Multilevel cervical degenerative disc disease (cddd)

Transcription

1 SPINE Volume 39, Number 23, pp , Lippincott Williams & Wilkins CERVICAL SPINE Fusion-Nonfusion Hybrid Construct Versus Anterior Cervical Hybrid Decompression and Fusion A Comparative Study for 3-Level Cervical Degenerative Disc Diseases Fan Ding, MD, * Zhiwei Jia, MD, * Yaohong Wu, MD, * Chao Li, MD, * Qing He, MD, * and Dike Ruan, MD, PhD * Study Design. A retrospective analysis. Objective. This study aimed to compare the safety and efficacy between the fusion-nonfusion hybrid construct (HC: anterior cervical corpectomy and fusion plus artificial disc replacement, ACCF plus cadr) and anterior cervical hybrid decompression and fusion (ACHDF: anterior cervical corpectomy and fusion plus discectomy and fusion, ACCF plus ACDF) for 3-level cervical degenerative disc diseases (cddd). Summary of Background Data. The optimal anterior technique for 3-level cddd remains uncertain. Long-segment fusion substantially induced biomechanical changes at adjacent levels, which may lead to symptomatic adjacent segment degeneration. Hybrid surgery consisting of ACDF and cadr has been reported with good results for 2-level cddd. In this context, ACCF combining with cadr may be an alternative to ACHDF for 3-level cddd. Methods. Between 2009 and 2012, 28 patients with 3-level cddd who underwent HC (n = 13) and ACHDF (15) were retrospectively reviewed. Clinical assessments were based on Neck Disability Index, Japanese Orthopedic Association disability scale, visual analogue scale, Japanese Orthopedic Association recovery rate, and Odom criteria. Radiological analysis included range of motion of C2 C7 and adjacent segments and cervical lordosis. Perioperative parameters, radiological adjacent-level changes, and the complications were also assessed. From the * Department of Orthopedics, Navy General Hospital, the Third Clinical College, Southern Medical University, Beijing, China; and Department of Orthopedics, Wuhan Pu Ai Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China. Acknowledgment date: May 20, Revision date: July 13, Acceptance date: August 15, The device(s)/drug(s) is/are FDA approved or approved by corresponding national agency for this indication. No funds were received in support of this work. No relevant financial activities outside the submitted work. Fan Ding and Zhiwei Jia contributed equally to this work. Address correspondence and reprint requests to Dike Ruan, MD, PhD, Department of Orthopedics, Navy General Hospital, the Third Clinical College, Southern Medical University, NO. 6 Fucheng Rd, Beijing, , China; ruandikengh@163.com DOI: /BRS Results. HC showed better Neck Disability Index improvement at 12 and 24 months, as well as Japanese Orthopedic Association and visual analogue scale improvement at 24 months postoperatively ( P < 0.05). HC had better outcome according to Odom criteria but not significantly ( P > 0.05). The range of motion of C2 C7 and adjacent segments was less compromised in HC ( P < 0.05). Both 2 groups showed significant lordosis recovery postoperatively ( P < 0.05), but no difference was found between groups ( P > 0.05). The incidence of adjacent-level degenerative changes and complications was higher in ACHDF but not significantly ( P > 0.05). Conclusion. HC may be an alternative to ACHDF for 3-level cddd due to the equivalent or superior early clinical outcomes, less compromised C2 C7 range of motion, and less impact at adjacent levels. Key words: hybrid surgery, arthroplasty, corpectomy, discectomy, fusion, degenerative disc disease, cervical spine. Level of Evidence: 3 Spine 2014;39: Multilevel cervical degenerative disc disease (cddd) is a common age-related neurological disorder, substantially impairing quality of life. 1 Surgical procedures for multilevel cddd have yielded good clinical results via several approaches. 2 4 When the topic is limited to anterior approaches, there is no consensus on which technique is the best. 5 Studies revealed that 3-level anterior cervical discectomy and fusion (ACDF) is associated with a higher incidence of nonunion because of increased graft-host interfaces, 6 whereas 2-level anterior cervical corpectomy and fusion (ACCF) has a higher morbidity of device-related complications. 7, 8 Anterior cervical hybrid decompression and fusion (ACHDF), consisting of ACCF and ACDF, has been introduced as an alternative procedure, 9 because it may avoid some drawbacks of traditional fusion techniques. However, biomechanical changes after long-segment fusion, including concentrated stress, increased compensatory motion, and stability loss at the adjacent segments, may result in symptomatic adjacent-segment degeneration (ASD). 10 As surgical technology progresses, November 2014

