Anti-NMDA Receptor Encephalitis

Reviewed and revised 8 July 2014


  • Anti-NMDA Receptor Encephalitis is an under-recognised progressive neurological disorder caused by antibodies against NR1-NR2 NMDA receptors
  • 60% of patients with anti-NMDA receptor encephalitis have the presence of a tumour (most commonly teratoma)


  • Up to 90% of patients are female
  • The disorder typically progresses over 1-2 weeks
  • An initial non specific flu-like prodrome (sub-febrile temperature, headache, fatigue)
  • followed by a psychotic stage with bizarre behaviour, disorientation, confusion, paranoid thoughts, visual or auditory hallucinations and memory deficits
  • In the following phase, decreased consciousness, hypoventilation, lethargy, seizures, autonomic instability and dyskinesias develop
  • evidence of a tumour (e.g. pelvic teratoma)


Diagnosis is often delayed due to resemblance to other conditions such as:

  • Infectious encephalitides (particularly HSV and HHV-6)
  • Other autoimmune etiologies (e.g. limbic encephalitis due to autoantibodies against Hu, Ma2, CV2 and amphiphysin)
  • Neuroleptic malignant syndrome
  • Lethal catatonia
  • Cerebral space-occupying lesions
  • Metabolic disorders – hyper/hypothyroidism, Cushing syndrome, Addison disease
  • Psychiatric disorders – schizophrenia, psychotic depression, pseudo-seizures
  • Drugs, toxins or withdrawal (e.g. ketamine, PCP, dextromethorphan, antipyschotic-induced movement disorders, etc)


  • NR1 and NR2 antibodies in CSF combined with a characteristic clinical picture have 100% sensitivity and specificity
  • pelvic ultrasound
  • further tests to exclude other causes of encephalopathy


  • Early removal of tumour if present
  • Immunotherapy includes consideration of corticosteroids, intravenous immunoglobulin and plasma exchange therapy in severe cases
  • supportive care and monitoring


  • Early identification and removal of tumour is associated with better outcomes (<4 months from symptom onset)
  • 47% Full Recovery
  • 28% Mild stable deficits
  • 18% Severe deficits
  • 7% Death

CCC Neurocritical Care Series


Journal articles

  • Dalmau J, Tüzün E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, Mason W, Sansing LH, Dichter MA, Rosenfeld MR, Lynch DR. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007 Jan;61(1):25-36. PMC2430743.
  • Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008 Dec;7(12):1091-8. PMC2607118.
  • Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol. 2010 Apr;257(4):509-17. PMID: 20035430.
  • Wandinger KP, Saschenbrecker S, Stoecker W, Dalmau J. Anti-NMDA-receptor encephalitis: a severe, multistage, treatable disorder presenting with psychosis. J Neuroimmunol. 2011 Feb;231(1-2):86-91. PMID: 20951441.
  • Young PJ, Baker S, Cavazzoni E, Erickson SJ, Krishnan A, Kruger PS, Rashid AH, Wibrow BA. A case series of critically ill patients with anti- N-methyl-D-aspartate receptor encephalitis. Crit Care Resusc. 2013 Mar;15(1):8-14. PMID: 23432495.

FOAM and web resources

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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