Magnetic Resonance Imaging Evaluation of Perivascular Space Abnormalities in Neuromyelitis Optica

OBJECTIVE: Astrocytes outline the perivascular space (PVS) and regulate fluid exchange through the aquaporin‐4 water channel. As neuromyelitis optica is an autoimmune astrocytopathy targeting aquaporin‐4, we hypothesized that it could be associatied with PVS abnormalities. METHODS: A total of 34 patients, and 46 age‐ and sex‐matched healthy controls from two independent cohorts (exploratory and validation dataset) underwent a standardized 3.0‐T magnetic resonance imaging protocol including conventional and diffusion tensor imaging. Susceptibility‐weighted imaging was also acquired in the exploratory dataset. We evaluated macroscopic and microstructural abnormalities of PVS in terms of enlargement and water diffusivity (DTI‐ALPS index). In the exploration dataset, a susceptibility‐weighted sequence was used to draw the regions of interest for the DTI‐ALPS index calculation in areas having veins perpendicular to lateral ventricles. Between‐group comparisons, correlations, and regression models were run to assess associations between PVS abnormalities, and clinical and magnetic resonance imaging variables. RESULTS: Patients had a higher frequency of severe PVS enlargement in the centrum semiovale (29.4% vs 8.7%), which correlated with brain atrophy, deep grey matter atrophy, and poorer cognitive performance (r‐values range: −0.44, −0.36; p values: 0.01–0.046). In both datasets, patients had reduced DTI‐ALPS index compared with controls (p values 0.004–0.038). Lower DTI‐ALPS index, deep gray matter volume, and cortical volume could discriminate between patients and controls (R (2) = 0.62), whereas lower DTI‐ALPS index, higher number of myelitis, and higher T2‐lesion volume were associated with worse disability (R (2) = 0.55). INTERPRETATION: Patients with neuromyelitis optica spectrum disorder are characterized by abnormal enlargement and impaired water diffusion along the PVS, whose clinical implications suggest a direct correlation with disease pathogenesis and severity. ANN NEUROL 2022;92:173–183