What is the management approach for autoimmune encephalitis?

Management of Autoimmune Encephalitis

Immediate First-Line Immunotherapy

Start high-dose corticosteroids immediately once infection is ruled out, without waiting for antibody results, as delayed treatment significantly worsens outcomes. 1, 2, 3

Standard First-Line Regimen

• Initiate intravenous methylprednisolone at 1-2 mg/kg/day, or use pulse dosing at 1g daily for 3-5 days in severe presentations 4, 2, 3
• Corticosteroids alone or combined with other agents were selected as first-line therapy by 84% of international experts for general presentations 1

Alternative First-Line Options Based on Clinical Context

• Use IVIG (0.4 g/kg/day for 5 days, total 2 g/kg) instead of steroids for agitated/combative patients, those with bleeding disorders, or difficulty with central line placement 2, 3
• Use plasma exchange (5-10 sessions every other day) for patients with severe hyponatremia, high thromboembolic risk, or associated brain/spinal demyelination 2, 3
• For severe initial presentations, combine steroids plus IVIG or steroids plus PLEX from the beginning rather than sequential monotherapy 4, 3

Treatment Escalation Timeline

Week 1-2: Initial Assessment Phase

• Administer chosen first-line therapy and monitor for clinical response 4
• If no improvement with corticosteroids alone, add IVIG or PLEX rather than continuing monotherapy 3

Week 2-4: Critical Decision Point

Add second-line immunotherapy if there is no meaningful clinical, radiological, or electrophysiological response after 2-4 weeks of optimized first-line therapy 4, 2

• 50% of experts wait for failure of more than one first-line agent before escalating 1, 4
• However, 32% escalate after failure of only one first-line agent, and progressive deterioration warrants immediate escalation regardless of timeline 4

Second-Line Immunotherapy Selection

For Antibody-Mediated Disease (Known or Unknown Antibodies)

Rituximab is the preferred second-line agent, chosen by 80% of experts for cases with unknown antibodies or neuronal surface antibodies 1, 4, 2

• Dose: 375 mg/m² IV weekly for 4 doses, or 1g on days 1 and 15 4
• Particularly effective for anti-NMDAR, anti-LGI1, or anti-CASPR2 antibodies 4

For Cell-Mediated Disease

Use cyclophosphamide (0.5-1 g/m² every 3 weeks for 4-6 months) for classical paraneoplastic encephalitis or suspected T-cell mediated mechanisms 4, 2

• Only 10% of experts chose cyclophosphamide for unknown antibody scenarios, making rituximab the safer default choice 1

Special Clinical Scenarios

Immune Checkpoint Inhibitor-Related Encephalitis

• Permanently discontinue the checkpoint inhibitor immediately 4, 3
• Initiate methylprednisolone pulse dosing (1g/day) 4
• Add IVIG or PLEX if no improvement or worsening after 3 days 4

Faciobrachial Dystonic Seizures

• 74% of experts use corticosteroids alone or combined with other first-line agents for this presentation 1

NMDAR Encephalitis

• 63% of experts use corticosteroids alone or combined with other agents as first-line 1
• Lower threshold for early rituximab escalation given known antibody-mediated pathogenesis 4

Classical Paraneoplastic Encephalitis

• Only 48.5% use corticosteroids as first-line; consider earlier cyclophosphamide 1
• Aggressive cancer screening is mandatory as tumor removal is critical 3, 5

Critical Pitfalls to Avoid

• Never delay immunotherapy while waiting for antibody results—treatment must begin once infection is excluded 4, 3
• Do not use corticosteroid monotherapy in severe cases; combine with IVIG or PLEX from the start 4, 3
• Do not underestimate the need for early escalation; 32% of experts add second-line agents after failure of only one first-line agent 4
• Do not neglect oncological screening with contrast-enhanced CT of chest, abdomen, and pelvis, as failure to identify paraneoplastic causes compromises treatment 4, 3
• Do not wait the full 4 weeks if there is progressive clinical deterioration, especially with hemodynamic compromise or severe dysfunction 4

Supportive Management

• Manage seizures with appropriate antiepileptic medications 3
• Monitor and treat dysautonomia including blood pressure/heart rate fluctuations; consider temporary pacemaker for severe dysrhythmia 3
• Implement fluid restriction for hyponatremia related to SIADH 3
• Monitor intracranial pressure in cases with massive inflammation and brain edema 3

Bridging and Maintenance Therapy

• After clinical improvement with first-line therapy, continue with gradual oral prednisone taper (chosen by 38% of experts) or monthly IVIG/methylprednisolone 4, 6
• For maintenance after second-line therapy, rituximab was chosen by 46% of experts 6
• Consider maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70% of experts) or seronegative autoimmune encephalitis (61%) 6