Is NMDA (N-methyl-D-aspartate) receptor antibody (serum) testing indicated in epilepsy?

NMDA Receptor Antibody Testing in Epilepsy

NMDA receptor antibody testing in serum is indicated 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

Clinical Scenarios Where NMDA Receptor Antibody Testing is Indicated

• 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 (psychosis, behavioral changes) 1
  • Cognitive dysfunction 1
  • Orofacial dyskinesias or abnormal movements 1
  • Autonomic instability 1
  • Decreased consciousness 1

Diagnostic Approach

• CSF testing for NMDA receptor antibodies is more sensitive than serum testing (100% vs 85.6% sensitivity) 2
• When testing for anti-NMDA receptor antibodies:
  • Both serum and CSF should be tested when possible 1, 2
  • CSF is the preferred specimen due to higher sensitivity 2
  • Antibody testing should be interpreted in the proper clinical context, as antibodies can be present in other conditions 1

Clinical Pearls and Pitfalls

• EEG findings that may suggest anti-NMDAR encephalitis include:
  • Focal slowing/seizures
  • Lateralized periodic discharges
  • "Extreme delta brush" pattern (occasionally seen) 1
• A normal EEG does not exclude anti-NMDAR encephalitis 1
• In cases with negative MRI but high clinical suspicion, brain FDG-PET can help confirm focal or multifocal brain abnormality 1, 3
• Anti-NMDAR antibodies have been detected in approximately 30% of individuals during herpes simplex encephalitis, so positive results must be interpreted in clinical context 1

Importance for Patient Outcomes

• Early diagnosis and treatment of anti-NMDAR encephalitis can significantly improve morbidity and mortality 1
• Higher antibody titers in CSF and serum are associated with poorer outcomes 2
• Seizures occur in approximately 80% of patients with anti-NMDAR encephalitis and represent a major cause of morbidity 4
• Recovery can be severely delayed (up to 3 years after onset) and may not follow a linear progression 5
• Immunotherapy (steroids, IVIG, plasma exchange, rituximab) can lead to significant clinical improvement even when initiated late in the disease course 5, 3

Special Considerations

• In patients with epilepsy of unknown etiology, especially those with psychiatric symptoms, anti-NMDAR antibody testing should be part of the diagnostic workup 1
• Screening for associated neoplasms (particularly ovarian teratomas) is recommended in patients with positive anti-NMDAR antibodies 1
• The presence of anti-NMDAR antibodies may guide treatment decisions toward immunotherapy rather than just antiepileptic drugs 6