Acute Disseminated Encephalomyelitis

What is ADEM?

Acute Disseminated Encephalomyelitis (ADEM) belongs to a group of disorders called Acquired demyelinating syndromes (ADSs). Acute Disseminated Encephalomyelitis. An acute demyelinating inflammatory monophasic polyfocal (multifocal) neurological disorder of childhood. Has encephalopathy with MRI T lesions as hallmarks. 

Acquired Demyelinating Syndromes

Neurological functional disorders characterized by immune-mediated injury to the myelin sheath in: CNS, Spinal cord, Optic nerve- sometimes

Most commonly mediated by 2 types of IgG antibodies → Responsible for demyelination: AQP4-Antibody

• Aquaporin 4 Antibody
• Aqueous water channel antibody
• Found on astrocyte plasma membrane
• Associated with NMO-SD (Neuromyelitis optica spectrum disorder)

MOG-antibody

• Myelin Oligodendrocyte Glycoprotein Antibody
• Found on the lamella and surface of oligodendrocyte
• Associated with ADEM (Acute Disseminated Encephalomyelitis)

Epidemiology & Variants

Mean age: 5-8 years, although any age can be affected. Most cases occur in the first decade of life.

Males > Females (1.3:1). Incidence: 0.1-0.6 per 100000 children per year.

Variants of ADEM (2% of cases)

• MDEM
  • Multiphasic Demyelinating Encephalomyelitis
  • If there is any recurrence of ADEM ≥3 months after the initial episode
  • 100 % of cases are positive for MOG-Ab
  • True variant
• · ADEM-ON
  • ADEM + Optic nerve involvement
    • Leading to optic neuritis
  • Most of the cases are positive for MOG-Ab
• · NMO-SD
  • Neuromyelitis optica spectrum disorder
    • Spinal cord involvement
    • Optic nerve involvement
    • With or without ADEM-like features
  • Positive for MOG-Ab and AQP4-Ab

Pathogenesis of ADEM

Initial infection (Usually viral GIT / Viral Respiratory)

↓

Trigger the formation of antibodies

↓

Antibodies cross-react with CNS autoantigens (AQP4 and MOG antigens)

(Molecular Mimicry)

↓

Cause demyelination & encephalopathy

Viral Triggers

• Influenza virus
• Epstein-Barr virus
• Varicella zoster virus
• Herpes simplex virus
• COVID-19
• Enterovirus
• Measles
• Mumps
• Rubella
• Mycoplasma pneumoniae

Clinical Picture

• Initial symptoms
  • Fever
  • Lethargy
  • Headache
  • Vomiting
  • Meningeal signs
  • Seizures
  • Status epilepticus
• Hallmark: Encephalopathy
  • Behavioural changes → Irritability → Sleep changes → Coma
• Neurological signs
  • Visual loss
  • Ataxia
  • Motor and sensory deficits
  • Cranial nerve palsies
• If the spinal cord is involved
  • Bladder and bowel dysfunction
• Often rapidly progressive & may need PICU care due to brainstem dysfunction or raised ICP.
  • More than 50% of cases generally require ICU care.

Laboratory Investigations

• Serum MOG-Antibody (IgG)
  • Positive in 50% ADEM
  • Positive in 100% MDEM
• CSF studies: Can be normal or abnormal
• Some patients can have
  • CSF pleocytosis with lymphocytic or monocytic predominance
  • CSF protein may be high
  • Raised CSF immunoglobulins may be seen
• EEG: Generalized slow waves
  • Suggesting encephalopathy
• In poly-regional demyelination
  • Focal slowing or epileptic discharges are present

Neuroimaging

• MRI is the investigation of choice: Evolution of lesions lags the clinical picture.
• T images are superior to T images 2 1: Involvement of white and grey matter
• T image shows: 2: Large, bilateral, multifocal edematous, mass-like lesions in cerebral
• hemispheres, cerebellum, thalamus, basal ganglia, and brainstem: Fuzzy lesions
• T signal enhancement with/without myelitis seen in the spinal cord 2
• Serial MRIs 3-12 months later show near complete resolution, but some may show residual gliosis.

Differential Diagnosis of ADEM

• Viral encephalitis
• Multiple sclerosis
• Leukodystrophies
• Tumours
• Mitochondrial disorders

Treatment

• DOC: High-dose IV Methylprednisolone 20-30 mg/kg/day × 5 days
• After 5 days, shift to Oral Prednisolone 1-2mg/kg/day & taper over 4-6 weeks
  • To avoid the persistence of lesions for longer duration
  • True relapses will not occur
• Refractory or severe cases: can consider
• IVIG: 2g/kg over 2-5 days
  • Plasmapheresis: 5-7 exchanges performed every alternate day
  • +/– Cyclophosphamide (not mentioned in Nelson)

Complication

Weston-Hurst disease

• Also known as Hyperacute ADEM
• Severe ADEM can sometimes progress to an acute hemorrhagic leukoencephalopathy, also called Weston-Hurst disease.
  • Characterized by large lesions, edema with mass effect, and raised ICP.
    • Raised ICP is seen (in >80% of cases)
  • CSF may show neutrophilic pleocytosis
  • Poor prognosis
  • Treatment
    • Steroids + Plasma exchange
  • Craniotomy may be needed to manage raised ICP
  • Very high mortality
    • Within 2-4 days of onset
    • Up to 70-80% mortality within 1st week
    • Up to 90% mortality in 2nd week

Prognosis

Most children attain full motor recovery in 1-3 months. No new MRI features or symptoms appear after 3months. Cognitive & behavioural issues may persist for long. Recovery starts within days of onset, but symptoms can fluctuate.

Hope you found this blog helpful for your NEET SS Pediatrics Neurology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.