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1 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 1 Technology and Health Care -1 (2017) DOI /THC IOS Press Ozone injection with or without percutaneous microdiscectomy for treatment of cervical disc herniation Haiting Wang, Yi Zhou and Zhongpu Jiang Department of Interventional Radiology, Kaifeng Central Hospital of Henan Province, Kaifeng, Henan, China Received 5 June 2017 Accepted 9 December 2017 Abstract. OBJECTIVE: This retrospective study compared the efficacy of combined percutaneous ozone injection and percutaneous discectomyto percutaneous ozone injection alone for the treatment of cervical disc herniation. METHODS: Patients with cervical disc herniation who were enrolled in our hospital from October 2010 to June 2015 were divided into two groups: 1) treated with percutaneous ozone injection alone (control; n = 19); and 2) those treated with combined ozone injection and percutaneous microdiscectomy (combined treatment; n = 28). The efficacy of the combined treatment was evaluated relative to the control by visual analogue scale (VAS) and the modified Macnab standard. Effective treatment was defined as excellent or good, and ineffective as fair or poor. RESULTS: No major complications occurred in either group. For the control group, the VAS scores dropped from 6.75 ± 2.34 before surgery to 2.78 ± 1.85 immediately after surgery, and to 4.18 ± 1.46 during the follow-ups. For patients who received the combined treatment, the VAS scores were 7.12 ± 2.03 before surgery, 3.86 ± 2.87 immediately after surgery, and 3.27 ± 1.53 during the follow-ups. At the 6-month follow-up, 73.7% (14 from 19 patients) in the control group and 89.2% (25 from 28 patients) in the treatment group were judged to have received effective treatment. Difference in efficacy between two groups of treatment was statistically significant (P = 0.033). CONCLUSION: The rate of effective treatment in patients who received combined percutaneous microdiscectomy and ozone injection was higher than that of patients who received ozone injection alone. Combination of percutaneous microdiscectomy and ozone injection might be an effective method to treat patients with cervical disk hernia. Keywords: Percutaneous microdiscectomy, ozone injection, cervical disc herniation, microdiscectomy Introduction Cervical disc herniation is the most common reason for cervical radiculopathy [1], causing irritation or injury to the cervical nerve root (compression or stimulation) [2]. Cervical disc herniation is also a component of a pathological syndrome with similar symptoms and clinical findings 3. The pathological Corresponding author: Haiting Wang, Department of Interventional Radiology, Kaifeng Central Hospital of Henan Province, No.85 Hedao Road, Kaifeng , Henan, China. Tel.: ; haiting1963@sina.com /17/$35.00 c 2017 IOS Press and the authors. All rights reserved

2 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 2 2 H. Wang et al. / Ozone injection for treatment of cervical disc process of cervical disc herniation may begin with degeneration of the cervical disc nucleus pulposus and annulus. Subsequently, under the influence of external factors, the intervertebral disc may rupture, or the spinal nucleus pulposus can prolapse. As a result of cervical disc herniation, parts of the body that are connected with nerves from the cervical nerve root the upper extremities, chest, and back are afflicted by pain, numbness, or weakness [2]. Patients may demonstrate gait instability, weakness, and other symptoms and signs. In the worst cases, patients may experience life-threatening paralysis. The current trend in surgical treatment for cervical disc herniation is toward less invasive techniques [4], with minimally invasive treatments aimed at removing nuclear material and lowering intradiscal pressure through devices inserted percutaneously into the intervertebral discs [5]. A number of techniques have recently been developed. For example, percutaneous ozone injection under the guidance of computed tomography (CT) or digital subtraction angiography is effective in treating disc herniation [6]. It is our hypothesis that a combination of ozone injection with traditional discectomy may result in a better clinical outcome for treatment of cervical disc herniation. However, to the best of our knowledge, no study has reported the efficacy of discectomy combined with ozone injection, compared to ozone injection alone. This study is a retrospective review of patients in our hospital from 2010 to 2015 who were treated for cervical disc herniation, to compare the efficacy of percutaneous microdiscectomy plus ozone injection relative to ozone injection alone. 