Onset of progressive motor impairment in patients with critical central nervous system demyelinating lesions

Roman M. Kassa, Elia Sechi, Eoin P. Flanagan, Timothy J. Kaufmann, Orhun H. Kantarci, Brian G. Weinshenker, Jay Mandrekar, William F. Schmalstieg, M. Mateo Paz Soldan, B. Mark Keegan

Research output: Contribution to journalArticlepeer-review


Objective: To compare progressive motor impairment onset attributable to a “critical” central nervous system (CNS) demyelinating lesion in patients with highly restricted versus unlimited magnetic resonance imaging (MRI) lesion burden. Methods: We identified 135 patients with progressive motor impairment for ⩾1 year attributable to a “critical” demyelinating lesion with: MRI burden of 1 lesion (“progressive solitary sclerosis”), 2–5 lesions (“progressive paucisclerosis”), or unrestricted (>5) lesions and “progressive unilateral hemiparesis.” Neuroradiology review of brain and spinal cord MRI documented unequivocally demyelinating lesions. Results: A total of 33 (24.4%) patients had progressive solitary sclerosis; 56 (41.5%) patients had progressive paucisclerosis; and 46 (34.1%) patients had progressive unilateral hemiparesis. Median age at onset of progressive motor impairment was younger in progressive solitary sclerosis (49 years; range 24–73) and progressive paucisclerosis (50 years; range 30–64) than in progressive unilateral hemiparesis (54 years; range 39–77; p = 0.02 and p = 0.003, respectively). Within progressive unilateral hemiparesis, motor-progression onset was similar between those with 4–10, 11–20, or >20 brain lesions (55, 54, 53 years of age, respectively; p = 0.44). Conclusion: Motor-progression age is similar, but paradoxically earlier, in cohorts with highly restricted CNS lesion burden than in those with unrestricted lesion burden with progressive unilateral hemiparetic MS. The “critical” demyelinating lesion rather than total brain MRI lesion burden is the major contributor to motor-progression onset in these cohorts.

Original languageEnglish (US)
Pages (from-to)895-902
Number of pages8
JournalMultiple Sclerosis Journal
Issue number6
StatePublished - May 2021


  • Multiple sclerosis
  • critical lesion
  • demyelinating disease
  • magnetic resonance imaging
  • motor impairment

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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