Anti-NMDA Receptor Encephalitis.

Anti-NMDA Receptor Encephalitis

This is an autoimmune disorder in which antibodies attack NMDA (N-methyl D aspartate) type glutamate receptors at central neuronal synapses. 




    • viral-like prodrome symptoms including lethargy, headache, upper respiratory symptoms, nausea, diarrhea, myalgias, and fever.


  • Duration: 1-2 weeks before onset of behavioral symptoms.


    • Most common symptoms: Psychotic symptoms in adults and manic symptoms in children.


    • Children can have abnormal movements as presenting complaints.


    • Personality changes.


  • Initial phases of cognitive deterioration (short term memory deficits) and abnormal speech (alogia, echolalia, perseveration, mumbling, and mutism).


    • Gradual worsening of sensorium with wide variation in motor state (from catatonia to agitation).


    • Abnormal movements: orofacial dyskinesias, dystonic posturing, and choreic like movements of limbs.


    • Autonomic instability. Note high risk of NMS (neuroleptic malignant syndrome) after addition of antipsychotics


  • Seizures: partial motor or complex.



    • Long term admission to hospital is needed in most patients (~3 months).


  • Pattern of symptoms resolution:

Autonomic symptoms >> Abnormal movements >> Cognitive and Psychiatric symptoms.

  • Relapse is considered low at 20-25%.




    • Detection of antibodies against NMDAR.


    • Serum is unreliable (14% false negative).


  • NR1 and NR2 antibodies in CSF combined with a characteristic clinical picture apparently have 100% sensitivity and specificity.
  • Once definitive diagnosis has been obtained, imaging studies such as pelvic ultrasound, MRI, computed tomography, and positron emission tomography may be used to evaluate for an underlying teratoma.


    • Normal in 50%.


    • T2 or FLAIR hyperintensities in cortical or subcortical brain regions.


  • Also to rule out ovarian teratoma (found in ~50% females >18 yr age).

If tumor is not identified, both FDG-PET and CT studies are recommended.



    • Removal of tumor, if present.


    • Plasma Exchanges and IVIG —-> Rituximab and Cyclophosphamide.


    • IVIG preferred over plasma exchanges for agitated patient and autonomic instability.


    • Cautious of using antipsychotics for high risk of EPS and NMS. Prefer Quetiapine for psychosis and agitation management. Chlorpromazine as second option.


  • Cases with good response to sedating medications like valproic acid, benzodiazepines and anticholinergics.


Additional Important Clinical Tips:

    • Patients with no detectable tumor: continue immunosuppression with azathioprine or mycophenolate for minimum 1 year with azathioprine or mycophenolate.


    • In females >12 yr age with no detectable tumor: screen for ovarian teratomas with pelvic MRI or ultrasound every 6 months for 4 years (monitor for development of ovarian teratoma).


  • After neurologic recovery in female patient of child bearing potentia: counsel them on contraception, particularly for those remaining on azathioprine and mycophenolate. 


** These patients have high likelihood of a positive outcome with early diagnosis and rapid treatment **



    1. Curr Psychiatry Rev. 2011; 7(3): 189–193.
    2. N Engl J Med 2018; 378:840-851.
    1. Gynecol Oncol Rep. 2015 Nov; 14: 1–3.



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Dr. Harvinder Singh, M.D. (Admin)

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