Background: The
rate, risk factors and consequence of adjacent level disease (ALD) in cervical
disc arthroplasty (CDA) remains unclear. The purpose of this study is to
determine the rate, risk factors and clinical outcome of ALD in CDA.
Methods:
Retrospective review of 166 patients with a minimum five-year follow-up of a
CDA was performed. Multi-level surgeries, including hybrid procedures, were
included. Multiple implant types were included. The two inter-vertebral discs
(IVD) cranial of the CDA were monitored for radiologic degeneration. No funding
was attained for this study and the authors declare no conflict of interest.
Results: The
rate of ALD in CDA was 28.3%, with most affecting the immediately adjacent IVD
(27.4% and 7.6% respectively p=0.000). Age (p=0.209) and sex (p=0.201) did not
relate to ALD, nor did pre-operative degeneration (p=0.117) or
spondylolisthesis (p=0.315) adjacent to the CDA. The number of operated levels
(p=0.890), number of fused levels (p=0.354), implant alignment (0.255), ROM
(p=0.569) and implant induced spondylolisthesis (p=0.402) did not affect the
rate of ALD. However, fusion of the most cranial implant significantly
increased the rate of ALD (p=0.032).
The visual analogue pain scale (VAS) was
significantly worse in those patients with ALD (VAS neck 2.7 versus 1.5
p=0.029; VAS arm 0.9 versus 2.3 p=0.002). The five-year functional outcomes
were worse in those who developed ALD (NDI 20.1 versus 12.3 p=0.011).
No patients required a reoperation during the course
of this study.
Conclusion: ALD is
common after CDA and worsens the patient’s functional outcome, but not their
need for revision surgery within five years. Fusion of the most cranial implant
is a major risk for developing ALD, whereas the initial implant alignment and
function do not construe a risk.
Keywords:
Adjacent level disease, Proximal junctional failure, Junctional kyphosis,
Cervical disc arthroplasty, Spondyloli
INTRODUCTION
Degenerative
disorders of the cervical spine are an increasing health burden and are
predicted to affect two-thirds of the population [1]. Most patients are
successfully treated non-operatively, but a select few require operative
intervention [2,3]. Traditionally, there have been two surgical approaches
(anterior or posterior) and two techniques (fusion or non-fusion) utilized,
depending on the pathology being treated.
For anterior
approaches, the most common procedures performed for inter-vertebral disc (IVD)
degeneration, are anterior cervical discectomy and fusion (ACDF) and cervical
disc arthroplasty (CDA). The presumed benefit of CDA is that it preserves
motion and therefore reduces the relative forces on the adjacent levels, which
is theoretically believed to reduce the risk of adjacent level degeneration
(ALD) [4,5]. However, to date there is no conclusive evidence to support the
notion that CDA reduces the rate of ALD when compared to ACDF, with the
relative rates of ALD, within the first five years being similar between the
procedures [6-8].
Unfortunately, the
limited number of publications assessing the outcome of CDA beyond five years
limits our understanding on whether CDA reduces the risk of longer term ALD.
However, it is likely that ALD is multi- factorial and not solely related
to adjacent stiffness. This is evidenced
When compared to
CDA, patients undergoing ACDF are more likely to be older, with more advanced
degeneration, including facet involvement, mal-alignment and disc space
collapse. Therefore, a selection bias may limit our understanding of the cause
of ALD if we simply compare ACDF to CDA. We therefore aimed to account for these
biases and solely analyze patients undergoing CDA to determine the rate, risk
factors and clinical outcome of adjacent level disease (ALD) within this
population.
MATERIALS AND METHODS
We hypothesized
that ALD in CDA patients is rare and most likely caused by subsequent
auto-fusion of the CDA. We performed a retrospective review of 166 patients
with prospectively collected standardized radiographs (AP, standing lateral and
flexion/extension) of CDAs performed within our institution with a minimum five-year
follow-up. Patients were included if they had pre-operative, early
post-operative (<3 months from procedure) and late post-operative (>5
years from procedure) radiographs. Patients were excluded if they had rigid
ankylosing conditions or severe mal-alignment requiring deformity correction
(chin-on-chest deformity and loss of horizontal gaze). Multi-level CDAs were
included, as well as hybrid procedures (multi-level surgery with CDA and
anterior cervical discectomy and fusion (ACDF)). Only sub axial articulations
were included and therefore the C1/2 articulation was excluded.
