title: The Effect of Dimethyl Fumarate on Cerebral Gray Matter Atrophy in Multiple Sclerosis.
abstract: BACKGROUND
  The objective of this pilot study was to compare cerebral gray matter (GM) atrophy over 1 year in patients starting dimethyl fumarate (DMF) for multiple sclerosis (MS) to that of patients on no disease-modifying treatment (noDMT). DMF is an established therapy for relapsing-remitting (RR) MS.
  
  
  METHODS
  We retrospectively analyzed 20 patients with RRMS at the start of DMF [age (mean ± SD) 46.1 ± 10.2 years, Expanded Disability Status Scale (EDSS) score 1.1 ± 1.2, timed 25-foot walk (T25FW) 4.6 ± 0.8 s] and eight patients on noDMT (age 42.5 ± 6.6 years, EDSS 1.7 ± 1.1, T25FW 4.4 ± 0.6 s). Baseline and 1-year 3D T1-weighted 3T MRI was processed with automated pipelines (SIENA, FSL-FIRST) to assess percentage whole brain volume change (PBVC) and deep GM (DGM) atrophy. Group differences were assessed by analysis of covariance, with time between MRI scans as a covariate.
  
  
  RESULTS
  Over 1 year, the DMF group showed a lower rate of whole brain atrophy than the noDMT group (PBVC: -0.37 ± 0.49% vs. -1.04 ± 0.67%, p = 0.005). The DMF group also had less change in putamen volume (-0.06 ± 0.22 vs. -0.32 ± 0.28 ml, p = 0.02). There were no significant on-study differences between groups in caudate, globus pallidus, thalamus, total DGM volume, T2 lesion volume, EDSS, or T25FW (all p > 0.20).
  
  
  CONCLUSIONS
  These results suggest a treatment effect of DMF on GM atrophy appearing at 1 year after starting therapy. However, due to the retrospective study design and sample size, these findings should be considered preliminary, and require confirmation in future investigations.
  
  
  BACKGROUND
  Biogen.
authors.affiliation: Department of Neurology, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Sheena L
authors.initials: SL
authors.lastname: Dupuy
authors.affiliation: Department of Neurology, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Shahamat
authors.initials: S
authors.lastname: Tauhid
authors.affiliation: Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Shelley
authors.initials: S
authors.lastname: Hurwitz
authors.affiliation: Department of Neurology, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Renxin
authors.initials: R
authors.lastname: Chu
authors.affiliation: Department of Neurology, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Fawad
authors.initials: F
authors.lastname: Yousuf
authors.affiliation: Departments of Neurology and Radiology, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. rbakshi@post.harvard.edu.
authors.forename: Rohit
authors.identifier: http://orcid.org/0000-0001-8601-5534
authors.initials: R
authors.lastname: Bakshi
keywords: Cerebral gray matter atrophy; Dimethyl fumarate; Multiple sclerosis