What is the initial treatment for autoimmune encephalitis?

Initial Treatment for Autoimmune Encephalitis

High-dose corticosteroids (intravenous methylprednisolone) should be the first-line treatment for autoimmune encephalitis once infection has been ruled out. 1

First-Line Treatment Options

The initial management of autoimmune encephalitis follows a stepwise approach:

1. First-line immunotherapy options:

   • Primary option: High-dose IV methylprednisolone (typically 1g daily for 3-5 days)
   • Alternative first-line options (if steroids are contraindicated):
     • Intravenous immunoglobulin (IVIG) - 0.4 g/kg/day for 5 days 2
     • Plasma exchange (PLEX) - 5-10 sessions every other day 3

2. Combined first-line therapy:

   • Consider combination therapy (steroids + IVIG or steroids + PLEX) from the outset in:
     • Severe NMDAR-antibody encephalitis
     • New-onset refractory status epilepticus (NORSE)
     • Cases with severe dysautonomia 3, 1

Treatment Response Assessment

• Evaluate clinical response after initial treatment (around day 8) 2
• If no meaningful response to the first agent:
  • 62% of experts recommend adding a different first-line therapy (sequential approach)
  • 26% recommend proceeding directly to second-line agents 3

Second-Line Treatment

If there is no meaningful clinical or radiological response to optimized first-line therapy after 2-4 weeks, second-line agents should be considered:

• Rituximab - preferred for antibody-mediated autoimmunity (e.g., NMDAR-antibody encephalitis)
  • Common dosing: 375 mg/m² weekly for 4 weeks or two 1000 mg doses 2 weeks apart 3
• Cyclophosphamide - preferred for cell-mediated autoimmunity (e.g., classical paraneoplastic syndromes)
  • Common dosing: 600-1000 mg/m² 3

Bridging Therapy

After acute treatment, initiate bridging therapy with:

• Gradual oral prednisone taper, or
• Monthly IVIG, or
• Monthly IV methylprednisolone 3, 1

Refractory Cases

For patients who don't respond to conventional second-line therapies, consider novel approaches:

• Tocilizumab (IL-6 inhibitor)
• Bortezomib (proteasome inhibitor) 3, 4

Important Clinical Considerations

• Early treatment is crucial: Prompt immunotherapy significantly impacts outcomes
• Cancer screening: Essential in all patients with autoimmune encephalitis, particularly those with certain antibody types 1
• Treatment selection nuances:
  • Rituximab is preferred by 80% of experts as second-line therapy when antibody status is unknown 3
  • PLEX may be particularly effective in refractory cases but has limitations including increased bleeding risk, volume shifts (problematic in dysautonomic patients), and the need for central line placement 3

Treatment Algorithm

1. Initial presentation: Start high-dose IV methylprednisolone
2. If severe presentation: Consider combined therapy (add IVIG or PLEX)
3. If no response after 8 days: Add alternative first-line agent or consider second-line therapy
4. If no response after 2-4 weeks: Add second-line agent (rituximab or cyclophosphamide)
5. If still refractory: Consider novel approaches (tocilizumab or bortezomib)
6. After acute phase: Implement bridging therapy

The evidence from a prospective clinical trial shows that IVIG improves neurological functional outcomes with improvement evident by day 8, with tolerable adverse effects 2, supporting its use as an alternative or additional first-line therapy.