Exploring subcortical pathology and processing speed in neuromyelitis optica spectrum disorder with myelin water imaging

Background and Purpose: Neuromyelitis 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). Methods: Seventeen NMOSD participants and 21 HC were scanned on a 3.0-Tesla MRI scanner using a multicomponent driven-equilibrium single-pulse observation of T-1 and T-2 protocol. Tissue compartment and thalamic volumes (normalized to intracranial volume), T-1 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. Results: Compared to HC, NMOSD participants had reduced white matter volume (-14.2%, p < .0001), increased T-1 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 T-1 (p = .714). Thalamic T-1 predicted SDMT score (adjusted R-2 = .51, p = .04) when controlling for age. Conclusions: NAWM 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.