2. Materials and patients The study was approved by the Medical Ethics Committee of the lcal Hospital. All patients signed informed consent forms Study design From October 2010 to June 2015, 47 patients with cervical disc herniation, including 29 men and 18 women were treated in Department of Interventional radiology in Kaifeng Central Hospital, at Kaifeng in Henan Province of China. The mean age of the patients was 48.1 years (range, 29 to 71 y). The medical records, images, and neurological evaluations of these patients were retrospectively reviewed. Cervical disc herniation was diagnosed based on clinical symptoms and radiological data, including X- ray and magnetic resonance imaging (MRI). For the analysis of this study, the 47 patients were divided into those treated with a percutaneous injection of ozone (the control group, n = 19), and those treated with percutaneous microdiscectomy in addition to ozone injection (combined treatment group, n = 28). All of the included subjects conformed to the following criteria: symptoms such as pain, numbness, sore swelling, and lack of force in the unilateral or bilateral occipital, neck, shoulders, back, chest, or upper extremity. Patients also had one- or two-levels traumatic cervical disc herniation as diagnosed by MRI, and their symptoms were verified by radiological examination. None of the patients had any of the following: spinal cord ischemia or degradation caused by compression from protruding discs; ossification of the posterior longitudinal ligament; severe cervical hyperosteogeny, and calcification of the cervical disc; severe cervical disc protrusion and stenosis of the cervical spinal canal; hypersensitive carotid sinus and carotid artery plaque; ozone allergies and contraindications; or other contraindication for surgery, such as implanted pacemaker, coagulation abnormalities, or cardiopulmonary dysfunction.

3 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 3 H. Wang et al. / Ozone injection for treatment of cervical disc Surgery preparation All patients underwent routine preoperative physical examination and routine laboratory tests, including coagulation, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor examination, electrocardiogram, anteroposterior chest X-ray, lateral cervical spine X-ray imaging, and MRI. The principles of surgery and surgical procedure were explained to the patients, to ease tension and fear; patients were also taught to do esophageal push activities to collaborate better with surgeons during the procedure. A neck brace was also prepared Equipment The suspended plate was manufactured by Semen s in Germany. Digital subtraction angiography (AX- IOM ArtisdTA), the 19G percutaneous discectomy device (Stryker, USC), and cabinet ozone generator (Medozon, HYPER-Medozon comfort) were also used during the surgery Surgical procedure An anterior approach was taken for the surgery. A Kirschner wire was used to locate lesions under lateral X-ray fluoroscopy. Puncture sites were marked. Anterior routine skin disinfection was performed. 1 2 ml of 1% lidocaine was used to infiltrate the puncture site and prevertebral fascia. Under guidance of the C-arm X-ray machine, a 21 G needle was used to puncture through the arterial sheath and internal sheath gap into the herniated disc, until the central part of the nucleus was reached. Under lateral monitoring, the needle tip was positioned at 1/3 of the junction in the intervertebral gap. Under the anteroposterior view, the tip was located in the middle or a bit more on the lesion side. The needle core was pulled out and 5 10 ml of 60 µg/ml ozone was then injected along the needle hub. If necessary, the needle depth and angle range was adjusted 2 mm, and the injection was repeated for complete ablation of the other segments. After injection, the skin was cleaned, disinfected, and covered with a sterile dressing. For patients in the combined treatment group, these patients were punctured with the 19 G needle, and the nucleus pulposus remover was delivered to the site of the lesion. A little nucleus was cut. The remover was withdrawn, and then immediately 5 10 ml of 60 µg/ml of ozone was injected into the intervertebral space. Neck collar protection was provided after surgery Post-surgery care for patients Patients were required to lay in bed for 24 to 48 hours after surgery. Patients were given 125 ml of mannitol by intravenous infusion, once a day for 3 consecutive days. Patients also received 100 ml of 0.9% sodium chloride; and 10 mg of dexamethasone, by intravenous infusion, once a day for 3 consecutive days. Vitamin B12 (0.15 mg) was given through intramuscular injection, 2 /d for 3 days Evaluation of clinical outcomes To assess clinical outcomes, patients were followed-up with questionnaires at one week, and 1, 3, and 6 months post-surgery. The pain before and after surgery was evaluated by visual analogue scale (VAS).

