoega B, Karrholm J, Lind B. Plate fixation adds stability to two-level anterior fusion in the cervical spine: a randomized study using radiostereometry. Eur Spine J. 1998;7(4): Zoega B, Karrholm J, Lind B. Outcome scores in degenerative cervical disc surgery. European Spine Journal. Apr 2000;9(2):

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201 Pain Physician 2010; 13: ISSN Randomized Trial The Effectiveness of Fluoroscopic Cervical Interlaminar Epidural Injections in Managing Chronic Cervical Disc Herniation and Radiculitis: Preliminary Results of a Randomized, Double- Blind, Controlled Trial Laxmaiah Manchikanti, MD, Kimberly A. Cash, RT, Vidyasagar Pampati, MSc, Bradley W. Wargo, DO, and Yogesh Malla, MD From: Pain Management Center of Paducah, Paducah, KY Dr. Manchikanti is Medical Director of the Pain Management Center of Paducah, Paducah, KY, and Associate Clinical Professor of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY Mrs. Cash is a Research Coordinator at the Pain Management Center of Paducah, Paducah, KY Mr. Pampati is a Statistician at the Pain Management Center of Paducah, Paducah, KY Dr. Wargo is an Interventional Pain Physician at the Pain Management Center of Paducah, Paducah, KY Dr. Malla is an Interventional Pain Physician at the Pain Management Center of Paducah, Paducah, KY Address correspondence: Laxmaiah Manchikanti, MD 2831 Lone Oak Road Paducah, Kentucky drlm@thepainmd.com Disclaimer: There was no external funding in the preparation of this manuscript. Conflict of interest: None. Manuscript received: 04/22/2010 Revised: 05/08/2010 Accepted for publication: 05/10/2010 Free full manuscript: Background: Chronic neck pain is a common problem in the adult population with a typical 12- month prevalence of 30% to 50%. Cervical disc herniation and radiculitis is one of the common conditions described responsible for chronic neck and upper extremity pain. Cervical epidural injections for managing chronic neck pain with disc herniation are one of the commonly performed non-surgical interventions in the United States. However, the literature supporting cervical interlaminar epidural steroids in managing chronic neck pain is scant. Study Design: A randomized, double-blind, controlled trial. Setting: A private interventional pain management practice and specialty referral center in the United States. Objectives: To evaluate the effectiveness of cervical interlaminar epidural injections of local anesthetic with or without steroids in providing effective and long-lasting relief in the management of chronic neck pain and upper extremity pain in patients with disc herniation and radiculitis, and to evaluate the differences between local anesthetic with or without steroids. Methods: Patients were randomly assigned to one of 2 groups: Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 ml); Group II patients received cervical interlaminar epidural injections with 0.5% lidocaine, 4 ml, mixed with 1 ml of nonparticulate betamethasone. Outcomes Assessment: Multiple outcome measures were utilized. They included the Numeric Rating Scale (NRS), the Neck Disability Index (NDI), employment status, and opioid intake. Assessments were done at baseline and 3, 6, and 12 months post-treatment. Significant pain relief was defined as 50% or more; significant improvement in disability score was defined as a reduction of 50% or more. Results: Significant pain relief ( 50%) was demonstrated in 77% of patients in both groups. Functional status improvement was demonstrated by a reduction (> 50%) in the NDI scores in 74% of Group I and 71% of Group II at 12 months. The overall average procedures per year were 3.7 ± 1.1 in Group I and 4.0 ± 0.91 in Group II; the average total relief per year was ± weeks in Group I and ± weeks in Group II over the 52 week study period in the patients defined as successful. The initial therapy was considered to be successful if a patient obtained consistent relief with 2 initial injections lasting at least 4 weeks. All others were considered failures. Limitations: The study results are limited by the lack of a placebo group and a preliminary report of 70 patients, 35 in each group. Conclusion: Cervical interlaminar epidural injections with local anesthetic with or without steroids might be effective in 77% of patients with chronic function-limiting neck pain and upper extremity pain secondary to cervical disc herniation and radiculitis. Key words: Chronic neck pain, cervical disc herniation, upper extremity pain, cervical epidural injections, epidural steroids, local anesthetics CLINICAL TRIAL: NCT Pain Physician ; 13:

202 Pain Physician: May/June 2010; 13: Neck pain is common in the adult general population. It is disabling and costly (1-6). Studies of the prevalence of chronic neck pain and its impact on general health showed 14% of patients reporting Grade II to IV neck pain with a high pain intensity leading to disability (4,5). Cervical disc herniation is considered one of the most common conditions of neck pain, causing radiculitis (7). In a study at the Mayo Clinic, the annual incidence of cervical radiculopathy was determined to be 83 per 100,000 of those between 13 and 91 years old (8). The most commonly involved levels for disc herniation include C6/C7 (45% to 60% of cases), C5/C6 (20% to 25%), and levels C4/C5 and C7/T1, each representing approximately 10% of cases (8). Among the various treatments available for managing cervical disc herniation and radiculitis, epidural steroid injections are one of the most common non-surgical interventions (1,9-15). Cervical epidural injections have been used to treat chronic axial neck and radicular pain from herniated discs, spinal stenosis, post-cervical surgery syndrome, and pain of discogenic origin. Epidural injections in the cervical spine are performed either by interlaminar or transforaminal approaches (1,14,16). However, the evidence for cervical interlaminar epidural injections has been a subject of debate and at best has only moderate success in managing cervical radiculopathy. Benyamin et al (1), in a systematic review of cervical interlaminar epidural injections, determined that the evidence was Level II-1 in managing chronic neck and upper extremity pain. Thus, the epidural injections continue to be controversial, similar to lumbar epidural injections, due to the design of the study (fluoroscopic versus non-fluoroscopic), study size, outcome parameters, duration of follow-up, bias exerted in review, and inappropriate methodology leading to inappropriate conclusions (1,17-27). Benyamin et al (1) included 3 studies meeting inclusion criteria (28-30); however, none were performed under fluoroscopic visualization. The underlying mechanism of epidurally administered local anesthetic and steroids is not clear. It has been hypothesized that the effects of a neural blockade are dependent on the anti-inflammatory properties of corticosteroids (31-38). However, there is also emerging evidence that local anesthetics may be equally effective as steroids in managing spinal pain accompanied with or without disc herniation, secondary to post laminectomy syndrome, and of facet joint origin as well as in multiple other types of nerve blocks (39-51). Cervical epidural injections have not been performed utilizing contemporary interventional pain management techniques with fluoroscopy and targeted delivery of medication. Consequently, this study is undertaken to evaluate the role of cervical interlaminar epidural injections in patients with chronic, functionlimiting, neck pain and upper extremity pain secondary to disc herniation using local anesthetic with or without steroids. The study is designed to evaluate 120 patients. This preliminary report includes 70 patients completing a one-year follow-up. Methods The study is being conducted in a private interventional pain management practice and specialty referral center in the United States. The study is being performed based on Consolidated Standards of Reporting Trials (CONSORT) guidelines (21,22,52,53). The study protocol was approved by the Institutional Review Board (IRB) and registered on the U.S. Clinical Trial Registry with an assigned number of NCT Participants Patients were assigned to one of 2 groups: Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 ml); Group II patients received cervical interlaminar epidural injections with 0.5% lidocaine, 4 ml, mixed with 1 ml or 6 mg of non-particulate betamethasone for a total of 5 ml of injectate. Interventions All patients were provided with the IRB-approved protocol and informed consent which described in detail all aspects of the study and withdrawal process. Pre-Enrollment Evaluation The pre-enrollment evaluation included demographic data, medical and surgical history with co-existing disease(s), radiologic investigations, physical examination, pain rating scores using the Numeric Rating Scale (NRS), work status, opioid intake, and functional status assessment using the Neck Disability Index (NDI). Inclusion Criteria Inclusion criteria were patients with cervical disc herniation or radiculitis; patients who were 18 years of age; patients with a history of chronic functionlimiting neck and upper extremity pain of at least 6 months duration; and patients who were competent to 224

203 Cervical Epidurals In Disc Herniation understand the study protocol and provide voluntary, written informed consent and participate in outcome measurements. Exclusion criteria were previous cervical spine surgery, radiculitis secondary to spinal stenosis without disc herniation, uncontrollable or unstable opioid use, uncontrolled psychiatric disorders, uncontrolled medical illness either acute or chronic, any conditions that could interfere with the interpretation of the outcome assessments, pregnant or lactating women, and patients with a history or potential for adverse reaction(s) to local anesthetics or steroid. Description of Interventions All cervical interlaminar epidural procedures were performed by one physician in an ambulatory surgery setting, in a sterile operating room, under fluoroscopy, with patients in the prone position, under appropriate monitoring with intravenous access and sedation with midazolam and fentanyl. Access to the epidural space was obtained under sterile conditions with loss of resistance techniques under fluoroscopic visualization. The epidural space was entered between C7 and T1 to C5 and C6 with confirmation by injection of non-ionic contrast. Following this, an injection of 5 ml of lidocaine hydrochloride 0.5% preservative free, or 4 ml of lidocaine preservative free mixed with 6 mg of non-particulate betamethasone, was carried out. Repeat cervical epidural injections were provided based on the response to prior cervical epidural injections evaluated by improvement in physical and functional status. Further, repeat cervical epidural injections were performed only when increased levels of pain were reported with deteriorating relief below 50%. Additional Interventions All patients underwent the treatments as assigned. A patient was unblinded on request or if an emergency situation arose. If a patient required additional cervical epidural injections, these were provided based on the patient s response, either after unblinding or without unblinding. If patients chose not to be unblinded, or were non-responsive, and different treatments other than cervical epidural injections were required, they were considered to be withdrawn from the study, and no subsequent data were collected. However, patients who were non-responsive and continued with conservative management were followed without further epidural injections with medical management, unless they requested unblinding. In addition, all patients who were lost to follow-up were considered withdrawn. If patients were unavailable for follow-up, they were considered as lost-to-follow-up. Co-Interventions Most patients were receiving opioids and nonopioid analgesics, adjuvant analgesics; some were involved in a therapeutic exercise program. If patients were improving significantly and the medical necessity for these drugs was lacking, medications were stopped or dosages were decreased. In addition, some dosages were increased, based on medical necessity. All patients continued previously directed exercise programs, as well as their work. Thus, in this study, there was no specific physical therapy, occupational therapy, bracing, or other interventions offered other than the study intervention. Objectives The study was designed to evaluate the effectiveness of cervical epidural injections with or without steroids in managing chronic neck and upper extremity pain secondary to disc herniation or radiculitis in providing effective and long-lasting pain relief and to evaluate the differences between local anesthetic with or without steroids. Outcomes Outcomes measured included NRS, NDI, work status, and opioid intake in terms of morphine equivalents. Assessments were done at baseline, 3, 6, and 12 months post-treatment. Significant improvement was defined as at least 50% pain relief associated with 50% improvement in NDI. The NDI has been shown to be valid and reliable in patients with mechanical neck pain (54-56). Opioid intake was evaluated based on the dosage frequency and schedule of the drug, with conversion to morphine equivalents (57). Patients unemployed or employed on a part-time basis with limited or no employment due to pain were classified as employable. Patients who chose not to work, were retired, or were homemakers (not working, but not due to pain) were not considered in the employment pool. Sample Size The sample size was calculated based on significant pain relief. Considering a 0.05 two-sided significance level, a power of 80%, and an allocation ratio 225

204 Pain Physician: May/June 2010; 13: of 1:1, 55 patients in each group were estimated (58). Allowing for a 10% attrition/ non-compliance rate, 60 subjects were required. Previous studies of interventional techniques identified 50 to 60 patients as appropriate (45-49,51,59). Randomization From a total of 120 patients, 60 patients were randomly assigned into each group. Sequence Generation Randomization was performed by computergenerated random allocations sequence by simple randomization. Allocation Concealment The operating room nurse assisting with the procedure randomized the patients and prepared the drugs appropriately. Implementation Participants were invited to enroll in the study if they met inclusion criteria. One of the 3 nurses assigned as coordinators of the study enrolled the participants and assigned participants to their respective groups. Blinding (Masking) Participants and those administering the interventions were blinded to group assignment. Both solutions were clear; it was impossible to identify if the steroid had been added or not. Further, blinding was ensured by mixing the patients with other patients receiving routine treatment and by not informing the physician performing the procedures which patients were in the study. All one-year follow-up patients were selected by a statistician not involved in patient care. The unblinding results were not disclosed to either the treating physician or other participants or patients. Thus, the nature of blinding was not interrupted. Statistical Methods Statistical analysis included the chi-squared statistic, Fisher s exact test, t-test, and paired t-test. Results were considered statistically significant if the P value was less than Chi-squared statistic was used to test the differences in proportions. Fisher s exact test was used wherever the expected value was less than 5; a paired t-test was used to compare the pre- and post-treatment results of average pain scores and NDI measurements at baseline versus 3, 6, and 12 months. For comparison of mean scores between groups, t-test was performed. Intent-to-Treat-Analysis An intent-to-treat-analysis was performed. Either the last follow-up data or initial data were utilized in patients who dropped out of the study and no other data were available. Sensitivity analysis was performed utilizing best case, worse case, and last follow-up data. Results Participant Flow Figure 1 illustrates the participant flow. Recruitment The recruitment period lasted from August 2007 to April Baseline Data Baseline demographic and clinical characteristics of each group are illustrated in Table 1. There were no significant differences noted. Of the 70 patients included in the study, disc herniation was noted at C5/6 in 9% of the patients, C6/7 in 64% of the patients, and at C7/T1 in 27% of the patients. Analysis of Data Numbers Analyzed A schematic illustration of patient flow is provided in Fig. 1. The study period for one-year follow-up lasted from August 2008 to April Seventy patients completed the one-year follow-up; 35 patients in each group. The data were available in the majority of the included patients. Intent-to-treat analysis was performed due to non-available data on 2 occasions on one patient in Group I, and on 3 occasions on 2 patients in Group II. Based on the number of treatments provided, lack of follow-up was found in 2 of 105 occasions in Group I (2%) or 1 of 35 patients (3%); 3 of 105 occasions (3%) in Group II with 2 of 35 patients (6%) at least one time. Sensitivity Analysis A sensitivity analysis with changes in the numeric pain scores was performed utilizing the last followup score, best case scenario, and worst case scenario. There were no significant differences; therefore, the intention-to-treat analysis with last follow-up visit was used

205 Cervical Epidurals In Disc Herniation Eligible Patients Assessed 166 Patients Excluded Patients Not Meeting Inclusion Criteria = 30 Patients Refusing to Participate = 16 Patients randomized 120 Patients included in this evaluation = 70 Group I (35) Group II (35) Cervical epidural with local anesthetics Cervical epidural with local anesthetics and steroids Patients included in analysis = 35 Patients included in analysis = 35 Patients unblinded or withdrawn = 0 Patients unblinded or withdrawn = 0 All patients received local anesthetic = 5 ml All patients received local anesthetic (4 ml) and non-particulate betamethasone (1mL) = 5 ml Intent to treat analysis was performed on 1 patient on 2 occasions, on 1 occasion at 6 months and at 12 months each for missing data Intent to treat analysis was performed in 2 patients on 1 and 2 occasions, on 1 occasion at 6 months, and on 2 occasions at 12 months for missing data Patients included in analysis = 35 Patients excluded in analysis = 0 Patients included in analysis = 35 Patients excluded in analysis = 0 Fig. 1. Schematic presentation of patient flow at 1-year follow-up

206 Pain Physician: May/June 2010; 13: Table 1. Baseline demographic characteristics. Gender Group 1 (35) Group II (35) Male 31% (11) 40% (14) Female 69% (24) 60% (21) P value Age Mean ± SD 46.7± ± Weight Mean ± SD ± ± Height Mean ± SD 66.0 ± ± Duration of Pain (months) Mean ± SD ± ± Onset of Pain Disc Herniation Levels (at multiple levels) Gradual 54% (19) 47% (16) Injury 46% (16) 53% (19) C3/4 20% (7) 14% (5) C4/5 37% (13) 29% (10) C5/6 63% (22) 63% (22) C6/7 49% (17) 54% (19) C7/T1 11% (4) 6% (2) Numeric Rating Score Mean ± SD 7.8 ± ± Neck Disability Index Mean ± SD 29.8 ± ± N/A Table 2. Pain relief characteristics. Numeric Rating Score Group I (35) Group II (35) Mean ± SD Mean ± SD P value Baseline 7.8 ± ± months 3.2* ± * ± months 3.2* ± * ± months 3.3* ± * ± * indicates significant difference with baseline values (P < 0.001) Outcomes Pain Relief Table 2 illustrates the NRS scores. Pain scores changed significantly from baseline at 3, 6, and 12 months in both groups There were no significant differences between the groups at the follow-up periods. The proportion of patients with significant pain relief of 50% or greater is illustrated in Fig. 2 showing 77% in both Groups I and II at 12 months. There were no significant differences between the groups at the 3-month to 6-month to 12-month periods. Fig. 2. Illustration of significant pain relief ( 50%)

207 Cervical Epidurals In Disc Herniation Functional Assessment Functional assessment results assessed by the NDI are illustrated in Table 3. Significant improvement was seen in the functional status in both groups from baseline to one year. Reduction of Neck Disability Index Scores of at least 50% was seen in 74% (Group I) and 71% (Group II) at 12-months as shown in Fig. 3. There were no significant differences between the groups during follow-up periods. Employment Characteristics Table 4 demonstrates employment characteristics in both groups. Table 3. Functional assessment evaluated by Neck Disability Index. Neck Disability Index Group I (35) Mean ± SD Group II (35) Mean ± SD P value Baseline 29.8 ± ± months 14.6* ± * ± months 13.1* ± * ± months 13.5* ± * ± * indicates significant difference with baseline values (P < 0.001) Fig. 3. Illustration of reduction (at least 50%) in Neck Disability Index from baseline. Table 4. Employment characteristics Employment status Group I Group II Baseline 12 months Baseline 12 months Employed part-time Employed full-time Unemployed (due to pain) Not working Eligible for employment Total Employed Housewife Disabled Retired Total Number of Patients

208 Pain Physician: May/June 2010; 13: Opioid Intake Table 5 illustrates opioid intake between the groups at baseline, at 3 months, at 6 months, and at 12 months. No significant increase in opioid intake was shown. However, opioid intake significantly decreased from the baseline in both groups at 3, 6, and 12 months. Therapeutic Procedural Characteristics Therapeutic procedural characteristics are illustrated in Table 6. Epidural entry was perfomed between C7 and T1 in 31% of patients, between C6 and C7 in 60% of patients, and between C5 and C6 in 9% of patients. Average relief per year showed no significant differences: ± weeks in Group I and ± weeks in Group II. The total number of injections per year was 3.7 ± 1.09 in Group I and 3.7 ± 1.22 in Group II. However, when patients were separated into successful and failed groups, the total number of injections per year was 3.7 ± 1.1 in Group I and 4.0 ± 0.91 in Group II in the successful group, and 4.0 ± 1.41 for Group I and 2.0 ± 2.0 for Group II in the failed group. Total relief of ± weeks was obtained in the successful group in Group I; in Group II it was ± In contrast, the relief was 11.5 ± in Group I and ± weeks in Group II for the failed groups. The initial therapy was considered to be successful if a patient obtained consistent relief with 2 initial injections lasting at least 4 weeks. All others were considered failures. Table 5. Opioid Intake (Morphine Equivalence mg) Opioid intake (Morphine Equivalence mg) Group I (35) Group II (35) Mean ± SD Mean ± SD P value Baseline 61.9 ± ± months 50.5# ± # ± months 48.5# ± # ± months 48.5# ± # ± # indicates significant difference with baseline values (P < 0.05) Table 6. Therapeutic procedural characteristics with procedural frequency, average relief per procedure, and average total relief in weeks over a period of one-year. Successful subjects Failed subjects Combined Group I (33) Group II (31) Group I (2) Group II (4) Group I (35) Group II (35) 1st procedure relief 8.67 ± 9.36 (33) 6.15 ± 4.32 (31) 1.75 ± 1.06 (2) 3.04 ± 4.21 (4) 8.27 ± 9.23 (35) 5.80 ± 4.37 (35) 2nd procedure relief ± 4.98 (32) ± 6.50 (31) 1.0± 1.41 (2) 2.00 (1) ± 5.38 (34) ± 6.61 (32) 3rd procedure relief ± 5.49 (28) ± 5.46 (28) 2.64 ± 3.34 (2) 9.00 (1) ± 5.87 (23) ± 5.40 (29) 4th procedure relief ± 2.20 (22) ± 2.38 (24) (1) ± 2.15 (23) ± 2.40 (25) 5th procedure relief 8.57 ± 5.13 (7) ± 2.60 (9) (1) 7.50 ± 5.63 (8) ± 2.50 (10) Number of procedures per year 3.7 ± 1.1 (33) 4.0 ± 0.91 (31) 4.0 ± 1.41 (2) 2.0 ± 2.0 (4) 3.7 ± 1.09 (35) 3.7 ± 1.22 (35) Average relief per procedure ± 8.25 (33) ± 3.42 (31) 2.50 ± 2.12 (2) 4.05 ± 4.73 (4) ± 8.31 (35) 9.82 ± 4.09 (35) Total relief per year (weeks) ± (33) ± (31) 11.5 ± (2) ± (4) ± (35) ± (35) 230

209 Cervical Epidurals In Disc Herniation Table 7. Characteristics of changes in weight. Weight (lbs) Changes in Weight There were no differences in change (gain or loss) in body weight from baseline in both groups (Table 7). Adverse Events Of the 262 cervical epidural procedures performed, there were 3 subarachnoid punctures. In all cases of subarachnoid entry, reentry was carried out at a different level and the procedure was completed. At the same time, all the patients were given 1,000 mg of caffeine infusion. None of them developed post lumbar puncture headaches. Nerve root irritation was observed in 3 patients without any long-term sequelae. All patients experiencing nerve root irritation, even though transient, were given 8 mg of Decadron intravenously. Discussion Group I (35) Group II (35) P Mean ± SD Mean ± SD value Weight at beginning ± ± Weight at one year ± ± Change -1.0 ± ± Lost weight 37% (13) 49% (17) No change 23% (8) 14% (5) Gained weight 40% (14) 37% (13) This preliminary report of the one-year follow-up of a randomized trial of 70 patients demonstrates significant pain relief ( 50%) in 77% of patients in both groups as well as significant improvement in functional status (50% or greater reduction in NDI scores) in 74% to 71% of patients. No significant differences are noted whether or not the injectates contained steroids. The overall average procedures per year was 3.7 ± 1.09 in Group I and 3.7 ± 1.22 in Group II, with an average total relief per year of ± weeks for Group I and ± weeks for Group II, for the 52 week period. Opioid intake was significantly reduced in both groups, along with pain relief and improvement in functional status. Despite significant use of epidural injections in the cervical spine, there have been only 2 systematic reviews (1,60), and a Cochrane review of medicinal and injection therapies for mechanical neck disorders (61). Of the randomized evaluations included in the evidence synthesis (28-30), Benyamin et al (1) concluded that all 3 studies showed positive results for short-term relief, whereas 2 were positive for long-term relief; the results of long-term relief were not available for one study (30), defining short-term relief as 6 months, and long-term relief as greater than 6 months. As illustrated in the present study, cervical interlaminar epidural injections of local anesthetic with or without steroids do not provide long-term relief, even though long-term relief can be achieved by appropriate patient evaluation and judicious use of repeat injection therapy. The study illustrates an average relief of to weeks in the therapeutic phase after 2 initial injections. These results are similar to patients with low back pain treated with caudal epidural injections with or without steroids with or without lumbar disc herniation utilizing the same methodology. In addition, previous observational studies included homogeneous population, which also included patients with discogenic pain; however, there have not been any randomized trials or observational studies incorporating only discogenic pain after exclusion of cervical facet joint pain. Thus, the results of this trial reinforce previous findings (28-30) of the effectiveness of cervical interlaminar epidural injections with longterm follow-up. Further, this study also provides insight into successful or failed groups based on the first 2 procedures. The patients in the successful group who had good pain relief with the first and second procedures showed average relief from to weeks out of 52 weeks. The average number of procedures per year was 3.7. In contrast, in the failed group, the average relief per procedure was 2.5 to 4.05 weeks, with overall 11.5 to weeks of relief in one year. One of the advantages of this evaluation is its generalizability to interventional pain management settings. Further, this is the first study performed under fluoroscopic visualization in the United States, which is considered to be a practical clinical trial, providing more generalizability than a placebo controlled trial. Consequently, the results of this study can be applied to individual patients or groups that differ from those controlled in the placebo trials. Pragmatic or practical clinical trials (with an active control) measuring effectiveness are considered more appropriate than explanatory trials measuring efficacy (20-24,62-67). Pragmatic trials are best designed to provide the results of treatment benefits produced in routine clinical practice, in contrast to explanatory trials (placebo control) that measure efficacy. Utilizing an active con

210 Pain Physician: May/June 2010; 13: trol design, as in this study, the evidence is based on head-to-head comparisons of clinically relevant alternatives used in routine clinical practice, which include local anesthetic with or without steroids. In contrast, a placebo control trial measures absolute effect size and shows the existence of effect. The present design with active control shows not only the existence of effect, but also compares 2 commonly used therapies (67). This study is also different from other studies since we used repeat cervical interlaminar epidural injections based on the requirement that there be an increase in pain and deterioration in functional status, rather than routinely providing 3 injections or being limited to 3 procedures or limiting them even to only one or 2 procedures. Further, this study also has taken into consideration that the initial 2 procedures do not last for long periods of time. If the initial relief did not last more than one to 3 weeks, then the procedures did not provide long-term relief in patients as observed in the failed subjects. The study may be criticized or considered as deficient due to the lack of a placebo group and preliminary analysis. Conducting clinical trials with a placebo group is extremely difficult in the United States with interventional techniques. External validity, also known as applicability, is the extent to which the results of the study can be generalized to other circumstances and the general population, and is best provided with pragmatic or active control trials such as this one. The issue of a lack of a placebo group is addressed in pragmatic trials with a treatment response that accounts for the total difference between 2 treatments, as well as associated placebo effects, thus providing the internal validity. This preliminary report might resolve to some extent the issue of local anesthetics with or without steroids in managing chronic function-limiting neck pain and upper extremity pain with disc herniation or radiculitis. These results describe a pattern of practice in the United States in an interventional pain management setting. Thus, the results may not be applicable in the general population unless the same methodology is utilized under fluoroscopy. In addition, the generalizability of the findings of any study might only be feasible if studies are conducted with larger populations in multiple settings. Placebo-controlled neural blockade is not realistic even though it has been misinterpreted (68,69). Some have mistakenly reported that any local anesthetic injection which yields similar results as steroids is considered a placebo. However, these interpretations are inaccurate. Further, the difference between injections of sodium chloride solution and dextrose have been shown (70). The experimental and clinical findings from investigation of the electrophysiological effects of 0.9% sodium chloride and dextrose 5% in water solution have added new knowledge and controversy to multiple aspects of neural stimulation used in regional anesthesia. The potential inaccuracy created by 0.9% sodium chloride solution versus 5% dextrose has been described (70,71). The evidence also has shown differing effects of sodium chloride solution when injected into either the disc, the facet joint, or paraspinal muscles (72,73). Indahl et al (72,73) studied the electromyographic response of the porcine multifidus musculature after nerve stimulation (73) and interaction between the porcine lumbar intervertebral disc, zygapophysial joints, and paraspinal muscles (72). They showed that stimulation of the disc and the facet joint capsule produced contractions in the multifidus fascicles (73). They also demonstrated the introduction of lidocaine into the facet joint resulted in a significantly reduced electromyographic response with the most drastic reduction seen when stimulating the facet joint capsule. Surprisingly, they (72) also showed that the introduction of physiologic saline into the zygapophysial joint reduced the stimulation pathway from the intervertebral disc to the paraspinal musculature. Consequently, they hypothesized that the paraspinal muscle activation caused by nerve stimulation in the annulus fibrosus of a lumbar intervertebral disc could be altered by a saline injection into the zygapophysial joint. While the mechanism of action of steroids and local anesthetic has been described (30-43,74-80), there is emerging evidence that local anesthetics may be equally as effective as steroids in managing low back and neck pain without disc herniation and also pain of facet joint origin (44-51). It has been reported that multiple pathophysiologic mechanisms involved in chronic pain, including noxious peripheral stimulation, excess nociception resulting in the sensitization of the pain pathways at several neuronal levels, and excess release of neurotransmitters causing complex central responses including hyperalgesia or wind-up (30), result in an increase in nociceptive sensitization of the nervous system (80,81) and phenotype changes which are also considered as part of the neuronal plasticity (80-82). Thus, there is evidence for the long-term effect of either local anesthetics or steroids in managing radicular pain. Corticosteroid anti-inflammatory 232

211 Cervical Epidurals In Disc Herniation properties have been associated with the inhibition of prostaglandin synthesis and decreases in regional levels or inflammatory mediators such as interleukin- 1, tumor necrosis factor, and phospholipase A2 (30-43,83-90). The results of this preliminary report show no significant improvement with corticosteroids in managing chronic neck pain with or without upper extremity pain. In addition, corticosteroids are also known to possess direct neurotoxic effects on peripheral nerve tissue unlike local anesthetics (74,91-93). In summary, the evidence in this preliminary evaluation of a randomized, controlled, double-blind trial demonstrates that cervical interlaminar epidural injections in patients with disc herniation and radiculitis supports that patients may be treated with cervical interlaminar epidural injections with or without steroids. Conclusion The assessment of preliminary results of this randomized, controlled, double-blind trial of cervical interlaminar epidural injections in chronic function-limiting neck pain and upper extremity pain with disc herniation and radiculitis demonstrated significant pain relief in 77% of patients with improvement in functional status, requiring 3.7 procedures per year and providing almost 38 weeks of relief during a 52-week period in appropriately selected patients. Acknowledgements The authors wish to thank Sekar Edem for assistance in search of literature, Tom Prigge for manuscript review, and Tonie M. Hatton and Diane E. Neihoff, transcriptionists, for their assistance in preparation of this manuscript. We would like to thank the editorial board of Pain Physician for review and criticism in improving the manuscript. References 1. Benyamin RM, Singh V, Parr AT, Conn A, Diwan S, Abdi S. Systematic review of the effectiveness of cervical epidurals in the management of chronic neck pain. Pain Physician 2009; 12: Manchikanti L. Singh V, Datta S, Cohen SP, Hirsch JA. Comprehensive review of epidemiology, scope, and impact of spinal pain. Pain Physician 2009; 12: E35-E Hogg-Johnson S, van der Velde G, Carroll LJ, Holm LW, Cassidy JD, Guzman J, Côté P, Haldeman S, Ammendolia C, Carragee E, Hurwitz E, Nordin M, Peloso P, Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders. The burden and determinants of neck pain in the general population: Results of the Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders. Spine (Phila Pa 1976) 2008; 33: S39-S Côté P, Cassidy JD, Carroll L. The Saskatchewan Health and Back Pain Survey. The prevalence of neck pain and related disability in Saskatchewan adults. Spine (Phila Pa 1976) 1998; 23: Côté P, Cassidy JD, Carroll LJ, Kristman V. The annual incidence and course of neck pain in the general population: A population-based cohort study. Pain 2004; 112: Côté P, Kristman V, Vidmar M, Van Eerd D, Hogg-Johnson S, Beaton D, Smith PM. The prevalence and incidence of work absenteeism involving neck pain: A cohort of Ontario lost-time claimants. Spine (Phila Pa 1976) 2008; 33:S192- S Carette S, Fehlings MG. Clinical practice. Cervical radiculopathy. N Engl J Med 2005; 353: Radhakrishnan K, Litchy WJ, O Fallon WM, Kurland LT. Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through Brain 1994; 117: Van Zundert J, Harney D, Joosten EA, Durieux ME, Patijn J, Prins MH, Van Kleef M. The role of the dorsal root ganglion in cervical radicular pain: Diagnosis, pathophysiology, and rationale for treatment. Reg Anesth Pain Med 2006; 31: Manchikanti L. Medicare in interventional pain management: A critical analysis. Pain Physician 2008; 11: Manchikanti L, Pampati V, Boswell MV, Smith HS, Hirsch JA. Analysis of the growth of epidural injections and costs in the Medicare population: A comparative evaluation of 1997, 2002, and 2006 data. Pain Physician 2010; 13: Manchikanti L, Singh V, Pampati V, Smith HS, Hirsch JA. Analysis of growth of interventional techniques in managing chronic pain in Medicare population: A 10-year evaluation from 1997 to Pain Physician 2009; 12: Manchikanti L, Singh V, Derby R, Schultz DM, Benyamin RM, Prager JP, Hirsch JA. Reassessment of evidence synthesis of occupational medicine practice guidelines for interventional pain management. Pain Physician 2008; 11: Manchikanti L, Boswell MV, Singh V, Benyamin RM, Fellows B, Abdi S, Buenaventura RM, Conn A, Datta S, Derby R, Falco FJE, Erhart S, Diwan S, Hayek SM, Helm S, Parr AT, Schultz DM, Smith HS, Wolfer LR, Hirsch JA. Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physi

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215 Pain Physician 2012; 15:E405-E434 ISSN Systematic Review Effectiveness of Cervical Epidural Injections in the Management of Chronic Neck and Upper Extremity Pain Sudhir A. Diwan, MD 1, Laxmaiah Manchikanti, MD 2, Ramsin M. Benyamin, MD 3, David A. Bryce, MD 4, Stephanie Geffert, MLIS 5, Haroon Hameed, MD 6, Manohar Lal Sharma, MD 7, Salahadin Abdi, MD, PhD 8, and Frank J.E. Falco, MD 9 From: 1 The Spine and Pain Institute of New York,, New York, NY; 2 Pain Management Center of Paducah, Paducah, KY; and University of Louisville, Louisville, KY; 3 Millennium Pain Center, Bloomington, IL; and 3 University of Illinois, Urbana-Champaign, IL; 4 Advanced Pain Management, Madison, WI; 5,9 Mid Atlantic Spine & Pain Physicians of Newark, Newark, De; and 5,9 Temple University Hospital, Philadelphia, PA; 6 The Johns Hopkins University School of Medicine, Baltimore, MD; 7 The Walton Centre for Neurology and Neurosurgery NHS Foundation Trust, Liverpool, United Kingdom; and 8 Beth Israel Deaconess Medical Center, Brookline, ME, and 8 Harvard Medical School, Boston, MA. Author affiliation information on page E425. Address correspondence: Sudhir A. Diwan, MD 860 5th Avenue New York, NY sudhir.diwan63@gmail. com Disclaimer: There was no external funding in the preparation of this manuscript. Conflict of interest: None. Manuscript received: 05/12/2012 Accepted for publication: 06/28/2012 Free full manuscript: www. painphysicianjournal.com Background: Chronic persistent neck pain with or without upper extremity pain is common in the general adult population with prevalence of 48% for women and 38% for men, with persistent complaints in 22% of women and 16% of men. Multiple modalities of treatments are exploding in managing chronic neck pain along with increasing prevalence. However, there is a paucity of evidence for all modalities of treatments in managing chronic neck pain. Cervical epidural injections for managing chronic neck pain are one of the commonly performed interventions in the United States. However, the literature supporting cervical epidural steroids in managing chronic pain problems has been scant. Study Design: A systematic review of cervical interlaminar epidural injections for cervical disc herniation, cervical axial discogenic pain, cervical central stenosis, and cervical postsurgery syndrome. Objective: To evaluate the effect of cervical interlaminar epidural injections in managing various types of chronic neck and upper extremity pain emanating as a result of cervical spine pathology. Methods: The available literature on cervical interlaminar epidural injections in managing chronic neck and upper extremity pain were reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria as utilized for interventional techniques for randomized trials and the criteria developed by the Newcastle-Ottawa Scale criteria for observational studies. The level of evidence was classified as good, fair, and limited based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to December 2011, and manual searches of the bibliographies of known primary and review articles. Outcome Measures: The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term > 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake. Results: For this systematic review, 34 studies were identified. Of these, 24 studies were excluded and a total of 9 randomized trials, with 2 duplicate studies, met inclusion criteria for methodological quality assessment. For cervical disc herniation, the evidence is good for cervical epidural with local anesthetic and steroids; whereas, it was fair with local anesthetic only. For axial or discogenic pain, the evidence is fair for local anesthetic, with or without steroids. For spinal stenosis, the evidence is fair for local anesthetic, with or without steroids. For postsurgery syndrome, the evidence is fair for local anesthetic, with or without steroids. Limitations: The limitations of this systematic review continue to be the paucity of literature. Conclusion: The evidence is good for radiculitis secondary to disc herniation with local anesthetics and steroids, fair with local anesthetic only; whereas, it is fair for local anesthetics with or without steroids, for axial or discogenic pain, pain of central spinal stenosis, and pain of post surgery syndrome. Key words: Cervical disc herniation, cervical axial discogenic pain, cervical central spinal stenosis, cervical post surgery syndrome, cervical radiculitis, cervical interlaminar epidural injections, local anesthetic, steroids Pain Physician 2012; 15:E405-E434

216 Pain Physician: July/August 2012; 15:E405-E434 Chronic persistent neck pain has been reported to be present in almost 50% of the individuals who report neck pain at some point (1-3). Further, neck pain is common in the general adult population with a prevalence of 48% in women and 38% in men, with persistent complaints of 22% in women and 16% in men. Studies of the prevalence of chronic neck pain (1-11) and its impact on general health (6,11,12) showed 14% of patients reporting Grade II to IV neck pain with high pain intensity with disability. Similar to low back pain, neck pain is also associated with significant economic, societal, and health impact, though not to the same extent as low back pain. In fact, neck pain has been well recognized as a source of disability in the working population (13-17). In addition, motor vehicle injuries result in 24% to 50% of those involved with persistent symptoms at 12 months (18,19). Multiple structures causing neck and upper extremity pain and headache include cervical intervertebral disc, cervical facet joints, atlanto-axial and atlanto-occipital joints, ligaments, fascia, muscles, and nerve root dura which are capable of transmitting pain. However, very little is known about the causes of neck pain. The epidemiologic studies do not reveal either the source or the cause of pain. Bogduk (20) described that neck pain and cervical radicular pain are distinct entities. Neck pain may be due to zygapophyseal or facet joints and intervertebral discs of the neck. Cervical radicular pain is pain perceived in the upper extremity, shooting or electric in quality, caused by irritation and/or injury of a cervical spinal nerve (20,21). Cervical radiculopathy is a neurological condition characterized by objective signs of loss of neurologic function: some combination of sensory loss, motor loss, or impaired reflexes, in a segmental distribution, however, without description of pain. Consequently, cervical radicular pain cannot be similarly attributed to the same cause as those of radiculopathy. Compression of axons does not elicit pain (20). If compression is to be invoked as a mechanism for pain it must explicitly relate to the compression of a dorsal root ganglion (22). In fact, laboratory experiments on lumbar nerve roots have shown that mechanical compression of nerve roots does not elicit activity in nociceptive afferent fibers (23). However, compression of a dorsal root ganglion does evoke sustained activity in afferent fibers; but, that activity occurs in A-beta fibers as well as C-fibers (23). Thus, in contrast to compression, there is growing evidence that cervical radicular pain may be caused by inflammation of the cervical nerve roots (20). This mechanism might be applicable to radicular pain caused by disc protrusions because inflammatory exudates have now been isolated from cervical disc material (24,25). The study from the Mayo Clinic shows an annual incidence of cervical radicular pain of 83 per 100,000 (26). According to this study, the most frequently involved level was C7 in 45% to 60% of the cases. Lotz and Ulrich (27) described that symptoms derived from a degenerated disc may be classified into 2 types: type 1, radicular pain secondary to stenosis and nerve root, and, type 2, discogenic pain due to internal disc disruption. Bogduk and Aprill (28) investigated the prevalence of zygapophysial and discogenic pain and the results showed discogenic pain without zygapophysial joint pain in 20% of the sample, whereas both a symptomatic disc and a symptomatic zygapophysial joint were identified in the same segment in 41% of the patients. Thus, based on controlled diagnostic blocks, cervical facet joints have been implicated as being responsible for pain in the neck, head, and upper extremities in 36% to 67% of patients (29-36), whereas reports of cervical discogenic pain (28,29) show a prevalence of 16% to 20%. Further, Yin and Bogduk (29) reported that of the 143 patients with chronic neck pain, only 5 patients were diagnosed with cervical radicular pain on the basis of history and clinical examination, while the remaining patients had idiopathic neck pain. It has been shown that, by far, the most common causes of cervical radicular pain are disc protrusion and cervical spondylosis (21,26,37-43). Numerous modalities of treatments have been described in managing chronic persistent neck pain with or without upper extremity pain (21,44-71), with exploding costs creating a health care financial crisis. Epidural injections for managing chronic neck pain are one of the commonly performed interventions in the United States (64,67,69-74). Cervical epidural injections have been used to treat radicular pain from herniated discs, spinal stenosis, chemical discs, chronic pain secondary to postcervical surgery syndrome, and chronic neck pain of discogenic origin. Epidural injections in the cervical spine are performed either by interlaminar or transforaminal approaches. Cervical epidural steroid injections, specifically utilizing the transforaminal approach, have been associated with significant complications (75-85). These complications are much more severe and significant with the transforaminal approach (75,76). However, significant complications also have been reported with interlaminar epidurals with spinal cord damage and quadriparesis (77,78). Complications E406

