title: Active brain changes after initiating fingolimod therapy in multiple sclerosis patients using individual voxel-based analyses for diffusion tensor imaging.
abstract: 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.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Neurology and Rehabilitation, Komaki City Hospital, Komaki, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Senda
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Brain and Mind Research Center, Nagoya University, Nagoya, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kuniyuki
authors.initials: K
authors.lastname: Endo
authors.affiliation: Department of Neurology, Nagoya Daini Red-cross Hospital, Nagoya, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yasui
authors.affiliation: Department of Neurology, Nagoya Daini Red-cross Hospital, Nagoya, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hawsegawa
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Yoneyama
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuboi
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Atsuta
authors.affiliation: Brain and Mind Research Center, Nagoya University, Nagoya, Japan.
authors.forename: Bagarinao
authors.initials: B
authors.lastname: Epifanio
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Naganawa
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
keywords: diffusion tensor imaging (DTI); fingolimod; fluid-attenuated inversion recovery (FLAIR) high-intensity signals.; multiple sclerosis (MS); voxel based morphometry (VBM)