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%.
- 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 **
- Curr Psychiatry Rev. 2011; 7(3): 189–193.
- N Engl J Med 2018; 378:840-851.
- Gynecol Oncol Rep. 2015 Nov; 14: 1–3.
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Dr. Harvinder Singh, M.D. (Admin)
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