Sagittal alignment
was based on the posterior vertebral line, on the early post-operative standing
lateral x-ray, as described by Harrison et al. [10]. The flexion and extension
views were used to determine the range of movement (ROM) and mid-flexion point
(defined as the mid-point between maximal flexion and maximal extension) based
on the angle between the upper and lower components of each implant, with
extension defined as posterior convergence and flexion defined as anterior
convergence (Figure 1).
Spondylolisthesis
was defined as a break in the posterior vertebral line on the flexion or
extension x-rays and graded according to the Meyerding classification [11]. IVD
degeneration was graded according to the Kettler criteria using the AP and
lateral standing profile views [12]. Post-operatively the adjacent levels were
monitored for progressive degeneration (ALD) defined as an increase in Kettler
grade [12]. Fusion of an implant was defined as 0° ROM on follow-up flexion/extension
x-rays.
Neck and arm visual
analogue pain scores (VAS) were recorded pre-operatively, early
post-operatively and at five years post-operative. Functional outcomes (Neck
Disability Index (NDI)), at five years post-operative. The clinical notes were
reviewed for revision procedures, including adjacent level procedures.
Statistical methods
Descriptive
statistics were conducted to describe the participants of this study. Following
this, chi-square analyses were conducted in order to determine the association
between ALD and age, sex, spondylolisthesis, implant type and level.
Mann-Whitney tests assessed the relationship between ALD and the various
post-operative non-parametric parameters (alignment, ROM, flexion, extension,
mid-flexion point, VAS score and NDI). Fisher exact tests were conducted to
determine the association between fusion of the upper instrumented level and
ALD.
Statistical
analysis was performed using SPSS software. Statistical significance was
defined as a two tailed p value of less than 0.05.
RESULTS
One hundred and
sixty-six patients were reviewed. The average age of the cohort was 45 years
(range 23-65 years), 51% were female (85 female, 81 male) and the average
follow-up was 6.5 years (range 5-10 years). The CDAs used were the Bryan®
disc from Medtronic (43 patients), the Discocerv® from Alphatech
Spine (38 patients), Mobi-C® from LDR (31 patients) and the
Baguera-C® from Spineart (54 patients). One hundred and sixty-six
IVDs were assessed immediately adjacent and a further 159 IVDs were assessed
two levels cranial to the most cranial implant.
Ninety-six patients
had a single-level CDA, 58 had a double-level (43 double CDA and 15 hybrid
procedures), 11 had a triple-level (five single-level CDA with double-level
ACDF; one double-level CDA with single-level ACDF) and one had a four-level
(triple-level CDA and single-level ACDF) procedure. Only two patients had an
ACDF as their most cranial implant and both cases successfully fused.
Adjacent level degeneration occurred in 47 patients (28.3%) and 57 (17.8%) of IVDs assessed. There was no significant difference of age (p=0.209) or sex (p=0.201) between those patients who did or did not develop ALD. The most common level of the most cranial implant was C5/6, (range C3/4-C6/7). There was no relationship identified between the cervical level of the most cranial implant and ALD (p=0.33). However, the rate of ALD was significantly higher for those IVDs immediately adjacent to the most cranial implant than the two IVD spaces cranial of the implant (27.4% and 7.6% respectively p=0.000) (Figure 2).
Radiological
evidence of pre-operative degeneration was seen in 13.0% of IVDs. The rate of
ALD was higher in those IVDs with pre-operative degeneration (27.0%) than in
those without pre-operative degeneration (16.5%), but this did not reach
statistical significance (p=0.117). A maximum of grade 1 (<25%)
pre-operative spondylolisthesis of the adjacent levels was identified and this
did not significantly increase the rate of post-operative degeneration (13.8%
ALD in those with pre-operative spondylolisthesis compared to 19.1% for those
without pre-operative spondylolisthesis p=0.315).
