For about half a century, anterior cervical discectomy and fusion (ACDF) has been the most widely used surgical technique for achieving cervical arthrodesis. In more recent years, the development of segmental posterior instrumentation has allowed spine surgeons to effectively manage multilevel stenosis combined with kyphosis and other complex deformities that develop in patients with advanced cervical spondylosis. What are the long-term consequences for spinal motion segments adjacent to these fusions?
In a classic study evaluating the long-term outcomes of ACDF in 374 consecutive patients with radiculopathy and/or myelopathy due to cervical spondylosis, Hilibrand et al1 determined that symptomatic adjacent segment changes occurred at a relatively constant rate of 2.9% per year, with 19% of patients symptomatic from adjacent segment disease (ASD) after a decade. After adjusting for the loss of follow-up over time, Kaplan-Meier analysis predicted that more than 25% of all patients would develop ASD during the first 10 years after ACDF.
Adjacent-level degeneration is reported in multiple studies, after both anterior and posterior fusions, single and multilevel; however, the reported incidence of this condition varies (Figure 1). Biomechanical studies suggest that the phenomenon may be due to increased adjacent-segment motion at the levels above and below a cervical fusion, and this effect is increased with multilevel fusions.2
It is important to differentiate between adjacent-segment degeneration, which is radiographical evidence of degeneration at the levels adjacent to a previous fusion, from ASD, which is the development of clinically significant symptoms and signs that correlate with imaging evidence of degeneration adjacent to a previous fusion. The true nature and scope of ASD remains poorly understood. Anatomical changes that develop many years after a fusion may be debated as being the result of the normal aging process rather than a consequence of eliminating spinal motion at the adjacent segment.3 The pathophysiology of ASD (mechanical and biological aspects) needs to be better understood so that it can be more accurately defined, classified, and studied in terms of its natural history.4
As noted elsewhere in this Focus Issue there is a lack of precision regarding the terminology used to describe these entities. The term adjacent-segment pathology (ASP) is proposed as an umbrella term to refer to the breadth of clinical and/or radiographical changes at adjacent motion segments that developed subsequent to a previous spinal intervention. Under this umbrella, radiological ASP and clinical ASP (CASP) are then used to categorize radiographical features (e.g., degenerative changes on magnetic resonance imaging) and clinical manifestations (e.g., new radiculopathy), respectively. The focus of this article is on “symptomatic ASD” in the cervical spine requiring treatment, which will be referred to as CASP to describe the results and future directions. The term ASD is retained for describing search methods and definitions used by authors of included articles.
Because spine surgeons have become more aware of the risks of ASP, motion-sparing options such as disc arthroplasty and methods of decompression that spare or limit damage to the stabilizing posterior structures (i.e., laminoplasty) have increased in popularity.5–7 The objective of this study is not to evaluate whether some surgical techniques are most likely to be associated with CASP—this is covered in this Focus Issue in articles under the section “Cervical: Prevention”. Rather, this systematic review focuses on a common problem faced by spine surgeons: what is the best method to treat a patient with CASP? We will attempt to answer the following key clinical questions:
Q1: What is the comparative effectiveness and safety of operative versus nonoperative treatments for cervical CASP?
Q2: Describe the outcomes of surgical treatment of cervical CASP.
MATERIALS AND METHODS
Electronic Literature Search
A systematic search of PubMed, the Cochrane Library, and Google Scholar for literature published through March 2, 2012. Only studies in humans, written in English language, and containing abstracts were considered for inclusion, but no limits were placed on the search. The focus was on identification of studies explicitly designed to evaluate the treatment of cervical ASD after previous cervical spine surgery. The search strategy included use of controlled vocabulary (medical subject headings [MeSH] and terms) and key words. Terms specific to ASD included: ASD, adjacent-segment breakdown, adjacent-segment degeneration, adjacent-segment biomechanical consequences, adjacent-segment biomechanics, adjacent-level disease, adjacent-level breakdown, adjacent-level degeneration, or adjacent-level biomechanical consequences. They were combined with terms specifying the cervical spine (“cervical vertebrae” [MeSH] or cervical [TIAB]) and those related to treatment or surgery. Studies comparing treatments for ASD were specifically sought. In the absence of comparative studies to answer the first 2 questions, case series were included to answer question 3. Case reports, meeting abstracts/proceedings, white papers, and editorials were excluded. The Pico table provides additional information on inclusion/exclusion criteria (Table 1).
From the included articles, the following data were extracted: study design and study purpose, patient demographics, inclusion and exclusion criteria, follow-up duration and the rate of follow-up for each treatment group, treatment interventions, and definition of ASD provided by the individual authors.