2 cervical artificial disk replacement (cadr) has gained popularity, which maintains motion of operative level and alleviates stress distribution at adjacent segments for preventing ASD. 11 However, the results of multilevel cadr are not well established, and hypermobility of operative segments, high risk of prosthesis-related complications, and high medical expense may be potential problems. 12, 13 Recently, a hybrid surgery consisting of ACDF and cadr has been reported with good outcomes The rationality behind this technique is that not all the diseased levels show the same type and extent of degeneration, and it is better to tailor the most suitable procedure according to the status of affected levels. Nonetheless, little information is documented regarding to the efficacy of ACCF combined with cadr. The objective of this study is to compare clinical outcomes, radiological findings, and complications between the fusion-nonfusion hybrid construct (HC: 1-ACCF plus 1-cADR) and anterior cervical hybrid decompression and fusion (ACHDF: 1-ACCF plus 1-ACDF) for 3-level cddd. MATERIALS AND METHODS Patient Data From January 2009 to January 2012, 28 patients (male/female: 18/10; mean age: 51.6 ± 7.7 yr) with 3-level cddd were retrospectively reviewed. All patients were followed clinically and radiologically for a minimum of 24 months. According to different anterior methods, the patients were divided into HC (13 patients) and ACHDF groups (15). The inclusion criteria included the following: (1) Cervical myelopathy and/or radiculopathy not responding to conservative treatment for 6 weeks. (2) Magnetic resonance image showed intervertebral disc degeneration and herniation. (3) Cervical pathology in 3 consecutive levels. (4) None or slight osteophyte at the posterior edge of vertebral body without significant spinal stenosis or posterior compression. The exclusion criteria included cervical stenosis caused by posterior compression, tumor, deformity, osteoporosis, and infection. cadr was performed in the segment that had less degenerative changes and had greater physiologic motion (C5 C6 > C4 C5 > C6 C7 > C3 C4), 15 whereas ACCF was done at the level with dynamic instability, severe disc degeneration, and retrovertebral compressive pathology. General Surgical Technique All the operations were performed by the same experienced spine surgeon. Anterior cervical discectomy and corpectomy were performed as well-guided previously. 17 For cadr, thorough decompression was performed including removal of the herniated nucleus pulposus, osteophytes, and hypertrophic posterior longitudinal ligament. After finishing the burring and milling processes of the 2 vertebral body endplates at the target disc space, a matching Mobi-C disc (LDR Medical, Troyes, France) was implanted. For ACCF, grafting bed was prepared with exposure of the subchondral bone. Then, titanium mesh filled with local autograft bone was used to span the defect generated by corpectomy. The space generated by ACDF was filled by either an iliac allograft alone or a cage (Syncage, Synthes, Mezzovico-Vira, Switzerland) packed with local bone. Anterior cervical plate (Medtronic Sofamor Danek, Memphis, TN) was placed over the entire fused segments with screws inserted into the vertebrae ( Figure 1A and 1B ). Drainage was taken out after 1 to 2 days postoperatively. All patients were immobilized with a collar for 8 to 12 weeks. Outcome Evaluation Perioperative parameters (operation time, blood loss, drainage volume, hospital stay, and follow-up duration) were collected. Neck Disability Index (NDI) was used to evaluate daily activities of the patients. Neurological status was Figure 1. A, Lateral radiograph of hybrid construct at 12 months postoperatively; measurement of Cobb angle at operative and adjacent levels. B, Lateral radiograph of anterior cervical hybrid decompression and fusion at 3 months postoperatively; measurement of C2 C7 Cobb angle. Spine

