Evaluation of Subcortical Pathology and Association with Cognition in Neuromyelitis Optica Spectrum Disorders with Myelin Water Imaging
Chia-Chen Tsai1, Anna Combes3, Shannon Kolind2, Anthony Traboulsee2
1Faculty of Medicine, 2Division of Neurology, Department of Medicine, University of British Columbia, 3Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, University College London
Objective:
To investigate cerebral normal-appearing white matter (NAWM) and thalamus abnormalities and association to cognition in neuromyelitis optica spectrum disorder (NMOSD) participants compared to healthy controls (HC) using myelin water imaging (MWI).
Background:
NMOSD, an inflammatory disease of the central nervous system, affects mainly the optic nerves and spinal cord but can also cause focal brain inflammation. Due to inconsistent magnetic resonance imaging (MRI) findings, NAWM and subcortical abnormalities and associations with cognition in NMOSD remain unclear. MWI, an MRI technique that quantifies myelin content through myelin water fraction (MWF), identifies myelin changes not visible on traditional MRI.
Design/Methods:
19 NMOSD participants and 21 age- and sex-matched HC were scanned on a 3.0T MRI scanner using a multi-component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) protocol. Tissue-compartment and thalamic volumes (normalized to intracranial volume), T1 relaxation time, and MWF were reported. 12 NMOSD participants underwent the Symbol Digit Modalities Test (SDMT) for cognitive evaluation. Group comparisons were performed using Student’s t-test. The association between thalamus metrics and SDMT score was assessed using multiple regression analysis with age as a covariate.
Results:
Compared to HC, NMOSD participants had higher T1 (+2.15%, p=0.024) and lower (though not reaching significance) MWF (-2.96%, p=0.068) across NAWM. NMOSD group had reduced, though insignificantly, thalamic volumes compared to HC (-5.35%, p=0.084). There was no significant difference in thalamus MWF (p=0.457) or T1 (p=0.636) between groups. There was a significant association of SDMT score with thalamus MWF (R=0.602, p=0.0226) and T1 (R=-0.772, p=0.002).
Conclusions:
NAWM in NMOSD demonstrates diffuse abnormalities with increased water content and possibly diffuse demyelination that could suggest a disease process overlooked by focal inflammation. Additionally, diffuse thalamic pathology including increased water, demyelination, and atrophy are strong predictors of cognitive performance in NMOSD. Finally, MWI detects myelin integrity changes, providing new insight into NMOSD brain pathology.