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NMDA Encephalitis

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NMDA Encephalitis, Anti-NMDA Receptor Encephalitis, NMDA Receptor Antibody Encephalitis, NMDARE

  • 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
  • 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 teratoma Neuronal tissue
  • 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
  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
  • Diagnostics
  1. Electroencephalogram (EEG)
    1. Seizures are common with NMDA Encephalitis (see above)
  • 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
  • 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
  • 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
  • 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)
  • 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]