Adjacent segment pathology (ASP) continues to be a challenge for spine providers. Since Hilibrand's landmark study1 in the cervical spine reporting a 25.6% likelihood for surgery at a level adjacent to a fusion within 10 years, there has been substantial discussion, research, and innovation devoted to the understanding, treatment and prevention of ASP. Indeed, ASP has been perhaps the most important driving force to the development of motion preservation technology in the spine.
Although the existence of ASP is universally accepted, the etiology for ASP is not. Cadaveric motion simulator studies have reported hypermobility and increased forces at levels adjacent to arthrodesed segment, thus suggesting that ASP is iatrogenically biomechanical in origin. Other authors have opined that ASP is a natural progression of arthritic disease rather than an effect of the fusion. Although Hilibrand's study is cited in motion preservation reports as ground for its development, it is interesting to note that the authors opined in this often-quoted study that “symptomatic adjacent segment disease is a result of progressive spondylosis... and that it is probably unaffected by the operative management.”
It seems somewhat intuitive that at least to some degree, the pre-existing degeneration at levels adjacent to an arthrodesis is likely to play a role in the development of clinical adjacent segment pathology. Although spinal arthrodesis occurs in patients with degenerative spinal disease, it also occurs in the pediatric and trauma population, as well as congenitally. Evaluating the risk of ASP in these populations may shed light on its etiology. Therefore, the purpose of this systematic review is to determine whether the following indications or reasons for spinal fusion are associated with different risks of subsequent radiographical adjacent segment pathology (RASP) in the lumbar and cervical spine:
- Surgical fusion for degenerative disease.
- Surgical fusion as a result of trauma.
- Surgical fusion for pediatrics conditions.
- Congenital fusion.
MATERIALS AND METHODS
Electronic Literature Search
A systematic search was conducted for articles published between January 1990 and December 2011. We searched PubMed and the Cochrane Library using key words to detect articles that used the term “adjacent segment” or “adjacent level” combined with cervical or lumbar spine fusion or congenital fusion. We limited our results to humans and to articles published in the English language. We included articles that reported ASP following fusion for degenerative disease, trauma, or conditions requiring fusion in the pediatric population. We also included studies recording RASP in patients with congenital fusion. We excluded articles that did not report ASP as an outcome. Other exclusions included case reports and studies with less than 10 subjects, as described in Table 1. Full text of potential articles meeting the inclusion criteria by both methods were reviewed by 2 independent investigators (J.R.D., M.J.L.) to obtain the final collection of included studies (Figure 1).
From the included articles, the following data were extracted: study design, patient demographics, study purpose, inclusion and exclusion criteria, follow-up duration and the rate of follow-up, indication for fusion, definition of ASP, and incidence or prevalence of ASP.
Study Quality and Overall Strength of Body of Literature
Level of evidence ratings were assigned to each article independently by 2 reviewers (C.E., J.R.D.) using criteria set by The Journal of Bone & Joint Surgery, American Volume2 for prognostic studies and modified to delineate criteria associated with methodological quality described elsewhere3 (see Appendix, Supplemental Digital Content 1, available at: http://links.lww.com/BRS/A694, for individual study ratings). 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 (GRADE) working group4 and recommendations made by the Agency for Healthcare Research and Quality (AHRQ).5 Risk of bias was evaluated during the individual study evaluation as described above. 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.3 The supplemental digital material contains the details of how we arrived at the strength of evidence for each key question (see Appendix, Supplemental Digital Content 1, available at: http://links.lww.com/BRS/A694).
Where the data were available, we reported incidence or prevalence of symptomatic ASP. For the incidence, we recorded, when provided, either the annual incidence rate or the risk (cumulative incidence) of ASP. The annual incidence rate was defined as the proportion of patients who were free of ASP at the start of a given year and had subsequent development of new ASP during that year. The risk (%) of ASP was defined as the proportion of patients who were free of ASP at the time of the index fusion and had subsequent development of new ASP at final follow-up. Prevalence was defined as the proportion of patients with ASP at follow-up given that some had ASP at the time of the index fusion. For these estimates of frequency, we used the number of new events (adjacent levels with ASP) in the numerator and the number of adjacent levels at risk in the denominator. For studies only providing the patient as the denominator, the proportion of patients with 1 or more levels of ASP was considered a count of 1 in the numerator and the number of patients at risk was counted in the denominator. These were recorded and noted in the text and appropriate tables. Data were summarized in tables but were not pooled between studies because of the limited number of studies available and the heterogeneity of patient populations and outcomes.
