Early second-line therapy is associated with improved episodic memory in anti-NMDA receptor encephalitis

Abstract

Objective: To investigate whether the early administration of intravenous second-line immunotherapy correlates with improved long-term cognition and the potential mechanisms via imaging in adult patients with moderate-to-severe anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. Methods: Sixteen adult patients with moderate-to-severe anti-NMDA receptor encephalitis past the acute stage and 15 healthy controls (HCs) performed a set of comprehensive neuropsychological tests, and underwent a resting-state fMRI study to analyze resting state functional connectivity (FC). In addition, correlation analyses were performed between hippocampal FC and cognitive performance. All patients were received intravenous first-line immunotherapy, and nine of them were also given intravenous second-line immunotherapy within 3 months of disease onset. Results: The patients who only received first-line immunotherapy showed significant verbal episodic memory impairments compared with HCs and those who received second-line immunotherapy, while no significant differences were noted between the patients with second-line immunotherapy and the HCs. In line with the results of neuropsychological tests, significant changes in bilateral hippocampal FC were observed in the patients who only received first-line immunotherapy compared with both HCs and those who received second-line immunotherapy. However, no significant differences in hippocampal FC were observed in the patients with second-line immunotherapy compared with the HCs. Importantly, hippocampal-medial prefrontal cortex (mPFC) connectivity positively correlated with memory performance. Interpretation: In the long term, early administration of intravenous second-line immunotherapy may be associated with more favorable verbal episodic memory outcomes in patients with moderate-to-severe anti-NMDA receptor encephalitis. These results may provide some evidence and guidance for the use of immunotherapy in this population.