Grey Matter Atrophy Sequence in Multiple Sclerosis Phenotypes

Brain MRI
Brain MRI
The posterior cingulate cortex, precuneus, and thalamus were among the earliest regions to become atrophic in both relapse-onset phenotypes and primary-progressive multiple sclerosis.

For patients with multiple sclerosis (MS), gray matter atrophy spreads over time, with a similar pattern of spreading across different MS phenotypes, according to results published in Brain.

The results also indicated that the spread of atrophy was associated with disease duration and with disability accumulation over time for patients with relapsing-remitting MS.

The study included participants with clinically isolated syndrome (n=253), relapsing-remitting MS (n=708), secondary-progressive MS (n=128), primary-progressive MS (n=125), and healthy controls (n=203) from 7 European centers. Participants underwent repeated magnetic resonance imaging during a mean follow-up of 2.41 years. The researchers scored disability using the Expanded Disability Status Scale. They assigned each participant to a specific event-based model stage based on the number of atrophic regions.

For participants with clinically isolated syndrome and relapse-onset MS, the first regions to become atrophic were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem, and thalamus.

For participants with primary-progressive MS, the first regions to atrophy were the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex.

The cerebellum, caudate, and putamen showed early atrophy in participants with relapse-onset MS and late atrophy in participants with primary-progressive MS.

Participants with secondary-progressive MS showed the highest event-based model stage (the highest number of atrophic regions, P <.0001) at baseline. Participants with all MS phenotypes except clinically isolated syndrome showed a faster rate of increase in the event-based model stage compared with healthy controls.

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Both, T2 lesion load and disease duration were associated with increased event-based model stage for all participants. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting MS, independent of disease duration (P <.0001).


Eshaghi A, Marinescu RV, Young AL, et al. Progression of regional gray matter atrophy in multiple sclerosis. Brain. 2018;141:1665-1677.