217 Effectivenss of Cervical Epidural injections of fluoroscopically guided interlaminar cervical epidural injections have been reported to be much less frequent and major complications are extremely rare (80-84,86). The safety of interlaminar epidurals may be due to vulnerable arteries and ischemic neurologic injuries after transforaminal epidural injections (85). Huston (84) reviewed both interlaminar and transforaminal epidural injections in the cervical region. Even though the prevalence of dural puncture is higher with interlaminar epidural injections, other major complications are less stout (84). A review of epidural steroid injections (83) for cervical radiculopathy concluded that there was greater risk of major and devastating complications with cervical transforaminal epidural injections compared to interlaminar epidural steroid injections related to the risk of arterial puncture and injection. In a national survey of technical aspects of epidural steroid injections Cluff et al (87) reported that only 39% of interlaminar epidural injections were performed under fluoroscopy in academic settings compared to 73% in private practice settings. Stojanovic et al (88) evaluated the role of fluoroscopy in cervical epidural steroid injections. They found a 53% rate of lose of resistance during the first attempt to enter the epidural space. Unilateral epidural contrast spread was found in 51% and ventral epidural spread was found in 28% of cases. The average number of cervical vertebral levels covered with 2 ml of contrast was 3.14, with significantly wider spread noted in those patients who had not had undergone previous cervical laminectomy. Multiple authors (88-90) studied epidurography contrast patterns. Kim et al (89) performed all epidural injections at C6-C7 levels with epidurography with injection of 1, 2, or 3 ml of contrast. The rate of ventral epidural spread of 56.7% in Group A with 1 ml of injection, 90% in Group B with 2 ml of contrast, and 93.3% in Group C with 3 ml of contrast. They concluded that 2 ml of contrast injection was optimal. Goel and Pollan (90), in their study with cervical epidural steroid injections performed in the midline at C6-C7 and C7-T1, found the contrast consistently covered the dorsal cervical epidural space bilaterally, irrespective of the volume used or neck flexion angle used. Goodman et al (91) described optimizing patient positioning and fluoroscopic imaging for the performance of cervical interlaminar epidural steroid injections. Compared to the lumbar spine, in the cervical spine, the epidural space is smaller (92,93). In addition, there is also reported to be a higher incidence of discontinuity in the ligamentum flavum. Consequently, both of these factors can result in a higher rate of dural puncture during cervical interlaminar epidural injections, which can lead to rare but potentially serious complications (92,93). There have been 2 systematic reviews (70,94), multiple guidelines (2), a Cochrane review of medicinal and injection therapies for mechanical neck disorders (7), and a document reassessing the evidence of the American College of Occupational and Environmental Medicine (ACOEM) guidelines (95) that included analysis of cervical epidural injections. However, the evidence for cervical interlaminar epidural injections has been a subject of debate and at best has had only moderate success in managing cervical radiculopathy, while there was no evidence available in the management of axial or discogenic neck pain, spinal stenosis, or postsurgery syndrome at the time of these evaluations. Benyamin et al (70) in a systematic review of the effectiveness of cervical epidurals in the management of chronic neck pain illustrated moderate evidence for cervical epidurals in the management of chronic neck and upper extremity pain. Recent publications of epidural injections utilizing fluoroscopy also provide the basis for emerging literature on the effectiveness of cervical epidural injections. Thus, the purpose of this systematic review is to evaluate cervical epidural injections with or without steroids in the management of chronic neck pain and upper extremity pain. 1.0 Methods The methodology utilized in this systematic review followed the review process derived from evidencebased systematic reviews and meta-analysis of randomized trials and observational studies (2,96-104), Consolidated Standards of Reporting Trials (CONSORT) guidelines for the conduct of randomized trials ( ), Standards for Reporting Observational Studies (STROBE) (109), Cochrane guidelines (96,101,102), Chou and Huffman s guidelines (110), and quality of reporting of analysis (98). 1.1 Criteria for Considering Studies for This Review Types of Studies Randomized controlled trials (RCTs) Non-randomized observational studies Case reports and reviews for adverse effects E407

218 Pain Physician: July/August 2012; 15:E405-E Types of Participants Participants of interest were adults aged at least 18 years with chronic neck and/or upper extremity pain of at least 3 months duration. Participants must have failed previous pharmacotherapy, exercise therapy, etc., prior to starting interventional pain management techniques Types of Interventions The interventions were cervical interlaminar epidural injections appropriately performed with proper technique preferably under fluoroscopic or CT guidance Types of Outcome Measures The primary outcome parameter was pain relief. The secondary outcome measures were functional improvement; change in psychological status; return to work; reduction or elimination of opioid use, other drugs, or other interventions; and complications. At least 2 of the review authors independently, in an unblinded standardized manner, assessed the outcomes measures. Any disagreements between reviewers were resolved by a third author and consensus. 1.2 Literature Search Searches were performed from the following sources without language restrictions: 1. PubMed from EMBASE from Cochrane Library 4. U.S. National Guideline Clearinghouse (NGC) 5. Previous systematic reviews and cross references 6. Clinical Trials The search period was from 1966 through December Search Strategy The search strategy emphasized chronic neck and upper extremity pain, disc herniation, discogenic pain, post cervical surgery syndrome, cervical spinal stenosis, and radiculitis or radiculopathy treated with cervical interlaminar epidural injections. At least 2 of the review authors independently, in an unblinded standardized manner, performed each search. Accuracy was confirmed by a statistician. All searches were combined to obtain a unified search strategy. Any disagreements between reviewers were resolved by a third author and consensus. 1.4 Data Collection and Analysis The review focused on randomized trials, observational studies, and reports of complications. The population of interest was patients suffering with chronic neck and upper extremity pain for at least 3 months. Only cervical interlaminar epidural injections with or without steroids were evaluated. All of the studies providing appropriate management and with outcome evaluations of one month or longer and statistical evaluations were reviewed. Reports without appropriate diagnosis, non-systematic reviews, book chapters, and case reports were excluded Selection of Studies In an unblinded standardized manner, 2 review authors screened the abstracts of all identified studies against the inclusion criteria. All articles with possible relevance were then retrieved in full text for comprehensive assessment of internal validity, quality, and adherence to inclusion criteria Inclusion and Exclusion Criteria The following are the inclusion and exclusion criteria: 1. Are the patients described in sufficient detail to allow one to decide whether they are comparable to those who are treated in interventional pain management clinical practices? A. Setting office, hospital, outpatient, inpatient B. Physician interventional pain physician, general physician, anesthesiologist, physiatrist, neurologist, rheumatologist, orthopedic surgeon, neurosurgeon, etc. C. Patient characteristics - duration of pain D. Non-interventional techniques or surgical intervention in the past 2. Is the intervention described in sufficient detail to enable one to apply its use to patients in interventional pain management settings? A. Nature of intervention B. Frequency of intervention C. Duration of intervention E408

219 Effectivenss of Cervical Epidural injections 3. Were clinically relevant outcomes measured? A. Proportion of pain relief B. Disorder/specific disability C. Functional improvement D. Allocation of eligible and non-eligible patients to return to work E. Ability to work Clinical Relevance The clinical relevance of the included studies were evaluated according to 5 questions recommended by the Cochrane Back Review Group (Table 1) (100,111). Each question was scored as positive (+) if the clinical relevance item was met, negative ( ) if the item was not met, and unclear (?) if data were not available to answer the question Methodological Quality or Validity Assessment Even though none of these instruments or criteria have been systematically assessed, the advantages and disadvantages of each system were debated. The methodological qualities assessment was performed by 2 review authors who independently assessed, in an unblinded standardized manner, the internal validity of all the studies. The methodological quality assessment was performed in a manner to avoid any discrepancies which were evaluated by a third reviewer and settled by consensus. The quality of each individual article used in this analysis was assessed by Cochrane review criteria (Table 2) (101) for randomized trials and Newcastle-Ottawa Table 1. Clinical relevance questions. A) Are the patients described in detail so that one can decide whether they are comparable to those who are treated in a clinical practice? B) Are the interventions and treatment settings described in sufficient detail to apply its use in clinical practice? C) Were clinically relevant outcomes measured and reported? D) Is the size of the effect clinically meaningful? E) Do the likely treatment benefits outweigh the potential harms? P (+) N (-) U (unclear) Scoring adapted and modified from Staal JB, et al. Injection therapy for subacute and chronic low-back pain. Cochrane Database Syst Rev 2008; 3:CD (111). Table 2. Randomized controlled trials quality rating system. A 1. Was the method of randomization adequate? A random (unpredictable) assignment sequence. Examples of adequate methods are coin toss (for studies with 2 groups), rolling a die (for studies with 2 or more groups), drawing of balls of different colors, drawing of ballots with the study group labels from a dark bag, computergenerated random sequence, pre-ordered sealed envelopes, sequentially ordered vials, telephone call to a central office, and pre-ordered list of treatment assignments. Examples of inadequate methods are alternation, birth date, social insurance/security number, date in which they are invited to participate in the study, and hospital registration number. Yes/No/ Unsure B 2. Was the treatment allocation concealed? Assignment generated by an independent person not responsible for determining the eligibility of the patients. This person has no information about the persons included in the trial and has no influence on the assignment sequence or on the decision about eligibility of the patient. Yes/No/ Unsure C Was knowledge of the allocated interventions adequately prevented during the study? 3. Was the patient blinded to the intervention? This item should be scored yes if the index and control groups are indistinguishable for the patients or if the success of blinding was tested among the patients and it was successful. Yes/No/ Unsure 4. Was the care provider blinded to the intervention? This item should be scored yes if the index and control groups are indistinguishable for the care providers or if the success of blinding was tested among the care providers and it was successful. Yes/No/ Unsure E409

220 Pain Physician: July/August 2012; 15:E405-E434 Table 2. Randomized controlled trials quality rating system. 5. Was the outcome assessor blinded to the intervention? Adequacy of blinding should be assessed for the primary outcomes. This item should be scored yes if the success of blinding was tested among the outcome assessors and it was successful or: for patient-reported outcomes in which the patient is the outcome assessor (e.g., pain, disability): the blinding procedure is adequate for outcome assessors if participant blinding is scored yes for outcome criteria assessed during scheduled visit and that supposes a contact between participants and outcome assessors (e.g., clinical examination): the blinding procedure is adequate if patients are blinded, and the treatment or adverse effects of the treatment cannot be noticed during clinical examination for outcome criteria that do not suppose a contact with participants (e.g., radiography, magnetic resonance imaging): the blinding procedure is adequate if the treatment or adverse effects of the treatment cannot be noticed when assessing the main outcome for outcome criteria that are clinical or therapeutic events that will be determined by the interaction between patients and care providers (e.g., co-interventions, hospitalization length, treatment failure), in which the care provider is the outcome assessor: the blinding procedure is adequate for outcome assessors if item 4 (caregivers) is scored yes for outcome criteria that are assessed from data of the medical forms: the blinding procedure is adequate if the treatment or adverse effects of the treatment cannot be noticed on the extracted data. Yes/No/ Unsure D Were incomplete outcome data adequately addressed? 6. Was the drop-out rate described and acceptable? The number of participants who were included in the study but did not complete the observation period or were not included in the analysis must be described and reasons given. If the percentage of withdrawals and drop-outs does not exceed 20% for short-term follow-up and 30% for long-term follow-up and does not lead to substantial bias a yes is scored. (N.B. these percentages are arbitrary, not supported by literature). Yes/No/ Unsure 7. Were all randomized participants analyzed in the group to which they were allocated? All randomized patients are reported/analyzed in the group they were allocated to by randomization for the most important moments of effect measurement (minus missing values) irrespective of non-compliance and co-interventions. Yes/No/ Unsure E 8. Are reports of the study free of suggestion of selective outcome reporting? In order to receive a yes, the review author determines if all the results from all pre-specified outcomes have been adequately reported in the published report of the trial. This information is either obtained by comparing the protocol and the report, or in the absence of the protocol, assessing that the published report includes enough information to make this judgment. Yes/No/ Unsure F Other sources of potential bias: 9. Were the groups similar at baseline regarding the most important prognostic indicators? In order to receive a yes, groups have to be similar at baseline regarding demographic factors, duration and severity of complaints, percentage of patients with neurological symptoms, and value of main outcome measure(s). Yes/No/ Unsure 10. Were co-interventions avoided or similar? This item should be scored yes if there were no co-interventions or they were similar between the index and control groups. Yes/No/ Unsure 11. Was the compliance acceptable in all groups? The reviewer determines if the compliance with the interventions is acceptable, based on the reported intensity, duration, number and frequency of sessions for both the index intervention and control intervention(s). For example, physiotherapy treatment is usually administered over several sessions; therefore, it is necessary to assess how many sessions each patient attended. For single-session interventions (e.g., surgery), this item is irrelevant. Yes/No/ Unsure 12. Was the timing of the outcome assessment similar in all groups? Timing of outcome assessment should be identical for all intervention groups and for all important outcome assessments. Yes/No/ Unsure Adapted and modified from Furlan AD, et al; Editorial Board, Cochrane Back Review Group updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine (Phila Pa 1976) 2009; 34: (101). E410

221 Effectivenss of Cervical Epidural injections Scale for observational studies (Tables 3 and 4) (112). For nonrandomized observational studies, the patient population should have had at least 50 total or at least 25 in each group if they were comparison groups. Authors with a perceived conflict of interest for any manuscript were recused from reviewing the manuscript. For adverse effects, confounding factors, etc., it Table 3. Newcastle-Ottawa quality assessment scale for case control studies Selection 1) Is the case definition adequate? a) yes, with independent validation * b) yes, e.g. record linkage or based on self reports c) no description 2) Representativeness of the cases a) consecutive or obviously representative series of cases * b) potential for selection biases or not stated 3) Selection of controls a) community controls * b) hospital controls c) no description 4) Definition of controls a) no history of disease (endpoint) * b) no description of source Comparability 1) Comparability of cases and controls on the basis of the design or analysis a) study controls for (Select the most important factor.) * b) study controls for any additional factor * (This criteria could be modified to indicate specific control for a second important factor.) Exposure 1) Ascertainment of exposure a) secure record (eg surgical records) * b) structured interview where blind to case/control status * c) interview not blinded to case/control status d) written self report or medical record only e) no description 2) Same method of ascertainment for cases and controls a) yes * b) no 3) Non-response rate a) same rate for both groups * b) non respondents described c) rate different and no designation Note: A study can be awarded a maximum of one star for each numbered item within the Selection and Exposure categories. A maximum of two stars can be given for Comparability. Wells GA, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis. (112). E411

222 Pain Physician: July/August 2012; 15:E405-E434 Table 4. Newcastle-Ottawa quality assessment scale for cohort studies. Selection 1) Representativeness of the exposed cohort a) truly representative of the average (describe) in the community * b) somewhat representative of the average in the community * c) selected group of users, e.g. nurses, volunteers d) no description of the derivation of the cohort 2) Selection of the non exposed cohort a) drawn from the same community as the exposed cohort * b) drawn from a different source c) no description of the derivation of the non exposed cohort 3) Ascertainment of exposure a) secure record (e.g. surgical records) * b) structured interview * c) written self report d) no description 4) Demonstration that outcome of interest was not present at start of study a) yes * b) no Comparability 1) Comparability of cohorts on the basis of the design or analysis a) study controls for (select the most important factor) * b) study controls for any additional factor * (This criteria could be modified to indicate specific control for a second important factor.) Outcome 1) Assessment of outcome a) independent blind assessment * b) record linkage * c) self report d) no description 2) Was follow-up long enough for outcomes to occur a) yes (select an adequate follow-up period for outcome of interest) * b) no 3) Adequacy of follow-up of cohorts a) complete follow-up - all subjects accounted for * b) subjects lost to follow-up unlikely to introduce bias - small number lost - > % (select an adequate %) follow-up, or description provided of those lost) * c) follow-up rate < % (select an adequate %) and no description of those lost d) no statement Note: A study can be awarded a maximum of one star for each numbered item within the Selection and Outcome categories. A maximum of two stars can be given for Comparability. Wells GA, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis. clinical_epidemiology/oxford.asp (112). E412

223 Effectivenss of Cervical Epidural injections was not possible to use quality assessment criteria. Thus, these were considered based on interpretation of the reports published and critical analysis of the literature. Only the randomized trials meeting the inclusion criteria with at least 6 of 12 criteria were utilized for analysis. However, studies scoring lower were described and provided with an opinion and critical analysis. Observational studies had to meet a minimum of 7 of the 13 criteria for cohort studies and 5 of 10 for casecontrol studies. Studies scoring less were also described and provided with an opinion and a critical analysis. If the literature search provided at least 5 randomized trials meeting the inclusion criteria and they were homogenous for each modality and condition evaluated, a meta-analysis was performed. All cervical interlaminar epidural injections will also be evaluated separately for disc herniation, discogenic pain, spinal stenosis, and post surgery-syndrome Data Extraction and Management Two review authors independently, in an unblinded standardized manner, extracted the data from the included studies. Disagreements were resolved by discussion between the 2 reviewers; if no consensus could be reached, a planned third author was called in to break the impasse Assessment of Heterogeneity Whenever meta-analyses were conducted, the I- squared (I2) statistic was used to identify heterogeneity (113). Combined results with I2 > 50% were considered substantially heterogenous. Analysis of the evidence was based on the condition (i.e., disc herniation or spinal stenosis) to reduce any clinical heterogeneity Measurement of Treatment Effect in Data Synthesis (Meta-Analysis) Data was summarized using meta-analysis when at least 5 studies per type of disorder were available that met the inclusion criteria (e.g., lumbar disc herniation or spinal stenosis, etc.). Qualitative (the direction of a treatment effect) and quantitative (the magnitude of a treatment effect) conclusions were evaluated. Random-effects metaanalysis to pool data was also used (114). The minimum amount of change in pain score to be clinically meaningful has been described as a 2-point change on a scale of 0 to 10 (or 20 percentage points), based on findings in trials studying general chronic pain (115), chronic musculoskeletal pain (116), and chronic low back pain (97,98,100,103,117,118), which have been commonly utilized. Recently robust measures with 50% change in pain relief and/or functional status have been published ( ). Consequently, for this analysis, we utilized clinically meaningful pain relief of at least a 3-point change on an 11-point scale of 0 to 10, or 50% pain relief from the baseline, as clinically significant, and functional status improvement of 40% or more Integration of Heterogeneity The evidence was assessed separately by administration to each condition (i.e., disc herniation, axial discogenic pain, spinal stenosis, or postsurgery syndrome). A meta-analysis was performed only if there were at least 5 studies meeting inclusion criteria for each variable. Statistical heterogeneity was explored using univariate meta-regression (141). 1.5 Summary Measures Summary measures included 50% or more reduction of pain or at least a 3 point decrease in pain scores in at least 40% of the patients, and a relative risk of adverse events including side effects. 1.6 Analysis of Evidence The analysis of the evidence was performed based on United States Preventive Services Task Force (USP- STF) criteria (142) as illustrated in Table 5, criteria which has been utilized by multiple authors (110, ). The analysis was conducted using 3 levels of evidence ranging from good, fair, and limited. Two of the review authors independently, in an unblinded standardized manner, analyzed the evidence. Any disagreements between reviewers were resolved by a third author and a consensus. If there were any conflicts of interest (e.g., authorship), those reviewers of those manuscripts did not participate in the assessment and analysis of those studies. 1.7 Outcome of the Studies In the randomized trials, a study was judged to be positive if the cervical interlaminar epidural injection therapy was clinically relevant and effective, either with a placebo control or active control. This indicates that the difference in effect for the primary outcome measure is statistically significant on the conventional 5% level. In a negative study, no difference between E413

224 Pain Physician: July/August 2012; 15:E405-E434 Table 5. Method for grading the overall strength of the evidence for an intervention. Grade Good Fair Limited or Poor Definition Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes (at least 2 consistent, higher-quality RCTs or studies of diagnostic test accuracy). Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, size, or consistency of included studies; generalizability to routine practice; or indirect nature of the evidence on health outcomes (at least one higher-quality trial or study of diagnostic test accuracy of sufficient sample size; 2 or more higher-quality trials or studies of diagnostic test accuracy with some inconsistency; at least 2 consistent, lower-quality trials or studies of diagnostic test accuracy, or multiple consistent observational studies with no significant methodological flaws). Evidence is insufficient to assess effects on health outcomes because of limited number or power of studies, large and unexplained inconsistency between higher-quality trials, important flaws in trial design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes. Adapted and modified from methods developed by U.S. Preventive Services Task Force (110,142). the study treatments or no improvement from baseline is identified. Further, the outcomes were judged at the reference point with positive or negative results reported at one month, 3 months, 6 months, and one year. For fluoroscopic observational studies, a study was judged to be positive if the epidural injection therapy was effective, with outcomes reported at the reference point with positive or negative results at one month, 3 months, 6 months, and one year. However, observational studies were only included in the evidence synthesis if there was less than 5 randomized trials meeting inclusion criteria for evidence synthesis for each condition (i.e., disc herniation, axial or discogenic pain, spinal stenosis, and post-surgery syndrome). 2.0 Results Figure 1 shows a flow diagram of study selection as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (99). There were 34 studies considered for inclusion ( , ). Of the 34 cervical interlaminar epidural trials identified ( , ), 24 studies were excluded ( ). Table 6 shows the reasons for exclusion. Of these, none were randomized trials. There were 3 studies evaluating a transforaminal approach (159,167,173). One of the studies described injection technique under computed tomography (CT) (169). A study which was titled, Epidural Steroid-Based Technique for Cervicogenic Headache Diagnosis was not available for review (170). Table 7 illustrates characteristics of studies considered for inclusion. There were 9 randomized trials ( , ) with 2 duplicate studies (130,131,134,135) meeting the inclusion criteria, thus there were a total of 7 trials evaluating various conditions. Only one study by Pasqualucci (153) was a follow-up of 6 months. All other studies included one year follow-up. There were no non-randomized or observational studies meeting the inclusion criteria. 2.1 Clinical Relevance Of the 7 trials assessed for clinical relevance, all of them met criteria with score of 3 of 5 or greater ( , ). Table 8 illustrates assessment of clinical relevance. 2.2 Methodological Quality Assessment A methodological quality assessment of the RCTs meeting inclusion criteria was carried out utilizing Cochrane review criteria as shown in Table 9. Studies achieving Cochrane scores of 9 or higher were considered as high quality, 6 to 8 were considered as moderate quality, and studies scoring less than 6 were excluded. There were 6 randomized trials (after combining duplicates) evaluating long-term response of 6 months or longer ( ,151,152) with one study (153) with a follow-up of 6 months. Four trials were considered high quality ( ) and 3 trials were considered moderate quality ( ). Of the included condition-specific studies, 4 trials included patients with disc herniation (130,134, ), one trial included patients with disc-related axial pain without disc herniation or radiculitis (131,135), one trial included patients with spinal stenosis (132), and one trial included patients with post surgery syndrome (133). E414

225 Effectivenss of Cervical Epidural injections Computerized and manual search of literature n = 1,849 Articles excluded by title and/or abstract n = 1,528 Potential articles n 321 Abstracts reviewed n = 321 Abstracts excluded n = 175 Full manuscripts reviewed n = 146 Manuscripts considered n = 34 Manuscripts not meeting inclusion criteria n = 25 Manuscripts considered for inclusion n = 9 Manuscripts considered for inclusion Randomized trials = 9 (2 duplicates) Non-randomized studies = 0 Fig. 1. The flow diagram illustrating published literature evaluating cervical interlaminar epidural injections. E415

226 Pain Physician: July/August 2012; 15:E405-E434 Table 6. List of excluded randomized trials and non-randomized studies. Manuscript Author(s) Condition Studied Number of Patients Follow-up Period Reason for Exclusion Other Reason(s) NON-RANDOMIZED Rowlingson & Cervical radiculitis months Blind retrospective evaluation in 25 patients. Kirschenbaum (154) Ferrante et al (155) Neck pain and cervical radiculopathy 100 NA Blind cervical interlaminar epidural injections with 26% cervical spondylosis, 6% spinal stenosis, 36% herniated disc, and no MRI abnormalities in 32%. Grenier et al (156) Chronic cervicobrachial months Blind technique in 29 patients. neuralgia Proano et al (157) Cervical disc herniation months Blind procedure with the ability to follow only two-thirds of the patients. Cicala et al (158) Neck and upper extremity pain 57 6 months Blind cervical epidural injections in 58 patients including 16 assigned to acute cervical myofascial strain, including patients with spondylosis = 25, strain = 16, and all other conditions = 17. Shakir et al (159) Cervical radicular pain 79 NA Retrospective evaluation with transforaminal approach. Kirpalani & Mitra (160) Nawani et al (161) Cervical radiculopathy 22 NA Authors evaluated in a long retrospective chart review of only 22 patients with chronic opioid use. Cervical and lumbosacral radiculopathies 50 6 weeks A total of 50 patients with cervical and lumbar radiculopathy utilizing a blind technique. Fish et al (162) Cervical radiculopathy 32 NA A retrospective evaluation of 32 patients involving disc herniation, nerve root compromise, neural foraminal stenosis, and central canal stenosis. Lasbleiz et al (163) Dirksen et al (164) Strub et al (165) Kwon et al (166) Mechanical cervicobrachial neuralgia Reflex sympathetic dystrophy Neck pain or cervical radicular pain Neck pain and cervical radiculopathy days A small study performed with CT-guided epidural injections also including 34 patients. 1 NA One blind epidural for reflex sympathetic dystrophy days A large study evaluating short-term results on factors influencing outcome with a 10-day follow up weeks Even though study is fluoroscopically directed, it was of a short-term follow-up evaluating prognostic factors. Lin et al (167) Cervical disc herniation months All cervical epidural steroid injections were administered by transforaminal route. Dougherty et al (168) Morcet et al (169) Martelletti et al (170) Cervical radiculopathy 20 One year This study included fluoroscopic cervical epidural injections in conjunction with spinal manipulation, however in only 20 patients. Cervicobrachial NA NA Technical description. neuralgia Cervicogenic headache diagnosis NA NA Appears to be technical description. The manuscript was not available for review. E416

227 Effectivenss of Cervical Epidural injections Table 6 (cont.). List of excluded randomized trials and non-randomized studies. Manuscript Author(s) Pawl et al (171) Mangar & Thomas (172) Condition Studied Cervical discogenic spondylosis Reason for Exclusion Number of Patients Follow-up Period Other Reason(s) months The study was performed blindly and the analysis was retrospective. Cervical pain syndrome 80 NA Injections were performed with a blind approach. Lee et al (173) Cervical disc herniation 159 One month Authors studied cervical transforaminal epidural steroids injection for the management of cervical radiculopathy for comparison of particulate versus non-particulate steroids. Bush & Hillier (174) Cervical radiculopathy 68 7 months Even though the study was performed under fluoroscopy, the average duration of pain was only 2 months, thus failing to meet the inclusion criteria. Shulman (175) Neck pain 155 NA A large number of patients with multiple injections, in a retrospective short review, but performed with a blind technique with multiple categories among them. Warfield et al (176) Cervical radiculitis 16 One year A small number of patients with a blind approach. Catchlove & Braha (177) Chronic head and neck pain 45 NA A retrospective evaluation performed blindly in 45 patients. 2.3 Meta-Analysis All randomized trials were evaluated for homogeneity for inclusion in the meta-analysis. There were no true placebo controlled trials and there was only one study which was described as placebo controlled, despite its active control design (152). Among the active controlled trials, there were 4 trials evaluating cervical disc herniation (130,134, ), one trial evaluating disc related axial pain without disc herniation (131,135), one trial evaluating central spinal stenosis (132), and another trial evaluating the effectiveness of post surgery syndrome (133). Consequently no metaanalysis was feasible. 2.4 Study Characteristics Table 10 illustrates the study characteristics of the included studies. 2.5 Analysis of Evidence The evidence was synthesized based on the specific condition for which the cervical interlaminar epidural injection was provided. Table 10 illustrates the results of randomized trials of the effectiveness of cervical interlaminar epidural injections in managing disc herniation or radiculitis, axial or discogenic pain, central spinal stenosis, and postsurgery syndrome Disc Herniation and Radiculitis There were a total of 4 studies meeting the inclusion criteria evaluating cervical interlaminar epidural injections in managing disc herniation or radiculitis (130,134, ). There was only one high quality randomized trial performed with an active control design under fluoroscopic evaluation (130,134). Two of the other 3 studies were performed blindly (151,152), one described as a placebo control design, though the control group received steroids (152). The second study utilized morphine as an additive to the solution (151). Finally, the last study (153) compared continuous versus single epidural injections providing up to approximately 8 injections in the single group and assessed only 6 month pain relief. The quality of these 3 studies performed without fluoroscopy was moderate. Among all the randomized trials, only one study utilized 120 participants with 60 patients in each group, E417

228 Pain Physician: July/August 2012; 15:E405-E434 Table 7. Assessment of randomized trials of cervical interlaminar epidural studies for inclusion criteria. Manuscript Author(s) Manchikanti et al (130,134) Manchikanti et al (131,135) Manchikanti et al (132) Manchikanti et al (133) Type of Study R, AC, F R, AC, F R, AC, F R, AC, F Condition Studied Number of Patients Disc herniation or radiculitis Discogenic pain without disc herniation Spinal stenosis Postsurgery Syndrome X 120 Local anesthetic only = 60 Local anesthetic with steroids = 60 X 120 Local anesthetic only = 60 Local anesthetic with steroids = 60 X 60 Local anesthetic only = 30 Local anesthetic with steroids = 30 X 56 Local anesthetic only = 28 Local anesthetic with steroids = 28 Control vs. Intervention or Comparator vs. Treatment Cervical epidural injection with local anesthetic 0.5%, 5 ml or with local anesthetic 0.5%, 4 ml with 6 mg (1 ml) of non-particulate Celestone Number of injections = 1 to 4 Cervical epidural injection with local anesthetic 0.5%, 5 ml or with local anesthetic 0.5%, 4 ml with 6 mg (1 ml) of non-particulate Celestone Number of injections = 1 to 4 Cervical epidural injection with local anesthetic 0.5%, 5 ml or with local anesthetic 0.5%, 4 ml with 6 mg (1 ml) of non-particulate Celestone Number of injections = 1 to 4 Cervical epidural injection with local anesthetic 0.5%, 5 ml or with local anesthetic 0.5%, 4 ml with 6 mg (1 ml) of non-particulate Celestone. Number of injections= 1 to 4 Followup Period Outcome Measures One year Significant improvement > 50% pain relief and > 50% functional status improvement One year Significant improvement > 50% pain relief and > 50% functional status improvement One year Significant improvement > 50% pain relief and > 50% functional status improvement One year Significant improvement > 50% pain relief and > 50% functional status improvement Comment(s) Authors concluded that cervical interlaminar epidural injections with local anesthetic with or without steroids might be effective in 77% with local anesthetic or 82% with steroids in the successful group. This is an active-control trial conducted with fluoroscopy under appropriate circumstances in a private practice with contemporary interventional pain management techniques. Authors concluded that cervical interlaminar epidural injections with local anesthetic with or without steroids might be effective in 78% in local anesthetic group and 73% in steroid group. This is an active-control trial conducted with fluoroscopy under appropriate circumstances in a private practice with contemporary interventional pain management techniques. This is an active-control trial conducted with fluoroscopy under appropriate circumstances in a private practice with contemporary interventional pain management techniques. Significant pain relief was seen in 87% in both groups, while in Group I, 77% and in Group II, 87% had functional status improvement. This is an active-control trial conducted with fluoroscopy under appropriate circumstances in a private practice with contemporary interventional pain management techniques. Significant pain relief was seen in 71% in Group I, and 68% in Group II. Functional status improvement was 71% in Group I and 64% in Group II. E418

229 Effectivenss of Cervical Epidural injections Table 7 (cont.). Assessment of randomized trials of cervical interlaminar epidural studies for inclusion criteria. Manuscript Author(s) Castagnera et al (151) Stav et al (152) Type of Study R, AC, B R, AC, B Condition Studied Number of Patients Disc herniation or radiculitis Discogenic pain without disc herniation Spinal stenosis Postsurgery Syndrome Control vs. Intervention or Comparator vs. Treatment X 24 Steroid group received in 14, 0.5% Lidocaine plus triamcinolone acetonide 10 mg per ml. The steroid plus morphine group received in 10, the same combination plus 2.5 mg of morphine sulfate Number of injections=1 X 42 One group treated with cervical epidural steroid/lidocaine injections and other treated with steroid/ lidocaine injections into the posterior neck muscles. Followup Period Outcome Measures One year Pain relief, VAS, work status One year Pain relief, change in range of motion, reduction of daily dose of analgesics, return to work. Pasqualucci et al (153) R, AC, B Number of injections=1 to 3 X 40 of 160 Patients received a single injection with 0.25% bupivacaine with epinephrine 1 in 200,000 in a volume of 6 ml with 80 mg of methylprednisolone acetate every 4-5 days to a maximum of 8 blocks. Continuous epidural group patients received catheterization with repeat injection hours and steroids 4-5 days. R = Randomized. AC = Active-Control. F = Fluoroscopy. B=Blind. VAS = Visual Analog Scale 6 months Pain control of greater than 80%, pain-free hours of sleep Comment(s) Success rate was 78.5% in the steroid group and 80% in the group with steroids and morphine. Pain relief remained stable with time with longterm follow-up of as much as 48 months with mean of 43 ± 18.1 months. Results suggested that a single cervical epidural steroid injection performed produces long-lasting pain relief which is not improved when morphine is combined with steroids. Authors concluded significant effectiveness. The results illustrated that one year after the treatment, 68% of the patients receiving epidural steroid injections had very good and good pain relief, whereas only 11.8% of group patients with intramuscular injections showed improvement. This is a wellperformed randomized active-control study, even though it was performed without fluoroscopy. There was significant decrease in pain control and increase of pain-free sleep with single as well as continued administrations in approximately 17 of 20 patients with single injection and 17 of 20 patients with continuous infusion at one month and 6 months. E419

230 Pain Physician: July/August 2012; 15:E405-E434 Table 8. Clinical relevance of included studies. Manuscript Author(s) A) Patient description B) Description of interventions and treatment settings C) Clinically relevant outcomes D) Clinical importance E) Benefits versus potential harms Total criteria met Manchikanti et al (130,134) /5 Manchikanti et al (131,135) /5 Manchikanti et al (132) /5 Manchikanti et al (133) /5 Castagnera et al (153) /5 Stav et al (152) /5 Pasqualucci et al (153) /5 + = positive; - = negative ; U = unclear Scoring adapted from Staal JB, et al. Injection therapy for subacute and chronic low-back pain. Cochrane Database Syst Rev 2008; 3:CD (111). Table 9. Methodological quality assessment of randomized trials. Randomization adequate Concealed treatment allocation Manchikanti et al (130,134) Manchikanti et al (131,135) Manchikanti et al (132) Manchikanti et al (133) Castagnera et al (151) Stav et al (152) Pasqualucci et al (153) Y Y Y Y U N N Y Y Y Y U N N Patient blinded Y Y Y Y U N N Care provider blinded Y Y Y Y U N N Outcome assessor blinded N N N N U N N Drop-out rate described Y Y Y Y Y Y Y All randomized participants analyzed in the group Reports of the study free of suggestion of selective outcome reporting Groups similar at baseline regarding most important prognostic indicators Co-interventions avoided or similar Compliance acceptable in all groups Time of outcome assessment in all groups similar Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y N N N Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Score 11/12 10/12 10/12 10/12 7/12 7/12 7/12 Y=yes; N=no; U=unclear E420

231 Effectivenss of Cervical Epidural injections Table 10. Results of randomized trials of effectiveness of cervical interlaminar epidural injections. Pain Relief and Function Results Study Study Characteristics Methodological Quality Scoring Participants Interventions 3 mos. 6 mos. 12 mos. Short-term Long-term 6 mos. > 6 mos. 1 year ST LA SAL ST LA SAL ST LA SAL Comment(s) DISC HERNIATION AND RADICULITIS Manchikanti et al (130,134) R, AC, F 11/ local anesthetic= 60 Local anesthetic with steroids = 60 Local anesthetic or with Celestone Number of injections = 1 to 4 83% vs. 70% 82% vs. 73% 72% vs. 68% P P NA P P NA P P NA Positive large study. Castagnera et al (151) R, AC, B 7/12 24 local anesthetic with steroid or steroid plus morphine Number of injections=1 79.2% 79.2% 79.2% P NA NA P N NA P NA NA A small study with positive results Stav et al (152) R, AC, B 7/12 42 local anesthetic with steroid or IM steroid Number of injections=1 to 3 NA NA 68% vs.11.8% NA NA NA NA NA NA P NA NA A small study showing satisfactory improvement Pasqualucci et al (153) R, AC, B 7/12 40 of 160 Bupivacaine with methylprednisolone acetate NA Single vs. continuous 58.5%, 73.7% improvement NA NA NA NA P NA NA NA NA NA Small study with positive results DISCOGENIC PAIN Manchikanti et al (131,135) R, AC, F 10/ Local anesthetic or with Celestone 68% vs. 77% 67% vs. 73% 72% vs. 68% P P NA P P NA P P NA Positive results SPINAL STENOSIS Manchikanti et al (132) R, AC, F 10/12 60 Local anesthetic or with Celestone 77% vs. 87% 87% vs. 80% 73% vs. 70% P P NA P P NA P P NA Positive results POST SURGERY SYNDROME Manchikanti et al (133) R, AC, F 10/12 56 Local anesthetic or with Celestone 68% vs. 68% 64% vs. 71% 71% vs. 64% P P NA P P NA P P NA Positive results R = Randomized; AC = Active-Control; F = Fluoroscopy; B=Blind; VAS = Visual Analog Scale; P = positive; N = negative; NA = not applicable E421

232 Pain Physician: July/August 2012; 15:E405-E434 either with local anesthetic or local anesthetic with steroids. All the studies showed significant improvement compared to baseline, while there was no significant improvement among the groups, except in the study by Stav et al (152) utilizing intramuscular steroid injection. However, this study included only a small proportion of patients and provided only one injection. These results have not been replicated with improvement in a significant proportion of patients with only one epidural injection. The largest randomized trial by Manchikanti et al (130,134) showed significant improvement from the baseline at all levels, including function as well as disability. Of the 4 randomized trials meeting the inclusion criteria evaluating cervical interlaminar epidural injections, all of them showed positive results for the long-term; however, the results were strong in only one study (130,134) Axial or Discogenic Pain There was only one study evaluating axial discogenic pain, the role of cervical interlaminar epidural injections, in patients without disc herniation, radiculitis, or facet joint arthropathy (131,135). This study showed positive results. This was a large study performed in a contemporary interventional management practice setting utilizing an active control design with 60 patients in each group. This study showed positive results at all levels whether local anesthetic was utilized alone or combined with steroids, both in pain relief as well as functional status Spinal Stenosis There was only one randomized trial meeting the inclusion criteria in the evaluation of central spinal stenosis in the cervical spine (132). This study was of an active control design and a preliminary report, but showed positive results Postsurgery Syndrome There was only one randomized trial evaluating the effectiveness of cervical interlaminar epidural injections in post surgery syndrome with or without steroids with an active control design, but with preliminary results (133). The results were positive at 3, 6, and 12 months both for pain and functional status with or without steroids. 2.6 Level of Evidence Based on the USPSTF criteria, the evidence is considered at 3 levels good, fair, and limited Cervical Disc Herniation For cervical disc herniation with radiculitis, based on one large fluoroscopically directed active control study with or without local anesthetic with steroids (130,134), in conjunction with 3 smaller randomized trials with positive results ( ), the evidence is good. Cervical epidural with local anesthetic only is supported by one randomized, fluoroscopically directed trial with 120 patients, showing positive results. However, due to the nature of only one study, the evidence is considered as fair Axial or Discogenic Pain There was only one study evaluating the results of cervical discogenic or axial pain (131,135), which showed positive results in 120 patients, thus, the level of evidence is fair Spinal Stenosis There was only one study evaluating the results of spinal stenosis (132), which showed positive results in 60 patients, thus, the level of evidence is fair Post Surgery Syndrome There was only one study evaluating the results of post surgery syndrome (133), which showed positive results in 56 patients, thus, the level of evidence is fair Summary of Evidence In summary, the evidence is good for radiculitis secondary to disc herniation with local anesthetics and steroids, fair with local anesthetic only; whereas, it is fair for local anesthetics with or without steroids for axial or discogenic pain, pain of central spinal stenosis, and pain of post surgery syndrome. 3.0 Complications Serious complications of cervical interlaminar epidural procedures include spinal cord trauma, spinal cord or epidural hematoma formation, nerve injury, subdural or subarachnoid injection, intravascular entry either venous or arterial, vascular injury or vascular embolism, and injection leading to abscess, even though serious complications are rarely seen E422