3 evaluated according to the Japanese Orthopedic Association (JOA) disability scale. The visual analogue scale (VAS) was used to assess the neck pain intensity. All evaluations were completed preoperatively and at 3, 6, 12, and 24 months postoperatively. JOA recovery rate was calculated using the Hirabayashi method 18 : (postoperative score preoperative score)/(17 preoperative score) 100%. Recovery rates were graded as follows: greater than 75%, excellent; 50% to 74%, good; 25% to 49%, fair; and less than 25%, poor. General clinical outcomes were graded according to Odom criteria. 19 Radiological analysis was conducted via lateral radiographs in flexion, extension, and in neutral position. The angular range of motion (ROM) of C2 C7 and adjacent segments and cervical lordosis were measured using the Cobb method 20 ( Figure 1 ). The radiological evidence of adjacentlevel changes including new disc herniation, new osteophyte formation, new narrowing of disc space, and new anterior longitudinal ligament (ALL) calcification was assessed. The incidence of complications was also recorded. Statistical Analysis All the measurements were performed 3 times independently and the mean values were used for statistical analysis. A Pearson χ 2 test or Fisher exact test was applied for qualitative data. A Wilcoxon test was used to assess changes between postoperative and preoperative parameters. Statistical comparisons between groups were performed using Mann- Whitney U test. All the statistical tests were completed by the Statistical Package for Social Sciences software for Windows (Version 19.0; SPSS Inc, Chicago, IL), and the difference was considered to be statistically significant at P < RESULTS Demographic Summary The male-to-female ratio, average age, involved levels, and preoperative symptoms in HC and ACHDF groups were recorded in Table 1. There were no statistical differences between 2 groups. Perioperative Parameters The average operation time, blood loss, and postoperative drainage volume were shown in Table 1. There were no significant differences between 2 groups. The hospital stay and the duration of follow-up were also comparable ( Table 1 ). TABLE 1. Patient Characteristics Characteristics Groups HC (n = 13) ACHDF (n = 15) Statistical Value P Male/female* 8/5 10/ Mean age (range), yr 50.6 ± 8.1 (34 69) 52.5 ± 7.6 (35 71) Involved levels * C3 C4, C4 C5, C5 C6 9 9 C4 C5, C5 C6, C6 C7 4 6 Symptoms Myelopathy 7 9 Radiculopathy 5 4 Both 1 2 Intraoperation Mean operation time (range), min ± 37.5( ) ± 31.7 ( ) Mean blood loss (range), ml ± 25.1( ) ± 22.9 ( ) Postoperation Mean drainage volume (range), ml 98.5 ± 24.4(80 130) ± 19.8 (90 140) Mean hospital stay (range), d 10.3 ± 1.8(7 14) 10.7 ± 2.1(7 15) Mean follow-up (range), mo 33.7 ± 8.1 (24 54) 35.3 ± 9.4 (24 60) Mann-Whitney U test. Pearson χ 2 test. HC indicates hybrid construct; ACHDF, anterior cervical hybrid decompression and fusion November 2014

4 P = 0.016, respectively; see Supplemental Digital Content Table 1, available at JOA Scores Compared with preoperative status, both groups showed significant JOA improvements at each time point ( Figure 3 ). There were no group differences at 3, 6, and 12 months postoperatively. However, HC group showed better JOA scores than that of ACHDF group at 24 months ( P = 0.018; see Supplemental Digital Content Table 1, available at links.lww.com/brs/a903). Figure 2. Mean NDI scores significantly decreased in both groups. HC group showed lower NDI scores at 12 and 24 months postoperatively; Mann-Whitney U test: a: P = 0.033; b: P = NDI indicates Neck Disability Index; ACHDF, anterior cervical hybrid decompression and fusion; HC, hybrid construct. Clinical Outcomes Evaluation NDI Scores Figure 2 depicts the mean NDI scores over time and shows that both HC and ACHDF groups exhibited a significant NDI recovery at each follow-up. Although no significant