Episodic Memory Impairment And Its Neurological Mechanism In Anti-NMDA Receptor Encephalitis

Part? Cognitive function recovery pattern in adult patients with severe anti-N-methyl-D-aspartate receptor encephalitis:a longitudinal studyObjective:To observe the dynamic characteristics of cognitive function following early application of immunotherapy in adult patients with severe anti N-methyl D-aspartate receptor(anti-NMDAR)encephalitis.Methods:Serial neuropsychological assessments were performed at three sequential time points in five adult patients with severe anti-NMDAR encephalitis following early-initiated immunotherapy.The three sequential points were 1-2 months,6 months and 11-12 months after treatment.Five normal subjects without psychological or neurological diseases were assessed as a control group.Results:Following early-initiated immunotherapy,all five patients demonstrated a gradual improvement of overall cognitive function over the one-year follow-up period.All patients had suffered from a comprehensive cognitive function disorder from the early stages of the illness.Six months after the immunotherapy,the treatment group showed no significant differences in verbal episodic memory function compared with the control group.One year after the immunotherapy,non-verbal episodic memory function in the treatment group had normalized.The results of other tests related to frontoparietal cognitive function revealed damage of varying degrees during these three phases.Conclusion:The results of this sequential observation study indicated a three-phase recovery pattern of cognitive function in adult patients with severe anti-NMDAR encephalitis following early initiated immunotherapy.These findings extend current understanding of the recovery mechanisms of cognitive function impairment in this disease.Part ? Early second-line immunotherapy improves verbal episodic memory in moderate-to-severe anti-NMDA receptor encephalitisObjective:To investigate whether early administration of intravenous second-line immunotherapy can improve 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,chronic-stage anti-NMDA receptor encephalitis and fifteen healthy controls(HCs)performed a set of comprehensive neuropsychological tests to assess cognitive performance,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 after disease onset.Results:The patients without second-line immunotherapy showed significant verbal episodic memory impairments compared to both HCs and the patients with 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 without second-line immunotherapy compared to both HCs and the patients with second-line immunotherapy.However,no significant differences in hippocampal FC were observed in the patients with second-line immunotherapy compared to the HCs.Importantly,hippocampal-medial prefrontal cortex(mPFC)connectivity was positively correlated with memory performance.Conclusion:In the long term,early administration of intravenous second-line immunotherapy may result in 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.Part ? Neurological mechanism of episodic memory encoding impairment in anti-NMDA receptor encephalitisObjective:To firstly explore dynamic changes in brain activation of memory-related networks during the encoding of episodic memory in patients with anti-NMDA receptor encephalitis.Methods:Fourteen adult patients with chronic-stage anti-NMDA receptor encephalitis and thirteen healthy controls(HCs)underwent a task-based fMRI study to analyze memory recall performance,general brain activation related to verbal episodic memory encoding,and compare group differences in encoding-related brain activation.In addition,we also examined the abnormal clusters of encoding-related brain activation with memory recall performance.Results:The patients showed significant verbal episodic memory impairments compared to both HCs.The beta maps of memory encoding versus Odd/Even baseline across all participants showed significant activation in a network of regions including the hippocampus,para hippocampus,fusiform gyrus(FG),middle temporal gyrus(MTG),superior temporal gyrus(STG),inferior temporal gyrus(ITG),angular gyrus(AG),insula,medial prefrontal cortex(MPFC),inferior frontal gyrus(IFG),and middle frontal gyrus(MFG).Importantly,relative to the controls,the patients showed greater activaiton in three clusters including the left FQ right MTG and MPFC during the period of verbal memory encoding.In addition,the patients showed a significant negative correlation between brain activation in the left FQ right MTG and memory recall performance.Conclusion:These results suggest that Disease-related impairments of neocortical structures rather than the hippocampus,including MPFC,MTG and FG,which mediated control and semantic processes,would influence appropriate auditory processing of verbal stimuli,impacting on verbal memory registration and hence encoding.These finding have important implications for our understanding of the neural basis underlying episodic memory impairment,and provide new biomarkers for treatment and prognostic assessment of anti-NMDA receptor encephalitis.