Treatment Options for Acute Necrotizing Encephalopathy in Children
High-dose intravenous methylprednisolone (1g daily for 3-5 days) combined with intravenous immunoglobulin (IVIG) at 2g/kg over 5 days should be initiated as first-line therapy for acute necrotizing encephalopathy in children. 1
Understanding Acute Necrotizing Encephalopathy (ANEC)
ANEC is a rare but severe neurological condition primarily triggered by viral infections, particularly influenza viruses. It is characterized by:
- Rapid progression from fever to encephalopathy and coma
- Bilateral thalamic involvement on neuroimaging
- Typically affects children aged 1-5 years
- Often follows a short febrile illness (2-4 days after respiratory symptoms)
Diagnostic Approach
Before initiating treatment, confirm diagnosis with:
- MRI (essential and diagnostic): Look for bilateral thalamic involvement, additional lesions in brainstem, cerebral white matter, or cerebellum 1
- CSF analysis: Typically shows increased protein without pleocytosis 1
- Laboratory tests: Check for viral etiology (particularly influenza), liver enzymes, and platelet count 2
- Genetic testing: Consider testing for RANBP2 variants which are present in approximately 34% of cases 2
Treatment Algorithm
1. Initial Management (First 24 Hours)
Stabilize and support: Follow hemodynamic support protocols for pediatric shock 3
- Maintain airway, breathing, circulation
- Establish IV/IO access
- Provide fluid resuscitation if needed
- Monitor for signs of increased intracranial pressure
Empiric therapy pending diagnosis:
2. Specific Immunomodulatory Treatment (Start as soon as diagnosis is suspected)
First-line therapy:
Second-line therapy (if no response to first-line):
Third-line therapy:
3. Supportive Care and Monitoring
- ICU admission for close monitoring (median ICU stay is 11 days) 2
- Monitor for and treat:
- Seizures
- Increased intracranial pressure
- Hemodynamic shock (present in many cases) 4
- Multi-organ dysfunction
4. Advanced Support for Refractory Cases
- For refractory shock or respiratory failure, consider ECMO (Extracorporeal Membrane Oxygenation) 3
- For fluid overload with inadequate urine output, consider CRRT (Continuous Renal Replacement Therapy) 3
Follow-up and Long-term Management
- Steroid taper over 4-6 weeks with monitoring for rebound symptoms 1
- Follow-up MRI at 4-6 weeks to evaluate lesion evolution 1
- Regular neurological examinations to assess treatment response 1
Prognosis and Outcomes
The prognosis for ANEC is generally poor:
- Mortality rate is high (27% in recent US cohort) 2
- Among survivors, 63% have at least moderate disability at 90-day follow-up 2
- Early intervention with immunomodulatory therapy may improve outcomes 1, 5
- Early administration of tocilizumab (within 24 hours) shows promise for better long-term outcomes 5
Important Clinical Considerations
- Early recognition and treatment are critical - Delay in treatment is associated with worse outcomes
- Genetic testing - Consider testing for RANBP2 variants which may predispose to ANEC
- Influenza prevention - Only 16% of affected children in a recent study had received age-appropriate influenza vaccination 2
- Timing matters - Evidence suggests that administration of immunomodulatory therapy, particularly tocilizumab, within the first 24 hours may lead to better outcomes 5
Emerging Therapies
Recent evidence suggests that IL-6 receptor blockade with tocilizumab as an add-on therapy within the first 24 hours may significantly improve long-term outcomes, particularly in high-risk patients 5. This approach is showing promise but requires further study before becoming standard of care.