Anti-NMDA Encephalitis

Today we are going to attempt to broaden your differential of altered mental status in the “young” patient.  While we attribute AMS or psychotic/bizarre behavior in many young patients to toxicologic causes or schizophrenia, there are other organic causes which are probably far more common than diagnosed. We are going to focus on one of these causes: Anti-NMDA Encephalitis



  • Many different presentations. Typically progresses in four stages.

  • Phase 1

o   May be prodrome of URI, flu-like syndrome, or headache.

  • Phase 2

o   Typically begins with a behavioral change

o   Cognition, memory, speech problems.

o   Odd behavior, however no prodrome: agitation, paranoia, psychosis.

o   Seizures

  • Phase 3

o   Automatisms: Twitching, lip smacking.

o   Catotonia, LOC

  • Phase 4

o   Autonomic dysfunction, hypoventiliation



  • Mean age is 21 years old!

  • Mainly affects women (~80%).

  • 38% have a paraneoplastic syndrome, almost all of these are women (97%), typically associated with a teratoma (which contain tissue with NMDA receptors).

  • It appears to be the most common individual cause of encephalitis in those youngers than age 30, even more common than HSV encephalitis.


  • Thought to be an autoimmune issue caused by an antagonist again the NR1 subunit of the NMDA receptor.

  • Some of this autoimmune activity is thought to be invoked by tumors (teratoma, ovarian).



Rule out other causes ruled out (meningitis, toxicologic causes, herpes, etc).

Should get CSF.  Send for oligoclonnal bands.  You should also send CSF to test for the anti-NMDA antibody (in addition to HSV, etc).

Otherwise patient should get EEG, MRI, CSF (probably already performed) which show non-specific abnormalities.


IVIG and Steroids (1G/day methylprednisone).  Consider plasmapheresis. Secondarily immunotherapy (rituximab) or cyclophosphamide.



Many patients take months to get better.  Phases of symptoms are generally reversed as patient improves. Those with masses do better as masses are removed. Additionally those with early treatment  do better.

Hopefully this helps to expand your differential in new onset AMS.  Remember to rule out other causes: meningitis, toxicologic, etc!

EM:RAP, David Carr


California Encephalitis Project