II. Epidemiology
-
Incidence
- May represent up to 4% of Encephalitis cases overall
- May represent up to 20% of Encephalitis cases under age 30 years old (more common than HSV Encephalitis)
- Young patients predominate
- Mean age of onset: 21 years old
- More than one third of cases are under age 18 years
- Age range is broad (8 months to 85 years)
- Ethnicity (correlates with highest risk groups for Ovarian Teratoma)
- Black patients
- Asian American
- Pacific Islander
III. Pathophysiology
- Autoimmune Encephalitis
- Auto-Antibody forms against the NR subunit of NMDA Glutamate receptors
- Paraneoplastic phenomenon in 38% of cases
- Associated with Ovarian Teratomas in 94% of patients
IV. Findings: Four Phases
- Phase 1: Prodrome (60-80% of cases)
- Headache
- Fever
- Upper Respiratory Infection symptoms
- Gastrointestinal Symptoms
- Phase 2: Psychosis (70-80% of cases)
- Onset within days to weeks
- Anterograde Amnesia and other memory changes
- Paranoia
- Aggression
- Labile (quickly varies from calm to agitated)
- Delusions
- Hallucinations
- Seizures (75% of cases)
- Speech changes
- Phase 3: Unresponsive
- Catatonia
- Choreiform movements
- Orofacial Dyskinesia or Tardive Dyskinesia (Dystonic Reaction-like facial changes)
- Lip smacking occurs in 85% of cases
- Unusual grimace
- Teeth Clenching
- Phase 4: Hyperkinesis
- Seizures
- Autonomic instability (70-90% of cases)
- Heart Rate with Bradycardia
- Functuating Blood Pressure (low to high)
- Altered Salivary function
- Respiratory depression
V. Differential Diagnosis
VI. Labs: Lumbar Puncture findings
-
CSF Cell Count
- Lymphocytic Pleocytosis (90% of cases)
- Other CSF Non-specific findings
- CSF Protein increased (variable)
- CSF Glucose normal
- CSF Oligoclonal bands (60% of cases)
- CSF Auto-Antibody (or xNMDA receptor Antibody)
- Immunofluorescent assay for NR1 receptor Antibody
VII. Diagnostics
-
Electroencephalogram (EEG)
- Seizures are common with NMDA Encephalitis (see above)
VIII. Imaging
-
MRI Brain
- Non-specific abnormalities in 40% of cases
- Exclude other neurologic causes
-
CT Abdomen and Pelvis
- Tumors are associated with NMDA Encephalitis in both male and female patients
IX. Evaluation
- Acute
- See Altered Level of Consciousness
- See Approach to Coma
- Longterm
- Age-appropriate malignancy evaluation
- Young women should be evaluated for Ovarian Teratoma
- Age-appropriate malignancy evaluation
X. Management
- Consult Neurology early
- Start empiric Antibiotics and Acyclovir for infectious Encephalitis until definitive diagnosis
- Start empiric management while awaiting lab results (which may be delayed up to 7-10 days)
- Intravenous Immunoglobulin (IVIG)
- High dose Systemic Corticosteroids
- Methylprednisolone 1 gram in divided doses daily for 5 days
- Supportive care (e.g. Intubation, continuous EEG)
- Other measures
- Definitive surgical management of Teratoma or other causative tumor
- Plasmapheresis
- Chemotherapy to suppress B-Cell Activity
XI. Prognosis
- Best outcomes are with early intervention
- Mortality 5-7%
- Related to complications (Status Epilepticus, Pneumonia, multisystem organ failure)
- Good outcome by 3 months: 81%
- Initial improvement is slow (only 15% are improved at 1 month)
XII. References
- Claudius and Behar in Herbert (2020) EM:Rap 20(11): 5-6
- Herbert and Carr in Herbert (2014) EM:Rap 14(6): 3-4
- Ferdinand (2012) J Clin Cell Immunol S10 [PubMed]
- Maramattom (2011) Ann Indian Acad Neurol 14(3): 153–157 [PubMed]
- Titulaer (2013) Lancet Neurol 12(2): 157-65 [PubMed]