233 Effectivenss of Cervical Epidural injections (70,75,77-85,94, ). Multiple minor side effects include increase in the neck pain, vasovagal reactions, headache, insomnia, increase in temperature, and dural puncture. Manchikanti et al (86) evaluated complications and side effects of epidural injections. Among these, 2,376 were performed in the cervical region with an interlaminar approach. The results illustrated intravascular entry in 4.2%, return of blood in 1.2%, profuse bleeding in 0.7%, bruising in 0.3%, vasovagal reaction in 0.04%, transient nerve root irritation in 0.25%, transient spinal cord irritation in 0.21%, dural puncture in 1%, postlumbar puncture headache in 0.08%, and facial flushing in 0.08%. 4.0 Discussion This systematic review evaluating the effectiveness of cervical interlaminar epidural injections in managing chronic neck pain and upper extremity pain caused by disc herniation with radiculitis showed good evidence for cervical interlaminar epidural injections with local anesthetic and steroids. This evaluation also showed fair evidence for cervical epidural with local anesthetic only in managing disc herniation and radiculitis due to the fact that there was only one study (130,134). The evaluation of disc herniation and radiculitis was included in 4 randomized trials, one of them being a large randomized, double-blind, active control trial in a contemporary interventional pain management practice. The evidence for axial neck pain or cervical discogenic pain is fair based on a single randomized, double-blind, active controlled trial with or without steroids with strong measures of outcome. The evidence is fair for central spinal stenosis and post surgery syndrome based on one manuscript for each condition with publication of only preliminary results. In this evaluation, a total of 7 randomized trials met the inclusion criteria. The remaining studies were all performed without fluoroscopic utilization blindly and were either retrospective or prospective but, observational. The previous systematic review by Benyamin et al (70) showed Level II-I evidence for cervical interlaminar epidural injections with steroids for patients with chronic neck and upper extremity pain based on a plurality of 3 studies. However, none of these studies were performed under fluoroscopy and none of the studies had more than 100 patients to be studied. In contrast, the present evaluation shows an additional 4 randomized trials, 2 of them with a large proportion of patients, while 2 were only preliminary, performed in a contemporary interventional pain management practice, after failure of conservative management, under fluoroscopy, based on specific disorders including disc herniation, axial or discogenic pain, central spinal stenosis, and post surgery syndrome. Compared to the studies of caudal and lumbar epidural injections, trials or studies of cervical epidural injections are rare. Cervical epidural steroid injections have been studied since 1985 (171). Historically, cervical epidural steroid injections originated from Pagés description of needle placement into the lumbar epidural space based on obstruction of free flow of spinal fluid from the needle and lack of resistance to injection of local anesthetic in 1921 (200). Dogliotti (201) was the first to describe the technique of cervical epidural block and also the first to describe, in 1933, the loss of resistance technique. The underlying mechanism of action of epidurally administered steroid and local anesthetic injection is still not well understood. A common problem encountered with any epidural injection is inaccurate needle placement, leading to inaccurate placement of the injectate (2,94,202). Consequently, proponents for fluoroscopic guidance in epidural steroid injections advocate utilizing this technique in order to assure that medications reach the appropriate and desired intervertebral space (202). In a study of 38 interlaminar cervical epidural steroid injections, they (202) found a 53% rate of false loss of resistance during the first attempt to enter the epidural space. They suggested using fluoroscopy can improve the accuracy of needle placement and medication delivery. Even with second and third attempts, the success rate improved only to 75% with loss of resistance technique without fluoroscopy (88). In addition, it was also shown that when cervical epidural steroid injections are performed in the midline at C6/7 and C7/T1 under fluoroscopy, the contrast consistently covers the dorsal cervical epidural space bilaterally, irrespective of the volume used or neck flexion angle used (90). Further, fluoroscopic guidance also helps to avoid potential intravascular injections (203). Fluoroscopic utilization with contrast injection will also delineate multiple filling patterns including subdural and subarachnoid patterns. Even though the underlying mechanism of action of epidurally administered steroid and local anesthetic is not well understood, it is believed that the achieved neural blockade alters or interrupts nociceptive input, reflex mechanism of the afferent fibers, selfsustaining activity of the neurons, and the pattern of central neuronal activities (2,94,178,188,202). Corticosteroids have been shown to reduce inflammation by E423

234 Pain Physician: July/August 2012; 15:E405-E434 inhibiting either the synthesis or release of a number of pro-inflammatory mediators and by causing a reversible local anesthetic effect (153, , ). The emerging evidence also shows that the long-lasting effect may be obtained with local anesthetics with or without steroids (122, ). Further, it has been shown in rat experiments that nerve root infiltration prevented mechanical allodynia, even though no additional benefit from using corticosteroid was identified (240). Thus, it is suggested that corticosteroid may be unnecessary for nerve root blocks; in fact, this concept has been reinforced by numerous randomized and observational studies (122,252,254, ). Finally, in evaluation of epidural local anesthetic plus corticosteroid for the treatment of cervical brachial radicular pain with either a single injection or a continuous infusion (153), continuous epidural showed better control of chronic cervicobrachial pain compared with single injection, even though a corticosteroid was utilized in both injections. Thus, local anesthetic provides an independent effect or an additive effect. Multiple studies have evaluated prognostic factors for cervical epidural injections including the duration of pain. One retrospective evaluation (160) also evaluated the influence of chronic opioid use as a negative predictive factor for response to cervical steroid injections. This small study of 22 patients with cervical radiculopathy in a retrospective evaluation illustrated a significant difference with opioid-naïve patients receiving better relief in the short-term than the patients on chronic opioid therapy (70% vs. 20%). Fish et al (162) evaluated the MRI prediction of therapeutic response to epidural steroid injections in patients with cervical radiculopathy and concluded that patients with central canal stenosis achieved a significantly better functional outcome after cervical epidural steroid injections than those without. Thus, they believed that the MRI finding of central canal stenosis is a potential indication for the cervical epidural injections. Strub et al (165) evaluated factors influencing the outcomes in the short-term in 161 patients with 280 interlaminar epidural injections. They also showed that patients who required narcotics for their symptoms before the procedure showed poor pain relief. However, in the modern era, the majority of the patients with chronic pain have received extensive opioid therapy prior to presenting to interventional pain management settings. The positive results illustrated in recent active controlled trials ( ) shows that even though there are changes in opioid intake, most patients continue to be on opioids, thus the difference illustrated in the above studies ( ) has not been replicated in long-term studies, rather the results are different from these reports ( ). One retrospective evaluation also showed manipulation after cervical epidural injection was effective (168). Kwon et al (166) in a short-term evaluation assessed the prognostic factors in a non-randomized fluoroscopically directed study in 76 patients. In the short-term, they concluded that the patients with herniated discs had significantly better results than patients with spinal stenosis. They also showed other non-significant predictors of an improved outcome including a symptom duration of less than 6 months, a young age, and the presence of cervical radiculopathy. Ferrante et al (155) reviewed 100 patients and attempted to classify predictors of therapeutic outcomes after cervical epidural steroid injections. They separated patients into 5 clinical groups with radiculopathy with structural abnormality, radiculopathy without structural abnormality, radiculitis with structural abnormality, radiculitis without structural abnormality, and cervical spondylosis. They also assessed symptoms and signs. They concluded that the presence of radicular pain predicted a better outcome, a radiologic diagnosis abnormality or herniated disc predicted a poor outcome. A multitude of other predictors they attempted to evaluate were non-significant, thus, these predictors are extremely confusing. Overall, the recent studies illustrated that ( ) the results are superior in patients with disc herniation and/or radiculitis or axial discogenic pain after facet joint pain has been ruled out. The limitations of this review include a paucity of literature specifically with proper design and utilization of fluoroscopy. Even though criticism has been offered for lack of placebo controlled trials, they are unrealistic in interventional pain management. Further, it also has been significantly misinterpreted ( ). Some authors also have mistakenly reported that any local anesthetic injection which yields similar results as steroids or another agent is considered a placebo. The experimental and clinical findings from investigations, electrophysiological effects, and muscle activation have shown differing results illustrating that there is no true placebo effect (268, ). However, the literature also has shown that appropriate design of placebo has in fact shown negative results ( ). The results of this systematic review may be applied in interventional pain management practices utilizing appropriate evaluations. We found only 7 articles were identified which met the inclusion criteria E424

235 Effectivenss of Cervical Epidural injections ( , ). In conclusion, the results of this systematic review have significant implications for clinical practices in interventional pain management. Appropriately performed interventions are illustrated to be effective based on the results of this systematic review. 5.0 Conclusion Review of 7 manuscripts meeting inclusion criteria showed good evidence for radiculitis secondary to disc herniation with local anesthetics and steroids, fair evidence with local anesthetic only; whereas, the evidence is fair for local anesthetics, with or without steroids, for axial or discogenic pain, pain of central spinal stenosis, and pain of post surgery syndrome. Author Affiliations Dr. Diwan is Executive Director of The Spine and Pain Institute of New York. Dr. Manchikanti is Medical Director of the Pain Management Center of Paducah, Paducah, KY, and Clinical Professor, Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY. Dr. Benyamin is the Medical Director, Millennium Pain Center, Bloomington, IL, and Clinical Assistant Professor of Surgery, College of Medicine, University of Illinois, Urbana-Champaign, IL Dr. Bryce is from Advanced Pain Management, Madison, WI. Ms. Geffert is Director of Research and Education and Administrative Assistant at Mid Atlantic Spine & Pain Physicians of Newark, DE, and Fellowship Coordinator at Temple University Hospital, Philadelphia, PA. Dr. Hameed is with the Department of Physical Medicine and Rehabilitation, The Johns Hopkins University School of Medicine, Baltimore, MD. Dr. Sharma is a Consultant in Pain Medicine, Department of Pain Medicine, The Walton Centre for Neurology and Neurosurgery NHS Foundation Trust, Liverpool, and a Fellow of the Faculty of Pain Medicine of the Royal College of Anaesthetists and Chair of British Pain Society Interventional Pain Medicine Special Interest Group, United Kingdom. Dr. Abdi is Chief, Division of Pain Medicine at Beth Israel Deaconess Medical Center, Brookline, MA, and Associate Professor of Anesthesiology, Harvard Medical School, Boston, MA. Dr. Falco is Medical Director of the Mid Atlantic Spine & Pain Physicians of Newark, DE, Director, Pain Medicine Fellowship, Temple University Hospital, Philadelphia, PA, and Associate Professor, Department of PM&R, Temple University Medical School, Philadelphia, PA. Acknowledgments The authors wish to thank Vidyasagar Pampati, MSc, for statistical assistance; Sekar Edem for assistance in the search of the literature; Laurie Swick, BS, for manuscript review; and Tonie M. Hatton and Diane E. Neihoff, transcriptionists, for their assistance in preparation of this manuscript. We would like to thank the editorial board of Pain Physician for review and criticism in improving the manuscript. References 1. Hogg-Johnson S, van der Velde G, Carroll LJ, Holm LW, Cassidy JD, Guzman J, Côté P, Haldeman S, Ammendolia C, Carragee E, Hurwitz E, Nordin M, Peloso P; Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders. The burden and determinants of neck pain in the general population: Results of the Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders. Spine (Phila Pa 1976) 2008; 33:S39-S Manchikanti L, Boswell MV, Singh V, Benyamin RM, Fellows B, Abdi S, Buenaventura RM, Conn A, Datta S, Derby R, Falco FJE, Erhart S, Diwan S, Hayek SM, Helm S, Parr AT, Schultz DM, Smith HS, Wolfer LR, Hirsch JA. Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician 2009; 12: Enthoven P, Skargren E, Oberg B. Clinical course in patients seeking primary care for back or neck pain: A prospective 5-year follow-up of outcome and health care consumption with subgroup analysis. Spine (Phila Pa 1976) 2004; 29: Gustavsson C, Denison E, von Koch L. Self-management of persistent neck pain: Two-year follow-up of a randomized controlled trial of a multicomponent group intervention in primary health care. Spine (Phila Pa 1976) 2011; 36: Guez M, Hildingsson C, Nilsson M, Toolanen G. The prevalence of neck pain: A population-based study from northern Sweden. Acta Orthop Scand 2002; 73: Côté P, Cassidy JD, Carroll L. The Saskatchewan Health and Back Pain Survey. The prevalence of neck pain and related disability in Saskatchewan adults. Spine (Phila Pa 1976) 1998; 23: Peloso PMJ, Gross A, Haines T, Trinh K, Goldsmith CH, Burnie SJ; Cervical Overview Group. Medicinal and injection therapies for mechanical neck disorders. Cochrane Database Syst Rev 2007; 3:CD Linton SJ, Hellsing AL, Hallden K. A population based study of spinal pain among year old individuals. Spine (Phila Pa 1976) 1998; 23: E425

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A double-blind, controlled evaluation of the value of Sarapin in neural blockade. Pain Physician 2004; 7: Manchikanti L, Damron KS, Cash KA, Manchukonda R, Pampati V. Therapeutic medial branch blocks in managing chronic neck pain: A preliminary report of a randomized, double-blind, controlled trial: Clinical Trial NCT Pain Physician 2006; 9: Manchikanti L, Manchikanti KN, Manchukonda R, Pampati V, Cash KA. Evaluation of therapeutic thoracic medial branch block effectiveness in chronic thoracic pain: A prospective outcome study with minimum one-year follow up. Pain Physician 2006; 9: Manchikanti L, Manchikanti K, Manchukonda R, Cash KA, Damron KS, Pampati V, McManus CD. Evaluation of lumbar facet joint nerve blocks in the management of chronic low back pain: A preliminary report of a randomized, double-blind controlled trial: Clinical Trial NCT Pain Physician 2007; 10: Manchikanti L, Giordano J, Fellows B, Hirsch JA. Placebo and nocebo in interventional pain management: A friend or a foe or simply foes? Pain Physician 2011; 14:E157-E Smuck M, Levin JH. RE: Manchikanti L, Singh V, Falco FJE, Cash KA, Fellows B. Cervical medial branch blocks for chronic cervical facet joint pain: A randomized double-blind, controlled trial with one-year follow-up. Spine (Phila Pa 1976) 2008; 33: Spine (Phila Pa 1976) 2009; 34: E433

244 Pain Physician: July/August 2012; 15:E405-E Manchikanti L, Singh V, Falco FJE. In response to Smuck M, Levin JH. RE: Manchikanti L, Singh V, Falco FJE, Cash KA, Fellows B. Cervical medial branch blocks for chronic cervical facet joint pain: A randomized double-blind, controlled trial with one-year follow-up. Spine (Phila PA 1976) 2008; 33: ; author reply 2009; 34: Pham Dang C, Lelong A, Guilley J, Nguyen JM, Volteau C, Venet G, Perrier C, Lejus C, Blanloeil Y. Effect on neurostimulation of injectates used for perineural space expansion before placement of a stimulating catheter: Normal saline versus dextrose 5% in water. Reg Anesth Pain Med 2009; 34: Tsui BC, Kropelin B, Ganapathy S, Finucane B. Dextrose 5% in water: Fluid medium maintaining electrical stimulation of peripheral nerve during stimulating catheter placement. Acta Anaesthesiol Scand 2005; 49: Indahl A, Kaigle AM, Reikeräs O, Holm SH. Interaction between the porcine lumbar intervertebral disc, zygapophysial joints, and paraspinal muscles. Spine (Phila Pa 1976) 1997; 22: Indahl A, Kaigle A, Reikeräs O, Holm S. Electromyographic response of the porcine multifidus musculature after nerve stimulation. Spine (Phila Pa 1976) 1995; 20: Ghahreman A, Ferch R, Bogduk N. The efficacy of transforaminal injection of steroids for the treatment of lumbar radicular pain. Pain Med 2010; 11: Karppinen J, Ohinmaa A, Malmivaara A, Kurunlahti M, Kyllönen E, Pienimäki T, Nieminen P, Tervonen O, Vanharanta H. Cost effectiveness of periradicular infiltration for sciatica: Subgroup analysis of a randomized controlled trial. Spine (Phila Pa 1976) 2001; 26: Iversen T, Solberg TK, Romner B, Wilsgaard T, Twisk J, Anke A, Nygaard O, Hasvold T, Ingebrigtsen T. Effect of caudal epidural steroid or saline injection in chronic lumbar radiculopathy: Multicentre, blinded, randomised controlled trial. BMJ 2011; 343:d5278. E434

245 6 Bulletin of the NYU Hospital for Joint Diseases 2012;70(1):6-10 Outcomes of Interlaminar and Transforminal Spinal Injections Joshua Landa, M.D., and Yong Kim, M.D. Abstract Epidural spinal injections can be administered via a translaminar or transforaminal route, depending on the clinical scenario. When it is more desirable to target a specific nerve root, a transforaminal approach is typically used, and when the target is more diffuse, a translaminar method is chosen. Both are commonly used and can be utilized similarly in the lumbar or cervical spine. However, it is essential that the clinician understand the risks and benefits of these injections. In the lumbar spine, both translaminar epidural steroid injections (TLESI) and transforaminal epidural steroid injections (TFESI) have been shown to provide up to 6 months of pain relief, though long-term benefits are less reliable. In the cervical spine, translaminar injections may provide longer relief and have a lower complication rate than cervical transforaminal injections. Proper technique is essential to minimize the rate of these rare but occasionally severe complications. Epidural spinal injections are commonly used in the nonoperative management of cervical and lumbar spine pathology. They can be useful for both diagnostic and therapeutic purposes. Indications include neck or lower back pain with or without radiculopathy. Complications have occasionally been reported and can be devastating. It is, therefore, imperative that the administering clinician understand the existing literature for injections so that they can help patients make an informed decision as to whether these injections are in their best interest. Joshua Landa, M.D., and Yong Kim, M.D., are in the Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, New York. Correspondence: Joshua Landa, M.D., Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, 301 East 17th Street, New York, New York 10016; joshua.landa@gmail.com. Spinal epidural steroid injections can be given in a translaminar or transforaminal fashion. Translaminar epidural steroid injections (TLESI) are more appropriate for patients with axial neck or lower back pain or spinal stenosis, while transforaminal epidural steroid injections (TFESI) are more appropriate for isolated lumbar or cervical nerve root irritation. Several studies have been performed to evaluate the efficacy of these injections, and there have been a number of reported complications of each type. Clinicians should be aware of the range of complications in order to best counsel their patients (Table 1). Lumbar TLESI Lumbar injections are commonly used in the nonoperative management of lower back pain with or without radiculopathy as well as for lumbar spinal stenosis. Contraindications such as previous laminectomy or active infection should be familiar to the practicing clinician. While the literature is still emerging with regard to efficacy, there are several valid randomized controlled trials that have sought to establish whether or not these injections should be used. Carette and colleagues conducted a randomized controlled double blind trial of 158 patients with herniated nucleus pulposis randomized to steroid or saline lumbar TLESI. 1 At 3 weeks, the steroid group had better Oswestry scores and finger-floor distance as well as less pain. At 6 weeks, the steroid group had less pain, with no difference in any of the other outcome measures assessed in this study. By 3 months, there were no differences found between the two groups. Additionally, the same percentage of patients in both groups went on to surgery. The WEST Study, published in Rheumatology in 2005, was a multi-center, double-blind, randomized, placebocontrolled, parallel-group trial that consisted of 288 patients that all had unilateral sciatica. 2 Patients were randomized into two groups; one group received three Lumbar TLESI Landa J, Kim Y. Outcomes of interlaminar and transforminal spinal injections. Bull NYU Hosp Jt Dis. 2012;70(1):6-10.

246 Bulletin of the NYU Hospital for Joint Diseases 2012;70(1): Table 1 Summary of Outcomes and Complications Regarding Spinal Injections Efficacy Complications Cervical TLESI Good evidence to support relief to one year or longer Serious complications have been reported but are rare Cervical TFESI Minimal evidence to support efficacy Many serious complications have been reported, though their true incidence is not known Lumbar TLESI Good evidence to supports short term (< 6 months) efficacy Complication have been reported but are uncommon and usually not serious Lumbar TFESI Good evidence to supports short term (< 6 months) efficacy Serious complications including paraplegia have been reported but are rare with steroid, and the other group received an injection with interligamentous saline. They used the Oswestry low back pain disability questionnaire to evaluate outcomes. The investigators found that at 3 weeks 12.5% of steroid injection group and 3.7% of interligamentous saline groups had 75% or more improvement, which was a significant difference between the two groups. However, outcomes from 6 to 52 weeks failed to show any benefit in the group the received the lumbar TLESI with steroid compared to the group that was given injections with interligamentous saline. These two studies demonstrated that there is excellent short-term relief in patients injected with lumbar TLESI. However, consistent long term relief is lacking. Supporting this idea was a study by Wilson-Macdonald and associates. 3 They studied 93 patients who were randomized to receive either an intramuscular steroid and anesthetic injection or lumbar TLESI for a compressed nerve root. They found a significant reduction in pain early on with TLESI without any long-term difference. Recently, a systematic review of lumbar TLESI with or without steroid injections was conducted by Parr and coworkers. 4 The review was performed using the Cochrane Musculoskeletal Review Group criteria for interventional techniques for randomized trials and the Agency for Healthcare Research and Quality criteria for observational studies. Short-term relief was classified as that lasting less than 6 months while long-term was considered relief for greater than 6 months. There is level II-2 positive evidence for pain relief from disc herniation and radiculitis. A significant limitation that they noted was that all studies involved injections that were blind, meaning that no fluoroscopy was used for localization. Blind injections were subject to problems including extra epidural placement of the needle, intravascular placement of the needle, preferential cranial flow of the solution, preferential posterior flow of the solution, and difficult placement, all of which could affect the results following lumbar TLESI. Fluoroscopic imaging is strongly recommended, as injections without the use of fluoroscopic assistance may have a rate of erroneous needle placement in as high as 30% to 40% of cases. 5 There have been a number of complications reported during the use of lumbar TLESI, such as infections (e.g., epidural abscess, meningitis, and discitis), epidural hematomas, seizures, transient blindness, hiccups, flushing, and gas emboli. Additionally, there are known side effects that are related to the use of steroids in the lumbar spine, such as pituitary suppression, osteonecrosis, osteoporosis, and weight gain, although these side effects are extremely rare when the recommended doses are used in the lumbar spine. 6 Most large series have no reported serious complications, however, and only case reports exist regarding these complications. Injections, therefore, are generally thought to carry a very low risk. Lumbar TFESI Lumbar TFESI has the benefit of being highly selective, especially in the treatment of lumbar radiculopathy, and it can be utilized in a diagnostic capacity in the preoperative patient to help identify symptomatic nerve roots. Fortunately, several high-quality randomized controlled trials regarding lumbar TFESI have been performed. Kolsi and colleagues 7 conducted a prospective, randomized, double-blind study consisting of 30 patients with refractory nerve root pain. Patients were randomized to lumbar TFESI or insterspinous sham injection. They were followed for 4 months, and pain on a 0 to 100 scale was used as the primary outcome. Pain relief was similar in both groups, going from 70 to 26 in the group that received a nerve root injection and from 63 to 23 in the interspinous group. Notable limitations in this study included short follow-up, unknown number of injections, and crossover. A prospective, randomized, controlled, double-blinded trial conducted by Riew and associates 8 supports the use of TFESI as a nonoperative modality that has the potential of avoiding surgery for lumbar radiculopathy. This study followed 55 patients who requested operative treatment with lumbar radicular pain (4 spine surgeons) with 13 to 28 month follow-up. Of these 55 patients, 9 of the 27 (33%) patients injected with bupivicaine alone decided to not have surgery while 20 of the 28 (71%) of patients injected with steroids decided to not have surgery (p < 0.004). Additional studies have shown that lumbar TFESI injections have good short-term outcomes in the setting of lumbar disc herniation 9 and spinal stenosis. 10 These studies all support the use of these injections, but these benefits must be weighed against the risk of complications.

247 8 Bulletin of the NYU Hospital for Joint Diseases 2012;70(1):6-10 Complication rates in studies have ranged from 0% to 1.9%. One serious event, retroperitoneal hematoma in a patient on anticoagulation treatment, was noted. Given the rarity of complications, there is no study to date with adequate power to detect the actual incidence of these problems. Several case reports exist of which the practitioner should be aware. Houten and Errico reported on a case series of three patients who suffered sudden paraplegia after lumbar (two patients) or sacral (one patient) nerve root block. 11 The hypothesized mechanism was arterial injection into an anatomic variant of the artery of Adamkiewicz, which runs from T9-L2 in 85% of patients. In that study, one patient improved to 3-4/5 strength in both lower extremities, the second had no recovery at 8 month follow-up, and the third had no recovery at 5 year follow-up. Other reported complications include infection, allergic reaction, and dural puncture. Suggested measures to reduce risk include monitoring patients for 15 to 20 minutes after their injections, the utilization of particulate free steroids, testing for intra-arterial injection with digital subtraction angiography, and preliminary injection of a local anesthetic. With good technique, serious complications can be minimized. Cervical TLESI Cervical radiculopathy is a relatively common problem facing the spinal surgeon, with an incidence of 83.2 per 100,000 people. 20 When initial nonoperative treatment fails, the treating physician can consider a cervical steroid injection. The use of cervical TLESI has been increasing. There are several studies that have investigated its use. While most investigators have found improvement with cervical TLESI, Castagnera and associates 12 did not. They performed translaminar cervical injections in 34 patients. Fourteen patients received a steroid injection while 10 were injected with morphine. Similar outcomes were seen, as both groups had 79% to 80% success rate at one year. Stav and coworkers 13 compared 25 patients with cervical TLESI to 17 patient with steroid injections into the posterior neck muscles. Results at 1 week demonstrated pain relief in 76% of patients injected with translaminar cervical epidural steroid compared to only 36% pain relief in patients injected in their deep neck muscles. Furthermore, significant differences were seen between these two groups at 1 year, with excellent pain relief in 68% of the TLESI group and only 12% of the deep neck muscles group. Ferrante and colleagues 14 performed a retrospective review of 100 patients with cervical TLESI. They used multiple regression analysis to determine predictors of outcome after cervical TLESI. Of all the factors studied, radicular pain was highly predictive of a good outcome (p = ). In a retrospective review of 45 cervical TLESI in 25 patients, Rowlingson and Kirschenbaum 15 studied patients who failed a long trial of nonoperative management. Sixty-four percent of these patients had a good or excellent long-term result, showing that cervical TLESI remains a viable option for patients in whom prolonged nonoperative treatment has remained ineffective. Benyamin and associates 16 carried out an extensive review using the Cochrane Musculoskeletal Review Group criteria. They concluded that there is level II-1 (with a grade 1C strong recommendation ) evidence for the use of cervical TLESI for both chronic neck and upper extremity pain. Cervical TLESI is an excellent option that has the potential for long-term benefits, especially in patients with radiculopathy as opposed to isolated neck pain. As in all types of epidural spinal injections, the benefits must be weighed against the risk of complications. Waldman and associates 17 in a prospective study of 790 blocks in 215 patients, found two dural punctures, two episodes of vasovagal syncope, and one late superficial infection. This study used only loss of resistance, not fluoroscopy, to localize the injections. In contrast, Botwin and coworkers 18 reported on a retrospective cohort analysis of 345 flouroscopically guided injections in 157 patients. A much higher overall complication rate of 26.8% was reported. These investigators noted increased neck pain in 6.7% of cases and headache for less than 24 hours in 4.6% of cases. Transient insomnia, vasovagal reactions, and facial flushing all occurred at a rate of under 2%. It is likely that the high overall rate of complications in this study was related to the sensitivity of labeling an event a complication, as the mentioned complications were relatively safe and temporary. However, there have been other reports of more serious complications. Epidural hematoma has been reported six times in the literature. Most occurrences were in patients who were also undergoing anticoagulation regimens. These patients generally went on to have laminectomies, and recovery ranged from full recovery to paraplegia, urinary retention, or long-term neck pain. Dural punctures with reported rates ranging from 0.25% to 2.65% have been reported. Other severe reported complications include neuropathic syndromes, pneumocephalus (found with use of air for loss of resistance in one case), venous air embolism, cervical epidural abscess, Cushing s syndrome, and death (only one report in the literature; in this case, a spinal hematoma led to acute meningitis that ultimately resulted in a cardiac arrest). Abbasi colleagues 19 conducted an extensive review on cervical TLESI. They reported that the consensus is that cervical TLESI is a safe procedure. While one study reported a complication rate of 16.8%, all of the complications were transient. Other studies reported lower complication rates. The incidence of vasovagal reactions, however, may be higher than for lumbar TLESI. Ultimately, while severe complications exist, they are rare and can be minimized by good technique. Cervical TFESI Use of a transforaminal approach can allow the practitioner to perform a diagnostic and therapeutic selective nerve root

248 Bulletin of the NYU Hospital for Joint Diseases 2012;70(1): block to help identify the affected level and the success of selective decompression in the future, should it become necessary. There are a limited number of reports in the literature regarding the efficacy of cervical TFESI, probably because these injections are performed less commonly due to concern about complications. In one study, Anderberg and coworkers 21 looked at 40 patients with cervical radiculopathy randomized to steroid and local anesthetic TFESI or saline with local anesthetic injections. No significant difference was found between the two groups. There are also only a few studies regarding the complications of transforaminal cervical epidural steroid injections. Most of the reported incidents are case reports, and therefore the true incidence of these complications is not yet known. One study of 1,036 injections in 844 patients found an overall complication rate of 1.64%. 22 In that study, there were five headaches, six transient neurologic deficits (pain or weakness), one hypersensitivity reaction, one vasovagal reaction, and one incident of transient global amnesia. In another study, Slipman and colleagues found three dural punctures, one vasovagal bradycardic response, one allergic reaction to local anesthetic leading to unresponsiveness, two allergic responses to contrast, and one posterior interosseous syndrome in their series of 888 procedures. While the complications in the study conducted by Ma and associates 22 were generally transient, others have reported much more serious adverse outcomes. For instance, Scanlon and coworkers 23 sent out 287 surveys to physicians and found 78 complications, of which 70 involved corticosteroids. Complications included 16 vertebrobasilar brain infarcts, 12 cervical spinal cord infarcts, and two combined brain and spinal cord infarcts. Additionally, there were five deaths of unspecified etiology, thee high spinal anesthesias, three transient ischemic attacks, two seizures, two severe headachse, two spinal cord edemas, one brainstem edema with herniation, one brain edema with reversible ischemic neurologic deficit, one cortical blindness due to air embolus, one cervical epidural hematoma, one paraspinal hematoma, one peripheral neurapraxia, and one vasovagal response. While this type of study likely includes a very large number of patients and does not allow us to know what the incidence of these injuries is, they are nevertheless serious complications and the practicing surgeon must be aware of the risks associated with this procedure. Conclusion There is good evidence that both transforaminal and translaminar epidural steroid injections can provide reliable pain relief for up to 6 months. In the lumbar spine, both TLESI and TFESI are relatively safe and efficacious. The exact complication rates of these injections are difficult to know given the existing literature but are thought to be low. In the cervical spine, there is good evidence to support TLESI, and reliable pain relief has been demonstrated at one year or longer in some studies. In contrast, cervical TFESI are used less often, and there is a paucity of literature evaluating these injections. There is to date no reliable studies demonstrating their efficacy, and there have been a number of potentially devastating complications reported. Since cervical radiculopathy can also be treated with TLESI, we urge caution before proceeding with cervical TFESI. Disclosure Statement The authors have no financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony. References 1. Carette S, Leclaire R, Marcoux S, et al. Epidural corticosteroid injections for sciatica due to herniated nucleus pulposus. N Engl J Med. 1997;336: Arden NK, Price C, Reading I, et al. A multicentre randomized controlled trial of epidural corticosteroid injections for sciatica: the WEST study. Rheumatology (Oxford). 2005;44: Wilson-MacDonald J, Burt G, Griffin D, Glynn C. Epidural steroid injection for nerve root compression. A randomised, controlled trial. J Bone Joint Surg Br. 2005;87: Parr AT, Diwan S, Abdi S. Lumbar interlaminar epidural injections in managing chronic low back and lower extremity pain: a systematic review. Pain Physician. 2009;12: Watanabe AT, Nishimura E, Garris J. Image-guided epidural steroid injections. Tech Vasc Interv Radiol. 2002;5: Yang SC, Fu TS, Lai PL, et al. Transforaminal epidural steroid injection for discectomy candidates: an outcome study with a minimum of two-year follow-up. Chang Gung Med J. 2006;29: Kolsi I, Delecrin J, Berthelot JM, et al. Efficacy of nerve root versus interspinous injections of glucocorticoids in the treatment of disk-related sciatica. A pilot, prospective, randomized, double-blind study. Joint Bone Spine. 2000;67: Riew KD, Yin Y, Gilula L, et al. The effect of nerve-root injections on the need for operative treatment of lumbar radicular pain. A prospective, randomized, controlled, double-blind study. J Bone Joint Surg Am. 2000;82: Schaufele MK, Hatch L, Jones W. Interlaminar versus transforaminal epidural injections for the treatment of symptomatic lumbar intervertebral disc herniations. Pain Physician. 2006;9: Lee JH, An JH, Lee SH. Comparison of the effectiveness of interlaminar and bilateral transforaminal epidural steroid injections in treatment of patients with lumbosacral disc herniation and spinal stenosis. Clin J Pain. 2009;25: Houten JK, Errico TJ. Paraplegia after lumbosacral nerve root block: report of three cases. Spine J. 2002;2: Castagnera L, Maurette P, Pointillart V, et al. Long-term results of cervical epidural steroid injection with and without morphine in chronic cervical radicular pain. Pain. 1994;58: Stav A, Ovadia L, Sternberg A, et al. Cervical epidural steroid injection for cervicobrachialgia. Acta Anaesthesiol Scand. 1993;37: Ferrante FM, Wilson SP, Iocobo C, et al. Clinical classification

249 10 Bulletin of the NYU Hospital for Joint Diseases 2012;70(1):6-10 as a predictor of therapeutic outcome after cervical epidural steroid injection. Spine (Phila Pa 1976). 1993;18: Rowlingson JC, Kirschenbaum LP. Epidural analgesic techniques in the management of cervical pain. Anesth Analg. 1986;65: Manchikanti L, Singh V, Pampati V, et al. Description of documentation in the management of chronic spinal pain. Pain Physician. 2009;12(4):E Waldman SD. Complications of cervical epidural nerve blocks with steroids: a prospective study of 790 consecutive blocks. Reg Anesth. 1989;14: Botwin KP, Castellanos R, Rao S, et al. Complications of fluoroscopically guided interlaminar cervical epidural injections. Arch Phys Med Rehabil. 2003;84(5): Abbasi A, Malhotra G, Malanga G, et al. Complications of interlaminar cervical epidural steroid injections: a review of the literature. Spine (Phila Pa 1976). 2007;32: Radhakrishnan K, Litchy WJ, O Fallon WM, Kurland LT. Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through Brain. 1994;117( Pt 2): Anderberg L, Annertz M, Persson L, et al. Transforaminal steroid injections for the treatment of cervical radiculopathy: a prospective and randomised study. Eur Spine J. 2007;16: Ma DJ, Gilula LA, Riew KD. Complications of fluoroscopically guided extraforaminal cervical nerve blocks. An analysis of 1036 injections. J Bone Joint Surg Am. 2005;87: Scanlon GC, Moeller-Betram T, Romanowsky SM, Wallace MS. Cervical tranforaminal epidural steroid injections: more dangerous than we think? Spine (Phila Pa 1976). 2007;32(11):

250 SPINE Volume 37, Number 12, pp , Lippincott Williams & Wilkins CERVICAL SPINE Clinical Outcomes of Cervical Radiculopathy Following Epidural Steroid Injection A Prospective Study With Follow-up for More Than 2 Years Sang-Hun Lee, MD, * Ki-Tack Kim, MD, * Dong-Hwan Kim, MD, Bong-Jae Lee, MD, Eun-Seok Son, MD, and Yoon-Ho Kwack, MD * Study Design. A prospective clinical outcome study. Objective. To analyze clinical outcome and prognostic factors of the epidural steroid injection (ESI) for cervical radiculopathy (CR) patients who were considered surgical candidates. Summary of Background Data. The clinical outcomes and prognostic factors of ESI for CR have not been consistently reported, and there has been no prospective study with long-term follow-up. Methods. ESI was administered in 98 patients (mean age = 50.1 yr, follow-up = 40.4 mo) with CR without major neurological deficit. A total of 3 or fewer ESIs were administered, using either the interlaminar or transforaminal technique. The patients were divided into 2 groups: those who did not have surgery and those who underwent surgery at the last follow-up. We analyzed statistical difference of relevant clinical (sex, age, duration of symptom, previous episode of CR, visual analogue scale [VAS] of arm pain, etc.), radiological factors (soft disc vs. hard disc, central disc vs. foraminal disc, single segment involvement vs. multiple segment involvement, degree of neural compression and degeneration, etc.) and clinical outcomes (VAS of arm pain, Odom s criteria, and neck disability index) between the 2 groups. Results. The patients received mean 1.8 ESI treatments. At the final follow-up, 79 of the patients (80.6%) did not undergo surgery, whereas the other 19 patients (19.4%) underwent surgery. Of the clinical factors, recurred CR (15.2% vs. 42.1%, P = 0.022) and mean VAS score of arm pain before (6.1 vs. 8.2, P = 0.000) and From the * Department of Orthopedic Surgery ; Physical Medicine and Rehabilitation ; Anesthesiology and Pain Medicine, Kyung Hee University Hospital at Gangdong, Seoul ; and Department of Orthopedic Surgery, Kei Myung University, College of Medicine, Daegu, Korea. Acknowledgment date: May 25, First revision date: August 10, Acceptance date: September 30, The manuscript submitted does not contain information about medical device(s)/drug(s). No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. Address correspondence and reprint requests to Sang-Hun Lee, MD, Department of Orthopaedic Surgery, Spine Center, Kyung Hee University Hospital at Gangdong, #149, Sangil-dong, Kangdong-gu, Seoul , Korea; shl6@khu.ac.kr DOI: /BRS.0b013e31823b4d1f after ESI (2.8 vs. 6.9, P = 0.000) were significantly different between both groups. Radiological factors and outcome parameters showed no significant difference. Conclusion. In more than 80% of patients with CR who were surgical candidates, surgery was avoided using ESI. The significant factors predisposing failure of ESI were intensity of symptom and a previous episode of CR. ESI is therefore considered a safe and effective treatment to choose before undergoing surgery. Key words: epidural steroid injection, cervical radiculopathy, outcomes, prognostic factors. Spine 2012 ; 37 : Although it is generally agreed that early surgical treatment is required for cervical radiculopathy (CR) accompanied by a major neurological deficit or progressive motor paralysis, the chief complaint of CR in most cases is arm pain, and conservative treatment has an excellent outcome in more than 80% of cases. 1 Epidural steroid injection (ESI) has been in use since the 1950s as a treatment for various pains with spinal origin. 2 As a mechanism that reduces the inflammatory response to neural compression and blocks the transmission of pain through nociceptive nerve fibers, its clinical success rates have varied from 40% to 80% in previous studies, and it is currently used extensively as a valuable method for conservatively treating CR. 3 5 However, evidence supporting the effectiveness of ESI is relatively weak compared with lumbar radiculopathy 6, 7 ; the principal reasons for this are that there are few prospective randomized studies, 8 the treatment results vary with each study, and the factors that predict the treatment results and ESI prognosis have not been consistently reported. In particular, most reports of the effectiveness of ESI treatment for CR are based on the results of a few weeks or months of follow-up, and more than 1- or 2-year follow-up studies are rare The purpose of this study was to analyze clinical outcomes and prognostic factors of ESI for a cohort of patients with CR who were considered surgical candidates and compare the clinical outcomes of the group that did not have surgery with the group that underwent surgery after long-term follow-up of more than 2 years. Spine Copyright 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

251 CERVICAL SPINE Epidural Steroid Injection for Cervical Radiculopathy Lee et al MATERIALS ESI was administered in a cohort of patients with CR prospectively from 2007 to Inclusion criteria were defined as patients with neck pain, arm pain, and/or neurological symptoms that did not improve after more than 4 weeks of other conservative treatment than ESI and with a magnetic resonance imaging (MRI) and computed tomography (CT) diagnosed cervical soft disc or hard disc causing nerve root compression and symptoms consistent with the lesion. Patients who previously received ESI treatment or underwent surgery in the cervical area, patients with definite motor weakness (with a muscle grade lower than IV), or patients presenting symptoms of myelopathy were excluded from the study. ESI was administered up to 3 times with 1- to 2-week time intervals, and the injection treatment was discontinued if the visual analogue scale (VAS) for arm pain became subjectively tolerable or when the initial pain was reduced by more than 80%. Patients chose surgical treatment if, either during or after ESI treatment, the pain did not become tolerable or neurological symptoms either occurred or worsened. Recurrence of symptom was defined as recurred pain more than 50% of initial VAS or subjectively intolerable pain after finishing of ESI with clinical improvement. Residual symptom was defined as pain less than 50% of initial VAS or subjectively tolerable pain. The patients who had residual symptoms took conservative management, including rest, medication, and/or physical treatment according to their severity of pain. Ninety-eight patients (60 males and 38 females), who were monitored for more than 2 years of follow-up, were divided into 2 groups: those who did not have surgery and those who underwent surgery by the time of their final follow-up. We then compared the relevant factors and clinical outcomes after the final follow-up visit. The mean patient age was 50.1 years (with a range of yr), and the mean follow-up duration was 40.4 months (with a range of mo). ESI Technique A total of 3 or fewer ESIs were administered, using either the interlaminar (IL) or transforaminal (TF) technique, which was based on image findings. Specifically, the IL technique was used in cases of central or paracentral disc herniation or when more than 2 levels of herniated disc were suspected, whereas the TF technique was used in single-level foraminal disc herniation or when a nerve root causing symptoms is suspected clearly, even in the case of multilevel disc herniation. After performing ESI with the first method, if the VAS for pain reduction was less than 50% (indicating that the improvement of symptoms was insufficient), both methods were then used alternatingly. All ESIs were administered by a rehabilitation physician (K.D.H) or a pain physician (L.B.J), who used a 22-gauge spinal or epidural needle under fluoroscopic guidance to inject 0.5 to 1 ml of contrast media (Omnipaque 300 [iohexol, 300 mg/ml iodine]; Amersham Health, Princeton, NJ). After confirming the placement of the needle, a solution of 0.5% lidocaine and 10 mg (2 ml) dexamethasone sodium phosphate (Cheil Pharmaceutical, Seoul, Korea) was prepared; 4 to 6 ml of this solution was injected for the IL technique, whereas 2 ml was injected for the TF technique. Analysis of Relevant Factors and Outcomes Clinical Factors The patients s sex, age, duration of CR symptoms, accompanying neck pain, a previous episode of CR, which is improved with conservative treatment other than ESI, presence of sensory and motor change not less than grade IV, existence of compensation including motor vehicle accidents and worker s compensation, and the methods and frequency of ESI and VAS for arm pain both initially and after the completion of ESI were measured. Radiological Factors The imaging characteristics of the neural compression were analyzed and included a comparison of soft discs versus hard discs confirmed by CT images, the location of neural compression; central discs versus foraminal discs, the neural compression ratio in the axial plane; single segments versus multiple segments involvement, the presence of segmental kyphosis based on plain lateral radiographic findings; the progression of degenerative changes in the relevant segments on the plain lateral radiograph according to the Kellgren classification system (grades 0 4) 15 ; and Pavlov s ratio of the fifth cervical vertebra and the location of affected segments causing symptoms ( e.g., C3/C4, C4/C5, C5/C6, C6/C7). The uncovertebral joint line on the T2 axial MRI was used to classify the location of neural compression. The disc herniation that compresses the neural structure at medial side of the line was considered to be a central disc and lateral side was considered to be a foraminal disc ( Figure 1 ). To measure the degree of neural compression at the axial plane, a line was drawn from the center of the anterior annulus to the point of maximal neural compression. The neural compression ratio was calculated based on this line as the ratio of the compressed spinal canal or foramen diameter to those of normal diameter on T2 axial MRI ( Figure 2 ). Clinical Outcomes To assess the clinical course after ESI, we analyzed the number of patients who had recurrence of symptoms and had residual symptoms, required other conservative management more than 4 weeks, during follow-up. We measured the following clinical outcomes at the medical record or telephone interview: VAS of arm pain at the time of final follow-up, percentage of excellent or good in a classification based on Odom s criteria, neck disability index (NDI), and whether the patients agree to repeat the same treatment in the future. Furthermore, any complications and/or recurrence of symptoms after ESI were analyzed. For statistical analyses, SPSS 17.0 (Chicago, IL) was used to perform an unpaired Student t test and a χ 2 test; differences with P < 0.05 were considered significant May 2012 Copyright 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

