Refining the psychiatric syndrome of anti-N-methyl-d-aspartate receptor encephalitis

Acta Psychiatr Scand. 2018 Nov;138(5):401-408. doi: 10.1111/acps.12941. Epub 2018 Jul 10.


Objective: To review the psychiatric symptoms of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, in an attempt to differentiate the presentation from a primary psychiatric disorder.

Method: A systematic literature review of PubMed and EMBASE of all published cases of anti-NMDA receptor encephalitis was performed from inception to January 2018.

Results: There were 706 cases of anti-NMDA receptor encephalitis identified. Cases were typically young (mean age 22.6 years, SD 14.8), female (F : M ratio 3.5 : 1) and presented with significant behavioural disturbance. Reported behaviour was most commonly severe agitation and aggression, abnormal speech, and catatonia. Psychosis occurred in 45.8% of cases. Investigation results were inconsistent (MRI abnormal in 35.6%, EEG abnormal in 83.0%) and non-specific. Psychiatric treatment often required multiple psychotropics, and there may be increased risk of significant side-effects such as neuroleptic malignant syndrome. Prognosis was usually good; however, cognitive and behavioral symptoms remained prominent during recovery, and psychiatrist involvement was required in this period.

Conclusion: The presentation of anti-NMDA receptor encephalitis is variable. However, there are often psychiatric features which are atypical to a primary psychiatric illness, such as severe agitation, speech abnormalities, and catatonia, which may help early identification.

Keywords: N-methyl-d-aspartate; autoimmune; encephalitis; psychiatric; psychosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aggression / physiology*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / complications
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / physiopathology*
  • Behavioral Symptoms / etiology
  • Behavioral Symptoms / physiopathology*
  • Female
  • Humans
  • Male
  • Psychomotor Agitation / etiology
  • Psychomotor Agitation / physiopathology*
  • Psychotic Disorders / etiology
  • Psychotic Disorders / physiopathology*
  • Speech Disorders / etiology
  • Speech Disorders / physiopathology*
  • Young Adult