differences existed between groups at 3 and 6 months ( P = 0.139, P = 0.055, respectively), HC group experienced a trend toward better results at 12 and 24 months ( P = 0.033, VAS Scores With respect to pain relief, no group differences existed at 3, 6, and 12 months postoperatively. However, HC group had a trend toward significantly lower VAS scores at 24 months as depicted in Figure 4 ( P = 0.041; see Supplemental Digital Content Table 1, available at A903). JOA Recovery Rate HC group exhibited a significantly better JOA recovery rate than that of ACHDF group as depicted in Table 2 ( P = 0.013). However, a Fisher exact test showed a similar neurological recovery grade between groups ( P = 0.084, Table 2 ). Odom Criteria As tabulated in Table 3, HC showed slightly better outcome than ACHDF but not significantly ( P = 0.333). Radiographical Evaluation C2 C7 ROM Both HC and ACHDF groups exhibited decreased ROM when compared with preoperative level ( P = 0.001). However, HC Figure 3. Mean JOA scores showed significant recovery in both groups. HC group showed higher JOA scores at 24 months postoperatively; a: Mann-Whitney U test, P = JOA indicates Japanese Orthopedic Association; ACHDF, anterior cervical hybrid decompression and fusion; HC, hybrid construct. Figure 4. Mean VAS scores showed significant decrease in both groups. HC group showed lower VAS scores at 24 months postoperatively; a: Mann-Whitney U test, P = VAS indicates visual analogue scale; ACHDF, anterior cervical hybrid decompression and fusion; HC, hybrid construct. Spine

5 TABLE 2. Japanese Orthopedic Association Recovery Rate HC (n = 13) ACHDF (n = 15) Statistical Value P Neurological recovery grade* Excellent ( 75%) 8 3 Good (50% 74%) 4 6 Fair (25% 49%) 0 5 Poor ( < 25%) 1` 1 Recovery rate 71.56% ± 15.78% 55.47% ± 18.11% u = Mann-Whitney U test. HC indicates hybrid construct; ACHDF, anterior cervical hybrid decompression and fusion. group showed less compromised ROM than ACHDF group ( P = 0.034, Figure 5 ; see Supplemental Digital Content Table 2, available at Adjacent-Segment ROM Figure 5 depicts a significant increased ROM at superior and inferior adjacent segments in both groups compared with preoperative values. However, the compensatory ROM was less in HC group (see Supplemental Digital Content Table 2, available at Cervical Lordosis Figure 6 demonstrates a significant recovery of cervical lordosis in both groups compared with baseline ( P = 0.004, P = 0.009, respectively). But no statistical difference was found between groups ( P = 0.945; see Supplemental Digital Content Table 2, available at A903). Radiological Adjacent-Level Changes New disc herniation was found in both groups. Osteophyte formations were found only in ACHDF group. Other degenerative changes such as narrowing of the disc space and anterior longitudinal ligament calcification were not observed in both groups. No significant difference was found between 2 groups ( P = 0.655, Table 4 ). Complications One patient with dysphagia and 1 with hoarseness were found in each group, but no C5 palsy occurred. In ACHDF group, 1 patient with cerebral fluid leakage and 1 with epidural hematoma were diagnosed. No infection developed in both groups. Heterotopic ossification (HO) was found in HC group. Titanium mesh subsidence was found in ACHDF group.no other complications such as plate and screw loosening, titanium mesh and cage dislodgment, and prostheses breakage were observed. There was no significant difference between groups ( P = 1.000, Table 5 ). DISCUSSION It remains controversial over the ideal option of anterior methods for multilevel cddd. Three-level ACDF was associated with high nonunion rate up to 54%. 21 This observation of high nonunion frequency may attribute to increased graft-host interfaces and resultant motion. 6, 21 Although the fusion rate improved with less graft-host interfaces, 21 2-ACCF had high risk of device-related complications that may need further revision. 7, 8 Therefore, ACHDF consisting of 1-ACCF and 1-ACDF was introduced with less graft-host interfaces than 3-ACDF and prior biomechanics than 2-ACCF and was thought to achieve good results with lower pseudarthrosis and complication rate. 9 However, long-segment fusion was associated with more concentrated stress, increased compensatory TABLE 3. Odom Criteria Grade HC (n = 13) ACHDF (n = 15) Statistical Value P Odom criteria grade Excellent 3 3 Good 9 8 Fair 1 3 Poor 0 1 Excellent + good ratio* 92.31% 73.33% HC indicates hybrid construct; ACHDF, anterior cervical hybrid decompression and fusion November 2014

