Neurometabolic changes in multiple sclerosis: Fingolimod versus beta interferon or glatiramer acetate therapy

Background and Purpose Fingolimod has been shown to be more effective in reducing relapse rate and disability than injectable therapies in clinical trials. An increase in N-acetylaspartate (NAA) as measured by MR spectroscopy is correlated with maintaining axonal metabolic functions. This study compared the neurometabolic and volumetric changes in relapsing-remitting multiple sclerosis (RRMS) patients on fingolimod or injectable therapies with healthy controls (HCs). Methods Ninety-eight RRMS (52 on fingolimod, 46 on injectable therapies (27 on glatiramer acetate and 19 on interferon) were age and sex-matched to 51 HCs. RRMS patients underwent cognitive, fatigue, and mental health assessments, as well as an Expanded disability status scale (EDSS). MRI/S was acquired from the hippocampus, posterior cingulate gyrus (PCG), and prefrontal cortex (PFC). Volumetric and neurometabolic measures were compared across cohorts using a univariate general linear model and correlated with clinical severity and neuropsychological scores. Results Clinical parameters, MR-volumetric, and neurometabolic profiles showed no differences between treatment groups (p > .05). Compared to HCs, both RRMS cohorts showed volume changes in white matter (-13%), gray matter (-16%), and cerebral spinal fluid (CSF) (+17-23%), as well as reduced NAA (-17%, p = .001, hippocampus), (-7%, p = .001, PCG), and (-9%, p = .001, PFC). MRI/S metrics in three regions were moderately correlated with cognition and fatigue functions. Conclusion While both treatment arms showed overall similar volumetric and neurometabolic profiles, longitudinal studies are warranted to clarify neurometabolic changes and associations with treatment efficacy.