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NMDA Receptor Antibody

The N-methyl-D-aspartate receptor (NMDR) is an ion channel located in pre and post-synaptic membrane that mediates synaptic transmission by glutamate. Development of autoantibody to the NR1 subunit of NMDR is associated with limbic encephalitis. Approximately 50% of cases are associated with ovarian teratoma, while 2% of cases are associated with other tumors including: germ cell tumors of the testis, mediastinal teratoma, small cell lung cancer, Hodgkin lymphoma, and neuroblastoma. Because of its association with cancer, NMDR encephalitis is considered to be a paraneoplastic syndrome. Infection with mycoplasma or varicella zoster may be a predisposing factor for NMDR encephalitis in patients without cancer.

NMDR encephalitis occurs approximately 8 times more commonly in women than in men. Patients usually present with flu-like symptoms including headache, fever, nausea, and vomiting. In a few days, the disease progresses to include: insomnia, psychosis, memory deficits, seizures, stupor, movement disorders and autonomic instability affecting blood pressure, temperature regulation and ventilation. Among patients younger than 18 years of age, the most common manifestations of anti–NMDA receptor encephalitis include behavioral changes and seizures. Movement disorders are common in children less than 12 years of age.

First-line treatment for anti–NMDA receptor encephalitis consists of intravenous glucocorticoids, intravenous immune globulin (IVIG), or plasma exchange. If a tumor is identified, surgical resection is also considered.

CSF may show lymphocytosis or oligoclonal bands. Diagnosis of anti-NMDAR encephalitis is confirmed by the detection of antibodies to the NR1 subunit of the NMDAR in serum or CSF. Autoantibody is synthesized intrathecally. The titer of antibodies in CSF correlates more closely with clinical outcome than serum antibodies. CSF antibodies usually remain elevated in patients with refractory disease, while serum antibodies may be decrease with treatment. Because of these differences, simultaneous testing of serum and CSF is recommended.

Other autoantibodies that are associated with limbic encephalitis include anti-AMPA receptor antibody, anti-VGKC antibody and anti-GABA-B receptor antibody.

NMDA receptor antibody is detected using immunofluoresence to detect IgG binding to human cells transfected with the NR1 receptor subunit. Transfected cells over-express the cognate protein, increasing the sensitivity of the test. Specimen requirements are a red top tube of blood for serum antibody and 1 mL of CSF in a sterile vial for CSF antibody.

Reference value is no antibody detected.


Gable MS, Gavali S, Radner A, et al. Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis 2009;28:1421-9.

Dalmau J, Tüzün E, Wu HY, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 61:25-36.

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