Recognizing psychiatric presentations of anti-NMDA receptor encephalitis in children and adolescents: A synthesis of published reports

Psychiatry Clin Neurosci. 2019 May;73(5):262-268. doi: 10.1111/pcn.12821. Epub 2019 Feb 21.


Aim: The aim of this study was to improve early recognition of anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDArE) in children and adolescents by identifying characteristic temporal patterns of clinical features in patients likely to be referred for psychiatric evaluation. In this form of autoimmune encephalitis, NMDAr hypofunction is caused by autoantibodies to receptor surface components. Clinical outcomes following prompt immunotherapy are usually good, but delayed treatment often results in a protracted course with significant residual disability or death. Anti-NMDArE frequently mimics psychiatric disorders, so most patients are referred initially to a psychiatrist and treated for days or weeks before being correctly diagnosed.

Methods: A systematic search of PubMed and EMBASE electronic databases identified all published reports of antibody-confirmed anti-NMDArE associated with psychiatric symptoms in patients <19 years old. Redundant reports were eliminated manually. For each patient, the order in which each feature was first observed was ranked relative to others. Median temporal ranks were used to compare the sequencing of individual features and major symptom domains.

Results: One hundred and sixty seven cases (121 females) met the inclusion criteria. The most common features were dyskinesias (77.8%), seizures (72.5%), mutism or staring (40.7%), insomnia (39.5%), language dysfunction (36.5%), fever (31.1%), disorientation/confusion (28.7%), reduced arousal (28.1%), and memory disturbance (26.9%). The configuration and temporal sequencing of features were highly variable between individuals.

Conclusion: Clinicians need to suspect this disorder: if new behavioral symptoms arise in the context of a recent viral prodrome; if they are accompanied by dyskinesias, seizures or insomnia; or if psychiatric symptoms are unusual (e.g., non-verbal auditory hallucinations).

Keywords: anti-NMDA; children; diagnosis; encephalitis; receptors.

Publication types

  • Systematic Review

MeSH terms

  • Adolescent
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / diagnosis*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / physiopathology*
  • Child
  • Female
  • Humans
  • Male