Treatment of Autoimmune Encephalitis

First-Line Treatment Options

The American Academy of Neurology recommends starting acute immunotherapy immediately once infection is ruled out, with high-dose corticosteroids, intravenous immunoglobulin (IVIG), or plasma exchange (PLEX) as first-line therapy 2
High-dose corticosteroids (intravenous methylprednisolone) are the most commonly used first-line therapy, with standard dosing at 1-2 mg/kg/day, and consideration of pulse dosing at 1g daily for 3-5 days in severe cases 4, 5
IVIG is preferred for patients who are agitated or combative, have bleeding disorders, or have difficulty with central line placement, and is typically administered at 0.4 g/kg/day for 5 days (total dose 2 g/kg) 6, 1
PLEX is preferred for patients with severe hyponatremia, high thromboembolic risk, or associated brain/spinal demyelination, and typically involves 5-10 sessions performed every other day 6, 1

The American Academy of Neurology recommends adding a second-line agent, such as rituximab or cyclophosphamide, if there is no meaningful clinical or radiological response to optimized first-line therapy after 2-4 weeks 1
Rituximab is the preferred second-line agent for antibody-mediated autoimmune encephalitis, chosen by 80% of experts in cases with unknown antibodies 3, 1
Cyclophosphamide should be considered for cell-mediated autoimmunity, and both rituximab and cyclophosphamide have shown good results as second-line agents for rescue therapy in autoimmune encephalitis 1

For immune checkpoint inhibitor-related autoimmune encephalitis, the National Comprehensive Cancer Network recommends permanently discontinuing the checkpoint inhibitor 4, 5
For encephalitis with positive autoimmune encephalopathy or paraneoplastic antibody and limited improvement, the American Society of Clinical Oncology recommends considering rituximab or plasmapheresis in consultation with neurology 4, 5