Ossification of Posterior Longitudinal Ligament
Three CoE III prospective cohort studies assessed risk and timing of symptom development and prognostic factors associated with symptom development in patients with OPLL without myelopathy.14–16
In a CoE III prospective cohort study,14 27 subjects with cervical OPLL in whom the cervical spinal canal on MRI was 12 mm or less were seen between April 2000 and March 2007 and had no clinical symptom of myelopathy (Table 2). Loss to follow-up was not reported, and it is unclear whether or not subjects were consecutively recruited for study participation. The baseline JOA score for all subjects was 17 points, and 63.0% (17/27) were classified with continuous type OPLL, 25.9% (7/27) with mixed type, and 11.1% (3/27) had segmental type OPLL. Subjects were followed for a mean of 59 (range: 12–95) months, and the clinical course was assessed using the JOA scoring system. None of the subjects developed myelopathy during the follow-up period, and risk factors for myelopathy development were not assessed.
In another CoE III multicenter prospective cohort study, Matsunaga et al15 evaluated radiography-, computed tomography-, and MRI-related predictors for the development of myelopathy in subjects with OPLL. Sixteen centers recruited 156 subjects with cervical OPLL and a minimum of 5-year follow-up (Table 2). OPLL was classified as continuous in 35.3% of subjects (55/156), mixed type in 35.9% (56/156), and segmental type OPLL in 28.8% (45/156). Subjects were followed for a mean of 123.6 (range: 60–276) months for neurological confirmation of myelopathy, although the time interval between follow-up evaluations was not reported. Myelopathy developed in 61.5% of subjects (96/156) and was observed in 100% of subjects (39/39) with 60% or more cervical spinal canal stenosis. In subjects with less than 60% canal stenosis, 48.7% (57/117) developed myelopathy during the follow-up period. In a univariate analysis, canal stenosis of 60% or more (RR = not calculable), increased cervical ROM (P = 0.03), and lateral deviated-type OPLL in axial view (RR: 2.1; 95% CI: 1.4–3.1) contributed to myelopathy development (Table 4).
Matsunaga et al16 prospectively followed 486 subjects with OPLL who had been seen at one institution since 1972 in a CoE III cohort study. This article reported on a larger population and provided longer follow-up than a previous article by the same authors.20 The authors reported a 92.6% (450/486) follow-up, in which clinical examinations and plain radiography were performed for a mean of 211.2 (range: 120–360) months. At first examination, 323 subjects had no myelopathy and represent the population reported in this systematic review. Subjects were followed annually for progression of disease, assessed with radiography and evaluation of clinical myelopathic features and concomitant ability to perform activities of daily living. Myelopathy was estimated using the Nurick classification system and JOA scale. Of these 323 subjects, 55 (17.0%) developed myelopathy during the follow-up period. The myelopathy-free rate in subjects without myelopathy at presentation was 71% on examination at 30-year follow-up. Although risk factors for myelopathy were reported in this article, the comparison groups did not allow for assessment of risk factors that contribute to myelopathy development.
International Survey to Spine Care Community
A total of 774 completed surveys were received during the 3-week period of response collection, representing a response rate of 3.9% (774/19,750). Table 5 provides a summary of respondent characteristics and surgical preferences. Notably, the majority of respondents underwent neurosurgical or orthopedic spine fellowship training (625/774; 80.7%) and reported their practice setting to be academic/university-based (464/774; 60.0%). In the presence of CSM and a maximum of 2 levels of continuous cervical stenosis, a total of 383 respondents (49.5%) identified anterior cervical discectomy and fusion (ACDF) as their procedure of choice. In the presence of cervical stenosis involving at least 4 contiguous levels, 246 respondents (31.8%) identified laminectomy with instrumented fusion as the operation of choice, followed very closely by laminoplasty (245/774; 31.7%). Regarding the natural history of patients with cervical stenosis but without myelopathy, respondents’ opinion seemed to vary depending on the presence or absence of radiculopathy (Figure 3). In the absence of radiculopathy, 417 respondents (53.9%) reported that patients are most likely to remain stable over time. However, in the presence of radiculopathy, only 211 respondents (27.3%) felt that a continued stable course was most likely, with the greatest proportion of respondents (264/774; 34.1%) predicting a gradual progressive decline over time. Among respondents, subjective complaints of lost hand dexterity and the objective presence of a radicular motor deficit were the most frequently identified symptom and sign, respectively, that would prompt surgical intervention in nonmyelopathic patients with cervical stenosis (Figure 4).
