Progressive cortical and sub-cortical alterations in patients with anti-N-methyl-D-aspartate receptor encephalitis

Advanced structural analyses are increasingly being highly valued to uncover pathophysiological understanding of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Therefore, we aimed to explore whether and how antibody-mediated NMDAR dysfunction affected cortical and sub-cortical brain morphology and their relationship with clinical symptoms.

We performed surface-based morphometry analyses, hippocampal segmentation, and correlational analyses in 24 patients with anti-NMDAR encephalitis after acute disease stage and 30 normal controls (NC) in this case-control study.

Patients showed significantly decreased cortical alterations mainly in language network (LN) and default mode network (DMN), as well as decreased gray matter volume in left cornu ammonis 1 (CA1) body of hippocampus. Further correlation analyses showed that the decreased cortical thickness in the right superior frontier gyrus was associated with decreased cognitive scores, the decreased cortical volume in the right pars triangulari and decreased surface area in the right pars operculari were associated with decreased memory scores, whereas decreased gray matter volume in the left CA1 body was significantly correlated with longer time between first symptom and imaging in the patients.

These results suggested that cognitive impairments resulted from long-term sequelae of the encephalitis were mainly associated with cortical alterations in LN and DMN and sub-cortical atrophy of left CA1 body, which can be served as effective features to assess disease progression in clinical routine examination.