From the Guidelines
NMDA receptor encephalitis should be treated with first-line immunotherapy, including corticosteroids, intravenous immunoglobulin, or plasma exchange, with 63% of experts selecting these options as initial therapy for NMDAR-IgG encephalitis 1. The treatment approach for NMDA receptor encephalitis involves a combination of immunotherapies to reduce inflammation and suppress the immune system's attack on the brain.
- First-line treatments include:
- High-dose corticosteroids, such as methylprednisolone 1g IV daily for 3-5 days
- Intravenous immunoglobulin (IVIG) at 2g/kg divided over 5 days
- Plasma exchange, typically 5-7 exchanges
- If patients do not respond to first-line therapy within 2-3 weeks, second-line therapies such as rituximab (375 mg/m² weekly for 4 weeks) or cyclophosphamide (750 mg/m² monthly for 3-6 months) should be considered, with 80% of experts choosing rituximab as the preferred second-line agent in a clinical scenario with unknown antibodies 1. Supportive care is crucial in managing symptoms and preventing complications, including:
- Antiepileptic medications for seizures, such as levetiracetam 500-1500mg twice daily
- Antipsychotics for psychiatric symptoms, such as quetiapine 25-100mg daily
- ICU management for autonomic instability if needed Tumor screening is essential, as approximately 38% of adult female patients have an underlying teratoma requiring surgical removal. Recovery from NMDA receptor encephalitis can take months to years, with 75-80% of patients achieving good outcomes with prompt treatment, and relapses occur in 20-25% of cases, necessitating long-term immunosuppression in some patients 1.
From the Research
Clinical Presentation of NMDA Encephalitis
- NMDA encephalitis is a rare autoimmune panencephalitis that typically presents with acute psychiatric disturbances and neurological deficits 2
- The clinical course usually begins with viral infection-like symptoms, followed by the rapid development of schizophrenia-like psychiatric symptoms and seizures 3
- Patients may have a decreased level of consciousness with central hypoventilation, frequently requiring mechanical ventilation 3
- The disease can progress through five stages, including a prodromal phase, psychotic and/or seizure phase, unresponsive and/or catatonic phase, hyperkinetic phase, and gradual recovery phase 3
Treatment Options for NMDA Encephalitis
- First-line therapy typically involves immunotherapy and tumor resection, if present, with up to 53% of patients experiencing improvement within 4 weeks 2
- Treatment options include intravenous immunoglobulin, plasma exchange, plasmapheresis, rituximab, cyclophosphamide, and tumor resection 4, 5, 6
- The efficacy of different treatment combinations has been compared, with results suggesting that treatment combinations including at least two categories (e.g. intravenous immunoglobulin, plasmapheresis, rituximab, and tumor removal) result in higher efficacy rates than treatment with a single form of therapy 6
- Plasmapheresis or plasma exchange may be as effective as intravenous immunoglobulin and rituximab or cyclophosphamide for male patients without tumor 5
Complications and Prognosis of NMDA Encephalitis
- Cardiac arrhythmias and increased intracranial pressure have been reported in anti-NMDA receptor encephalitis, and may require placement of a permanent cardiac pacemaker 2
- Autonomic dysfunction, including bradycardia and asystole, can occur and may be refractory to treatment 2
- Elevated intracranial pressure may contribute to autonomic instability 2
- Early treatment is crucial to improve prognosis, and converting to other therapies may be more likely to result in early recovery than continuing on the original therapy 6