The Nurick grade was used by Barnes and Saunders31 to assess neurological change at a mean follow-up of 8.2 years. Thirteen percent of patients deteriorated, 20% improved, and 67% were unchanged after 8 years (Table 3).
Conversion to Surgery
Seven studies reported on the percentage of patients who eventually underwent surgery because of worsening neurological or functional symptoms.36–42,45 The proportion of patients who converted to surgery after failed nonoperative care ranged from 4% to 40% during a period of 3 of 7 years (Figure 4).
Activities of Daily Living.
Two studies (5 publications) evaluated the change in ADLs scores over time32,33,39,43,46 (Table 5). The prospective series by Kadanka et al 33–35,43 reported an increasing proportion of patients with worse function over time—6.3% after 1 year, 27.3% after 3 years, and 56% after 10 years of follow-up—compared with baseline. Likewise, a low-quality retrospective study by Sampath et al,46 in 2000, reported worsening ADLs scores after 11 months compared with baseline; the number of activities that worsened patients’ symptoms (ranging from 0 to 5) increased from an initial 1.8 to a final 2.5.
Timed 10-m Walk.
Kadanka et al 33–35,43 evaluated the timed 10-m walk test in conservatively treated patients with CSM during a 10-year follow-up period. They reported no difference in 10-m walk times throughout the 10-year follow-up period. At the 1-, 2-, 3- and 10-year follow-up times, Kadanka et al 33 reported times of 7.4, 7.5, 7.5, and 7.1 seconds, respectively, compared with baseline (7.4 s).
Overall Functional Status Rating.
Sampath et al 46 assessed the overall functional status rating of patients with CSM on the basis of a 4-point scale of usual work and social activities. At a 1-year follow-up, patients had nonsignificant improvements in overall functional status, work, and social activities.
Seven studies evaluated prognostic factors associated with the change in status over time in patients with CSM who received nonoperative care,31,35,37–39,41,42 but only 2 used multivariate analyses to control for other potential prognostic factors.39,42
Shimomura et al 42 evaluated prognostic factors associated with neurological deterioration in patients with CSM. They found that circumferential cord compression was associated with neurological deterioration (adjusted odds ratio: 26.6; 95% CI: 1.7–421.5). There was no significant association between age, sex, developmental factor, dynamic factor or high T2WI signal intensity, and neurological deterioration (Figure 5). Barnes and Saunders,31 in 1984, compared patients who did and did not have worse neurological status after a mean follow-up of 8.2 years. Using univariate analysis, they reported that female sex (P < 0.01), greater neck ROM (P < 0.05), greater head ROM (P < 0.01), and total head and neck ROM difference (P < 0.01) were associated with a progressively worse neurological condition.
Four studies evaluated factors associated with improved neurological status after conservative care. Kadanka et al 33 reported that older age before treatment (P < 0.05), larger transverse area of the spinal cord (P < 0.05), lower height (P < 0.05), higher value of Pavlov Index (P < 0.05), and lower entry mJOA score (P < 0.05) were predictors of an improved JOA score at 6-month and 3-year follow-up.35 Yoshimatsu et al 41 reported that shorter duration of disease was associated with improvement in JOA score, P = 0.001. They found no other prognostic factors, such as age or radiographical factors, to be statistically significant.
There is low evidence demonstrating that milder disability before treatment as measured by the motor JOA scale was associated with achieving a “no disability” status on the motor JOA scale at 6-year follow-up after conservative treatment.38 No disability status was significantly influenced by the degree of disability before treatment. Younger patients (<52 yr) and those with a shorter history of symptoms (<6 mo) achieved the level of “no disability” more frequently than their counterparts; however, these trends were not statistically significant. In another retrospective study, there were no statistically significant findings relating T2WI to a poor JOA outcome or severity of myelopathy after conservative treatment in patients with mild CSM.
Conversion to Surgery
One study by Oshima et al 39 used multivariate analysis to evaluate risk factors for patients with CSM treated nonoperatively with conversion to surgery. They reported that total cervical ROM (≥50°) (adjusted hazard ratio: 3.3), segmental kyphosis in the maximum compression segment (adjusted hazard ratio: 4.5), or presence of a local slip (adjusted hazard ratio: 4.7) was independently associated with an increased risk of requiring surgery (Figure 6). Age 60 years and more, sex, C2–C7 alignment, spinal cord diameter less than 50%, developmental canal stenosis, and segmental ROM were not statistically associated with surgery.
Although mean scores on the JOA scale tended to remain constant over time, there is moderate evidence that the proportion of patients who deteriorate by at least 1 point 3 to 6 years after the initial diagnosis of CSM ranges between 20% and 62%. Furthermore, the proportion of patients who have difficulty in performing ADLs increases over time and can be as high as 56% 10 years after diagnosis. There is low evidence that circumferential spinal cord compression compared with partial cord compression is associated with a deteriorating JOA score. There is insufficient evidence that age, sex, height, ROM, or other radiological factors influence the rate of progression of CSM (Table 6).
