Neuroimmunocardiac Disease Mimicking Primary Psychiatric Disorders: A Systematic Review and Deep Phenotyping of Individual Patient Data
DOI:
https://doi.org/10.70577/1hvqqh24Keywords:
Anti-NMDAR encephalitis; Systematic review; Deep phenotyping; Sinus node dysfunction; Autoimmune psychosisAbstract
Background: Anti-NMDA receptor encephalitis (anti-NMDAR) frequently presents with psychiatric symptoms that are difficult to distinguish from primary psychiatric disorders. A subset of patients develops cardiac autonomic dysfunction, constituting a "neuroimmunocardiac disease" (NICD) spectrum. Objective: To systematically synthesize psychopathological features, autoantibody profiles, and cardiac involvement evidence in anti-NMDAR encephalitis. Methods: Following PRISMA 2020 guidelines, PubMed, Europe PMC, and Google Scholar were systematically searched through September 30, 2026. Studies reporting individual patient psychopathology or cardiac adverse events were included. Deep phenotyping extracted 50 fine-grained psychopathological features and cardiac event data. Results: Of 1588 records, 333 studies met inclusion criteria describing 1100 patients; 464 had detailed psychopathological descriptions. Behaviour (68%), psychosis (67%), mood (47%), catatonia (30%), and sleep disturbance (21%) were the five most frequent categories. International comparative analysis showed that anti-NMDAR encephalitis presents with hyperacute accumulation of psychopathology (median onset: 1 day vs. 180 days in primary psychoses, p<0.0001), with 21 of 58 mental state features over-represented (including catatonia and visual hallucinations) and 12 under-represented (including classic affective and psychotic symptoms). Regarding cardiac involvement, pooled analysis of 28 sinus node dysfunction (SND) cases found that 76.92% achieved complete or partial recovery following immunotherapy, with sinus arrest duration of 5.71–9.23 seconds (Tang et al., 2026). Conclusions: The neurobehavioural syndrome of anti-NMDAR encephalitis is characterized by hyperacute, dynamic, and stereotyped accumulation of psychopathology, for which the term "delirium praecox" is proposed. Associated SND is reversible in most cases with immunotherapy, though temporary pacing support may be required. Deep phenotyping provides an evidence-based foundation for identifying this treatable neuroimmunocardiac disease among primary psychiatric disorders.
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Copyright (c) 2026 Adriana Michelle Mazaquiza Lalaleo, Nataly Daniela Ocaña Arguello, Alejandro André Matamoros Delgado, Rosa Elizabeth Castillo Ebla, Katherine de los Angeles Colcha Saigua (Autor/a)
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