Consensus statements were made through a modified Delphi approach by applying the GRADE/AHRQ criteria that impart 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.3
We identified 362 total citations from our literature search: 124 related to fusion as a result of degeneration of the lumbar or cervical spine, 79 related to fusion as a result of trauma, 87 related to pediatrics conditions, and 72 related to congenital fusion (Figure 1). Of these, 299 were excluded by the title/abstract and 63 full-text articles were evaluated to determine whether they met the inclusion criteria. From these studies, 44 were excluded primarily because there was no radiographical evaluation of ASP. Details of the excluded articles can be found in the supplemental digital material (see Appendix, Supplemental Digital Content 1, available at: http://links.lww.com/BRS/A694). The remaining 19 studies—7 for spine degeneration, 1 for trauma, 6 for pediatric condition, and 5 for congenital fusion—met our inclusion criteria and are summarized in this report.
Overview of Included Studies
Spine Fusion as a Result of Degenerative Disease
Seven studies were identified, which provided information regarding the risk of radiographic ASP among patients who received fusion for lumbar (3 studies)6–8 and cervical (4 studies)9–12 degeneration. Of the lumbar studies, there was 1 randomized controlled trial (RCT) and 2 retrospective cohorts with a total of 278 patients who underwent fusion. Males comprised between 49.4% and 68.0% of the populations and mean ages ranged from 39 to 58 years. Mean follow-up periods ranged from 5.0 to 12.6 years. Only 1 study reported a follow-up rate that was 81.8%.6 RASP was defined in a variety of ways across the 3 studies (see Table 2 for details). Of the 4 cervical studies, there was 1 RCT and 3 prospective cohorts with total 310 patients who underwent fusion. Males comprised between 42.9% and 63.0% of the populations and mean ages ranged from 43.9 to 53.0 years. Mean follow-up periods ranged from 1.6 to 3.0 years. Only 1 study reported a follow-up rate that was 86.5%.9 Radiographical ASP was defined in a variety of ways across the 4 studies.
Spine Fusion as a Result of Trauma
Three studies reported RASP following fusion for trauma. One was a prospective cohort study (83% male, N = 25) that defined RASP as anterior osteophytes at the first disc level above or below the fusion or at both levels, or ossification of the anterior longitudinal ligament.13 Two were retrospective cohort studies. One included 26 patients (81% male) with subaxial cervical spine injuries.14 RASP was defined using the modified grading system of Kellgren. The other included 58 patients (81% male) and defined RASP as less than 50% of normal disc height with anterior or posterior osteophyte formation.15
Spine Fusion as a Result of Pediatric Conditions
Six cohort studies were identified that reported the risk of RASP following fusion for pediatric conditions.16–21 A total of 1252 patients with adolescent idiopathic scoliosis were analyzed across all studies. The populations were primarily female (range, 81.0%–88.0%) and mean ages ranged from 14 to 15 years. Mean follow-up periods varied from 2 to 7.3 years, with only one large study reporting a follow-up rate (100%).17 RASP was defined as evidence of proximal junction kyphosis, which was diagnosed using various criteria across the 6 studies.
Five cohort studies were identified that reported the risk of RASP following congenital fusion.22–26 Across all studies, a total of 203 patients with Klippel-Feil syndrome were reviewed, the majority of which were female (range, 58.0%–71.0%). Mean ages ranged from 12 to 35 years. The mean lengths of follow-up across all studies were extensive, ranging from 12 to 35 years, with follow-up rates reported by 2 studies only and were 74%24 and 90.1%.23 RASP was defined a variety of ways across the studies (e.g., disc protrusion, stenosis or spondylosis, subluxation, hypermobility, and instability).
What Is the Risk of Subsequent RASP in the Lumbar and Cervical Spine Following Surgical Fusion for Degenerative Disease?
The definition of RASP varied across 7 studies (Table 2). Regardless of how degeneration was defined, the cumulative incidence of RASP following fusion for degenerative disease ranged from 6.3% to 44.4% during 1.6 to 12.6 years of mean follow-up.6–12 The risk of cervical RASP was higher than that of lumbar RASP despite the shorter mean follow-up periods (Figure 2).
