Accelerated grey matter degeneration in relapsing remitting multiple sclerosis

Grey matter (GM) atrophy has been suggested as the most accurate marker of neurodegeneration in multiple sclerosis (MS) progression. However, long-term comparisons between MS and healthy controls (HC) are rare, and the most significantly atrophying brain regions and their clinical importance still need robust and longitudinal validation.

This multi-cohort longitudinal observational study used two relapsing remitting MS (RRMS) cohorts (N=386, T₁w-scans=940) sampled for up to 12 years to map grey matter atrophy localisation and disease progression (Expanded Disability Status Scale (EDSS), Paced Auditory Serial Addition Test (PASAT), Fatigue Severity Scale (FSS)). The identified region-specific significant atrophy was compared with 2,163 HCs (T₁w-scans=4,326).

The strongest, replicable, significant brain atrophy patterns in RRMS were found in the frontal lobes, specifically, in the superior frontal cortex (SFC, β_age≤-0.27), pars orbitalis (β_age≤-0.25), and thalami (β_age≤-0.20). Across samples, the examined significant atrophy patterns in MS were more pronounced than in a sample of more than 20-years older HCs in the right SFC (Z>2.41, p<0.009), caudal-middle frontal cortex (Z>2.08, p<0.019), caudate (Z>2.09, p<0.019), and the left frontal pole (Z>2.42, p<0.008). The replicability of associations between volumetric and clinical outcome changes was limited and better described by whole-brain than regional volume changes.

Our findings indicate accelerated GM atrophy in people with RRMS, specific to the SFL and thalamus and related to disability-progression. These results can inform further studies examining the role of thalamic and SFC atrophy as MS-biomarkers.