6 Figure 5. HC group showed less decreased C2 C7 ROM and less compensatory ROM at adjacent segments; Mann-Whitney U test, a: P = 0.034; b: P = 0.023; c: P = ROM indicates range of motion; HC, hybrid construct; ACHDF, anterior cervical hybrid decompression and fusion. motion, and stability loss at adjacent segments, which could result in ASD. 10, 22 A cadr was designed to address the issue and gained popularity for 1-level cddd. 11, 23 The clinical and biomechanical outcomes of multilevel cadr, however, have not been well established, because it may cause excessive motion, high prosthesis-related complication rate, and high medical costs. 12, 13, 24 Therefore, optimal anterior surgical procedure for multilevel cddd deserves to be ameliorated. Shin et al 15 reported that hybrid surgery consisting of 1-ACDF and 1-cADR exhibited better clinical and radiographical results than that of 2-ACDF for 2-level cddd. Kang et al 25 revealed that a combination of 2-cADR with 1-ACDF in the middle level was prior to 2-ACCF for 3-level cddd. Because not all the diseased levels show the same type and extent of degeneration, it is reasonable to tailor the most suitable procedure according to the status of affected levels. In this study, a comparison between HC and ACHDF was performed in patients with 3-level cddd. Compared with preoperative status, HC showed significant improvements of NDI, JOA, and VAS scores at each follow-up, demonstrating a definite Figure 6. Both groups showed recovery of C2 C7 Cobb angle, but no difference was found between 2 groups; Wilcoxon test, a: P = 0.004; b: P = HC, hybrid construct; ACHDF, anterior cervical hybrid decompression and fusion. efficacy. Moreover, HC exhibited better NDI improvement than ACHDF at 12 and 24 months postoperatively, which was in accordance with previous studies. 15, 25 Furthermore, HC group also showed better JOA and VAS recovery at 24 months. With regard to intra- and postoperative parameters, there is no significant difference between 2 groups in terms of operation time, blood loss, and postoperative drainage, which may attribute to the same approach and decompression process. C2 C7 ROM decreased in both groups compared with preoperative status but significantly decreased in ACHDF group. Furthermore, superior and inferior adjacent-segment ROM increased significantly in ACHDF, whereas HC showed less compensatory ROM at adjacent levels. Our results were in close agreements with previous studies. 15, Despite no symptomatic ASD, which requires a further surgical intervention, was observed during 24-month follow-up, still we report here the radiological evidence of adjacent-segment degenerative changes. Two cases in both HC and ACHDF were found TABLE 4. Radiological Evidence of Adjacent-Level Changes HC (n = 13) ACHDF (n = 15) Statistical Value P New disc herniation 2/13 2/15 New osteophyte formation 0 2/15 New narrowing of disc space 0 0 New ALL calcification 0 0 Total* 2/13 4/ HC indicates hybrid construct; ACHDF, anterior cervical hybrid decompression and fusion; ALL, anterior longitudinal ligament. Spine

7 TABLE 5. Complications HC (n = 13) ACHDF (n = 15) Statistical Value P Operation-related complications Dysphagia 1/13 1/15 Hoarseness 1/13 1/15 C5 palsy 0 0 Cerebral fluid leakage 0 1/15 Epidural hematoma 0 1/15 Infection 0 0 Heterotopic ossification 1/13 0 Total* 3/13 4/ Device-related complications Subsidence 0 1/15 Dislodgment 0 0 Wear, breakage 0 0 Total* 0 1/ HC indicates hybrid construct; ACHDF, anterior cervical hybrid decompression and fusion. to have slightly new disc herniation, and 2 cases in ACHDF had new osteophyte formation. It is hard to clarify whether the changes were induced by fusion or native degeneration, yet the increased ROM at adjacent segments may predispose to ASD. 10, 27, 28 In contrast, less compensatory ROM