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

Eur J Neurol. 2018 Mar;25(3):584-e36. doi: 10.1111/ene.13562.


Background and purpose: 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.

Methods: 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.

Results: 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 24 months 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 24 months (P < 0.05).

Conclusions: The lack of changes in diffusion tensor imaging metrics in patients with MS over 24 months possibly indicates a neuroprotective role of DMF. These findings provide additional evidence of the beneficial effect of DMF on MS-related pathology.

Keywords: magnetic resonance imaging; diffusion tensor imaging; healthy individuals; multiple sclerosis; normal-appearing white matter; thalamus; tract-based spatial statistics.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diffusion Tensor Imaging
  • Dimethyl Fumarate / pharmacology*
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Neuroprotective Agents / pharmacology*
  • Single-Blind Method
  • Thalamus / diagnostic imaging
  • Thalamus / pathology*
  • White Matter / diagnostic imaging
  • White Matter / pathology*


  • Immunosuppressive Agents
  • Neuroprotective Agents
  • Dimethyl Fumarate