Study Quality and Overall Strength of Body of Literature
Level of evidence ratings were assigned to each article independently by 2 reviewers (E.M.V., A.S.) using criteria set by The Journal of Bone and Joint Surgery8 for therapeutic studies and modified to delineate criteria associated with methodological quality and described elsewhere (see Supplemental Digital Material, Supplemental Digital Content 1, available at http://links.lww.com/BRS/A701 for individual study ratings).9 The overall body of evidence with respect to each clinical question was determined based on precepts outlined by the Grades of Recommendation Assessment, Development and Evaluation working group10 and recommendations made by the Agency for Healthcare Research and Quality.11 Risk of bias was evaluated during the individual study evaluation described earlier in the section “Study Quality.” This system, which derives a strength of evidence grade for each outcome or clinical question of “high,” “moderate,” “low,” or “insufficient,” is described in further detail in the methods article for this focus issue.9 The supplemental digital material contains the details of how we arrived at the strength of evidence for each key question (see Supplemental Digital Content 1, available at http://links.lww.com/BRS/A701).
Descriptive statistics for all studies were reported because there was only 1 comparative study identified. If reported by the authors, risk factors that were associated with outcome were reported based on the analytical statistics reported by the authors.
Clinical Recommendations and Consensus Statements
Clinical recommendations or consensus statements were made through a modified Delphi approach by applying the Grades of Recommendation Assessment, Development, and Evaluation/Agency for Healthcare Research and Quality criteria that imparts a deliberate separation between the strength of the evidence (i.e., high, moderate, low, or insufficient) from the strength of the recommendation. When appropriate, recommendations or statements “for” or “against” were given “strong” or “weak” designations based on the quality of the evidence, the balance of benefits/harms, and values and patient preferences. In some instances, costs may have been considered. A more thorough description of this process can be found in the focus issue methods article.9
The search strategy yielded 234 potentially relevant citations; of these, 224 were excluded based on title and/or abstract. Ten were selected for full-text review. Five additional studies were excluded on the basis of full-text review. One did not report on treatment of ASD,12 1 reported on lumbar ASD treatment,13 1 had a sample size fewer than 10 patients,14 in 1 it was not clear whether the intervention was at the original index level or at an adjacent level but it seemed that only 9 patents may have been treated for ASD,15 and in 1 study of artificial disc replacement (ADR), outcomes for those receiving ADR after fusion were not separated from those receiving primary ADR.16
A total of 5 studies were selected for inclusion and are summarized in this report (Figure 2). Table 2 provides a summary of characteristics for included studies.
Q1: What is the comparative effectiveness and safety of operative versus nonoperative treatments for cervical CASP?
No comparative studies were found to answer this question.
Q2: Describe the outcomes of surgical treatment of cervical ASP.
The evidence base available to answer this question consisted of 5 studies: 1 comparative study17 and 4 case series of more than 10 patients.5–7,18 The comparative study17 and 1 series described fusion,18 2 evaluated laminoplasty5,6 and 1 reported on use of artificial discs.7 No studies describing subsequent development or advancement of CASP after reconstructive surgery were found.
Two small level of evidence IV case series evaluated laminoplasty for treatment of clinical ASP.5,6 Clinical outcome based on Japanese Orthopaedic Association score recovery rate was reported in both studies with 38% of the patients being categorized as having excellent or good outcome in the largest study6 and 55% in the smaller study.5 Operative indication reportedly did not influence recovery rate in the larger study, but results from the smaller study suggest otherwise (Table 3).
Two poor-quality (level of evidence III) retrospective cohort studies compared ACDF with corpectomy for the treatment of CASP after previous cervical surgery.17,18 One study, however, evaluated only 7 persons with corpectomy and fusion and was therefore treated as a case series study because no meaningful comparisons could be made.18
The retrospective cohort study (level of evidence III) by Hilibrand et al17 studied persons who had previous anterior cervical decompressive procedures with arthrodesis who then presented with signs and symptoms of new ASD (new radiculopathy in a distribution referable to segments adjacent to previous anterior cervical fusion combined with radiographical evidence of degeneration) and in whom cervical orthosis, physical therapy, and anti-inflammatory medications failed to relieve symptoms. Other surgical indications included persistent radiculopathy (with or without neurological deficit) and myelopathy with spinal cord compression on imaging. Single-level ACDF (autogenous iliac crest graft) was done in 11 patients and multilevel in 13 patients. Subtotal vertebrectomy or corpectomy with fusion using strut grafting with autogenous iliac crest grafting used in 1- and 2-level corpectomies and fibular graft in 3-level procedures. With the exception of 6 patients who had 3-level corpectomy who were immobilized in a halo vest (6 wk), all others had a rigid orthosis for 6 wk. Only patients with a minimum of 2-year follow-up were analyzed and mean follow-up time was 68 months (24–183 mo). The basis for allocation to the treatment groups was not described. A 37.5% risk difference favoring corpectomy was observed and the majority of persons in both treatment groups had excellent or good clinical results (Table 4). The authors report no difference in arthrodesis rates between single- and multilevel procedures for the discectomy group. Overall, 26 of 29 patients with solid fusion had excellent or good clinical results.
