The Natural History of Degenerative Cervical Myelopathy : Clinical Spine Surgery

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Current Concepts Diagnosis & Management—CSRS Supplement 2022

The Natural History of Degenerative Cervical Myelopathy

Houten, John K. MD*,†; Shahsavarani, Shaya MD*; Verma, Rohit B. MD*

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Clinical Spine Surgery 35(10):p 396-402, December 2022. | DOI: 10.1097/BSD.0000000000001405
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Abstract

Degenerative cervical myelopathy (DCM) is the most frequent cause of spinal cord dysfunction and injury in the adult population and leads to significant loss of quality of life and economic impact from its associated medical care expenditures and loss of work.1,2 The condition is caused by progressive narrowing of the cervical spinal canal from cervical spondylosis, ossification of the posterior longitudinal ligament (OPLL), and ossification of the ligamentum flavum (OLF), conditions that tend to progress with advancing age and lead to the compression of the cervical spinal cord. Initial symptoms tend to manifest in the hands, characterized by nondermatomal numbness that starts in the fingertips and loss of manual dexterity.3,4 Patients also tend to notice dyscoordination of gait, and as the condition progresses, objective weakness becomes appreciable on examination, which is typically more prominent in the distal upper extremities. In advanced disease, the condition may lead to bowel and bladder incontinence and severe quadraparesis. An alternative mode of presentation of DCM can occur following trauma, causing signs and symptoms of central cord syndrome.5 Surgical intervention is recommended for patients manifesting progressing neurological signs and symptoms of myelopathy, but the optimal management in individuals who have mild and clinically stable disease manifestations is controversial.6,7 Understanding the natural history of DCM is, thus, important in assessing patients and identifying those most appropriately indicated for surgical management.

HISTORICAL BACKGROUND

In 1963, Lees and Turner8 published observations made in a group of 44 patients that had myelographic evidence of spondylosis and clinical spinal cord dysfunction, many of whom were followed for more than 10 years. They noted that these patients generally had long periods of stable disability interrupted by “bouts” of active symptom progression that tended to stabilize; some patients, however, demonstrated progressive deterioration. They viewed their work as building upon the early observations of Brain et al9 who viewed cervical spondylosis as a condition for which the natural tendency was to become arrested, albeit with degrees of disability. This impression that DCM was a generally a relatively benign and static condition was further echoed by Nurick.10

An opposing view that DCM is a progressive disease, however, was advanced in the work of Clarke and Robinson, who published a series of 120 patients in 1956 with degenerative spinal cord compression diagnosed by myelography, autopsy, or operation in whom progressive neurological deterioration was generally seen with rare remission They noted that “the patient who had adjusted himself more successfully to his disabilities often regarded himself as improved”; a sentiment echoed in the work of Phillips, who criticized Lees and Turner’s failure to employ the use of any standardized scale to measure myelopathic disability.11,12 Most recent literature conforms to the view that neurological dysfunction from DCM, at least in a large proportion of patients, does progress; but Nouri et al13,14 point out that the largest gap in our knowledge of DCM remains a full understanding of the disease course in nonoperatively treated patients

NATURAL HISTORY STUDIES

Many published investigations of the natural history of DCM have been limited in impact by their reliance upon poor-quality retrospective studies.15 Matsumoto et al published the results of patients with mild cervical spondylotic myelopathy (CSM) treated conservatively for at least 6 months and concluded that conservative treatment was effective in over half of such patients.16 This study, however, focused on soft disk herniation, which may have a different natural history from DCM due to stenosis caused by osteophytic ridging or OPLL; for soft disk material may desiccate and involute, leading to regression of the severity of spinal cord compression. The limited number of prospective investigations of the natural course of CSM has tended to involve small populations of patients, and each has shortcomings that tend to limit the ability to draw general inferences from their conclusions. For example, Kadanka and colleagues published a 10-year prospective study evaluating the outcome of 64 patients with nonprogressive or slowly progressive DCM that generally fell within a mild degree of the deficit on the modified Japanese Orthopedic Association (mJOA) score that was randomized to either surgery or conservative treatment. No significant difference was noted between the 2 groups. During the study course, however, some patients worsened and some improved; 17 patients expired, and 2 crossed over from the nonoperative to the surgical group; and the authors acknowledged that a power analysis of the study indicated that it likely lacked the ability to provide any definitive answer to the underlying question.17 In a systemic literature review of 10 studies that comprised 16 publications considering the natural history of DCM, Karadimas et al18 found moderate-strength evidence that 20–60% of patients will deteriorate over time without surgical intervention. Figures 1 and 2 provide illustrations of instances of the appearance or progression of clinical myelopathy during long-term observation.