252 CERVICAL SPINE Epidural Steroid Injection for Cervical Radiculopathy Lee et al Figure 1. The location of neural compression on T2 axial image. The disc herniation that compresses the neural structure at medial side of the line of uncovertebral joint was considered to be a central disc ( A ) and lateral side was considered to be a foraminal disc ( B ). If the disc herniation compresses the neural structure at both medial and lateral sides of the uncovertebral joint, which was classified as both types ( C ). RESULTS On average, patients received 1.8 ESI treatments (with a range of 1 3 treatments); the IL and TF techniques were performed on an average of 1.3 (with a range of 1 3) and 0.5 (with a range of 1 3) times, respectively. At the final follow-up, 79 of the patients (80.6%) did not undergo surgery, whereas the other 19 patients (19.4%) underwent surgery. Relevant Clinical Factors We compared the nonsurgical and surgical groups and found no significant difference for the following parameters: percentage of male patients (59.3% vs. 68.4%, P = 0.603); mean age (50.4 yr vs yr, P = 0.503); average duration of CR symptoms (4 mo vs. 2.3 mo, P = 0.298); percentage of patients with accompanying neck pain (70.9% vs. 73.7%, P = 1.000); percentage of patients with accompanying sensory change (16.5% vs. 21.1%, P = 0.736); percentage of patients with accompanying motor change (8.9% vs. 10.5%, P = 1.000); percentage of patients with evidence of compensation (5.1% vs. 10.5%, P = 0.329); and average number of ESI treatments (IL: 1.3 vs. 1.26, P = 0.844; TF: 0.52 vs. 0.58, P = 0.751; Table 1 ). In contrast, the following parameters were significantly different between the nonsurgical and surgical groups: percentage of patients who had a previous episode of CR (15.2% vs. 42.1%, P = 0.022); average VAS score of arm pain before ESI (6.1 vs. 8.2, P = 0.000); and average VAS score of arm pain after completion of ESI (2.8 vs. 6.9, P = 0.000). TABLE 1. Clinical Parameters for Cervical Radiculopathy Patients Total No. of Cases Nonsurgery Group Surgery Group 79 (80.6%) 19 (19.4%) M:F ratio 47:32 13: Age 50.4 ± ± Duration of Sx. (mo) 4 ± ± Previous episode of cervical radiculopathy 12 (15.2%) 8 (42.1%) 0.022* Symptoms Neck pain 56 (70.9%) 14 (73.7%) Sensory change 13 (16.5%) 4 (21.1%) Motor change 7 (8.9%) 2 (10.5%) Compensation 4 (5.1%) 2 (10.5%) No. of ESI ILESI 1.3 ± ± TFESI 0.52 ± ± VAS score of arm pain Pre-ESI 6.1 ± ± * Post-ESI 2.8 ± ± * P * P < Figure 2. A T2 axial image on C5-6 showing measurement method of ESI indicates epidural steroid injection; ILESI, interlaminar epidural steroid injection; TFESI, transforaminal epidural steroid injection; Sx., symptoms. the neural compression ratio ; A/B 100 (%). Spine Copyright 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

253 CERVICAL SPINE Epidural Steroid Injection for Cervical Radiculopathy Lee et al TABLE 2. Radiological Parameters for Prediction of Prognosis of Epidural Steroid Injection for Cervical Radiculopathy Nonsurgery Group (N = 79) Surgery Group (N = 19) P Soft:hard disc ratio 49:30 12: Location of compression Central 20 (25.3%) 4 (21%) Foraminal 36 (45.6%) 11 (57.9%) Both 23 (29.1%) 4 (21%) Compression ratio (%) 59.7 ± ± Multilevel 32 (40.5%) 11 (57.9%) involvement Segmental kyphosis 8 (10.1%) 4 (21.1%) Kellgren grade 1.6 ± ± C5 Pavlov ratio 0.9 ± ± Involved segments C3/C4/C5 8 (10.1%) 3 (15.8%) C5/C6 40 (50.6%) 6 (31.6%) C6/C7 31 (39.2%) 10 (52.6%) Relevant Radiological Factors We compared the percentage of nonsurgical and surgical patients with a soft disc ratio (89.9% vs. 78.9%, P = 0.240; Table 2 ). Moreover, we examined the location of the disc herniation (central/foraminal/both) in the nonsurgical group (20/36/23 patients) and surgical group (4/11/4 patients) and found no significant differences between the 2 groups ( P = 0.619, 0.617, and 0.837, respectively). The other parameters were not significantly different between the nonsurgical and surgical groups: percentage of patients with neural compression ratio (59.7% vs. 61.9%, P = 0.462); incidence of multilevel nerve compression (40.5% vs. 57.9%, P = 0.203); percentage of patients with segmental kyphosis (10.1% vs. 21.1%, P = 0.240); grade of degenerative change according to the Kellgren classification (1.59 vs. 1.57, P = 0.929), C5 Pavlov ratio (0.9 vs. 0.87, P = 0.372); and number of patients with C3/C4/C5:C5/C6:C6/C7 involvement (8:40:31 patients vs. 3:6:10 patients; P = 0.310, 0.313, 0.649, respectively). Surgical Treatment Surgery was performed in a total of 19 cases (19.4% of all patients in the cohort), an average of 5.6 weeks (range, 2 24 wk) after the completion of ESI treatment. Sixteen patients elected to have surgery due to intolerable pain, whereas the remaining 3 patients chose surgery on the basis of their progression of neurological symptoms. Fifteen patients underwent an anterior cervical discectomy and fusion, 3 patients TABLE 3. Comparison of Clinical Outcomes in Both Groups Nonsurgery Group (N = 79) Surgery Group (N = 19) P VAS score of arm pain 2.7 ± ± Odom s criteria; excellent 63 (79.7%) 15 (78.9%) and good NDI 8.3 ± ± Repeat the same treatment 60 (75.9%) 11 (57.9%) VAS indicates visual analogue scale; NDI, neck disability index. underwent an artificial disc replacement, and 1 patient underwent posterior laminoforaminotomy. Clinical Outcomes The outcome parameters of all patients were checked at the clinic for 74 patients (75.5%) and by a telephone interview for 24 patients (24.5%; Table 3 ). The nonsurgical and surgical patients averaged a VAS score for arm pain at their final follow-up of 2.7 and 2.2, respectively ( P = 0.290). The percentage of patients with a good or excellent Odom s score was similar between nonsurgical (79.7%) and surgical (78.9%) patients ( P = 0.938); the average NDI score was also not significantly different between the nonsurgical and surgical groups (8.3 vs. 9.1, P = 0.680). Sixty of the nonsurgical patients (75.9%) and 11 of the surgical patients (57.9%) agreed to repeat the same treatment in the future; this difference was not significantly different ( P = 0.152; Figure 3 ). Complications and Recurrence of Symptoms With regard to complications after ESI with the IL technique, 1 patient experienced an episode of syncope due to a vasovagal reaction and 1 patient experienced transient paresthesia following dural puncture after the IL procedure; both patients improved with conservative treatment. There were no complications after ESI with the TF technique. After ESI treatment, a total of 16 patients (16.3%) showed recurrent symptoms during the follow-up period. Six of these patients were in the nonsurgical group (7.6%) and showed a recurrence of symptoms after an average of 1.6 months (with a range of 1 3 mo) that improved after additional ESI and other conservative treatments; the remaining 10 patients were in the surgical group (40%) and showed a recurrence of symptoms after an average of 1.2 months (with a range of 1 6 mo). A total of 18 patients (18.4%) have taken other kind of conservative treatment for more than 4 weeks for their residual symptom. Mean duration of conservative treatment was 5.5 weeks (with a range of 4 7 wk), but none of the patients who had residual symptoms underwent surgery May 2012 Copyright 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

254 CERVICAL SPINE Epidural Steroid Injection for Cervical Radiculopathy Lee et al Figure 3. Initial axial T1 and T2 magnetic resonance images on C6-7 ( A and B ) of a 29-year-old male patient with cervical radiculopathy (visual analogue scale [VAS] score of arm pain, 8) caused by central and foraminal soft disc herniation on the right-hand side. A total of 2 transforaminal ESIs were administered with 2 weeks interval. Magnetic resonance images were taken after 6 months follow-up ( C and D ) showing substantial amount of resorption of the herniated cervical disc with excellent clinical outcome (VAS score of arm pain, 1.5). DISCUSSION The first case using ESI to treat CR was reported in 1961; since then, several studies have reported various treatment outcomes. 16 In 1996, Bush and Hillier 17 performed either IL or TF ESI or cervical plexus block in 68 patients with CR who had symptoms for more than 1 month and were considered surgical candidates. They reported that all 68 patients no longer required surgery after showing marked improvement in their symptoms. Other studies have reported excellent clinical outcomes in 60% to 83% of cases, using the IL or TF ESI method However, several other studies have reported that only about 20% of cases showed improved symptoms or avoided surgery 13, 14 ; in particular, a 2007 study by Anderberg et al 8 which is the only reported prospective randomized study to date reported that using local anesthetics alone was as effective as using transforaminal epidural steroid injection with steroids, and only about 16% to 17% of cases showed improved symptoms. Thus, there is currently no consensus regarding the effectiveness of ESI for CR. In this study, we administered ESI prospectively to all patients in a cohort of patients with CR who were considered to be surgical candidates; we then observed the clinical outcome of these patients, more than 80% of whom were able to avoid surgery. This is similar to (or even better than) the outcome of previous studies, presumably because of our study design, in which CR patients accompanied by definite motor weakness less than grade IV were excluded, and only those patients who had not previously received ESI were included; in addition, both ESI methods (IL and TF) were used, depending on the clinical symptoms. When we compared the clinical outcome of nonsurgical and surgical patients at their final follow-up, the groups did not differ significantly in terms of their Odom s criteria, NDI, or whether they agreed to repeat the same treatment. This agrees with previous studies that reported no significant difference between the groups after long-term follow-up of surgical and conservative treatment of lumbar disc herniation or 18, 19 lumbar spinal stenosis. Previous studies have analyzed the factors that affect the prognosis for ESI treatment, but they have reported contradictory results. First, with regard to symptom duration, a 2004 study by Cyteval et al 20 claimed that the duration of symptoms does not influence the prediction of prognosis; however, in 2007, Kwon et al 10 reported that prognosis is improved when symptoms persist for less than 6 months. There are also conflicting reports with regard to patient age; in one report, young patients showed a good outcome, 10 whereas another report showed that patients older than 50 years had a better outcome. 12 In addition, it has been reported that post-esi prognosis is improved when central canal stenosis is present as an anatomical factor 21 and that disc herniation shows a better prognosis than foraminal stenosis. 10 This study analyzed as many clinical and radiological factors as possible, including some of the factors that were analyzed in previous studies; however, the factors that were reported to affect prognosis the male/female disparity and the duration and pattern of symptoms did not show differences in this study. Moreover, generally presumed radiological factors such as hard versus soft disc, foraminal versus central disc, severity of the radiological neural compression, location of the involved segment, Pavlov ratio, and involvement of multiple levels involvement all were not significantly different. The only factors that were significantly different were a previous episode of CR, the initial intensity of arm pain was more severe, and the pain did not improve after ESI treatment. A correlation between the degree of neural compression and the severity of the resulting symptoms (and how they react to ESI) has not yet been clearly established. In our study, surgery was performed when the patient s subjective pain did not become tolerable after ESI treatment or when neurological symptoms progressed; however, the surgical patients had significantly less pain improvement from ESI when compared with the nonsurgical group (VAS scores were 6.9 and 2.8, respectively; P = 0.000), and recurrence rate after ESI was relatively high compared with nonsurgical group (40:7.6%). Recently, Golish et al 22 reported that a molecular complex containing fibronectin and aggrecan is a biomarker that can predict the treatment prognosis of lumbar ESI in radiculopathy, and Kim et al 23 reported that the A3 allele of the IL1RN gene both reduces the effectiveness of ESI in treating lumbar herniated disc and contributes to symptom progression. No equivalent study for CR has been reported; however, based on the results of our study, this may be due to the patients Spine Copyright 2012 Lippincott Williams & Wilkins. 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255 CERVICAL SPINE Epidural Steroid Injection for Cervical Radiculopathy Lee et al pain response and sensitivity, including an anti-inflammatory reaction to ESI in the epidural space, rather than clinical symptoms or radiological findings. Future studies of this are needed. Various ESI complications have been reported, and these range from mild nerve irritation to serious complications leading to paraplegia or brain injury caused by epidural hematoma or infection. The incidence of these complications ranges from 1.64% for TF and up to 16.8% for IL 24, 25 ; however, in this study, only 2 patients experienced temporary minor complications. Moreover, recent advances in fluoroscopy and CT-guided methods have resulted in a trend of improved safety. 26 On the basis of the results of our study, attempting ESI treatment in a CR patient without neurological symptoms is reasonable before deciding surgery, regardless of the degree of neural compression or the characteristics observed from imaging. Furthermore, although the impact of ESI on the natural progress of CR is not yet fully understood, the important therapeutic aspects of relieving the clinical symptoms and avoiding surgical intervention together with the fact that it can be useful for both localizing the segments that are suspected to be the cause of the symptoms from current radiological findings and predicting the outcomes after surgery 27, 28 add to its usefulness. Limitations of this study should be noted. First, the ESI methods could not be standardized. The first ESI session was selected on the basis of the area of neural compression, but the method performed ( i.e., IL or TF) was chosen on the basis of the symptoms; thus, the selection criterion for the ESI methods in this study could not be expressed clearly. However, although there have been reports of the advantages and disadvantages of each method (as well as their respective complications), no single study compares and analyzes both methods, and this needs to be investigated in the future. Second, conservative treatment modalities after finishing ESI were not standardized. More than 18% of the cohort, who are even not included in the recurrence group, had taken rest, medication, and/or physical treatment for more than 4 weeks for their residual symptom. But their choice of conservative treatment method was not analyzed in this study. Finally, and most importantly, the effectiveness of ESI was not compared with natural history of CR. An argument could be made that ESI could just provide a temporary effect without actual benefit on the long-term result. Until now, the conservative treatment, including rest, medication, physical treatment, and ESI, has not been demonstrated as an evidence to alter the natural history of CR, except anecdotal improvement. The result of this study is not outcomes of ESI as a general treatment option for CR but the outcomes and related factors of ESI for the patients whose symptoms were not improved by other conservative treatment for more than 4 weeks; i.e., possible surgical candidate. The effectiveness of ESI on CR comparing with natural history should be studied with a prospective, randomized design and larger number of cases in the future. CONCLUSION In more than 80% of patients with CR who were surgical candidates, surgery was avoided without complications using ESI. The significant factors predisposing failure of ESI were intensity of symptom and a previous episode of CR. With long-term follow-up, no difference was found in the clinical outcome between the surgical and nonsurgical groups. ESI is therefore considered a safe and effective treatment to choose before undergoing surgery. Key Points The clinical outcomes and prognostic factors of ESI for CR have not been consistently reported. In more than 80% of patients with CR who were surgical candidates, surgery was avoided using ESI. The significant factors predisposing failure of ESI were intensity of symptom and a previous episode of CR. Radiological factors and outcome parameters showed no significant difference between the nonsurgical and surgical patients. ESI is therefore considered a safe and effective treatment to choose before undergoing surgery. References 1. Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine 1996 ; 21 : Lievre JA, Bloch-Michel H, Attali P. Epidural hydrocortisone in the treatment of sciatica. Rev Rhum Mal Osteoartic 1955 ; 22 : Johansson A, Hao J, Sjolund B. Local corticosteroid application blocks transmission in normal nociceptive C-fibres. Acta Anaesthesiol Scand 1990 ; 34 : Olmarker K, Byrod G, Cornefjord M, et al. Effects of methylprednisolone on nucleus pulposus-induced nerve root injury. Spine 1994 ; 19 : Lee HM, Weinstein JN, Meller ST, et al. The role of steroids and their effects on phospholipase A2 An animal model of radiculopathy. Spine 1998 ; 23 : Cynthia P, Hodler J. Evidence based radiology (part 1): Is there sufficient research to support the use of therapeutic injections for the spine and sacroiliac joint? Skeletal Radiol 2010 ; 39 : Manchlkantl L, Boswell MV, Datta S, et al. Comprehensive evidence-based guideline for interventional techniques in the management of chronic spinal pain. Pain Physician 2009 ; 12 : E Anderberg L, Anenrtz M, Persson L, et al. Transforaminal steroid injection for the treatment of cervical radiculopathy: a prospective and randomized study. Eur Spine J 2007 ; 16 : Lee JW, Park KW, Chung SK, et al. Cervical transforaminal epidural steroid injection for the management of cervical radiculopathy: a comparative study of particulate versus non-particulate steroids. Skeletal Radiol 2009 ; 38 : Kwon JW, Lee JW, Kim SH, et al. Cervical interlaminar epidural steroid injection for neck pain and cervical radiculopathy: effect and prognostic factors. Skeletal Radiol 2007 ; 36 : Strub WM, Brown TA, Ying J, et al. Translaminar cervical epidural steroid injection: short-term results and factors influencing outcome. J Vasc Interv Radiol 2007 ; 18 : Lin EL, Lieu V, Halevi L, et al. Cervical epidural steroid injections for symptomatic disc herniations. J Spinal Disord Tech 2006 ; 19 : Razzaq AA, O Brien D, Mattew B, et al. Efficacy and durability of fluoroscopically guided cervical nerve root block. 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256 CERVICAL SPINE Epidural Steroid Injection for Cervical Radiculopathy Lee et al 14. Kolstad F, Leivseth G, Nygaard OP. Transforaminal steroid injections in the treatment of cervical radiculopathy. A prospective outcome study. Acta Neurochir (Wien) 2005 ; 147 : Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957 ; 16 : Thierry-Mieg J. Cervical epidural injections of corticoids in hyperalgic cervico-brachial neuralgias. 1st cervical epidurographical pictures. Rev Rhum Mal Osteoartic 1961 ; 28 : Bush K, Hillier S. Outcome of cervical radiculopathy treated with periradicular/epidural corticosteroid injections: a prospective study with independent clinical review. Eur Spine J 1996 ; 5 : Weber H. Lumbar disc herniation. A controlled, prospective study with ten years of observation. Spine 1983 ; 8 : Atlas SJ, Keller RB, Wu YA, et al. Long-term outcomes of surgical and nonsurgical management of lumbar spinal stenosis: 8 to 10 year results from the Maine Lumbar Spine Study. Spine 2005 ; 30 : Cyteval C, Thomas E, Decoux E, et al. Cervical radiculopathy: open study on percutaneous periradicular foraminal steroid infiltration under CT control in 30 patients. Am J Neuradiol 2004 ; 25 : Fish DE, Kobayashi HW, Chang TL, et al. MRI prediction of therapeutic response to epidural steroid injection in patients with cervical radiculopathy. Am J Phys Med Rehabil 2009 ; 88 : Golish S, Hanna LS, Bowser RP, et al. Outcome of lumbar epidural steroid injection in predicted by assay of a complex of fibronectin and aggrecan from epidural lavage. Spine 2011 ; 36 : Kim DH, Lee SH, Kim KT, et al. Association of interleukin-1 receptor antagonist gene polymorphism with response to conservative treatment of lumbar herniated nucleus pulposus. Spine 2010 ; 35 : Abbasi A, Malhotra G, Malanga G, et al. Complications of interlaminar cervical epidural steroid injections. A review of the literature. Spine 2007 ; 32 : Malhotra G, Abbasi A, Rhee M. Complications of transforaminal cervical epidural steroid injections. Spine 2009 ; 34 : Stout A. Epidural steroid injections for cervical radiculopathy. Phys Med Rehabil Clin North Am 2011 ; 22 : Sasso R, Macadaeg K, Nordmann D, et al. Selective nerve root injections can predict surgical outcome for lumbar and cervical radiculopathy. J Spinal Disord Tech 2005 ; 18 : Anderberg L, Annertz M, Brandt L, et al. Selective diagnostic nerve root block-correlation with clinical symptoms and MRI-pathology. Acta Neurochir (Wien) 2004 ; 146 : Rhee JM, Yoon T, Riew KD. Cervical radiculopathy. J Am Acad Orthop Surg 2007 ; 15 : Levine MJ, Albert TJ, Smith MD. Cervical radiculopathy: diagnosis and nonoperative treatment. J Am Acad Orthop Surg 1996 ; 4 : Graham N, Gross A, Goldsmith CH, et al. Mechanical traction for neck pain with or without radiculopathy. Cochrane Database Syst Rev 2008 ; 3 : CD Zundert JV, Huntoon M, Patijn J, et al. Cervical radicular pain. Pain Pract 2010 ; 10 : Spine Copyright 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

257 Pain Physician 2012; 15:E59-E70 ISSN Randomized Trial Fluoroscopic Epidural Injections in Cervical Spinal Stenosis: Preliminary Results of a Randomized, Double-Blind, Active Control Trial Laxmaiah Manchikanti, MD 1,2, Yogesh Malla, MD 1, Kimberly A. Cash, RT 1, Carla D. McManus, RN 1, and Vidyasagar Pampati, MSc 1 From: 1 Pain Management Center of Paducah, Paducah, KY; and 2 University of Louisville, Louisville, KY Dr. Manchikanti is Medical Director of the Pain Management Center of Paducah, Paducah, KY and Associate Clinical Professor, Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY. Dr. Malla is an Interventional Pain Physician at the Pain Management Center of Paducah, Paducah, KY. Kimberly A. Cash is a Research Coordinator at the Pain Management Center of Paducah, Paducah, KY. Carla D. McManus is a Nursing Administrator at the Pain Management Center of Paducah, Paducah, KY. Vidyasagar Pampati is a Statistician at the Pain Management Center of Paducah, Paducah, KY. Address correspondence: Laxmaiah Manchikanti, MD 2831 Lone Oak Road Paducah, KY drlm@thepainmd.com Disclaimer: There was no external funding in the preparation of this manuscript. Conflict of interest: None. Manuscript received: 11/10/2011 Accepted for publication: 12/16/2011 Free full manuscript: Background: Cervical spinal stenosis is a common disease that results in considerable morbidity and disability. There are multiple modalities of treatments, including surgical interventions and multiple interventional techniques including epidural injections. The literature on the effectiveness of cervical epidural steroids is sporadic. Emerging evidence for cervical interlaminar epidurals for various conditions in the cervical spine is positive; however, the effect of fluoroscopic epidural injections in cervical spinal stenosis has not been studied. Study Design: A randomized, double-blind, active control trial. Setting: A private interventional pain management practice, a specialty referral center in the United States. Objectives: To evaluate the effectiveness of cervical interlaminar epidural injections with local anesthetic with or without steroids in the management of chronic neck pain with upper extremity pain in patients with cervical central spinal stenosis. Methods: Patients with cervical central spinal stenosis were randomly assigned to one of 2 groups: injection of local anesthetic only or local anesthetic mixed with non-particulate betamethasone. Sixty patients were included in this analysis. Randomization was performed by computer-generated random allocation sequence by simple randomization. Outcomes Assessment: Multiple outcome measures were utilized including the Numeric Rating Scale (NRS), the Neck Disability Index (NDI), employment status, and opioid intake with assessment at 3, 6, and 12 months post-treatment. Significant pain relief or functional status was defined as a 50% or more reduction of NRS or NDI scores. Results: Significant pain relief was seen in 73% in Group I and 70% in Group II, in Group II showing both significant pain relief and functional status improvements. Group I s average relief per procedures was 11.3 ± 5.8 weeks; for Group II it was 8.6 ± 3.6 weeks, whereas after initial 2 procedures, average relief was 13.7 ± 8.7 weeks in Group I, and 13.6 ± 4.7 weeks in Group II. In the successful group, the average total relief in a one-year period was 42.2 ± 14.7 weeks in Group I and 34.3 ± 13.4 weeks in Group II, with 76% in Group I and 77% in Group II. Limitations: Study limitations include the lack of a placebo group and that this is a preliminary report of only 60 patients, 30 in each group. Conclusion: Patients who have chronic function-limiting pain that is secondary to cervical central stenosis might receive relief with cervical interlaminar epidurals of local anesthetic, whether with or without steroids. Key words: Chronic neck pain, cervical disc herniation, cervical stenosis, cervical central stenosis, cervical epidural injections, epidural steroids, local anesthetics CLINICAL TRIAL: NCT Pain Physician 2012; 15:E59-E70

258 Pain Physician: January/February 2012; 15:E59-E70 Chronic recurrent neck pain in adults is common. The 12-month prevalence is 30% to 50%; intense pain and disability are seen in 14% of adults (1-3). Common causes include cervical spondylosis, cervical disc herniation, cervical stenosis, cervical facet joint arthritis, radiculopathy, and cervical discogenic abnormalities (4-7). Cervical spinal stenosis is a common disease that results in considerable morbidity and disability (8-10). Degenerative change is the most common cause of cervical stenosis and can be due to disc herniation, osteophyte formation, or a combination of both, namely disc-osteophyte complex (8). Tandem spinal stenosis (TSS) is a degenerative disease that describes a double stenotic lesion involving the cervical and lumbar spine (11,12). Historically, TSS accounts for between 5% and 25% of all cases of stenosis (11,12). However, cervical spinal stenosis is less common than lumbar spinal stenosis. With increasing age, a large proportion of the population exhibit radiological signs of discopathy or spondylosis, leading to constriction of the spinal canal (9). Thus, cervical spinal stenosis has been detected in 26% of asymptomatic group of older individuals (13) Despite multiple modalities of treatments, including surgical interventions and various other modalities for diagnosis and treatment of spinal pain, with exploding health care costs, the treatment modalities for cervical spinal stenosis have not been well described (1,3-6,11,12,14-40). Apart from surgical interventions, epidural steroid injections are one of the most common interventions in the non-surgical management of neck and upper extremity pain secondary to disc herniation and radiculitis, spinal stenosis, post surgery syndrome, and discogenic pain (1,14-20,25,41-43). Benyamin et al (1) in a systematic review of cervical interlaminar epidural injections determined that the evidence was moderate in managing chronic neck and upper extremity pain; however, this evidence has been related to mostly disc herniation and radiculitis even though some studies have included patients with different etiologies. Further, Manchikanti et al in 2 studies, in their preliminary reports (14,25) showed the effectiveness of cervical interlaminar epidural injections with or without steroids in over 75% of the patients with axial neck pain or disc herniation and radiculitis. Even then, the evidence has been questioned and continues to be debated similar to lumbar epidural injections due to the design of the studies, fluoroscopic utilization, study size, outcome parameters, duration of follow-up, and bias exerted peer reviews, along with inappropriate methodology, leading to inappropriate conclusions (1,20). A Cochrane review of medicinal and injection therapies for mechanical neck disorders (37) have shown no significant evidence for cervical epidural injections. However, the role of epidural injections in managing chronic persistent pain of cervical spinal stenosis has not been evaluated. Evaluating the role of cervical interlaminar epidural injections with or without steroids in a certain patient population is the present study s purpose specifically, in patients who have chronic, functionlimiting neck pain and disability secondary to central cervical spinal stenosis. This preliminary report describes data from 60 patients who have completed a one year follow-up; the full report will have data on 120 patients. Methods The present study was performed in the United States in a private pain management practice and specialty referral center. Consolidated Standards of Reporting Trials (CONSORT) guidelines were followed (44). The Institutional Review Board (IRB) approved the study s protocol; the study is registered with the U.S. Clinical Trial Registry, NCT Participants New patients presenting for interventional pain management were recruited for the study and assigned to one of two groups. Interventions Both groups received cervical interlaminar epidural injections. Group I patients received 5 ml of 0.5% lidocaine; Group II received 4 ml of 0.5% lidocaine mixed with 1 ml or 6 mg of nonparticulate betamethasone. The IRB-approved protocol and informed consent, which describe the study in detail, were given to the patients. Pre-enrollment Evaluation A pre-enrollment evaluation was conducted. Data collected during the evaluation included work status, demographic data, opioid intake, physical examination, medical and surgical history with coexisting disease(s), Numeric Rating Scale (NRS) pain rating scores, functional status assessment with the Neck Disability Index (NDI), and radiologic investigations. E60

259 Fluoroscopic Epidural Injections in Cervical Spinal Stenosis Inclusion and Exclusion Criteria Inclusion criteria were a diagnosis of cervical central spinal stenosis with or without foraminal stenosis, patients over 30 years old and with a history of chronic functionlimiting neck pain and upper extremity pain of at least 6 on a scale of 0-10, pain for at least 6 months in duration, and patients who were competent to understand the study protocol and provide voluntary, written informed consent, and participate in outcome measurements. Further inclusion criteria included patients who failed to improve substantially with conservative management including, but not limited to, physical therapy, chiropractic manipulation, exercises, drug therapy, and bed rest. Exclusion criteria were a history of cervical spinal surgery, foraminal stenosis without central stenosis, uncontrollable or unstable opioid use, uncontrolled psychiatric disorders, uncontrolled medical illness (either acute or chronic), any conditions that could interfere with the interpretation of the outcome assessments, pregnant or lactating women, and patients with a history or potential for adverse reaction(s) to local anesthetics or steroids. Description of Interventions A single physician performed all procedures in an ambulatory surgery s sterile operating room. Patients were prone, appropriately monitored, and sedated with midazolam and fentanyl. Under fluoroscopy, the epidural space between C7 and T1 to C5 and C6 was entered, using the loss of resistance technique and confirmed with nonionic contrast medium. Then, the appropriate injection, based on the group the patient was assigned, was made. Additional Interventions Patients remained blinded unless they requested unblinding or if an emergency arose. Treatments were performed as assigned. Additional cervical epidural injections were given depending on a patient s response. Nonresponsive patients continued conservative management without further injections, unless they requested unblinding. If physical and functional status improved, then repeat injections were given. Also, only when there was increased pain and deteriorating relief below 50% were repeat injections given. Co-Interventions Patients did not receive bracing, specific physical or occupational therapy, or any intervention other than the assigned study intervention. However, patients did continue exercise programs already started as well as their occupation. Most were already taking adjuvant analgesics, both opioid and nonopioid. If they improved enough, these adjuvants were either stopped or dosages decreased. For some, dosages were increased. Objectives This study seeks to evaluate whether cervical epidural injections, with or without steroids, are effective for managing pain caused by chronic neck and upper extremity pain secondary to cervical central spinal stenosis. Outcomes The following outcomes were measured at baseline and at 3, 6, and 12 months post-treatment: opioid intake measured in morphine equivalent; work status; NDI; and NRS. Pain relief of 50% associated with a 50% improvement in NDI was considered significant. The NRS and NDI have been shown to be valid and reliable in patients with mechanical neck pain (45-47). Morphine equivalents were used to measure opioid intake (48). Patients unemployed due to pain and those employed only part-time due to pain were considered employable. Those not working, but not due to pain, including those retired or who chose not to work and homemakers were not considered employable. Sample Size The sample size needed for each group was determined to be 60 patients. This is based on a 10% attrition/noncompliance rate, as well as a 0.05 two-sided significance level, a power of 80%, and a 1:1 allocation ratio (49). Fifty to 60 patients in a group is considered appropriate (50-61). Randomization Sixty patients are expected to be randomly assigned to each group. Sequence Generation A computer-generated random allocation sequence performed the randomization. Allocation Concealment Patient randomizing and appropriate drug preparing were done by an operating room nurse who assisted with the procedure. E61

260 Pain Physician: January/February 2012; 15:E59-E70 Implementation If they met inclusion criteria, patients were invited to become study participants. A nurse assigned as one of the study s 3 coordinators enrolled them and gave them their group assignment. Blinding (Masking) Group assignments were blinded to the participants and the physicians performing the interventions. The injectates were clear; it was impossible to tell if it contained steroid. Also, participants were mixed with patients not enrolled in the study who were presenting for routine treatment. The physician was not informed who was and who was not a study participant. A statistician not involved with patient care selected those chosen for one-year follow-up. If unblinding did occur, the physician and other patients were not informed, thus preserving the integrity of the blinding. Statistical Methods Four statistical analyses were performed: for differences in proportions, Chi-squared statistic; if the expected value was less than 5, Fisher s exact test; t test for comparing mean scores between groups; paired t test for comparing pre- and post-treatment average pain scores and NDI measurements at baseline against scores at 3, 6, and 12 months. Statistical significance was P < Intent-to-Treat-Analysis The last follow-up data or initial patient data from study dropouts was used for the intent-to-treat analysis. A sensitivity analysis used best and worst case scenarios and last follow-up scores. Results Participant Flow Figure 1 illustrates the participant flow. Eligible Patients Assessed 136 Patients randomized 98 Patients Excluded Patients Not Meeting Inclusion Criteria = 22 Patients Refusing to Participate = 16 Patients included in this evaluation = 60 Group I 30 Group II 30 Cervical epidural with local anesthetics Cervical epidural with local anesthetics and one of the steroids Participants included in analysis = 30 Participants included in analysis = months 93% (28) participants available for follow-up 100% (30) participants included in analysis 12 months 90% (27) participants available for follow-up 100% (30) participants included in analysis Fig. 1. Schematic presentation of patient flow. E62

261 Fluoroscopic Epidural Injections in Cervical Spinal Stenosis Recruitment Enrollment period started in August 2007 and continues. Baseline Data Table 1 shows baseline characteristics. There were no significant differences observed in any of the aspects except mean weight which was higher in Group I compared to Group II. Tables 2 and 3 illustrate severity and levels of spinal stenosis. Analysis of Data Intention-to-treat analysis was carried out by last follow-up data, as there were no significant differences noted with sensitivity analysis. Outcomes Pain Relief NRS scores are shown in Table 4. At 12 months, 73% of Group I participants and 70% of Group II participant showed significant pain relief. However, the proportion Table 1. Baseline demographic characteristics. Group 1 (30) Group II (30) P value Gender Male 30% (9) 43% (13) Female 70% (21) 57% (17) Age Mean ± SD 49.9 ± ± Weight Mean ± SD ± ± Height Mean ± SD 66.5 ± ± Duration of pain (months) Mean ± SD ± ± Onset of the pain Gradual 60% (18) 53% (16) Injury 40% (12) 47% (14) Neck Pain only 18% (5) 11% (3) Pain ratio Neck worse than Upper extremity 68% (19) 54% (15) Upper extremity worse than Neck 7% (2) 3% (1) Both equal 7% (2) 32% (9) Right 10% (3) 17% (5) Neck Pain Distribution Left 20% (6) 10% (3) Bilateral 70% (21) 73% (22) Numeric rating score Mean ± SD 7.9 ± ± Neck Disability Index Mean ± SD 29.2 ± ± Table 2. Spinal stenosis: Severity and involved level(s) as classified by radiologist(s) (MRI or CT scan). Group Severe Moderate Mild C3/4 C4/5 C5/6 C6/7 C7/T1 C3/4 C4/5 C5/6 C6/7 C7/T1 C3/4 C4/5 C5/6 C6/7 C7/T1 Primary* I II Total Secondary I II Total *Primary: Indicates worst level of stenosis or same type stenosis at multiple levels in participants with multiple level stenosis and all participants with single level stenosis. E63

262 Pain Physician: January/February 2012; 15:E59-E70 Table 3. Number of stenosis levels involved in the study population. Group I (30) Group II (30) Total One Level Two Levels Three Levels Four Levels Table 4. Mean pain relief of NRS scores and proportion of patients with significant pain relief ( 50%). Numeric Rating Score Group I (30) Group II (30) Mean ± SD Mean ± SD P value Baseline 7.9 ± ± months 6 months 12 months 3.7* ± 1.2 (87%) 3.4 * ± 0.9 (90%) 3.6* ± 1.1 (73%) 3.5* ± 0.9 (87%) 3.7* ± 1.0 (80%) 3.8* ± 1.2 (70%) Percentages in parentheses indicate proportion of participants with significant relief ( 50% reduction in Numeric Rating Score from baseline) * indicates significant difference with baseline values (P < 0.001) Table 5. Illustration of functional assessment scores by Neck Disability Index and proportion of patients with significant improvement ( 50%). Neck Disability Index Group I (30) Mean ± SD Group II (30) Mean ± SD P value Baseline 29.2 ± ± months 6 months 12 months 15.1* ± 5.8 (77%) 13.2* ± 4.8 (87%) 13.2* ± 5.4 (77%) 13.6* ± 3.8 (87%) 13.5* ± 4.6 (83%) 13.9* ± 4.5 (70%) Percentages in parenthesis indicate proportion of patients with significant improvement with NDI scores from baseline ( 50%). * indicates significant difference with baseline values (P < 0.001) of participants in the successful categories reporting significant pain relief was 76% in Group I and 77% in Group II. Functional Assessment Table 5 shows functional assessment evaluated by NDI. Significant improvement was shown in both groups at 12 months: 77% in Group I and 70% in Group II. When further separated into failed and successful categories, the successful categories showed improvement in 79% of Group I and 77% of Group II. Pain Relief and Functional Improvement The proportion of participants with significant changes in pain and function are shown in Fig. 2. At 12 months, the changes are 73% in Group I and 70% in Group II. When successful categories are examined, there was improvement of 76% in Group I and 77% in Group II. Employment Characteristics Table 6 demonstrates employment characteristics in both groups. Opioid Intake Table 7 illustrates opioid intake characteristics. Therapeutic Procedural Characteristics Therapeutic procedural characteristics are illustrated in Table 8. Epidural entry was as follows: 10% between C5 and C6, 52% between C6 and C7, and 38% between C7 and T1 vertebral interspaces. Average relief per year was 40.8 ± 16.3 weeks in Group I and 30.4 ± 16.1 weeks in Group II. The average number of injections per year was 3.7 ± 1.2 in Group I and 3.6 ± 1.2 in Group II. However, when patients were separated into successful and failed groups, the average number of injections per year was 3.8 ± 1.1 in Group I and 3.6 ± 1.2 in Group II in the successful group, with total relief of 42.2 ± 14.7 weeks in Group I and 34.3 ± 13.4 weeks in Group II with significant difference. If a patient s relief lasted at least 3 weeks with 2 initial injections, then it was considered successful; if not, then it was considered a failure. E64

263 Fluoroscopic Epidural Injections in Cervical Spinal Stenosis Group I Group II 100% 80% 60% 40% 20% 0% 92% 90% 89% 79% 3 months 6 months 76% 77% 12 months 50% 0% 0% 0% 3 months 25% 25% 6 months 12 months 87% 77% 3 months 87% 80% 6 months Successful groups Failed groups Overall results 73% 70% 12 months Fig. 2. Illustration of reduction (at least 50%) in average pain and Neck Disability Index from baseline. Table 6. Employment characteristics. Employment status Group I (30) Group II (30) Baseline 12 months Baseline 12 months Employed part-time Employed full-time Unemployed (due to pain) Not working Eligible for employment Total Employed Housewife Disabled Retired Total Number of Patients Table 7. Opioid intake (morphine equivalence mg) characteristics. Opioid Intake (morphine equivalence mg) Group I (30) Group II (30) Mean ± SD Mean ± SD P value Baseline ± ± months ± * ± months ± * ± months ± * ± * indicates significant difference with baseline values (P < 0.001) Changes in Weight Even though the 2 groups had a significant weight difference from each other at baseline, Table 9 illustrates that neither group showed a change in body weight from baseline. Adverse Events Two subarachnoid punctures, one intravascular entry and one report of soreness lasting one week were reported from the 214 procedures performed. No postoperative headache was reported in both patients after subarachnoid puncture. E65