There was no
relationship between the number of levels operated and the risk of ALD (p=0.890)
(Table 1).
In addition, in multi-level surgery, there was no discernable relationship between ALD and the number of levels fused (p=0.354) (Table 2) or the total number of fused or replaced levels (including congenital fusions) (p=0.883). However, there was a statistically significant, although clinically insignificant, relationship between the average ROM per level and the rate of ALD (7.2° for those without ALD and 5.3° for those with ALD p=0.04).
Auto-fusion of the most cranial implant occurred in
32 patients (19.3%) and was associated with a significantly increased risk of
ALD (28.3% with fusion in contrast to 16.3% without fusion p=0.032) (Figure
3).
There was no
significant relationship between the most cranial CDA early alignment
(p=0.255), ROM (p=0.569), maximal flexion (p=0.433), maximal extension
(p=0.511) and mid-flexion point (p=0.510) with ALD (Table 3).
Furthermore, in multi-level surgery, there was no significant difference
between the early average alignment of each operated level (p=0.255) and ALD.
There was a significantly higher rate of ALD seen in
the Bryan® CDA compared to all other prostheses (p=0.005) (Table
4). This trend was also apparent when only the immediately adjacent IVD was
assessed, although this failed to reach statistical significance (14.3% for the
Bryan® compared to an average 7.6% for all implant types p=0.205).
There was no significant difference in pre-operative adjacent level degeneration and fusion of the most cranial implant identified between prosthetic types (p=0.130 and p=0.297, respectively) (Table 5).
Only a maximum of
grade 1 spondylolisthesis of the most cranial implant was identified.
Spondylolisthesis of the most cranial implant itself was not related to an
increased rate of ALD (17.4% ALD in those with spondylolisthesis of the most
cranial CDA in contrast to 18.6% ALD for those without spondylolisthesis
p=0.402).
No patients
required further surgery on their cervical spine during the timeframe of this
study. This included reoperations or revisions of their implants and extension
for ALD. There was no significant difference in the pre- and early
post-operative VAS scores between those who developed and those who did not
develop ALD (Table 6). However, after five years there were
significantly worse neck and arm pain scores identified in those with ALD.
Functional outcomes were significantly worse in
those patients who developed ALD (NDI 20.1 versus 12.3 p=0.011).
DISCUSSION
This study has
found that radiographic ALD is common and occurs in 28.3% of patients
undergoing CDA. We found no evidence that the patient’s age or sex predisposed
to ALD. However, our results illustrate that ALD most commonly occurs at the
IVD immediately adjacent to the most cranial implant, rather than the IVD two
spaces from the implant (27.4% and 7.6%, respectively, p=0.000). In addition,
we found that there was a significantly higher rate of ALD in patients with
auto-fusion of the most cranial CDA (28.3% with fusion in contrast to 16.3%
without fusion p=0.032).
This confirms that
a stiffened motion segment is a risk factor for ALD and therefore supports the
notion of motion preservation. However, this does not, in itself, support the
use of a CDA in the most cranial operated level [13,14]. In this series an
overall CDA fusion rate of 18.1% was identified. Thus, CDAs do not eliminate
the concern of motion segment stiffness. Furthermore, the long-term outcome of
CDA, particularly when coupled with adjacent fusion procedures, remains
unknown. Therefore, to extrapolate our results to support the use of “topping
off” multi-level surgery with a CDA is unfounded.
Intuitively, it
seems likely that pre-operative adjacent level degeneration increases the risk
of ALD. Our results support this presumption (27.0% rate of ALD in those with
pre-operative degeneration in contrast to 16.5% without pre-operative
degeneration), although this result did not reach statistical significance
(p=0.117). Further research with higher numbers of patients is required to
confirm this finding.
