What is the initial treatment for Acute Necrotizing Encephalitis of Childhood (ANEC) versus Acute Disseminated Encephalomyelitis (ADEM)?

Initial Treatment for Acute Necrotizing Encephalitis of Childhood (ANEC) versus Acute Disseminated Encephalomyelitis (ADEM)

For ADEM, high-dose intravenous corticosteroids (methylprednisolone, 1 g intravenously daily for 3-5 days) are the first-line treatment, while ANEC requires a more aggressive approach with early combination therapy including corticosteroids, IVIG, and potentially IL-6 receptor blockade with tocilizumab within the first 24 hours.

Acute Disseminated Encephalomyelitis (ADEM) Treatment

First-Line Treatment

• High-dose intravenous corticosteroids:
  • Methylprednisolone 1 g intravenously daily for 3-5 days 1
  • Follow with oral prednisone taper over 4-6 weeks 1

Second-Line Treatments (if poor response to corticosteroids)

• Plasma exchange (PLEX):

  • 5-10 sessions every other day 1
  • Consider PLEX first in patients with:
    • Severe hyponatremia
    • High thromboembolic risk
    • Associated brain or spinal demyelination 1

• Intravenous immunoglobulin (IVIG):

  • 2 g/kg divided over 5 days 1
  • Consider IVIG first in:
    • Agitated patients
    • Patients with bleeding disorders 1

Combination Therapy

• Consider starting with combination therapy (steroids + IVIG or steroids + PLEX) for severe presentations 1

Acute Necrotizing Encephalitis of Childhood (ANEC) Treatment

First-Line Treatment (Aggressive Approach)

• Early combination immunotherapy within first 24 hours 2:
  • High-dose corticosteroids (methylprednisolone or dexamethasone)
  • IVIG (2 g/kg divided over 5 days)
  • IL-6 receptor blockade with tocilizumab - critical for improved outcomes 2

Timing Considerations

• Evidence suggests that administration of tocilizumab within the first 24 hours significantly improves long-term outcomes compared to delayed administration 2
• Early aggressive immunotherapy is essential due to the rapid progression and high mortality rate of ANEC 3

Key Differences in Management

Diagnostic Workup for Both Conditions

1. Neuroimaging: MRI with contrast of brain, cervical, and thoracic spine 1, 4
2. Lumbar puncture: CSF analysis including autoimmune encephalitis panel, oligoclonal bands, and viral PCRs 1, 4
3. EEG: To evaluate for subclinical seizures 1, 4
4. Serum studies: To rule out other conditions 1, 4

Critical Distinctions

• ADEM: Primarily responds to corticosteroids alone; additional therapies added sequentially if needed 1, 5
• ANEC: Requires immediate aggressive combination therapy including IL-6 blockade; sequential approach associated with poorer outcomes 2, 3
• Mortality risk: ANEC has significantly higher mortality (estimated 30%) compared to ADEM (estimated 10%) 6

ICU Considerations

• Both conditions may require ICU admission for:
  • Airway protection
  • Management of increased intracranial pressure
  • Treatment of seizures or status epilepticus 1, 4

Important Caveats and Pitfalls

1. Do not delay immunotherapy while awaiting complete diagnostic workup in suspected ANEC due to its rapid progression and high mortality 2, 3

2. Rule out infectious causes before starting immunotherapy, but empiric antimicrobial coverage may be needed while awaiting results 1, 4, 7

3. Monitor for treatment complications:

   • Steroid-induced hyperglycemia, hypertension, and psychiatric effects
   • IVIG-related thrombotic events
   • PLEX-related bleeding risk and hemodynamic instability 1

4. Consider transfer to a specialized center with neurological expertise if diagnosis is uncertain or if the patient fails to improve with initial therapy 4

5. Avoid misdiagnosis: ANEC can be mistaken for viral encephalitis; consider both diagnoses in the appropriate clinical context 7, 6