264 Pain Physician: January/February 2012; 15:E59-E70 Table 8. Therapeutic procedural characteristics with procedural frequency, average relief per procedure, and average total relief in weeks over a period of one year. Successful Patients Failed Patients Combined Group I (29) Group II (26) Group I (1) Group II (4) Group I (30) Group II (30) 1st procedure relief 7.1* ± 5.5 (29) 4.5 ± 3.8 (26) 0 (1) 1.6 ± 2.3 (4) 6.8* ± 5.6 (30) 4.1 ± 3.7 (30) 2nd procedure relief 11.6 ± 7.9 (28) 8.4 ± 2.9 (24) - 1 ± 1.2 (4) 11.6* ± 7.9 (28) 7.4 ± 3.8 (28) 3rd procedure relief 13.6 ± 9.1 (25) 4th procedure relief 12.9 ± 0.9 (20) 5th procedure relief 12.4 ± 1.5 (7) Number of procedures per year 13.4 ± 5.1 (22) 12.8 ± 1.8 (16) 12.7 ± 0.8 (6) - 10 (1) ± 9.1 (25) 12.9 ± 0.9 (20) 12.4 ± 1.5 (7) 13.2 ± 5.1 (23) 12.8 ± 1.8 (16) 12.7 ± 0.8 (6) 3.8 ± ± ± ± ± 1.2 Average relief per procedure 11.7 ± ± ± * ± ± 3.6 Average relief per procedure after initial 2 procedures 13.7 ± ± ± ± 4.7 Total relief per year (weeks) 42.2* ± ± ± * ± ± 16.1 Table 9. Characteristics of changes in weight. Weight (lbs) Group I (30) Group II (30) P Mean ± SD Mean ± SD value Weight at beginning ± ± Weight at one year ± ± Change -5.3 ± ± Lost weight 63% 47% No change 17% 17% Gained weight 20% 36% Discussion The fluoroscopic epidural injections in cervical spinal stenosis evaluated by randomized, double-blind, controlled trial showed significant pain relief in 73% in Group I and 70% in Group II with functional status improvement in 77% in Group I and 70% in Group II. The study also showed decrease in opioid usage. However, this study s results show no significant differences in pain relief or functional status whether patients received injections with steroids or without steroids. Specific data are illustrated in the tables above. Cervical epidural injections are quite common, but systematic reviews are limited (14). There is one Cochrane review of medicinal and injection therapies for mechanical neck disorders (37). Benyamin et al (1) looked at the randomized evaluations included in the evidence synthesis (41-43). Their conclusions were that that positive results were shown for short-term relief in all 3 studies; positive results for long-term relief were shown in 2 studies, and the results of long-term relief were not available for one study (43). Short-term relief was defined as 6 months and long-term relief was defined as more than 6 months. Manchikanti et al, in 2 studies (51,52) evaluating the role of cervical epidural injections with or without steroids in patients with axial neck pain or disc herniation, showed significant improvement in physical and functional status in approximately 70% to 80% of the patients. But interlaminar epidural injections of local anesthetic with or without steroids do not provide long-term relief for patients with cervical spinal stenosis as shown in the present study. However, if patient evaluation is done appropriately and repeat injections are performed judiciously, long term relief can be achieved. The study has illustrated an average of 9.6 to 13.8 weeks of relief. Similar results have been shown for cervical epidurals using the same methodology for disc herniation (14), axial pain without disc herniation or facet joint pain (25), or cer- E66

265 Fluoroscopic Epidural Injections in Cervical Spinal Stenosis vical post-surgery syndrome (55). The same is true for caudal and lumbar interlaminar epidurals ifor disc herniation, discogenic pain without disc herniation, spinal stenosis, and post surgery syndrome (51-54). This study provides an understanding of the procedure s effectiveness for successful and failed categories in the two groups. Our results are generalizable for interventional pain management settings. It is also the first such study performed in an American private practice and that used fluoroscopy. Active control studies, such as the present one, measure effectiveness rather than efficacy like an explanatory trial, thus providing useful data (1,17-20,31,32,62-64). Such an active control design compares 2 commonly used therapies, rather than just an existence of effect or absolute effect size (65). Another difference in this study are the repeat injections given based on an increase in pain and functional status decline, rather than the normal routine of 3 injections or limiting the number of procedures. The lack of a placebo group is a limitation for this study, but having a placebo group for interventional procedures in studies done in the United States is difficult (43,66-71). Unless the same methodology is used, along with fluoroscopic guidance, the results might not apply to the general patient population. Despite these caveats, this study does help shed light on whether steroids should be used with local anesthetic in injections.corticosteroids appear to make no difference in a patient s improvement for managing chronic neck pain of spinal stenosis. There were differences in weight, but failed to influence results. The mechanism of the action of steroids and local anesthetic has been described (43,72-92). There is also emerging evidence that local anesthetics may be equally as effective as steroids in managing low back and neck pain without disc herniation and also pain of facet joint origin (50-57,76-85). Multiple complications also have been described with cervical epidural injections, including infection, bleeding, neural trauma, etc. (1,93-98); however, none were observed in this evaluation except 2 cases of subarachnoid puncture without further side effects. Conclusion This randomized, double-blind, controlled trial of cervical interlaminar epidural injections shows a 71.5% rate of effectiveness in pain reduction and functional status improvement for patients with chronic functionlimiting neck pain and upper extremity pain secondary to central spinal stenosis. Acknowledgments The authors wish to thank Sekar Edem for assistance in search of literature, Tom Prigge, MA, for manuscript review, and Tonie M. Hatton and Diane E. Neihoff, transcriptionists, for their assistance in preparation of this manuscript. We would like to thank the editorial board of Pain Physician for review and criticism in improving the manuscript. References 1. Benyamin RM, Singh V, Parr AT, Conn A, Diwan S, Abdi S. Systematic review of the effectiveness of cervical epidurals in the management of chronic neck pain. Pain Physician 2009; 12: Manchikanti L, Singh V, Datta S, Cohen SP, Hirsch JA. Comprehensive review of epidemiology, scope, and impact of spinal pain. Pain Physician 2009; 12:E35- E Hogg-Johnson S, van der Velde G, Carroll LJ, Holm LW, Cassidy JD, Guzman J, Côté P, Haldeman S, Ammendolia C, Carragee E, Hurwitz E, Nordin M, Peloso P, Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders. The burden and determinants of neck pain in the general population: Results of the Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders. Spine (Phila Pa 1976) 2008; 33:S39-S Carette S, Fehlings MG. Clinical practice. Cervical radiculopathy. N Engl J Med 2005; 353: Falco FJE, Erhart S, Wargo BW, Bryce DA, Atluri S, Datta S, Hayek SM. Systematic review of diagnostic utility and therapeutic effectiveness of cervical facet joint interventions. Pain Physician 2009; 12: Manchikanti L, Dunbar EE, Wargo BW, Shah RV, Derby R, Cohen SP. Systematic review of cervical discography as a diagnostic test for chronic spinal pain. Pain Physician 2009; 12: Yin W, Bogduk N. The nature of neck pain in a private pain clinic in the United States. Pain Medicine 2008; 9: Stafira JS, Sonnad JR, Yuh WT, Huard DR, Acker RE, Nguyen DL, Maley JE, Ramji FG, Li WB, Loftus CM. Qualitative assessment of cervical spinal stenosis: observer variability on CT and MR images. AJNR Am J Neuroradiol 2003; 24: Meyer F, Börm W, Thorné C. Degenerative cervical spinal stenosis: Current strategies in diagnosis and treatment. Dtsch Arztebl Int 2008; 105: Morishita Y, Naito M, Hymanson H, Mi- E67

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269 Int. J. Med. Sci. 2012, Ivyspring International Publisher Research Paper International Journal of Medical Sciences 2012; 9(6): doi: /ijms.4444 Management of Chronic Pain of Cervical Disc Herniation and Radiculitis with Fluoroscopic Cervical Interlaminar Epidural Injections Laxmaiah Manchikanti 1, Kimberly A. Cash 2, Vidyasagar Pampati 3, Bradley W. Wargo 4, Yogesh Malla 5 1. Medical Director of the Pain Management Center of Paducah, Paducah, KY and Clinical Professor, Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY, USA 2. Research Coordinator at the Pain Management Center of Paducah, Paducah, KY, USA 3. Statistician at the Pain Management Center of Paducah, Paducah, KY, USA 4. Was an Interventional Pain Physician at the Pain Management Center of Paducah, Paducah, KY. He is presently at The McFarland Clinic, Mary Greeley Medical Center, Ames, IA, USA 5. Interventional Pain Physician at the Pain Management Center of Paducah, Paducah, KY, USA. Corresponding author: Laxmaiah Manchikanti, M.D Lone Oak Road, Paducah, Kentucky Phone: ext Fax: drlm@thepainmd.com Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License ( licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: ; Accepted: ; Published: Abstract Study Design: A randomized, double-blind, active controlled trial. Objective: To evaluate the effectiveness of cervical interlaminar epidural injections of local anesthetic with or without steroids in the management of chronic neck pain and upper extremity pain in patients with disc herniation and radiculitis. Summary of Background Data: Epidural injections in managing chronic neck and upper extremity pain are commonly employed interventions. However, their long-term effectiveness, indications, and medical necessity, of their use and their role in various pathologies responsible for persistent neck and upper extremity pain continue to be debated, even though, neck and upper extremity pain secondary to disc herniation and radiculitis, is described as the common indication. There is also paucity of high quality literature. Methods: One-hundred twenty patients were randomly assigned to one of 2 groups: Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 ml); Group II patients received 0.5% lidocaine, 4 ml, mixed with 1 ml of nonparticulate betamethasone. Primary outcome measure was 50 improvement in pain and function. Outcome assessments included Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), opioid intake, employment, and changes in weight. Results: Significant pain relief and functional status improvement ( 50%) was demonstrated in 72% of patients who received local anesthetic only and 68% who received local anesthetic and steroids. In the successful group of participants, significant improvement was illustrated in 77% in local anesthetic group and 82% in local anesthetic with steroid group. Conclusions: Cervical interlaminar epidural injections with or without steroids may provide significant improvement in pain and function for patients with cervical disc herniation and radiculitis. Key words: Chronic neck pain, cervical disc herniation, upper extremity pain, cervical epidural injections, epidural steroids, local anesthetics

270 Int. J. Med. Sci. 2012, Introduction Neck pain is one of the 4 most commonly reported musculoskeletal disorders [1]. Chronic neck pain is common in the adult population, presenting in 60% of patients for 5 years or longer after the initial episode [2-4]. The study of the prevalence of neck pain and the impact on general health showed 14% of patients reporting Grade II to IV neck pain, defined as high pain intensity with disability [4]. Thus, chronic, function-limiting neck pain is not only common, but is also associated with a significant economic, social, and health impact [1,2,4]. Among the multiple structures responsible for neck and upper extremity pain and headaches, cervical intervertebral discs, cervical facet joints, ligaments, fascia, muscles, and nerve root dura have been described to be commonly responsible [5]. Consequently, cervical disc herniation with radiculitis is considered one of the most common conditions of neck and upper extremity pain [6,7]. Even though the natural history of cervical disc herniation and cervical radicular pain is not described in detail in the literature, based on the most frequently used epidemiologic data from the Mayo Clinic, an annual incidence of cervical radiculopathy was determined to be 83 per 100,000 of those between 13 and 91 years old [7]. The economic burden of managing neck pain is second only to low back pain, with both having extensive treatment modalities and exponential growth [2,4,5,8-26]. Epidural injections for managing chronic neck and upper extremity pain are one of the commonly performed interventions in the United States [5,13-19]. However, the evidence for cervical interlaminar epidural injections has been a subject of debate and has been reported to be moderate. Benyamin et al [5], in a systematic review of cervical interlaminar epidural injections, determined that the evidence was moderate for managing chronic neck and upper extremity pain. Even then, the role of cervical epidural injections continues to be debated, mostly based on the evidence for lumbar epidural injections, due to multiple factors, including the design of the study (fluoroscopic versus non-fluoroscopic, placebo control versus active control, study size, outcome parameters, duration of follow-up, and bias exerted in reviews secondary to inappropriate methodology leading to inappropriate conclusions) [5,16,17,27-32]. In the systematic review by Benyamin et al [5], the evidence was derived from 3 randomized trials meeting the inclusion criteria [33-35], which were all performed without fluoroscopic visualization. However, Manchikanti et al [36], in a preliminary report of a randomized, double-blind, active controlled trial studying the effectiveness of fluoroscopic cervical interlaminar epidural injections for managing chronic cervical disc herniation and radiculitis, reported significant pain relief ( 50%) in 77% of the patients in both groups, along with functional status improvement in 74% of the patients receiving local anesthetic and 71% of the patients receiving local anesthetics with steroids at 12 months. Utilizing strong outcome parameters, this preliminary report showed positive results. These results are similar to the management of lumbar and thoracic disc herniations [37-39] and superior to epidural injections for axial or discogenic pain, spinal stenosis, and post surgery syndrome in the cervical or lumbar spine [40-47]. The underlying mechanism of action of epidurally administered local anesthetics and steroids is not clear, however, it has been hypothesized that the effects of neural blockade are dependent on various mechanisms for both local anesthetics and steroids, including anti-inflammatory properties. Findings in clinical and experimental studies indicate that local anesthetic injections may provide relief similar to corticosteroids [37-56]. Consequently, the current study was undertaken to evaluate the role of cervical interlaminar epidural injections in patients with chronic, function-limiting, neck and upper extremity pain secondary to disc herniation utilizing local anesthetic with or without steroids in a randomized, double-blind, active controlled design with 120 patients. This study involves assessment of patients with cervical disc herniation and radiculitis, whereas, protocol includes multiple other studies including thoracic pathologies, cervical disc related pain, cervical spinal stenosis, and cervical post surgery syndrome. The preliminary report of this study was previously published [36]. Materials & Methods This randomized, double-blind, active controlled trial was conducted based on Consolidated Standards of Reporting Trials (CONSORT) guidelines [57]. The study was performed in an interventional pain management referral center in the United States, after approval by the Institutional Review Board (IRB) and registration with the U.S. Clinical Trial Registry with an assigned number (NCT ). This study was conducted with internal resources of the practice without any external funding, either from industry or elsewhere. Participants All study patients were derived from new patients of the interventional pain management practice.

271 Int. J. Med. Sci. 2012, They were provided with the IRB-approved protocol and informed consent, which described in detail all aspects of the study and withdrawal process. Interventions Study patients were assigned into one of 2 groups; Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5% 5 ml), whereas Group II patients received cervical interlaminar epidural injections with 0.5% lidocaine, 4 ml, mixed with 1 ml or 6 mg of non-particulate betamethasone for a total of 5 ml of injectate. Pre-Enrollment Evaluation Prior to starting the cervical interlaminar epidural injections and after patients were selected to participate, data, including demographics, medical and surgical history with co-existing disease(s), radiological investigations (magnetic resonance imaging/or computed tomography), nerve conduction studies, findings of physical examination, numeric pain rating scores, functional status assessment using the Neck Disability Index, work status, and opioid intake information were obtained. Inclusion Criteria Inclusion criteria were limited to patients with cervical disc herniation or radiculitis. The age limits were 18 years or older. Patients invited to participate were those who also presented with a history of chronic, function-limiting neck and upper extremity pain of at least 6 months duration, were competent to understand the study protocol, provide voluntary written informed consent, and participate in outcome measures. Other criteria included a failure to respond to conservative treatment modalities, including, but not limited to, physical therapy, a structured exercise program, and drug therapy. Exclusion criteria included previous cervical spine surgery; radiculitis secondary to spinal stenosis; discogenic pain without disc herniation; uncontrollable or unstable opioid use; uncontrolled psychiatric disorders; uncontrolled medical illness, either acute or chronic; any condition that could interfere with the interpretation of the outcome assessment; pregnancy and lactation; or a history of adverse reactions to local anesthetics or steroids. Description of Interventions Cervical interlaminar epidural procedures were performed by one physician (LM) in an Ambulatory Surgery Center (ASC), in a sterile operating room, under fluoroscopy. Patients were in the prone position with appropriate monitoring and intravenous access, and sedation with midazolam and fentanyl when indicated. After sterile preparation, the epidural space was entered with the loss of resistance technique under fluoroscopic visualization between C7 and T1 to C5 and C6 with confirmation by injection of non-ionic contrast medium. Subsequent to the confirmation of entry into the epidural space, 5 ml of lidocaine hydrochloride 0.5% preservative free, or 4 ml of lidocaine preservative free mixed with 6 mg of non-particulate betamethasone was injected. Repeat cervical epidural injections were provided based on the response to prior cervical epidural injections. The response was assessed by improvement in physical and functional status and repeat procedures were only provided when increased levels of pain were reported with deterioration of functional status and pain relief to below 50%. Co-interventions No specific physical therapy, occupational therapy, or other interventions were offered other than the study intervention to all patients in both groups. However, patients continued their drug therapy with either opioids or non-opioid analgesics, therapeutic exercise program, and normal activities, including work. Objectives The study was designed to evaluate the effectiveness of cervical interlaminar epidural injections with or without steroids under fluoroscopy in managing chronic neck and upper extremity pain secondary to disc herniation or radiculitis. Outcomes The primary outcome measure was combined improvement in pain scores and functional status improvement. The numeric rating scale (NRS), Neck Disability Index (NDI), work status, and opioid intake in terms of morphine equivalence, were assessed at baseline, 3, 6, and 12 months post-treatment. Significant improvement was defined as at least 50% pain relief associated with at least 50% improvement in functional status measured by NRS and NDI. The NRS and NDI have been shown to be valid and reliable in patients with mechanical neck pain [58,59]. Significant improvement is a robust measure compared to previous evaluations. Based on the dosage frequency and schedule of the drug, opioid intake was converted to morphine equivalent and changes in intake were assessed [60]. Employable patients were determined based on

272 Int. J. Med. Sci. 2012, their unemployment or employment on a part-time basis or full-time employment. However, patients who chose not to work, were retired, or were homemakers without the necessity or desire to work outside the home, but not due to pain, were not considered in the employment pool. Sample Size The sample size was calculated based on significant pain relief. Considering a 0.05 two-sided significance level, a power of 80%, and an allocation ratio of 1:1, 55 patients in each group were estimated [61]. Allowing for a 10% attrition/ non-compliance rate, 60 patients in each group were required. Randomization Sixty patients were randomly assigned into each group. Sequence Generation Computer-generated random allocations sequence by simple randomization was utilized. Allocation Concealment One of the 3 coordinators of the study randomized the patients into 2 groups and prepared the drugs appropriately. Blinding (Masking) Appropriate blinding (masking) was achieved by blinding the group assignment to all involved, including the physician and the patients. Both solutions were clear with the inability to identify the group assignment. Further, all the study patients were mixed with other patients receiving routine treatments, and the physician performing the procedure was not informed of the nature of the patients participating in the study. At one-year follow-up, a statistician not involved in patient care (VP) collected the data on all the patients with information not being revealed to anyone else. Thus, overall the nature of blinding and masking were not interrupted. Statistical Methods The chi-squared statistic, Fisher s exact test, t-test, and paired t-test were used for statistical analysis. Chi-squared statistic was used to test the differences in proportions. Fisher s exact test was used wherever the expected value was less than 5; a paired t-test was used to compare the pre- and post-treatment results of average pain scores and NDI measurements at baseline versus 3, 6, and 12 months. For comparison of mean scores between groups, t-test was performed. The average per procedure and yearly relief were assessed by simple calculations. Intent-to-Treat-Analysis An intent-to-treat analysis, along with sensitivity analysis, were performed utilizing either the last follow-up data or initial data for the patients withdrawn, with the sensitivity analysis utilizing best case, worse case, and last follow-up data. Results Patient Flow Figure 1 illustrates the patient flow. The recruitment period lasted from August 2007 through June Demographic Data Baseline demographic and clinical characteristics of each group are illustrated in Table 1. Group I patients mean weight was significantly more than the Group II patients mean weight. Table 1. Baseline demographic characteristics. Group 1 (60) Group II (60) P value Sex Male 47% (28) 42% (25) Female 53% (32) 58% (35) Age Mean ± SD 46.2 ± ± Weight Mean ± SD ± ± Height Mean ± SD 67.3 ± ± Duration of Pain (months) Onset of the Pain Neck Pain Distribution Disc Herniation Levels (at multiple levels) Numeric Rating Score Neck Disability Index Mean ± SD ± ± Gradual 53% (32) 52% (31) Injury 47% (28) 48% (29) Neck pain only 15% (9) 17% (10) Neck pain worse than upper extremity Upper extremity worse than neck pain 57% (34) 55% (33) 8% (5) 7% (4) Both equal 20% (12) 22% (13) C3/4 13% (8) 13% (8) NA C4/5 30% (18) 20% (12) C5/6 50% (30) 60% (36) C6/7 40% (24) 47% (28) C7/T1 10% (6) 12% (7) Mean ± SD 7.9 ± ± Mean ± SD 29.6 ± ±

273 Int. J. Med. Sci. 2012, Fig 1. Schematic presentation of patients flow at one-year follow-up of 120 patients. Pain Relief Table 2 illustrates the NRS scores. Pain scores significantly decreased from baseline at 3, 6, and 12 months in all groups, with no significant differences between the groups at follow-up periods. Functional Assessment Functional assessment results assessed by the NDI are illustrated in Table 3. Pain Relief and Functional Assessment Figure 2 illustrates the proportion of patients with a significant reduction in the NRS and NDI with greater than 50% reduction from baseline. Successful patients showed better results compared to all patients with results illustrating at 12 months an improvement of 72% in Group I and 68% in Group II for all patients compared to 77% and 82% in the successful groups. Table 2. Characteristics of pain relief of the numeric rating scale and proportion of patients with significant relief. Numeric Rating Scale Group I (60) Group II (60) P value Mean ± SD Mean ± SD Baseline 7.9 ± ± months 3.7* ± 1.4 (85%) 6 months 3.5* ± 1.4 (83%) 12 months 3.7* ± 1.5 (72%) 3.8* ± 1.4 (75%) 3.9* ± 1.5 (73%) 3.9* ± 1.5 (72%) Percentages in parentheses indicate proportion of participants with significant relief ( 50% reduction in Numeric Rating Scale from baseline) * indicates significant difference with baseline values (P < 0.01)

274 Int. J. Med. Sci. 2012, Table 3. Illustration of functional assessment scores by the Neck Disability Index and proportion of patients with significant improvement (> 50%). Neck Disability Index Group I (60) Mean ± SD Group II (60) Mean ± SD P value Baseline 29.6 ± ± months 14.7* ± 5.5 (85%) 6 months 13.8* ± 5.4 (83%) 12 months 13.8* ± 5.7 (75%) 15.6* ± 6.3 (70%) 15.3* ± 6.9 (73%) 15.1* ± 7.0 (68%) Percentages in parentheses indicate the proportion of patients with significant relief ( 50% reduction in Neck Disability Index from baseline) * indicates significant difference with baseline values (P < 0.01) Therapeutic Procedural Characteristics Therapeutic procedural characteristics are illustrated in Table 4. Epidural entry was performed between C7 and T1 in 28% of patients, between C6 and C7 in 60% of patients, and between C5 and C6 in 12% of patients. Average relief per year showed significant differences: 37.6 ± 16.4 weeks in Group I and 31.0 ± 18.5 weeks in Group II. The total number of injections per year was 3.6 ± 1.2 in Group I and 3.4 ± 1.3 in Group II. However, when patients were separated into successful and failed groups, the total number of injections per year was 3.7 ± 1.1 in Group I and 3.7 ± 1.2 in Group II in the successful groups, and 2.7 ± 1.5 for Group I and 2.0 ± 1.2 for Group II in the failed groups. Total relief of 41.4 ± 12.7 weeks was obtained in the successful group in Group I; in Group II it was 36.3 ± In contrast, the relief was 9.0 ± 13.4 in Group I and 4.2 ± 10.9 weeks in Group II for the failed groups. The initial therapy was considered to be successful if a patient obtained consistent relief with 2 initial injections lasting at least 3 weeks. All others were considered failures. Employment Characteristics Table 5 demonstrates employment characteristics in both groups. Opioid Intake Table 6 illustrates opioid intake. Changes in Weight There were no differences in change (gain or loss) in body weight from baseline in both groups (Table 7). Adverse Events Of the 418 procedures performed, there was one subarachnoid puncture, 3 intravascular penetrations, and one report of soreness lasting one week. No postoperative headache was reported after subarachnoid puncture. Fig. 2. Proportion of patients with significant reduction in Numeric Rating Scale and Neck Disability Index ( 50% reduction from baseline).

275 Int. J. Med. Sci. 2012, Table 4. Therapeutic procedural characteristics with procedural frequency, average relief per procedure, and average total relief in weeks over a period of one year. Successful Patients Failed Patients Combined Group I (53) Group II (53) Group I (7) Group II (7) Group I (60) Group II (60) 1 st procedure relief 7.8 ± ± ± ± ± ± nd procedure relief 11.9 ± 7.1 (51) 3 rd procedure relief 14.8 ± 9.1 (43) 4 th procedure relief 12.3 ± 2.4 (35) 5 th procedure relief 12.6 ± 0.9 (14) Average Number of Procedures for One Year Average Relief per Procedure for Initial Two Procedures in Weeks Average Relief per Procedure After Initial Two Procedures 10.1 ± 8.8 (48) 12.5 ± 4.4 (40) 12.6 ± 2.3 (31) 12.3 ± 2.2 (14) 1.2 ± 1.3 (5) 5.8 ± 6.3 (4) 9.5 ± 4.9 (2) 12.0 (1) 0.8 ± 0.8 (6) 7.0 ± 8.5 (2) 10.0 (1) 11.0 (1) 10.9 ± 7.4 (56) 14.0 ± 9.2 (47) 12.1 ± 2.5 (37) 12.6 ± 0.9 (15) 9.1 ± 8.8 (54) 12.2 ± 4.6 (42) 12.5 ± 2.3 (32) 12.2 ± 2.1 (15) 3.7 ± ± ± ± ± ± # ± 7.9 (104) 13.5 ± 6.5 (92) Average Relief per Procedure 11.5 # ± 7.5 (196) Average Total Relief For One Year (Weeks) # indicates significant difference with Group II (P < 0.05) 7.8 ± 8.1 (98) 12.5 ± 3.4 (85) 10.0 ± 6.7 (183) 0.8 ± 1.1 (12) 7.7 ± 5.5 (7) 3.3 ± 4.8 (19) 0.5 ± 0.6 (16) 8.8 ± 5.3 (4) 2.1 ± 4.0 (20) 8.8 ± 8.0 (116) 13.1 ± 6.6 (99) 10.8 ± 7.6 (215) 6.8 ± 7.9 (114) 12.3 ± 3.5 (89) 9.2 ± 6.9 (203) 41.4 ± ± ± ± # ± ± 18.5 Table 5. Employment characteristics. Employment Status Group I Group II Baseline 12 Months Baseline 12 Months Employed part-time Employed full-time Unemployed (due to pain) Not Working Eligible for Employment at Baseline Total Employed Housewife Disabled Retired Total Number of Patients Table 6. Opioid intake (morphine equivalence mg). Opioid Intake (Morphine Equivalence mg) Group I (60) Group II (60) P value Mean ± SD Mean ± SD Baseline 57.0 ± ± Months 34.4* ± * ± Months 33.0* ± * ± Months 34.7* ± * ± * indicates significant difference with baseline values (P < 0.05)

276 Int. J. Med. Sci. 2012, Table 7. Characteristics of changes in weight. Weight (lbs) Group I (60) Group II (60) P value Mean ± SD Mean ± SD Weight at Beginning ± ± Weight at One Year ± ± Change -3.5 ± ± Lost Weight 57% (34) 43% (26) No Change 20% (13) 25% (15) Gained Weight 22% (13) 32% (19) Discussion This randomized, active controlled, double-blind evaluation of 120 patients receiving fluoroscopically directed cervical epidural injections of local anesthetic with or without steroids demonstrated significant improvement for both groups, with 72% of the patients in the local anesthetic group and 68% patients in the local anesthetic with steroids group getting significant improvement in their pain. Significant improvement has been defined with robust outcome measures utilizing at least 50% pain relief and at least 50% improvement in functional status as measured by NRS and NDI. The results of this study illustrate that in selected patients, those judged as successful participants, that is, the ones who responded to the first 2 initial procedures, combined pain relief and improvement in functional status was observed in 77% in Group I and 82% in Group II at one-year follow-up. The improvement in the successful participants was superior to the overall improvement in all patients. This study confirms that the treatment of cervical disc herniation with radiculitis with cervical epidural injections of steroids or local anesthetics administered under fluoroscopy has clinically important effects. The overall average procedures per year was 3.6 in Group I and 3.4 in Group II, with an average total relief per year of 38 weeks for Group I patients and 31 weeks for Group II patients. Opioid intake was significantly reduced in both groups. While the literature is replete with multiple studies and systematic reviews in favor of and against epidural injections in general, the specific literature in the cervical spine is limited with only 2 systematic reviews available [5,8]. Benyamin et al [5] concluded that all 3 studies showed positive results for short-term relief, whereas only 2 were positive for long-term relief, which was defined as greater than 6 months. As illustrated in the present evaluation, cervical interlaminar epidural injections of local anesthetics with or without steroids, though they do not provide long-term relief, long-term relief can however be achieved through appropriate patient evaluation and judicious use of injection therapy, as illustrated in the successful group. This study specifically included only patients with disc herniation and radiculitis rather than a heterogenous group of patients with post laminectomy syndrome, spinal stenosis, axial discogenic pain, or radiculitis without disc herniation. In the past multiple studies have been criticized, most importantly for their design and their inability to confirm the location of the injection by not using fluoroscopy. Further, systematic reviews also have been criticized for their methodology by evaluating the studies inappropriately, reaching inaccurate conclusions. In contrast to the previous studies, this study provides insight into successful or failed groups based on the first 2 procedures. The patients in the successful group, those who had good pain relief with the first and second procedures, constituting over 80% of the enrolled patients, showed average relief from 36.3 to 41.4 weeks out of 52 weeks. Further, the average number of procedures per year was 3.7. However, in the failed group, the average relief per procedure was 0.5 to 0.8 weeks, with overall relief of 4.2 to 9.0 weeks over a period of one year. There were no significant differences noted whether a steroid was utilized or not in the proportion of failed patients as well as the duration of relief. This is in contrast to lumbar disc herniation, which demonstrated a superiority of improvement in the steroid group [37]. The results differ from caudal epidural injections in lumbar disc herniation, which showed superior results with steroids [37]. The strengths of this evaluation include its comparative evaluation, as comparative effectiveness research has been considered pivotal to evidence-based medicine [27,28,30,62]. Even though this trial is limited to a single center, it is randomized, double-blind, active controlled, and designed to determine whether fluoroscopically directed cervical interlaminar epidural injections with or without ster-

277 Int. J. Med. Sci. 2012, oids with the usual volumes injected in practice are effective in providing pain relief. Further, patient selection was not only practical, but it was also met with great sensitivity and included only patients with chronic, persistent neck and upper extremity pain due to disc herniation and radiculitis. The repeat procedures were provided based on principles of contemporary interventional pain management and guidelines [28], with only deterioration in relief and functional status being the criteria, rather than based on a schedule, or the number of injections, or only one procedure being offered throughout one-year. Consequently, this study meets the criteria for practical clinical trials with an active controlled group instead of a placebo group, and measures effectiveness, which is considered more appropriate than measuring efficacy. The study may be criticized for its lack of a placebo group and also early published results after one-year instead of waiting for 2 years. In reference to placebo, most studies in the past have utilized inappropriate methodology involving placebo groups [16,17,27-30,63-67]. The appropriate placebo design by Ghahreman et al [65] showed no significant effect with sodium chloride solution when injected into an inactive structure. In addition, the concepts including local anesthetic transformed into placebo are not only methodologically and conceptually inaccurate, they also result in misleading conclusions, since inactive substances injected into active structures have been shown to result in various types of effects [64-72]. Further, local anesthetics have been shown to provide long-term improvement in patients both in clinical as well as experimental settings [38-50,54-56]. The present study was published with one year results, rather than waiting for 2 years, as there are no fluoroscopically performed studies, except the preliminary report of this study, and there are no large-scale reports performed in a practical setting. The only difference noted in the demographic characteristics was the weight at baseline, which failed to show any significant influence on the results. Implications of this trial are widespread in an era of evidence-based medicine, comparative effectiveness research, and exploding health care costs. Studies with proper methodology in practical settings are crucial, but rare. Proper application of the interventions will improve patients pain and function, reduce drug use, and may return them to the workforce. However, inappropriate interventions may incur substantial expenses and may not provide any benefit, but rather may be harmful to the patient because of the depletion of resources, resulting in denying access to patients. By the same token, inappropriately performed evaluations that lead to inaccurate conclusions may reduce health care expenditures, but will also increase patient suffering, increase drug use, and impede access to medical care. Conclusions This randomized, double-blind, active controlled trial of 120 patients treated with fluoroscopically guided cervical interlaminar epidural injections of local anesthetic with or without steroids for chronic neck and upper extremity pain secondary to disc herniation and radiculitis illustrated effectiveness in 77% of patients in the local anesthetic group and 82% in the steroid group, with improvement in pain and functional status in the successful groups, requiring an average of 3.5 procedures over a one-year period. Acknowledgments The authors wish to thank Vidyasagar Pampati, MSc, for statistical assistance, Sekar Edem for assistance in the search of the literature, Tom Prigge, MA, for manuscript review, and Tonie M. Hatton and Diane E. 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280 Journal of Back and Musculoskeletal Rehabilitation 26 (2013) DOI /BMR IOS Press Fluoroscopy guided cervical interlaminar steroid injections in patients with cervical pain syndromes: A retrospective study Serbülent Gökhan Beyaz a, and Ali Eman b a Anesthesiology and Pain Management Center, Sakarya University Medical School, Sakarya, Turkey b Ipekyolu State Hospital of Van, Anesthesiology, Van, Turkey Abstract. OBJECTIVE: Theobjective of thisretrospective study was to examine theefficacy of fluoroscopically guided cervical interlaminar epidural steroid injections (CILESI). MATERIALS AND METHODS: Sixty-five patients who received their first fluoroscopically guided CILESI over a 12 month interval were retrospectively identified. Patients who had failed conservative non-surgical management and patients who were otherwise candidates of surgery were included in this trial of CILESI. The verbal numerical rating scales (VNRS) before the treatment, within one hour after the treatment, and upon follow-up, were analyzed. RESULTS: The most preferred intervention level of CILESI was C5-C6. There was a statistically significant improvement in the VNRS scores from before the injection to immediately after the injection, and upon follow-up. Fifty-one patients (80%) had perfect/good scores. No major complications were encountered after CILESI, but one patient (1.54%) had a vasovagal reaction and another patient (1.54%) had a transient increase of pain after injection. CONCLUSION: Fluoroscopy guided CILESI is a safe and an effective treatment for patients with cervical pain syndromes. The success rates show that a large percentage of the patients may obtain relief from radicular symptoms and avoid surgery for the follow-up period up to 12 months. Keywords: Cervical, epidural, steroid, injection, interlaminar, complication 1. Introduction Cervical epidural steroid injections are usually used to treat acute and chronic pain conditions involving the head, neck, and upper extremities [1,2]. The most common causes are spinal nerve compression secondary to stenosis with spondylosis or herniation of the nucleus pulposus. There are a diversity of conservative therapy options to treat this type of pain, including physical therapy, analgesia, and injections. Despite these conservative treatment options, pain may still persist [3]. Corresponding author; Dr. Serbülent Gökhan Beyaz, Associate Professor, Anesthesiology and Pain Management Center, Sakarya University Medical School, Sakarya,Turkey. Mobile: ; Fax: ; sgbeyaz@gmail.com. There are prospective studies documenting a significant reduction in extremity pain following cervical epidural steroid injections [4,5]. Despite the ongoing debate on the long-term outcome following epidural corticosteroid injections [6, 7], prolonged pain relief may depend on the underlying structural and psychological pathology. Two main approaches exist for the delivery of drugs into the cervical epidural space: interlaminar and transforaminal. The choice of which approach to use is commonly made by evaluating the patient s structural pathology, one s skill in performing each procedure, and then weighing the advantages versus the risks associated the particular technique. When multilevel pathology is present, the interlaminar route may facilitate multilevel spread [7]. AUTHOR COPY ISSN /13/$ IOS Press and the authors. All rights reserved

281 86 S.G. Beyaz and A. Eman / Effect of CILESI In clinical practice, the most commonly used technique for identifying the epidural space is the loss of resistance to air or saline technique. The loss of resistance technique (without fluoroscopy guidance) may be inadequate for identifying the epidural space [1]. There has also been a report on the incidence of discontinuity in the ligamentum flavum in the cervical region [8]. The use of fluoroscopy can diminish these risks. The purpose of our study was to assess the outcomes following cervical interlaminar epidural steroid injections (CILESI) for all etiologies of cervical pain syndromes in terms of the short-term effect. 2. Materials and methods After the ethical committee approval of the university, 65 CILESI patients were retrospectively enrolled and evaluated in this study. All patients were treated between February 2010 and February 2011 in Ordu University Training and Research Hospital s pain management centre. Written and oral informed consent was obtained from all patients. This study included patients who had 6 month duration of symptoms of neck pain and unilateral or bilateral arm pain that had shown no positive responses to medical or physical therapy. Medical therapies included NSAIDs, muscle relaxants, and in some cases, opioids. Physical therapies were used if there was no pain relief after two weeks of medical therapies. All patients had significant clinical symptoms of cervical spinal pathologies. An experienced radiologist detected cervical pathologic levels using magnetic resonance image (MRI). The exclusion criteria were coagulopathy, pregnancy, sepsis, and an allergy to the contrast material/drug to be used. Patients who did not accept intervention, or who had previous cervical epidural injections, or who had previous cervical spine surgery, or who had neurological deficits, were also excluded. All patients were examined and imaging studies were reviewed by the first author prior to the injection. All injections were performed in the same way, as follows. If routine hemograms, biochemical and coagulation parameters were within normal limits and confirmed, patients were taken into OR. Starvation protocol was 6 8hoursontheinjectionday. Atthefluoroscopy table, standard anesthesia monitorization (non invasive blood pressure, pulse oxymeter, ECG) was performed. Saline solution (NaCl 0.9%) infusion was started intravenously. The intervention site was cleaned with an iodine based antiseptic solution, and covered with caution using sterile drapes. 1 2 mg midazolam and micrograms of fentanyl were administered intravenously and conscious sedation was performed. All cervical injections were performed using C-armed fluoroscopy. The intervention site was locally anesthetized with 0.5 ml of 2% prilocaine which was injected into skin and subcutaneous tissue. The injection level was determined after clinical evaluation and MRI. The needle was inserted in the closest point to the pathology. If there were multiple levels of pathologies, one middle point was selected for insertion considering cephalade and caudal dissemination. The cervical interlaminar epidural steroid injections (CILESI) approach took place after the all patients were placed prone on the fluoroscopy table. Each CILESI was given at the same institution using the interlaminar technique at the level of the pathology. The position of the interspaces was confirmed with palpation using arockingmotioninthesuperiorandinferiorplanes. After the midline of selected interspaces was identified by palpation and fluoroscopy, a 22 gauge 2 1 / 2 -inch tuohy needle was advanced directly perpendicular to the skin. At posterior to anterior direction, the loss-ofresistance to air technique was used in order to identify the epidural space. After negative aspiration for cerebrospinal fluid or blood, 0.5 ml of non-ionic contrast material was injected in order to document appropriate contrast spread into the epidural space. Next, a combination of a total of 5 ml of 80 mg of triamcinolone acetonide with 3 ml bupivacaine 0.25% was injected into the epidural space. Diabetic patients with unstable blood glucose levels received 40 mg of triamcinolone acetate (the decreased dose). After intervention, patients rested on the intervention table for 5 minutes. Then, they were transported to the recovery room. They stayed there for 2 hours, if no complication developed. All ofthecomplicationsthat occurred during the procedure were recorded. Patients AUTHOR COPY were asked to sit, stand and walk before rating their pain score using the Verbal Numerical Rating Scale (VNRS, 0 10 scale). All the data obtained from the patients was recorded on the patient s charts. The patients were then discharged from the hospital and asked to return immediately to our pain clinic if unexpected events developed. At the follow-up (1, 3, 6, 9 and 12 months after the injection), the patients were asked for probable therapeutic effects, VNRS or complications. The obtained findings were recorded on the patients charts for post-interventional follow-up. Moreover, their age, gender and MRI findings were also collected. The patients charts were then reviewed one year after the initial procedure for confirmation purposes.

