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

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.