Structural disconnection is associated with disability in the neuromyelitis optica spectrum disorder

Abstract

Objectives: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system. Accumulating evidence suggests there is a distinct pattern of brain lesions characteristic of NMOSD, and brain MRI has potential prognostic implications. However, the question of how the brain lesions in NMOSD are associated with its distinct clinical course remains incompletely understood. Here, we aimed to investigate the association between neurological impairment and brain lesions via brain structural disconnection.

Methods: Twenty patients were diagnosed with NMOSD according to the 2015 International Panel for NMO Diagnosis criteria. The white matter lesions were manually drawn section by section. Whole-brain structural disconnection was estimated, and connectome-based predictive modeling (CPM) was used to estimate the patient's Expanded Disability Status Scale score (EDSS) from their disconnection severity matrix. Furthermore, correlational tractography was performed to assess the fractional anisotropy (FA) and axial diffusivity (AD) of white matter fibers, which negatively correlated with the EDSS score.

Results: CPM successfully predicted the EDSS using the disconnection severity matrix (r = 0.506, p = 0.028; q² = 0.274). Among the important edges in the prediction process, the majority of edges connected the motor to the frontoparietal network. Correlational tractography identified a decreased FA and AD value according to EDSS scores in periependymal white matter tracts.

Discussion: Structural disconnection-based predictive modeling and local connectome analysis showed that frontoparietal and periependymal white matter disconnection is predictive and associated with the EDSS score of NMOSD patients.

Keywords: Disability; Local connectome; Neuromyelitis optica spectrum disorder; Structural disconnection.