Glymphatic dysfunction as an indicator of disease burden and a potential biomarker in anti-NMDAR encephalitis.
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OBJECTIVE: This study aimed to explore the utility of these biomarkers for evaluating glymphatic dysfunction in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and establish their effectiveness in differentiating patients from healthy controls (HCs). METHOD: In this study, we enrolled 20 patients with anti-NMDAR encephalitis and 17 HCs. Glymphatic function was assessed using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, free water in white matter (FW-WM), and perivascular space volume fraction (PVSVF). Among the patient cohort, 13 completed follow-up MRI examinations at 3 months post-discharge. We performed correlation analyses between these glymphatic MRI indices and clinical parameters, and compared glymphatic function between patients with normal structural MRI findings and HCs. RESULTS: Patients exhibited impaired glymphatic function compared to HCs, evidenced by a lower DTI-ALPS (1.44 ± 0.16 vs. 1.62 ± 0.10, q < 0.001) and elevated FW-WM (0.21 ± 0.02 vs. 0.18 ± 0.01, q < 0.001) and PVSVF (all q < 0.05). Notably, these differences persisted even in patients with normal structural MRI (DTI-ALPS: 1.43 ± 0.22 vs. 1.62 ± 0.10, q = 0.014; FW-WM: 0.20 ± 0.02 vs. 0.18 ± 0.01, q = 0.005). Glymphatic dysfunction correlated with disease severity, showing a negative association between DTI-ALPS and CASE scores. Longitudinal analysis of the participants available for follow-up revealed improved glymphatic function (DTI-ALPS index: from 1.41 ± 0.17 to 1.50 ± 0.12; q = 0.042), alongside clinical recovery (CASE score: from 16 to 2, q = 0.005; mRS: from 5 to 1, q = 0.039). CONCLUSION: The glymphatic system could be impaired in patients with anti-NMDAR encephalitis. MRI indices of the glymphatic system may serve as biomarkers to differentiate these patients from HCs and evaluate disease severity.