Gause et al18 documented solid arthrodesis in 81.6% (40/49) of the patients with CASP treated with ACDF. Union rates based on whether arthrodesis was performed in segments cranial or caudal to the index fusion or both were 89.3% (25/28), 75% (12/16), and 33% (1/3), respectively, with the author reporting a marginally significant difference (P = 0.05) for the influence of location (Table 5). Nonunion occurred in 23.1% (3/13) of those using tobacco products compared with 16.7% (3/18) who did not.
One study reported treatment of symptomatic cervical ASP with the use of porous coated motion artificial discs.7 A subgroup of 26 patients who had previous “adjacent level” fusion surgery were compared with the other 126 patients in the porous coated motion artificial cervical disc Investigational Device Exemption trial who did not have a previous fusion (“primary” group). Both groups had similar outcomes (neck disability index and visual analog scores) at all time points; however, large SDs suggest great variability (lack of stability) in the estimates (Table 6). Phillips et al7 concluded that disc replacement adjacent to a previous fusion had comparable outcomes to primary disc replacement surgery, but given the small number of subjects in the “adjacent level” group, and limited follow-up, definitive conclusions could not be made.
The overall strength of evidence on the treatment of CASP in the cervical spine was deemed to be insufficient, indicating that we have low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the effect estimate and it is likely to change the estimate of effect given that the evidence either is unavailable or does not permit a conclusion (Table 7).
In an analysis of trends and variations in Medicare claims for cervical spine surgery in the United States between 1992 and 2005, the most common procedure was cervical fusion (70%), with anterior cervical fusion accounting for 58% of all cervical spine surgery.19 Even after demographic adjustment, rates of cervical fusions rose 206% during that time (14.7–45 cervical fusions/100,000 beneficiaries with the relative increase calculated as 45–14.7 cervical fusions, divided by 14.7/100,000 in 1992) (P < 0.05). Meanwhile, rates of posterior nonfusion surgery remained relatively stable. Although cervical disc arthroplasty is increasingly popular, it is still dwarfed by cervical fusion. Furthermore, as patients live longer after surgery, it is foreseeable that ASP will develop in increasing numbers of patients.
In recent years, surgical techniques that aim to prevent ASP, in particular disc arthroplasty, are responsible for an ever-expanding body of literature regarding the relative merits (in the short term and the long term) of these devices compared with fusion. On the contrary, the peer-reviewed literature regarding treatment of cervical CASP is rather scarce. What is the surgeon to do when confronted with a patient with myelopathy, refractory radiculopathy, or mechanical pain that correlates with imaging evidence of cervical CASP? We undertook this systematic review to critically review and summarize the evidence in an attempt to determine the best treatment(s).
There were no comparative studies regarding the effectiveness and safety of operative versus nonoperative treatments for cervical CASP. However, it makes sense that nonoperative treatments (medications, mechanical therapies, etc.) should be attempted first for all but the most symptomatic patients (e.g., severe myelopathy or significant mechanical pain due to overt instability). Initial treatment for most patients with cervical CASP would thus be the same as for those patients who have not had a previous fusion.
There is insufficient evidence from the 1 small, poor quality comparative study identified to evaluate the comparative effectiveness of ACDF with corpectomy.17 All revision surgery described in this series was apparently noninstrumented, and therefore it is difficult to generalize the results to current practice. Potential biases in this study include loss to follow-up (inclusion of only those with a minimum 2-yr follow-up) and factors used to determine which procedure to perform. This study is likely to be underpowered to detect differences between treatments, particularly for rare events.