4 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 4 4 H. Wang et al. / Ozone injection for treatment of cervical disc Table 1 Cervical disc herniation levels of the control and combined treatment groups, n (%) Control Combined treatment Total subjects, n C3/4 1 (5.2%) 1 (3.6%) C4/5 1 (5.2%) 2 (7.1%) C5/6 3 (15.8%) 4 (14.2%) C3/4 + C4/5 2 (10.5%) 1 (3.6%) C4/5 + C5/6 3 (15.8%) 3 (10.7%) C3/4 + C4/5 + C5/6 8 (42.1%) 15 (53.6%) C4/5 + C5/6 + C6/7 1 (5.2%) 0 (0%) C3/4 + C4/5 + C6/7 1 (5.2%) 1 (3.6%) The difference between two group of patients is not statistically different. χ2 = 1.597; P = Efficacy of outcome was also assessed according to the modified Macnab grading standards, as excellent, good, fair, or poor, as defined below. Effective treatment was considered a modified Macnab grade of excellent or good, while ineffective treatment was determined by a Macnab grade of fair or poor. Excellent: no pain, no limitation on movement, with normal work and activities resumed. Good: occasional non-radicular pain, relief of main symptoms and signs, able to perform less demanding work after surgery. Fair: function improved to some extent, symptoms absent or improved after surgery, work and life remain affected. Poor: with nerve root injury, recurrent symptoms after surgery, or no difference in work or life quality from before surgery Statistical analysis Data are expressed as mean ± standard deviation. The scores before and after surgery were compared with the paired t-test. Comparisons between the two groups were analyzed with the chi-squared test. P < 0.05 was considered statistically significant. SPSS 10.0 statistical software was used for statistical analyses. 3. Results Patients were assigned to two groups, depending on the treatment they received to repair cervical disc herniation. The control group was treated with percutaneous injection of ozone only, and comprised 19 patients, 11 men and 8 women, mean age 46.3 years (range, years), average length of history 3 years (range, 6 months-13 year). The combined treatment group received percutaneous microdiscectomy plus ozone injection, and consisted of 28 patients, 18 men and 10 women, mean age 49.9 years (range, years), average length of history 2.5 years (range, 4 month-15 year). These demographic data of the two groups were not significantly different. The distribution of herniated disc levels is listed in Table 1. The operative time was 30 to 80 min, with an average of 39 min. Hospitalizations ranged from 5 to 9 days, with an average of 6 days. All 47 patients completed the follow-ups of 1 to 6 months. The average follow-up time was 4.5 months. X-rays and MRIs were performed before and after the surgery to show the vertebra (Fig. 1). The efficacy was determined by the results of the VAS scores and Macnab grades at the latest follow-up (Tables 2

5 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 5 5 un co rre ct ed pr oo fv er si on H. Wang et al. / Ozone injection for treatment of cervical disc Fig. 1. MRI showed a 54 years old male had his dural sac been depressed by herniated C5-6 and C6-7 discs. Examination was performed on October 13th, Reexamination on December 8th 2015, showed that depression of dural sac by herniated C5-6 and C6-7 discs was released. (A) Sagittal view before surgery (October 13th, 2014). (B) Sagittal view after surgery (December 8th 2015). (C) Transverse view of C5-6 disc before surgery (October 13th, 2014). (D) Transverse view of C5-6 disc after surgery (December 8th 2015). (E) Transverse view of C6-7 disc before surgery (October 13th, 2014). (F) Transverse view of C6-7 disc after surgery (December 8th 2015).

