How often is adjacent segment disease reported?

         Degenerative changes in the cervical spine causing symptomatic myelopathy and/or radiculopathy are common indications for anterior cervical decompression and fusion (ACDF). ACDF has a disease-free survival rate of 86% at 5 years and is considered the gold standard to treat these conditions.1 Despite the success of ACDF in this setting, symptomatic adjacent segment disease (ASD) remains a concern as a long-term complication of this intervention. ASD is the onset YSSPS : 446 Model7 pp:126ðcol:fig: : NILÞ 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1040-7383/$ - see front matter & 2013 Published by Elsevier Inc. n Q5 Corresponding author. E-mail address: (K. Radcliff). S EMIN S PINE S URG ] (2013) ]]] – ]]] of degenerative changes adjacent to the site of a successful arthrodesis severe enough to cause symptoms of radiculopathy or myelopathy. The incidence of ASD has been widely accepted as 2.9% per year and 25.6% over 10 years after cervical fusion.1 The cause of ASD, however, remains widely debated. Although some authors believe the incidence represents a natural progression of cervical disc disease, others suggest that this process is iatrogenic due to altered biomechanics at levels adjacent to an arthrodesis.2,3 Concern for adjacent levels has spawned the development of motion-preserving interventions such as total disc arthoplasty (TDA). Previous studies have shown the biomechanical and radiographic advantages of TDA over ACDF.4–6 These remain, however, secondary measures of disc preservation. Secondary measures are useful, but cannot be definitely linked to a decrease in ASD as the etiology of the disease is not fully known. 

         This systematic review aims to identify those prospective studies reporting the incidence of ASD between ACDF and TDA. Our hypothesis is that ASD is overall under reported in randomized trials. We aim to highlight the importance of reporting ASD as an outcome in future prospective studies. 2. Methods 2.1. Selection of papers for review Medline and Cochrane databases were searched to uncover relevant studies. The criteria for inclusion in this review are T1 listed in Table 1. Prospective, comparative studies (level I, level II, or level III) comparing a population of patients who underwent ACDF versus a population who underwent TDA for single- and two-level degenerative cervical disease (myelopathy or radiculopathy) were included in the initial literature search. To be included in this review, studies needed to have at least 2 years of follow-up and needed to report the incidence of ASD in their study populations. Other primary outcomes (e.g. clinical outcomes, radiographic findings, and/or complication rates) of TDA compared to ACDF were not evaluated. Although clinical success in the reviewed literature is reported in our discussion, it is not the focus of this review. Retrospective studies and non-comparative studies were excluded.

         In addition, studies that reported data from a single clinical site part of a multicenter trial were eliminated to avoid repetition of results. Studies that published papers reporting results from the same clinical trial were excluded, and only the article reporting the longest follow-up of the study was included. 2.1.1. Medline (PubMed) The evidence-based method PICO6 (P: population of interest, I: intervention, C: comparison intervention, and O: outcome of interest) was used to create the following search in PubMed: {[(“Cervical Vertebrae”(Mesh) AND “Radiculopathy” (Mesh)) OR “Spinal Cord Diseases”(Mesh)] AND [“Arthrodesis”(Mesh) OR “Arthroplasty, Replacement”(Mesh)]}. This search produced 1889 results. Also, a simple MEDLINE text search for “cervical disc arthroplasty,” “cervical disc replacement,” “total disc replacement,” and “total disc arthroplasty” was used to produce 853 results. When pooled, these two searches produced 2690 unique results.

         These results were then screened with the previously described criteria to find papers suitable for inclusion (Fig. 1). F1 2.1.2. The Cochrane Library In a similar fashion, the Cochrane Library was searched for “cervical disc arthroplasty,” “cervical disc replacement,” “total disc replacement,” and “total disc arthroplasty.” This produced 106 clinical trial results. These results were again screened using the inclusion and exclusion criteria. No additional unique studies were captured by this method (Fig. 2). F2 3. Results Data from the six studies in this review were pooled. The overall sample size was 1586 (ACDF ¼ 777, TDA ¼ 809) and at final follow-up was 1110, giving an overall follow-up of 70%. Of 1586 surgically treated patients, 51 (3.2%, ACDF ¼ 30, TDA ¼ 21) required revision surgery at an adjacent level at 2–5 years of follow-up (Table 2). T2 YSSPS : 446 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 Table 1 – Criteria used for inclusion and exclusion in our systematic review.

