Introduction

  • Acute, immune-mediated perivenous demyelinating disorder.
  • Characterized by rapid onset of neurological symptoms and signs.
  • Generally monophasic illness.
  • Primarily affects children (mean age 5–8 years).

Etiology & Pathogenesis

  • Occurs 1–3 weeks post-precipitating viral illness or immunization.
  • Triggers cross-reactive immune response to infectious agent or vaccine.
  • Initiates inflammatory demyelinating response.
  • Autoantibodies to Myelin Basic Protein (MBP) and Myelin Oligodendrocyte Glycoprotein (MOG) detected in CSF/serum. MOG-Ab present in ~50% of affected children.

Common Triggers

  • Viral Infections: Measles (1 in 1000 cases), varicella (1 in 4000–10000), rubella, mumps, influenza, parainfluenza, Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), HIV, dengue, Zika, COVID-19.
  • Bacterial Infections: Mycoplasma pneumoniae.
  • Vaccinations: Live measles, smallpox, Semple rabies, Japanese encephalitis. Modern vaccines reduce ADEM risk.

Clinical Features

  • Rapid progression over hours to days.
  • Follows viral illness or exanthem resolution.

Hallmark Sign

  • Encephalopathy: Essential diagnostic feature. Ranges from behavioral changes and persistent irritability to coma.

Neurological Signs

  • Fever, headache, meningismus.
  • Altered sensorium.
  • Seizures (partial/generalized, status epilepticus).
  • Hemiparesis/paraparesis.
  • Cranial nerve deficits.
  • Optic neuritis (typically bilateral).
  • Cerebellar ataxia (especially prominent post-varicella).
  • Bladder/bowel disturbances.
  • Myoclonus/involuntary movements.

Investigations

Neuroimaging

  • MRI Brain/Spine: Modality of choice.
    • Multiple hyperintensities on T2/FLAIR images.
    • Lesions large, fluffy, poorly demarcated.
    • Involves cerebral white matter, basal ganglia, cortical grey matter, brainstem, cerebellum, and spinal cord.
    • Contrast enhancement variable.
  • CT Scan: Multiple hypodensities in white matter; may enhance with contrast.
  • Follow-up MRI: Complete/near-complete resolution typical at 3–12 months. No new lesions expected.

Cerebrospinal Fluid (CSF)

  • Often normal.
  • Mild lymphocytic pleocytosis (100–200 cells/cm³).
  • Mildly raised proteins (0.5–1.5 g/L).
  • Oligoclonal bands (OCB) typically negative (distinguishes from Multiple Sclerosis).

Differential Diagnosis

ADEM vs. Multiple Sclerosis (MS)

FeatureADEMMultiple Sclerosis (MS)
Age & Sex<10 years, Male = Female>10 years, Female preponderance
SeizuresPresentAbsent
EncephalopathyPresentAbsent
Fever/VomitingPresentAbsent
Optic NeuritisBilateralUnilateral
SymptomsPolysymptomaticMonosymptomatic
CSF ProfilePleocytosis, OCB negativeAcellular, OCB positive
MRI LesionsLarge, fluffy, poorly demarcated T2 lesions involving white and gray matterOvoid T2 lesions (juxtacortical, periventricular, infratentorial), T1 hypointense
MRI Follow-up (>30 days)No new lesionsNew lesions seen

Management

First-Line Therapy

  • High-dose intravenous steroids.
  • Methylprednisolone 20–30 mg/kg/day (max 1000 mg/day) OR Dexamethasone 5 mg/kg/day for 5 days.
  • Followed by oral prednisolone taper (1–2 mg/kg/day) over 10–14 days (may extend 4–6 weeks).

Refractory/Severe Cases

  • Intravenous Immunoglobulin (IVIG): 2 g/kg over 2–5 days. Useful if differentiation from viral encephalitis difficult.
  • Plasmapheresis: 5–7 exchanges administered every other day.

Prognosis & Variants

  • Mostly full motor recovery.
  • Residual deficits (cognitive impairment, behavioral changes) common.
  • Mortality 5–20% in severe cases.
  • Acute Hemorrhagic Leukoencephalitis (Weston-Hurst disease): Severe progression variant. Leukodystrophy-like MRI. Edema with mass effect. Polymorphonuclear cell pleocytosis.
  • Multiphasic ADEM (MDEM): Recurrence $\ge$ 3 months post-initial event. Almost exclusively MOG-Ab positive.
  • ADEM-ON: ADEM followed by isolated optic neuritis relapse. MOG-Ab associated.