Today we discussed a very interesting case of a young female who presented with 3 months of progressive behavioral disturbances, hallucinations, headache, insomnia, and a seizure. In young females with progressive symptoms and seizures, anti-NMDA receptor encephalitis is an important diagnostic consideration, although it is quite rare.

Illness Script for NMDA encephalitis:

• occurs in young females with ovarian teratomas, but can be associated with other tumors as well and is sometimes seen in men and children
• proposed association with a history of HSV encephalitis (in one study 20-30% of HSV encephalitis patients who didn’t have anti-NMDAR antibodies during their episode of encephalitis developed them later)
• Clinical presentation: headache, fever, viral-like prodrome followed by multistage progressive symptoms:
  • psychiatric manifestations: anxiety, agitation, bizarre behavior, hallucinations, delusions, disorganized thinking
  • insomnia
  • memory deficits
  • language dysfunction: diminished language output, mutism, echolalia
  • seizures
  • decreased level of consciousness, stupor with catatonic features
  • dyskinesias: orofacial, choreoathetoid movements, dystonia, rigidity, opisthotonic postures
  • autonomic instability: hyperthermia, fluctuations of BP, tachycardia, bradycardia, cardiac pauses, hypoventilation
• LP: can be initially negative or have lymphocytic pleocytosis or oligoclonal bands
• EEG: Can have infrequent epileptiform activity, but frequently slow, disordganized activity that doesn’t correlate with patient’s abnormal movements
  • Unique pattern associated with prolonged illness: extreme delta brush
• MRI: Usually normal, but can have transient FLAIR abnormalities
• Diagnosis: CSF anti-GluN1 antibodies + clinical symptoms, abnormal EEG + oligoclonal bands, and reasonable exclusion of other disorders
• Treatment:
  • Tumor resection when possible
  • Methylprednisolone 1g IV daily x5d
  • IVIG 400mg/kg IV daily x5d OR plasma exchange
  • If sypmtoms very severe, consider Rituximab