To determine if progressive unilateral motor impairment in multiple sclerosis (MS) patients with unlimited lesion burden can be attributable to a single critical demyelinating lesion.

Progressive motor impairment can be anatomically attributable to a single demyelinating lesion in “progressive solitary sclerosis” and MS patients with highly restricted central nervous system (CNS) lesion burden (≤5 lesions). These “critical lesions” are generally prominent, atrophic and located on specific corticospinal tract segments more susceptible to focal damage.

We included Mayo Clinic patients (1996-2017) with: (1) ≥1 year of exclusively unilateral motor progression; (2) >5 CNS demyelinating lesions; (3) MS diagnosis by 2017 McDonald criteria. A blinded neuroradiologist evaluated the last available brain and spinal cord MRI to identify a single potential critical lesion on the base of previously identified characteristics: (1) prominent size; (2) focal atrophy; (3) critical corticospinal tract location (spinal cord lateral column, medullary pyramid, cerebral peduncle or internal capsule).

Thirty-eight patients were included: primary progressive MS, 20 (53%); secondary progressive MS, 18 (47%). Median age at progression onset was 55 years (range, 39-73). Median EDSS was 5 (range, 2.5-7.5) at last follow-up (median, 120 months from symptom onset; range, 22-418). Progressive unilateral motor impairment was characterized by (face-sparing) hemiparesis or monoparesis. The neuroradiologist identified a potential critical lesion in 25 cases (66%): cervical cord, 19; thoracic cord, 6. In all, the progressive motor deficits were attributable to the selected lesion. The remaining 13 cases had ≥1 potential critical lesions; at least one for each patient was attributable to the motor deficit. The overall likelihood to find at least one demyelinating lesion along the corticospinal tract where the deficit localized was higher (100%) than on the contralateral side (39%) (p<0.0001).

In MS patients with unilateral motor progression, a single critical corticospinal tract lesion may be responsible.