NMDA Receptor Antibody Testing in Epilepsy

Clinical Scenarios Where NMDA Receptor Antibody Testing is Indicated

The American Academy of Neurology recommends NMDA receptor antibody testing in patients with epilepsy when there is clinical suspicion of autoimmune encephalitis, particularly in cases of new-onset refractory status epilepticus (NORSE) or when epilepsy presents with psychiatric symptoms, cognitive dysfunction, and autonomic instability 1, 2
Anti-NMDA receptor encephalitis is a major cause of new onset refractory status epilepticus (NORSE), which can be convulsive or non-convulsive 1
Testing should be considered in patients with epilepsy accompanied by prominent psychiatric symptoms, such as psychosis or behavioral changes, as recommended by the American Psychiatric Association 3, 4
Cognitive dysfunction is another indication for NMDA receptor antibody testing in patients with epilepsy, according to the American Academy of Neurology 5, 6
Orofacial dyskinesias or abnormal movements, as well as autonomic instability, are also indications for testing, as suggested by the European Academy of Neurology 4, 7
Decreased consciousness is another clinical scenario where NMDA receptor antibody testing is indicated, as recommended by the American College of Physicians 7

Both serum and CSF should be tested for NMDA receptor antibodies when possible, as recommended by the American Academy of Neurology 2
Antibody testing should be interpreted in the proper clinical context, as antibodies can be present in other conditions, according to the Infectious Diseases Society of America 5

EEG findings that may suggest anti-NMDAR encephalitis include focal slowing/seizures, lateralized periodic discharges, and "extreme delta brush" pattern, as described by the American Clinical Neurophysiology Society 1
A normal EEG does not exclude anti-NMDAR encephalitis, as noted by the American Academy of Neurology 1
In cases with negative MRI but high clinical suspicion, brain FDG-PET can help confirm focal or multifocal brain abnormality, as recommended by the Society of Nuclear Medicine and Molecular Imaging 1
Anti-NMDAR antibodies have been detected in approximately 30% of individuals during herpes simplex encephalitis, so positive results must be interpreted in clinical context, according to the Infectious Diseases Society of America 5

Early diagnosis and treatment of anti-NMDAR encephalitis can significantly improve morbidity and mortality, as emphasized by the European Society of Clinical Microbiology and Infectious Diseases 7

In patients with epilepsy of unknown etiology, especially those with psychiatric symptoms, anti-NMDAR antibody testing should be part of the diagnostic workup, as recommended by the International League Against Epilepsy 7, 4
Screening for associated neoplasms, particularly ovarian teratomas, is recommended in patients with positive anti-NMDAR antibodies, as suggested by the American College of Obstetricians and Gynecologists 2, 4