Michael Gurevich1, Roy Waknin1, Evan Stone1, Anat Achiron1,2. 1. Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel. 2. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Abstract
AIMS: Fingolimod hydrochloride is an effective immunomodulatory drug in improving relapsing-remitting multiple sclerosis (RRMS). However, data on the neuroradiologic effects on white matter (WM) have not been demonstrated. In this study, we aimed elucidating the impact of 1-year fingolimod treatment on WM integrity in patients with RRMS. METHODS: Diffusion tensor imaging (DTI) was applied to assess axonal and myelin integrity in specific WM tracts of patients with RRMS prior to and 1 year postfingolimod treatment (n = 30). The fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity were analyzed using tract-based spatial statistics on specific regions of interest associated with impaired Expanded Disability Status Scale functional scores before treatment. RESULTS: In patients with impaired pyramidal function at baseline (average score 2.3 ± 0.2, n = 25), fingolimod induced a significant increase in FA (P = 0.002) and decrease in RD (P = 0.03) in the corticospinal tract. In patients with impaired cerebellar function at baseline (average score 2.0 ± 0.1, n = 19), significant increases in FA and decreases in RD were observed in the superior (P = 0.02, P = 0.01, respectively) and inferior (P = 0.03, P = 0.05, respectively) cerebellar peduncles. CONCLUSION: The observed results suggest increased microstructural integrity and decreased demyelination of damaged WM tracts and support the possible direct mechanism of fingolimod action.
AIMS: Fingolimod hydrochloride is an effective immunomodulatory drug in improving relapsing-remitting multiple sclerosis (RRMS). However, data on the neuroradiologic effects on white matter (WM) have not been demonstrated. In this study, we aimed elucidating the impact of 1-year fingolimod treatment on WM integrity in patients with RRMS. METHODS: Diffusion tensor imaging (DTI) was applied to assess axonal and myelin integrity in specific WM tracts of patients with RRMS prior to and 1 year postfingolimod treatment (n = 30). The fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity were analyzed using tract-based spatial statistics on specific regions of interest associated with impaired Expanded Disability Status Scale functional scores before treatment. RESULTS: In patients with impaired pyramidal function at baseline (average score 2.3 ± 0.2, n = 25), fingolimod induced a significant increase in FA (P = 0.002) and decrease in RD (P = 0.03) in the corticospinal tract. In patients with impaired cerebellar function at baseline (average score 2.0 ± 0.1, n = 19), significant increases in FA and decreases in RD were observed in the superior (P = 0.02, P = 0.01, respectively) and inferior (P = 0.03, P = 0.05, respectively) cerebellar peduncles. CONCLUSION: The observed results suggest increased microstructural integrity and decreased demyelination of damaged WM tracts and support the possible direct mechanism of fingolimod action.
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