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
Early online dateJul 15 2020
StatePublished - May 2021

Bibliographical note

Funding Information:
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R. M. K. has nothing to disclose. E. S. has nothing to disclose. E. P. F. is a site principal investigator in a randomized placebo-controlled clinical trial of Inebilizumab (A CD19 inhibitor) in neuromyelitis optica spectrum disorders funded by MedImmune/Viela Bio and has served on its advisory board. B. G. W. receives royalties from RSR Ltd, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for NMO and related disorders, served on adjudication committee for clinical trials in NMO being conducted by MedImmune and Alexion, and consulted for Chugai and Mitsubishi Tanabe regarding a clinical trial for NMO. J. M. has nothing to disclose. O. H. K. received speaker honoraria from Novartis and Biogen, performed a grant review for The National Multiple Sclerosis Society, and received research support from Biogen, the Multiple Sclerosis Society, the Mayo Foundation, and the Hilton Foundation. T. J. K. is a consultant for SpineThera. W. F. S. has received research support from the National Center for Advancing Translational Science. M. M. P. S. has received research funding from Biogen, Western Institute for Biomedical Research, National Multiple Sclerosis Society, and National Institutes of Health. B. M. K. has research funded by Biogen and receives publishing royalties for Common Pitfalls in Multiple Sclerosis and CNS Demyelinating Diseases. He is an editorial board member of Multiple Sclerosis and Related Disorders.

Publisher Copyright:
© The Author(s), 2020.


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

PubMed: MeSH publication types

  • Journal Article


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