         Inclusion Exclusion Prospective study design Greater than or equal to 2 year follow-up Comparative study of cervical arthroplasty and cervical arthrodesis Examines adjacent level degeneration or secondary surgery for adjacent level degeneration Animal studies Retrospective studies, meta-analyses, biomechanical or kinematic studies, review articles, or in vitro studies Single site results as a part of multicenter trial (to avoid repetition of data) Non-comparative studies Non-prospective studies Less than 2 years of follow-up Does not address adjacent level degeneration or secondary surgery for adjacent level degeneration Published in languages other than English Studies that examine lumbar disc replacement 2 S EMIN S PINE S URG ] (2013) ]]] – ]]] 3.1. Review of studies Ultimately, six studies were selected. These studies were all randomized controlled trials (RCT) with at least 2 years of follow-up that specifically compared TDA versus ACDF.

         Nabhan et al.7 conducted a 3-year, prospective, randomized, controlled trial with 41 patients randomized to ACDF (n ¼ 21) and arthroplasty (n ¼ 20) with 3 years of follow-up. Although the sample size was limited, there was one reported case of ASD in the fusion group, but none in the arthoplasty group after 3 years of follow-up. Although segmental motion was significantly improved between arthroplasty and ACDF, the scarcity prevents any comparison of ASD rates. Porchet et al.8 described early experiences with the Prestige II cervical disc. They conducted a multicenter, prospective study with 55 patients randomized to arthroplasty (n ¼ 27) and ACDF with iliac crest autograph (n ¼ 28). No patients suffered from adjacent level disease at 2 years. This study reported on the early efficacy of the Prestige cervical disc and met the inclusion criteria of this review. However, the vast majority of patients were lost to follow-up by 2 years (83% lost to follow-up). Sasso et al.9 conducted a prospective, randomized, controlled trial with 463 patients.

         Of the total, 319 patients completed 4 years of follow-up. Patients were randomized to either the arthroplasty (investigation) or ACDF (control) group. The Bryan disc was the investigatory device used in the arthroplasty group. At the 4-year postoperative mark, Q7 overall success was improved in the arthoplasty group (85.1%) as compared with the fusion group (72.5%). At 4 years, the rate of revision surgery for ASD was equivocal between the treatment groups: ten revisions performed in the TDA group compared with nine revisions in the fusion group. At 4 years of postoperation, follow-up data was available from 62% of the patients obtaining a fusion as compared with 75% of patients obtaining an arthroplasty. Coric et al.10 reported results from a prospective clinical trial with 269 patients randomized to ACDF or TDA. The investigatory device in this study was the Kineflex|C. At the 2-year postoperative mark, overall success was improved in the arthoplasty group (85%) as compared to the fusion group (71%). Follow-up rate was excellent at 2 years (89%, n ¼ 239). At 2-year follow-up, 24.8% of ACDF patients showed radiographic signs of severe ASD as compared to 9% in the TDA group. Range of motion improved as well in the TDA group.

         Surgery for ASD was equivalent: seven patients in the ACDF group and nine patients in the TDA group. Murrey et al.11 conducted a prospective clinical trial with ProDisc-C and reported outcomes at 2 years from surgery. A total of 209 patients were randomized to either the arthroplasty (investigation, n ¼ 103) or ACDF (control, n ¼ 106) group. At 2 years, there was a 96.5% follow-up rate. Success rate was equivocal: 84.8% in the TDA group compared to 85.9% in the ACDF group. Although nine patients in the fusion group and two patients in the ACDF group required repeat Q8 surgery for various reasons, only one revision in the ACDF group was performed due to ASD. Burkus et al.12 conducted a non-IDE clinical trial with the Prestige disc. Patients were followed for 5 years postoperatively.

         Patients were randomized to either the arthroplasty (investigation, n ¼ 276) or ACDF (control, n ¼ 265) group. At 5 years, there was follow-up data from 52.2% of TDA patients (n ¼ 127) and 47.9% of ACDF patients (n ¼ 144). At 5 years, there was a trend toward improved success in the YSSPS : 446 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 Fig. 1 – Search protocol used for systematic review of the literat Q9 ure in PubMed. (Color version of figure is available online.) Fig. 2 – Search protocol used for systematic review of the literature in Cochrane Library. (Color version of figure is available online.) S EMIN S PINE S URG ] (2013) ]]] – ]]] 3 arthoplasty group (95.0% versus 88.9%, p ¼ 0.051). There were 13 patients requiring surgery for ASD in the ACDF group compared with eight patients in the TDA group (10.2% versus 5.5%, respectively). This difference was not statistically significant. 4.

