Glymphatic dysfunction in autoimmune encephalitis: A prospective assessment with MR DTI-ALPS index

Abstract

Objective: This study aimed to evaluate glymphatic system function in patients with Autoimmune Encephalitis (AE) by utilizing the Diffusion Tensor Imaging Along the Perivascular Space (DTI- ALPS) index, with the goal of exploring its relationship with clinical outcomes.

Methods: Fifty three AE patients and 33 healthy controls (HCs) were enrolled and underwent 3T MRI examinations incorporating DTI sequences. To achieve this objective, the ALPS index, which derived by quantifying diffusivity within the perivascular spaces (PVS) surrounding the lateral ventricles, was computed. To evaluate disease progression, the modified Rankin Scale (mRS) was employed for severity assessment. Additional, relationships between the ALPS value, clinical evaluation results, and cerebrospinal fluid (CSF) indicators (including white blood cell count, total protein concentration) were explored through statistical analysis.

Results: AE patients showed significantly lower ALPS indices compared to HCs (1.34 ± 0.12 vs. 1.43 ± 0.12, p < 0.001). A moderate negative correlation was observed between the ALPS index and mRS scores (r = -0.66, p < 0.001). Among anti-NMDAR encephalitis cases, the ALPS indices recorded were found to be the lowest at 1.28 ± 0.09. The ALPS index showed a weak inverse relationship with CSF protein levels (r = -0.44, p = 0.013) but not with CSF WBC count. Early immunotherapy responders demonstrated significant glymphatic functional recovery, corresponding to an increase in the ALPS index from 1.35 ± 0.13 to 1.41 ± 0.13 (p < 0.001).

Conclusion: The ALPS index shows great potential as a non-invasive biomarker for evaluating glymphatic system impairment, and it might also be useful for tracking how well patients respond to various therapeutic interventions in the context of AE. These results indicate that glymphatic system impairment could play a role in the disease process underlying AE.