282 S.G. Beyaz and A. Eman / Effect of CILESI 87 Score Bad Moderate Good Perfect Table 1 Modified North American Spine Society patient satisfactory score No change of complaints; even worse. Epidural steroid helped me but I won t let this procedure again. Most of the complaints are relieved and I would again let this procedure if my complaints reappear. Epidural steroid satisfied me and fulfilled my expectations. Patients were called by telephone and questioned. A modified North American Spine Society (NASS) patient satisfaction score was recorded using a 4-grade scale (Table 1). 3. Statistical analysis The SPSS (Statistical Package for Social Sciences) for Windows 17.0 software program was used with descriptive statistical methods (frequency analysis, cross table analysis, percentage, mean, standard deviation). The study data was evaluated and a statistical analysis was performed. Initial values and values at 1, 3, 6, 9 and 12 months were analyzed with ANOVA one-way variance analysis. The results were evaluated with a 95% CI (confidence interval). A value of p<0.05 was accepted as significant. 4. Results Atotalof65patientswereincluded. Demographic features of patients were presented in Table 2. The mean age was 58.7 ± 13.6 years (range years, Fig. 1). The mean weight was 65.8 ± 10.4 kg. The mean height was 159 ± 9.5 cm. 49 of them were female and 16 of them were male. The duration of symptoms was 1.8 ± 0.6 years. Fig. 1. Patients age distribution. Table 2 Demographic features of patients of CILESI implementation Age, years 58.7 ± 13.6 Gender M/F 16/49 Weight, kg 65.8 ± 10.4 Height, cm 159 ± 9.5 Duration of symptoms, years 1.8 ± 0.6 Values are the mean ± SD and patient number. On the evaluation of the MRI of patients, disc herniation, spinal degeneration, facet hypertrophy, spinal stenosis and many similar findings were recorded. Disc pathologies were classified into four classes and evaluated accordingly. Bulging, protrusion, extrusion and sequestration were the classes. The most affected site was the level of C5-C6 (Table 3). Bulging was the most encountered problem whereas no sequestrated disc was reported. Twenty-six patients had only discal pathologies. Twenty-two patients had both a discal pathology and some degeneration. Eleven patients had severe degeneration. Nine patients had spinal stenosis. Five patients had facet hypertrophy. The most preferred CILESI intervention site was the C5-C6 level (Fig. 2). Pre-injection VNRS scores were average at 7.6 ± 2.2. With the post-injection at 1, 3, 6, 9, and 12 months, VNRS scores dropped significantly (p <0.001, Fig. 3). There were no statistically significant differences between follow-up scores. The satisfaction scores were average 3.3 ± (80%) patients were classified as perfect or good satisfaction (Perfect: 36 patients; good: AUTHOR COPY

283 88 S.G. Beyaz and A. Eman / Effect of CILESI Fig. 2. Levels of CILESI performed. The most preferred CILESI intervention site was the C5-C6 level. Table 3 Distribution of discal herniation levels C3-4 C4-5 C5-6 C6-7 C7-Th1 Bulging Protrusion Extrusion Sequestration CILESI Levels CILESI performed. 16 patients, Fig. 4). Only one patient was then operated on because of intractable pain. Satisfaction scores were decreased with other of the addition of MRI to disc pathologies in patients (p <0.05). CILESI patients had no major complications (epidural hematoma, subdural complications, dural puncture and post-dural puncture headache, neuropathic symptoms, intracranial hypotension and epidural granuloma, permanent spinal cord injury, intravascular uptake of injectate, pneumocephalus, venous air embolism, cervical epidural abscess, Cushing s syndrome, death) [9]. Minor complications (common complications reported include increased axial neck pain [10, 11], non-positional headache [10], facial flushing [11] and vasovagal episodes [9,10,12,13]) were seen in one patient (1.54%) as vasovagal reaction, and another patient (1.54%) had a transient increase of post-injection pain. No repeated injection was performed on any patient. 5. Discussion Cervical pain syndromes have a reported incidence of 83 per (approximately) [9,14]. The most common cause of cervical pain syndrome was a herniated disc, which accounted for 40% in this study. The initial treatment of these symptoms was conservative, non-interventional management which included bed rest, physiotherapy and medications [15,16]. Cervical steroid injections were often tried for patients whose pain did not relieve despite weeks or months of conservative management [12,17]. The chronic spinal pain syndrome treatment involves epidural steroid injections which are frequently preferred [18,19]. The belief is that the use of corticosteroids has actions other than antiinflammatory. Corticosteroids stabilize nerve membranes by inhibiting ectopic impulses, inhibiting ion conductance,hyperpolarizing spinal neurons, and inhibiting C fiber transmission. These latter properties of corticosteroids can explain relief symptoms in noninflammatory states [14]. Cicala et al. [17] reviewed the results of cervical epidural steroid injections in 79 patients with axial neck pain in At 6 months post injection, they found that 71% (perfect 41.4%, good 29%, poor 29.3%) of the patients had good to perfect relief from their symp- AUTHOR COPY toms. Ferrante et al. [12] conducted a retrospective study in 1993 and evaluated 100 patients. 67% of patients relieved after injection. A retrospective study in 1986 by Rowlings and Kirschenbaum [4] evaluated 25 patients over 9 months of follow-up. 75% of patients were relieved after injection. Mangar and Thomas [20] conducted a study on 40 patients who have cervical pathologies. 68% of them were relieved after injection. In a study in 1996 on 68 cervical radiculopathy patients conducted by Bush and Hillier [6], a corticosteroid injection was performed on 64 of them using imagingtechniques. Follow-up was an average of 39 months. If necessary, the injection was repeated (2.5 injections per patients were administered more than once serially for pain relief). They reported that there were no arm (upper extremity) pains in 46 patients (76%). They concluded that repeated epidural steroid injections provide satisfactory results in cervical radiculopathy. Surgery could be postponed or avoided for 39 months. However, our CILESI study was conducted on potential surgery patients and showed that single-dose CILE- SI under the guidance of fluoroscopy provided a significant decrease of VNRS scores afterinjection(during 12 month follow-up). Although VNRS scores gradually increased until the 12th month, this increase was not statistically significant between follow-up scores. Only 5 (7.7%) of the patients reported a satisfaction score as bad. In other words, 92.3% of the patients were satisfied after intervention. 80% of them were in the perfect/good classification.

284 S.G. Beyaz and A. Eman / Effect of CILESI 89 Fig. 3. Distribution of VNRS scores versus months. Statistically significance differences between baseline VNRS scores and follow-up scores with ANOVA p< We performed CILESI via the midline interlaminar approach, which was relatively easy. The transforaminal approach offers anotherroutetotheepiduralspace, but this is considered technically difficult and it has catastrophic complications [21]. However, no study has yet compared the clinical effects of the interlaminar and transforaminal approaches. The complications of CILESI are infrequent and minor [17]. In our series, no serious complications occurred during or after CILESI. Only one patient had increased neck pain and one patient had a vasovagal reaction (total of 2 patients, 3.08%). Catcholove et al. [22] conducted a study on 45 CILESI patients and they reported 6 hypotension, 1 respiratory failure and 1unidentified unilateral block (complications rate was 17.7%). Waldman [13] conducted a prospective study on 215 patients; 23 of them did not return (23 lost to follow- up), 3 patients had minor complications and 3 patients had major complications (3 patients had vasovagal reactions, 2 had a dural puncture and 1 patient Fig. 4. Satisfaction scores of patients. Data are given as number of patients. had a superficial abscess with a total complication rate of 3.13%). On investigation of the relevant reviews in the literature, it is seen that most of the CILESI studies before 2000 were conducted via blind loss of resistance or the hanging drop technique [9,12,13,17,22]. However, this study was conducted via fluoroscopy guidance, therefore our minor complication rate was lower than any other studies. No major complication was seen. Many CILESI studies have been performed without imaging guidance. However, fluoroscopy guided techniques increase the procedure precision and help confirm the correct needle placement. Because fluoroscopy-guided techniques should lead to better results and reduce complication rates, they are now becoming more popular than ever [11,23]. The loss of resistance technique may be inadequate for ensuring accurateneedleplacement during unguided cervical epidural injections [10]. Besides, the VNRS scores of our patients were also lower at the 12 month follow-up. Satisfaction rates were accordingly higher. These successful results may be as- AUTHOR COPY

285 90 S.G. Beyaz and A. Eman / Effect of CILESI sociated with our closer injections to the site of CILESI pathology. Botwin et al. [10] conducted a prospective study which had the highest minor complication rate in the literature (16.8%). This highest complication rate may be associated with a thick and long needle (18-gauge, 9-mm Tuohy needle). Our CILESI needles were much thinner and shorter (22 gauge, 2 1 /2 -inch Tuohy needle). Nevertheless, one patient in our study underwent surgery. From this, they hoped to extrapolate the possible benefits of CILESI in preventing decompressive surgery. The data showed that their rates of cervical decompression surgery decreased during the period of CILESI use. While these studies are being evaluated, it is controversial how to classify these complications. For example, some studies classify a dural puncture as minor complication [13,14,19] whereas some studies classify a dural puncture as a major complication [9,24,25]. Therefore, we believe that this issue should not be ignored while interpreting results. The strongest feature of this study is that all CILESI were performed by the same first author. Of course, there are also some limitations to our study; for example, being a retrospective review and is not a controlled, blinded and randomized study, as some other studies [26 28]. It is well known that in invasive studies which it is not so easy to design randomized controlled trails because of logistic difficulties and also the typical double-blinded pharmacological trials with the inclusion of a drug against placeboandbeingabletoinclude acontrolgroup.whileashamgroupthattheotherpart of the procedure could be adjoined as a control group, it would pose further ethical and medico-legal dilemmas. It is very hard to predict the real etiology of pain which appears to have multiple associated pathologies with increasing age in a patient of chronic cervical spinal pain syndrome. That s why we evaluated all the effects of injections as a whole regardless of their etiologies. Our clinical follow-up of 12 months may not be sufficient in defining long-term success for the patients who did experience significant relief. However, we believe it may be equally important in defining significant shortterm symptomatic improvement for a relatively benign procedure, particularly in these patient populations. In conclusion, this presented study of chronic cervical spinal pain showed that fluoroscopy guided CILESI is a safe and effective method of treatment with high patient satisfaction rates and minimum complications. In the literature, there are no other studies which have this low rate of minor complications with no major complication. However, our results suggest that approximately more than 90% of patients with symptomatic cervical spinal syndromes can be treated effectively and avoid surgery for up to 12 months, and possibly longer, with a trial of CILESI. References [1] Kim KS, Shin SS, Kim TS, Jeong CY, Yoon MH, Choi JI. Fluoroscopically guided cervical interlaminar epidural injections using the midline approach: an analysis of epidurography contrast patterns. Anesth Analg. 2009;108(5): [2] Lin EL, Lieu V, Halevi L, Shamie AN, Wang JC. Cervical epidural steroid injections for symptomatic disc herniations. J Spinal Disord Tech. 2006;19(3): [3] Benny B, Azari P, Briones D. Complications of cervical transforaminal epidural steroid injections. Am J Phys Med Rehabil. 2010;89(7): [4] Rowlingson JC, Kirschenbaum LP. Epidural analgesic techniques in the management of cervical pain. Anesth Analg. 1986;65(9): [5] Cicala RS, Westbrook L, Angel JJ. Side effects and complications of cervical epidural steroid injections. J Pain Symptom Manage. 1989;4(2):64-6. [6] Bush K, Hillier S. Outcome of cervical radiculopathy treated with periradicular/epidural corticosteroid injections: A prospective study with independent clinical review. 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[12] Ferrante FM, Wilson SP, Iacobo C, Orav EJ, Rocco AG, Lipson S. Clinical classification as a predictor of therapeutic outcome after cervical epidural steroid injection. Spine (Phila Pa 1976). 1993;18(6): [13] Waldman SD. Complications of cervical epidural nerve blocks with steroids: A prospective study of 790 consecutive blocks. Reg Anesth. 1989;14(3): [14] Huston CW. Cervical epidural steroid injections in the management of cervical radiculitis: Interlaminar versus transforaminal. A review. Curr Rev Musculoskelet Med. 2009; 2(1):0-42. Epub 2009 Jan 7. [15] Wolff MW, Levine LA. Cervical radiculopathies: Conservative approaches to management. Phys Med Rehabil Clin N Am Aug;13(3): AUTHOR COPY

286 S.G. Beyaz and A. Eman / Effect of CILESI 91 [16] Nawani DP, Agrawal S, Asthana V. Single shot epidural injection for cervical and lumbosaccral radiculopathies: A preliminary study. Korean J Pain. 2010;23(4): Epub 2010 Dec 1. [17] Cicala RS, Thoni K, Angel JJ. Long-term results of cervical epidural steroid injections. Clin J Pain. 1989; 5(2): [18] Manchikanti L, Cash KA, Pampati V, Wargo BW, Malla Y. Cervical epidural injections in chronic discogenic neck pain without disc herniation or radiculitis: preliminary results of a randomized, double-blind, controlled trial. Pain Physician. 2010;13(4):E [19] Abdi S, Datta S, Trescot AM, Schultz DM, Adlaka R, Atluri SL, et al. Epidural steroids in the management of chronic spinal pain: A systematic review. Pain Physician. 2007;10(1): [20] Mangar D, Thomas PS. Epidural steroid injections in the treatment of cervical and lumbar pain syndromes. Reg Anesth. 1991;16(4):246. [21] Malhotra G, Abbasi A, Rhee M. Complications of transforaminal cervical epidural steroid injections. Spine 2009;34: [22] Catchlove RF, Braha R. The use of cervical epidural nerve blocks in the management of chronic head and neck pain. Can Anaesth Soc J. 1984;31(2): [23] Silbergleit R, Mehta BA, Sanders WP, Talati SJ. Imagingguided injection techniques with fluoroscopy and CT for spinal pain management. Radiographics. 2001;21(4):927-39; discussion [24] Darvish B, Gupta A, Alahuhta S, Dahl V, Helbo-Hansen S, Thorsteinsson A, et al. Management of accidental dural puncture and post-dural puncture headache after labour: A Nordic survey. Acta Anaesthesiol Scand. 2011;55(1): doi: /j x [25] Imarengiaye C, Ekwere I. Postdural puncture headache: A cross-sectional study of incidence and severity in a new obstetric anaesthesia unit. Afr J Med Med Sci. 2006; 35(1): [26] Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. NEnglJMed.22Jun2000;342(25): [27] Benson K, Hartz AJ. A comparison of observational studies and randomized, controlled trials. N Engl J Med. 2000; 342(25): [28] Manchikanti L, Heavner JE, Racz GB, Mekhail N, Schultz DM, Hansen HC et al. Methods for evidence synthesis in interventional pain management. Pain Physician. 2003;6(1): AUTHOR COPY

287 CLINICAL CONCEPTS AND COMMENTARY Richard B. Weiskopf, M.D., Editor Anesthesiology 2004; 100: American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Cervical Transforaminal Injection of Steroids James P. Rathmell, M.D.,* Charles Aprill, M.D., Nikolai Bogduk, M.D., Ph.D., D.Sc. CERVICAL radicular pain is pain perceived in the upper limb caused by irritation of a cervical spinal nerve. It affects approximately 1 person per 1,000 population per year 1 and is most often caused by a disc herniation or foraminal stenosis. Its natural history can be favorable, 2 but not all patients recover naturally. Many remain severely disabled and require treatment. Surgery is the mainstay of treatment. 3,4 For relieving cervical radicular pain, surgery has a good reputation, but scientifically, it is based only on multiple observational or descriptive studies. 2 However, surgery is not without risks and constitutes a major undertaking for patients. Conservative therapy, typically including graduated exercise and oral analgesics, is supported only by observational studies, which have not controlled for natural history or nonspecific effects of treatment. Some have reported complete resolution of pain and neurologic dysfunction in as many as 80% of cases, 5,6 but others have attested to resolution of radiculopathy in less than 40%. 7,8 The controlled studies that have been conducted have shown no significant benefit for traction 9 11 or exercises. 10 The failure of conventional, conservative treatments to provide a cure for cervical radicular pain fostered the development of alternatives. Prominent among these has become transforaminal injection of steroids. Rationale * Professor, Department of Anesthesiology, University of Vermont. Clinical Assistant Professor, Departments of Radiology and Physical Medicine and Rehabilitation, Louisiana State University. Professor, Department of Clinical Research, University of Newcastle, Royal Newcastle Hospital. Received from the Department of Anesthesiology, University of Vermont, Burlington, Vermont; the Departments of Radiology and Physical Medicine and Rehabilitation, Louisiana State University, New Orleans, Louisiana; and the Department of Clinical Research, University of Newcastle, Royal Newcastle Hospital, Newcastle, Australia. Submitted for publication July 21, Accepted for publication January 30, Support was provided solely from institutional and/or departmental sources. The illustration for this section is prepared by Dimitri Karetnikov, 7 Tennyson Drive, Plainsboro, New Jersey Address correspondence to Dr. Rathmell: Department of Anesthesiology, University of Vermont College of Medicine, 111 Colchester Avenue, Burlington, Vermont Address electronic mail to: james.rathmell@vtmednet.org. The rationale for injecting steroids is that they suppress inflammation of the nerve, which, in many instances, is believed to be the basis for radicular pain. 12,13 The rationale for using a transforaminal route of injection rather than an interlaminar route is that the injectate is delivered directly onto the target nerve. This ensures that the medication reaches the site of the suspected pathology in maximum concentration. Anatomy At typical cervical levels, the ventral and dorsal roots of the spinal nerves descend in the vertebral canal to form the spinal nerve in their intervertebral foramen. The foramen faces obliquely forward and laterally. Its roof and floor are formed by the pedicles of consecutive vertebrae. Its posterolateral wall is formed largely by the superior articular process of the lower vertebra and in part by the inferior articular process of the upper vertebra and the capsule of the zygapophysial joint formed between the two articular processes. The anteromedial wall is formed by the lower end of the upper vertebral body, the uncinate process of the lower vertebra, and the posterolateral corner of the intervertebral disc. Immediately lateral to the external opening of the foramen, the vertebral artery rises closely in front of the articular pillars of the zygapophysial joint (fig. 1). The spinal nerve, in its dural sleeve, lies in the lower half of the foramen. The upper half is occupied by epiradicular veins. The ventral ramus of the spinal nerve arises just lateral to the intervertebral foramen and passes forward and laterally onto the transverse process. Radicular arteries arise from the vertebral artery and the ascending cervical artery and accompany the spinal nerve and its roots to the spinal cord. Technique Cervical transforaminal injections can be performed with the patient lying in a supine, an oblique, or a lateral decubitus position, depending on operator preference and patient comfort. The position must allow adequate visualization of the cervical intervertebral foramina in anteroposterior, lateral, and oblique planes. The critical first step is to obtain a correct oblique view of the target foramen. In this view, the foramen is maximally wide transversely, and the anterior wall of the superior articular process projects onto the silhouette of the lamina. Through a puncture point overlying the posterior half of the target foramen, a needle is passed into the neck. Its tip should always lie over the anterior Anesthesiology, V 100, No 6, Jun

288 1596 RATHMELL ET AL. Fig. 1. Illustration of an axial view of the cervical intervertebral foramen and adjacent structures at the level of C6 with a needle inserted parallel to the axis of the foramen along its posterior wall. Note the proximity of adjacent structures: C6 vertebral body of C6; CA common carotid artery; IJV internal jugular vein; sap superior articular process of C5 C6 zygapophysial joint; ScA anterior scalene muscle; ScM middle scalene muscle; VA vertebral artery. half of the superior articular process, lest it be inserted prematurely and too far into the foramen. When the needle has reached the superior articular process, the needle is then readjusted to enter the foramen tangential to its posterior wall, opposite the equator of the foramen (fig. 2A). Above this level, the needle may encounter veins; below it, the needle may encounter the spinal nerve and its arteries. Using an anteroposterior view, the tip of the needle should finally be adjusted to lie opposite the sagittal midline the articular pillars. Insertion beyond this depth risks puncturing the dural sleeve or thecal sac. The final position should be checked and recorded on an oblique view (fig. 2A), which documents placement against the posterior wall of the foramen, and on an anteroposterior view (fig. 2B), which documents depth of insertion. Under direct, real-time fluoroscopy in the anteroposterior view, a small volume of nonionic contrast medium Fig. 2. (A) Right anterior oblique radiograph demonstrating a needle in position along the posterior aspect of the right C6 C7 intervertebral foramen. Inset of midportion of image with bony structures labeled: C6 C6 vertebral body; C7 C7 vertebral body; IAP inferior articular process; LA lamina; Ped pedicle; SAP superior articular process; SpP spinous process. (B) Anteroposterior radiograph demonstrating needle in final position within the right C6 C7 intervertebral foramen. The needle lies halfway between the medial and lateral borders of the articular pillars. Inset of midportion of image with bony structures labeled: Facets medial and lateral aspect of the facet column; SpP spinous processes of C5, C6, and C7; TrP (T1) transverse process of T1. Anesthesiology, V 100, No 6, Jun 2004

289 CERVICAL TRANSFORAMINAL INJECTION OF STEROIDS 1597 Fig. 3. Anteroposterior radiograph demonstrating needle in final position within the right C6 C7 intervertebral foramen after injection of 1 ml radiographic contrast medium (180 mg/ml iohexol). Contrast outlines the exiting nerve root (arrowheads) and extends along the lateral aspect of the epidural space below the foramen (small arrows). (1.0 ml or less) is injected. The solution should outline the proximal end of the exiting nerve root and spread centrally toward the epidural space (fig. 3). Real-time fluoroscopy is essential to check for inadvertent intraarterial injection, which may occur even if the needle is correctly placed (fig. 4). Intraarterial injection is manifest by rapid clearance of the injected contrast. Contrast medium may also fill epiradicular veins, which are recognized by the slow clearance of the contrast, characteristic of venous flow. Only a small volume of contrast medium (1.0 ml or less) is required to outline the dural sleeve of the spinal Fig. 4. An anteroposterior view of an angiogram obtained after injection of contrast medium, before planned transforaminal injection of corticosteroids. (A) Image as seen on fluoroscopy. The needle lies in the left C7 T1 intervertebral foramen no further medially than its mediolateral point. Contrast medium outlines the exiting nerve root (arrowhead). The radicular artery appears as a thin thread passing medially from the site of injection (small arrow). (B) Digital subtraction angiogram reveals the radicular artery extending medially more clearly (small arrow). (C) Digital subtraction angiogram after pixel-shift reregistration reveals that the radicular artery (small arrow) extends to the midline to join the anterior spinal artery. Anesthesiology, V 100, No 6, Jun 2004

290 1598 RATHMELL ET AL. nerve. As it spreads onto the thecal sac, the contrast medium assumes a linear configuration (fig. 3). Rapid dilution of the contrast medium implies subarachnoid spread, which may occur if the needle has punctured the thecal sac or a lateral dilatation of the dural root sleeve into the intervertebral foramen. When the target nerve has been correctly outlined, a small volume of a shortacting local anesthetic and corticosteroid are injected. Indications The indication for cervical transforaminal injection of steroids is for the treatment of cervical radicular pain with or without radiculopathy. The difficulties in making this diagnosis have been reviewed elsewhere. 14 The only constant feature of cervical radicular pain is pain in a dynatomal distribution (the distribution of referred symptoms caused by cervical root irritation), which may resemble the distribution of classic dermatomal maps for cervical nerve roots but not infrequently is provoked outside of the distribution of these classic dermatomal maps. 15 Confidence in the diagnosis is enhanced if the patient also has radiculopathy, but this may not always be the case. Paresthesias, segmental numbness, weakness, and loss of reflexes are reliable and valid signs of radiculopathy that allow the diagnosis to be made clinically, without recourse to investigations. Disc protrusion and foraminal stenosis are the most common causes, but diagnostic imaging is required to exclude tumors and other infrequent causes such as infection, trauma, or inflammatory arthritides. 16 Efficacy In a prospective cohort study, Bush and Hillier 17 treated 68 patients with cervical radiculopathy using a sequence of procedures in which patients who failed to respond to an injection of corticosteroids into the scalene region were treated with a transforaminal injection; those who failed to respond to transforaminal injection were, in turn, treated with an interlaminar injection of steroids. They reported that 76% of patients achieved complete relief of arm pain, but it is not possible from their report to derive what proportion responded explicitly to transforaminal injections. Slipman et al. 18 reported a retrospective analysis of transforaminal injection of steroids in 20 patients with cervical radicular pain due to cervical spondylosis and clinical, radiographic, and electrodiagnostic findings consistent with nerve root involvement due to foraminal stenosis. Outcomes were measured using a functional outcome categorization that combined measures of pain, work status, medication use, and patient satisfaction. The investigators reported pain reduction, return to fulltime work status, reduction or elimination in analgesic use, and satisfaction with treatment in 60% of patients at months follow-up (average, 21.7 months) after treatment with an average of 2.2 injections. Using a prospective cohort design, Vallee et al. 19 performed transforaminal injection of steroids in 30 patients with cervical radicular pain of more than 2 months duration and foraminal stenosis observed on computed tomography or magnetic resonance imaging. They observed greater than 75% diminution or complete resolution of pain in 53% of patients at 6 months after an average of 1.3 injections. At 3 months, 29% of patients had complete resolution of pain. This proportion persisted at 6 months but diminished to 20% at 12 months. At 3 months, an additional 29% of patients reported at least 50% diminution of their pain. This proportion persisted at 6 months but decreased to 18% at 12 months. Together, the studies of Slipman et al. 18 and Vallee et al. 19 suggest possible efficacy of cervical transforaminal injections of corticosteroids. They suggest that some 30% of patients can obtain partial but lasting relief of their pain, and a further 30% can obtain complete relief. However, these studies were observational studies without any comparison treatment. Their outcomes may be due to the natural history of cervical radicular pain syndromes or nonspecific treatment effects. Cervical epidural steroids placed by the interlaminar route have also been advocated for the treatment of radicular pain The reported studies have been retrospective, often with short or unstated periods of follow-up. They attest to variable efficacy, with 0 29% of patients obtaining complete relief of pain and between 0 and 40% of patients achieving at least 75% relief after 6 months There have been no studies published to date comparing translaminar versus transforaminal approaches to epidural steroid injection. Complications Some investigators have reported no complications resulting from the use of cervical transforaminal injection of steroids. 26 This has not been the case in other situations. The literature reports one case of fatal spinal cord infarction attributed to a transforaminal injection of corticosteroids. 27 As well, the current authors are aware of three other cases in Australia, another in Europe, and 11 in the United States, in which patients have experienced severe neurologic sequelae, including spinal cord or brainstem infarction. These cases have not been published in the literature either because they are still sub judice or because lawyers and patients have declined to have their case records released into the medical literature. In some of the unpublished cases, it seems that steroids have been injected into the vertebral artery. Correct needle placement should ensure that the needle is not in the vertebral artery, and due attention to the flow of a test dose of contrast medium would reveal if it is. Anesthesiology, V 100, No 6, Jun 2004

291 CERVICAL TRANSFORAMINAL INJECTION OF STEROIDS 1599 In the published case, and in most of the unpublished cases, no radiographic records are available to establish exactly where the needle was placed. In these cases, the basis for neurologic complications remains unclear. The leading conjecture has been that, somehow, a radicular artery was compromised. Baker et al. 28 reported a case in which a transforaminal injection was initiated at the C6 C7 level. Digital subtraction, real-time fluoroscopic imaging revealed contrast medium filling a tiny vessel that ran transversely, directly to the spinal cord: clearly a radicular artery. On seeing this image, the operator promptly abandoned the procedure. The patient experienced no ill effects. These cases provide circumstantial evidence of the mechanism of spinal cord injury after cervical transforaminal injection of steroids. Material can be injected inadvertently into radicular arteries. It seems feasible that particulate matter in depot preparations of corticosteroids might act as an embolus, and if it enters an artery that happens to be a critical reinforcing supply to the anterior spinal artery, the spinal cord would be infarcted. Large caliber vessels that reinforce the anterior spinal artery are variable in incidence and in location and can occur anywhere from C3 to C8. 28 Longitudinal spread of intraneuronally injected local anesthetic can lead to unexpected spinal anesthesia. 29 It is also feasible that intraneuronal injection of steroid solution with longitudinal spread to the spinal cord could result in spinal cord injury. Discussion A compelling evidence base for conservative treatment of cervical radicular pain is lacking, and patients with severe pain may not benefit from conservative therapy. The choice then lies between surgery and transforaminal injection of steroids. There have been no controlled studies of cervical transforaminal injection of steroids. Consequently, their efficacy has not been established. Nevertheless, the results of observational studies render transforaminal injection of steroids an option. Similarly, the efficacy of surgery has not been demonstrated by a prospective, randomized, controlled trial. The one controlled trial, conducted in Scandinavia, found surgery to be no more effective than conservative therapy, 30 but the outcomes from surgery in that study were considerably worse than those reported in observational studies conducted in the United States and Australia. 2 Those observational studies variously attest to good or excellent outcomes in anywhere from 53% to more than 90% of cases. No studies, however, have reported exactly what proportions of patients are rendered completely pain free or for how long. The singular disadvantage of cervical transforaminal injection of steroids is the risk of serious complications. Were it not for the risk of spinal cord injury, cervical transforaminal injection of steroids would probably find a place in the management of cervical radicular pain, even in the absence of controlled studies. The incidence of serious complications from cervical surgery is not known. If these are similar in nature and similar in incidence to those of cervical transforaminal injections, some proponents of injections would argue that the risk of complications is not grounds for denying patients the option of treatment with injections. There is clearly a need for better data on the efficacy of cervical transforaminal injection of steroids as well as surgery for radicular pain. To this end, a comparison of surgery and cervical transforaminal injection of steroids in a prospective clinical trial is warranted. There is also a need for accurate data on the incidence of complications from either treatment. It is disappointing that lawyers, the practitioners involved, and their patients have not released the available material regarding complications. That information could shed light on how the complications occurred. Intraarterial injection might prove not to be the mechanism of injury. Nevertheless, practitioners who elect to continue using this procedure should be conscious of the hazards and ensure that their technique is optimal. Critical to the safety of cervical transforaminal injection of steroids is an understanding of the anatomy of the cervical intervertebral foramina and their contents, coupled with disciplined and accurate imaging. Under correct, oblique views, the needle must always remain in contact with the posterior wall of the foramen. This avoids contact with the spinal nerve, its roots, and their accompanying vessels (fig. 2A). Aspiration before injection is an unreliable means of detecting intravascular needle placement, perhaps because of the small caliber of the vessels in this region. Injection of a test dose of contrast medium is important to the safe execution of the procedure. Previously, this was used to indicate correct location of the injection and to exclude intrathecal injection, whereas it now also serves to identify inadvertent intraarterial injection. This must be done under real-time imaging because spot films taken after the injection may not show contrast medium that has been rapidly cleared. Summary Because of the encouraging results of uncontrolled reports, cervical transforaminal injection of steroids is being used to treat patients with cervical radicular pain who do not have improvement with conservative therapy. There is a need for better data on both efficacy and safety because this treatment carries a risk of serious complications, including spinal cord injury. Critical to Anesthesiology, V 100, No 6, Jun 2004

292 1600 RATHMELL ET AL. the safety of this technique is an understanding of the anatomy coupled with disciplined and accurate use of imaging. References 1. Radhakrishnan K, Litchy WJ, O Fallon WM, Kurland LT: Epidemiology of cervical radiculopathy: A population-based study of Rochester, Minnesota, 1976 through Brain 1994; 117: Bogduk N: Medical Management of Acute Cervical Radicular Pain: An Evidence-Based Approach. Newcastle, Australia, Newcastle Bone and Joint Institute, Chestnut RM, Abithol JJ, Garfin SR: Surgical management of cervical radiculopathy. Orthop Clin North Am 1992; 23: Ahlgren BR, Garfin SR: Cervical radiculopathy. Orthop Clin North Am 1996; 27: Honet JC, Puri K: Cervical radiculitis: Treatment and results in 82 patients. Arch Phys Med Rehabil 1976; 57: Saal JS, Saal JA, Yurth EF: Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine 1996; 21: Martin GM, Corbin KB: An evaluation of conservative treatment for patients with cervical disk syndrome. Arch Phys Med Rehabil 1954; 35: Arnasson O, Carlsson CA, Pellettieri L: Surgical and conservative treatment of cervical spondylotic radiculopathy and myelopathy. Acta Neurochir 1987; 84: British Association of Physical Medicine: Pain in the neck and arm: A multicentre trial of the effects of physiotherapy. BMJ 1966; 1: Goldie I, Landquist A: Evaluation of the effects of different forms of physiotherapy in cervical pain. Scand J Rehab Med 1970; 2 3: Klaber Moffett JA, Hughes GI, Griffiths P: An investigation of the effects of cervical traction: I. Clinical effectiveness. Clin Rehab 1990; 4: Kang JD, Georgescu HI, McIntyre-Larkin L, Stanovic-Racic M, Evans CH: Herniated cervical intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6 and prostaglandin E 2. Spine 1995; 22: Furusawa N, Baba H, Miyoshi N, Maezawa Y, Uchida K, Kokubo Y, Fukuda M: Herniation of cervical intervertebral disc: Immunohistochemical examination and measurement of nitric oxide production. Spine 2001; 26: Bogduk N: Cervical pain, Diseases of the Nervous System: Clinical Neuroscience and Therapeutic Principles, 3rd edition. Vol I. Edited by Ashbury AK, McKhann GM, McDonald WI, Goadsby PJ, McArthur JC. Cambridge, Cambridge University Press, 2002, pp Slipman CW, Plastaras CT, Palmitier RA, Huston CW, Sterenfeld EB Symptom provocation of fluoroscopically guided cervical nerve root stimulation: Are dynatomal maps identical to dermatomal maps? Spine 1998; 23: Boyce BH, Wang JC: Evaluation of neck pain, radiculopathy, and myelopathy: Imaging, conservative treatment, and surgical indications. Instr Course Lect 2003; 52: Bush K, Hillier S: Outcome of cervical radiculopathy treated with periradicular/epidural corticosteroid injections: A prospective study with independent clinical review. Eur Spine J 1996; 5: Slipman CW, Lipetz JS, Jackson HB, Rogers DP, Vresilovic EJ: Therapeutic selective nerve root block in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain: A retrospective analysis with independent clinical review. Arch Phys Med Rehabil 2000; 81: Vallee JN, Feydy A, Carlier RY, Mutschler C, Mompoint D, Vallee CA: Chronic cervical radiculopathy: Lateral approach periradicular corticosteroid injection. Radiology 2001; 218: Rowlingson JC, Kirschenbaum LP: Epidural analgesic techniques in the management of cervical pain. Anesth Analg 1986; 65: Warfield CA, Biber MP, Cres DA, Dwarakanath GK: Epidural steroid injections as a treatment for cervical radiculitis. Clin J Pain 1988; 4: Cicala RS, Thoni K, Angel JJ: Long-term results of cervical epidural steroid injections. Clin J Pain 1989; 5: Ferrante FM, Wilson SP, Iacobo C, Orav EJ, Rocco AG, Lipson S: Clinical classification as a predictor of therapeutic outcome after cervical epidural steroid injection. Spine 1993; 18: Shulman M: Treatment of neck pain with cervical epidural steroid injection. Reg Anesth 1986; 11: Castagnera L, Maurette P, Paintillart V, Vital JM, Erny P, Senegas J: Longterm results of cervical epidural steroid injection with and without morphine in chronic cervical radicular pain. Pain 1994; 58: Furman MB, Giovanniello MT, O Brien EM: Incidence of intravascular penetration in transforaminal cervical epidural steroid injections. Spine 2003; 28: Brouwers PJAM, Kottnik EJBL, Simon MAM, Prevo RL: A cervical anterior spinal artery syndrome after diagnostic blockade of the right C6-nerve root. Pain 2001; 91: Baker R, Dreyfuss P, Mercer S, Bogduk N: Cervical transforaminal injection of corticosteroids into a radicular artery: A possible mechanism for spinal cord injury. Pain 2002; 103: Selander D, Sjöstrand J: Longitudinal spread of intraneuronally injected local anesthetics. Acta Anaesth Scand 1978; 22: Persson LCG, Carlsson CA, Carlsson JY: Long-lasting cervical radicular pain managed with surgery, physiotherapy or a cervical collar: A prospective, randomized study. Spine 1997; 22:751 8 Anesthesiology, V 100, No 6, Jun 2004

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301 bs_bs_banner Pain Medicine 2014; 15: Wiley Periodicals, Inc. Review Article The Effectiveness and Risks of Fluoroscopically Guided Cervical Transforaminal Injections of Steroids: A Systematic Review with Comprehensive Analysis of the Published Data Andrew Engel, MD,* Wade King, MMedSc MMed(Pain), John MacVicar, MB ChB MPainMed, and on behalf of the Standards Division of the International Spine Intervention Society *Continental Anesthesia, Oak Brook, Illinois, USA; Pendlebury Pain Management, Pendlebury Clinic, Newcastle, New South Wales, Australia; Southern Rehabilitation Institute, Christchurch, New Zealand Reprint requests to: Andrew Engel, MD, Continental Anesthesia, 1301 W 22nd St # 610, Oak Brook, IL 60523, USA. Tel: ; Fax: ; engel.andrew@gmail.com. Conflicts of interest: None of the authors has any financial conflicts of interest to disclose. Abstract Objective. To determine the effectiveness and risks of fluoroscopically guided cervical transforaminal injection of corticosteroids in the treatment of radicular pain. Design. Systematic review of the literature with comprehensive analysis of the published data. Interventions. Three reviewers with formal training in evidence-based medicine searched the literature on fluoroscopically guided cervical transforaminal injection of steroids (CTFIS). Each reviewer independently assessed the methodology of studies found and appraised the quality of the evidence presented. Outcome Measures. The primary outcome assessed was relief of radicular pain. Other outcomes such as reduction in surgery rate and complications were noted if reported. The evidence on each outcome was appraised in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system of evaluating evidence. Results. The searches yielded 16 primary publications on effectiveness. Available evidence, derived mainly from observational studies, suggests that approximately 50% of patients experience 50% relief of radicular pain for at least 4 weeks after CTFIS, and the intervention may have surgery-sparing effects. The literature also contains 21 articles with primary reports of serious complications, including 13 deaths and many catastrophic neurological injuries. The evidence of pain-relieving effects, of surgerysparing effects, and of risks of CTFIS were all rated as of very low quality according to the GRADE system. Conclusions. In patients with cervical radicular pain, fluoroscopically guided CTFIS may be effective in easing pain and reducing need for surgery. However, the evidence of effectiveness is of very low quality, and the benefits of the procedure are compromised by the risks of serious complications. Key Words. Radicular Pain; Cervical; Transforaminal; Fluoroscopy; Injection; Steroids Introduction In 1933, Dogliotti described cervical epidural steroid injection, employing the interlaminar route, as a treatment for cervical radicular pain [1]. The procedure was found to be effective in some cases but the technique was hazardous 386 Downloaded from by guest on 18 February 2018

302 Cervical Transforaminal Injection of Steroids because of the narrow width of the cervical epidural space between the ligamentum flavum and the dura mater covering the spinal cord. Transforaminal injection of corticosteroids was introduced as a treatment for sciatica in 1952 by Robecchi and Capra [2]. They described injection by a sacral, transforaminal route, passing a needle through the first dorsal sacral foramen to inject hydrocortisone around the first sacral nerve root. Later, the procedure was adapted to the lumbar spine, and transforaminal injection of steroids has been proven to be an effective treatment for many patients with lumbar and sacral radicular pain [3]. In 1988, Bard and Laredo described cervical epidural steroid injection via a transforaminal route for cervical radicular pain [4]. Cervical transforaminal injection of steroids (CTFIS) continues to be administered for this indication, although cervical interlaminar epidural steroid injection has remained in use. Both procedures have literature that suggests these injections could be effective, but both are also known to be associated with risks, including epidural hematoma, paralysis, and death. The purported advantage of transforaminal injections over interlaminar injections is precise placement of steroid onto the spinal nerve that is assumed to be the source of radicular pain. Risks include injection into the vertebral artery or a radiculomedullary artery that supplies the spinal cord, and overpenetration of the needle through the foramen into the spinal cord. The use of real-time fluoroscopy enables the physician to visualize dispersal of contrast medium and the injectate around the target nerve. The purpose of this project was to identify all publications on fluoroscopically guided CTFIS for the treatment of radicular pain and to assess the data on the effectiveness and risks of the procedure in preparation for the development of appropriate use criteria. Those data should be considered in the light of the natural history of cervical radicular pain, its expected course in the absence of treatment. Natural history has a bearing on all such data produced over time; it provides a fundamental reference for prognosis and sets outcomes after treatment in perspective. Unfortunately, there are no rigorous epidemiological data on the natural history of cervical radicular pain so such comparisons are not possible. Studies of patients with neck pain who were treated conservatively do suggest that the long-term outcomes of cervical pain are favorable, but not all patients in these studies had radicular pain so it is not clear if they reflect the natural history of cervical radicular pain [5 7]. Methods The three investigators, who all have formal training in evidence-based medicine and are members of the Standards Division of the International Spine Intervention Society (ISIS), searched the scientific literature independently for publications on the effectiveness and any unwanted effects of fluoroscopically guided cervical transforaminal injection of steroids (CTFIS). Initially, they each conducted digital searches using the search engine Ovid to explore the databases Embase, Medline, PubMed, and EBM Reviews, using the keywords transforaminal, cervical, injection, corticosteroids, steroids, nerve root sleeve, radicular pain, and radiculopathy. The searches encompassed all scientific articles published until June The only exclusions were non- English language articles, non-human studies, conference abstracts, and case reports, unless they were reports of complications. When suitable articles were retrieved, the references of each were perused for relevant citations that had not been identified by the database searches. The articles retrieved by the searches were sorted by each of the investigators into two groups: primary publications (reports of studies that produced original data) and secondary publications (those not producing original data, such as literature reviews, editorials, and letters). The primary publications on the effectiveness of fluoroscopically guided CTFIS were then classified by each of the investigators into three types of study, termed observational studies, pragmatic studies, and explanatory studies. Observational studies were defined as those that simply described the outcomes observed after the use of an intervention; note was taken of whether the observational study design was prospective or retrospective. Pragmatic studies were defined as those in which the outcomes of one intervention were compared with those of another intervention expected to have a therapeutic effect. Explanatory studies were defined as those in which the outcomes of an intervention were compared with those of an intervention not expected to have a therapeutic effect. The three investigators then compared their individual classifications of articles, and any differences were discussed until they reached consensus about the class in which each primary study belonged. The primary articles on effectiveness of fluoroscopically guided CTFIS were then appraised by each of the investigators independently, using an instrument developed by the ISIS Standards Division to facilitate reliable assessment of studies of therapeutic effectiveness. The instrument assesses study design and objective; the study population; the intervention under study and any other intervention used for comparison; the outcomes considered and the instruments used to evaluate them; the results reported and the times they were observed after the intervention; any methodological limitations apparent, including nonblinded observers; and losses to follow-up, etc. It also records the reviewer s assessment of the article and the data it reported, with specific attention to any apparent biases or inconsistencies, the precision of estimates of effect (including confidence intervals of data), and any confounding factors. Each reviewer then made a general comment led by the question: Irrespective of what the authors may or may not have written, does the study provide valid data on the effectiveness of fluoroscopicallyguided CTFIS, and if so, how compelling are those data? When the investigators had each completed their independent appraisals of the effectiveness articles, they 387 Downloaded from by guest on 18 February 2018

