4.7 Article

Neuropsychiatric phenotypes of anti-NMDAR encephalitis: a prospective study

Journal

PSYCHOLOGICAL MEDICINE
Volume 53, Issue 9, Pages 4266-4274

Publisher

CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0033291722001027

Keywords

Anti-NMDAR encephalitis; autoimmune encephalitis; autoimmune psychosis; catatonia; delirium; neurology; neuropsychiatry; psychiatry; psychosis

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This study aimed to determine the behavioral hallmarks of anti-NMDA receptor encephalitis (ANMDARE). After systematic neuropsychiatric and cognitive assessments on 160 patients, the typical neuropsychiatric patterns of ANMDARE were found to be psychosis, delirium, catatonia, anxiety-depression, and mania. Cognitive function was also significantly impaired, with 34% of patients presenting predominantly neuropsychiatric symptoms without seizures.
Background Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. Methods A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. Results After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. Conclusions Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

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