Tumefactive Demyelination at Multiple Sclerosis Onset Associates With Less Severe Long-term Disability
Albert Aboseif1, Nur Neyal2, Elizabeth Atkinson3, Caitlin Tarlton4, Christopher Schwarz2, Paul Decker3, Matthew Kosel3, Jiye Son2, Mark Keegan1, Kejal Kantarci2, Orhun Kantarci1, W. Tobin1, Burcu Zeydan1
1Division of Multiple Sclerosis and Autoimmune Neurology, Department of Neurology, 2Department of Radiology, 3Department of Quantitative Health Sciences, Mayo Clinic, 4Division of Neurology, Department of Medicine, Dalhousie University
Objective:
To determine whether frequency of spinal cord lesions and progressive disease, and severity of long-term disability differ between tumefactive (TMS) and non-tumefactive multiple sclerosis (nTMS).
Background:
Tumefactive demyelination affects ~2% of people with MS and frequently represents the index attack in TMS. Symptomatic onset is often more severe in TMS than in nTMS. Whether clinical outcomes differ between groups warrants investigation.
Design/Methods:
Individuals ≥ 18 years fulfilling 2024 McDonald Criteria were stratified into cohorts: 1) TMS with ≥ 1 tumefactive (≥ 2 cm in diameter) lesion at presentation, 2) nTMS. EDSS at last follow-up, cord lesion presence/location, progressive disease, and disease modifying therapy (DMT) exposure were compared via Kruskal-Wallis and Chi-Square tests. Multivariate logistic regression evaluated likelihood of progressive disease, adjusting for age, sex, disease duration, spinal cord lesions, any DMT exposure, and early induction therapy.
Results:
A total of 226 individuals were included: nTMS (n=158) and TMS (n=68). Median age and follow-up time of the total cohort was 48 (IQR 40,58) and 8.5 (2.3,17.0) years, respectively. nTMS had a higher frequency of spinal cord lesions (83% vs. 50%, p<0.001), lateral tract lesions (77% vs. 40%, p<0.001), upper cervical cord (C1-C3) lesions (61% vs. 24%; p<0.001), progressive disease course (32% vs. 6%, p<0.001), and severe (>5.5) EDSS at last follow-up (19% vs. 5%, p<0.006). nTMS experienced a longer time to DMT (19 [5.0,75.0] vs. 4.5 [2.0,9.3] months; p<0.001) and high-efficacy DMT (78.5 [18.3,109.3] vs. 9.0 [3.0,35.0] months; p<0.001) initiation. After adjustment, nTMS were approximately 5 times more likely to experience progressive disease than TMS (OR:5.1; p=0.02).
Conclusions:
Individuals with TMS are less likely to develop spinal cord disease, progressive disease, and severe disability compared with nTMS. Variation in DMT exposure may influence but does not fully account for dissimilar rates of progressive disease and severe disability among cohorts.
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