Abstract

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 < 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.

Highlights

  • To compare free-water corrected diffusion tensor imaging (DTI) measures in the normal-appearing periependymal area between AQP4-IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) to investigate occult pathophysiology

  • We conducted a single-centered prospective study, enrolling fifty-seven patients (n = 57) with the following inclusion/exclusion criteria: (1) diagnosed with MS according to the McDonald criteria; (2) diagnosed with NMOSD with AQP4-IgG according to the 2015 International Panel for NMO Diagnosis (IPND) criteria; (3) underwent MRI including diffusion tensor imaging (DTI) with three-dimensional isotropic T2-weighted fluid attenuated inversion recovery (FLAIR) and three-dimensional magnetization-prepared rapid gradient-echo (3D MPRAGE) T1-weighted MRI, both of which allow thin-section and high-resolution imaging; and other patients were excluded if (1) the MR study was incomplete (n = 6); (2) there was an image processing failure (n = 1), and (3) clinical data were unavailable (n = 7)

  • We investigated occult changes in the periependymal area in patients with NMOSD with AQP4-IgG using free-water corrected DTI, an advanced MRI technique for detecting WM changes, compared to patients with MS, which is the most confusing differential diagnosis in clinical settings

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Summary

Introduction

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. Abbreviations DTI Diffusion tensor imaging AQP4 Aquaporin 4 NMOSD Neuromyelitis optica spectrum disorder MS Multiple sclerosis MANCOVA Multivariate analysis of covariance FA Fractional anisotropy MD Mean diffusivity AD Axial diffusivity RD Radial diffusivity EDSS Expanded disability status scale. We use the term “NMOSD group” to refer to NMOSD with AQP4-IgG5,6

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