What Is the Risk of Subsequent RASP in the Lumbar and Cervical Spine Following Surgical Fusion for Trauma?
The cumulative incidence of RASP ranged from 5% after 2.5 years to 60% after 7 years. Song etal15 evaluated 58 patients for 2.5 years following the use of the PEEK (polyetheretherketone) cage and plate construct in anterior interbody fusions for traumatic cervical spine injuries. The investigators report 3 cases of new RASP (5%) as defined by less than 50% of normal disc height with anterior or posterior osteophyte formation. Using the modified grading system of Kellgren etal,27 one study reported the risk of radiographical ASP at the first adjacent cephalad and at the first adjacent caudal level following fusion for subaxial injuries of the cervical spine.14 The cumulative incidence of subsequent RASP during a 5.6-year period was 41.2% and 50.0% at the cephalad and caudal level, respectively. The prevalence at final follow-up was 65.4% and 63.6%, respectively. Progressive degeneration of an already existing RASP was also reported with a greater progression observed in the cephalad (47.1%) compared with the caudal (28.6%) level, P = 0.001. Goffin etal13 followed 25 patients (61%) for a mean 7 years (range, 5–9 yr) following Caspar plate fixation for traumatic injuries to the cervical spine. Defining RASP as either anterior osteophytes at the first disc level above and/or below the fusion, or ossification of the anterior longitudinal ligament, the authors report that 60% developed RASP (28% “mild,” 32% “moderate,” or “severe”). In this series, 24% developed RASP at the first adjacent cephalad level, 28% at the first adjacent caudal level, and 8% at both levels (Figure 2).
What Is the Risk of Subsequent RASP in the Lumbar and Cervical Spine Following Spinal Fusion for Pediatric Conditions (Adolescent Idiopathic Scoliosis)?
Proximal junction kyphosis was the only radiographical adjacent segment assessment made in the 6 studies evaluating the effect of fusion in adolescent patients with scoliosis. The definition of abnormal kyphosis varied with 3 studies choosing sagittal Cobb angle 10° or more18,19,21; one choosing an increased postoperative compared with preoperative angle of 15° or more16; one choosing an increased angle using the posterior wall as the reference, no particular cutoff value reported17; and one using more than 5° above the summed normal angular segments.20 The cumulative incidence of radiographical spine degeneration ranged from 3% to 46% during a 2- to 7-year follow-up period. Kim etal18 report data at 2 follow-up time periods allowing us to compare the effect of time on proximal junctional kyphosis; the cumulative incidence of proximal junction kyphosis was 21% for 2 years following surgery and 26% for 7 years after fusion (Figure 2).
What Is the Risk of Subsequent RASP in the Lumbar and Cervical Spine Following Congenital Fusion (Klippel-Feil Syndrome)?
The definition of RASP varied across 5 studies22–26 (Table 2). Regardless of how it was defined, the cumulative incidence of RASP following congential fusion ranged from 20.8% to 68.0% during 12 to 35 years of mean follow-up. One of the studies with 12 years of follow-up reported age-specific incidences of RASP (either subluxation >5 mm or stenosis ≤9 mm) in their patient population, with the risk increasing with older age: 12.5% in patients at 3 to 10 years of age, 49.9% in those at 11 to 15 years of age, and 80.0% in those at 16 to 22 years of age (Figure 2).24
The overall strength of evidence evaluating the frequency of RASP following congenital fusion or fusion for degenerative disease is “low,” that is, we have low confidence in the absolute estimate and further research may change the estimate. The overall strength of evidence is “insufficient” to permit a conclusion on the frequency of RASP following fusion for trauma or fusion in the pediatric population.
In the course of evaluating ASP, the question of etiology has been extensively discussed. The notion that spinal arthrodesis biomechanically transfers additional stress to the adjacent level has played a large role in the development of motion preservation technology in the spine. Conversely, many have opined that adjacent segment pathology is merely a progression of natural arthritic disease and not secondary to the biomechanical effect of the arthrodesis.
Spinal arthrodesis is performed largely for deformity, instability, and pain; however, the specific indication or reason for fusion can vary. Although a substantial number of fusions occur in an older population with pre-existing degeneration, many occur in patients with a lesser degree of pre-existing degeneration, such as the trauma and pediatric population. We hypothesized that if adjacent segment pathology is largely secondary to natural arthritic disease and not the biomechanical effect of fusion, we would observe a lower rate of ASP in populations where there is less likely to be pre-existing spinal degenerative changes.