6 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 6 6 H. Wang et al. / Ozone injection for treatment of cervical disc Table 2 VAS scores of the control and combined treatment groups Control Combined treatment Case number, n Follow-up time, no 4-5 ± ± 1-3 Operation time, min 33 ± ± 15 VAS Preoperative 6-75 ± ± 2-03 VAS Postoperative 2-78 ± ± 2-87 VAS Follow-up 4-18 ± ± 1-53 P = 0.024, comparing VAS before and after surgery Table 3 Efficacy of treatment as measured by the modified Macnab standard grades at the latest follow-up, n Macnab grade Control Combined treatment Effective Excellent 5 12 Good 9 13 Ineffective Acceptable 3 2 Poor 2 1 Overall rate of effectiveness 73.70% 89.30% P < 0.033, comparison of the groups. and 3). For the control group, the VAS scores were 6.75 ± 2.34 before surgery, 2.78 ± 1.85 immediately after surgery, and 4.18 ± 1.46 during the follow-ups. For patients who received the combined treatment, the VAS scores were 7.12 ± 2.03 before surgery, 3.86 ± 2.87 immediately after surgery, and 3.27 ± 1.53 during the follow-ups. According to the modified Macnab grading standards, in the control group 14/19 outcomes were considered effective (overall efficiency, 73.7%), which was significantly (P = 0.033) less than that of the combined treatment group (25/28 patients, overall efficiency, 89.3%). In the both groups, the VAS scores before the surgery were significantly higher than that after surgery (analyzed by paired t-test, P < 0.05). The VAS scores of the patients in the combined treatment group were significantly lower than that of the control group (P < 0.05). After the surgery, 7 of the 28 patients in the combined treatment group complained of varying degrees of neck and shoulder pain and discomfort. Among the 7 cases, the pain of 5 resolved by itself within 2 to 4 hours of surgery; 2 patients were given oxygen inhalation, and sedation within 12 hours. No vascular or nerve damage was reported after the surgery. No hematoma, puncture infection or other complications occurred. 4. Discussion In this study, we combined percutaneous microdiscectomy with ozone injection to treat cervical disc herniation, and compared the clinical outcome with that of ozone injection alone. The overall efficacy of the group that received the combined treatment was 89.3%, which was significantly higher than the overall efficacy of the control group (73.7%). Regarding pain relief, significantly better than ozone ablation alone. No complications occurred in either groups. During cervical disc discectomy, the incisions were small and surgeons should carefully avoid touching the thyroid, trachea, esophagus, jugular vein, recurrent laryngeal nerve, or neck longus [7]. Surgeons should also take care to avoid hurting the thoracic duct. In particular, the depth of the needle and cannula must not exceed one-third of the vertebral body margin [8]. Intraoperative fluoroscopy should be used

7 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 7 H. Wang et al. / Ozone injection for treatment of cervical disc to monitor the location of the needle, and surgeons should communicate by talking with the patient, for feedback [9]. Moreover, the trocar inserted into the disc should be parallelwith the disc plane. Otherwise, it may damage the cartilage, cause bleeding, postoperative pain, or intervertebral disc endplate symptoms [10]. Discectomy is the resection of the lesion or herniated disc nucleus pulposus tissue, using a dedicated cervical nucleus pulposus remover under guidance of digital subtraction angiography [11]. The purpose of discectomy is to reduce the disc volume, and release the pressure inside the disc. During the surgery, the protruding or ruptured intervertebral disc is pushed back or the herniated disc is removed directly [12]. After the surgery, compression caused by the herniated disc should be absent. Thus, the surrounding tissue edema and inflammation will subside, and the oppression of the spinal cord and nerve roots may be alleviated. Ozone ablation utilizes the strong oxidizing activity of ozone to oxidize the proteoglycan within the nucleus. The oxidation causes dehydration, degeneration, and atrophy of the nucleus and reduction of the disc volume, thus exerts an anti-inflammatory effect due to the breakdown or neutralization of intra-disc inflammatory factors and enzymes [13]. Ozone also has an analgesic effect, because ozone injection can inhibit the free fiber cord injury receptors, activate the body s regenerative system to repair tissue damage, and stimulate the release of enkephalin and