303 Engel et al. shared the results of their assessments and discussed any differences of opinion on particular articles until they reached consensus on the value of each article s contribution to the published evidence of the effectiveness of CTFIS. The assessments were then appraised by other members of the ISIS Standards Division (all also trained in evidence-based medicine). The results of studies that produced categorical data for individual patients were tabulated (see below). The data produced from all of the studies were appraised, and the resultant body of evidence was analyzed to determine whether it provided evidence of effectiveness of the procedure. That body of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system of appraisal to determine the quality of the evidence of the effectiveness of CTFIS. The three investigators also searched the scientific literature independently for publications on the risks and any unwanted effects of fluoroscopically guided CTFIS. Again they conducted digital searches using the search engine Ovid to explore the databases Embase, Medline, PubMed, and EBM Reviews, using the same keywords and the terms safety, complications, and unwanted effects. As before, they perused the references of each article retrieved for relevant citations that had not been identified by the database searches. The articles reporting complications and unwanted effects were also appraised by each of the investigators. The investigators then shared their findings and discussed any differences of opinion on particular articles until they reached consensus on the value of each article s contribution to the published body of evidence of the risks, complications, and unwanted effects of fluoroscopically guided CTFIS. The information provided in the reports of complications was collated, and the resultant body of evidence was evaluated using the GRADE system of appraisal to determine the quality of the evidence of the risks of CTFIS. The quality of the published evidence of effectiveness and the published evidence of risks were then both taken into account, and conclusions were drawn in accordance with the GRADE system about the strength of recommendations for use of CTFIS based on all published data on the procedure. Results The literature searches yielded 24 articles on the effectiveness of fluoroscopically guided CTFIS. Of these, 16 were primary studies producing original data on the effectiveness of the procedure, and the other eight articles were reviews or essays that discussed effectiveness but did not provide original data [8 15]. The literature searches also yielded 45 publications that discussed aspects of the safety of the procedure and its associated risks. Of these, 21 were articles reporting original data on significant complications. Effectiveness The 16 primary studies of effectiveness included 13 observational studies and 3 pragmatic studies. There were no explanatory studies. The 16 study reports were appraised using the standard instrument, and their data were assessed by 2 measures of outcome: relief of radicular pain and avoidance of surgery. The standard adopted in most studies for success in pain relief was at least 50% relief of radicular pain; that degree of relief for at least 4 weeks after CTFIS was considered by the reviewers a minimal standard of successful outcome in that regard. Data on the avoidance of surgery were extracted from studies that reported the outcomes of patients who were on waiting lists for surgery but after CTFIS did not go on to have the surgery that had been planned. The results of primary studies that yielded such data were then analyzed to determine what the whole body of published evidence shows about the effectiveness of fluoroscopically guided CTFIS for relieving radicular pain and reducing the need for surgery. Observational Studies The first article on the effectiveness of CTFIS was published in 1996; it was a prospective, observational study of 68 consecutive patients with cervical radicular pain treated with injections of lidocaine and triamcinolone by three different routes including CTFIS [16]. The outcomes were not stratified according to the types of injection administered, so the results were not able to be included in this review. In 2000, the report of a retrospective, observational study showed the outcomes of 20 patients treated with therapeutic selective nerve root blocks (CTFIS) for atraumatic cervical spondylotic pain [17]. The symptomatic level was determined by reflex changes or myotomal weakness on physical examination, or in some cases by electrodiagnostic testing. If physical signs and electrodiagnosis did not identify the source of symptoms, a diagnostic selective nerve root block was done; if it produced 80% relief, the patient was offered CTFIS. Data were collected on average for 21 months after patients were discharged from treatment (range months). Twenty patients were treated with CTFIS, and 12 of them were described as having good or excellent results for a set of outcomes measured by a questionnaire. With respect to pain scores, average visual analog scale (VAS) levels at initial presentation were provided, and good and excellent results were defined as verbal pain ratings of 3 4 and 0 2, respectively, but these group results were not suitable for inclusion in the tabulated data of this review. In 2001, a prospective observational study was published of 32 patients with cervical radicular pain persisting after at least 2 months of conservative treatment [18]. Two patients had bilateral pain so the study involved 34 pain sources. Twenty-six patients had cervical spondylosis, five patients had disc herniations, and one patient had cervical spondylosis and a disc herniation. The patients had either 388 Downloaded from by guest on 18 February 2018

304 Cervical Transforaminal Injection of Steroids one or two fluoroscopically guided CTFIS of 50 mg prednisolone, in conjunction with medical treatment which included wearing a cervical collar. After the injections, pain relief was assessed using a 100 mm VAS. The results showed radicular pain was relieved by at least 50% for up to 3 months in 18 of the 32 patients or 56% (CI %), and of those 18, 16 patients or 50% (CI %) reported sustained relief at 6 months. Patients who had no relief at 14 days did not experience any benefit later. Follow-up data 6 months after CTFIS showed the treatments were successful in 18 patients or 56% (CI %) who were able to resume their full lifestyles, and unsuccessful in 14 or 44% (CI %) who were unable to return to work or other activities. The authors stated that after eight of the 43 procedures, or 19% (CI %) of them, patients had minor neurovegetative manifestations, which were not further defined. This article does not provide compelling data of the effectiveness of CTFIS for several reasons, including the possible effects of co-interventions. In 2004, the same group who had published in 2000 reported a retrospective, observational study of the effectiveness of CTFIS for radicular pain induced by motor vehicle accidents, sporting injuries, falls, and other forms of trauma [19]. The subjects were 15 patients with cervical spondylosis and radicular pain diagnosed by clinical assessment, magnetic resonance imaging (MRI), electrodiagnostic criteria, and selective nerve root blocks with local anesthetic. All 15 had CTFIS using betamethasone; an average of 3.7 therapeutic injections was administered. Follow-up data collected at an average of 20.7 months after treatment claimed a good or excellent outcome for three patients, or 20% (CI %). Average verbal pain ratings were provided for all patients at initial presentation and at follow-up for patients who had avoided surgery, but because of the long times before follow-up, the results were not suitable for inclusion in the data of this review. In 2005, an article was published reporting a prospective, observational study of outcomes after CTFIS in 21 patients with cervical radicular pain [20]. The patients had chronic, unilateral C6 or C7 radicular pain diagnosed by clinical assessment and corresponding imaging findings on MRI or myelography; 14 patients had cervical spondylosis, and seven had disc herniations. All patients had been deemed to need anterior cervical discectomy and fusion, and were on a waiting list for surgery. Each patient was treated with two CTFIs of triamcinolone, 2 weeks apart. Five patients registered relief of pain (as measured on a 100 mm VAS) almost immediately, and the positive effects were clearly measurable at the 6-week and 4-month follow-up evaluations. Of the 21 patients, five or 24% (CI %) had significant relief of radicular pain and no longer needed surgery, whereas the other 16 patients or 76% (CI %) proceeded to surgery. The outcomes were not stratified according to the original diagnosis of cervical spondylosis or disc herniation. These data provide some evidence of the effectiveness of CTFIS for relief of radicular pain and avoidance of surgery. It is noteworthy that this study was originally designed to follow 60 patients but it was stopped at 21 patients because other articles had been published reporting serious complications of the procedure. In 2006, another retrospective, observational study reported the outcomes of 70 patients with cervical radicular pain treated by CTFIS [21]. The patients had cervical disc herniations causing nerve root compression, demonstrated on MRI, and all had failed to improve after conservative management including physical therapy and nonsteroidal anti-inflammatory medications. The patients had opted for surgical management and were offered a trial of CTFIS in attempts to delay or prevent surgery. The number of injections in the study group ranged from one to four (with a mean of 1.46); 48 patients had only one CTFIS, 13 patients had two injections, seven patients had three injections, and two patients had four CTFIS. Of the 70 patients followed for an average of 13 months, 44 or 63% (CI %) had substantial relief of their symptoms, as assessed by Odom s criteria, and were able to avoid surgery. Numerical pain scores were not provided so data for pain relief were not able to be included in this review. In 2007, a retrospective, observational study was published of 24 consecutive patients with cervical radicular pain treated with CTFIS [22]. Five of the patients were lost to follow-up, so the outcomes reported were actually for 19 non-consecutive patients, 17 of whom were each treated with single CTFIS and two received two CTFIS, using triamcinolone. The results published showed that of the 24 patients, clinically significant sustained relief of radicular pain was reported by six or 25% (CI %), while two or 8% (CI %) had moderate (50%) relief. A successful outcome was defined as reduction of pain by greater than 40 points on a VAS for at least 6 months. The authors conclusions that CTFIS may be effective for cervical radicular pain in some cases were qualified by their recognition of the limitations of the study. In 2008, another retrospective, observational study was published [23]. It reported the outcomes of 33 consecutive patients with cervical radicular pain persisting after conservative treatment with rest, analgesia, and physiotherapy for at least 2 months and corresponding findings of cervical disc disease and/or foraminal stenosis on MRI. The patients were treated with CTFIS using triamcinolone. Two patients were lost to follow-up and another three patients had surgery, which left 28 non-consecutive patients for follow-up. All 28 of these patients reported pain relief within hours after CTFIS and that relief was sustained at 6 weeks and a year after the treatment. Only group data were presented: the mean pre-treatment VAS pain score was stated as 7.4 (range 5 10), which improved to 2.2 (range 0 7) at 6 weeks and 2.0 (range 0 4) at 1 year; the improvements were statistically significant. Twenty-one patients had cervical spondylosis, and 12 patients had disc herniations. There was no significant difference in outcome between these groups. These data provide some evidence of the effectiveness of CTFIS for 389 Downloaded from by guest on 18 February 2018

305 Engel et al. radicular pain but are not compelling on their own because only group data were presented and the effect sizes were moderate. As categorical data were not provided, the results were not suitable for inclusion in the tabulated data of this review. In 2009, a report was published of a retrospective, observational study of 159 consecutive patients treated for cervical radicular pain with CTFIS using either triamcinolone or dexamethasone [24]. Outcomes were assessed within a month of treatment, at an average of 15.8 days (range 4 31 days), using a 5-point scale of no pain, much improved, slightly improved, same as before, worse. For most patients, there was no long-term follow-up; that and the lack of numerical pain scores made the results unsuitable for inclusion in the review data. In 2012, a prospective, observational study of 98 patients with cervical radicular pain was published [25]. All patients had pain persisting after 4 weeks of conservative treatment and corresponding imaging findings of cervical disc herniation and nerve root compression, so they were considered candidates for surgery. They were treated with up to three (mean 1.8) epidural injections of dexamethasone, by either an interlaminar or a transforaminal route, and in some cases both. The outcome data were not stratified according to the type of injection administered, so the results were not included in this review. Also published in 2012 was another prospective, observational study of 145 consecutive patients treated with CTFIS for cervical radicular pain [26]. The patients all had chronic neck pain and arm pain of radicular type, MRI findings indicating cervical nerve root origin based on degenerative disease, and positive selective transforaminal diagnostic nerve root blocks with local anesthetics resulting in at least 50% temporary arm pain reduction. They were treated with CTFIS performed three times at intervals of 3 weeks, except for five patients who had one injection only. The authors of the original article only followed the 140 patients who completed the study; therefore, the five dropouts were considered failures in accordance with the convention of worst case analysis. The injectate was not specified. At follow-up weeks after the first CTFIS, 69 of the original 145 patients or 48% (CI %) reported more than 50% relief of arm pain, and 38 or 26% (CI %) reported complete relief of arm pain. These data too provide evidence of the effectiveness of CTFIS for relief of radicular pain. Another article published in 2012 was the report of a retrospective study of 28 consecutive patients treated with CTFIS for cervical radicular pain [27]. All patients had a single nerve root involved and imaging findings suggesting either spondylosis (19 patients or 68%) or disc herniation (nine patients or 32%), and all had failed to respond to at least 2 months of conservative treatment. CTFIS was performed using a mixture of triamcinolone and bupivacaine, and repeated at 2-week intervals up to a total of three injections; the mean number of injections per patient was 2.8. Only group data were reported. The mean pain score before treatment was 7.8; at follow-up after 1 week, the mean pain score was reduced to 3.6, and at 3 months, it was 2.9. After that, the mean pain scores rose again to 3.3 at 6 months and 4.6 at a year. These data add to the evidence of the effectiveness of CTFIS but as only group data were provided, the results are not suitable for inclusion in the tabulated data of this review. In 2013, a retrospective observational study was published involving 441 patients with cervical radicular pain treated with CTFIS over a 5-year period [28]. The patients had either disc protrusions or foraminal stenosis demonstrated on MRI. The first 220 were treated with one to three CTFIS using triamcinolone and 1% lidocaine. The next 221 were treated with a similar number of injections using dexamethasone and 1% lidocaine. The main aim of the study was to compare the effects of the two steroids. Only group data were provided. In the triamcinolone group, the mean pain score before treatment was 6.61, and at follow-up 4 weeks after the last injection, it was reduced by a mean of In the dexamethasone group, the pre-treatment mean pain score of 6.59 was reduced by a mean of The differences were not statistically significant. There was no indication whether patients were consecutive, and no information provided about loss to follow-up. The procedure was described as a selective nerve root block but patients were injected with 0.5 ml of steroid, 2 ml of local anesthetic, and 2 ml of saline, a volume of injectate that would suggest the procedure was not selective. It is also noted that while reductions in mean VAS were reported, there were also increased requests for medication. For example, at 12 months, mean VAS decreased by 41%, but 46% of patients requested increased medication. As only group mean results were provided, the data for pain relief were not able to be included in the tabulated data of this review. Pragmatic Studies The three pragmatic studies were published between 2006 and A pragmatic study published in 2006 compared outcomes after CTFIS using dexamethasone with those after CTFIS using triamcinolone for treatment of cervical radicular pain [29]. The subjects were 30 consecutive patients with cervical radicular pain, corresponding unilateral nerve root compression at a single segmental level as seen on computed tomography (CT) or MRI, and no litigation, worker s compensation, or disability remuneration. They were randomly allocated for treatment with a single CTFIS using either dexamethasone or triamcinolone and followed up 4 weeks later. Of 15 patients in the dexamethasone group, at least 50% relief of pain was reported by nine or 60% (CI %) and of 15 in the triamcinolone group, at least 50% relief of pain was reported by 10 or 67% (CI %); the overlap of confidence intervals shows there was no statistically significant difference between these results. Overall, significant pain relief was reported after CTFIS by 19 of the 30 patients or 63% (CI %). 390 Downloaded from by guest on 18 February 2018

306 Cervical Transforaminal Injection of Steroids These data provide further evidence of the effectiveness of CTFIS for relief of cervical radicular pain but, as both arms of the study used CTFIS, the results were considered as those of an observational study for the purposes of this review. In 2007, a pragmatic study of 40 consecutive patients with cervical radicular pain treated with either transforaminal injections of local anesthetic and steroid, or local anesthetic and saline was published [30]. All patients had unilateral cervical radicular pain associated with degenerative disease of the cervical spine, corresponding signs at one or two levels on MRI and a positive response, assessed as at least 50% pain relief, after a diagnostic transforaminal selective nerve root block at the level(s) identified by MRI. They were randomized into two equal groups for treatment with either CTFIS using methylprednisolone and mepivacaine or a transforaminal injection of a similar volume of saline and mepivacaine. At follow-up 3 weeks later, they were asked 10 questions about any changes in pain and other subjective effects at 1, 2, and 3 weeks after treatment. In both groups of 20 patients, at least short-term relief was reported by seven or 35% (CI %) but the degree to which pain reduced in intensity was not reported. Clearly, there was no statistically significant difference between the outcomes of the two groups. These data raise questions about the effectiveness of CTFIS for relief of cervical radicular pain but are of uncertain value because of the unvalidated outcome measure used and other limitations of the study design. The short-term follow-up made the results unsuitable for inclusion in the data of this review. In 2011, a third pragmatic study was published, comparing outcomes of CTFIS guided by CT fluoroscopy and CTFIS guided by C-arm fluoroscopy [31]. The 116 patients all had intense cervical radicular pain, persisting for at least 3 months and not relieved by oral medications, along with corresponding MRI findings of cervical disc herniation at a single segmental level. They were allocated randomly for treatment with CTFIS using dexamethasone mixed with lidocaine, performed under either CT fluoroscopy or C-arm fluoroscopy. Eight weeks after treatment, the majority of patients in each group reported successful outcomes, defined as 50% or more reduction in Numeric Rating Scale and/or at least 40% reduction in Neck Disability Index scores. In the CT group of 51 patients, successful results for arm pain relief were obtained by 37 or 73% (CI %). In the C-arm group of 65 patients, successful results for arm pain were obtained by 36 or 55% (CI %). The differences between the group results were stated as statistically significant but the overlapping confidence intervals suggest otherwise. While questions can be raised (and were, by the journal editors) about the attribution of the claimed differences, the C-arm subgroup data do provide some evidence of the effectiveness of CTFIS for relief of cervical radicular pain. Effectively, the C-arm data were considered as those of an observational study for the purpose of this review. Table 1 Reported radicular pain-relieving effects of CTFIS Study Evidence for Relief of Radicular Pain Radicular Pain Relieved by at Least 50% Vallée et al [18] 18/32 56% (CI %) Kolstad et al [20] 5/21 24% (CI %) Dreyfuss et al [29] 19/30 63% (CI %) Razzaq et al [22] 8/24 33% (CI %) Lee JH et al [31] 36/65 55% (CI %) Persson and Anderberg 2012 [26] 69/145 48% (CI %) The numbers of patients and their percentages (with confidence intervals) reported in six studies as having at least 50% relief of radicular pain for at least 4 weeks after CTFIS. Six primary studies reported patients having at least 50% relief of radicular pain for at least 4 weeks after CTFIS. The results are set out in Table 1. Some data were reported for longer-term durations of pain relief. Outcomes at 4 months post-treatment were provided for six of the 21 patients involved in one study; five of the 21 patients or 24% (CI %) had at least 50% relief of radicular pain for that period [20]. In another study, the pain relief reported at 2 months was found to be maintained at 6 months in eight of the 24 patients, or 33% (CI %) [22]. Outcome data at 6 months were also available for 32 patients in another study; 18 or 56% (CI %) had at least 50% relief of radicular pain for that period [18]. Data were available at 12 months posttreatment for 32 patients in one study; 12 or 38% (CI %) had at least 50% relief of radicular pain for that period [18]. One study reported significant benefit that persisted for a year but the article did not provide categorical data; only group data were presented and the pre-operative mean VAS score was 7.4 (range 5 10), which improved to 2.2 (range 0 7) at 6 weeks and 2.0 (range 0 4) at 1 year after CTFIS [23]. The standard accepted as denoting success in these studies, at least 50% relief, is far from a truly satisfactory outcome for cervical radicular pain that is intense and disabling. Patients with such pain want complete relief if possible. Five studies reported patients achieving complete relief of radicular pain for at least 4 weeks after CTFIS and the success rates for that outcome are much lower, as shown in Table 2. The patients in one of these studies were diagnosed with disc herniations [31] and patients in one study had cervical spondylosis [26]. Patients with either cervical spondylosis or disc herniations were treated in two studies, with the majority of patients in each of these studies diagnosed with cervical spondylosis [18,20]. The radiological diagnosis is not described in the remaining studies [22,29]. These 391 Downloaded from by guest on 18 February 2018

307 Engel et al. Table 2 Reported radicular pain-relieving effects of CTFIS Study studies do not suggest a trend of CTFIS being more effective for one diagnosis than the other. Evidence of Surgery-Sparing Effects Radicular Pain Abolished Vallée et al [18] 9/32 28% (CI %) Kolstad et al [20] 2/21 10% (CI %) Dreyfuss et al [29] 5/30 17% (CI %) Razzaq et al [22] 3/24 13% (CI %) Persson and Anderberg 2012 [26] 38/145 26% (CI %) The numbers of patients and their percentages (with confidence intervals) reported in five studies as having complete relief of radicular pain for at least 4 weeks after CTFIS. Two primary studies reported patients on surgical waiting lists who did not go on to have surgery after CTFIS. Surgery was avoided in 24% (CI %) of patients in one study [20] and in 63% (CI %) in the other study [21]. It is of note that the 95% confidence intervals do not overlap (Table 3). The patients in the study which reported a higher success rate with respect to surgery-saving had disc herniations [21], and the majority of the patients in the study which reported poorer outcomes had cervical spondylosis [20]. Further studies would be required to determine whether or not CTFIS is more likely to prevent surgery in patients with disc herniations than in patients with cervical spondylosis. GRADE Evaluation of Evidence of Effectiveness The effectiveness data were evaluated in accordance with the GRADE system of rating quality of evidence. The data for the two main outcomes were evaluated separately. The evidence of the reported radicular pain-relieving effects of CTFIS was found to be of very low quality. The evidence of the surgery-sparing effects of CTFIS was also found to be of very low quality. Table 3 CTFIS Study Reported surgery-sparing effects of Surgery Avoided Kolstad et al [20] 5/21 24% (CI %) Lin et al [21] 44/70 63% (CI %) The numbers of patients and their percentages (with confidence intervals) reported in two studies as not going on to have surgery at various time periods after CTFIS. The starting point in the GRADE system is the types of study from which data are produced to form the relevant body of evidence. That body of evidence is then rated as of lower quality if there are particular methodological problems in it, or as of higher quality if there are factors such as a large magnitude of effect. The evidence for radicular pain-relieving effects comes from two pragmatic studies [29,31] and four observational studies [18,20,22,26] that reported successful outcomes for radicular pain after treatment with CTFIS. As there were no explanatory studies, the best evidence would be expected to come from the pragmatic studies. In both pragmatic studies the study design meant the results were effectively those of an observational study for the purposes of this review, as explained above [29,31]. When the data of the observational studies were added, the body of evidence for relief of radicular pain was downgraded further because of multiple limitations in the study designs introducing risks of bias. There was no reason to upgrade the body of evidence. Accordingly, the evidence for relief of radicular pain by CTFIS is of very low quality. The true effect is likely to be substantially different from the estimate of effect, and further research is likely to change the presented conclusions. Without explanatory studies, the degree to which any reported benefit of CTFIS is due to non-specific factors, including the natural history of the causative condition, is unknown. Though not directly related to the quality of the literature, there is work that questions whether steroids are even necessary in CTFIS. There was one randomized controlled trial (RCT) that was excluded from this review because it used a non-validated outcome measure, and the follow-up did not reach 4 weeks, but that study s results suggested that the effectiveness of CTFIS was indistinguishable from that of placebo [30]. The evidence of reported surgery-sparing effects is also not compelling. The body of evidence came from two observational studies [20,21]. The evidence from the two studies produced evidence of a very low quality for the same reasons as stated above for the evidence for radicular pain relief. The authors have limited confidence in the estimate, and the true effect may be substantially different from the estimate of effect. A portent of this likelihood has appeared in abstract form [32]. Its authors found no surgery-sparing effect of CTFIS, though the full data could not be reviewed since only an abstract has been published. Further research is likely to change the presented conclusions significantly and help us understand better why some patients who have CTFIS go on to avoid surgery. The data currently available fall short of establishing CTFIS in terms of cause and effect in this regard. There are many reasons why patients do not have spinal surgery; not least is that most people try to avoid spinal surgery if they possibly can. Some use analgesic medications and other biomedical interventions to control the pain and some just adapt to life with the pain, perhaps with the aid of psychological interventions, hoping it will settle over time. 392 Downloaded from by guest on 18 February 2018

308 Cervical Transforaminal Injection of Steroids Readers must be careful not to confuse evidence of very low quality with evidence of very low effectiveness. What the GRADE rating signifies is not that the existing evidence shows the effectiveness to be poor but that the evidence itself is poor so better evidence is required before the issue of effectiveness can be determined. Risks The published evidence of severe risks of CTFIS is comprised of 23 original case reports of serious complications that occurred during or just after a CTFIS procedure and 25 other publications, including one survey report that detailed 63 other significant unwanted effects. The 23 original case reports and the survey report were appraised and are outlined below in the chronological order of their publication. Where the information was provided in the article, particular attention was given in the appraisals to injection technique; use of precautionary checks such as radiographic confirmation of position, aspiration, injection of contrast medium under digital subtraction angiography (DSA), neurography, and administration of a test dose of local anesthetic; and whether particulate or nonparticulate steroids were injected. The other 24 complication publications were not included in this review because they provided no new cases of major complications. These articles not included were four reviews [33 36], five letters [37 41], one survey [42], eight studies associated with vascular uptake [43 50], one cadaveric study [51], one device study [52], three observational studies [53 55], and one steroid study [56]. Primary Literature Reporting Complications Spinal Cord Infarction Leading to Death The first case report of a major complication of CTFIS was published in 2001 [57]. A 48-year-old man with intractable neck pain radiating into his right arm underwent CTFIS targeting the right C6 nerve root, using a 22 gauge (G) spinal needle. When the needle tip was in position, as seen on the fluoroscope, aspiration showed no sign of blood or cerebrospinal fluid. Contrast medium was injected and seen to flow along the nerve root. A mixture of bupivacaine and triamcinolone was then injected. Within a minute, the patient suffered flaccid paralysis; resuscitation was attempted but he went on to develop an anterior spinal cord syndrome and died in a hospital after a complicated stay. MRI post-injection showed extensive spinal cord infarction. It seems likely that particulate steroid was injected into a radiculomedullary artery. Cerebral Injury and Cortical Blindness In 2003, a 54-year-old male with right-sided radicular pain and past history of C3 C7 decompression and C6 7 fusion was treated with TFIS at C5 6 on the right, using a 22G spinal needle [58]. When the needle seemed in position, bright red blood was aspirated, suggesting arterial puncture. The needle was repositioned and aspiration was negative. Loss of resistance to 1 ml of injected air was followed by injection of 2 ml of nonionic contrast medium, which did not produce a satisfactory epidurogram. No other agents were injected but within seconds, the patient developed lateral nystagmus and within 45 minutes had total bilateral blindness. After a complicated hospital course, he was discharged a month later with mild shortterm memory loss and persistent right homonymous hemianopia. Arterial air embolism was considered a likely cause. Vertebral Artery Occlusion Leading to Death Also reported in 2003 was another case of fatal complications after CTFIS [59]. A 44-year-old woman with intermittent left neck pain radiating into her left shoulder and arm had TFIS at C6 7 with a 25G needle. When its tip was judged to be in position, aspiration showed blood. The needle was repositioned until aspiration was negative. Contrast medium was injected, producing a C7 neurogram. Then 3 ml of a mixture of methylprednisolone and bupivacaine was injected. The patient became unconscious immediately. She was transferred to the hospital and treated intensively but died the following day. Autopsy showed massive cerebral edema due to dissection and thrombosis of the left vertebral artery. Lateral Spinal Cord Infarction Another article published in 2003 reported three cases of serious complications after CTFIS [9]. A 39-year-old woman with left neck and shoulder pain after a motor vehicle accident had an MRI showing a C6 7 disc bulge to the right without neural compression. Treatment was planned with alternating right and left C7 TFIS at weekly intervals. The first procedure, right C7 TFIS, was done without complication. A week later, left C7 TFIS was attempted using a 25G needle. During the procedure, the patient felt severe pain in the left arm so the C7 injection was aborted and left C6 TFIS was performed instead. Afterwards, the patient s left arm was numb and weak, consistent with C7 radiculopathy, which was persisting a year later when the report was published. MRI after the CTFIS showed signs of petechial hemorrhage in the lateral spinal cord. Cerebral Ischemia and Hippocampal Atrophy The second of the three cases reported in the 2003 article involved non-fatal brain injury [9]. A 65-year-old male had neck and left arm pain associated with cervical spondylosis. Left C5 6 TFIS was performed using a 25G needle. The needle position was checked on anteroposterior and lateral fluoroscopic views. Aspiration was not mentioned in the report. Contrast medium was injected and a C6 neurogram recorded. Then the treating physician began injecting 2.5 ml of a mixture of betamethasone and bupivacaine. During this injection, the patient became unconscious and had generalized seizures for 3 4 minutes, then went into a post-ictal state, which lasted for 393 Downloaded from by guest on 18 February 2018

309 Engel et al. about 45 minutes. He recovered over time but was left with an organic brain syndrome, which prevented return to work. MRI undertaken within 24 hours of the TFIS showed normal findings. Follow-up MRI 6 and 12 months later demonstrated atrophy of the hippocampus. Posterior Spinal Cord Infarction and Cerebellar Infarction The third of the three cases reported in the 2003 article involved a 39-year-old male with left radicular pain and a left C5 6 disc bulge shown on MRI [9]. Left C6 TFIS was undertaken using a 22G needle placed in the left C5 6 foramen under fluoroscopic guidance. Aspiration was not mentioned in the report. A small amount of contrast medium was injected and an appropriate pattern was seen. Injection was then begun of 2.5 ml of a mixture of lidocaine and betamethasone solutions. When 1.5 ml had been delivered, the patient said he felt light-headed and became unconscious. The procedure was aborted and resuscitation commenced. The patient regained consciousness within 10 minutes but had dysarthria, left arm paralysis, and lower limb ataxia. His condition improved over a period of weeks but his left arm remained permanently weak and numb. Subsequent MRI showed signs of infarction of both the posterior spinal cord at the C1 C4 levels and the cerebellum. Cerebellar and Cerebral Infarction Leading to Death In 2004, another case of fatal complications after CTFIS was reported [60]. A 48-year-old woman had right C6 radiculopathy confirmed by electrophysiological testing and C5 6 disc herniation demonstrated on MRI. CTFIS was performed at C5 6 using a 25G needle. When fluoroscopy showed the needle tip in the required position, aspiration was negative for blood. Nonionic contrast medium was injected, and an appropriate epidurogram was produced with spread along the C6 nerve root. A mixture of bupivacaine and triamcinolone was injected with intermittent aspirations to check for blood, all negative. While being transferred from the C-arm table, the patient became unconscious and had respiratory arrest. She was resuscitated and regained consciousness, but had quadriparesis. She was taken to neurosurgical intensive care and underwent surgical decompression of the brain stem. She died the following day. Autopsy revealed cerebellar infarction and infarction of the left occipital cortex, suggesting vertebral artery injection. Temporary Quadriplegia Also published in 2004 was a case report of temporary paralysis after local anesthetic injection in what was planned as a CTFIS procedure [61]. A 55-year-old woman had cervical radicular pain that had been relieved previously by CTFIS. A right C6 7 TFIS procedure was initiated. The needle was positioned under fluoroscopic guidance and contrast medium injection demonstrated filling of the intervertebral foramen with no vascular uptake. A test dose of local anesthetic, 0.8 ml of 2% lidocaine, was then injected. After 60 seconds, the patient reported feeling unwell and the procedure was aborted. Over the next few minutes, she reported weakness and physical examination showed paralysis of all four limbs. Respiration was not affected. She was transferred to a recovery suite and monitored closely. After 20 minutes, all symptoms resolved and the patient had no lasting impairment due to the event. The authors of the case report believe there was inadvertent arterial uptake of local anesthetic. Spinal Cord Infarction Leading to Quadriplegia In 2005, a report was published of a 53-year-old man with a history of neck pain and left arm pain of radicular quality, and broad-based disc protrusions at multiple levels but no foraminal stenosis on MRI [62]. Left C6 TFIS was undertaken using a 25G needle positioned under fluoroscopic guidance. Injection of contrast medium under live fluoroscopy showed spread along the C6 nerve root and no sign of vascular uptake. Aspiration showed no blood. A mixture of bupivacaine and triamcinolone was then injected. The patient seemed well immediately afterwards but 10 minutes later reported weakness of his left arm and both legs. The weakness persisted and the patient s final outcome was classified as score C on the American Spinal Injury Association (ASIA) Impairment Scale incomplete quadriplegia. MRI 24 hours after the CTFIS showed increased signal in the spinal cord from C2 to C5 and in the upper thoracic region, in the territories of both anterior and posterior spinal arteries. Cerebellar Infarction and Brainstem Herniation In 2006, the case was reported of a 31-year-old man with a 3-week history of pain in his neck and right arm, right hand paresthesia and weakness, and herniation of the C7 T1 disc to the right on MRI [63]. CTFIS was performed with a 25G needle placed in the right C7 T1 foramen under fluoroscopic guidance. Contrast medium was injected under continuous fluoroscopy in the postero-anterior view and seen to flow along the right C8 nerve root with no sign of vascular uptake. Aspiration was negative for blood. A mixture of methylprednisolone and lidocaine was then injected slowly, but during the injection, the patient complained of neck pain and headache so the injection was stopped. The patient was transferred to recovery, where he had continuing headache and nausea, and vomited when he sat up. Later he seemed to recover and was discharged. At home that night, his wife noticed his breathing was abnormal and he was taken to a hospital, where he had respiratory arrest. CT and MRI showed cerebellar infarction and hydrocephalus, and emergency surgery was undertaken to relieve cerebellar herniation into the foramen magnum. The patient recovered over time but had residual diplopia and persistent difficulties with concentration and shortterm memory loss. The cause was suspected as inadvertent intra-arterial injection. 394 Downloaded from by guest on 18 February 2018

310 Cervical Transforaminal Injection of Steroids Temporary Cortical Blindness and Paresis of Face and Upper Limbs In 2007, a case was reported of a 41-year-old man who became profoundly confused and developed weakness of his face and left arm while undergoing left C5 TFIS under fluoroscopic guidance, without sedation, at an outpatient pain clinic [64]. No other details of the procedure were stated. The patient was transferred to the hospital where CT revealed subintimal contrast medium in the left vertebral artery extending from C3 to C6. He was admitted to a neurological intensive care unit for management. A left vertebral arteriogram obtained there showed dissection of the left vertebral artery consistent with the previous CT findings. After intensive treatment, the patient made a full recovery. Spinal Cord Infarction Leading to Quadriplegia Another article published in 2007 reported multilevel infarction of the spinal cord after CTFIS [65]. A 72-year-old woman with a long history of neck pain and left arm pain, of radicular type, had undergone anterior cervical discectomy and fusion at C4 5 and C5 6 with some effect, but radicular pain had recurred. TFIS was performed at C5 6 and C6 7 on the left, using 25 G needles. At each level, after the needle tip position was considered appropriate on fluoroscopic views, contrast medium was injected and its spread observed under live fluoroscopy. Aspiration was not mentioned in the report. After confirmation of contrast medium around the nerve root sleeve and no evidence of vascular uptake, a mixture of methylprednisolone and bupivacaine was injected at each level. The patient seemed well immediately after the procedure but about 30 minutes later, she complained of leg weakness. Her condition deteriorated and she developed persistent incomplete quadriplegia classified as ASIA-C. MRI demonstrated spinal cord infarction at multiple levels up to the cervicomedullary junction. Temporary Paralysis of Right Leg A third article published in 2007 reported temporary paralysis of one leg after CTFIS [66]. A 45-year-old male with chronic cervical pain after trauma underwent C6 7 TFIS using a 22G needle. It was inserted into the foramen under fluoroscopic guidance and its position was checked on biplanar views. Repeated aspirations throughout the procedure were negative for blood. Contrast medium injection under live fluoroscopic screening produced a C7 neurogram and showed no sign of vascular uptake. A mixture of triamcinolone and saline was injected. After about 30 seconds, the patient complained of numbness and paresthesia in his right leg, and within 2 minutes, his right leg was paralyzed. Treatment was instituted with nifedipine, heparin, and aspirin, and 3 hours later, the complications had resolved. MRI revealed no nerve damage or bleeding, but showed hypoplasia of the right vertebral artery (which is found in up to 40% of arteriograms). Epidural Hematoma Causing Paraplegia Also published in 2007 was the case of a 38-year-old woman who had radicular pain in her right arm after a motor vehicle accident and was treated with a series of three C7 T1 TFIS [67]. No details of the injections were reported. About 4 days after the third CTFIS, the patient awakened with severe upper thoracic back pain and she went on to develop progressive loss of sensation from the waist down and dense paralysis of both legs. MRI showed an epidural mass compressing the spinal cord from T1 to T5 levels. Surgical decompression was undertaken and a clot was removed. The patient s condition improved postoperatively, and after 6 months, she recovered fully. Grand Mal Seizure A fifth article published in 2007 was a case series of selective cervical nerve root block injections including a case with a major complication not published elsewhere [68]. A 45-year-old man had a therapeutic injection of betamethasone and lidocaine along a C6 nerve root. Within 10 seconds, the patient had a grand mal seizure lasting 3 4 minutes. He recovered completely within 30 minutes. No details were reported of the procedural technique used in this case, so it is not known what findings there might have been on aspiration or contrast medium injection. Spinal Cord Injury Leading to Quadriparesis In 2008, a case report was published involving a 55-yearold man with neck pain radiating into his left arm, considered to be in a C7 distribution [69]. TFIS was undertaken with a 23G needle introduced into the left C6 7 neural foramen under fluoroscopic guidance. On direction of the needle into what was thought to be the epidural space, the patient complained of sharp pain, which was considered due to irritation of the nerve root. The needle tip position was not verified by fluoroscopy: the reason given was that the patient was in an inappropriate posture due to severe pain. Rather, to determine the needle tip position, 0.5 ml of contrast medium was injected. During this injection, the patient reported a shock-like pain radiating to the left hand. The procedure was terminated. Over the next 2 3 minutes, the patient developed incomplete quadriplegia, classified as ASIA-C. CT demonstrated an air bubble and a hyperdense mass inside the spinal cord at C6 7. Apparently, the contrast medium had been injected directly into the cord. Treatment was instituted and the patient s condition improved somewhat, but 1 year later, he still had motor weakness in the left arm, weakness of the left hand, and a claw hand deformity. He also still had refractory pain in his left arm. Transient Quadriplegia In 2010, a report was published of a 43-year-old man with cerebral palsy and radicular pain in his left arm, associated with a cervical disc herniation [70]. He was treated surgically with laminectomy and C3 5 interbody fusion, but 395 Downloaded from by guest on 18 February 2018

311 Engel et al. postoperatively had persistent left C5 radicular pain. TFIS was then performed, targeting the left C5 nerve root. A needle was placed in position under fluoroscopic guidance. Contrast medium was injected and seen to spread epidurally along the nerve root, with no sign of vascular uptake. During the injection, the patient complained of paresthesia, which was thought to be caused by injection needles (sic). On aspiration, no blood was seen. A mixture of triamcinolone and mepivacaine was infused. Within 3 minutes of the injection, the patient had total loss of sensation and motor function in all four limbs. He was transferred to intensive care and monitored, but did not require ventilation. He made a spontaneous and complete recovery over 2 hours. Cerebral Edema and Cortical Blindness In 2011, a article reported the case of a 54-year-old woman with recurrent neck pain radiating into her left arm [71]. She had one C5 6 TFIS and the pain settled but it recurred and another CTFIS was planned. A 23G spinal needle was directed into the C5 6 foramen under fluoroscopy. Contrast medium was injected twice, under realtime fluoroscopy in the anteroposterior view, to confirm the needle tip position. There was no evidence of intravascular injection, and on aspiration, no blood was seen. A mixture of triamcinolone and lidocaine was injected. Immediately after this the patient complained of headache, nausea, and dizziness, and 6 hours later, she had bilateral visual disturbance that worsened progressively until she could barely detect hand movements 30 cm in front of her eyes; the light reflex was prompt bilaterally, suggesting cortical blindness. MRI showed bilateral subcortical lesions in the occipital lobes. Over 48 hours the patient s vision returned to normal and at follow-up 6 months later, MRI was normal. The diagnosis was reversible posterior leukoencephalopathy syndrome. Grand Mal Seizure after Local Anesthetic Test Dose Also published in 2011 was the case of a 49-year-old woman with left C6 radicular pain associated with a C5 6 disc bulge [72]. The patient had obtained temporary relief from two previous CTFIS treatments and was scheduled for another. A 25G needle was introduced into the left C5 6 foramen under fluoroscopic guidance and adjusted until its tip seemed in the correct position. Contrast medium was injected, and its flow showed venous uptake. The needle tip was repositioned and more contrast medium was injected, producing what was considered a satisfactory proximal neurogram and outlining of the epidural space. A syringe was then connected directly to the needle hub, and 1% lidocaine was injected as a test dose. The patient was asked whether she felt dizzy or had any altered sensations but she did not answer even when the question was repeated several times. The drapes were taken down and the patient was found to be having a grand mal seizure. The procedure was aborted and resuscitation commenced. The patient recovered with no residual deficit. Retrospective review of the stored images revealed that what had been interpreted during the procedure as a satisfactory epidurogram was not; a dark wavy contrast medium line taken as the medial borders of the pedicles was actually the wall of the vertebral artery, which suggests the needle tip was in the vertebral artery when the lidocaine was injected. Permanent Horner s Syndrome Another case reported in 2011 involved a 31-year-old man with cervical degenerative disc disease who was treated with a right C7 TFIS [73]. No details of the technique were provided. Following the procedure, the patient had right ptosis and miosis, and pharmacologic testing confirmed a right Horner s syndrome, which persisted to become permanent. MRI and MRA showed no arterial dissection. Temporary Flaccid Paralysis after Local Anesthetic Test Dose In 2012, a article reported the case of a 40-year-old woman with severe right-sided cervical radicular pain who was booked for a CTFIS procedure [74]. A 23G spinal needle was introduced into the right C5 C6 intervertebral foramen and its placement checked in the anteroposterior view. A syringe filled with contrast medium was connected to the needle via an extension tube. Contrast medium was injected, and its spread along the nerve root was observed by right C6 neurography, although not with real-time fluoroscopy. The extension tube used for the radiculography was removed from the spinal needle and another extension tube with a syringe filled with lidocaine connected in its place. An aspiration test was negative for blood. The physician then injected 1.5 ml of 1.0% lidocaine slowly around the C6 nerve root. Immediately after the injection of local anesthetic, the patient developed flaccid paralysis, she became unresponsive, and her respiratory pattern was uncoordinated. Resuscitation was started, and after 20 minutes, she regained consciousness, and her sensation and limb muscle strength returned to normal. Transient Causalgia Also published in 2012 was an observational study of 28 patients of whom two suffered neurological complications [27]. One patient was reported as having causalgia for 5 months after the CTFIS treatment. No other details were provided. Transient Horner s Syndrome The other patient reported in the 2012 study as having neurological complications developed Horner s syndrome with ptosis after the CTFIS [27]. The condition lasted for a week but then resolved. Other Reported Complications In 2007, a article was published reporting the results of an anonymous survey of all U.S. physician members of the American Pain Society [75]. Overall response rate was 396 Downloaded from by guest on 18 February 2018

