• Chia-Chen Tsai, Anna Combes, Katrina McMullen, Shannon H Kolind, and Anthony L Traboulsee.
• Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
• J Neuroimaging. 2024 Nov 7.

Background And PurposeNeuromyelitis optica spectrum disorder (NMOSD) affects the optic nerves and spinal cord but can also cause focal brain inflammation. Subcortical pathology may contribute to the etiology of cognitive deficits in NMOSD. Using myelin water imaging, we investigated cerebral normal-appearing white matter (NAWM) and thalamic metrics and their association with cognition in NMOSD participants compared to healthy controls (HC).MethodsSeventeen NMOSD participants and 21 HC were scanned on a 3.0-Tesla MRI scanner using a multicomponent driven-equilibrium single-pulse observation of T1 and T2 protocol. Tissue compartment and thalamic volumes (normalized to intracranial volume), T1 relaxation time, and myelin water fraction (MWF) were reported. Eleven NMOSD participants underwent the Symbol Digit Modalities Test (SDMT) for cognitive evaluation. Group comparisons were performed using Student's t-test. The association between thalamic metrics and SDMT score was assessed using multiple regression analysis with age as a covariate.ResultsCompared to HC, NMOSD participants had reduced white matter volume (-14.2%, p < .0001), increased T1 relaxation time (+2.29%, p = .022), and lower MWF (-3.64%, p = .024) in NAWM. NMOSD group had a trend for smaller thalamic volumes than HC (-5.52%, p = .082) and no differences in thalamic MWF (p = .258) or T1 (p = .714). Thalamic T1 predicted SDMT score (adjusted R2 = .51, p = .04) when controlling for age.ConclusionsNAWM in NMOSD demonstrates diffuse abnormalities with increased water content and demyelination, suggesting a diffuse disease process overlooked by focal inflammation measures. Increased water content, as a biomarker for diffuse thalamic pathology, may partially explain cognitive impairment in NMOSD.© 2024 The Author(s). Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.

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