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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 top 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
  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
  2. Phase 2: Psychosis (70-80% of cases)
    1. Onset within days to weeks
    2. Anterograde amnesia and other memory changes
    3. Paranoia
    4. Delusions
    5. Hallucinations
    6. Seizures (75% of cases)
  3. Phase 3: Unresponsive
    1. Catatonia
    2. Choreiform movements
    3. Orofacial Dyskinesia or Tardive Dyskinesia
      1. Lip smacking occurs in 85% of cases
  4. Phase 4: Hyperkinesis
    1. Autonomic instability (70-90% of cases)
      1. Fluctuating Heart Rate and Blood Pressure
      2. Altered Salivary function
  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
  • 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)
  • Prognosis
  1. Best outcomes are with early intervention
  2. Good outcome by 3 months: 81%
    1. Initial improvement is slow (only 15% are improved at 1 month)