Association of Specific “Critical” Demyelinating Lesions and Motor Impairment in Progressive Multiple Sclerosis: A Prospective Study
Rowaid Ahmad1, Caitlin S. Jackson-Tarlton2, Eoin P. Flanagan3, Steven Messina5, Dustin Duffy4, W. Oliver Tobin3, Michel Toledano5, Sean J. Pittock3, Claudia F. Lucchinetti3, Brian G. Weinshenker3, Orhun H. Kantarci3, B. Mark Keegan3
1Department of Neurology, University of Texas Medical Branch Glaveston, 2Neurology, Division of Neurology, Department of Medicine, Dalhousie University, Halifax, NS, Canada, 3Neurology, 45. Department of Quantitative Health Sciences, Mayo Clinic Rochester, 5Mayo Clinic
Objective:
We aimed to determine the frequency of “critical” lesions in individuals with progressive Multiple Sclerosis at a tertiary MS clinic.
Background:
“Critical” demyelinating lesions are anatomically associated with progressive motor impairment in highly selected cohorts with demyelinating disease.
Design/Methods:
Prospective, consecutively enrolled, observational cohort study of established and newly evaluated people with progressive MS at Mayo Clinic from July 1, 2021, to March 31, 2022. Comprehensive neurological examination was performed by subspecialty MS experts and clinical information and brain and spinal cord MRIs were reviewed. Progressive MS was determined to be predominantly progressive motor, cognitive, cerebellar or sensory impairment. MRI assessment was compared to clinical progressive motor impairment to determine those with: 1) one or two “tandem” “critical” demyelinating lesions with anatomic association to progressive motor impairment, often with lateral axial spinal cord distribution and focal lesion associated atrophy, 2) demyelinating lesion burden too large to identify specific lesion-associated motor progression
Results:
196 consecutive people with progressive MS (126, 64.3% SPMS, 70, 35.7% PPMS) were included (128, 65.3% established in the MS clinic and 68, 34.7% newly evaluated). 181, 92.3% people had progressive motor impairment as their presentation, 13, 6.2% ataxic and 2, 1% sensory. Among those with progressive motor impairment, 149, 76% had lesion burden too large to determine specific, lesion-associated motor progression. A specific focal “critical” lesion anatomically associated with progressive motor impairment was found in 47 (24%) (38 [19.4%] with one “critical” and 9 [4.6%] two “tandem” “critical” lesions). “Critical” demyelinating lesions were most commonly found within the lateral column of the cervical spinal cord.
Conclusions:
A statistically significant number of individuals (24%) with progressive MS have specific “critical” demyelinating lesions anatomically associated with progressive motor impairment. “Critical” demyelinating lesions are potential prognostic and therapeutic targets for progressive motor impairment in some people with MS.