F1
FIGURE 1:
MR images of a 77-year-old woman presenting with complaints of neck pain going back at least 10 years. She reported ~1 year of worsening numbness in her hands and mild gait difficulty. Neurological examination was consistent with cervical myelopathy, with findings of mild triceps and hand intrinsic weakness, increased deep tendon reflexes, and positive Hoffmann signs. Sagittal T1-weighted and T2-weighted MRI from 5 years prior (A and B), acquired to evaluate complaints of neck pain, demonstrated canal narrowing with ventral flattening of the spinal cord at C3/4. Comparable images at the time of neurosurgical assessment after the onset of myelopathic complaints (C, D) shows the progression of degenerative changes with spinal cord compression, most serious at C4/5, where cord signal change is evident.
F2
FIGURE 2:
MR T2-weighted images of a 70-year-old woman who initially presented with complaints of hand numbness but without neurological abnormalities on examination except for a unilateral Hoffman sign. She had been offered surgery but declined. Approximately 18 months later, she complained of worsening hand weakness/clumsiness and had developed appreciable weakness in the triceps and hand intrinsic muscles bilaterally. The earlier MRI (left) showed spondylosis with cord impingement at C4/5 and C6/7, findings similar to the latter MRI (right), but the follow-up study also showed interval development of T2 cord change at C6/7.

PROGNOSTIC FACTORS

Surveying the cervical myelopathy literature, many factors appear to influence the clinical course in DCM. For this reason, well-designed, prospective investigations may falter when studying highly heterogeneous populations of patients. Thus, in the absence of conclusive evidence as to the overall natural history of DCM, a clinician treating a given patient may be helped by knowledge of any patient-specific factors that might influence the expected disease course.

mJOA Score

A pattern noted in many studies of DCM patients is that surgically-managed patients tend to have more advanced myelopathy as measured by the mJOA score. Fehlings and colleagues suggest that patients with mJOA scores (as found in Table) of 14 or less (12–14 moderate, 0–11 severe scores) should be referred to spine surgery, as a systematic review of the literature showed a significant improvement in mJOA at 6–12 month, 13–36 month, and 36+ month intervals. Another study by Fehlings and colleagues demonstrated that the magnitude of improvement in mJOA scores in those with preoperative mJOA <12 was 4.91. The evidence for benefit from surgical intervention was also persuasive in those with moderate myelopathy defined as mJOA 12–14, in whom there was a mean improvement of 2.58.19

Evidence supporting surgery is less strong for those with mild myelopathy (mJOA 15–17). Kadanka et al in their randomized clinical trial published in 2011, found that milder myelopathy patients (mJOA>=14) had no significant difference in mJOA scores at 1, 2, 3, and 10 years after the presentation when comparing surgically-managed and nonsurgically-managed patients and that surgical patients had slower 10-meter walk test than nonsurgical patients.17 Thus, the guideline for this group proposed by Fehlings et al20 was a weak recommendation for surgery based on very low-quality evidence for those with mild myelopathy and consideration of nonoperative observation for those with imaging evidence of spinal cord compression without myelopathy.

Duration of Symptoms

Though some studies suggest a duration of symptoms before surgery is not a significant indicator of the degree of improvement of mJOA in patients with DCM21–23 a prospective study and a systemic literature review by Tetrault et al24,25 suggested otherwise. In the 2015 systemic review describing 13 articles in the literature at the time, 9 reported a negative significant association between the length of duration of symptoms and improved outcome scores (either mJOA, JOA, or Nurick).25

