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.

Background: Anti-NMDA receptor encephalitis is an autoimmune disease characterized by severe neuropsychiatric disturbances, often misdiagnosed as a primary psychiatric disorder. Early diagnosis is crucial, as delayed immunotherapy is associated with worse outcomes. Electroencephalography (EEG) is a widely available tool for detecting abnormalities that may aid in early detection of cases that should undergo a thorough approach. Although EEG has high sensitivity, its specificity remains a challenge. Methods: This case-control study was carried out in the National Institute of Neurology and Neurosurgery of Mexico and included 241 patients with acute or subacute neuropsychiatric disturbances, raising the suspicion of autoimmune encephalitis and leading to the determination of NMDA receptor antibodies in the cerebrospinal fluid (CSF). EEG patterns were analyzed to determine the frequency of abnormal findings and their diagnostic value. Results: 140 patients were diagnosed as having definite anti-NMDA receptor encephalitis, whereas 101 had a negative determination of NMDA receptor antibodies. Psychosis was very frequent in both groups. However, severe cognitive dysfunction and catatonia were significantly more frequent in anti-NMDA receptor encephalitis patients. EEG abnormalities were significantly more frequent in patients with anti-NMDA receptor encephalitis patients (87.2% vs. 61.2%, p < 0.001). Diffuse slowing (75.7% vs. 46.6%, p < 0.001) and the extreme delta brush pattern (8.8% vs. 0%, OR = 20.6, p = 0.002) were significantly associated with anti-NMDA receptor encephalitis. Logistic regression analysis confirmed that an abnormal EEG remained strongly associated with anti-NMDA receptor encephalitis after adjusting for confounders. Conclusions: EEG abnormalities, particularly diffuse slowing and the extreme delta brush pattern, provide important diagnostic clues in patients with a clinical suspicion of anti-NMDA receptor encephalitis. While EEG has high sensitivity, its specificity is enhanced by recognizing distinct patterns. These findings support the integration of EEG into diagnostic algorithms to guide early detection and management of autoimmune encephalitis.

It is well known that as part of their response to infectious agents such as viruses, microglia transition from a quiescent state to an activated state that includes proinflammatory and anti-inflammatory phases; this behavior has been described through in vitro studies. However, recent in vivo studies on the function of microglia have questioned the two-phase paradigm; therefore, a change in the frequency of in vitro studies is expected. A systematic review was carried out to identify the microglial cytokine profile against viral infection that has been further evaluated through in vitro studies (pro-inflammatory or anti-inflammatory), along with analysis of its publication frequency over the years. For this review, 531 articles published in the English language were collected from PubMed, Web of Science, EBSCO and ResearchGate. Only 27 papers met the inclusion criteria for this systematic review. In total, 19 cytokines were evaluated in these studies, most of which are proinflammatory; the most common are IL-6, followed by TNF-α and IL-1β. It should be pointed out that half of the studies were published between 2015 and 2022 (raw data available in https://github.com/dadriba05/SystematicReview.git). In this review, we identified that evaluation of pro-inflammatory cytokines released by microglia against viral infections has been performed more frequently than that of anti-inflammatory cytokines; additionally, a higher frequency of evaluation of the response of microglia cells to viral infection through in vitro studies from 2015 and beyond was noted. Graphical Abstract In vitro assessment of microglia-released cytokines upon viral infection has been more frequent since 2015 and has focused more on pro-inflammatory cytokines.

Background: Brain MRI abnormalities in anti–NMDA receptor encephalitis (ANMDARE) are classically described in limbic structures, particularly the medial temporal lobe. Paralimbic, neocortical, and meningeal abnormalities have been less consistently reported. Objective: To evaluate the diagnostic value of brain MRI ab-normalities in patients with definite ANMDARE. Methods: We conducted a case–control study including 115 patients with ANMDARE and 115 controls with primary psychotic disorders or antibody-negative autoimmune encephalitis. Structural MRI studies were systematically reviewed by an expert neuroradiologist blinded to clinical diagnosis. Results: ANMDARE patients were younger and more frequently presented with seizures, dyskinesia, severe neuropsychiatric disturbances, abnormal cerebrospi-nal fluid and EEG findings, and worse outcomes, including mortality. T2-T2-FLAIR abnormalities commonly involved medial temporal limbic structures, paralimbic re-gions (anterior cingulate and insular cortices), and neocortical areas (parieto-occipital cortices). Pachymeningeal enhancement was observed in 26.1% of patients. MRI find-ings clearly differentiated ANMDARE from primary psychotic disorders but largely overlapped with antibody-negative autoimmune encephalitis, except for limited parie-tal and occipital differences. Conclusions: T2-FLAIR MRI abnormalities involving me-dial temporal, paralimbic, and posterior neocortical regions are common in ANMDARE. Pachymeningeal enhancement is not rare. While useful for distinguishing ANMDARE from primary psychotic disorders, a substantial overlap with anti-body-negative autoimmune encephalitis was observed.