What is the management of acute demyelinating encephalopathy of childhood, including presentation differentials?

Management of Acute Demyelinating Encephalopathy of Childhood: Presentation Differentials and Treatment

Immediate high-dose intravenous methylprednisolone (1g daily for 3-5 days) should be initiated as first-line treatment for acute demyelinating encephalopathy of childhood once the diagnosis is suspected, following appropriate diagnostic workup. 1

Clinical Presentation and Differential Diagnosis

Key Clinical Features Suggesting Acute Demyelinating Encephalopathy

• Current or recent febrile illness with altered behavior, personality, cognition, or consciousness
• New onset seizures or focal neurological signs 2
• Motor system abnormalities and altered consciousness (most common presenting symptoms) 3
• Ataxia, headache, and weakness (frequently observed) 4
• Acute hemiparesis (76%), long tract signs (85%), and mental status changes (69%) in pediatric cases 5

Important Differential Diagnoses

1. Infectious encephalitis (viral, bacterial, parasitic, fungal)
2. Para-infectious immune-mediated processes:
   • Acute Disseminated Encephalomyelitis (ADEM)
   • Tumefactive demyelinating lesions
3. Autoimmune encephalitis:
   • NMDA receptor antibody encephalitis
   • Voltage-gated potassium channel antibodies
4. Metabolic encephalopathies
5. Vascular disorders
6. Neoplastic/paraneoplastic syndromes
7. Toxic encephalopathies 2

Features Suggesting Non-Encephalitic Process

• Past history of similar episodes
• Symmetrical neurological findings
• Myoclonus
• Clinical signs of liver failure
• Lack of fever
• Acidosis or alkalosis 2

Diagnostic Approach

Immediate Investigations

1. Neuroimaging:

   • MRI brain (investigation of choice) 4
   • Look for:
     • Open or incomplete ring enhancement pattern
     • Multiple lesions at different stages of evolution
     • Periventricular white matter involvement
     • Corpus callosum involvement 1
     • Thalamic and basal ganglia involvement (common in ADEM) 6

2. CSF Analysis:

   • Cell count and differential
   • Protein and glucose
   • Oligoclonal bands (typically absent in ADEM) 5
   • CNS demyelinating disease antibodies
   • JCV PCR (to exclude progressive multifocal leukoencephalopathy)
   • Viral PCRs (including HSV) 2, 1

3. Serology:

   • Myelin oligodendrocyte glycoprotein (MOG) antibodies (may indicate relapsing potential) 7
   • Autoimmune encephalopathy or paraneoplastic antibodies 1

Treatment Algorithm

First-Line Treatment

• High-dose intravenous methylprednisolone (1g daily for 3-5 days) 1, 3
• This treatment is associated with better outcomes and complete recovery 3

For Severe or Progressive Symptoms

• Continue pulse corticosteroids
• Consider adding:
  • IVIG (2g/kg over 5 days at 0.4g/kg/day) OR
  • Plasmapheresis if no response to steroids 1

Maintenance Phase

• Oral steroid taper over at least 4-6 weeks 1
• Longer tapering periods (>3 weeks) are associated with lower relapse rates 3

For Limited or No Improvement

• Consider rituximab in consultation with neurology, especially if positive for autoimmune encephalopathy or paraneoplastic antibodies 1

Important Caution

• Avoid TNF antagonist therapy as these agents are contraindicated in demyelinating diseases 1

Monitoring and Follow-up

1. During Treatment:

   • Regular neurological examinations to assess treatment response
   • Monitor for rebound symptoms during steroid taper 1

2. Post-Treatment:

   • Follow-up MRI at 4-6 weeks to evaluate lesion evolution 1
   • Be aware that MRI lesions may persist even in asymptomatic patients
   • Periventricular lesions tend to disappear later than other lesions 3

Prognosis

• Generally favorable outcome in pediatric patients (89% with minimal or no disability) 5
• Complete clinical recovery is common, and serious complications are rare 3
• Approximately 10-33% may experience relapses 3, 5
• Risk factors for poorer outcomes:
  • Optic nerve involvement at presentation 5
  • Inadequate duration of steroid treatment 3
  • Positive MOG antibodies (associated with relapsing disease) 7

Common Pitfalls to Avoid

1. Delayed diagnosis due to reliance on CT scans (often normal and falsely reassuring) 4
2. Inadequate steroid treatment duration (tapering too quickly increases relapse risk) 3
3. Failure to consider autoimmune causes in sub-acute presentations (weeks to months) 2
4. Missing relapsing forms of disease (10% may have biphasic course) 5
5. Overlooking cognitive deficits during follow-up (can occur even without other neurologic sequelae) 6