Introduction
Since the 1950s Anterior Cervical Discectomy and Fusion (ACDF) has been an accepted modality of treatment for cervical radiculopathy and myelopathy. Though it alleviates all the mechanical and radicular symptoms, the long term effects of inter-body fusion in cervical spine have been a subject of debate. Adjacent motion segment degeneration is a common radiological finding reported in up to 92% of patients undergoing ACDF and annual incidence of re-operation, between 1.4%-5% (Williams, Gore, Bohlman, Hilibrand). As there is an increase in the rates of cervical fusion in younger patients and with the availability of newer motion preserving implants (e.g. cervical disc replacements) the clinical significance of adjacent motion segment radiological change remains controversial. Natural history and the circumstances that predispose to symptomatic disease are fundamental to the controversy of adjacent level disc degeneration. One of the theories include the idea that surgical fusion significantly alters normal cervical physiology and kinematics, and induces faster degeneration of adjacent-level. Biomechanical studies have documented hypermobility and increased stress in in-vitro studies (Eck, Fuller). Another school of thought centres on the notion that regardless of treatment, adjacent-level disc degeneration is a natural progression of the degenerative process.

Literature Review
Clinical Evidence
Hilibrand and Robbins reported clinically significant adjacent level disc disease in a review of 409 ACDFs with an annual incidence of 2.9% per year. Although only 14% of the procedures went on to develop adjacent motion segment degeneration, survivorship analysis predicted that over 25% of patients would develop adjacent segment degeneration by 10 years. Katsuura and colleagues noted degenerative changes on radiological examination in levels adjacent to a fused segment in 21 of 42 (50%) patients at 9.8 years average follow-up after ACDF.

Goffin reported on 181 patients treated by anterior cervical interbody fusion with an average follow-up of eight years with radiological changes, which did not correlate with clinical symptoms. Similar rates of adjacent segment problems resulting from ACDF, anterior discectomy alone, and posterior foraminotomy have been reported (Lunsford, Henderson, Baba, Gore).

On the other hand, Herkowitz et al reported radiological outcomes comparing posterior laminoforaminotomy with anterior fusion surgery for cervical radiculopathy. Adjacent level degeneration after the posterior non-fusion procedures was higher compared to anterior fusion (50 and 41%, respectively) at a mean 4.2 years follow-up; indicating that fusion alone may not be the only etiology of adjacent motion segment degeneration.

In a review of 116 single-level corpectomies, Epstein et al reported only one reoperation for adjacent level disease at an average of 3.2 years follow-up. Ishihara et al reported similar rates of new onset myelopathy attributable to adjacent disease (16% at 10 years based on Kaplan-Meier survivorship). Papadopoulos et al reported in patients with three level ACDF procedures, adjacent degeneration in 11/46 (24%) with a 4% reoperation rate at 33 months.

Another evaluation of long-term outcomes after anterior stand alone multilevel fusion with corpectomy also found adjacent degeneration in one of 31 patients with no reoperations related to adjacent motion segment degeneration (Ikenaga). Yue and associates evaluated clinical and radiologic outcomes at an average of 7.2 years following anterior cervical discectomy and fusion. In this series, 12 of 71 patients (16.9%) required second procedures for symptomatic adjacent level disease at an average of 41.8 months following the index procedure.

Biomechanical studies
The sub-axial cervical spine, where most fusion procedures are performed, is bordered by a highly mobile upper cervical region that provides nearly half of all cervical motion. Numerous biomechanical studies examining the effects of arthrodesis on adjacent levels have been reported although none have utilised a model which includes the upper cervical region.

In experimental studies segmental motion loss at the fusion level is transferred to segments above and below with the majority of increased stress, intradiscal pressure, and motion compensated at the levels immediately adjacent to the fusion level (Eck, Fuller). Other studies have substantiated these observations, demonstrating increased stress responses in adjacent levels (Maiman, Kim, Panjabi).

This is further corroborated by recent cadaver studies, which also note stress concentration above a single-level or double level fusion as measured by intradiscal pressure manometry, segmental motion analysis, and force calculations (Schwab, Park). Lopez-Espina and associates noted a 96% increase in stresses at the nucleus, annulus, and endplate of levels adjacent to fused cervical motion segments, utilising finite element analysis in a cadaveric model. Increased adjacent level stresses were noted following two-level fusions when compared to single-level. In-vivo kinetic studies did not show the same dramatic increase in stress or motion.

