II. Epidemiology

  1. Incidence
    1. May represent up to 4% of Encephalitis cases overall
    2. May represent up to 20% of Encephalitis cases under age 30 years old (more common than HSV Encephalitis)
  2. Young patients predominate
    1. Mean age of onset: 21 years old
    2. More than one third of cases are under age 18 years
    3. Age range is broad (8 months to 85 years)
  3. Ethnicity (correlates with highest risk groups for Ovarian Teratoma)
    1. Black patients
    2. Asian American
    3. Pacific Islander

III. Pathophysiology

  1. Autoimmune Encephalitis
  2. Auto-Antibody forms against the NR subunit of NMDA glutamate receptors
  3. Paraneoplastic phenomenon in 38% of cases
  4. Associated with Ovarian Teratomas in 94% of patients
    1. Sensitization to NMDA receptors within TeratomaNeuronal tissue

IV. Findings: Four Phases

  1. Phase 1: Prodrome (60-80% of cases)
    1. Headache
    2. Fever
    3. Upper Respiratory Infection symptoms
    4. Gastrointestinal Symptoms
  2. Phase 2: Psychosis (70-80% of cases)
    1. Onset within days to weeks
    2. Anterograde Amnesia and other memory changes
    3. Paranoia
    4. Aggression
    5. Labile (quickly varies from calm to agitated)
    6. Delusions
    7. Hallucinations
    8. Seizures (75% of cases)
    9. Speech changes
  3. Phase 3: Unresponsive
    1. Catatonia
    2. Choreiform movements
    3. Orofacial Dyskinesia or Tardive Dyskinesia (Dystonic Reaction-like facial changes)
      1. Lip smacking occurs in 85% of cases
      2. Unusual grimace
      3. Teeth Clenching
  4. Phase 4: Hyperkinesis
    1. Seizures
    2. Autonomic instability (70-90% of cases)
      1. Heart Rate with Bradycardia
      2. Functuating Blood Pressure (low to high)
      3. Altered Salivary function
    3. Respiratory depression

VI. Labs: Lumbar Puncture findings

  1. CSF Cell Count
    1. Lymphocytic Pleocytosis (90% of cases)
  2. Other CSF Non-specific findings
    1. CSF Protein increased (variable)
    2. CSF Glucose normal
    3. CSF Oligoclonal bands (60% of cases)
  3. CSF Auto-Antibody (or xNMDA receptor Antibody)
    1. Immunofluorescent assay for NR1 receptor Antibody

VII. Diagnostics

  1. Electroencephalogram (EEG)
    1. Seizures are common with NMDA Encephalitis (see above)

VIII. Imaging

  1. MRI Brain
    1. Non-specific abnormalities in 40% of cases
    2. Exclude other neurologic causes
  2. CT Abdomen and Pelvis
    1. Tumors are associated with NMDA Encephalitis in both male and female patients

IX. Evaluation

  1. Acute
    1. See Altered Level of Consciousness
    2. See Approach to Coma
  2. Longterm
    1. Age-appropriate malignancy evaluation
      1. Young women should be evaluated for Ovarian Teratoma

X. Management

  1. Consult Neurology early
  2. Start empiric antibiotics and Acyclovir for infectious Encephalitis until definitive diagnosis
  3. Start empiric management while awaiting lab results (which may be delayed up to 7-10 days)
  4. Intravenous Immunoglobulin (IVIG)
  5. High dose Systemic Corticosteroids
    1. Methylprednisolone 1 gram in divided doses daily for 5 days
  6. Supportive care (e.g. Intubation, continuous EEG)
  7. Other measures
    1. Definitive surgical management of Teratoma or other causative tumor
    2. Plasmapheresis
    3. Chemotherapy to suppress B-Cell Activity

XI. Prognosis

  1. Best outcomes are with early intervention
  2. Mortality 5-7%
    1. Related to complications (Status Epilepticus, Pneumonia, multisystem organ failure)
  3. Good outcome by 3 months: 81%
    1. Initial improvement is slow (only 15% are improved at 1 month)

