Regional patterns of grey matter volume decline in relapsing-remitting multiple sclerosis relative to healthy ageing.

BACKGROUND

Grey matter volume loss (GM-VL) is an accurate marker of multiple sclerosis (MS)-related progression. However, long-term comparisons of GM-VL between MS and healthy controls (HC) are rare, and the brain regions with most significant GM-VL and their clinical importance still need robust and longitudinal validation.

METHODS

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 localise grey matter volume loss (GM-VL) and disease progression (Expanded Disability Status Scale (EDSS), Paced Auditory Serial Addition Test (PASAT), Fatigue Severity Scale (FSS)). The identified region-specific significant GM-VL was compared with 2163 HCs (T1w-scans=4326).

RESULTS

The strongest, replicable, significant patterns of brain GM-VL in RRMS were found in the frontal lobes, specifically, in the superior frontal cortex (SFC, βage≤-0.27), pars orbitalis (βage≤-0.25), and thalami (βage≤-0.20). Compared with healthy controls (HCs) >20 years older, MS showed greater GM-VL in the right SFC, caudal-middle frontal cortex, caudate, and left frontal pole (all Z > 2.08, p < 0.019). The overlap of associations between volumetric and clinical outcome changes was limited to EDSS, which was significantly related to left hippocampal volumes βEDSS≤-0.19 in both cohorts.

CONCLUSIONS

Our findings indicate GM-VL in people with RRMS comparable to 20-year older HC, and stronger in the SFC and thalamus, and cohort-specific relationships with disability-progression.