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.

Understanding Seizures and Prognosis of the Extreme Delta Brush Pattern in Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis: A Systematic Review

“…shows the outcome and prognosis of the EDP[4,10,13,14,15,16].No differences in age and sex were observed when comparing patients with and without EDB, however, all the men in the series (4/15) had an EEG without EDB. All patients with EDB had seizures vs only 4 (40%) patients without EDB.…”

“…We found six observational studies discussing the extreme delta brush and seizures on NMDA encephalitis. Table 1 discusses the main findings in these studies [ 4 , 10 , 13 , 14 , 15 , 16 ].…”

“…Table 3 shows the bias analysis of the systematic review using the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-1) tool [ 4 , 10 , 13 , 14 , 15 , 16 ].…”

“…Limitations in Wang et al’s study were due to sample size and study design that can lead to selection bias. Additionally, this study did not focus on mild cases of anti-NMDAR encephalitis and had difficulty following up with patients [ 15 ].…”

“…In the study of Wang et al, there was a statistically significant difference between patients who receive only first-line treatments (steroids, intravenous immunoglobulin, plasmapheresis) vs first-line plus second-line therapy (rituximab, cyclophosphamide) in the relationship of seizures or EDB. Overall, using second-line therapy significantly improved verbal episodic memory outcomes in patients with anti-NMDAR encephalitis [ 15 ].…”