The Neuropsychiatric Phenotype of anti-NMDAr Encephalitis

Published: 25 March 2022| Version 2 | DOI: 10.17632/rrg4pnm36z.2


A prospective and longitudinal study was conducted, with patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis along a time window of seven years. Systematic clinical assessments were conducted before knowing NMDAR antibodies' results, including a bespoke inventory to register a broad scope of neuropsychiatric features, and different scales to measure the behavioral, cognitive, and functional features. CSF antibodies against the NR1 subunit of the NMDA receptor were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Outcome measures were registered.


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The sample included all patients admitted to our Institution with a diagnostic suspicion of antiNMDAR encephalitis, given by the Graus et al., criteria for possible autoimmune encephalitis, which require the following: 1) A subacute onset (rapid progression of less than 3 months) of short term memory loss, altered mental status, or psychiatric symptoms, along with at least one of the following: a) new focal central nervous system findings, b) seizures not explained by a previously known seizure disorder, c) CSF pleocytosis, d) MRI features suggestive of encephalitis, and 2) Reasonable exclusion of other causes (12). Since some patients with an acute episode of psychosis and anti-NMDAR antibodies might not fulfill Graus criteria, we also used a red flag system to suspect this entity, including 1) catatonia and/or delirium, 2) neuroleptic malignant syndrome or worsening of symptoms with antipsychotics, 3) autonomic instability, 4) dyskinesia, 5) decreased level of consciousness, 6) aphasia or dysarthria, 7) headache, 8) cognitive impairment, and/or 9) Flu-like prodrome (14). Sampling was consecutive according to inclusion and exclusion criteria. Clinical data were registered prospectively using a structured format, including sociodemographic variables, red flags and diagnostic criteria for possible autoimmune encephalitis, as well as probable anti-NMDAR encephalitis. A bespoke inventory was used at admission to register a broad scope of neurological and psychiatric features which are seen in the highly polymorphic states of acute encephalitis. This measurement tool was obtained through a review of former cases of acute encephalitis attended at our center since 1991. The Neuropsychiatric Inventory was rated in all participants at admission. The Bush and Francis Catatonia Rating Scale (BFCRS), and the Confusion Assessment Method (CAM) were used at admission and rated by trained neuropsychiatrists. To diagnose catatonia, we used the DSM-5 criteria of catatonic disorder due to a medical condition, excluding item D, as this item states that catatonia cannot be diagnosed if delirium is present. Recent research shows that delirium and catatonia may coexist and that the comorbidity is relevant. Delirium was diagnosed using the CAM algorithm and DSM-5 criteria ; it was classified as hyperactive, hypoactive, or mixed, according to Lipowski. The Montreal Cognitive Assessment (MoCA), and the Rankin scale were used to measure cognitive performance and global functional and physical disability, respectively. All clinical measures were obtained before the start of immunotherapy, and before knowing the results of antibodies determination. All individuals were assessed daily by the neurology and neuropsychiatry departments to register complications. At discharge, we registered the days of hospitalization, the Rankin scale, the MOCA and the Neuropsychiatric Inventory.


Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez