Frequency and temporal sequence of clinical features in adults with anti-NMDA receptor encephalitis presenting with psychiatric symptoms

Psychol Med. 2019 Dec;49(16):2709-2716. doi: 10.1017/S0033291718003665. Epub 2018 Dec 18.


Background: Anti-NMDA receptor (NMDAr) encephalitis is the most common autoimmune encephalitis in adults. It mimics psychiatric disorders so often that most patients are initially referred to a psychiatrist, and many are misdiagnosed. Without prompt and effective treatment, patients are likely to suffer a protracted course with significant residual disability, or death. This study focuses on the frequency and chronology of salient clinical features in adults with anti-NMDAr encephalitis who are likely to be first evaluated by a psychiatrist because their presentation suggests a primary psychiatric disorder.

Methods: A systematic search of PubMed and EMBASE databases identified published reports of anti-NMDAr encephalitis associated with prominent behavioral or psychiatric symptoms. After eliminating redundancies, the frequencies and relative timing of clinical features were tabulated. Signs and symptoms were assigned temporal ranks based on the timing of their first appearance relative to the first appearance of other signs and symptoms in each patient; median ranks were used to compare temporal sequencing of both individual features and major symptom domains.

Results: Two hundred thirty unique cases (185 female) met study inclusion criteria. The most common features were seizures (60.4%), disorientation/confusion (42.6%), orofacial dyskinesias (39.1%), and mutism/staring (37.4%). Seizures, fever, and cognitive dysfunction were often the earliest features to emerge, but psychiatric features predominated and sequencing varied greatly between individuals.

Conclusions: Clinicians should consider anti-NMDAr encephalitis when new psychiatric symptoms are accompanied by a recent viral prodrome, seizures or unexplained fever, or when the quality of the psychiatric symptoms is unusual (e.g. non-verbal auditory hallucinations).

Keywords: NMDA receptor; anti-NMDA; diagnosis; encephalitis.

MeSH terms

  • Adult
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / diagnosis*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / physiopathology*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / psychology*
  • Databases, Factual
  • Female
  • Fever / etiology
  • Hallucinations / etiology
  • Humans
  • Male
  • Seizures / etiology