What is the initial treatment for autoimmune encephalitis?

Initial Treatment for Autoimmune Encephalitis

High-dose corticosteroids (intravenous methylprednisolone) are the preferred initial treatment for autoimmune encephalitis in most cases. 1, 2

First-Line Treatment Algorithm

1. Initial Immunotherapy Selection:

   • Intravenous methylprednisolone (IVMP) is the first choice for most autoimmune encephalitis cases
   • 84% of experts choose corticosteroids alone (65%) or in combination with other agents (19%) for initial immunotherapy 1

2. Alternative First-Line Options (if steroids are contraindicated):

   • IVIG (Intravenous Immunoglobulin)
   • PLEX (Plasma Exchange)
   • Consider these alternatives when:
     • Uncontrolled hypertension
     • Uncontrolled diabetes
     • Acute peptic ulcer
     • Severe behavioral symptoms that worsen with steroids
     • High thromboembolic risk
     • Severe hyponatremia 1

3. Combination First-Line Therapy (recommended for severe cases):

   • Consider immediate combination therapy for:
     • NMDAR-antibody encephalitis
     • New-onset refractory status epilepticus (NORSE)
     • Cases with severe dysautonomia 2
   • Combinations include:
     • Steroids + IVIG
     • Steroids + PLEX 2

Response Assessment and Escalation

1. If No Improvement After Initial Treatment:

   • 62% of experts recommend adding a different first-line therapy
   • 26% recommend proceeding directly to second-line agents 2
   • Add IVIG or PLEX if initial IVMP fails 1

2. Second-Line Therapy (for refractory cases):

   • Rituximab (preferred for antibody-mediated autoimmunity)
     • Dosing: 375 mg/m² weekly for 4 weeks OR two 1000 mg doses 2 weeks apart 2
   • Cyclophosphamide (preferred for cell-mediated autoimmunity)
     • Dosing: 600-1000 mg/m² 2

3. Refractory Cases:

   • Consider experimental therapies:
     • IL-6 inhibitors (tocilizumab)
     • Bortezomib (proteasome inhibitor) 1, 3

Important Considerations

• Tumor Screening: Perform cancer screening with CT chest, abdomen, and pelvis with contrast in relevant cases 1, 2
• Timing is Critical: Early immune suppression results in improved outcomes; delays in escalating therapy are associated with poorer outcomes 2, 4
• Bridging Therapy: After acute treatment, initiate:
  • Gradual oral prednisone taper
  • Monthly IVIG
  • Monthly IV methylprednisolone 2

Supportive Management

• Monitor and manage hyponatremia (common in autoimmune encephalitis)

  • Usually related to inappropriate antidiuretic hormone secretion
  • Fluid restriction is typically sufficient
  • Control slow correction of sodium levels to avoid central pontine myelinolysis 1

• Address seizures, dysautonomia, and psychiatric symptoms as they arise

Common Pitfalls to Avoid

1. Delayed Treatment: Waiting for antibody results before initiating therapy can worsen outcomes. Start treatment once infection is ruled out and autoimmune encephalitis is suspected 1, 5

2. Inadequate Escalation: Approximately half of patients require second-line therapy. Be prepared to escalate quickly if first-line treatments fail 4, 5

3. Missing Associated Tumors: Thorough cancer screening is essential, particularly with certain antibody types 2

4. Premature Discontinuation: Maintenance immunotherapy is often needed to prevent relapses, especially after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) 6