Progressive motor impairment from a critically located lesion in highly restricted CNS-demyelinating disease

Objective: To report progressive motor impairment from a critically located central nervous system (CNS) demyelinating lesion in patients with restricted magnetic resonance imaging (MRI)-lesion burden. Methods: We identified 38 patients with progressive upper motor-neuron impairment for >1 year, 2–5 MRI CNS-demyelinating lesions, with one seemingly anatomically responsible for progressive motor impairment. Patients with any alternative etiology for progressive motor impairment were excluded. A neuroradiologist blinded to clinical evaluation reviewed multiple brain and spinal-cord MRI, selecting a candidate critically located demyelinating lesion. Lesion characteristics were determined and subsequently compared with clinical course. Results: Median onset age was 47.5 years (24–64); 23 (61%) women. Median follow-up was 94 months (18–442); median Expanded Disability Status Scale Score (EDSS) at last follow-up was 4.5 (2–10). Clinical presentations were progressive: hemiparesis/monoparesis 31; quadriparesis 5; and paraparesis 2; 27 patients had progression from onset; 11 progression post-relapse. Total MRI lesions were 2 (n = 8), 3 (n = 12), 4 (n = 12), and 5 (n = 6). Critical lesions were located on corticospinal tracts, chronically atrophic in 26/38 (68%) and involved cervical spinal cord in 27, cervicomedullary/brainstem region in 6, thoracic spinal cord in 4, and subcortical white matter in 1. Conclusion: Progressive motor impairment may ascribe to a critically located CNS-demyelinating lesion in patients with highly restricted MRI burden. Motor progression from a specific demyelinating lesion has implications for understanding multiple sclerosis (MS) progression.