What is Acute Disseminated Encephalomyelitis (ADEM)?

Acute Disseminated Encephalomyelitis (ADEM)

Acute Disseminated Encephalomyelitis (ADEM) is an immune-mediated inflammatory demyelinating disorder of the central nervous system characterized by encephalopathy and multifocal neurologic deficits that typically follows a viral infection or vaccination.

Definition and Classification

• ADEM is defined as inflammation of the brain parenchyma that causes a syndrome of neurological dysfunction, often occurring as a post-infectious or post-vaccination autoimmune response 1
• It is considered a monophasic illness, distinguishing it from other demyelinating disorders like multiple sclerosis, although recurrent cases (termed multiphasic disseminated encephalomyelitis) have been reported 2
• ADEM is classified among the inflammatory demyelinating diseases of the central nervous system that can affect both brain and spinal cord 3

Epidemiology

• ADEM predominantly affects children, with reported incidences of approximately 10.5 to 13.8 per 100,000 children in Western settings 1
• In the UK, this translates to approximately 1-2 children per year in a typical district general hospital and 8-10 in a large tertiary children's hospital 1
• Adult-onset ADEM is less common but does occur 4

Etiology

• ADEM typically develops following a viral or bacterial infection (post-infectious ADEM) or vaccination (post-vaccination ADEM) 1, 3
• Common infectious triggers include measles, mumps, rubella, varicella zoster, Epstein-Barr virus, cytomegalovirus, herpes simplex, hepatitis A, influenza, and enterovirus infections 1, 3
• Vaccines that have been temporally associated with ADEM include those against anthrax, Japanese encephalitis, yellow fever, measles, influenza, smallpox, and rabies 1, 3

Clinical Presentation

• Encephalopathy is a required component for diagnosis, ranging from confusion to coma 3
• Multifocal neurologic deficits affecting various parts of the central nervous system are characteristic 3, 2
• Common neurological manifestations include:
  • Optic neuritis (often bilateral) 3
  • Myelitis (frequently longitudinally extensive) 3
  • Brainstem encephalitis 3
  • Cerebellar ataxia 3
  • Motor deficits 3
  • Seizures 3
• Symptoms typically develop 1-14 days after vaccination or 1 week after the appearance of a rash in an exanthematous illness 1
• Fever is usually absent at the onset of neurological illness 1
• In hyperacute cases, rapid progression to coma can occur within 24 hours of the first neurological symptom 5

Diagnostic Evaluation

• MRI is the imaging modality of choice, revealing characteristic findings such as 3:
  • Large, confluent T2 hyperintense brain lesions
  • Multifocal, subcortical white matter abnormalities
  • Involvement of thalami and basal ganglia
  • Longitudinally extensive spinal cord lesions
  • Perioptic enhancement during acute optic neuritis
• CSF analysis typically shows 3, 2:
  • Lymphomonocytic pleocytosis
  • Elevated protein levels
  • Normal glucose levels
  • Oligoclonal bands may be absent or transient (unlike in multiple sclerosis)
• Diagnostic criteria require exclusion of other conditions that can mimic ADEM 1, 2

Differential Diagnosis

• Multiple sclerosis (the major differential diagnosis) 6
• Infectious encephalitis (viral, bacterial, fungal, parasitic) 1
• Neuromyelitis optica spectrum disorder 7
• Antibody-associated encephalitis (e.g., anti-NMDA receptor encephalitis) 1
• Metabolic encephalopathies 1
• Neoplastic conditions 7
• Toxic encephalopathies 1

Treatment

• First-line treatment is high-dose intravenous methylprednisolone, followed by oral corticosteroid taper over 4-6 weeks 3, 7
• For patients who don't respond to corticosteroids, second-line treatments include 7:
  • Intravenous immunoglobulin (IVIG)
  • Therapeutic plasma exchange (plasmapheresis)
• Symptoms may flare during steroid tapering, suggesting steroid-dependence in some cases 3
• In cases of hyperacute ADEM with rapid deterioration, aggressive immunotherapy including combination treatments may be necessary 5

Prognosis

• The outcome is generally favorable in pediatric patients, with most cases being self-limiting 6
• Complete recovery is more common in children than adults 4, 6
• Some patients may have significant morbidity related to the severity of acute illness 7
• Cognitive deficits have been reported even in the absence of other neurologic sequelae 2
• The hyperacute form of ADEM has a higher mortality rate 5

Follow-up

• Follow-up MRI is recommended to confirm resolution or improvement of lesions 4
• Long-term monitoring is important to distinguish monophasic ADEM from the first presentation of multiple sclerosis or other relapsing demyelinating disorders 2