Background: Rapidly reversible weakness with neck flexion (McArdle sign) is common in patients with multiple sclerosis (MS). The pathophysiology is unknown. Objective: To evaluate changes in central motor conduction time (CMCT) in patients with and without McArdle sign. Methods: We measured McArdle sign with a torque cell and CMCT with neck flexed and extended in patients with MS, other causes of myelopathy, and healthy controls. Results: CMCT was prolonged with neck flexion disproportionately in those with MS-associated myelopathy (MSAM) with prominent McArdle sign compared to MS patients with lesser degrees of McArdle sign, and to controls. Conclusion: McArdle sign may result from stretch-induced slowing of conduction due to demyelination.