Gause et al18 demonstrated that fusion was related to the number of preoperative levels fused (P = 0.03), but not the number of levels currently undergoing arthrodesis adjacent to the previous fusion (P = 0.10). The fusion rate for single-level ACDF next to a 1-level fusion was 95.2%, but dropped significantly when performed in patients who had previous 2-level (81.3%) or 3-level (57.1%) arthrodesis, despite the use of instrumentation and iliac crest autograft. The influence of location was only marginally significant, but ACDF performed caudal to a previous fusion had a lower rate of arthrodesis (75%) compared with rostral (89.3%). Probably, the most relevant data from this study is that ACDF or corpectomy with tricortical iliac crest autograft and plating achieved a solid fusion in only 81.6% of patients with ASD. It is reasonable to consider adjunctive posterior stabilization to optimize the fusion rate in high-risk cases.
Matsumoto et al6 reported that although moderate neurological recovery was achieved in patients with myelopathy due to stenosis adjacent to a previous ACDF, the results were not as satisfactory as those who received open-door laminoplasty as the initial surgery. The average recovery rate of Japanese Orthopaedic Association scores was 37.1% and 50.0%, respectively. Baba et al5 had a smaller series (n = 18) and no primary myelopathy controls. The overall Japanese Orthopaedic Association score improvement rate was 51% in that study, with excellent (>75%) or good (50%–74%) neurological recovery found in just over half of the patients.
Phillips et al7 provided the only prospective study identified in this systematic review. However, as noted, the limited number of patients in the ASD group (n = 26) significantly limited statistical power. Surgery time, blood loss, and clinical outcome (Neck Disability Index, visual analogue scale pain scores) were similar between patients who underwent disc arthroplasty adjacent to fusion and patients with primary disc arthroplasty. The porous coated motion device restored motion at the operated adjacent level, and the range of motion of the disc arthroplasty level was generally increased over levels seen in primary disc arthroplasty. This is likely due to kinematic alterations imposed on the level adjacent to the fusion. Increased intradiscal pressures, high shear strains, and increased motion relative to the unoperated spine all place increased demands on the prosthesis. Phillips et al7 blame these factors for early migration of the prosthesis in 2 patients. A major limitation of this study is relatively short follow-up (12 mo) considering the long-term need for durability of the construct. In addition, the stability of the estimates (large SDs) needs to be considered.
It is important to consider the symptomatology and imaging carefully in determining the most appropriate surgical strategy for cervical CASP. In the articles we reviewed, fusion was performed for radiculopathy or myelopathy,17,18 but would also be indicated for mechanical neck pain due to instability. Laminoplasty was indicated for myelopathy.5,6 Disc arthroplasty was limited to radiculopathy or mild myelopathy, with no evidence of cervical instability or congenital canal stenosis.7
There is a dearth of information about the treatment of CASP in the literature. Although limited data are available from the included studies on the use of laminoplasty, fusion, and one type of arthroplasty; the small sample sizes, limited follow-up, quality of most studies, and stability of estimates preclude making conclusions regarding treatment options. No studies on use of laminectomy, foraminotomy, or posterior decompression and fusion were found. Studies with sufficient statistical power that carefully document the development and manifestations of ASP (using standard definitions) and directly compare treatment options are needed. Competent evaluation of treatment options needs to include measurement and evaluation of potential confounding factors (e.g., age, severity of CASP and types of symptoms, type of index treatment, timing of treatment, comorbidities). In addition, future studies should use validated outcomes measures and defined study protocols with explicit criteria for diagnosis, treatment, and follow-up.
CONSENSUS STATEMENTS AND CLINICAL RECOMMENDATIONS
- Arthroplasty, laminoplasty and fusion for treatment of cervical CASP were described in the studies found. These seem to be effective for treatment of cervical CASP. No studies on foraminotomy, laminectomy and posterior decompression and fusion were found.
Level of Evidence: Insufficient
Strength of Statement: Strong
Recommendation #1: Despite the importance of this topic, a dearth of literature was found. We recommend further studies on this topic
Level of Evidence: Insufficient
Strength of Recommendation: Strong
- There are little data regarding the optimal treatment for cervical ASP.
- There are no comparative data to guide best option(s) for surgical management.
- Case series report favorable results for fusion, laminoplasty, and disc arthroplasty, but small patient numbers and largely retrospective methodology limit definitive conclusions. No studies of other treatment options were found.
The authors thank Nancy Holmes, RN, and Chi Lam for their administrative assistance and Daniel Hadidi and Ellen VanAlstyne for assistance with data abstraction and literature searching. The authors J.D. and D.F. contributed toward study concept, interpretation, manuscript preparation, and manuscript revision. Author A.C.S. contributed toward data analysis and interpretation, manuscript preparation, and manuscript revision.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.spinejournal.com).
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