White matter lesion location correlates with disability in relapsing multiple sclerosis

Laura Gaetano; Baldur Magnusson; Petya Kindalova; Davorka Tomic; Diego Silva; Anna Altermatt; Stefano Magon; Nicole Müller-Lenke; Ernst-Wilhelm Radue; David Leppert; Ludwig Kappos; Jens Wuerfel; Dieter A Häring; Till Sprenger

doi:10.1177/2055217320906844

White matter lesion location correlates with disability in relapsing multiple sclerosis

Mult Scler J Exp Transl Clin. 2020 Feb 18;6(1):2055217320906844. doi: 10.1177/2055217320906844. eCollection 2020 Jan-Mar.

Affiliations

¹ Medical Image Analysis Center, Switzerland.
² Novartis Pharma, Switzerland.
³ Department of Statistics, University of Oxford, UK.
⁴ Biomedical Research and Training, Biomedical Research, Switzerland.
⁵ Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Switzerland.

Abstract

Background: Lesion location is a prognostic factor of disease progression and disability accrual.

Objective: To investigate lesion formation in 11 brain regions, assess correlation between lesion location and physical and cognitive disability measures and investigate treatment effects by region.

Methods: In 2355 relapsing-remitting multiple sclerosis patients from the FREEDOMS and FREEDOMS II studies, we extracted T2-weighted lesion number, volume and density for each brain region; we investigated the (Spearman) correlation in lesion formation between brain regions, studied association between location and disability (at baseline and change over 2 years) using linear/logistic regression and assessed the regional effects of fingolimod versus placebo in negative binomial models.

Results: At baseline, the majority of lesions were found in the supratentorial brain. New and enlarging lesions over 24 months developed mainly in the frontal and sublobar regions and were substantially correlated to pre-existing lesions at baseline in the supratentorial brain (p = 0.37-0.52), less so infratentorially (p = -0.04-0.23). High sublobar lesion density was consistently and significantly associated with most disability measures at baseline and worsening of physical disability over 24 months. The treatment effect of fingolimod 0.5 mg was consistent across the investigated areas and tracts.

Conclusion: These results highlight the role of sublobar lesions for the accrual of disability in relapsing-remitting multiple sclerosis.

Keywords: White matter lesion; demyelination; disability; fingolimod; frontal lobe; multiple sclerosis and neuroinflammation; multiple sclerosis: imaging.