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Frequency, Timing, and Predictors of Neurological Dysfunction in the Nonmyelopathic Patient With Cervical Spinal Cord Compression, Canal Stenosis, and/or Ossification of the Posterior Longitudinal Ligament

Wilson, Jefferson R., MD*; Barry, Sean, MD; Fischer, Dena J., DDS, MSD, MS; Skelly, Andrea C., PhD, MPH; Arnold, Paul M., MD§; Riew, K. Daniel, MD; Shaffrey, Christopher I., MD; Traynelis, Vincent C., MD**; Fehlings, Michael G., MD, PhD, FRCSC, FACS*

doi: 10.1097/BRS.0b013e3182a7f2e7
Role of Non-Surgical Management in Cervical Spondylotic Myelopathy
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Study Design. Systematic review and survey.

Objective. To perform an evidence synthesis of the literature and obtain information from the global spine care community assessing the frequency, timing, and predictors of symptom development in patients with radiographical evidence of cervical spinal cord compression, spinal canal narrowing, and/or ossification of posterior longitudinal ligament (OPLL) but no symptoms of myelopathy.

Summary of Background Data. Evidence for a marker to predict symptom development remains sparse, and there is controversy surrounding the management of asymptomatic patients.

Methods. We conducted a systematic review of the English language literature and an international survey of spine surgeons to answer the following key questions in patients with radiographical evidence of cervical spinal cord compression, spinal canal narrowing, and/or OPLL but no symptoms of myelopathy: (1) What are the frequency and timing of symptom development? (2) What are the clinical, radiographical, and electrophysiological predictors of symptom development? (3) What clinical and/or radiographical features influence treatment decisions based on an international survey of spine care professionals?

Results. The initial literature search yielded 388 citations. Applying the inclusion/exclusion criteria narrowed this to 5 articles. Two of these dealt with the same population. For patients with spinal cord compression secondary to spondylosis, one study reported the frequency of myelopathy development to be 22.6%. The presence of symptomatic radiculopathy, cervical cord hyperintensity on magnetic resonance imaging, and prolonged somatosensory- and motor-evoked potentials were reported in one study as significant independent predictors of myelopathy development. In contrast, the lack of magnetic resonance imaging hyperintensity was found to be a positive predictor of early myelopathy development (≤12-mo follow-up). For subjects with OPLL, frequency of myelopathy development was reported in 3 articles and ranged from 0.0% to 61.5% of subjects. One of these studies reported canal stenosis of 60% or more, lateral deviated OPLL, and increased cervical range of motion as significant predictors of myelopathy development. In a survey of 774 spine surgeons, the majority deemed the presence of clinically symptomatic radiculopathy to predict progression to myelopathy in nonmyelopathic patients with cervical stenosis. Survey responses pertaining to 3 patient case vignettes are also presented and discussed in the context of the current literature.

Conclusion. On the basis of these results, we provide a series of evidence-based recommendations related to the frequency, timing, and predictors of myelopathy development in asymptomatic patients with cervical stenosis secondary to spondylosis or OPLL. Future prospective studies are required to refine our understanding of this topic.

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

Summary Statements.

  • 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 been shown to predict early myelopathy development (<12-mo follow-up) and the presence of such signal has been 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.

A systematic review was conducted to assess the frequency, timing, and predictors of symptom development in patients with radiographical evidence of cervical spinal cord compression, spinal canal narrowing, and/or ossification of the posterior longitudinal ligament. This review, supplemented by an international survey, was used to produce a series of evidence-based recommendations on the topic.

*Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada

Division of Neurosurgery, Dalhousie University, Halifax, Nova Scotia, Canada

Spectrum Research, Inc., Tacoma, WA

§The University of Kansas Hospital, Kansas City, KS

Washington University School of Medicine, Saint Louis, MO

Department of Neurological Surgery, University of Virginia, Charlottesville, VA; and

**Neurosurgery, Rush University Medical Center, Chicago, IL.

Address correspondence and reprint requests to Michael G. Fehlings, MD, PhD, FRCSC, FACS, Toronto Western Hospital, 399 Bathurst St., Toronto, ON M5T 2S8, Canada; E-mail: Michael.Fehlings@uhn.on.ca

Acknowledgment date: March 7, 2013. First revision date: May 28, 2013. Acceptance date: July 12, 2013.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Supported by AOSpine North America, Inc. Analytic support for this work was provided by Spectrum Research, Inc., with funding from the AOSpine North America.

Relevant financial activities outside the submitted work: support for travel to meetings for the study or other purposes, fees for participation in review activities such as data monitoring boards, statistical analysis, end point committees, and the like, payment for writing or reviewing the manuscript, board membership, consultancy, grants/grants pending, expert testimony, patents, royalties, stock/stock options, travel/accommodations/meeting expenses, payment for lectures, and payment for development of educational presentations.

Degenerative cervical myelopathy, which results from a variety of pathologies including cervical spondylosis and ossification of the posterior longitudinal ligament (OPLL), is the most common cause of spinal cord dysfunction. However, the majority of patients with degenerative cervical stenosis due to spondylosis or OPLL never develop signs or symptoms of myelopathy.1 As evidence of this, cross-sectional radiographical studies have shown that 95% of males and 70% of females older than 70 years demonstrate evidence of cervical spondylosis.2 Regarding OPLL, prevalence estimates range from 1.5% to 4.3%, dependent upon the population examined.3 Furthermore, in a recent cadaveric study considering both spondylosis and OPLL, 9% of patients older than 70 years had evidence of significant cervical spinal canal stenosis postmortem.4 Despite these high prevalence rates, clinical experience informs that only a small percentage of patients with these findings present for medical care with symptomatic myelopathy and the need for surgical decompressive treatment.

Given the low specificity associated with radiographical findings of spondylosis or OPLL in predicting the development of myelopathy in asymptomatic patients, the clinical challenge is identifying the few patients within this larger group who have the greatest risk for future symptom development. After identification, such high-risk patients could be followed closely over time, delaying surgery until the appearance of symptoms or, alternatively, they could be offered prophylactic treatment at the presymptomatic stage, with the overall goal of averting disability development. However, such a process is contingent upon the development or identification of sensitive and specific clinical, radiological, and/or electrophysiological markers that could reliably predict symptom development and/or progression. Unfortunately, evidence for such a marker remains sparse, and consequently, there is continued controversy surrounding the management of asymptomatic patients, particularly in the setting of attendant spinal canal narrowing and cord compression.

We present a systematic review of the literature, followed by the results of a survey administered to obtain information from the global community regarding symptom development and treatment decisions in patients with asymptomatic cervical spinal cord compression, spinal canal narrowing, or OPLL. We sought to answer the following key questions in patients with radiographical evidence of cervical spinal cord compression, spinal canal narrowing, and/or OPLL but no symptoms of myelopathy:

  1. What are the frequency and timing of symptom development?
  2. What are the clinical, radiographical, and electrophysiological predictors of symptom development?
  3. What clinical and/or radiographical features influence treatment decisions based on an international survey of spine care professionals?
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MATERIALS AND METHODS

