What is the recommended management for a patient with suspected autoimmune encephalitis?

Management of Suspected Autoimmune Encephalitis

Initiate high-dose 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

Diagnostic Workup Before Treatment Initiation

Perform the following essential tests to confirm autoimmune encephalitis and exclude mimics:

• Brain MRI and EEG to identify focal or multifocal brain abnormalities consistent with inflammatory encephalitis 1
• Lumbar puncture to confirm inflammatory cerebrospinal fluid profile and definitively exclude infectious causes (bacterial, viral, fungal) 1
• Neuronal autoantibody testing in both cerebrospinal fluid and serum, though treatment should NOT be delayed waiting for results 1
• Cancer screening with contrast-enhanced CT of chest, abdomen, and pelvis to identify paraneoplastic triggers 1
• Brain FDG-PET when clinical suspicion remains high despite unrevealing MRI and EEG 1

First-Line Immunotherapy Algorithm

Standard Approach: High-Dose Corticosteroids

Administer intravenous methylprednisolone at 1-2 mg/kg/day, or use pulse dosing at 1g daily for 3-5 days in severe presentations. 1, 2

Alternative First-Line Options Based on Patient Factors

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

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

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

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

Severe Presentations Require Combination Therapy

For patients with severe initial presentations, initiate combination therapy with steroids PLUS IVIG or steroids PLUS PLEX from the outset rather than sequential monotherapy. 1, 2, 3

Treatment Escalation Strategy

When to Add Second Agent

If no clinical, radiological, or electrophysiological improvement occurs after initial monotherapy, add IVIG or PLEX to the corticosteroid regimen. 1, 3

Timeline for Second-Line Therapy

Escalate to second-line agents (rituximab or cyclophosphamide) if no meaningful clinical or radiological response occurs after 2-4 weeks of optimized first-line therapy. 2, 4

Second-Line Immunotherapy Selection

Antibody-Mediated Disease

Rituximab is the preferred second-line agent for antibody-mediated autoimmune encephalitis, chosen by 80% of experts and recommended by the American Academy of Neurology. 1, 2

Cell-Mediated Disease

Cyclophosphamide should be selected for cell-mediated autoimmunity patterns. 1, 2

Both agents have demonstrated good efficacy as rescue therapy in refractory cases. 2, 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

Essential Supportive Care Measures

Seizure Management

Treat seizures with appropriate antiepileptic medications as they occur. 1

Autonomic Dysfunction

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

Metabolic and Intracranial Pressure Management

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

Critical Pitfalls to Avoid

Timing of Treatment Initiation

The most dangerous error is delaying immunotherapy while waiting for antibody test results—treatment must be initiated promptly once infection is ruled out, as delays worsen outcomes. 1, 2 The diagnostic approach should achieve "possible" or "probable" autoimmune encephalitis based on clinical syndrome and conventional testing, which is sufficient to start treatment. 5

Malignancy Screening

Failure to screen for underlying malignancy may miss paraneoplastic causes, which fundamentally changes management and prognosis. 1

Immune Checkpoint Inhibitor-Related Cases

For autoimmune encephalitis triggered by immune checkpoint inhibitors, permanently discontinue the checkpoint inhibitor immediately. 1, 2 This is a non-negotiable step recommended by the National Comprehensive Cancer Network. 2

Predictors of Poor Outcome

Early escalation to second-line therapy improves prognosis, particularly in patients with modified Rankin score ≥4 at worst neurologic status or those requiring intensive care unit admission. 4 Do not wait excessively long before escalating therapy in severe cases.