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To compare free-water corrected diffusion tensor imaging (DTI) measures in the normal-appearing periependymal area between AQP4-IgG-seropositive NMOSD and multiple sclerosis (MS) to investigate occult pathophysiology. This prospective study included 44 patients (mean age, 39.52 ± 11.90 years; 14 men) with AQP4-IgG-seropositive NMOSD (n = 20) and MS (n = 24) who underwent DTI between April 2014 and April 2020. Based on free-water corrected DTI measures obtained from normal-appearing periependymal voxels of (1) lateral ventricles and (2) the 3rd and 4th ventricles as dependent variables, MANCOVA was conducted to compare the two groups, using clinical variables as covariates. A significant difference was found between AQP4-IgG-seropositive NMOSD and MS in the 3rd and 4th periependymal voxels (λ = 0.462,  P  = 0.001). Fractional anisotropy, axial diffusivity was significantly decreased and radial diffusivity was increased in AQP4-IgG-seropositive NMOSD in post-hoc analysis, compared with MS ( F  = 27.616,  P  &lt; 0.001,  F  = 7.336,  P  = 0.011, and  F  = 5.800,  P  = 0.022, respectively). Free-water corrected DTI measures differ in the periependymal area surrounding the diencephalon and brain stem/cerebellum between MS and NMOSD, which may suggest occult white matter injury in areas with distribution of AQP-4 in NMOSD.

Free-water diffusion tensor imaging detects occult periependymal abnormality in the AQP4-IgG-seropositive neuromyelitis optica spectrum disorder