Anti-NMDA Receptor Antibody Encephalitis – In one page

Clinical Presentation – Typically affects Females > males. Age range 8 months to >45 years

 Prodromal symptoms of headache, fever, viral-like illness

 Days later, start having a progression of neuropsychiatric symptoms including
o Agitation, bizarre behavior, psychosis (hallucinations, delusions) (more prominent in peds)
o Insomnia, memory deficits
o Seizures (focal or generalized, up to 76% in large study)
o Altered level of consciousness; stuporous with catatonic features
o Dyskinesias- Orofacial, dystonia, rigidity, opisthotonus, choreoathetosis
o Autonomic instability; temp, HR, BP lability, cardiac pauses, hypoventilation (less in peds)
o Language dysfunction: Decreased language output, mutism, echolalia

Diagnostic Workup

 CBC, CMP, CXR, UA – Ensure no obvious metabolic or infectious cause

 LP with CSF analysis – Looking for a lymphocytic pleiocytosis (though can be normal early on),
increased protein, also can send autoimmune encephalitis panel, looking for GluN1 IgG antibodies
 MRI Brain – Rule out structural or other cause. Often is normal, but can have T2 Flair
hyperintensities or contrast enhancement (cortex, and subcortical). PET (not routine) can have a
frontal to occipital gradient of glucose metabolism correlating with disease severity
 EEG – Eval for seizures, generally slow, disorganized. In prolonged illness, can see extreme Δ brush.
 Malignancy Screen – Abdominal imaging looking for ovarian teratoma (50% in F >18)

Treatment

 No RCT for guidance, based on retrospective data, opinion, extrapolation from other autoimmune
disease
 Initial therapy (part 1): IV Steroids (methylprednisolone), typicall dosed at 1g/day x 5 days
 Initial therapy (part 2): Either IVIG or Plasmapheresis. No data for doing both, physiologically if doing
both, should do plasmapheresis first.
 Second line therapy: Immunosuppression Rituximab (anti-CD 20 Ab), cyclophosphamide
 -Increasing practice is to start rituximab earlier, with first salvo of steroid and IVIG/Plex
 If tumour is identified, tumour should be removed as typically get better outcomes

Prognosis (based on a retrospective study of 501 patients)

 Half improved within first 4 weeks (and 97% of that half had a good outcome at 24 month follow up
 Of those 221 who did not improve within first 4 weeks, approximately half got second line therapy,
and getting second line therapy had better chance of good outcome (OR 2.7 [1.2-5.8 95% CI]
 By 24 months, 80 % achieved a good outcome (mrs 0-2), 6% died
 12% relapsed within first two years – No tumour and those who did not get second line therapy
tended to be at higher risk for relapse.
Modified rankin scale 0: No sx || 1: No sig. disability || 2: Slight disability, can’t do all prev. activities, but can look after own affairs without
assistance || 3: Mod disability, requires help, able to walk || 4: Unable to walk or attend bodily needs without help || 5: Constant nursing
attention ||6: Dead