Anti-NMDA Receptor Encephalitis
Reviewed and revised 8 July 2014
OVERVIEW
- 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)
CLINICAL PRESENTATION
- 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)
DIFFERENTIAL DIAGNOSIS
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)
INVESTIGATIONS
- 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
MANAGEMENT
- Early removal of tumour if present
- Immunotherapy includes consideration of corticosteroids, intravenous immunoglobulin and plasma exchange therapy in severe cases
- supportive care and monitoring
PROGNOSIS
- 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
References and Links
CCC Neurocritical Care Series
Emergencies: Brain Herniation, Eclampsia, Elevated ICP, Status Epilepticus, Status Epilepticus in Paeds
DDx: Acute Non-Traumatic Weakness, Bulbar Dysfunction, Coma, Coma-like Syndromes, Delayed Awakening, Hearing Loss in ICU, ICU acquired Weakness, Post-Op Confusion, Pseudocoma, Pupillary Abnormalities
Neurology: Anti-NMDA Encephalitis, Basilar Artery Occlusion, Central Diabetes Insipidus, Cerebral Oedema, Cerebral Venous Sinus Thrombosis, Cervical (Carotid / Vertebral) Artery Dissections, Delirium, GBS vs CIP, GBS vs MG vs MND, Guillain-Barre Syndrome, Horner’s Syndrome, Hypoxic Brain Injury, Intracerebral Haemorrhage (ICH), Myasthenia Gravis, Non-convulsive Status Epilepticus, Post-Hypoxic Myoclonus, PRES, Stroke Thrombolysis, Transverse Myelitis, Watershed Infarcts, Wernicke’s Encephalopathy
Neurosurgery: Cerebral Salt Wasting, Decompressive Craniectomy, Decompressive Craniectomy for Malignant MCA Syndrome, Intracerebral Haemorrhage (ICH)
— SCI: Anatomy and Syndromes, Acute Traumatic Spinal Cord Injury, C-Spine Assessment, C-Spine Fractures, Spinal Cord Infarction, Syndomes,
— SAH: Acute management, Coiling vs Clipping, Complications, Grading Systems, Literature Summaries, ICU Management, Monitoring, Overview, Prognostication, Vasospasm
— TBI: Assessment, Base of skull fracture, Brain Impact Apnoea, Cerebral Perfusion Pressure (CPP), DI in TBI, Elevated ICP, Limitations of CT, Lund Concept, Management, Moderate Head Injury, Monitoring, Overview, Paediatric TBI, Polyuria incl. CSW, Prognosis, Seizures, Temperature
ID in NeuroCrit. Care: Aseptic Meningitis, Bacterial Meningitis, Botulism, Cryptococcosis, Encephalitis, HSV Encephalitis, Meningococcaemia, Spinal Epidural Abscess
Equipment/Investigations: BIS Monitoring, Codman ICP Monitor, Continuous EEG, CSF Analysis, CT Head, CT Head Interpretation, EEG, Extradural ICP Monitors, External Ventricular Drain (EVD), Evoked Potentials, Jugular Bulb Oxygen Saturation, MRI Head, MRI and the Critically Ill, Train of Four (TOF), Transcranial Doppler
Pharmacology: Desmopressin, Hypertonic Saline, Levetiracetam (Keppra), Mannitol, Midazolam, Sedation in ICU, Thiopentone
MISC: Brainstem Rules of 4, Cognitive Impairment in Critically Ill, Eye Movements in Coma, Examination of the Unconscious Patient, Glasgow Coma Scale (GCS), Hiccoughs, Myopathy vs Neuropathy, Neurology Literature Summaries, NSx Literature Summaries, Occulocephalic and occulovestibular reflexes, Prognosis after Cardiac Arrest, SIADH vs Cerebral Salt Wasting, Sleep in ICU
LITFL
- Neurological Mind-boggler 011 — Medically cleared?
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
- TPR — Must-read: Anti-NMDA Receptor Encephalitis (2013)
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
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