Spinal Cord Changes on MRI

Ever since MRI became widely available and bright signal in the cord on T2-weighted images was appreciated in some individuals with DCM, there has been an interest in determining whether these changes carry prognostic significance. In their prospective study published in 2001, Suri and colleagues compiled data on 146 cervical spine procedure patients with preoperative MRI imaging and in the 44 patients who also had postoperative imaging. They found greater motor function improvement in those without signal changes or patients with only changes on T2-weighted images (T2WI) when compared with patients with changes on both T1WI and T2WI.26 Furthermore, patients with regression of intramedullary signal changes had significantly improved postoperative outcomes.26 Nouri et al prospectively looked at 419 DCM patients regarding baseline MRI findings and postoperative outcomes, dividing subjects into 3 groups: no signal changes, T2WI-hyperintensity only, and T2WI-hyperintensity with T1WI-hypointensity.27 The mJOA score was lowest in those with T2WI and T1WI changes but mildest in those without cord signal change on MRI. There were no differences in surgical outcomes between the no signal change and T2WI-only groups; however, the T2WI with T1WI-hypointensity groups was associated with a significantly worse surgical outcome as determined by a significantly decreased odds ratio of achieving an mJOA score of 16 or more at 2-years follow-up, findings that were echoed in a meta-analysis by Chen et al.27,28

The utility of MRI utility in follow-up assessment of conservatively-managed patients is unclear. Ferreira et al reported a small case series of 7 patients with DSM of whom 3 refused surgery. All 3 patients had T2WI changes whereas only 2 had T1WI changes on initial evaluation and were followed up at different time intervals. Two exhibited slow progression of their clinical symptoms, but the other exhibited partial recovery of symptoms.29 Despite the study’s obvious limitations, it hints that the clinical course from conservative management of DCM may not be readily predicted from MRI changes. An example of patient deterioration during the course of nonoperative follow-up is seen in Figure 1.

Minor Trauma and Cervical Instability

Chronic microtrauma to the spinal cord is thought to be an important mechanism of injury in DCM, and sudden changes in spinal canal diameter that accentuate compression from relatively minor trauma can have devastating consequences.30 Nouri et al31 argued that dynamic imaging was necessary to capture the full extent of stenosis in the cervical spine region. Matsunaga et al32 published a retrospective study of OPLL patients where those with stenosis between 6 mm and 14 mm preferentially developed myelopathy if they had an increased range of motion and Fengbin et al33 found that the recovery rate in the JOA score in DCM patients with preexisting instability was worse than that for those with stability. Nouri et al31 argued that dynamic imaging was necessary to capture the full extent of stenosis in the cervical spine region and, thus, flexion-extension x-rays and/or MRI should be considered in indicating surgery for certain patients with mild DCM.31

Neurophysiology

Somatosenory-evoked potentials (SSEPs) and motor-evoked potentials (MEPs) have also been utilized in the literature to characterize the best candidates for DCM surgery. Sevorino et al assessed 36 DCM patients with preoperative and postoperative central conduction time (CCT), as determined from MEP, and peak latencies, as determined by SSEP, and found a significant, inverse correlation between CCT and mJOA preoperatively slowed CCTs correlated with worse mJOA scores, but no significant relationship was found between the SSEP findings and mJOA scores preoperatively. There was a significant, negative correlation between fractional anisotropy and latencies at the L1 spinous process preoperatively and fractional anisotropy significantly positively correlated with mJOA scores postoperatively findings that suggest that patients with increased CCTs and SSEP latencies are likely to benefit the most from surgery.34

Electromyography (EMG) has been described in the literature as a preoperative prognostic factor of surgical intervention in DCM. Liu and colleagues studied 94 DCM patients that underwent surgery and had preoperative MRI and EMG, grouping subjects into 4 categories based on preoperative positive or negative MRI/EMG findings. They found “excellent” surgical outcomes correlated best with those with abnormal MRI and EMGs, and that EMG normal patients had a greater proportion of poor outcomes compared with EMG abnormal patients, independent of MRI findings.35 As such, those with abnormalities in both EMG and MRI likely may have poorer outcomes than those with normal findings on both.

Less investigation has been made into whether there is a role of neurophysiology in following those with DCM managed with observation.36 Bednarik and colleagues published a prospective study describing the “presymptomatic” period of CSM in 199 patients using SSEP, MEP, and EMG findings. The patients were included in the study if they initially had axial pain or radiculopathy without any clinical signs of cervical cord involvement. Of these, 45 of 199 ultimately developed clinical myelopathy after 2-year follow-up. Abnormal EMG, MEP, and SSEP findings on initial evaluation was significantly associated with increased chance of developing CSM; furthermore, such abnormal findings among all patients who ultimately developed CSM was positively significantly correlated with an earlier time to develop CSM (< 12 mo).37 More investigation may clarify the utility of neurophysiology in determining which DCM patients will worsen without surgical intervention and the expected time course of neurological deterioration.