Reitman et al reported that prospective fluoroscopic analysis in 21 patients showed no consistent increase in motion at the adjacent segments after single-level fusion. Kolstad et al prospective fluoroscopic analysis of 46 patients undergoing C5-6 ACDF, showed preoperative segmental motion did not significantly differ from postoperative motion and the iatrogenic hypermobility adjacent to a cervical fusion could not be confirmed at 12 months after surgery.

In contrast, Cheng et al in their in-vivo study of three groups of volunteers (healthy, with spondylosis, and with single-level ACDF) using fluoroscopic motion analysis found that there was increased segmental motion (and calculated force) adjacent to the level of fusion. Comparisons were made between separate groups of patients and no significant difference was found for average and relative range of motion at the adjacent levels, though the authors did calculate significant differences in relative rotation as a potential source for additional stress at the adjacent disc.

In a prospective randomised trial of Bryan cervical disc replacement Sasso et al reported normal motion preservation at the surgical level without significant increase at the adjacent levels, near normal pre-operative kinematics, and no significant change in the centre of rotation.

Overall neck range of motion had improved following cervical disc replacement in their study indicating it may help in reducing adjacent level disc stress concentration and may improve motion. Interestingly, this improvement in global motion also was observed by Hilibrand (spine 2006) in their clinical study comparing preoperative and postoperative motion in patients undergoing single-level and multilevel ACDF.

Plate position
In a retrospective review of 118 patients after healed anterior cervical fusion with plating, a significant positive association of adjacent level ossification disease (ALOD) was noted with plates that were within 5mm of the adjacent intervertebral disc at approximately two-year follow-up (Park et al). A recent retrospective clinical outcome study by Ipsen et al challenges this notion and reports no statistically significant association of adjacent level degeneration with plate position or orientation at 18-month follow up.

Deformity
Recent literature has highlighted the importance of sagittal alignment and its relation to the development of adjacent level degeneration. In Katsuura's study a total of 43% of patients with adjacent level degeneration had malalignment of the cervical spine at the time of diagnosis. Degenerative change in adjacent intervertebral levels was observed in 77% of segments fused in kyphosis. Patients with preoperative kyphosis tended to maintain their kyphotic alignment and those with new focal kyphosis after fusion also tended to show accelerated adjacent segment disease.

Kulkarni et al noted that at 17 months, there is increased rate of adjacent segment stenosis in patients with kyphosis after surgery and that the stenosis was caused by hypertrophy of the posterior longitudinal ligament and ligamentum flavum rather than by the loss of disc height.

Kumar and co-workers performed a similar studying lumbar spine analysing the relationship between lumbar sagittal imbalance and the development of adjacent segment degeneration with 38% evidence of adjacent level degeneration above the level of the fusion at an average of 5.2 years following the index procedure. An animal study of lumbar spine in sheep showed fusion in kyphosis produces compensatory lordosis (Oda et al).

Figure 1: Post-op X-ray C4-5, C5-6 ACDF Figure 2: Adjacent-level degeneration 2 years following surgery

Motion sparing technology
Natural history plays a substantial part in the development of adjacent level disease according to the literature. This is most evident in patients who undergo posterior decompression procedures for symptomatic radiculopathy. A recent retrospective review by Clarke et al of 303 patients who had undergone posterior laminoforaminotomy showed that at an average 7.1 year follow-up, the rate of adjacent level disease was 15 of 303 (5%) of which nine (3%) required reoperation.

The authors also noted that C5-6 and C6-7 were most at risk for developing adjacent level disease consistent with prior studies and a 6.7% rate at 10 years based on Kaplan-Meier survivorship analysis. Interestingly, the rate of symptomatic same segment disease (10 of 303) was comparable and required three reoperations. This study is limited by incomplete follow-up data and lack of systematic long-term clinical outcomes evaluation. On the other hand, detailed analysis of recent literature on cervical disc replacement (CDR) shows increased rate of adjacent disc degeneration following fusion.