may benefit for preventing ASD. 27, 28 A major advantage of anterior approaches for multilevel cddd is to restore the cervical lordosis. Lin et al 29 indicated that cervical lordosis improvement may contribute to better NDI scores. Du et al 30 revealed that JOA and NDI recovery are correlated with cervical lordosis improvement. In this study, reconstruction of cervical lordosis was achieved in both groups and the result was comparable. Therefore, HC may be equivalent to fusion for reconstruction of cervical lordosis with less compromised cervical ROM and subsequently may generate better clinical results. Dysphagia, hoarseness, and C5 palsy were recognized as common complications after multilevel anterior cervical surgery, and the morbidity was correlated to time-consuming and cervical lordosis restoration process. 31 In this study, 1 patient with dysphagia and 1 with hoarseness were found in each group but no C5 palsy occurred. One patient with cerebral fluid leakage and 1 with epidural hematoma were observed in ACHDF. No infection developed in both groups. Regarding device-related complications, 1 case with titanium mesh subsidence was found in ACHDF. No other complications were observed. It is beyond our goal to discuss the complications of various anterior fusion approaches, and ACHDF does exhibit superiority to multilevel ACDF or ACCF. 31 Despite no significant difference existed, HC seemed to be a safe procedure equally to ACHDF. For HC group, prevention of HO at cadr level is as important as solid fusion at the fused level. One patient developed HO but not severely (McAfee grade 1). Limiting the use of bone wax, slightly larger prostheses to fully cover the endplates, and administration of nonsteroidal anti-inflammatory drugs may benefit reducing HO. 16 Finally, all complications were attenuated gradually and none of them needed revision surgery. When simply combining cadr with fusion, one must be aware of the following questions: (1) Is the behavior of cadr adjacent to fusion comparable with that of stand-alone cadr? (2) Is the cadr adjacent to fusion able to accommodate the increased loads without undue wear during the expected life? (3) Can the fusion rate be affected by cadr? Several studies have been conducted toward the issues. Mobbs et al 32 performed cadr adjacent to a fused level, reporting that there was no prosthetic disc loosening and the disc had a good ROM. In a biomechanical study, Lee et al 33 revealed that fusion did not significantly affect the behavior of the cadr. Barbagallo et al 14 and Shin et al 15, as well as Cardoso et al 34 have demonstrated 100% fusion rate without any prosthesisrelated complication in HC. These results highlighted that fusion did not interfere with the normal function of cadr, and the cadr did not halt the fusion process. However, the biomechanics of 1-stage HC may not be analogous to performing cadr adjacent to a prior fused level where chronic adjacent-level hypermobility may have already developed. 35 Furthermore, ACCF would significantly increase the stress on adjacent segments compared with 1-ACDF. 36 Therefore, further biomechanical studies need to be explored on combining ACCF with cadr. For cadr, as a procedure similar to ACDF, we chose Mobi-C prosthesis because it is relatively simple, safe, and November 2014

8 reproducible for surgical insertion, and the implant holder easily allows the adjustment of position, axis, and depth. 37 Furthermore, this nonconstrained device has obvious advantages in design such as low-profile, mobile-bearing, and excellent mechanical properties Most importantly, Mobi-C is designed with elimination of features such as keels, screws, or implant protruding anterior to the disc space, all of which accommodate a multilevel surgical technique without risk of interference from adjacent-level implants. 