To evaluate whether alterations in the volume of deep gray matter (DGM) and thalamic sub-nuclei correlate with clinical endpoints in placebo-treated patients in TEMSO.

Brain volume loss appears to occur early in DGM nuclei in multiple sclerosis (MS). DGM volume loss, particularly thalamic atrophy, is associated with disability progression in MS (Gaetano, Neurology 2018;90:e132432). Sensitive methods to quantify changes in these regions are therefore important and may offer promise as trial endpoints.

Patients in TEMSO were randomized 1:1:1 to placebo, teriflunomide 7 mg, or teriflunomide 14 mg for ≤108 weeks. A blinded post hoc analysis was conducted on a randomly selected subset of placebo-treated patients (n=95). T1-weighted images were analyzed using a multiple automatically generated templates (MAGeT) algorithm that segments DGM structures. Annualized percent DGM volume changes from baseline to Year 2 were compared between patients with and without relapses using rank analysis of covariance.

At Year 2, patients with (n=36) and without (n=59) relapses showed volume loss in DGM regions (thalamus, striatum, globus pallidus); median volume loss was significantly greater in patients with relapses (thalamus = −3.26% [P=0.0062]; striatum = −3.20% [P=0.0061]) vs those without (thalamus = −0.80%, striatum = −2.15%). Within sub-thalamic regions at Year 2, both groups showed volume loss in the medial geniculate, medial dorsal, lateral posterior, ventral posterior, pulvinar, ventral lateral, lateral geniculate, and central nuclei. Median volume loss was significantly greater in patients with relapses (pulvinar = −7.68% [P=0.0107], ventral lateral nucleus = −4.32% [P=0.0087]) vs those without (pulvinar = −3.08%, ventral lateral nucleus = −1.13%).

This MRI method offers promise in understanding neurodegenerative processes in specific brain regions in MS. Patients with relapses had more DGM and sub-thalamic volume loss than those without relapses, supporting the emerging idea of using DGM and thalamic atrophy as trial endpoints.