Mummineni et al in their RCT of cervical disc replacement at two years shows 1.1% re-operation for CDR when compared to 3.4% following ACDF (p<0.05). They had higher rates of failures and re-operation in patients with ACDF (12%) than reported in literature, which may be a confounding factor to assess the results of ACDF. The authors also noted significantly better clinical results (neck pain) in the CDR group; however, based on their fusion criteria (<4º motion), symptomatic pseudarthrosis cannot be excluded as a source of failure in the ACDF group.

Further confounding the analysis is the possibility that a subset of patients may have had adjacent level problems in addition to pseudarthrosis. Robertson and co-workers compared the prevalence of adjacent segment degeneration at two-year follow-up in recipients of the Bryan cervical disc replacement to those who underwent single-level cervical discectomy and fusion. Fusion was found to be significantly more associated with increased radiologic (odds ratio: 2.44) and clinical (odds ratio: 35.8) adjacent level disease. The authors reported 22 of 158 (14%) symptomatic adjacent disease for fusion vs. 1 of 74 (1.3%) for CDR requiring five and one reoperations, respectively, (not statistically significant).

They concluded that motion-sparing procedures in the cervical spine may be protective of adjacent levels when compared to fusion. Interestingly, although the rate of adjacent segment degeneration at two years after ACDF in this study was much higher than that reported in the literature, the percentage of reoperation for adjacent-level disease was actually higher (4% vs. 3.2%) for CDR than ACDF. In a prospective randomised multicentre clinical trial, reported by Sasso et al arthroplasty preserved motion at the surgical level and clinical outcomes compare favourably with ACDF. Analysis of the reported data shows that at two year follow-up, three of 36 (8.3%) patients that underwent CDR required re-operations for adjacent level problems compared with two of 35 (5.7%) of control ACDF patients, indicating possibly similar rate of adjacent level disease.

Discussion
Prevention of adjacent level degenerative disease is a complicated and controversial topic. There are no established guidelines for the treatment of degenerative disc disease. Clinical outcome studies mirror the statistical rates from classic published reports confirming the continued presence of adjacent level disease, despite new innovations and treatment options.

Some recent evidence of the technique associated iatrogenic causes of adjacent level degeneration (i.e. plate position, kyphotic alignment) may be correctable and optimise outcomes after traditional ACDF. Many would agree that there may be instances when prophylactic adjacent segment fusion may be beneficial, such as in those patients with sagittal mal-alignment, instability, or overwhelming axial pain.

Furthermore, clinical observation shows that severe spondylotic change does not often occur in isolation. If a segment is stiff for a long time prior to intervention, there would be a greater likelihood that adjacent segment degeneration will occur because of pre-existing degenerative change above or below. In a study by Hilibrand and Carlson that evaluated adjacent level degeneration following ACDF, it was demonstrated that the risk of new disease at an adjacent level was significantly lower following a multilevel ACDF than it was following a single-level.

The study concluded that all degenerated segments causing radiculopathy or myelopathy should be included in an anterior cervical arthrodesis. It was their belief that further degeneration is likely secondary to progression of the disease process rather than the result of the fusion itself. Pimenta et al reported improved clinical outcomes measured from multilevel CDR as compared with the single-level CDR. Failures of CDR may include those patients who already exhibit mild adjacent degeneration or in whom the motion preservation was inadequate to prevent adjacent level stress.

The current evidence shows that the natural history of a disc under increased stress or motion is to degenerate. This can occur naturally (congenital fusions, severe spondylosis) or iatrogenically from surgery. Regardless of the etiology, once the segment biomechanically exhibits decreased motion, the adjacent levels may incur additional stress and load. This has been observed in the analysis of fusions in younger patients (congenital, post traumatic, Klippel–Feil) in which there has been increased disc degeneration at the segments adjacent to the fused levels (Gullie).

Conclusion
The development of adjacent level degeneration following ACDF is most likely related to several postoperative mechanical factors as well as the normal aging process of the spine. The literature seems to support a multivariate etiology of this phenomenon. The observation of increased motion and stress at adjacent levels may provide some rationale for treatment utilising motion preservation technologies. The short-term results of CDR indicate that motion preservation may only be one component of a multifactorial problem. More long-term data is needed to determine the influence of motion sparing alternatives on the development of adjacent segment degeneration.

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