Effect of dimethyl fumarate on gray and white matter pathology in subjects with relapsing multiple sclerosis: a longitudinal study.

Abstract

Dimethyl fumarate (DMF) is an oral treatment for relapsing-remitting multiple sclerosis (MS) with anti-inflammatory and possible neuroprotective properties. Its effect on white matter and gray matter pathology is still not fully understood. The aim of the study was to characterize the effect of DMF on normal-appearing white matter (NAWM) and thalamic pathology longitudinally. In this observational, longitudinal, 24-month magnetic resonance imaging study, 75 patients with relapsing-remitting MS treated with DMF and 40 age- and sex-matched healthy individuals were enrolled. Regional diffusion tensor imaging metrics and tract-based spatial statistics analyses were used to assess differences between groups. Mean diffusivity, axial diffusivity, radial diffusivity and fractional anisotropy were measured in the thalamus and NAWM. Baseline differences and changes over time were evaluated within and between study groups. At baseline, patients with MS showed significantly increased diffusivity and decreased fractional anisotropy in the thalamus (P<0.001 for mean diffusivity, axial diffusivity and radial diffusivity) and NAWM (all P<0.016) compared with healthy individuals. No significant within-group difference was found in diffusion tensor imaging measures over 24months in either group. Healthy individuals showed a significantly greater rate of increased diffusivity parameters in the thalamus and NAWM compared with patients with MS, over 24months (P<0.05). The lack of changes in diffusion tensor imaging metrics in patients with MS over 24months possibly indicates a neuroprotective role of DMF. These findings provide additional evidence of the beneficial effect of DMF on MS-related pathology.