41 Therefore, a Mobi-C prosthesis adjacent to an instrumented fusion may be rational and may potentially benefit the result of hybrid construct. However, there is a paucity of high-quality evidence for hybrid construct, 42 and the role of Mobi-C in hybrid construct needs to be further investigated in both biomechanical and clinical studies. A major limitation of this study is the nature of retrospective analysis, which may have potential bias. Another limitation is the small population with short-term follow-up. Furthermore, HC was limited to carefully selected patients according to the strict indications of cadr. Further large, randomized controlled trials are desired. CONCLUSION In this study, HC showed superiority to ACHDF in terms of equivalent or superior early clinical outcomes, less compromised C2 C7 ROM, and less impact at adjacent levels. Therefore, HC may be an alternative to ACHDF for 3-level cddd. Key Points ACHDF consisting of 1-ACCF and 1-ACDF was shown to be safe and effective for 3-level cddd. Compared with ACHDF, HC consisting of 1-ACCF and 1-cADR exhibited better NDI, JOA, and VAS improvements; less compromised C2 C7 ROM; and less impact at adjacent levels. HC may be an alternative to ACHDF for 3-level cddd. Supplemental digital content is available for this article. Direct URL citations appearing in the printed text are provided in the HTML and PDF version of this article on the journal s web site ( ). References 1. Rao RD, Gourab K, David KS. Operative treatment of cervical spondylotic myelopathy. J Bone Joint Surg Am 2006 ; 88 : Song KJ, Lee KB, Song JH. Efficacy of multilevel anterior cervical discectomy and fusion versus corpectomy and fusion for multilevel cervical spondylotic myelopathy: a minimum 5-year follow-up study. Eur Spine J 2012 ; 21 : Mummaneni PV, Kaiser MG, Matz PG, et al. Cervical surgical techniques for the treatment of cervical spondylotic myelopathy. J Neurosurg Spine 2009 ; 11 : Cunningham MR, Hershman S, Bendo J. Systematic review of cohort studies comparing surgical treatments for cervical spondylotic myelopathy. Spine 2010 ; 35 : Guo Q, Bi X, Ni B, et al. Outcomes of three anterior decompression and fusion techniques in the treatment of three-level cervical spondylosis. Eur Spine J 2011 ; 20 : Fraser JF, Hartl R. Anterior approaches to fusion of the cervical spine: a metaanalysis of fusion rates. J Neurosurg Spine 2007 ; 6 : Vaccaro AR, Falatyn SP, Scuderi GJ, et al. Early failure of long segment anterior cervical plate fixation. J Spinal Disord 1998 ; 11 : Sasso RC, Ruggiero RA, Jr Reilly TM, et al. Early reconstruction failures after multilevel cervical corpectomy. Spine 2003 ; 28 : Ashkenazi E, Smorgick Y, Rand N, et al. Anterior decompression combined with corpectomies and discectomies in the management of multilevel cervical myelopathy: a hybrid decompression and fixation technique. J Neurosurg Spine 2005 ; 3 : Lopez-Espina CG, Amirouche F, Havalad V. Multilevel cervical fusion and its effect on disc degeneration and osteophyte formation. Spine 2006 ; 31 : Liu F, Cheng J, Komistek RD, et al. In vivo evaluation of dynamic characteristics of the normal, fused, and disc replacement cervical spines. Spine 2007 ; 32 : Huppert J, Beaurain J, Steib JP, et al. Comparison between singleand multi-level patients: clinical and radiological outcomes 2 years after cervical disc replacement. Eur Spine J 2011 ; 20 : Auerbach JD, Jones KJ, Fras CI, et al. The prevalence of indications and contraindications to cervical total disc replacement. Spine J 2008 ; 8 : Barbagallo GM, Assietti R, Corbino L, et al. Early results and review of the literature of a novel hybrid surgical technique combining cervical arthrodesis and disc arthroplasty for treating multilevel degenerative disc disease: opposite or complementary techniques? Eur Spine J 2009 ; 18 ( suppl ): Shin DA, Yi S, Yoon DH, et al. Artificial disc replacement combined with fusion versus two-level fusion in cervical two-level disc disease. Spine 2009 ; 34 : ; discussion Ren X, Chu T, Jiang T, et al. Cervical disc replacement combined with cage fusion for the treatment of multi-level cervical disc herniation [published online ahead of print July 24, 2014]. J Spinal Disord Tech Medow JE, Trost G, Sandin J. Surgical management of cervical myelopathy: indications and techniques for surgical corpectomy. Spine J 2006 ; 6 : 233S 41S. 18. Hirabayashi K, Miyakawa J, Satomi K, et al. Operative results and postoperative progression of ossification among patients with ossification of cervical posterior longitudinal ligament. Spine 