Differential Myelin and Axon-Dependent Recovery Based on Symptom Duration in Degenerative Cervical Myelopathy

BACKGROUND AND OBJECTIVES: Demyelination and axonal injury are the principal pathological substrates in degenerative cervical myelopathy (DCM) and vary with duration of symptoms. Distinguishing potentially reversible and persistent microstructural spinal cord injury is expected to improve prognostication of postsurgical outcomes. In this study, we aimed to determine how symptom duration modulates the prognostic value of quantitative MRI measures of demyelination and axonal injury. METHODS: DCM patients from a single academic medical center underwent presurgical quantitative cervical spinal cord MRI as well as baseline and postsurgical (3 months after surgery) functional assessments. Demyelination was quantified using magnetization transfer ratios (MTR) both above and below the level of maximum spinal cord compression, and axonal injury was quantified using filtered diffusion weighted imaging (Daxial). Linear mixed effects models were used to determine the prognostic value of quantitative MRI and the effect of symptom duration on the prognostic value of each MRI metric. RESULTS: Sixty-five patients (median age 63 years, 60% male) were included. Baseline symptom scores and hand dexterity were significantly associated with white matter MTR rostral to the level of maximum cord compression and white matter Daxial at the caudal level. Longer symptom duration attenuated the association between rostral MTR and dexterity recovery (β = -0.27, 95% CI: [-0.52, -0.02], P = .043) but strengthened the association between caudal Daxial, dexterity (β = -7.83, 95% CI: [-13.00, -2.66], P = .003) and modified Japanese Orthopedic Association score recovery (β = 3.32, 95% CI: [0.40, 6.24], P = .025). CONCLUSION: In patients with DCM, symptom duration modulates the relative prognostic contributions of demyelination and axonal injury. Myelin integrity was the dominant predictor of baseline function and postsurgical recovery, particularly rostral to the level of compression and in earlier disease, whereas axonal injury was increasingly prognostic with longer symptom duration, more prominently at the caudal level.