ADEM
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
- Viral Encephalitis.
- Multiple Sclerosis (MS).
ADEM vs. Multiple Sclerosis (MS)
| Feature | ADEM | Multiple Sclerosis (MS) |
|---|---|---|
| Age & Sex | <10 years, Male = Female | >10 years, Female preponderance |
| Seizures | Present | Absent |
| Encephalopathy | Present | Absent |
| Fever/Vomiting | Present | Absent |
| Optic Neuritis | Bilateral | Unilateral |
| Symptoms | Polysymptomatic | Monosymptomatic |
| CSF Profile | Pleocytosis, OCB negative | Acellular, OCB positive |
| MRI Lesions | Large, fluffy, poorly demarcated T2 lesions involving white and gray matter | Ovoid T2 lesions (juxtacortical, periventricular, infratentorial), T1 hypointense |
| MRI Follow-up (>30 days) | No new lesions | New 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
3 months post-initial event. Almost exclusively MOG-Ab positive. - ADEM-ON: ADEM followed by isolated optic neuritis relapse. MOG-Ab associated.