1981 ; 6 : Odom GL, Finney W, Woodhall B. Cervical disk lesions. J Am Med Assoc 1958 ; 166 : Takeshita K, Murakami M, Kobayashi A, et al. Relationship between cervical curvature index (Ishihara) and cervical spine angle (C2 7). J Orthop Sci 2001 ; 6 : Swank ML, Lowery GL, Bhat AL, et al. Anterior cervical allograft arthrodesis and instrumentation: multilevel interbody grafting or strut graft reconstruction. Eur Spine J 1997 ; 6 : Katsuura A, Hukuda S, Saruhashi Y, et al. Kyphotic malalignment after anterior cervical fusion is one of the factors promoting the degenerative process in adjacent intervertebral levels. Eur Spine J 2001 ; 10 : Traynelis VC. The prestige cervical disc. Neurosurg Clin N Am 2005 ; 16 : 621 8, vi. 24. Cardoso MJ, Rosner MK. Multilevel cervical arthroplasty with artificial disc replacement. Neurosurg Focus 2010 ; 28 : e Kang L, Lin D, Ding Z, et al. Artificial disk replacement combined with midlevel ACDF versus multilevel fusion for cervical disk disease involving 3 levels. Orthopedics 2013 ; 36 : e88 e Faizan A, Goel VK, Biyani A, et al. Adjacent level effects of bi level disc replacement, bi level fusion and disc replacement plus fusion in cervical spine a finite element based study. Clin Biomech (Bristol, Avon) 2012 ; 27 : Cho BY, Lim J, Sim HB, et al. Biomechanical analysis of the range of motion after placement of a two-level cervical ProDisc-C versus hybrid construct. Spine 2010 ; 35 : Spine

9 28. Eck JC, Humphreys SC, Lim TH, et al. Biomechanical study on the effect of cervical spine fusion on adjacent-level intradiscal pressure and segmental motion. Spine 2002 ; 27 : Lin Q, Zhou X, Wang X, et al. A comparison of anterior cervical discectomy and corpectomy in patients with multilevel cervical spondylotic myelopathy. Eur Spine J 2012 ; 21 : Du W, Wang L, Shen Y, et al. Long-term impacts of different posterior operations on curvature, neurological recovery and axial symptoms for multilevel cervical degenerative myelopathy. Eur Spine J 2013 ; 22 : Liu Y, Qi M, Chen H, et al. Comparative analysis of complications of different reconstructive techniques following anterior decompression for multilevel cervical spondylotic myelopathy. Eur Spine J 2012 ; 21 : Mobbs RJ, Mehan N, Khong P. Cervical arthroplasty for myelopathy adjacent to previous multisegmental fusion. J Clin Neurosci 2009 ; 16 : Lee MJ, Dumonski M, Phillips FM, et al. Disc replacement adjacent to cervical fusion: a biomechanical comparison of hybrid construct versus two-level fusion. Spine 2011 ; 36 : Cardoso MJ, Mendelsohn A, Rosner MK. Cervical hybrid arthroplasty with 2 unique fusion techniques. J Neurosurg Spine 2011 ; 15 : Phillips FM, Allen TR, Regan JJ, et al. Cervical disc replacement in patients with and without previous adjacent level fusion surgery: a prospective study. Spine 2009 ; 34 : Martin S, Ghanayem AJ, Tzermiadianos MN, et al. Kinematics of cervical total disc replacement adjacent to a two-level, straight versus lordotic fusion. Spine (Phila Pa 1976) 2011 ; 36 : Park JH, Roh KH, Cho JY, et al. Comparative analysis of cervical arthroplasty using mobi-c(r) and anterior cervical discectomy and fusion using the solis(r) -cage. J Korean Neurosurg Soc 2008 ; 44 : Beaurain J, Bernard P, Dufour T, et al. Intermediate clinical and radiological results of cervical TDR (Mobi-C) with up to 2 years of follow-up. Eur Spine J 2009 ; 18 : Kim SH, Shin HC, Shin DA, et al. Early clinical experience with the mobi-c disc prosthesis. Yonsei Med J 2007 ; 48 : Lee SH, Im YJ, Kim KT, et al. Comparison of cervical spine biomechanics after fixed- and mobile-core artificial disc replacement: a finite element analysis. Spine (Phila Pa 1976) 2011 ; 36 : Davis RJ, Kim KD, Hisey MS, et al. Cervical total disc replacement with the Mobi-C cervical artificial disc compared with anterior discectomy and fusion for treatment of 2-level symptomatic degenerative disc disease: a prospective, randomized, controlled multicenter clinical trial: clinical article. J Neurosurg Spine 2013 ; 19 : Jia Z, Mo Z, Ding F, et al. Hybrid surgery for multilevel cervical degenerative disc diseases: a systematic review of biomechanical and clinical evidence. Eur Spine J 2014 ; 23 : November 2014