Related Experiment Video
Updated: Nov 30, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Occurrence and microstructural features of slowly expanding lesions on fingolimod or natalizumab treatment in
Paolo Preziosa1, Elisabetta Pagani2, Lucia Moiola3
1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy/Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Background:
In multiple sclerosis (MS), up to 57% of white matter lesions are chronically active. These slowly expanding lesions (SELs) contribute to disability progression.
Objective:
The aim of this study is to compare fingolimod and natalizumab effects on progressive linearly enlarging lesions (i.e. SELs), a putative biomarker of smouldering inflammation.
Methods:
Relapsing-remitting MS patients starting fingolimod (n = 24) or natalizumab (n = 28) underwent 3T brain magnetic resonance imaging (MRI) at baseline, months 6, 12 and 24. SELs were identified among baseline-visible lesions showing ⩾ 12.5% of annual increase, calculated by linearly fitting the Jacobian of the nonlinear deformation field between timepoints obtained combining T1- and T2-weighted scans. SEL burden, magnetization transfer ratio (MTR) and T1 signal intensity were compared using linear models.
Results:
The prevalences of fingolimod (75%) and natalizumab patients (46%) with ⩾ 1 SEL were not significantly different (adjusted-p = 0.08). Fingolimod group had higher SEL number and volume (adjusted-p ⩽ 0.047, not false discovery rate (FDR) survived). In both groups, SELs versus non-SELs showed lower MTR and T1 signal intensity (adjusted-p ⩽ 0.01, FDR-survived). Longitudinally, non-SEL MTR increased in both treatment groups (adjusted-p ⩽ 0.005, FDR-survived). T1 signal intensity decreased in SELs with both treatments (adjusted-p ⩽ 0.049, FDR-survived in fingolimod group) and increased in natalizumab non-SELs (adjusted-p = 0.03, FDR-survived).
Conclusion:
The effects of natalizumab and fingolimod on SEL occurrence seem modest, with natalizumab being slightly more effective. Both treatments may promote reparative mechanisms in stable or chronic inactive lesions.
