Glymphatic dysfunction as an indicator of disease burden and a potential biomarker in anti-NMDAR encephalitis

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).

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.

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).

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.