Treatment of Autoimmune Encephalitis
Start high-dose intravenous corticosteroids immediately once infection is ruled out, as this is the most commonly used and recommended first-line therapy for autoimmune encephalitis. 1, 2
Initial Treatment Strategy
First-Line Immunotherapy Options
The American Academy of Neurology recommends initiating acute immunotherapy as soon as cerebrospinal fluid results exclude infection and primary CNS lymphoma or neurosarcoidosis are not considerations. 1, 3 You have three first-line options:
High-dose corticosteroids (preferred initial choice):
- Standard dosing: intravenous methylprednisolone 1-2 mg/kg/day 1, 2
- Pulse dosing for severe cases: 1g daily for 3-5 days 1, 2
- This is the most commonly used first-line therapy 2
IVIG (use when steroids are contraindicated or in specific patient populations):
- Dosing: 0.4 g/kg/day for 5 days (total dose 2 g/kg) 1, 3
- Preferred for patients who are agitated or combative 1, 3
- Preferred for patients with bleeding disorders or coagulopathy 3, 2
- Preferred when central line placement is difficult 1, 3
PLEX (use in specific clinical scenarios):
- 5-10 sessions performed every other day 1, 3
- Preferred for patients with severe hyponatremia 1, 3
- Preferred for high thromboembolic risk 1, 3
- Preferred when associated brain or spinal demyelination is present 1, 3
Combination Therapy for Severe Presentations
For patients with severe initial presentations, start combination therapy immediately with steroids plus IVIG or steroids plus PLEX from the beginning rather than sequential monotherapy. 3, 2 This aggressive upfront approach is warranted when patients present with profound altered mental status, refractory seizures, or dysautonomia requiring ICU admission. 4
Treatment Escalation Algorithm
When to Add Second-Line Therapy
Add a second-line agent if there is no meaningful clinical, radiological, or electrophysiological improvement after 2-4 weeks of optimized first-line therapy. 1 The American Academy of Neurology specifically recommends this timeframe for reassessment. 1
If no improvement occurs after initial corticosteroids alone, add IVIG or PLEX before proceeding to second-line agents. 3, 2
Second-Line Agent Selection
Rituximab is the preferred second-line agent for autoimmune encephalitis, chosen by 80% of experts in cases with unknown antibodies. 5, 1 This preference reflects its efficacy in antibody-mediated autoimmune encephalitis. 1, 2
Cyclophosphamide should be considered specifically for cell-mediated autoimmunity rather than antibody-mediated disease. 1, 2 Only 10% of experts chose cyclophosphamide as their preferred agent when antibodies are unknown. 5
Bridging and Maintenance Therapy
After acute treatment, initiate bridging therapy with one of the following options: 3
Critical Pitfalls to Avoid
Do not delay immunotherapy while waiting for antibody test results—this is the most common and harmful error in management. 2 Commercial antibody panels often take weeks to return, and current panels cannot detect all forms of autoimmune encephalitis, including T-cell mediated cases. 5 Treatment decisions must be made based on clinical presentation, not antibody confirmation. 5
Do not fail to screen for underlying malignancy, as paraneoplastic causes require tumor treatment in addition to immunotherapy. 2 Perform contrast-enhanced CT of chest, abdomen, and pelvis in relevant cases. 2
Special Clinical Scenarios
Immune Checkpoint Inhibitor-Related Encephalitis
Permanently discontinue the checkpoint inhibitor immediately if autoimmune encephalitis develops during cancer immunotherapy. 1, 2 The National Comprehensive Cancer Network makes this a firm recommendation. 1
Refractory Cases
For the minority of patients who remain refractory to both first-line and second-line therapies, consider third-line options including cytokine-based drugs (tocilizumab, anakinra, tofacitinib), plasma cell-depleting agents (bortezomib, daratumumab), or treatments targeting intrathecal immune cells (intrathecal methotrexate, natalizumab). 6 However, evidence for these agents is limited to case reports and small case series. 6
Essential Supportive Care
Manage seizures with appropriate antiepileptic medications, as seizures are a common presenting feature. 2 Monitor and treat blood pressure and heart rate fluctuations in patients with dysautonomia, considering temporary pacemaker for severe dysrhythmia. 2 Implement fluid restriction for hyponatremia related to inappropriate antidiuretic hormone secretion. 2