XII. References

  1. Claudius and Behar in Herbert (2020) EM:Rap 20(11): 5-6
  2. Herbert and Carr in Herbert (2014) EM:Rap 14(6): 3-4
  3. Ferdinand (2012) J Clin Cell Immunol S10 [PubMed]
  4. Maramattom (2011) Ann Indian Acad Neurol 14(3): 153–157 [PubMed]
  5. Titulaer (2013) Lancet Neurol 12(2): 157-65 [PubMed]

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Related Studies

Ontology: Anti-N-Methyl-D-Aspartate Receptor Encephalitis (C2986717)

Definition (MSH) Disorder characterized by symptoms of CATATONIA; HYPOVENTILATION; DYSKINESIAS; ENCEPHALITIS; and SEIZURES followed by a reduced CONSCIOUSNESS. It is often followed by a viral-like prodrome. Many cases are self-limiting and respond well to IMMUNOMODULATORY THERAPIES against the NMDA RECEPTORS antibodies.
Definition (NCI) An autoimmune acute encephalitis caused by antibodies against the glutamate NMDA receptor. It usually affects females and in the majority of cases it is associated with the presence of a tumor, most commonly an ovarian teratoma. The presence of a tumor in patients with this form of encephalitis implies that the latter is a paraneoplastic syndrome. It is manifested with psychiatric symptoms and epileptic seizures. It is a potentially lethal disorder; however, it is usually reversible with the prompt removal of the tumor.
Concepts Disease or Syndrome (T047)
MSH D060426
English Anti NMDA Receptor Encephalitis, Receptor Encephalitides, Anti-NMDA, Anti NMDAR Encephalitis, Encephalitides, Anti-NMDAR, Anti-N-Methyl-D-Aspartate Receptor Encephalitides, Encephalitis, Anti-NMDAR, Encephalitis, Anti-NMDA Receptor, Anti-NMDA Receptor Encephalitis, Anti-NMDAR Encephalitis, Anti N Methyl D Aspartate Receptor Encephalitis, Encephalitis, Anti-N-Methyl-D-Aspartate Receptor, Anti-NMDA Receptor Encephalitides, Encephalitides, Anti-NMDA Receptor, Anti-NMDAR Encephalitides, Anti-N-Methyl-D-Aspartate Receptor Encephalitis, Encephalitides, Anti-N-Methyl-D-Aspartate Receptor, Receptor Encephalitis, Anti-NMDA, Anti-N-Methyl-D-Aspartate Receptor Encephalitis [Disease/Finding], Anti-NMDA receptor encephalitis
French Encéphalite à anticorps anti-récepteur du NMDA, Encéphalite à anticorps anti-NMDAR, Encéphalite à anticorps anti-récepteur N-méthyl-D-aspartate, Encéphalite à anticorps anti-récepteur au NMDA, Encéphalite à anticorps anti-récepteur du N-méthyl-D-aspartate, Encéphalite à anticorps anti-récepteur au N-méthyl-D-aspartate, Encéphalite à anticorps anti-récepteur NMDA
Portuguese Encefalite Anti-Receptor de N-Metil-D-Aspartato, Encefalite por anticorpos anti-receptor do NMDA, Encefalite Antirreceptor de NMDA
Spanish Encefalitis Anti-Receptor N-Metil-D-Aspartato, Encefalitis por anticuerpos contra el receptor de NMDA
Czech encefalitida s protilátkami proti NMDA receptorům, Encefalitida s protilátkami proti NMDA receptoru
Polish Zapalenie mózgu związane z przeciwciałami przeciw receptorowi NMDA
Italian Encefalite limbica associata ad anticorpi anti-recettore NMDA, Encefalite da anticorpi anti recettore NMDA
German Anti-NMDA-Rezeptor-Enzephalitis, Anti-NMDAR-Enzephalitis, Anti-N-Methyl-D-Aspartat-Rezeptor-Enzephalitis
Dutch anti-NMDA-receptor-encefaltis
Hungarian Anti-NMDA receptor encephalitis
Japanese コウNMDAジュヨウタイノウエン, 抗NMDA受容体脳炎
Norwegian Anti-NMDA-reseptor-encefalitt, Anti-N-metyl-D-aspartat-reseptor-encefalitt