         Discussion Numerous studies have sought to compare clinical and radiographic outcomes between cervical fusion and cervical disc arthoplasty. No study has shown a reduced incidence of adjacent segment disease that is managed by either nonoperative or operative means. In addition, limited clinical data is available regarding the proportion of patients with ASD who go on to require surgical intervention. Secondary measures—beyond the scope of this review—have been well reported, including biomechanical studies, radiographic analyses, and assessment of clinical outcomes with validated outcome questionnaires. These secondary measures have all shown some promise for disc replacement over single-level fusion. Development of adjacent segment pathology has led to an expansion of motion-preserving implants that promise to better mimic normal cervical kinematics and therefore reduce re-operations at adjacent level. This review aimed to identify prospective studies comparing ACDF versus TDA that included reoperation for ASD as an outcome measure. The incidence of new-onset ASD, however, has not been well reported in prospective studies, only the incidence of repeat surgery to include an adjacent level.

         Therefore, these studies necessarily exclude patients who develop symptomatic ASD and choose to undergo nonsurgical treatment. Furthermore, there is a significant difference in the incidence of patients who undergo reoperation for ASD following ACDF inside and outside the parameters of an IDE trial.13 For the trials reviewed, the rates of reoperation for ASD are equivalent between fusion and arthoplasty groups.9–11 Overall, there was a 3.2% reported rate of re-operation due to ASD at 2–5 years of follow-up. In the same way, the number of patients with ASD who were managed non-operatively is unclear. Future studies may benefit from a systematic assessment and documentation of patient symptoms attributable to an adjacent level, improved patient follow-up, and reporting of both operative and non-operative treatments utilized for patients who develop ASD.


1 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. 1999;81:519–528.

2 Lund T, Oxland TR. Adjacent level disk disease—is it really a fusion disease? Orthop Clin North Am. 2011;42:529–541 [viii].

3 Hilibrand AS, Robbins M. Adjacent segment degeneration and adjacent segment disease: the consequences of spinal fusion? Spine J. 2004;4:190S–194S.

4 DiAngelo DJ, Roberston JT, Metcalf NH, McVay BJ, Davis RC. Biomechanical testing of an artificial cervical joint and an anterior cervical plate. J Spinal Disord Tech. 2003;16:314–323.

5 Wigfield C, Gill S, Nelson R, Langdon I, Metcalf N, Robertson J. Influence of an artificial cervical joint compared with fusion on adjacent-level motion in the treatment of degenerative cervical disc disease. J Neurosurg. 2002;96:17–21.

6 Bragge P. Asking good clinical research questions and choosing the right study design. Injury. 2010;41(suppl 1):S3–S6.

7 Nabhan A, Steudel WI, Pape D, Ishak B. Segmental kinematics and adjacent level degeneration following disc replacement versus fusion: RCT with three years of follow-up. J Long Term Eff Med Implants. 2007;17:229–236.

8 Porchet F, Metcalf NH. Clinical outcomes with the Prestige II cervical disc: preliminary results from a prospective randomized clinical trial. Neurosurg Focus. 2004;17:E6.

9 Sasso RC, Anderson PA, Riew KD, Heller JG. Results of cervical arthroplasty compared with anterior discectomy and fusion: four-year clinical outcomes in a prospective, randomized controlled trial. J Bone Joint Surg Am. 2011;93:1684–1692.

10 Coric D, Nunley PD, Guyer RD, et al. Prospective, randomized, multicenter study of cervical arthroplasty: 269 patients from the Kineflex|C artificial disc investigational device exemption study with a minimum 2-year follow-up: clinical article. J Neurosurg Spine. 2011;15:348–358.

11 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. 2009;9:275–286.

12 Burkus JK, Haid RW, Traynelis VC, Mummaneni PV. Long-term clinical and radiographic outcomes of cervical disc replacement with the Prestige disc: results from a prospective randomized controlled clinical trial. J Neurosurg Spine. 2010; 13:308–318.

13 Singh K, Phillips FM, Park DK, Pelton MA, An HS, Goldberg EJ. Factors affecting reoperations after anterior cervical discectomy and fusion within and outside of a Federal Drug Administration investigational device exemption cervical disc replacement trial. Spine J. 2012;12:372–378.

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