From the Guidelines
NMDA receptor encephalitis is an autoimmune disorder that requires prompt immunotherapy to improve outcomes, with first-line options including corticosteroids, intravenous immunoglobulin (IVIG), and plasma exchange, and second-line therapies including rituximab and cyclophosphamide for non-responders. The treatment of NMDA receptor encephalitis involves a combination of immunosuppressive strategies, with the goal of reducing the production of antibodies against NMDA receptors in the brain. According to the study by 1, treatment started within 4 weeks of symptom onset confers the best recovery, with approximately 74% of patients achieving full or substantial recovery at 1 year after immunotherapy or tumor removal.
Associations and Treatment Options
The associations of NMDA receptor encephalitis include:
- Neuropsychiatric symptoms, such as seizures, psychosis, and autonomic instability
- Ovarian teratoma, particularly in women, which can improve outcomes with tumor removal
- Relapses, which can occur in approximately 30% of patients despite treatment
Treatment options for NMDA receptor encephalitis include:
- First-line immunotherapies: corticosteroids (methylprednisolone 1g IV daily for 3-5 days), IVIG (2g/kg divided over 5 days), and plasma exchange (5-7 exchanges over 10-14 days)
- Second-line therapies: rituximab (375 mg/m² weekly for 4 weeks) and cyclophosphamide (750 mg/m² monthly for 3-6 months) for non-responders
- Supportive care: antiepileptic drugs for seizures, antipsychotics for psychiatric symptoms, and ICU management for autonomic instability
- Long-term immunosuppression: mycophenolate mofetil (starting at 500mg twice daily, increasing to 1000mg twice daily) or azathioprine (1-3 mg/kg/day) for 1-2 years to prevent relapses, as suggested by 1 and 1.
Key Considerations
- Early diagnosis and aggressive immunotherapy are key to improving prognosis
- Tumor screening should be performed annually for several years, particularly if the treatment response is poor or relapses occur
- Weaning of immunosuppressive therapy should be done carefully, with serial estimations of antibody levels in serum and CSF, as recommended by 1.
From the Research
Associations of NMDA Receptor Encephalitis
- NMDA receptor encephalitis is commonly associated with ovarian teratomas, particularly in young female patients 2, 3, 4.
- The presence of ovarian teratomas can lead to the development of anti-NMDA receptor autoantibodies, disrupting NMDA function and resulting in psychosis, seizures, and autonomic dysfunction 3.
- The disease can also present with acute psychiatric disturbances and neurological deficits, and is associated with certain tumors, most commonly ovarian teratomas 5.
Treatment Options for NMDA Receptor Encephalitis
- First-line therapy typically involves immunotherapy and tumor resection, if present, with up to 53% of patients experiencing improvement within 4 weeks 5.
- Treatment options may include:
- Removal of the ovarian teratoma to improve prognosis and decrease the risk of recurrence 2, 4.
- Immunotherapy, such as intravenous immunoglobulin (IVIG) therapy, plasmapheresis, and methylprednisolone 2, 5.
- Second-line immunotherapy with cyclophosphamide and rituximab for refractory cases 5.
- Intrathecal injection of methotrexate and dexamethasone may be beneficial for treatment of refractory cases 2.
- In some cases, additional treatments may be necessary, such as bilateral salpingo-oophorectomy 2, 5 or chemotherapy for the associated teratoma 6.