Electronic Literature Search

We conducted a systematic search in MEDLINE, the Cochrane Collaboration Library, and Google Scholar for literature published through January 15, 2013. The search results were limited to human studies published in the English language containing abstracts. Identification of studies explicitly designed to evaluate myelopathic symptom development in patients with radiographical evidence of cervical spinal cord compression, spinal canal narrowing, and/or OPLL but no symptoms of myelopathy were the primary focus. Terms specific to spinal cord compression, cervical spondylosis, cervical stenosis, and/or OPLL ((cervical spine OR cervical vertebrae) AND (spondylo* OR spondylosis[MeSH] OR compress* OR spinal cord compression[MeSH] OR steno* OR spinal stenosis[MeSH] OR ossification of posterior longitudinal ligament[MeSH])), as well as those related to disease progression and risk factors for disease progression, were used. Reference lists of key articles were also systematically checked to identify additional eligible articles. For questions 1 and 2, we sought to identify longitudinal cohort studies of subjects with asymptomatic spinal cord compression or spinal canal narrowing, and/or OPLL without myelopathy who were followed for development of myelopathy symptoms. Articles were excluded if patients were pediatric or had a history of tumor, vertebral fracture or spinal cord injury, infection, or ankylosing spondylitis. Meeting abstracts/proceedings, white papers, editorials, case reports, cross-sectional studies, cadaver or biomechanical studies, and studies with less than 10 subjects for questions 1 and 2 were also excluded. Question 3 involved a survey administered to the global community to address clinical and/or radiographical features that may contribute to treatment decisions in patients with asymptomatic cervical spinal cord compression or spinal stenosis.

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Data Extraction

Full text of potential articles meeting the inclusion criteria were reviewed by 2 independent investigators (D.J.F., A.C.S.) to obtain the final collection of included studies. From the included articles, the following data were extracted: study design, patient demographics, inclusion and exclusion criteria, baseline population/disease characteristics, disease definition and course, potential prognostic factors evaluated, follow-up duration and the rate of follow-up (if reported or calculable), frequency and timing of myelopathy development, and significant prognostic factors for myelopathy development.

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Overall Strength of Body of Literature

Class of evidence (CoE) ratings were assigned to each included article independently by 2 reviewers (D.J.F., A.C.S.) using criteria set by The Journal of Bone & Joint Surgery, American Volume,5 for therapeutic studies and modified to delineate criteria associated with methodological quality and risk of bias based on recommendations made by the Agency for Healthcare Research and Quality (AHRQ).6,7 The appraisal system used in this article accounts for features of methodological quality and important sources of bias by combining epidemiological principles with characteristics of study design to determine the CoE and are consistent with those used in previous focus issues.8 (See Supplemental Digital material, available at http://links.lww.com/BRS/A834, for study ratings.)

After individual article evaluation, the overall body of evidence with respect to each outcome was determined on the basis of precepts outlined by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group9,10 and recommendations made by the AHRQ.6,7 Qualitative analysis is performed considering AHRQ-required and additional domains.11

The initial strength of the overall body of evidence was considered “high” if the majority of the studies were class I or II and “low” if the majority of the studies were class III or IV. Criteria for downgrading published evidence 1 or 2 levels included (1) inconsistency of results, (2) indirectness of evidence, (3) imprecision of the effect estimates (e.g., wide confidence intervals [CIs]) or (4) non–a priori statement of subgroup analyses. Alternatively, the body of evidence could be upgraded 1 or 2 levels on the basis of the following factors: (1) large magnitude of effect or (2) dose-response gradient. The final overall strength of the body of literature expresses our confidence that the effect size lies close to the true effect and the extent to which it is thought to be stable based on the adequacy or deficiencies in the body of evidence. An overall strength of “high” means we are very confident that the true effect lies close to that of the estimated effect. A “moderate” rating means that we are moderately confident in the effect estimate; the true effect is likely to be close to the estimated effect, but there is a possibility that it is substantially different. An overall strength of “low” means that our confidence in the effect estimate is limited: The true effect may be substantially different from the estimated effect. Finally, a rating of “insufficient” means that we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimated effect. In addition, this rating may be used if there is no evidence or it is not possible to estimate an effect. The Supplemental Digital Content (available at http://links.lww.com/BRS/A834) contains the details of how we arrived at the strength of evidence for each key question.