other substances form inhibitory middle neurons [14]. In the present study, a combined treatment of the two methods significantly improved clinical outcomes for treating cervical disc herniation. Although the VSA scores indicated that the treatments in both groups were effective, the combined treatment had better effects in reduction of patient pain, improvement of neck and shoulder function, reduction of the incidence of complications, and improvement of patients long-term work, study, and life quality. This suggests that the efficacy of percutaneous discectomy combined with ozone injection was better than ozone injection alone. The average rate of efficacy for all decompression techniques used for treating herniated discs varies from 75% to 94% [15 17]. This is generally better than the rate of efficacy of conservative therapy or infiltrations, as indicated by better and longer pain relief, in randomized, prospective, and comparative trials [17,18]. However, among various percutaneous techniques, there were no significant differences [19], and also none found among percutaneous decompression, open discectomy, or percutaneous discectomytechniques [20,21]. In these studies, discectomy and percutaneous decompression techniques were considered separately. In our present study, we report for the first time the combination of percutaneous ozone injection and percutaneous discectomyand compare it to ozone injection alone. Compared to traditional open surgery, percutaneous decompression techniques such as ozone injection have the advantage of minimum destruction of the neighboring tissues. In addition, it generally reduces treatment cost by 25% to 30%, relative to open surgery [16]. If we take into account the better clinical outcome, combined discectomy and ozone injection may be considered an improvement. The mean rate of complications associated with decompression techniques is about 0.5% [17]. It is extremely rare to have intra-operative complications such as reflex sympathetic dystrophy, allergic reactions, puncture of the thecal sac, hemorrhage, or neurologic injury when applying percutaneous decompression techniques. This is because imaging guidance aids the surgeon to preform proper injections, increases the injection efficacy, and at the same time minimizes the rate of such complications. Referring to the cervical spine, vasovagal reactions can occur during percutaneous decompression techniques [22,23]. In the present study, we had 7 patients in the combined treatment group who complained of pain and discomfort in the neck and shoulder, 5 of whom experienced spontaneous relief within 2 to 4 hours. The remaining 2 patients were relieved with 12 hours after the administration of

8 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 8 8 H. Wang et al. / Ozone injection for treatment of cervical disc oxygen inhalation and sedation. Thus, there were 2 patients among 28 who experienced minor complications, a rate of 7%. This is a bit higher compared to routine decompression techniques, due to the complexity of the combined treatment. However, we had no case of major complication, such as vascular or nerve damage, hematoma, or puncture infection. The limitations of the current study include a small sample size and its retrospective nature. A cohort of 47 patients is large enough to provide statistical significance for comparing 2 groups of patients. However, larger samples would be helpful to corroborate the efficacy of the two treatments, and a randomized control trial, or at least a prospective study, could overcome the limitations inherent in a retrospective analysis. In conclusion, the clinical efficacy of percutaneous microdiscectomy combined with ozone ablation was better than that of ozone injection alone. This combined method provides a minimally invasive, accurate, and effective treatment that is ideal for correcting cervical disc herniation. Conflict of interest All authors declared there were no conflicts of interest involved. References [1] Abbed KM, Coumans JV. Cervical radiculopathy: pathophysiology, presentation, and clinical evaluation. Neurosurgery Jan; 60(1 Suppl 1): S PubMed PMID: [2] Jackson R. The classic: the cervical syndrome Clinical Orthopaedics and Related Research Jul; 468(7): PubMed PMID: Pubmed Central PMCID: [3] Wong JJ, Cote P, Quesnele JJ, Stern PJ, Mior SA. The course and prognostic factors of symptomatic cervical disc herniation with radiculopathy: a systematic review of the literature. The Spine Journal: Official Journal of the North American Spine Society Aug 1; 14(8): PubMed PMID: [4] Benglis DM, Guest JD, Wang MY. Clinical feasibility of minimally invasive cervical laminoplasty. Neurosurgical Focus. 