Literature Review

Deep Gray Matter Volume Loss May Drive Disability Worsening in MS

Deep gray matter atrophy may be a useful outcome measure in neuroprotective clinical trials.


Deep gray matter volume loss drives disability accumulation in multiple sclerosis (MS), according to a multicenter, longitudinal study published in the February issue of Annals of Neurology.

The results “suggest that the development of deep gray matter atrophy may drive disability accumulation irrespective of clinical phenotypes, thereby becoming a useful outcome measure in neuroprotective clinical trials,” said Arman Eshaghi, MD, of the Queen Square MS Centre at the University College London Institute of Neurology, and colleagues.

Arman Eshaghi, MD

Gray matter atrophy occurs in all MS phenotypes. To investigate whether a spatiotemporal pattern of gray matter atrophy is associated with faster disability accumulation in MS, the investigators analyzed 3,604 high-resolution T1-weighted MRI brain scans from 1,417 participants. The investigators retrospectively collected the scans from seven European centers in the MRI in MS (MAGNIMS) network.

The study included 253 patients with clinically isolated syndrome (CIS), 708 patients with relapsing-remitting MS, 128 patients with secondary progressive MS and 125 patients with primary progressive MS with an average follow-up of 2.41 years, as well as 203 healthy controls with an average follow-up of 1.83 years. The researchers assessed disability using the Expanded Disability Status Scale (EDSS). They obtained volumes of deep gray matter; temporal, frontal, parietal, occipital, and cerebellar gray matter; brainstem; and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time to EDSS progression.

Of all baseline regional volumes, only deep gray matter predicted time to EDSS progression. For every standard deviation decrease in baseline deep gray matter volume, the risk of having a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, deep gray matter had the fastest annual rate of atrophy. This rate was faster in secondary progressive MS (–1.45%), primary progressive MS (–1.66%), and relapsing-remitting MS (–1.34%) than in CIS (–0.88%) and controls (–0.94%). The rate of temporal gray matter atrophy in secondary progressive MS (–1.21%) was significantly faster than in relapsing-remitting MS (–0.76%), CIS (–0.75%), and healthy controls (–0.51%). Only the atrophy rate in deep gray matter was significantly associated with disability accumulation, however.

—Jake Remaly

Suggested Reading

Eshaghi A, Prados F, Brownlee WJ, et al. Deep gray matter volume loss drives disability worsening in multiple sclerosis. Ann Neurol. 2018;83(2):210-222.

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