Acute disseminated encephalomyelitis (ADEM)

This guide covers theoretical aspects in the case of Acute disseminated encephalomyelitis(ADEM). This may help you answer the following viva questions.

• Define ADEM?
• When does (age) ADEM commonly present?
• Explain the etiopathogenesis?
• Name a few vaccines which are found to be associated with ADEM?
• What could be the presenting complaint in a child with ADEM?
• How will you investigate the case of ADEM?
• What is an oligoclonal band, State the conditions it is associated with?
• What are the EEG findings in ADEM?
• What could be the differential diagnosis?
• How will you differentiate between MS and ADEM?
• What are the management options for ADEM?

Definition - What is acute disseminated encephalomyelitis (ADEM)?

ADEM is an inflammatory demyelinating disease of the central nervous system with multifocal neurologic deficits, typically accompanied by encephalopathy.

Demography

• Boys more than girls 3:1
• Mean age between 5 and 8 yr
• One fourth may need PICU admission
• ADEM occurs once in the majority of cases.

Etiopathogenesis

ADEM is also called postinfectious encephalomyelitis. Many patients experience a transient febrile illness in the month (4 to 6weeks) prior to the onset of ADEM

Molecular mimicry induced by infectious exposure or vaccine may trigger the production of CNS autoantigens and autoantibodies in genetically susceptible individuals.

Myelin autoantigens which might be responsible for this mimicry are

1. Myelin basic protein,
2. Proteolipid protein, and
3. Myelin oligodendrocyte glycoprotein IgG antibodies. Remember this simply as MOG IgG antibodies.

Preceding infections associated with ADEM include

1. Influenza,
2. Epstein-Barr virus,
3. Cytomegalovirus,
4. Varicella,
5. Enterovirus,
6. Measles, mumps, rubella,
7. Herpes simplex, and
8. Mycoplasma pneumoniae.
9. Covid-19

Post-vaccination ADEM

ADEM has been reported following immunizations for

1. Rabies vaccine
2. Smallpox vaccine
3. Measles Mumps Rubella vaccine
4. Japanese encephalitis B vaccine
5. Pertussis vaccine
6. Diphtheria-polio-tetanus vaccine
7. Influenza vaccine

Clinical Manifestations

CLinical clues from the history of ADEM

1. History of Transient febrile illness, 4 to 6weeks prior to the onset of ADEM
2. Acute onset and
3. Rapid progression of symptoms

Pediatric history taking and examination

Initial symptoms

Initial symptoms of ADEM may include

1. Lethargy,
2. fever,
3. headache,
4. vomiting,
5. meningeal signs, and
6. seizures, including status epilepticus.
7. Trouble in balancing

Encephalopathy

Encephalopathy is a hallmark of ADEM.

Other neurologic signs in ADEM

The symptoms can be varied and depend on which part of the brain and or spinal cord is demyelinating. Therefore any combination of signs and symptom is possible in ADEM.

Common neurologic signs in ADEM include

1. visual loss,
2. cranial neuropathies,
3. ataxia,
4. motor, and sensory deficits,
5. Bladder/bowel dysfunction with concurrent spinal cord demyelination.

Less than 2 years old can have a fulminant course of symptoms.

Diagnosis

Neuroimaging

Head CT

Head CT may be normal or show hypodense regions, however, its use is limited only to the acute and unstable patients who may not tolerate the long time and sedation required for MRI and when the facility for MRI is not available.

MRI and follow up MRI scans

1. Cranial MRI, is the imaging study of choice.
2. It typically shows the involvement of white matter. The lesions are large, and asymmetrical with ill-defined margins. 
3. White matter lesions are more characteristic. Grey matter lesions are seen less often.
4. MRI scan can be used initially to confirm or rule out other differentials like the first episode of MS
5. Serial imaging at 3-12 months following ADEM treatment should show improvement and often complete resolution of T2 abnormalities although residual gliosis may remain. New abnormalities on follow-up strongly support the alternate diagnosis.

Electroencephalograms (EEG)

EEG often shows generalized slowing, consistent with encephalopathy. Here is how to identify a slow EEG waveform?

Laboratory Findings

There is no biological marker as such for ADEM and laboratory findings can vary widely.

CSF studies

CSF often exhibits pleocytosis. CSF protein can be elevated. Up to 10% of ADEM may have oligoclonal bands in the CSF.

They can be seen in CSF as well as plasma (paired samples).

Differential Diagnosis

Follow-up MRI examinations 3-12 mo after ADEM should show improvement. New or enlarging T2 lesions should prompt re-evaluation for other etiologies such as

1. MS,
2. Leukodystrophies,
3. CNS tumor,
4. CNS vasculitis
5. Mitochondrial or metabolic diseases
6. Rheumatologic disorders involving CNS
7. Leukodystrophies,
8. CNS tumor,
9. CNS vasculitis
10. Mitochondrial or metabolic diseases
11. Rheumatologic disorders involving CNS

Clinical and MRI features that distinguish ADEM from the first attack of MS.

Both ADEM and MS are autoimmune responses to myelin causing demyelination in the brain and spinal cord. Obviously, they share a similar clinical presentation which makes it important to differentiate between them.

Children who have ADEM in past can later develop MS

Can ADEM have a relapse?

Very rarely, yes. If a relapse occurs after the ADEM diagnosis, the usual reasons could be an infection or withdrawal of steroids. In such cases call it MDEM (multiphasic disseminated encephalomyelitis).

Treatment

Steroids

High-dose intravenous steroids are commonly used. Typically methylprednisolone in a dose of 20-30 mg/kg per day for 5 days with a maximum dose of 1,000 mg per day is used. Oral prednisone is then used to taper over 1 month to prevent relapse.

IVIG and Plasmapheresis

Other treatment options include intravenous immune globulin (IVIG usually 2 g/kg administered over 2-5 days) or plasmapheresis (typically 5-7 exchanges administered every other day).

Many children experience full recovery after ADEM but some are left with residual motor and/or cognitive deficits. ADEM is usually a monophasic illness but demyelinating symptoms can fluctuate for several months.

Prognosis

1. Marked improvement within 30 days, mortality up to 3%
2. Follow-up MRI within 4 months usually shows complete resolution, few may have residual findings.
3. For the majority, ADEM occurs once with no relapse, however, relapses does occur especially when the MOG antibody is positive.
4. The long-term prognosis for children with ADEM is good with the majority making a complete recovery. This includes even those with initially severe symptoms.
5. Those MOG+ can develop epilepsy.
6. For the majority, recovery begins within days but continues for up to one year. A small group can have residual symptoms.

Want to explore neurology further?

1. Brain abscess
2. Cerebral palsy
3. Questions on neurology
4. History taking  neurology

Further reading

1. Stonehouse M, Gupte G, Wassmer E, et al. Acute disseminated encephalomyelitis: recognition in the hands of general pediatricians. Archives of Disease in Childhood 2003;88:122-124.
2. Serena Massa, Adriana Fracchiolla, Cosimo Neglia, Alberto Argentiero and Susanna Esposito. Update on Acute Disseminated Encephalomyelitis in Children. Children 2021, 8, 280

Author

Ajay Agade | DNB(Pediatrics), FNB(Pediatric Intensive Care), Fellowship in Pediatric pulmonology and LTV

Ajay is a Paediatric Intensivist, currently working in Pediatric Pulmonology & LTV at Great Ormond Street Hospital NHS, London