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Updated: Jul 21, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Patterns of brain atrophy in recently-diagnosed relapsing-remitting multiple sclerosis
Rozanna Meijboom1,2, Elizabeth N York1,2,3, Agniete Kampaite1,2
1Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Abstract:
Recurrent neuroinflammation in relapsing-remitting MS (RRMS) is thought to lead to neurodegeneration, resulting in progressive disability. Repeated magnetic resonance imaging (MRI) of the brain provides non-invasive measures of atrophy over time, a key marker of neurodegeneration. This study investigates regional neurodegeneration of the brain in recently-diagnosed RRMS using volumetry and voxel-based morphometry (VBM). RRMS patients (N = 354) underwent 3T structural MRI <6 months after diagnosis and 1-year follow-up, as part of the Scottish multicentre 'FutureMS' study. MRI data were processed using FreeSurfer to derive volumetrics, and FSL for VBM (grey matter (GM) only), to establish regional patterns of change in GM and normal-appearing white matter (NAWM) over time throughout the brain. Volumetric analyses showed a decrease over time (q<0.05) in bilateral cortical GM and NAWM, cerebellar GM, brainstem, amygdala, basal ganglia, hippocampus, accumbens, thalamus and ventral diencephalon. Additionally, NAWM and GM volume decreased respectively in the following cortical regions, frontal: 14 out of 26 regions and 16/26; temporal: 18/18 and 15/18; parietal: 14/14 and 11/14; occipital: 7/8 and 8/8. Left GM and NAWM asymmetry was observed in the frontal lobe. GM VBM analysis showed three major clusters of decrease over time: 1) temporal and subcortical areas, 2) cerebellum, 3) anterior cingulum and supplementary motor cortex; and four smaller clusters within the occipital lobe. Widespread GM and NAWM atrophy was observed in this large recently-diagnosed RRMS cohort, particularly in the brainstem, cerebellar GM, and subcortical and occipital-temporal regions; indicative of neurodegeneration across tissue types, and in accord with limited previous studies in early disease. Volumetric and VBM results emphasise different features of longitudinal lobar and loco-regional change, however identify consistent atrophy patterns across individuals. Atrophy measures targeted to specific brain regions may provide improved markers of neurodegeneration, and potential future imaging stratifiers and endpoints for clinical decision making and therapeutic trials.
Insights
Relapsing-remitting multiple sclerosis (RRMS) patients show widespread brain atrophy, particularly in the brainstem and cerebellum, within a year of diagnosis. These findings highlight neurodegeneration
Area of Science:
- Neuroimaging
- Neurodegeneration
- Multiple Sclerosis Research
Background:
- Recurrent neuroinflammation in relapsing-remitting multiple sclerosis (RRMS) is linked to progressive neurodegeneration and disability.
- Brain atrophy, measurable via serial magnetic resonance imaging (MRI), serves as a key indicator of neurodegeneration.
- Understanding regional brain changes in early RRMS is crucial for tracking disease progression.
Purpose of the Study:
- To investigate regional neurodegeneration patterns in recently-diagnosed RRMS patients.
- To utilize volumetric and voxel-based morphometry (VBM) analyses on structural MRI data.
- To identify specific brain regions exhibiting atrophy over a one-year period.
Main Methods:
- 3T structural MRI scans were acquired from 354 RRMS patients within six months of diagnosis and at a one-year follow-up.
- MRI data were processed using FreeSurfer for volumetric analysis and FSL for grey matter (GM) VBM.
- Analyses focused on changes in GM and normal-appearing white matter (NAWM) across the brain.
Main Results:
- Significant decreases in GM and NAWM volume were observed over one year in numerous brain regions, including cortical areas, cerebellum, brainstem, amygdala, basal ganglia, hippocampus, accumbens, thalamus, and ventral diencephalon.
- VBM analysis revealed significant GM decrease clusters in temporal/subcortical areas, cerebellum, anterior cingulum, supplementary motor cortex, and occipital lobe.
- Widespread atrophy was evident across tissue types, particularly in the brainstem, cerebellar GM, and subcortical and occipital-temporal regions.
Conclusions:
- This large cohort study demonstrates widespread GM and NAWM atrophy in early RRMS, confirming neurodegeneration across multiple brain regions.
- Volumetric and VBM analyses provide complementary insights into longitudinal regional brain changes.
- Targeted atrophy measures may serve as improved biomarkers for neurodegeneration, aiding clinical decision-making and therapeutic trial design in RRMS.
