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STUDY DESIGN A retrospective case-control study. OBJECTIVE To differentiate neurodegenerative diseases from compressive cervical myelopathy (CCM) using motor evoked potentials (MEPs). SUMMARY OF BACKGROUND DATA When considering surgery for CCM, it may be necessary to differentiate the condition from a neurodegenerative disease. METHODS A total of 30 healthy volunteers, 52 typical CCM patients with single-level compression of the spinal cord at C4-5 or C5-6, seven patients with amyotrophic lateral sclerosis (ALS), and 12 patients with demyelinating disease of the central nervous system (DDC), including 11 patients with multiple sclerosis and one patient with neuromyelitis optica spectrum disorder, formed our study population. MEPs were recorded from the bilateral abductor digiti minimi (ADM) and abductor hallucis (AH) muscles using transcranial magnetic stimulation and electrical stimulation of the ulnar and tibial nerves. Central motor conduction time (CMCT), peripheral conduction time, amplitude of MEPs, and frequency of F-waves were evaluated. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off value for distinguishing between CCM and ALS. RESULTS Significant differences were observed in the amplitude of MEPs and frequency of F-waves evoked by peripheral nerve stimulation between patients with CCM and ALS. The MEP amplitude of AH was more accurate in differentiating between the two diseases compared to ADM (cut-off value, 11.2mV, sensitivity, 87.5%; specificity, 85.7%). All seven patients with ALS showed reduced frequency of F waves from ADM or AH, but none of the healthy volunteers or patients with other diseases demonstrated this finding. Moreover, there were no significant differences between CCM and DDC in any of the assessments. CONCLUSION The amplitude of MEPs and frequency of F waves evoked by peripheral nerve stimulation could be helpful in differentiating ALS from CCM.