Table 6 provides a summary of survey responses pertaining to the clinical cases. The first case involves an asymptomatic patient with MRI evidence of cord compression and intramedullary T2 hyperintensity. There were 525 respondents (67.8%) who indicated that they would offer surgical decompression, with ACDF being the most common procedure (391/525; 74.5%). The majority of these respondents (359/525; 68.4%) suggested that the primary goal of operation would be prevention of myelopathy development. The second case depicts a nonmyelopathic patient with a C6 radiculopathy and MRI evidence of cord compression as well as intramedullary T2 hyperintensity. There were 665 respondents (85.9%) who indicated a preference for surgical management. Laminectomy + fusion was the most common first-choice operation (216/665; 32.5%), followed closely by ACDF (172/665; 25.9%) and laminoplasty (159/665; 23.9%). Similar to the first case, the majority of respondents (425/665; 63.9%) reported prevention of myelopathy development as the primary operative goal. Finally, the third case illustrated a patient with mild clinical evidence of myelopathy and MRI findings of mild cord compression with no attendant intramedullary signal change. A total of 504 respondents (65.1%) indicated a preference for surgical management. Among these respondents, the vast majority (405/504; 80.4%) identified ACDF as the operation of choice. Prevention of myelopathy progression was the most common treatment goal (294/504; 58.3%), with improvement in myelopathy symptoms cited by only 28.2% of respondents (142/504).
The overall strength of evidence ratings for each key question and related outcomes are detailed in Table 7. For question 1, the frequency of myelopathy development in subjects with cervical cord compression or canal stenosis was 22.6% at a median of 44-month follow-up, with 8% progressing to myelopathy at or before 12-month follow-up. The overall strength of evidence for the frequency and timing of myelopathy development in subjects with asymptomatic cervical cord compression or canal stenosis was considered “low,” meaning that our confidence in the effect estimates is limited; the true effect may be substantially different from the estimate. In asymptomatic subjects with OPLL, the frequency of myelopathy development ranged from 0% to 61.5% across 3 studies, with mean follow-up ranging from 50 to 211 months. The rating for frequency and timing of myelopathy development in the context of OPLL was “insufficient,” meaning that we have very little confidence in the estimated effects. Inconsistency or unknown consistency in results reporting and concerns regarding precision were the primary reasons the evidence strength was downgraded.
For question 2, clinical and electrophysiological evidence of cervical radiculopathy was a positive predictor of myelopathy development in patients with cervical spondylosis and cord compression. In the same patient group, MRI evidence of T2 hyperintensity was a positive predictor of myelopathy development; however, interestingly, the absence of this finding was a positive predictor of early progression (≤12-mo follow-up). The overall strength of evidence was considered “low” for demographic/clinical, radiographical, and electrophysiological predictors of myelopathy development in subjects with asymptomatic cervical cord compression or canal stenosis. Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate. The available evidence is based on a single study that assessed risk factors for myelopathy development using a univariate analysis; consequently, unknown consistency of results, high risk for bias, and concerns about precision led to downgrading the evidence quality. Regarding predictors of early (≤12 mo) myelopathy development in subjects with asymptomatic cervical cord compression or canal stenosis, the rating was “moderate,” meaning that we are moderately confident that effect size estimates lie close to the true effect, but there is a possibility that it is substantially different. Unknown consistency of results and concerns about precision led to a downgrade in the strength of evidence.
In subjects with OPLL, the overall strength of evidence was considered “insufficient” for demographic/clinical, radiographical, and electrophysiological predictors of myelopathy development, meaning that we have very little confidence in the effect estimates. The absence of data for demographic/clinical and electrophysiological predictors, unknown consistency of results, imprecision, and a high risk for bias were the primary reasons the evidence strength was downgraded.
The goal of this study was to evaluate the current evidence and obtain clinical opinion surrounding the natural history of nonmyelopathic patients with radiographical evidence of cervical spinal cord compression, spinal canal narrowing, and/or OPLL. A systematic review of the literature, supplemented by an international survey of spinal surgeons, was performed to answer 3 key questions related to the development of symptomatic myelopathy in this patient population. Although a paucity of studies examining this topic were identified in the literature review, the results of the survey, as well as discussion among the study authors, were used to develop a series of clinical recommendations.
What Is the Frequency of Myelopathy Development?
In the single prospective cohort study addressing nonmyelopathic patients with MRI signs of spondylotic cord compression,13 22.6% (45/199) developed clinical evidence of myelopathy, with a median follow-up duration of 44 months. Dissecting these results further, of the 45 subjects who developed myelopathy, 60.0% (27/45) had clinically symptomatic radiculopathy at initial presentation, with this finding observed in only 20.1% of subjects (31/154) who did not develop myelopathy. In general, clinical opinion aligns with the literature on this topic. In the absence of neurological findings on initial assessment, the majority of respondents (417/774, 53.9%) stated that patients with radiographical cervical stenosis are likely to remain asymptomatic over time. However, in the presence of radiculopathy, the majority of respondents (460/774, 59.4%) reported clinical progression as the most likely outcome, with 27.3% (211/774) having indicated a continued asymptomatic course to be most likely. Although clinical opinion supports the findings of the literature series, the prevalence of myelopathy progression presented in this single article must be treated as preliminary.
