What is the treatment for autoimmune encephalitis?

Treatment of Autoimmune Encephalitis

First-line immunotherapy with corticosteroids, followed by IVIG or plasma exchange if no improvement, is the standard initial treatment for autoimmune encephalitis, with escalation to rituximab or cyclophosphamide as second-line therapy for refractory cases. 1

Initial Management Algorithm

First-Line Therapy

1. High-dose corticosteroids:

   • Intravenous methylprednisolone (IVMP) is the preferred initial treatment in most cases 1
   • Typical dosing: 1g daily for 3-5 days followed by oral prednisone taper

2. If corticosteroids are contraindicated or in specific scenarios:

   • Use IVIG (Intravenous Immunoglobulin) 2g/kg divided over 2-5 days OR
   • PLEX (Plasma Exchange) - typically 5-7 exchanges over 10-14 days 1
   • Consider IVIG first in patients with high thromboembolic risk or severe hyponatremia 1

3. For severe presentations (e.g., NMDAR-antibody encephalitis, status epilepticus, severe dysautonomia):

   • Combination therapy from the outset (steroids plus IVIG or steroids plus PLEX) 1, 2

Second-Line Therapy (if no improvement with first-line)

1. Rituximab:

   • Preferred for antibody-mediated autoimmunity 2
   • Dosing: 375 mg/m² weekly for 4 weeks OR two 1000 mg doses 2 weeks apart 2

2. Cyclophosphamide:

   • Preferred for cell-mediated autoimmunity 2
   • Dosing: 600-1000 mg/m² 2

Refractory Cases

For patients not responding to first and second-line therapies:

• Consider experimental therapies such as IL-6 inhibitors (tocilizumab) or proteasome inhibitors (bortezomib) 1, 3

Special Considerations

Tumor Screening

• Thorough cancer screening is essential, particularly with certain antibody types 1, 2
• Recommended screening:
  • CT chest, abdomen, and pelvis with contrast (or MRI when CT is contraindicated)
  • If negative, consider mammogram/breast MRI, pelvic ultrasound, and/or whole body FDG-PET based on clinical presentation and cancer risk factors 1

Monitoring During Treatment

• Clinical response
• Seizure frequency
• CD19+ B-cell counts (when using rituximab)
• Potential adverse effects of immunotherapies 2

Maintenance Therapy

• After acute treatment, consider bridging therapy with:
  • Gradual oral prednisone taper
  • Monthly IVIG
  • Monthly IV methylprednisolone 2

Treatment Outcomes and Prognosis

• Early aggressive treatment is associated with better functional outcomes and fewer relapses 4
• Approximately 50% of patients require second-line immunotherapy 4
• A small but significant proportion of patients are refractory to all first- and second-line therapies 3

Common Pitfalls to Avoid

1. Delayed treatment initiation: Early immune suppression results in improved outcomes 2
2. Inadequate duration of immunotherapy: Consider maintenance therapy for 6+ months 2
3. Missing associated malignancy: Complete thorough tumor screening 1
4. Underestimating severity: Be prepared to escalate therapy quickly in severe or deteriorating cases 1
5. Overlooking supportive care: Address seizures, dysautonomia, and other complications 1

The evidence supporting these treatment recommendations is primarily based on observational studies, retrospective series, and expert opinion rather than randomized controlled trials 5. However, the guidelines from the Journal of Neurology, Neurosurgery and Psychiatry represent the most comprehensive consensus on management approaches 1.