Active brain changes after initiating fingolimod therapy in multiple sclerosis patients using individual voxel-based analyses for diffusion tensor imaging

Joe Senda, Hirohisa Watanabe, Kuniyuki Endo, Keizo Yasui, Yasuhiro Hawsegawa, Noritaka Yoneyama, Takashi Tsuboi, Kazuhiro Hara, Mizuki Ito, Naoki Atsuta, Bagarinao Epifanio, Masahisa Katsuno, Shinji Naganawa, Gen Sobue

Voxel-based analysis (VBA) of diffusion tensor images (DTI) and voxel-based morphometry (VBM) in patients with multiple sclerosis (MS) can sensitively detect occult tissue damage that underlies pathological changes in the brain. In the present study, both at the start of fingolimod and post-four months clinical remission, we assessed four patients with MS who were evaluated with VBA of DTI, VBM, and fluid-attenuated inversion recovery (FLAIR). DTI images for all four patients showed widespread areas of increased mean diffusivity (MD) and decreased fractional anisotropy (FA) that were beyond the high-intensity signal areas across images. After four months of continuous fingolimod therapy, DTI abnormalities progressed; in particular, MD was significantly increased, while brain volume and high-intensity signals were unchanged. These findings suggest that VBA of DTI (e.g., MD) may help assess MS demyelination as neuroinflammatory conditions, even though clinical manifestations of MS appear to be in complete remission during fingolimod.