There are limitations to this systematic review. First, there is no agreed upon classification of adjacent segment pathology. As a result, authors use different definitions for adjacent segment degeneration that make comparisons from study to study difficult. Second, we limited our systematic review to studies that reported radiographical evidence of ASP in different populations. We initially sought to include studies reporting clinical ASP; however, we observed that studies examining ASP in our target populations primarily reported radiographic ASP. Thus, in an effort to maintain parity between the compared populations, we included studies reporting radiographical ASP and not clinical ASP. However, we recognize that radiographical degeneration may not necessarily correlate with clinically symptomatic disease. One strength of the current review is that we identify the effect of fusion on the risk of RASP in patients with differing indications or reasons for fusion. As far as we know, this is the first attempt at doing so.
It should be noted that there is wide variation between studies within the same population group. For example, in studies of ASP following lumbar fusion for degenerative disease, Kanayama etal7 reported an ASP rate of 37%, whereas Satoh etal8 reported a rate of 8.6%. This may be secondary to age differences between the 2 studies and ASP definition differences between the 2 studies and these are presented in Table 2. Furthermore, there are differences in follow-up between populations. In the Klippel-Feil population the mean follow-up was more than 20 years, whereas in all other groups the mean follow-up was less than 6 years.
Despite our efforts to maintain parity by examining comparable outcome (RASP), we still encountered considerable variation between study groups beyond what is expected for a systematic review. This variation certainly reflects the dearth of quality literature available to render a strong recommendation. However, more importantly this highlights a lack of universal agreement on the definition of ASP in the scientific community. Definitions for ASP in this systematic review included junctional kyphosis, spondylolisthesis, stenosis, disc degeneration, and osteophytosis. Although these were observed to occur at the level adjacent to the arthrodesis and technically fall in the category for “adjacent segment pathology,” theses definitions represent a wide spectrum of disease. The comparison of the rate of adjacent level osteophytosis to the rate of adjacent level of junctional kyphosis may not be a valid comparison. A clear definition and classification of ASP is needed to assure “apples to apples” comparisons, and this is the focus of another article in this issue of Spine.
This review suggests that although rates of RASP in the cervical spine are comparable between the congenital fusion group and those fused for degenerative reasons, there is a wide difference between follow-up. This difference in follow-up suggests a slower rate of RASP in the congenitally fused, and this in turn suggests that the pre-fusion status of the adjacent level may play a role in the development of RASP. However, the strength of this statement is weak. Our analysis demonstrates that ASP encompasses a wide spectrum of disease and to compare rates of ASP between groups requires universal understanding and agreement on its definition and classification. Because of limitations of literature, we utilized RASP as our outcome of measure.
As with most research questions, higher quality future studies are needed to better answer the key questions. Studies can be improved by the tightening of parameters in defining ASP and normalization of covariates and specifically analyzing the influence of age, which may be an acceptable surrogate for health of the adjacent disc. Such a study would require substantial control, numbers, and coordination likely from a multicenter effort. The age of the patient at the time of fusion may be regarded as a surrogate for health of adjacent motion segments. Perhaps future studies with examining more closely the influence of age on ASP may provide further insight.
In the cervical spine, the rate of RASP in patients with fusion for degenerative reasons indications is greater than the rate of RASP in patients with congenital fusion, suggesting that the pre-existing health and status of the adjacent level at the time of fusion may play a contributory role in the development of ASP.
Strength of Statement: Weak
- Observed rates of radiographical ASP after fusion in patients with varying amounts of pre-existing spondylosis appeared to be comparable; however, in the cervical spine the rates of ASP in congenital fusion appeared to be slower than the rates in fusion done for degenerative reasons. This suggests that the pre-existing health of the adjacent segment may contribute to the development of ASP.
- This finding should be interpreted cautiously as there is significant variation between studies in patient characteristics, follow-up, and RASP definition.
- Further clarification on the definition and classification of ASP is needed to appropriately compare different patient populations.
We are thankful to Joel Hashimoto, MS, and Erika Brodt, BS, for their assistance in data abstraction. In addition, we are indebted to Ms. Nancy Holmes, RN, for her administrative assistance.
Supplemental digital contents are 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.org).
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