312 Cervical Transforaminal Injection of Steroids 21.4% (287 of 1,340). In all, 78 complications were reported, including 16 vertebrobasilar brain infarcts, 12 cervical spinal cord infarcts, and 2 combined brain/spinal cord infarcts. Brain infarcts invariably involved the cerebellum, brainstem, or posterior cerebral artery territory. Thirteen cases resulted in a fatal outcome: five with brain infarcts, one with combined brain/spinal cord infarcts, one following high spinal anesthesia, one associated with a seizure, and five with unspecified etiology. All four cases with corticosteroid alone involved methylprednisolone, resulting in three cerebellar infarcts and one posterior cerebral territory infarct. Of these, three had fatal outcomes, and two autopsies revealed no vertebral artery trauma. It is not known how many of the 24 case reports described above were included in the complications reported in this anonymous survey; if it is assumed that all 15 that occurred up until 2007 were included (so as to avoid exaggeration of the evidence), the results of the survey add another 10 fatal events and 53 other serious consequences to the complications reported specifically in the literature. The reports of significant complications are summarized in Table 4. Procedural Factors The reports of serious and catastrophic complications raise questions about procedural factors that may help minimize such sequelae. Some proceduralists advise precautionary checks including radiographic confirmation of needle tip position, use of small-volume extension tubing, repeated aspiration, injection of contrast medium under live fluoroscopic screening, use of DSA, proximal neurography, and administration of a test dose of local anesthetic. The evidence shows that none of these precautions, or combinations of them, is entirely protective against the serious complications of CTFIS. Nonetheless, all are worthy of consideration. Radiographic confirmation of needle tip position is mentioned in most of the case reports describing serious complications (although many reports do not state whether both antero-posterior and foraminal views were used); so, important as it is, radiographic confirmation does not seem to be of great value in preventing such events. Fitting a small-volume extension tube to the hub of the spinal needle, rather than connecting syringes directly to Table 4 Report Reported risks of CTFIS, expressed as complications described specifically in the literature Complications Brouwers et al [57] McMillan and Crumpton 2003 [58] Rozin et al [59] Windsor et al [9] Windsor et al [9] Windsor et al [9] Tiso et al [60] Karasek and Bogduk 2004 [61] Ludwig and Burns 2005 [62] Beckman et al [63] Wallace et al [64] Muro et al [65] Ruppen et al [66] Lee JY et al [67] Schellhas et al [68] Lee JH et al [69] Lee MH et al [70] Kim et al [71] Chung SG 2011 [72] Kaplowitz and Lee AG 2011 [73] Tofuku et al [74] Chung JY et al [27] Chung JY et al [27] Scanlon et al [75] Scanlon et al [75] Total Spinal cord infarction leading to death Cerebral injury and cortical blindness (persistent) Vertebral artery occlusion leading to death Lateral spinal cord infarction (persistent) Cerebral ischemia and hippocampal atrophy (persistent) Posterior spinal cord and cerebellar infarction (persistent) Cerebellar and cerebral infarction leading to death Quadriplegia (transient) Spinal cord infarction leading to quadriplegia (persistent) Cerebellar infarction and brainstem herniation (persistent) Cortical blindness, paresis of face, and upper limbs (transient) Spinal cord infarction leading to quadriplegia (persistent) Paralysis of right leg (transient) Epidural hematoma causing paraplegia (transient) Grand mal seizure (transient) Spinal cord injury leading to quadriparesis (persistent) Quadriplegia (transient) Cerebral edema and cortical blindness (transient) Grand mal seizure (transient) Horner s syndrome (persistent) Flaccid paralysis (transient) Causalgia (transient) Horner s syndrome (transient) 10 additional complications causing death 53 additional serious but non-fatal complications 13 deaths 31 brain and spinal cord infarctions Numerous other serious and persistent CNS injuries 397 Downloaded from by guest on 18 February 2018

313 Engel et al. it, in theory reduces the chance of the needle tip moving during or between injections. Aspiration to check for blood is a traditional practice that has been assessed for validity: the evidence shows that blood seen on aspiration has 97.9% specificity but only 44.7% sensitivity for intravascular needle tip placement [66]; thus, there is no guarantee that the absence of blood on aspiration signifies extravascular injection. Intra-arterial injection stands out as a factor in many of the reports of serious complications and thus is one of the major risks. In this regard, it should be noted that a recent article has shown the vertebral artery to lie within 2 mm of ideal needle location in at least one posterior neural foramen in 29% of 198 consecutive patients whose CT angiograms were studied [76]. Severity of foraminal stenosis correlated with proximity of the vertebral artery to typical needle location. Ideal needle placement therefore does not guarantee protection from injury to, or injection into, the vertebral artery during CTFIS. The authors of that article recommended that physicians examine T2 axial MRI to check the location of the vertebral artery before performing CTFIS. Visualization of the spread of injected contrast medium is supposed to aid in identifying correct needle tip placement but is of no help, and actually causes harm, if the needle is in a dangerous position such as inside the spinal cord as in the report of Lee JH et al. [69]. Visualization is better under live fluoroscopic screening and better still under DSA but identifying a problem more readily is no protection if it has already occurred; that said, there were no reports of major complications when DSA was used and there are many observational studies that demonstrate the value of DSA in preventing subsequent intravascular injection [42,43,45,46,50]. The production of a proximal neurogram (a fluoroscopic image of the target nerve root outlined by contrast medium injected into the epidural space) is another measure supposedly protective against injection at an inappropriate site. The theory is sound but the evidence shows that what is interpreted as a proximal neurogram may not be; for example, in the case reported by Chung SG [72], what was interpreted as outlining of the epidural space was actually contrast medium spreading up along the walls of the vertebral artery. The injection of a local anesthetic test dose is another measure thought to protect against injection (of steroid) at an inappropriate site. Theoretical considerations suggest it may be worthwhile as a precautionary measure, on the grounds that the effects of local anesthetic are less enduring than those of steroid. The evidence includes three cases in which local anesthetic test doses produced effects that caused the procedures to be terminated before injection of steroids, which if injected at the same sites may have caused more serious complications [61,72,74]. There is no reported case of serious, long-term sequelae in which a local anesthetic test dose was used. Another factor raised is whether particulate or soluble (non-particulate) steroids should be used for the therapeutic injectate. The evidence suggests that the risks of CTFIS may be increased if particulate steroids are injected. Certainly particulate steroids were used in most of the cases involving catastrophic complications, including all those that were fatal, but it is not clear that steroid particles were responsible for all the effects that occurred. On one hand, a complication like dissection of a vertebral artery would be serious whatever was injected into it, and on the other hand, there are several reports of serious complications after procedures in which particulate steroids were not used. GRADE Assessment of Risks of CTFIS When attempting to assess the quality of the evidence on the risks of CTFIS in accordance with the GRADE system, it is noted that the published evidence consists only of case reports. Accordingly, the body of evidence is of very low quality: we have very little confidence in the effect estimate and the true effect is likely to be substantially different from the estimate of effect. Readers must be careful not to confuse evidence of very low quality with evidence of little significance and perhaps go on to dismiss the risks of CTFIS as too rare to be of concern. The evidence of risks is of very low quality because few cases of serious complications have been published. This may reflect publication bias. There is a tendency for serious complications not to be publicized in articles; indeed in one of the descriptive articles, the authors mentioned an additional 15 cases they knew of that were not being published because they were sub judice [36]. Thus, the frequency of complications after CTFIS is uncertain but when they do occur they can be catastrophic and even fatal. Discussion This systematic review of the literature is comprehensive, including evidence from all studies published, not just from RCTs as do some systematic reviews. The whole body of published, peer-reviewed evidence was appraised reliably in accordance with the GRADE system of evaluating evidence. In taking this approach, the authors have sought to honor the method advocated by Dr. Archie Cochrane, pioneer of evidence-based medicine. Cochrane advised consideration of all published evidence, giving weighting to the data included in it on the basis of the types and methodologies of studies from which they came, with those from RCTs weighted highest. In his book Effectiveness and Efficiency, 1977, he wrote: In writing this section in praise of the RCT I do not want to give the impression that it is the only technique of any value in medical research (p. 25) [77]. He wrote of the value of observational evidence... (especially when efforts are made for) the exclusion of possible bias from the measurements (p. 21). He also classified therapies as (inter alia) Those therapies backed by RCTs and those where there is good experimental evidence of some effect, but no evidence from RCTs (p. 30). The current authors feel that the systematic review of all published evidence, 398 Downloaded from by guest on 18 February 2018

314 Cervical Transforaminal Injection of Steroids appraised reliably in accordance with the GRADE guidelines, is very close to what Cochrane tried to get medical science to adopt. A literature review helps a physician determine if an intervention benefits patients but it does not necessarily show to which patients a physician should offer that intervention. That is the role of appropriate use criteria. When an intervention is known to have catastrophic complications, there is no published resource that can determine if it should be offered to a particular patient. A patient s decision to have such an intervention should be based on an honest discussion between the patient and the treating physician of the potential benefits and risks. Only with all the information known about the intervention can a patient give properly informed consent to have it and decide if the attendant risks are worth taking. The literature seems to indicate that CTFIS helps some patients with short-term relief of radicular pain and questionable long-term benefit. It shows that CTFIS relieves radicular pain in some cases and is associated with reduced rates of spinal surgery. When quantified, the benefit of CTFIS appears limited in the proportion of patients who benefit (approximately 40%), the extent to which they benefit (50% relief of radicular pain), and the duration of effect (4 weeks). Fewer patients, possibly 20%, achieve complete relief, but the confidence intervals approach and include zero. At 3, 6, and 12 months, the proportions of patients with any degree of benefit attenuate, as does the quality of the literature. It also shows clearly that CTFIS carries risks of serious and catastrophic complications, including permanent quadriplegia and death. The published evidence does not clearly identify the causes of those serious complications and does not show conclusively how they can be avoided. The purposes of this review are to present all the data that have been published on CTFIS in all sorts of articles and to evaluate the resultant evidence of the intervention s effectiveness for relief of cervical radicular pain and its associated risks in accordance with the GRADE system of evaluating evidence. The authors have deliberately avoided giving any further interpretation of the procedure s potential benefits and risks so this review should not be interpreted in any way as a guide to criteria for its appropriate use. We leave that for others to determine. Conclusions CTFIS seems to help some patients with cervical radicular pain. The evidence of the effectiveness of CTFIS was rated according to the GRADE system as of very low quality for pain-relieving effects and as of very low quality for surgery-sparing effects. The authors are not confident of the estimates of effectiveness, and their true values may be substantially different. Further research is likely to change the presented conclusions significantly. CTFIS is associated with serious complications which, although rarely reported, are catastrophic and even fatal in some cases. The evidence of the risks of CTFIS is rated according to the GRADE system as of very low quality: we can have very little confidence in what the evidence seems to show and the true effect is likely to be substantially different from the estimate of effect. In accordance with the GRADE system, based on all published data on the procedure and taking into account the balance between desirable and undesirable effects, and the qualities of the evidence for each, the strength of recommendations for use of CTFIS is weak. That is an evidence-based appraisal of the procedure, limited by the available literature. If CTFIS is to be applied as an intervention for cervical radicular pain, its use would require the development of appropriate use criteria, which this article does not purport to address. The evidence supporting these conclusions was revealed by systematic review and comprehensive analysis of all published data and found to be much more compelling than it would have been if the literature review had been of the limited scope of a systematic review of RCTs only. Acknowledgments The authors wish to thank the other members of the ISIS Standards Division, D Scott Kreiner MD, Milton Landers DO PhD, Devi Nampiaparampil MD, and Anil Sharma MD, who read the final draft and offered comments on it. They also wish to acknowledge Professor Nikolai Bogduk, who although not involved in the preparation of this article provided the inspiration for it by advocating this style of systematic review, stratifying RCTs as pragmatic and explanatory studies. 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316 Cervical Transforaminal Injection of Steroids 31 Lee J, Lee S-H. Comparison of clinical effectiveness of cervical transforaminal steroid injection according to different radiological guidances (C-arm fluoroscopy vs. computed tomography fluoroscopy). Spine J 2011;11: Riew K, Kim Y, Gilula L, Kim Y-B. Can cervical nerve root blocks prevent surgery for cervical radiculopathy? A prospective, randomized, controlled, double-blind study. Spine J 2006;6:2S. 33 Benny B, Azari P, Briones D. Complications of cervical transforaminal epidural steroid injections. Am J Phys Med Rehabil 2010;89(7): Bogduk N, Dreyfuss P, Baker R, et al. Complications of spinal diagnostic and treatment procedures. Pain Med 2008;9:S Malhotra G, Abbasi A, Rhee M. Complications of transforaminal cervical epidural steroid injections. Spine 2009;34(7): Rathmell JP, Aprill C, Bogduk N. Cervical transforaminal injection of steroids. Anesthesiology 2004;100(6): de Leon-Casasola OA. Transforaminal cervical epidural injections. Reg Anesth Pain Med 2008;33(2): Helm S 2nd, Jasper JF, Racz GB. Complications of transforaminal epidural injections. Pain Physician 2003;6(3): Provenzano DA, Fanciullo G. Cervical transforaminal epidural steroid injections: Should we be performing them? Reg Anesth Pain Med 2007;32(2):168; author reply Schultz D. Risk of transforaminal epidural injections. Pain Physician 2004;7(2): Dominguez E. The practice of cervical transforaminal injection of steroids deserves more scrutiny. Pain Physician 2005;8(3): Derby R, Lee SH, Kim BJ, Chen Y, Seo KS. Complications following cervical epidural steroid injections by expert interventionalists in Pain Physician 2004;7(4): Baker R, Dreyfuss P, Mercer S, Bogduk N. Cervical transforaminal injection of corticosteroids into a radicular artery: A possible mechanism for spinal cord injury. Pain 2003;103(1 2): Furman MB, Giovanniello MT, O Brien EM. Incidence of intravascular penetration in transforaminal cervical epidural steroid injections. Spine 2003;28(1): Jasper JF. Role of digital subtraction fluoroscopic imaging in detecting intravascular injections. Pain Physician 2003;6(3): McLean JP, Sigler JD, Plastaras CT, Garvan CW, Rittenberg JD. The rate of detection of intravascular injection in cervical transforaminal epidural steroid injections with and without digital subtraction angiography. PM R 2009;1(7): Nahm FS, Lee CJ, Lee SH, et al. Risk of intravascular injection in transforaminal epidural injections. Anaesthesia 2010;65(9): Smuck M, Leung D. Inadvertent injection of a cervical radicular artery using an atraumatic pencil-point needle. Spine 2011;36(3):E Smuck M, Maxwell MD, Kennedy D, et al. Utility of the anesthetic test dose to avoid catastrophic injury during cervical transforaminal epidural injections. Spine J 2010;10(10): Verrills P, Nowesenitz G, Barnard A. Penetration of a cervical radicular artery during a transforaminal epidural injection. Pain Med 2010;11(2): Hoeft MA, Rathmell JP, Monsey RD, Fonda BJ. Cervical transforaminal injection and the radicular artery: Variation in anatomical location within the cervical intervertebral foramina. Reg Anesth Pain Med 2006; 31(3): Kloth DS, Calodney AK, Derby R, et al. Improving the safety of transforaminal epidural steroid injections in the treatment of cervical radiculopathy. Pain Physician 2011;14(3): Huston CW, Slipman CW, Garvin C. Complications and side effects of cervical and lumbosacral selective nerve root injections. Arch Phys Med Rehabil 2005;86(2): Ma DJ, Gilula LA, Riew KD. Complications of fluoroscopically guided extraforaminal cervical nerve blocks. An analysis of 1036 injections. J Bone Joint Surg Am 2005;87(5): Pobiel RS, Schellhas KP, Eklund JA, et al. Selective cervical nerve root blockade: Prospective study of immediate and longer term complications. AJNR Am J Neuroradiol 2009;30(3): Derby R, Lee SH, Date ES, Lee JH, Lee CH. Size and aggregation of corticosteroids used for epidural injections. Pain Med 2008;9(2): Brouwers PJ, Kottink EJ, Simon MA, Prevo RL. A cervical anterior spinal artery syndrome after diagnostic blockade of the right C6-nerve root. Pain 2001;91(3): Downloaded from by guest on 18 February 2018

317 Engel et al. 58 McMillan MR, Crumpton C. Cortical blindness and neurologic injury complicating cervical transforaminal injection for cervical radiculopathy. Anesthesiology 2003;99(2): Rozin L, Rozin R, Koehler SA, et al. Death during transforaminal epidural steroid nerve root block (C7) due to perforation of the left vertebral artery. Am J Forensic Med Pathol 2003;24(4): Tiso RL, Cutler T, Catania JA, Whalen K. Adverse central nervous system sequelae after selective transforaminal block: The role of corticosteroids. Spine J 2004;4(4): Karasek M, Bogduk N. Temporary neurologic deficit after cervical transforaminal injection of local anesthetic. Pain Med 2004;5(2): Ludwig MA, Burns SP. Spinal cord infarction following cervical transforaminal epidural injection: A case report. Spine 2005;30(10):E Beckman WA, Mendez RJ, Paine GF, Mazzilli MA. Cerebellar herniation after cervical transforaminal epidural injection. Reg Anesth Pain Med 2006;31(3): Wallace MA, Fukui MB, Williams RL, Ku A, Baghai P. Complications of cervical selective nerve root blocks performed with fluoroscopic guidance. AJR Am J Roentgenol 2007;188(5): Muro K, O Shaughnessy B, Ganju A. Infarction of the cervical spinal cord following multilevel transforaminal epidural steroid injection: Case report and review of the literature. J Spinal Cord Med 2007;30(4): Ruppen W, Hugli R, Reuss S, Aeschbach A, Urwyler A. Neurological symptoms after cervical transforaminal injection with steroids in a patient with hypoplasia of the vertebral artery. Acta Anaesthesiol Scand 2008;52(1): Lee JY, Nassr A, Ponnappan RK. Epidural hematoma causing paraplegia after a fluoroscopically guided cervical nerve-root injection. A case report. J Bone Joint Surg Am 2007;89(9): Schellhas KP, Pollei SR, Johnson BA, et al. Selective cervical nerve root blockade: Experience with a safe and reliable technique using an anterolateral approach for needle placement. AJNR Am J Neuroradiol 2007;28(10): Lee JH, Lee JK, Seo BR, et al. Spinal cord injury produced by direct damage during cervical transforaminal epidural injection. Reg Anesth Pain Med 2008;33(4): Lee MH, Cha YD, Song JH, et al. Transient quadriplegia after fluoroscopic-guided selective cervical nerve root block in a patient who received cervical interbody fusion A case report. Korean J Anesthesiol 2010; 59(suppl):S Kim W, Kim JS, Lim SC, Kim YI, Moon DE. Reversible posterior leukoencephalopathy syndrome after cervical transforaminal epidural steroid injection presenting as transient blindness. Anesth Analg 2011;112(4): Chung SG. Convulsion caused by a lidocaine test in cervical transforaminal epidural steroid injection. PM R 2011;3(7): Kaplowitz K, Lee AG. Horner syndrome following a selective cervical nerve root block. J Neuroophthalmol 2011;31(1): Tofuku K, Koga H, Komiya S. Subdural spread of injected local anesthetic in a selective transforaminal cervical nerve root block: A case report. J Med Case Rep 2012;6(1): Scanlon GC, Moeller-Bertram T, Romanowsky SM, Wallace MS. Cervical transforaminal epidural steroid injections: More dangerous than we think? Spine 2007;32(11): Beckworth WJ, Sood R, Katzer AF, Wu B. Anomalous location of the vertebral artery in relation to the neural foramen. Implications for cervical transforaminal epidural steroid injections. Pain Med 2013;14(8): Cochrane A. Effectiveness and Efficiency. Cambridge: Cambridge University Press; 1977: Downloaded from by guest on 18 February 2018

318 PM R 9 (2017) Analytical Review Systematic Review of the Efficacy of Particulate Versus Nonparticulate Corticosteroids in Epidural Injections Priyesh Mehta, DO, Isaac Syrop, MD, Jaspal Ricky Singh, MD, Jonathan Kirschner, MD Objective: To systematically analyze published studies in regard to the comparative efficacy of particulate versus nonparticulate corticosteroids for cervical and lumbosacral epidural steroid injections (ESI) in reducing pain and improving function. Type: Systematic review. Literature Survey: MEDLINE (Ovid), EMBASE, and Cochrane databases were searched from the period of 1950 to December Methodology: Criteria for inclusion in this review were (1) randomized controlled trials and (2) retrospective studies that compared particulate versus nonparticulate medication in fluoroscopically guided injections via a transforaminal (TF) or interlaminar (IL) approach. Each study was assigned a level of evidence (I-V) based on criteria for therapeutic studies. A grade of recommendation (A, B, C, or I) was assigned to each statement. Categorical analysis of the data was reported when available, with success defined by the minimal clinically important difference for appendicular radicular painda reduction of at least 2 on the visual analog scale. When data were available, additional categorical analysis included the proportion of individuals with a reduction in pain of at least 50%, 70%, or 75%. Follow-up was included at all reported intervals from 2 weeks to 6 months. Synthesis: Three cervical ESI and 6 lumbar ESI studies were found to be suitable for review. Of the 3 cervical ESI studies, 2 were retrospective studies with grade III level of evidence and 1 was a randomized controlled trial with grade II evidence. Of 4 lumbar ESI studies that used a TF approach, the 2 randomized double-blinded controlled trials were grade I evidence and 2 retrospective studies were grade II and III level of evidence. One randomized controlled trial using the lumbar IL approach was level II evidence. One retrospective cohort study using the lumbar TF, IL and caudal approach was level III evidence. Conclusions: There is no statistically significant difference in terms of pain reduction or improved functional outcome between particulate and nonparticulate preparations in cervical ESI and, therefore, the authors recommend using nonparticulate steroid when performing cervical TFESI (Grade of Recommendation: B). In patients with lumbar radiculopathy due to stenosis or disk herniation, TFESI using particulate versus non-particulate is equivocal in reducing pain (Grade of Recommendation: B) and improving function (Grade of Recommendation: C) and therefore the authors recommend the use of nonparticulate steroids for lumbar TFESI in patients with lumbar radicular pain (Grade of Recommendation: B). There is insufficient information to make a recommendation of one steroid preparation over the other in lumbar ILESI (Grade of Recommendation: I). Given the lack of strong data favoring the efficacy of one steroid preparation over the other, and the potential risk of catastrophic complications, all of which have been reported with particulate steroids, nonparticulate steroids should be considered as first line agents when performing ESIs. Level of Evidence: III Introduction There are several options of corticosteroids available for both transforaminal epidural steroid injections (TFESIs) and interlaminar epidural steroid injections (ILESIs). The corticosteroids are divided between particulate (triamcinolone, methylprednisolone, betamethasone) and nonparticulate (dexamethasone) formulations. Since first described in 2002 by Houten and Errico, there have been 13 reported cases of spinal cord ischemia and posterior circulation infarction after cervical epidural steroid injection (ESI) [1-11] and an additional 19 cases associated with lumbosacral ESIs [12-23]. Specifically, reports on spinal cord ischemia after transforaminal injections have raised concerns about the potential for embolization of particulate corticosteroids during the procedure. Proposed mechanisms involve direct injury to the artery of Adamkiewicz or other radiculomedullary arteries in the intervertebral foramen and intra-arterial corticosteroid injection with distal embolization [24] /$ - see front matter ª 2017 by the American Academy of Physical Medicine and Rehabilitation Downloaded for Anonymous User (n/a) at Hospital For Special Surgery in New York from ClinicalKey.com by Elsevier on June 20, For personal use only. No other uses without permission. Copyright Elsevier Inc. All rights reserved.

319 P. Mehta et al. / PM R 9 (2017) Distinct from the most widely agreed-on mechanism of injurydparticulate size resulting in embolizationdnew research demonstrates an alternative mechanism of injury. As demonstrated in a mouse model, several particulate steroids have an immediate and massive effect on microvascular perfusion because of formation of red blood cell (RBC) aggregates associated with the transformation of RBCs into spiculated RBCs [25]. In 2011, the Food and Drug Administration (FDA) required a label change for triamcinolone, stating it should not be used for ESIs. After the label change, multiple organizations published recommendations using nonparticulate steroids as first-line agents for ESIs. Nonetheless, particulate steroids continue to be used because of a theoretical advantage of pain relief secondary to delayed clearance from the spinal canal [26-28]. The objective of this review is to systematically analyze published studies regarding particulate versus nonparticulate corticosteroids for cervical and lumbosacral ESIs in reducing pain and improving function. Methods MEDLINE (Ovid), EMBASE, and Cochrane databases were searched from the period of 1950 to December 2015 for the following key words: epidural steroid injection, transforaminal epidural steroid injection, interlaminar epidural steroid injection, dexamethasone, triamcinolone, methylprednisolone, betamethasone, particulate, and nonparticulate. The references cited in these studies also were screened. Only articles published in English were included. Criteria for inclusion in this review were (1) randomized controlled trials (RCTs) and retrospective studies; (2) fluoroscopically guided injections that used a TFESI or ILESI approach; (3) only studies that compared particulate versus nonparticulate medication. Studies meeting these criteria were appraised for quality. A quality checklist was used for initial screening. This was modeled after the 2009 PRISMA statement: Preferred Reporting items for Systematic Reviews and Meta-Analyses [29]. The checklist included 27 items within the categories of title, abstract, introduction, methods, results, discussion, and funding. Only those studies that included a majority of these items were reviewed. Each study was assigned a level of evidence (I-V) based on criteria set by Wright for therapeutic studies [30]. Table 1 illustrates the criteria used to assign levels of evidence. RCTs are assigned either a level I or a level II based on this system. Each study is summarized with a description of the study population, type of intervention, medications used, method of blinding, outcome measures recorded, follow-up duration, summarized results with particular attention to categorical analysis, medical complications, and study limitations. If the authors did not perform a categorical analysis yet data Table 1 Levels of Evidence for therapeutic studies Levels of Evidence Criteria Level I Randomized controlled trial With a significant difference With no significant difference but narrow confidence intervals Systematic review of Level I randomized controlled trials Level II Prospective cohort study Randomized controlled trials Poor quality (unblinded evaluators, low power, poor randomization, <80% follow-up) Systematic review Level II studies Nonhomogenous Level I studies Level III Case-controlled study Retrospective cohort study Systematic review of Level III studies Level IV Case series Level V Expert opinion were available, a categorical analysis was conducted. Success was defined by the minimal clinically important difference (MCID) for appendicular radicular pain e a reduction of at least 2 on the visual analog scale (VAS) [31]. When data were available, additional categorical analysis included the proportion of individuals with a reduction in pain of at least 50%, 70%, and 75%. The Jadad score was used to assess bias in the RCT publications [32]. This score is on a 5-point scale, based on adequate randomization, adequate blinding, and accounting for loss to follow-up within studies (see Tables 3-6). The principle summary measures were related to pain and either the Numeric Rating Scale (NRS), VAS, verbal integer scale, and/or McGill pain questionnaire at baseline and follow-up. Additional summary measures included satisfaction and function/disability, scored by the Oswestry Disability Index (ODI), Roland-Morris (R-M) disability questionnaire, and/or Activities of Daily Living Table 2 Grades of recommendation Grades of Recommendation A B C I Description Good evidence for or against recommending intervention (ie, Level 1 studies with consistent findings) Fair evidence for or against recommending intervention (ie, Level II or III studies with consistent findings) Conflicting or poor-quality evidence not allowing a recommendation for or against intervention (ie, Level IV or V studies) There is insufficient evidence to make a recommendation Downloaded for Anonymous User (n/a) at Hospital For Special Surgery in New York from ClinicalKey.com by Elsevier on June 20, For personal use only. No other uses without permission. Copyright Elsevier Inc. All rights reserved.

320 504 Particulate vs Nonparticulate Corticosteroid in ES Table 3 Cervical TFESI Outcome Measures (Time of Measurements) Results Level of Evidence Number of Patients Selection Criteria Interventions Reference Year Design III NRS (1mo) No significant difference in variance of pain or MCID 2 between steroids. TFESI with 1 ml of 1% lidocaine þ either: A: dexamethasone 15 mg B: triamcinolone 40 mg 441 patients with cervical radiculopathy from disk protrusion or stenosis Shakir et al, 2013 [35] Retrospective Jadad score n/a III NRS (1 mo) No significant difference in proportion of those with pain improvement between steroids. TFESI with either: A: dexamethasone 10 mg B: triamcinolone 40 mg 159 patients with cervical radiculopathy who failed ILESI or had previous surgery Lee et al, 2009 [36] Retrospective Jadad score n/a II VAS (1 mo) No significant difference in mean pain or >50% reduction between steroids. Significant difference in ADLs in favor of particulate; however, not based on a validated functional outcome measure. TFESI with ml 4% lidocaine þ either: A: dexamethasone 12.5 mg B: triamcinolone 60 mg 30 patients with unilateral cervical radiculopathy Dreyfuss et al, 2006 [37] Randomized Jadad score 2 TFESI ¼ transforaminal epidural steroid injection; n/a ¼ not available; MCID ¼ minimal clinically important difference; ILESI ¼ interlaminar epidural steroid injection; NRS ¼ Numeric Rating Scale; VAS ¼ visual analog scale; ADL ¼ activities of daily living. assessment performed at baseline and follow-up. Follow-up included all reported time intervals at 2 weeks to 6 months. In the Discussion section of the article, the studies are appraised and a recommendation statement is made based on the summary of the studies. A grade of recommendation (A, B, C, or I) is assigned to each statement based on the Grades of Recommendation set by Wright et al in 2005 [30] (Table 2). Results Three cervical and 6 lumbar studies were found to be suitable for review. Two abstracts reporting on particulate and nonparticulate used in lumbar TFESI were excluded on the basis of not meeting inclusion criteria and PRISMA screening [33,34] (Figure 1). Cervical TFESI Particulate Versus Nonparticulate Shakir et al [35] compared dexamethasone with triamcinolone for cervical TFESI in subjects with neck and limb pain due to cervical stenosis or disk herniation. The authors retrospectively reviewed 441 patients treated with between 1 and 3 cervical TFESI from C4 to C7. All injections were performed by the same physician using 40 mg of triamcinolone or 15 mg of dexamethasone. The primary outcome was a 10-point self-reported NRS scale within 2 weeks before the injection compared with 4 weeks after injection. The mean reduction in pain score for those treated with triamcinolone was 2.33 and for those treated with dexamethasone was 2.38, both satisfying an MCID of 2 or more; however, the authors report no statistically significant difference in the variance between the 2 groups for the patient selfreported pain score. Furthermore, when data extrapolated from the study were used, based on an MCID of 2 or more on the NRS scale, the triamcinolone group demonstrated a 57% improvement compared with the dexamethasone group of 61% improvement, and, as calculated with the Pearson c 2 test, there is no statistically significant difference between the 2 groups (for P ¼.05; c 2 ¼ 0.32 with 3 degrees of freedom; 2-tailed P ¼.92). Medical complications included 1 subject with a deep vein thrombosis, later found to have factor V Leiden disorder, and 3 subjects with superficial thrombophlebitis. Limitations of the study include its retrospective design, lack of dose equivalency between the 2 steroid groups, and susceptibility to selection bias with a single clinical site and single physician. Level III (Retrospective). Lee et al [36] studied the effect of dexamethasone and triamcinolone for cervical TFESI. The authors retrospectively reviewed 159 patients with pain or tingling sensation in the limb and performed a cervical TFESI injection at the levels C4-C7 with either 40 mg of Downloaded for Anonymous User (n/a) at Hospital For Special Surgery in New York from ClinicalKey.com by Elsevier on June 20, For personal use only. No other uses without permission. Copyright Elsevier Inc. All rights reserved.

321 Downloaded for Anonymous User (n/a) at Hospital For Special Surgery in New York from ClinicalKey.com by Elsevier on June 20, For personal use only. No other uses without permission. Copyright Elsevier Inc. All rights reserved. Table 4 Lumbar TFESI Reference Year Design Subjects Interventions Denis et al, 2015 [38] Double-blind, 56 patients with lumbar TFESI randomized radicular pain A: dexamethasone 7.5 mg Jadad score 4 B: betamethasone 6.0 mg Park et al, 2010 [41] Kennedy et al, 2014 [39] El-Yahchouchi et al, 2013 [40] Randomized Jadad score 2 Double-blind, randomized Jadad score 5 Retrospective Jadad score n/a 106 patients with lumbosacral radiculopathy 78 patients with unilateral radicular symptoms secondary to disk herniation <6 mo 2958 patients with lumbosacral radiculopathy secondary to disk herniation, foraminal or lateral recess stenosis TFESI with 1 ml 1% lidocaine with either: A: dexamethasone 7.5 mg B: triamcinolone 40 mg TFESI with 2 ml 1% anesthetic test dose, then either: A: Dexamethasone 15 mg B: Triamcinolone 60 mg TFESI with either: A: dexamethasone 10 mg (1 ml) B: triamcinolone 80 mg (2 ml) C: betamethasone 12 mg (2 ml) Outcome Measures (Time of Measurements) VAS, ODI (1 mo, 3 mo, 6 mo) ODI, McGill Pain Question, VAS (1 mo) NRS, ODI (2 wk, 3 mo, 6 mo) NRS, Roland Morris disability (2 wk, 2 mo) TFESI ¼ transforaminal epidural steroid injection; VAS ¼ visual analog scale; ODI ¼ Oswestry Disability Scale; MCID ¼ minimal clinically important difference. Results No significant difference in mean pain, >50% reduction, >75% reduction, or ODI between steroids. With multivariate regression, significant difference in ODI in favor of dexamethasone. Significant difference in mean pain, >50% reduction, and >70% reduction between steroids. MCID of 2 in 100% of the particulate group. No significant difference in McGill or ODI between steroids. No significant difference in 50% reduction in pain or ODI between steroids. Significant difference in number of injections in favor of particulate (fewer injections). Significant difference in mean pain and function at 2 mo in favor of particulate. No significant difference in 50% reduction or categorical analysis of function between steroids. Level of Evidence I II I III P. Mehta et al. / PM R 9 (2017)

322 506 Particulate vs Nonparticulate Corticosteroid in ES Table 5 Lumbar ILESI Reference Year Design Subjects Interventions Kim and Brown, 2011 [42] Single-blind, randomized Jadad score 3 60 patients with lumbosacral radiculopathy 6 mo ILESI with 10 ml consisting of 2 ml 0.25% bupivacaine þ NS þ either: A: dexamethasone 15 mg B: methylprednisolone 80 mg ILESI ¼ interlaminar epidural steroid injection; VAS ¼ visual analog scale. Outcome Measures (Time of Measurements) VAS (1-2 mo) Results No significant difference in mean pain between steroids. Level of Evidence II triamcinolone or 10mg of dexamethasone. Pain improvement on a 5-point scale (no pain; much improved; slightly improved; same as before; aggravated) was recorded within 4 weeks after injection. At this time interval, no pain and much improved were classified as effective, whereas the other pain groups were classified as ineffective. Those subjects who were deemed effective were followed until symptoms recurred. Overall, cervical TFESI was effective in 76.1% of patients within 4 weeks; however, there was no statistically significant difference between triamcinolone (80.4%) and dexamethasone (69.4%). There are was no statistically significant difference between the groups when examining median symptom-free interval. Based on the data reported, categorical analysis of MCID of 2 or more on a pain scale was unable to be determined. Medical complications were not included in the study. Limitations of the study include retrospective in design, no functional outcome measure, and no long-term follow-up. Level III (Retrospective) Dreyfuss et al [37] performed a RCT comparing cervical ESI using dexamethasone versus triamcinolone in 30 patients with unilateral nerve root compression at a single segmental level diagnosed by magnetic resonance imaging (MRI). All patients were treated with a single injection between C5 and C7 via a TFESI approach. Patients either received 12.5 mg of dexamethasone or 60 mg of triamcinolone. The primary outcome measure was the VAS at 4 weeks postinjection, and secondary outcome measures included a patient-specified functional outcome score at 4 weeks. Based on the mean VAS at baseline and 4 weeks, both groups exhibited a statistically significant improvement; however, there was no significant difference between the 2 groups. Furthermore, based on the author s categorical analysis, described as at least a 50% relief of pain, there was no statistically significant difference between dexamethasone (60%) and triamcinolone (67%). Based on the data reported, categorical analysis of MCID of 2 or more on a pain scale was unable to be determined. Although the triamcinolone group demonstrated a significant restoration of 4 patient-specified activities of daily living, as compared with dexamethasone, a validated functional outcome measure was not used. Medical complications were not included in the study. The main limitation of the study is a small sample size, with a power of 7%. Level II (RCT, nonblinded). Lumbar TFESI Particulate Versus Nonparticulate Denis et al [38] compared dexamethasone with betamethasone for lumbar TFESI in subjects with radicular pain caused by disk herniation or foraminal stenosis confirmed with computed tomography scan or MRI. The authors randomized 56 subjects into 2 groups: 27 patients were administered 6 mg of betamethasone sodium acetate and 29 received 7.5 mg of dexamethasone sodium phosphate. Both mixtures were combined with 0.25 ml of 0.9% saline for a total volume of 1 ml. TFESIs were given at 1 or 2 adjacent levels depending on the radicular pain pattern in patients and based on Table 6 Lumbar IL/TF/caudal ESI Reference Year Design Subjects Interventions Outcome Measures (Time of Measurements) Results Level of Evidence Kim et al, 2016 [43] Intraindividual retrospective cohort Jadad score n/a 162 patients with lumbar radiculopathy secondary to stenosis or herniated disk ESI with 10 mg dexamethasone and 40 mg triamcinolone Satisfaction (5-point scale), injection-free interval, injection frequency at 6 months Relative satisfaction with triamcinolone was significantly better than dexamethasone in the same patient, and injection-free interval of triamcinolone was significantly longer than dexamethasone III IL ¼ interlaminar; TF ¼ transforaminal; ESI ¼ epidural steroid injection. Downloaded for Anonymous User (n/a) at Hospital For Special Surgery in New York from ClinicalKey.com by Elsevier on June 20, For personal use only. No other uses without permission. Copyright Elsevier Inc. All rights reserved.

323 P. Mehta et al. / PM R 9 (2017) Initial results: MEDLINE (Ovid): 2,784 EMBASE: 3,308 Cochrane: 132 n=6,224 Review of references of full text inclusions: n=1 Records after duplicates removed: n=3,645 Records screened for relevance: n=3,645 Records excluded: n=3,602 Full-text articles assessed dfor eligibility: n=43 Records excluded (did not meet inclusion criteria of English, RCT/retrospective, TF/IL-ESI, part versus nonpart comparison) Studies included in systematic review: n=9 Figure 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. RCT¼ randomized controlled trial; TF¼ transforaminal; IL¼ interlaminar; ESI¼ epidural steroid injection. decision of the treating physician. The primary outcome was pain reduction on a VAS. Secondary outcomes were functional improvements as measured by the ODI and number of complications. These outcomes were measured at 1, 3, and 6 months after the injection. After TFESIs, both groups showed statistically significant VAS decreases over time and statistically significant decrease in ODI at 3 and 6 months. There was no statistically significant difference on the VAS as measured at all time intervals between the groups. In addition, categorical analysis by the authors, with success defined as 50% and 75% improvement of VAS between baseline and 3 months, failed to show a statistically significant difference between dexamethasone (59% at 50% success; 24% at 75% success) and betamethasone (33% at 50% success; 22% at 75% success). Based on the data reported, categorical analysis of MCID of 2 or more on the VAS was unable to be determined. As for functional outcomes, there was no statistically significant difference in ODI score at both 3 months and 6 months, with the difference at 6 months at the limit of statistical significance (P ¼.05). Furthermore, after a multivariate regression analysis of 17 demographic and clinical variables, the results remained nonstatistically significant between the 2 groups at all time periods for pain, whereas the difference became statistically significant at 6 months in favor of dexamethasone for functional improvement. The main limitation of the study is a small sample size with limited power in detecting a difference between steroids. Medical complications were minor and typically resolved within minutes to days. The most serious complication was postdural puncture headache, resolved with a blood patch. Level I (RCT, double-blinded). Downloaded for Anonymous User (n/a) at Hospital For Special Surgery in New York from ClinicalKey.com by Elsevier on June 20, For personal use only. No other uses without permission. Copyright Elsevier Inc. All rights reserved.