Patterns of Gray Matter Atrophy Linked to MS Disease Progression

computer with MR-scan of human brain
Study researchers used source-based morphometry to characterize gray matter atrophy and its 1-year evolution across different multiple sclerosis phenotypes.

Multiple sclerosis (MS) disease subtypes are associated with differing patterns of gray matter (GM) atrophy, according to study findings published in Neurology.

This was a large, multicenter study in which researchers recruited patients (n=398) with MS and healthy controls (n=170) at 8 centers in Europe from the Magnetic Resonance Imaging in MS (MAGNIMS) study consortium. Study researchers assessed patients at baseline and 1 year by magnetic resonance imaging and by the Expanded Disability Status Scale (EDSS). They quantified GM using a source-based morphometry (SBM) methodology.

The MS cohort comprised patients with relapsing-remitting MS (RRMS; n=226), secondary progressive MS (SPMS; n=95), primary progressive MS (PPMS; n=43), and clinically isolated syndrome (CIS; n=34).

At 1 year, 57 control group participants and 144 patients with MS remained in the study. Among the MS cohort, 15% presented with worsening MS, in which 2 patients progressed from CIS to RRMS and 3 from RRMS to SPMS. The patients who had worsening MS differed significantly by sex (P =.01), percentage of brain volume change (P =.02), brain T2 lesion volume (P =.04), and baseline EDSS (P =.05).

In the SBM analysis, study researchers identified 26 GM features among 98 independent components. All components indicated significant GM atrophy among the patients with MS compared with the control group participants (all P £.036) except for a component in the default-mode network (P =.07) and the frontoparietal network (P =.11).

Among patient subtypes, those with RRMS compared with those with CIS exhibited more GM atrophy for a component in the subcortical and default-mode networks (all P £.04). For patients with SPMS compared with those with PPMS, findings indicated increased GM atrophy in subcortical components (all P £.01). There was greater GM atrophy in sensorimotor components among patients with PPMS compared with those with SPMS (P <.001).

GM volume remained stable among the control cohort participants. For the MS cohort participants, however, it progressively declined in components of the cerebellar, subcortical, sensorimotor, auditory, and frontoparietal networks (all P £.04). This pattern was primarily driven by patients with progressive MS subtypes.

High baseline EDSS (r2, 0.65) was associated with lower normalized brain volume (b, -0.13; P =.001), increased GM atrophy in the sensorimotor network (b, -0.12; P =.002), and longer disease duration (b, 0.09; P =.04).

This study was limited by the low retention of patients with progressive MS at 1 year, reducing the power to assess GM atrophy among patients with severe MS phenotypes.

The study authors found that atrophy in cerebellar and sensorimotor GM was associated with clinical worsening of MS and that differing networks of GM atrophy were associated with disease subtypes. Findings “revealed a differential involvement in various GM networks across disease stages, which progressed at 1-year in MS” while “sensorimotor and cerebellar GM atrophy explained baseline disability and clinical worsening,” they concluded.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Rocca MA, Valsasina P, Meani A, et al. Association of gray matter atrophy patterns with clinical phenotype and progression in multiple sclerosis. Neurology. Published online January 13, 2021. doi:10.1212/WNL.0000000000011494