We found no
evidence that pre-operative adjacent spondylolisthesis predisposes to ALD.
However, we only had patients with mild (<25%) spondylolisthesis identified
in this series, thus the effect of more severe slippage remains unknown.
We hypothesized
that the most cranial implants alignment and mobility contributed to the rate
of ALD. However, we found no relationship between ALD and the most cranial
implants early post-operative alignment, ROM, maximal flexion, maximal
extension or mid-flexion point.
Because this study
excluded severe deformity we did not assess the global cervical alignment.
However, we did assess the alignment of each operated level as a pragmatic
surrogate to what surgeons can achieve intra-operatively if corrective
osteotomies are not performed. We found no relationship between individual
level alignment and ALD. Therefore our results suggest that surgeons do not
need to modify implant sizing to correct cervical alignment in order to prevent
ALD in such a population group.
We also found no
relationship between ALD and the total number of levels operated or the number
of levels fused. Although, we did find a statistically significant increase in
ALD with less ROM per operated level. However, despite being statistically
significant (p=0.04), we feel the less than 2° difference per level between
those who developed ALD and those who did not (5.3° versus 7.2°, respectively),
is clinically insignificant and within the inaccuracies of radiographic
measurements. We therefore feel that this finding supports surgeons treating
each IVD on its own merits in multi-level surgery, including fusing a segment
when appropriate, rather than solely performing CDAs at every level.
We are uncertain as
to why the Bryan® CDA had a significantly higher rate of ALD than
the other prostheses assessed (p=0.005). Our findings show that auto-fusion of
the most cranial implant significantly increases the rate of ALD (p=0.032) and
therefore a higher rate of implant auto-fusion would account for this finding.
However, the Bryan® CDA was not found to have a significantly higher
rate of auto-fusion of the most cranial implant when compared to the other CDAs
(p=0.297). In addition, although the increased rate of ALD in adjacent level
pre-operative degeneration failed to reach statistical significance (p=0.117),
it may affect the prosthetic result. Again, however, patients with the Bryan®
CDA did not have a significantly increased rate of pre-operative adjacent level
degeneration (p=0.130). We are therefore uncertain as to why there is a higher
rate of ALD in our cohort of patients who underwent a Bryan® CDA and
therefore further research into the implant specific rates of ALD are
advocated.
We feel that ALD
can be defined radiologically, clinically (with severe symptomatic and
functional impact) and surgically (with a surgical indication). Our study
specifically utilized a radiological approach to the diagnosis of ALD, with
subsequent review of the clinical and surgical implications.
To date, there is
no radiographic score that can accurately define the prognosis and therefore
treatment of disc degeneration [15]. We used the Kettler criteria because it is
reportedly the most reliable and specific x-ray measure for disc degeneration
in the cervical spine [12,15]. Although cross-sectional MRI imaging would offer
earlier identification of ALD, our cohort did not undergo such follow-up scans.
Because none of our cases required a reoperation we feel that the x-ray
follow-up was sufficient to identify significant ALD in our cohort.
Despite none of our
patients requiring a reoperation on their cervical spine within the timeframe
of this study, we found that patients meeting the radiographic criteria for ALD
had significantly worse five-year neck and arm pain scores as well as worse
functional outcomes (p=0.011). While it should be recognized that the cause of
the poorer pain scores and functional outcomes may relate to factors other than
ALD, the statistical significance suggests that the radiographic ALD identified
in this study represents a clinically important condition and warrants
longer-term follow-up to determine if delayed operative intervention is necessary.
In conclusion, the
rate of ALD in this cohort of patients undergoing CDA was 28.3%. Most ALD
affects the immediately adjacent IVD and auto-fusion of the most cranial
implant is an important risk factor. However, pre-operative adjacent level
spondylolisthesis, the number of levels operated or fused and the early
post-operative alignment and function of each CDA do not affect the rate of
ALD. ALD is associated with increased pain and functional disability but not an
increased rate of reoperation within five-years.
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