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. 

 


CLINICAL FEATURES (PHASES):

(A) PRODROMAL PHASE (1-2 WEEKS):

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

 

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

(B) INITIAL NEUROPSYCHIATRIC SYMPTOMS (1-3 WEEKS):

    • 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).

(C) NEUROLOGIC COMPLICATIONS (WEEKS-MONTHS):

    • 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.

 


DURATION OF ILLNESS:

    • 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%.

 


DIAGNOSIS:

CSF:

    • 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.

BRAIN MRI:

    • 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.

 


TREATMENT:

    • 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 **

 


Source:

    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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