2008; 25(2): E3. PubMed PMID: [5] Ni CH, Yu CS, Lu HF, Yang JS, Huang HY, Chen PY, et al. Chrysophanol-induced cell death (necrosis) in human lung cancer A549 cells is mediated through increasing reactive oxygen species and decreasing the level of mitochondrial membrane potential. Environmental Toxicology May; 29(7): PubMed PMID: [6] Alexandre A, Coro L, Azuelos A, Buric J, Salgado H, Murga M, et al. Intradiscal injection of oxygen-ozone gas mixture for the treatment of cervical disc herniations. Acta Neurochirurgica Supplement. 2005; 92: PubMed PMID: [7] Kreiner DS, Hwang SW, Easa JE, Resnick DK, Baisden JL, Bess S, et al. An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy. The Spine Journal: Official Journal of the North American Spine Society Jan; 14(1): PubMed PMID: [8] Ahn Y, Lee SH, Chung SE, Park HS, Shin SW. Percutaneous endoscopic cervical discectomy for discogenic cervical headache due to soft disc herniation. Neuroradiology Dec; 47(12): PubMed PMID: [9] Kelekis A, Filippiadis DK. Percutaneous treatment of cervical and lumbar herniated disc. European Journal of Radiology May; 84(5): PubMed PMID: [10] Ryang YM, Oertel MF, Mayfrank L, Gilsbach JM, Rohde V. Transmuscular trocar technique minimal access spine surgery for far lateral lumbar disc herniations. Minimally Invasive Neurosurgery: MIN Oct; 50(5): PubMed PMID: [11] Kotilainen E. Percutaneous nucleotomy in the treatment of cervical disc herniation: report of three cases and review. Minimally Invasive Neurosurgery: MIN Sep; 42(3): PubMed PMID: [12] Clatterbuck RE, Belzberg AJ, Ducker TB. Intradural cervical disc herniation and Brown-Sequard s syndrome. Report of three cases and review of the literature. Journal of Neurosurgery Apr; 92(2 Suppl): PubMed PMID: [13] Leon Fernandez OS, Pantoja M, Diaz Soto MT, Dranguet J, Garcia Insua M, Viebhan-Hansler R, et al. Ozone oxidative post-conditioning reduces oxidative protein damage in patients with disc hernia. Neurological Research Jan; 34(1): PubMed PMID:

9 Galley Proof 4/01/2018; 9:37 File: thc 1-thc tex; BOKCTP/xjm p. 9 H. Wang et al. / Ozone injection for treatment of cervical disc [14] Bo W, Longyi C, Jian T, Guangfu H, Hailong F, Weidong L, et al. A pyogenic discitis at c3-c4 with associated ventral epidural abscess involving c1-c4 after intradiscal oxygen-ozone chemonucleolysis: a case report. Spine Apr 15; 34(8): E PubMed PMID: [15] Amoretti N, Huwart L, Marcy PY, Foti P, Hauger O, Boileau P. CT- and fluoroscopy-guided percutaneous discectomy for lumbar radiculopathy related to disc herniation: a comparative prospective study comparing lateral to medial herniated discs. Skeletal Radiology Jan; 42(1): PubMed PMID: [16] Gangi A, Tsoumakidou G, Buy X, Cabral JF, Garnon J. Percutaneous techniques for cervical pain of discal origin. Seminars in Musculoskeletal Radiology Apr; 15(2): PubMed PMID: [17] Kelekis AD, Filippiadis DK, Martin JB, Brountzos E. Standards of practice: quality assurance guidelines for percutaneous treatments of intervertebral discs. Cardiovascular and Interventional Radiology Oct; 33(5): PubMed PMID: [18] Gerszten PC, Smuck M, Rathmell JP, Simopoulos TT, Bhagia SM, Mocek CK, et al. Plasma disc decompression compared with fluoroscopy-guided transforaminal epidural steroid injections for symptomatic contained lumbar disc herniation: a prospective, randomized, controlled trial. Journal of Neurosurgery Spine Apr; 12(4): PubMed PMID: [19] Lemcke J, Al-Zain F, Mutze S, Meier U. Minimally invasive spinal surgery using nucleoplasty and the Dekompressor tool: a comparison of two methods in a one year follow-up. Minimally Invasive Neurosurgery: MIN Oct; 53(5-6): PubMed PMID: [20] Adam D, Pevzner E, Gepstein R. Comparison of percutaneous nucleoplasty and open discectomy in patients with lumbar disc protrusions. Chirurgia Jan-Feb; 108(1): PubMed PMID: [21] Liu WG, Wu XT, Guo JH, Zhuang SY, Teng GJ. Long-term outcomes of patients with lumbar disc herniation treated with percutaneous discectomy: comparative study with microendoscopic discectomy. Cardiovascular and Interventional Radiology Aug; 33(4): PubMed PMID: [22] Zeidman SM, Thompson K, Ducker TB. Complications of cervical discography: analysis of 4400 diagnostic disc injections. Neurosurgery Sep; 37(3): PubMed PMID: [23] Connor PM, Darden BV, 2nd. Cervical discography complications and clinical efficacy. Spine Oct 15; 18(14): PubMed PMID:

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