Abstract Details

Thalamic atrophy is known to be associated with clinical and cognitive disability in progressive multiple sclerosis (MS), however it is unclear to what extent a treatment with neuroprotective potential may modulate thalamic atrophy.

To investigate the treatment effect of Ibudilast on thalamic atrophy over 96 weeks in progressive MS.

We used data from SPRINT-MS (n = 231), a 96-week randomized controlled trial testing the effect of Ibudilast treatment on global brain atrophy measures in people with progressive MS. We used a semi-automated Bayesian Sequence Adaptive Multimodal Segmentation tool which incorporated T1, FLAIR, and fractional anisotropy (FA) maps to segment the thalamus. We investigated associations between thalamic volume and treatment groups, MS subtype [primary progressive (PPMS) vs. secondary progressive (SPMS)], and measures of clinical and cognitive disability using multivariate regression at baseline and mixed effects models for longitudinal analysis. The p-values were corrected for multiple comparisons using false discovery rate correction.  

Lower thalamic volume at baseline was associated with significantly worse cognitive, visual, and functional disability determined by the Symbol Digit Modalities Test (adjusted R² = 0.17, β = 0.004, p < 0.001), Low-Contrast Visual Acuity Test (adjusted R² = 0.03,  β = 0.001, p < 0.05), and Multiple Sclerosis Functional Composite score (adjusted R² = 0.13, β = .0002, p < 0.001), respectively. Participants receiving placebo had significantly greater atrophy on average at 48 weeks (β = -56.41, p < 0.001) and 96 weeks (β = -54.41, p < 0.01) than participants on Ibudilast. There was no significant difference on average in thalamic atrophy over the course of 96 weeks between participants with PPMS and SPMS.

Thalamic atrophy is associated with cognitive, visual, and functional disability in patients with progressive multiple sclerosis. Ibudilast appears to protect against thalamic atrophy compared to placebo.