Unilateral motor progression in MS Association with a critical corticospinal tract lesion

Objective Progressive motor impairment anatomically attributable to a single critical demyelinating lesion on eloquent corticospinal tract locations occurs in progressive solitary sclerosis and in some patients with multiple sclerosis (MS) with highly restricted CNS lesion burden (2-5 lesions). We determined whether a similar critical lesion is found in patients with MS with unilateral motor progression and unlimited lesion burden. Methods In this observational study, we retrospectively identified Mayo Clinic patients (January 1, 1996-December 31, 2017) with an MS diagnosis (2017 McDonald criteria), >= 1 year of exclusively unilateral motor progression, and >5 demyelinating lesions on MRI. A blinded neuroradiologist identified a single critical lesion (last available MRI) based on prominent size, atrophy, and eloquent corticospinal tract location (spinal cord lateral columns, medullary pyramids, cerebral peduncles, internal capsules). We then determined whether the motor impairment was anatomically attributable to the identified lesion. Results Thirty-eight patients with MS were included: 20 (53%) with primary progressive MS and 18 (47%) with secondary progressive MS. Median age at progression onset was 54 (range 39-73) years. Median Expanded Disability Status Scale score was 5 (range 2.5-7.5) at the last follow-up (median 132.5 months from symptom onset, range 23-390 months). A single critical lesion was identified in 25 of 38 cases (66%): 19 in the cervical cord and 6 in the thoracic cord. In the remaining patients, >1 potential critical lesions were present. The overall probability to detect demyelinating lesions was higher along the corticospinal tract where the motor deficit localized (38 of 38 [100%]) than on the contralateral side (15 of 38 [39%]) (p < 0.0001). Conclusions In patients with MS with unilateral motor progression, the motor deficit may be attributable to a single critical corticospinal tract lesion.