Regarding asymptomatic OPLL, the incidence of myelopathy development ranged from 0% in subjects (0/27) followed for a mean of 59 months14 to 17.0% in subjects (55/323) who underwent a mean follow-up of 211.2 months16 to 61.5% in subjects (96/156) with a mean 123.6-month follow-up.15 The heterogeneity of results, coupled with the variability in patient eligibility criteria and follow-up duration observed across these studies, precludes the identification of an estimate for the incidence rate of myelopathy development in asymptomatic patients with OPLL.
What Are the Clinical, Radiographical, and Electrophysiological Predictors of Symptom Development?
Two studies provided information about predictors of symptomatic progression, with one of these pertaining to spondylotic cervical stenosis and the second focused on OPLL. In a multivariate analysis, the presence of symptomatic radiculopathy, electrophysiological characteristics including prolonged SEPs and MEPs, and lack of intramedullary T2 hyperintensity on MRI were independent predictors of early (≤12 mo) myelopathy progression in subjects with asymptomatic spondylotic cervical stenosis.13
Although questions directly relating to electrophysiology were not included within the survey, it is clear that respondents felt the clinical presence of radiculopathy to be an important indicator of symptomatic progression. Motor radiculopathy was the most commonly selected physical sign likely to prompt surgical intervention when considering a patient with cervical stenosis without overt myelopathy. The limited existing literature and current surgical opinion identify radiculopathy as a premyelopathic state, indicating a higher likelihood of future symptomatic progression. Regarding imaging, it is interesting to note that cases 1 and 2, which described no overt signs or symptoms of myelopathy but showed MRI evidence of T2 intramedullary hyperintensity, garnered more support for surgical intervention than case 3, where early signs and symptoms of myelopathy were present without MRI evidence of T2 hyperintensity. We speculate that imaging evidence of spinal cord structural change, as demonstrated by signal abnormality on MRI, was more important to some respondents than early clinical evidence of myelopathy in predicting deleterious clinical progression over time.
In subjects with OPLL, Matsunaga et al15 performed univariate analyses that associated laterally deviated pattern of ossification, increased cervical ROM, and at least 60% canal stenosis with an increased likelihood of myelopathy development. It is probable that the association between myelopathy progression and laterally deviated OPLL relates to smaller canal diameter at more lateral positions. Regarding the ROM association, it is speculated that the patients with OPLL and increased ROM may be more susceptible to dynamic cord compression and injury than those with reduced ROM. Although these associations are logical from a clinical standpoint, they have yet to be validated by follow-up confirmatory studies.
What Clinical and/or Radiographical Features Influence Treatment Decisions Based on an International Survey of Spine Care Professionals?
Given the paucity of studies identified on this topic, the survey provided an opportunity to understand how surgeons internationally are approaching the management of asymptomatic cervical stenosis based on their own anecdotal experiences. Of the 3 cases presented, the second case, which combined clinical evidence of radiculopathy but no myelopathy with MRI evidence of multilevel spinal cord compression and intramedullary T2 hyperintensity, led respondents to most frequently prefer operative management to conservative management (665/774; 85.9%), with the majority (425/665; 63.9%) indicating that the primary goal of surgery is prevention of myelopathy development. These findings suggest that, in the case of cervical stenosis with MRI evidence of cord compression, respondents felt more comfortable recommending surgery in a patient who has radiculopathy (case 2) than in a patient who has only neck pain (case 1). On this point, respondent opinion seemed well aligned with the existing clinical evidence that supports the importance of radiculopathy as a predictor of future myelopathy development.
Case 3 differed from the other cases in that the patient demonstrated early symptoms and signs of myelopathy but had a comparatively less severe radiographical picture, with evidence of mild compression at a single disc level and no abnormal T2 signal change. Interestingly, despite clinical evidence of myelopathy, an even smaller proportion of respondents favored surgical management for this case (504/774; 65.1%). We think that this finding may be explained in the following manner. First, given the comparatively mild radiographical picture in case 3, it is possible that respondents thought that a separate pathology unrelated to the mild cord compression was responsible for the observed clinical findings and favored further diagnostic workup before proceeding with operation. Second, it is possible that some respondents have shifted to prioritizing the use of MRI findings over clinical history and examination to guide treatment decision making in patients with asymptomatic or minimally symptomatic cervical stenosis. In either case, the results of this survey clearly indicate the current importance of MRI evaluation as an adjunct to clinical assessment in guiding surgeons’ clinical decision making for this patient population. Despite this observation, the literature does not clearly support the importance of MRI, specifically T2 hyperintensity, in predicting progression of symptoms. Although Bednarik et al13 found the absence of such signal change to be a positive predictor of progression at 1 year, at a mean follow-up of 44 months, the presence of this finding was a positive predictor of symptomatic progression. Clearly, identification of radiological markers more sensitive for identifying clinical deterioration are needed to guide clinicians’ surgical decision making. Because no cases or survey questions were related to OPLL, the results discussed are relevant only to spondylotic-related cervical stenosis.
