What are the causes and clinical signs and symptoms of Acute Disseminated Encephalomyelitis (ADEM)?

Causes and Clinical Signs and Symptoms of Acute Disseminated Encephalomyelitis (ADEM)

Acute Disseminated Encephalomyelitis (ADEM) is primarily caused by post-infectious or post-vaccination autoimmune responses, characterized by multifocal neurologic deficits, encephalopathy, and inflammatory demyelination of the central nervous system. 1

Etiology

• ADEM is typically triggered by an environmental stimulus in genetically susceptible individuals, most commonly following a viral or bacterial infection (1-2 weeks prior to neurological symptoms) or vaccination (days to 4 weeks after) 1, 2
• Common infectious triggers include:
  • Viral infections: measles, mumps, rubella, varicella zoster, Epstein-Barr virus, cytomegalovirus, herpes simplex, hepatitis A, influenza, and enterovirus infections 2
  • Bacterial infections: various pathogens can trigger ADEM through molecular mimicry mechanisms 1
  • COVID-19 has been recently identified as a potential trigger for ADEM 3
• Vaccination-related ADEM has been associated with vaccines against:
  • Anthrax, Japanese encephalitis, yellow fever, measles, influenza, smallpox, and rabies 2
  • Yellow fever vaccine-associated neurologic disease (YEL-AND) can manifest as ADEM typically 7-20 days post-vaccination 2

Clinical Signs and Symptoms

Neurological Manifestations

• Encephalopathy (altered mental status) is a required component for diagnosis, ranging from confusion to coma 2, 4
• Multifocal neurologic deficits affecting various parts of the central nervous system 1, 4:
  • Optic neuritis (may be bilateral) 2
  • Myelitis (often longitudinally extensive) 2
  • Brainstem encephalitis 2
  • Cerebellar ataxia 2
  • Motor deficits (hemiparesis, tetraparesis) 2
  • Sensory disturbances 1
  • Cranial nerve palsies 1

Systemic Symptoms

• Fever is typically present during the prodromal infectious illness but may be absent at the onset of neurological symptoms 2
• Headache is common 2
• Meningeal signs may be present 4
• Seizures can occur, especially in severe cases 2

Distinctive Clinical Patterns

• ADEM-like presentation with large white matter lesions and disturbance of consciousness 2
• Simultaneous optic neuritis and longitudinally extensive transverse myelitis 2
• Acute respiratory insufficiency, behavioral changes, or epileptic seizures may occur in severe cases 2
• Sphincter and erectile disorders can occur with spinal cord involvement 2

Diagnostic Features

Cerebrospinal Fluid (CSF) Findings

• Lymphomonocytic pleocytosis (sometimes with neutrophils) 2
• Elevated protein levels 1
• Oligoclonal bands are typically absent or transient (unlike in multiple sclerosis) 1, 4

Neuroimaging Findings

• MRI is the imaging modality of choice 5
• Characteristic findings include:
  • Large, confluent T2 brain lesions 2
  • Multifocal, subcortical white matter abnormalities 1
  • Gray matter involvement (thalami and basal ganglia) 4
  • Longitudinally extensive spinal cord lesions in some cases 2
  • Perioptic enhancement during acute optic neuritis 2

Clinical Course and Variants

• Typically monophasic, but recurrent ("multiphasic ADEM") and multiphasic courses have been described 4, 6
• Acute hemorrhagic leukoencephalitis (AHEM) is a more severe, often fatal variant 6
• Symptoms may flare up after tapering of oral steroids, suggesting steroid-dependence in some cases 2
• Most patients respond well to immunosuppressive treatment 7

Treatment Approach

• First-line treatment consists of high-dose intravenous methylprednisolone (20-30 mg/kg/day, maximum 1g/day) for 3-5 days, followed by oral corticosteroid taper over 4-6 weeks 5, 7
• For patients with insufficient response to corticosteroids, intravenous immunoglobulin (IVIG) at 2g/kg divided over 2-5 days is recommended 7
• Plasmapheresis should be considered early for severe or life-threatening cases 7
• Decompressive craniectomy may be necessary in cases with severe intracranial hypertension 7

Differential Diagnosis

• Multiple sclerosis (MS) is the major differential diagnosis, particularly challenging at initial presentation 4, 6
• Other conditions to consider include:
  • Neuromyelitis optica (NMO) 7
  • CNS infections (viral, bacterial encephalitis) 2
  • Other autoimmune CNS disorders 7
  • Neurometabolic disorders 7