What is the summary of Acute Disseminated Encephalomyelitis (ADEM)?

Acute Disseminated Encephalomyelitis (ADEM): A Comprehensive Overview

ADEM is an immune-mediated inflammatory demyelinating disorder of the central nervous system characterized by multifocal neurologic deficits including encephalopathy, typically occurring after an infection or vaccination. 1

Definition and Pathophysiology

ADEM is defined as inflammation of the brain parenchyma (encephalitis) with associated demyelination. It is primarily considered an autoimmune response to a preceding antigenic challenge, such as:

• Viral infections (measles, mumps, rubella, varicella zoster, Epstein-Barr virus, cytomegalovirus, herpes simplex, hepatitis A, influenza, enterovirus) 1
• Bacterial infections (particularly Mycoplasma pneumoniae) 2
• Vaccinations (typically occurring 1-14 days post-vaccination) 1, 2

Epidemiology

• More common in children than adults 1, 3
• Incidence in children: approximately 10.5-13.8 per 100,000 1, 4
• Bimodal age distribution with peaks in childhood and elderly 1

Clinical Presentation

ADEM typically presents with:

• Encephalopathy (altered mental status, confusion, behavioral changes) 1
• Multifocal neurological deficits occurring simultaneously 5
• Fever is usually absent at onset of neurological symptoms 1
• Symptoms typically develop 1-4 weeks after a preceding infection or vaccination 1, 2

Common neurological manifestations include:

• Visual disturbances (optic neuritis) 1, 5
• Motor deficits (weakness, hemiplegia) 5, 6
• Sensory abnormalities 2
• Ataxia and postural imbalance 5
• Seizures 6
• Urinary retention 2

Diagnostic Approach

Cerebrospinal Fluid (CSF) Analysis

• Lymphomonocytic pleocytosis (sometimes with neutrophils) 1, 5
• Elevated protein levels 5, 3
• Normal glucose levels 5
• Oligoclonal bands typically absent or transient (important distinction from MS) 1, 5, 3
• Elevated myelin basic protein may be present 2

Neuroimaging

• MRI is the imaging modality of choice 5, 3
• Characteristic findings include:
  • Multiple, multifocal T2-weighted hyperintense lesions 5
  • Involvement of both white and gray matter 6
  • Supratentorial and infratentorial lesions 5
  • Large, confluent T2 brain lesions 1
  • No lesions adjacent to lateral ventricles that are ovoid/round or associated with inferior temporal lobe lesions (Matthews-Jurynczyk criteria) 1

Differential Diagnosis

• Multiple sclerosis (MS) 1, 3
• Viral encephalitis 6
• Neuromyelitis optica (NMO) 7
• MOG antibody-associated disease 1
• Metabolic encephalopathies 7

Treatment

The standard treatment approach includes:

1. First-line therapy: High-dose intravenous corticosteroids

   • Methylprednisolone 20-30 mg/kg/day (maximum 1 g/day) for 3-5 days 7
   • Followed by oral corticosteroid taper over 4-6 weeks 7

2. Second-line therapy (for insufficient response or contraindications to steroids):

   • Intravenous immunoglobulin (IVIG) 2 g/kg divided over 2-5 days 7

3. For severe or life-threatening cases:

   • Plasma exchange (plasmapheresis) should be considered early 7, 2
   • Decompressive craniectomy may be necessary for intracranial hypertension 7

4. Empiric antimicrobial therapy:

   • Antibacterial and antiviral treatment (including acyclovir) should be initiated until infectious causes are ruled out 7, 6

Prognosis

• ADEM is typically monophasic (single episode) with favorable outcomes 7, 3
• However, recurrent and multiphasic courses have been described 7
• Complete recovery occurs in most cases with prompt treatment 5, 7
• Follow-up MRI is recommended to confirm improvement of lesions 5, 2

Clinical Pearls and Pitfalls

• Diagnostic pitfalls:

  • ADEM can mimic viral encephalitis on imaging; consider both diagnoses in patients with encephalopathy 6
  • ADEM can be the initial presentation of other demyelinating disorders like MS or NMO 7
  • Absence of preceding infection/vaccination does not rule out ADEM 3

• Treatment considerations:

  • Early immunotherapy is crucial for favorable outcomes, especially in fulminant cases 6
  • Delayed treatment beyond 48 hours after hospital admission is associated with worse outcomes 4
  • In patients with relapsing demyelinating events, consider chronic autoimmune CNS diseases like MS or NMO 7

• Special populations:

  • Immunocompromised patients may have atypical presentations and should be evaluated for opportunistic infections 4
  • ADEM in adults is rare but should be considered in the differential diagnosis of acute-onset multifocal neurological deficits 5, 2