Fronto‐striatal damage may contribute to resistance to fatigue‐lowering medications in multiple sclerosis

Abstract

AbstractBackground and PurposeCommonly used fatigue‐lowering medications have not been proven effective in treating multiple sclerosis (MS)‐related fatigue. A neuroanatomical basis for treatment‐resistant fatigue in MS has not been explored. The aim of this study was to investigate the association between brain diffusion abnormality patterns and resistance to fatigue‐lowering treatment.MethodsRetrospective patient stratification: 1. treatment‐resistant (n = 22) received anti‐fatigue and/or anti‐depressant and/or anxiolytic medication and the latest two Modified Fatigue Impact Scale (MFIS) score≥38; 2. responder (n = 16): received anti‐fatigue and/or antidepressant and/or anxiolytic medication while the latest MFIS was <38, and minimum one previous MFIS was ≥38; 3. non‐treated never‐fatigued (n = 26): received none of the above‐mentioned medications and MFIS was always<38 (over minimum four years assessed with MFIS every 1–2 years). 3T brain MRI was used to perform a cross‐sectional voxel‐wise comparison of fractional anisotropy (FA) between the groups.ResultsTreatment‐resistant versus responder patients showed more extensive brain damage (ie, lower FA) favoring the fronto‐striatal pathways. Both groups showed more widespread brain damage than non‐treated never‐fatigued patients. A mean fronto‐striatal FA value of 0.26 could perfectly predict response to modafinil/armodafinil.ConclusionFronto‐striatal damage may play a role in the development of resistance to fatigue‐lowering treatment. Fronto‐striatal FA may serve as a biomarker to predict response to fatigue‐lowering medications in MS.