What is the recommended treatment for autoimmune encephalitis using Intravenous Immunoglobulin (IVIG) or Plasma Exchange (PLEX)?

Treatment of Autoimmune Encephalitis with IVIG or PLEX

For autoimmune encephalitis, both IVIG and PLEX are effective first-line immunotherapies, with the choice between them guided by patient-specific factors: IVIG is preferred for agitated patients and those with bleeding disorders, while PLEX is preferred for patients with severe hyponatremia, high thromboembolic risk, or associated brain/spinal demyelination. 1

First-Line Treatment Approach

Initial Treatment Selection

• High-dose corticosteroids are typically the first-line treatment for autoimmune encephalitis, but IVIG or PLEX should be used when steroids are contraindicated or ineffective 1
• IVIG is administered at 0.4 g/kg/day for 5 days, while PLEX typically involves 5-10 sessions performed every other day 1, 2
• Treatment should be initiated as soon as infection is ruled out based on CSF results and when primary CNS lymphoma or neurosarcoidosis is not a consideration 1

Patient-Specific Considerations for IVIG vs. PLEX

• IVIG is preferred when:

  • The patient is agitated or combative (as PLEX requires patient cooperation) 1
  • There are bleeding disorders or coagulopathy present 1
  • Central line placement would be difficult or risky 1

• PLEX is preferred when:

  • The patient has severe hyponatremia 1
  • There is high thromboembolic risk (cancer, smoking history, hypertension, diabetes, hyperlipidemia, hypercoagulable states) 1
  • The clinical presentation includes brain or spinal demyelination 1
  • The condition resembles neuromyelitis optica spectrum disorder (NMOSD) 1

Treatment Escalation

Sequential or Combination Therapy

• If there is no clinical, radiological, or electrophysiological improvement after initial treatment with corticosteroids, add IVIG or PLEX as the next step 1
• For severe initial presentations (e.g., severe NMDAR-antibody encephalitis, new-onset refractory status epilepticus, severe dysautonomia), consider combination therapy with steroids plus IVIG or steroids plus PLEX from the beginning 1
• In a recent study, there was no significant difference in outcomes between IVIG+steroids versus PLEX+steroids in encephalitis caused by antibodies against NMDAR, LGI1, or CASPR2 3

Second-Line Therapy

• If no improvement is seen 2-4 weeks after completion of combined first-line therapy, consider second-line agents such as rituximab or cyclophosphamide 1
• Rituximab is preferred for antibody-mediated autoimmunity (e.g., NMDAR-antibody encephalitis) 1, 4
• Cyclophosphamide is preferred for cell-mediated autoimmunity (e.g., classical paraneoplastic syndrome) 1

Efficacy and Safety Considerations

IVIG Efficacy and Safety

• IVIG has been shown to improve neurological functional outcomes in autoimmune encephalitis, with improvement evident by day 8 in a prospective clinical trial 2
• Adverse effects of IVIG are generally mild and tolerable 2
• IVIG can be administered without the need for central line placement 1

PLEX Efficacy and Safety

• PLEX has shown effectiveness in autoimmune encephalitis, particularly in refractory cases 1
• A small retrospective study showed that patients with NMDAR-antibody encephalitis treated with both corticosteroids and PLEX had better improvement in the modified Rankin score than those treated with corticosteroids alone 1
• Major limitations of PLEX include increased bleeding risk, volume shifts (problematic in dysautonomic patients), and the need for central line placement 1

Common Pitfalls and Caveats

• Delaying immunotherapy while waiting for antibody results can worsen outcomes; treatment should be initiated promptly when autoimmune encephalitis is suspected 5
• PLEX may be challenging in agitated patients who cannot cooperate with the procedure 1
• Volume shifts during PLEX can be problematic in patients with dysautonomia 1
• The specific method of plasma exchange (plasmapheresis or immunoadsorption) does not appear to affect outcomes 3
• Despite treatment, almost all patients have some residual neuropsychiatric deficits, and many experience clinical relapses 5

Bridging and Maintenance Therapy

• After acute treatment, start bridging therapy with gradual oral prednisone taper, monthly IVIG, or monthly intravenous methylprednisolone 1
• Long-term follow-up is essential as residual deficits are common despite appropriate treatment 5