What is the treatment approach for autoimmune encephalitis?

Treatment Approach for Autoimmune Encephalitis

Start high-dose intravenous corticosteroids immediately once infection is ruled out by cerebrospinal fluid analysis, as this is the most commonly used and recommended first-line therapy for autoimmune encephalitis. 1, 2

First-Line Immunotherapy Algorithm

Standard First-Line: High-Dose Corticosteroids

• Administer intravenous methylprednisolone at 1-2 mg/kg/day for standard cases 1, 2
• Use pulse dosing at 1g daily for 3-5 days in severe presentations 1, 2
• Initiate treatment immediately after ruling out infection—do not wait for antibody test results, as delays worsen outcomes 1

Alternative First-Line Options Based on Patient-Specific Factors

Choose IVIG (0.4 g/kg/day for 5 days, total 2 g/kg) when: 1, 3, 2

• Patient is agitated or combative
• Bleeding disorders or coagulopathy present
• Contraindications to corticosteroids exist
• Difficulty with central line placement

Choose PLEX (5-10 sessions every other day) when: 1, 3, 2

• Severe hyponatremia present
• High thromboembolic risk
• Associated brain or spinal demyelination identified

Combination First-Line Therapy

• For severe initial presentations (comatose, catatonic, mechanically ventilated), start combination therapy with steroids plus IVIG or steroids plus PLEX from the beginning rather than sequential monotherapy 1, 3

Treatment Escalation Strategy

When to Add Second Agent

• If no clinical, radiological, or electrophysiological improvement occurs after initial corticosteroid monotherapy, add IVIG or PLEX to the regimen 1, 3
• Reassess response at 2-4 weeks before escalating to second-line agents 2

Second-Line Immunotherapy

Rituximab is the preferred second-line agent for antibody-mediated autoimmune encephalitis and should be added if there is no meaningful response to optimized first-line therapy after 2-4 weeks. 1, 2

• Rituximab is chosen by 80% of experts for cases with unknown antibodies 2
• Consider cyclophosphamide specifically for cell-mediated autoimmunity rather than antibody-mediated disease 1, 2

Refractory Cases (Third-Line Options)

For patients who remain refractory after first and second-line therapies, consider: 4, 5

• Intrathecal methotrexate (has shown favorable outcomes in severely refractory cases, including patients who were comatose or under consideration for palliative care) 5
• Cytokine-based drugs (tocilizumab, basiliximab, anakinra, tofacitinib) 4
• Plasma cell-depleting agents (bortezomib, daratumumab) 4

Bridging and Maintenance Therapy

After acute treatment response, initiate bridging therapy with one of the following: 3

• Gradual oral prednisone taper
• Monthly IVIG infusions
• Monthly intravenous methylprednisolone

Critical Supportive Care Measures

Seizure Management

• Treat seizures with appropriate antiepileptic medications as they occur 1

Dysautonomia Management

• Monitor and treat blood pressure and heart rate fluctuations actively 1
• Consider temporary pacemaker placement for severe dysrhythmia 1

Metabolic Complications

• Implement fluid restriction for hyponatremia related to inappropriate antidiuretic hormone secretion 1
• Monitor intracranial pressure in cases with massive inflammation and brain edema 1

Essential Concurrent Actions

Malignancy Screening

• Perform cancer screening with contrast-enhanced CT of chest, abdomen, and pelvis to identify paraneoplastic causes 1
• Failure to screen for underlying malignancy may miss treatable paraneoplastic triggers 1

Immune Checkpoint Inhibitor-Related Cases

• Permanently discontinue the checkpoint inhibitor immediately if autoimmune encephalitis is related to immune checkpoint inhibitor therapy 1, 2

Critical Pitfalls to Avoid

• Never delay immunotherapy while waiting for antibody test results—treatment must begin once infection is excluded, as delays significantly worsen outcomes 1
• Do not dismiss the diagnosis based on negative antibody testing alone, as a subgroup of patients with genuine autoimmune encephalitis remain seronegative 6
• Do not use corticosteroids if primary CNS lymphoma or neurosarcoidosis remains under consideration, as this may obscure the diagnosis 3