Although CSM is the most common cause of spinal cord impairment in adults, the amount and, most importantly, the merit of the clinical studies examining the natural history of this common and unique condition have not been sufficient to provide a clear picture about the natural history of the disease or the risk factors implicated in the progression of the disease.
Moderate evidence coming from mainly small prospective and retrospective studies suggests that the proportion of patients who progressively deteriorate (as defined by at least 1-point decrease in the JOA scale) ranges from 20% to 62%. This large variation could be explained by the different definitions of “deterioration” used in different studies. Moreover, there is moderate evidence showing that patients with CSM experience progressive difficulty in performing ADLs with nonoperative treatment. On the contrary, there is moderate evidence that there is no change in JOA 3 years after the initial assessment. Altogether, it seems that the natural history of CSM varies between patients with some of them exhibiting a slow progressive deterioration and others experiencing long periods of quiescence or slight improvement. Future basic science studies in experimental models that simulate the chronic and progressive nature of the human disease may be most appropriate to elucidate why certain patients remain stable for a long period of time and others progress.
With regard to risk factors that affect the progression of the disease, the available evidence does not suggest age as an associated factor with either the likelihood of deterioration or having surgery. It is worth noting that the available evidence is still insufficient at this point. Furthermore, there is insufficient evidence to indicate that female sex and low body height are associated with a progressively worse neurological condition. Regarding the association of radiographical characteristics, there is insufficient evidence to show that a larger transverse area of the spinal cord is associated with neurological improvement. However, low-grade evidence is available showing that circumferential spinal cord compression is associated with deteriorating neurological conditions.
Recent experimental evidence emerging from novel murine models of CSM indicates that chronic and progressive compression of the cervical spinal cord causes microvascular dysfunction, which seems to be critical for the worsening of symptoms in the CSM animals. Because microvascular dysfunction is an important component of diabetes pathophysiology, diabetes may represent an important risk factor affecting the natural history of the disease. Although our literature search revealed few studies47 that dealt with the surgical outcomes in patients with diabetes experiencing CSM, currently there are no studies examining the interrelation of diabetes with CSM. Thus, exploration of the role of diabetes as a potential risk factor for CSM should be conducted.
Finally, the lack of sensitive outcome measurements to assess the disruption of locomotion, the loss of manual dexterity, and the sensory changes at and below the level of the compression in patients with CSM in a quantitative manner have been considered to be a limiting factor in trying to accurately depict the natural history of CSM. We suggest that there is a need to develop functional outcome measures that will satisfy these conditions and in turn will allow for consistency in the international diagnosis, stratification of severity, and classification of deterioration of CSM. This is covered further in the article by Kalsi-Ryan et al 1 in this focus issue.
With an aging population, the frequency of CSM will continue to increase. Surprisingly, the narrative review we conducted indicates that the natural history of the disease remains to be fully clarified. Thus, the elucidation of the pathobiology and molecular mechanisms of neural degeneration of this unique disease is of crucial importance. Experimental research studies will serve to better direct the clinical studies toward the risk factors responsible for the progression of the disease that will lead to elucidation of the natural history of CSM. We anticipate that preclinical translational research in CSM will enable clinical trials of therapeutic modalities that will complement existing surgical treatments. In addition, careful multicenter clinical registries are needed to define the incidence and prevalence of CSM more accurately and to track the natural history of this common, debilitating condition.
Evidence-Based Clinical Recommendations.
Recommendation. Evidence concerning the natural history of CSM suggests that 20 to 60% of patients will deteriorate neurologically over time without surgical intervention. Therefore, we recommend that patients with mild CSM be counseled regarding the natural history of CSM and have the option of surgical decompression explained.
Overall Strength of Evidence. Moderate
Strength of Recommendation. Strong
Summary Statements. Chronic compression of the spinal cord results in progressive neural cell loss related to secondary mechanisms including apoptosis, neuro-inflammation, and vascular disruption.
- CSM has a unique series of pathobiological mechanisms related to chronic, progressive, spinal cord compression that distinguished this condition from traumatic SCI.
- Chronic neuroinflammation, cellular apoptosis, and microvascular compromise contribute to the pathobiology of neural degeneration in CSM.
- The neurological status of 20% to 60% of patients with mild CSM deteriorates over time without surgical intervention.
Author contributions are as follows: M.G.F.: Study design, data analysis and interpretation, manuscript preparation, and manuscript revision; S.K.: Study design, data analysis and interpretation, manuscript preparation, and manuscript revision; M.W.E.: Study design, data analysis and interpretation, manuscript preparation, and manuscript revision; J.R.D.: Study design, data analysis and interpretation, manuscript preparation, and manuscript revision; C.G.E.: Data analysis and interpretation, manuscript preparation, and manuscript revision.
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Keywords:© 2013 by Lippincott Williams & Wilkins
spinal cord microvasculature; blood-spinal cord barrier; cervical; conservative treatment; myelopathy; natural history; nonoperative; ossification of the posterior longitudinal ligament; pathophysiology; spondylosis