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Data Analysis

Descriptive statistics for all studies were reported as presented in the articles because there was variability in the reporting of prognostic factors and frequency of outcomes. Most prognostic factors were reported as proportions (e.g., % with Pavlov ratio <0.8), and as such, we reported the raw data and calculated relative risks (RRs) and their 95% CIs if not provided by the authors. For continuous prognostic factors (e.g., neck range of motion [ROM]), we reported the raw data and analytical statistics as detailed by the authors. Comparative statistics were recorded if included in the referenced articles. All calculations were performed using Stata 9.1.12

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Clinical Recommendations and Consensus Statements

Clinical recommendations or 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. A more thorough description of this process can be found in the focus issue Methods article and has been described previously.8

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International Survey

An English language 18-question survey was designed to address clinical and/or radiographical features that may influence treatment decisions in patients with asymptomatic cervical spinal cord compression/canal stenosis. AOSpine International members were invited via e-mail to participate in an online survey, which was available electronically on SurveyMonkey for 21 days, and 2 reminder e-mails were sent 10 days apart. The AOSpine International membership includes a large number of spine surgeons from many different countries and practice settings and is thought to be representative of the global spine surgery community. All surveys were completed anonymously. Descriptive statistics were used to summarize the data.

The first section of the survey consisted of 5 questions that obtained basic information about the respondent's time in practice, type of practice setting, fellowship experience, and preferred surgical approach to cervical spondylotic myelopathy (CSM). The second section consisted of 4 questions that inquired about the respondent's understanding of the natural history of asymptomatic cervical stenosis and his or her opinion about the clinical findings that would most justify operating on an asymptomatic patient. The third section consisted of 3 patient scenarios with history and physical examination details as well as representative magnetic resonance images (Figure 1). On the basis of these cases, respondents were asked to make a decision regarding operative versus nonoperative management. Those opting for surgical treatment were asked to select their preference for operative approach and their primary surgical goal in each case. A basic description of each case is provided in the following text:

Figure 1

Figure 1

  • Case 1: 47-year-old healthy and active female who presented with a normal neurological examination and axial neck pain as her only symptom. Magnetic resonance imaging (MRI) demonstrated multilevel spondylosis and cord compression with T2 intramedullary signal change seen on the mid-sagittal image.
  • Case 2: 67-year-old healthy male who presented with history and physical examination findings consistent with a right-sided C6 radiculopathy. MRI demonstrated multilevel spondylosis, canal and foraminal narrowing, as well as spinal cord compression with hyperintense cord signal change seen on the T2 mid-sagittal image.
  • Case 3: 61-year-old healthy female who presented with bilateral finger paresthesias (right > left), slight loss of hand dexterity, and mild gait instability. Physical examination revealed bilateral positive Hoffman sign and brisk deep tendon reflexes in all extremities. MRI demonstrated canal narrowing and mild anterior cord compression at a single disc level with no evidence of abnormal intramedullary signal change.
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RESULTS

Study Selection

The literature search yielded 388 unique, potentially relevant citations, which were evaluated against the inclusion/exclusion criteria set a priori (Table 1). Two investigators independently considered studies for inclusion, and discrepancies in selection were resolved by discussion and, where necessary, evaluation of the full text. Because questions 1 and 2 are related, we combined the search results for both questions. The majority of citations (n = 354) were excluded on the basis of title and abstract evaluation, and the full text of 34 were reviewed to determine whether they met the inclusion/exclusion criteria. Of these, the majority of articles did not meet inclusion criteria (n = 12), did not assess outcomes of interest (n = 7), or reported on subject populations that overlapped with included studies (n = 4). Six other articles were excluded because they were cross-sectional comparative studies that addressed the presence/absence of disease but did not evaluate disease progression in patients with cervical spinal cord compression, spinal canal narrowing, and/or OPLL. After excluding 29 full-text articles, we identified 5 that met our inclusion criteria and are summarized in this report (Figure 2). The 5 articles represent 4 prospective cohort studies, with 2 of these articles presenting different outcomes in the same subject population.13–17 Details of the excluded articles are listed in the Supplemental Digital Content material (available at http://links.lww.com/BRS/A834).