In relation to the survey, it should be mentioned that although the absolute number of respondents was high, the response rate of 3.9% was low. As a result, we cannot exclude the possibility of response bias and that survey results may have differed if a larger proportion of responses had been garnered.
Clinical experience informs that a proportion of asymptomatic patients with cervical stenosis secondary to spondylosis or OPLL will develop myelopathy over time. On the basis of the current literature, for patients with cervical canal stenosis and cord compression without clinical evidence of myelopathy, approximately 8.0% at 12 months and 22.6% at a median follow-up of 44 months will develop myelopathy. The same literature supports the importance of clinical and electrophysiological evidence of nerve root dysfunction as an important predictor of progression to myelopathy in this patient population. Current surgical opinion, as measured by the large international survey of spine surgeons presented here, by and large supports the conclusions gleaned from the existing literature. Regarding nonmyelopathic patients with OPLL, no recommendation can be given about the incidence or predictors of progression to myelopathy. Further future studies will be required to refine our understanding of the frequency, timing, and predictors of myelopathy development in asymptomatic patients with cervical stenosis secondary to spondylosis or OPLL.
Evidence-Based Clinical Recommendations.
Recommendation. Patients with cervical canal stenosis and cord compression secondary to spondylosis, without clinical evidence of myelopathy, and who present with clinical or electrophysiological evidence of cervical radicular dysfunction or central conduction deficits seem to be at higher risk for developing myelopathy and should be counseled to consider surgical treatment.
Overall Strength of Evidence. Moderate
Strength of Recommendation. Strong
- Statement 1: On the basis of the current literature, for patients with cervical canal stenosis and cord compression secondary to spondylosis, without clinical evidence of myelopathy, approximately 8% at 1-year follow-up and 23% at a median of 44-months follow-up develop clinical evidence of myelopathy.
- Statement 2: For patients with cervical canal stenosis and cord compression secondary to spondylosis, without clinical evidence of myelopathy, the absence of magnetic resonance imaging intramedullary T2 hyperintensity has shown to predict early myelopathy development (< 12-mo follow-up) and the presence of such signal has shown to predict late myelopathy development (mean 44-mo follow-up). In light of this discrepancy, no definite recommendation can be made surrounding the utility of this finding in predicting myelopathy development.
- Statement 3: For patients with OPLL but without myelopathy, no recommendation can be made regarding the incidence or predictors of progression to myelopathy.
- On the basis of the current literature, for patients with cervical canal stenosis and cord compression without clinical evidence of myelopathy, approximately 8% at 1-year follow-up and 23% at a median of 44-month follow-up develop clinical evidence of myelopathy.
- Patients with cervical canal stenosis and cord compression, without clinical evidence of myelopathy, and who have clinical or electrophysiological evidence of cervical radicular dysfunction or central conduction deficits are at higher risk for developing myelopathy within 1 year from initial assessment.
- Patients with cervical canal stenosis and cord compression, without clinical evidence of myelopathy, and who demonstrate MRI evidence of T2 intramedullary hyperintensity are at higher risk of developing clinically symptomatic myelopathy over long-term follow-up.
- For patients with OPLL but without myelopathy, no recommendation can be given regarding the incidence or predictors of progression to myelopathy.
The authors thank Nancy Holmes and Ms. Chi Lam for their administrative assistance.
Author contributions are as follows: M.F.: study concept, interpretation, manuscript preparation, and manuscript revision; J.W.: study concept, interpretation, manuscript preparation, and manuscript revision; S.B.: study concept, interpretation, manuscript preparation, and manuscript revision; P.A.: study concept, interpretation, manuscript preparation, and manuscript revision; D.R.: study concept, interpretation, manuscript preparation, and manuscript revision; C.S.: study concept, interpretation, manuscript preparation, and manuscript revision; V.T.: study concept, interpretation, manuscript preparation, and manuscript revision; D.J.F.: data analysis and interpretation, manuscript preparation, and manuscript revision; and A.C.S.: data analysis and interpretation, manuscript preparation, and manuscript revision.
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cervical spine; spinal cord compression; spinal canal stenosis; ossification of posterior longitudinal ligament; myelopathy
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