From the Guidelines
The best treatment for seronegative autoimmune encephalitis typically involves immunotherapy, starting with first-line agents such as high-dose corticosteroids, intravenous immunoglobulin (IVIG), or plasma exchange (PLEX), as recommended by the most recent and highest quality study 1. The treatment approach should be individualized based on the patient's clinical presentation and response to therapy.
- First-line therapies include:
- High-dose corticosteroids (methylprednisolone 1000 mg IV daily for 3-5 days, followed by oral prednisone taper)
- IVIG at 2 g/kg divided over 2-5 days
- PLEX (5-7 exchanges over 10-14 days) These treatments should be initiated promptly upon clinical suspicion, even before antibody results return, as early intervention improves outcomes 1. If patients show inadequate response to first-line therapies within 2-4 weeks, second-line treatments should be considered, including:
- Rituximab (375 mg/m² weekly for 4 weeks or 1000 mg given twice, two weeks apart)
- Cyclophosphamide (750-1000 mg/m² monthly) The choice of second-line agent may depend on the clinical suspicion of antibody-mediated or cell-mediated autoimmunity, with rituximab preferred for antibody-mediated cases and cyclophosphamide for cell-mediated cases 1. Some patients may require maintenance immunosuppression for 6-12 months or longer with agents like mycophenolate mofetil or azathioprine. Treatment efficacy should be monitored through clinical improvement, and therapy duration is individualized based on response. The rationale for immunotherapy is to suppress the abnormal immune response targeting neuronal structures, reducing inflammation and preventing further neuronal damage, even when specific antibodies cannot be identified.
From the Research
Treatment Approaches for Seronegative Autoimmune Encephalitis
The treatment for seronegative autoimmune encephalitis typically involves immunotherapy, with the goal of reducing inflammation and modulating the immune system.
- First-line treatments often include steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PLEX) 2, 3.
- Second-line therapy may involve rituximab, particularly for patients who do not respond to first-line treatments or have a high risk of poor outcomes 4, 2.
- The combination of steroid, immunoglobulin, rituximab, and tocilizumab may be associated with better outcomes in patients with high risk for poor 2-year outcomes 4.
- Maintenance immunosuppression may be considered after a second relapse in patients with seronegative autoimmune encephalitis, with rituximab being a popular choice for maintenance therapy 5.
Factors Associated with Outcomes
Several factors can influence the outcomes of patients with seronegative autoimmune encephalitis, including:
- Delay in immunotherapy, with delays of more than 1 month associated with poorer outcomes 4.
- Age of onset, with older patients (≥60 years) having poorer outcomes 4.
- Presence of refractory status epilepticus, which can indicate a poorer prognosis 4.
- Infratentorial involvement, which may be associated with poorer outcomes 4.
- Development of cerebellar atrophy on MRI, which can indicate poor outcomes 4.
Immunotherapy Duration and Effectiveness
The duration and effectiveness of immunotherapy can vary depending on the patient's response and risk factors.