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A Longitudinal, Observational Study of the Effect of Dimethyl Fumarate on Hippocampal Metabolites in RRMS using 1H-MR Spectroscopy

Background: Dimethyl fumarate (DMF), an oral diseasemodifying treatment for Multiple Sclerosis (MS), displays anti-oxidative properties, thought to be via modulation of glutathione (GSH). However, to date, the effect of DMF on the metabolic profile of MS brains has not been evaluated. The aim of this study was to measure cross-sectional changes in hippocampal neurometabolites in Relapsing- Remitting MS (RRMS) patients, compared to Healthy Controls (HCs) and then evaluate the metabolic impact of DMF treatment longitudinally over 24 months.

Methods: 1H-MRS was undertaken on 20 RRMS patients prior to and up to 24 months post-inception of DMF treatment and 20 age sex-matched HCs. Spectroscopic data was acquired from the hippocampus using single voxel spectroscopy (6.75 mL, PRESS, TE 30 ms) at 3T.

Results: We identified a significant reduction in hippocampal N-acetylaspartate (NAA, -13%, p=0.0001) and increased myoinositol (mI, +9%, p=0.02) in RRMS patients, before starting DMF, compared to HCs. Following treatment onset, GSH levels differed significantly over 24 months in the RRMS group (F=3.5, p<0.05). There was a reduction in GSH from baseline to 1 month of treatment (p=0.014). This reduction remained statistically significant after 6 months of treatment (p=0.04), but slightly increased after 12 and 24 months of treatment (p=0.15 and 0.18, respectively), approaching levels seen in HCs.

Conclusions: The trend for the rebound effect of GSH following 24 months of DMF treatment is suggestive of recovery from the inflammatory event and is the first demonstration of an anti-oxidative effect in the MS brain following DMF treatment.


Oun Al-Iedani, Karen Ribbons, Rod Lea, Saadallah Ramadan and Jeannette Lechner-Scott

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