Treatment of Acute Necrotizing Encephalitis with IVIG, Tocilizumab, and PLEX
High-dose intravenous methylprednisolone initiated early (within 24 hours of symptom onset) should be the first-line treatment for acute necrotizing encephalitis, with the addition of tocilizumab and plasma exchange (PLEX) showing significant benefit in improving outcomes, while intravenous immunoglobulin (IVIG) may be added but has shown less clear benefit when used alone. 1
Initial Treatment Approach
- Begin high-dose intravenous methylprednisolone (HD-IV-MP) as soon as possible after diagnosis, ideally within 24 hours of neurologic symptom onset, as early initiation significantly improves outcomes 1
- Consider adding tocilizumab (IL-6 receptor antagonist) early in the disease course, especially in combination with HD-IV-MP, as this combination has shown favorable outcomes in severe cases 2, 3
- PLEX should be implemented as part of the treatment regimen as it has been shown to improve survival in acute necrotizing encephalitis 1
- IVIG (0.4 g/kg/day for 5 days) can be added to the regimen, though meta-analysis data shows no significant difference in outcomes between patients treated with or without IVIG 1, 4
Treatment Algorithm Based on Severity
For All Confirmed Cases:
- Initiate high-dose IV methylprednisolone immediately (within 24 hours if possible) 1
- Rule out infectious causes before starting immunosuppressive therapy 4
For Severe Cases (Rapid Neurological Deterioration or Coma):
- Combine HD-IV-MP with tocilizumab early in treatment course 2, 3
- Add PLEX (5-10 sessions performed every other day) 4, 1
- Consider IVIG as adjunctive therapy 5
Patient-Specific Considerations for IVIG vs. PLEX
- IVIG is preferred for patients who are agitated or combative, have bleeding disorders or coagulopathy, or have difficulty with central line placement 4
- PLEX is preferred for patients with severe hyponatremia, high thromboembolic risk, or associated brain demyelination 4
- For patients with ANE specifically, PLEX has shown better survival outcomes than IVIG alone 1
Monitoring and Response Assessment
- Monitor interleukin-6 (IL-6) levels if available, as increased blood IL-6 levels correlate with poor outcomes in ANE 2
- Perform serial neuroimaging to assess response to treatment, with reduction in thalamic and other brain lesions indicating treatment effectiveness 3
- Assess for clinical improvement in consciousness, seizure control, and neurological function 2
Important Considerations and Caveats
- The pathogenesis of ANE is linked to genetic susceptibility and cytokine storm, with IL-6 playing a central role, which explains the effectiveness of tocilizumab 3
- Despite aggressive treatment, ANE can still result in long-term neurological sequelae, making early intervention crucial 5, 6
- Timing of treatment initiation appears to be a critical factor in outcomes, with earlier treatment associated with better prognosis 1, 2
- The combination of multiple immunomodulatory therapies (HD-IV-MP, tocilizumab, and PLEX) appears to be more effective than monotherapy in severe cases 1, 2
Treatment Escalation for Refractory Cases
- If no clinical improvement is observed within 48-72 hours of initial treatment, consider escalating immunosuppression 4
- For patients not responding to the combination of HD-IV-MP, tocilizumab, and IVIG, adding PLEX may provide additional benefit 1
- Consider additional doses of tocilizumab in cases with persistent elevated inflammatory markers 2, 3