ArticleFrontiers in immunology2026
Glymphatic surrogate, choroid plexus remodeling, and exploratory brain network analysis in the post-acute phase of anti-NMDAR encephalitis: multimodal MRI evidence for cognitive associations and differential white matter mediation.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis typically presents with acute neuroinflammation, and many patients often experience persistent cognitive impairment during the post-acute/recovery phase. While impaired cerebrospinal fluid (CSF)-related markers-including glymphatic function and choroid plexus (CP) structural remodeling-are well documented in neurodegenerative diseases, their role in acute autoimmune brain injury remains unclear. Objective: To evaluate a glymphatic surrogate (diffusion tensor image analysis along the perivascular space (DTI-ALPS) index), choroid plexus structural remodeling (CP/intracranial volume (ICV) ratio), white matter microstructural integrity (global fractional anisotropy (FA) using tract-based spatial statistics (TBSS)), and structural covariance network (SCN) topology in anti-NMDAR encephalitis using multimodal MRI, and to investigate their associations with cognition, with an exploratory mediation analysis examining whether white matter microstructure mediates these associations. Methods: A total of 103 anti-NMDAR encephalitis patients and 97 healthy controls (HCs) with comparable sex distribution were enrolled. The glymphatic surrogate was evaluated by DTI-ALPS and CP structural remodeling was quantified by CP. White matter microstructural differences were analyzed using TBSS; mean FA values were extracted from all statistically significant clusters within the white matter skeleton (FA threshold = 0.2) after TFCE correction ( Results: Compared to HCs, patients with anti-NMDAR encephalitis showed significantly decreased bilateral DTI-ALPS indices (left: 1.361 ± 0.196 vs. 1.489 ± 0.178; right: 1.335 ± 0.183 vs. 1.483 ± 0.174; Conclusions: Patients with anti-NMDAR encephalitis exhibit concurrent glymphatic function, CP structural remodeling, widespread white matter microstructural damage, and topological reorganization. The CP/ICV ratio emerged as the primary imaging correlate of cognitive dysfunction. Although exploratory mediation suggested that FA partially accounted for the ALPS-cognition association, this likely reflects shared methodological collinearity rather than a distinct biological pathway, reinforcing CP/ICV as the more robust clinically relevant marker.These findings extend the concept of glymphatic-choroid plexus pathology from neurodegenerative diseases to post-acute autoimmune brain injury, providing a framework for non-invasive biomarkers in anti-NMDAR encephalitis.
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