Congenital Parameters, Conditions, and Genetics

The normal sagittal spinal canal diameter is typically 17–18 mm between C3 and C7, and the literature describes a diameter <13 mm as a risk factor for developing cervical myelopathy.38 The Torg-Pavlov method attempts to rectify differences among patients by comparing spinal canal diameter with that of the corresponding vertebral body; a ratio of 0.82 or less suggests significant cervical spinal stenosis and, thus, a greater risk of cervical myelopathy.39,40 An illustration of Torg-Pavlov Ratio (TPR) is depicted in Figure 2.

Certain genetic conditions, including Down syndrome (DS), Ehlers-Danlos syndrome (EDS), and Morquio Syndrome are more susceptible to developing DCM, typically from a congenitally narrow spinal canal and/or ligamentous laxity with hypermobility.41,42 Klippel-Feil syndrome (KFS) causes congenital fusion of cervical vertebra and may lead to increased biomechanical stress on adjacent unfused segments and accelerated cervical spondylosis.43 Newer studies have assessed genetic factors not specific to a syndrome that predispose patients to DCM. For example, Setzer et al44,45 found ApoEϵ4 gene polymorphism correlated with an increased propensity to develop myelopathy and had delayed neurological improvement compared with their ApoE3 counterparts after decompression surgery.

Inflammatory and Other Types of Markers

The process of active spinal injury in DCM involves chemotaxis of inflammatory cells that cause local injury to the spinal cord and atrophy of interneurons and the anterior horn cells.46,47 Setzer et al describe increased TNF-alpha, IL-6, CCL3, and CXCL9 concentrations in ApoE4-positive mice.44,45 These findings raise the question as to whether the assessment of the levels of these proinflammatory markers may inform whether a patient is in an active phase of the disease and, thus, susceptible to deterioration, requiring more prompt and urgent surgical attention. Laliberte and colleagues described MIR21-5p, a microRNA central in regulating neuroinflammation in DCM. The authors found that upregulation in human and rodent studies correlated with worse initial symptoms and poorer treatment outcomes.48 Xu et al49 described other microRNAs, such as MIR-10a, −210, and −563, that may be correlated with OPLL diagnosis and may be particularly useful in high-risk populations.

Medical Comorbidities

Diabetes mellitus (DM) has been shown to negatively affect the magnitude of the deficit from DCM and the results of surgical treatment.3,24 Machino et al50 described their prospective study of 105 patients who underwent double-door laminoplasty where poor postoperative outcomes were defined as an improvement of 50% or less in the mJOA score, those with HbA1c levels 6.5% or greater were 2.591 times as likely to have poor postoperative outcomes as those with lower HbA1c levels, and those with 10 years or longer were 2.245 times as likely to have poor postoperative outcomes. Kusin et al also found in their retrospective study that DM status had a significant relationship on improvement of Nurick score after surgery for CSM, with non-diabetics having greater improvement in the Nurick score than diabetics.51

Smoking has also been implicated in negatively affecting DCM. Kim et al51 found that smoking and DM together had a higher significant odds ratio (4.01) than DM alone (2.92) in producing a poorer outcome following decompressive surgery. Kusin et al52 found that smoking may decrease benefit of earlier surgery in DCM patients.

CONCLUSIONS

Although many patients with degenerative cervical myelopathy appear to clinically deteriorate without surgery, our understanding of the natural history of DCM remains incomplete. Multiple factors appear to affect the tendency for clinical dysfunction to progress under nonoperative observation and the magnitude of clinical response to surgical decompression. Surgical management is advised for patients with moderate and severe disease and for those exhibiting clinical progression. Clinicians should assess patients with mild myelopathy and those harboring asymptomatic cervical spinal cord compression individually when making treatment decisions, and an understanding of the various factors that may influence natural history may aid in identifying those best indicated for surgery. Further investigations will likely identify how variables that affect natural history can be used in devising more precise treatment algorithms.

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Keywords:

cervical spondylotic myelopathy; cord signal change; degenerative cervical myelopathy; natural history; nonoperative management; risk factors; spinal surgery

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