Figure 2

Figure 2

TABLE 1

TABLE 1

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Cervical Spinal Cord Compression or Canal Stenosis

One study that evaluated prognostic factors associated with symptom development in patients with asymptomatic cervical spinal cord compression or spinal stenosis met our inclusion criteria. Results from this prospective cohort study were published in 2 different articles, which received a CoE grade of II and III.13,17

Bednarik et al13,17–19 published numerous articles on a cohort of subjects followed prospectively for development of CSM. The 2 most recent articles13,17 represent the largest subject population and longest follow-up of this cohort and are included in this review. Both articles report on the same population of 199 subjects who were recruited consecutively from patients seen between January 1993 and 2005, were followed through July 2007, and underwent at least 2-year follow-up (Table 2). For inclusion, subjects had spondylogenic or discogenic compression of the cervical spinal cord with or without concomitant change in signal intensity from the cervical cord on MRI, axial pain or clinical signs and/or symptoms of radiculopathy that could be controlled by conservative treatment, and the absence of any current clinical signs and symptoms that could be possibly attributed to cervical cord involvement. At baseline, subjects underwent a clinical examination, electrophysiological evaluation, and radiographical imaging and were followed prospectively every 6 months for the first 2 years and annually thereafter. At study entry, 70.9% of subjects (141/199) had a maximum modified Japanese Orthopaedic Assessment (mJOA) score of 18 points, and 29.1% subjects (58/199) had a decreased mJOA score of 16 or 17. Myelopathy was defined as development of clinical signs and symptoms of compressive cervical myelopathy corresponding with a decrease in mJOA score of at least 1 point.

TABLE 2-a

TABLE 2-a

TABLE 2-b

TABLE 2-b

TABLE 2-c

TABLE 2-c

Clinical evidence of the first signs and symptoms of CSM and a decrease in the mJOA score of at least 1 point were found in 22.6% of subjects (45/199), with a median follow-up duration of 44 (range: 24–144) months. In a univariate analysis, electromyographic signs of anterior horn cell lesion (RR: 2.4; 95% CI: 1.5–3.9), prolonged somatosensory-evoked potentials (SEPs; RR: 2.9; 95% CI: 1.7–5.1), prolonged motor-evoked potentials (MEPs; RR: 3.2; 95% CI: 1.9–5.6), MRI hyperintensity (RR: 1.7; 95% CI: 1.0–2.7), and clinically symptomatic radiculopathy (RR: 3.0; 95% CI: 2.0–4.4) were associated with development of myelopathy (Table 3); a multivariate analysis was not performed. Potential risk factors that were not associated with myelopathy development included age, sex, type of compression (osteophytes and/or herniation), number of stenotic levels, Pavlov ratio less than 0.8, compression ratio 0.4 or less, and spinal cord area 70 mm2 or less. Furthermore, in 8.0% of subjects (16/199), symptomatic myelopathy developed within 12 months of study entry, and the time at which 25% of subjects progressed to clinically manifested myelopathy was 48.4 months. A multivariate Cox proportional regression model revealed that prolonged SEPs (P = 0.007) and MEPs (P = 0.033), clinically symptomatic radiculopathy (P = 0.007), and a lack of MRI hyperintensity (P = 0.036) were associated with early (≤12 mo) CSM development. The 2011 article of Bednarik et al17 assessed traumatic events as a risk factor for subsequent myelopathy development and found no statistically significant association in a univariate analysis (RR: 0.9; 95% CI: 0.3–3.2).

TABLE 3-a

TABLE 3-a

TABLE 3-b

TABLE 3-b

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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).

TABLE 4

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.

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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).

Figure 3

Figure 3

Figure 4

Figure 4

TABLE 5

TABLE 5

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).

TABLE 6

TABLE 6

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Evidence Summary

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.

TABLE 7

TABLE 7

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.

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DISCUSSION

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.

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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.

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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.

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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.

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CONCLUSION

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

Summary Statements.

  • 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.
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Key Points

  • 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.
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Acknowledgments

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.

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.spinejournal.com).

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Keywords:

cervical spine; spinal cord compression; spinal canal stenosis; ossification of posterior longitudinal ligament; myelopathy

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