Acute Disseminated Encephalomyelitis (ADEM)

Authors:

Nazish Najeeb MBBS,

Junaid Kalia MD

Introduction

• Acute disseminated encephalomyelitis (ADEM)

• Is an immune-mediated demyelinating disease of CNS

• Involves white matter in the brain and spinal cord.

• Grey matter (basal ganglia, thalamus, and even cortical grey matter) may be involved.

Epidemiology

• ADEM is a rare illness

• Estimated 1 in 125,000-250,000 individuals affected each year.

• It mostly occurs in children (majority <10 yr, remainder 10-20yr)

• More commonly in males than in females (male to female ratio 1.3:1)

• More common in winter and spring

Etiology

• Post-infection (67%)

• Post-vaccination

• Genetic susceptibility (rarely)

Table 1: Etiological factors of ADEM

Pathophysiology

1. Molecular mimicry

2. T cell-mediated inflammation

Molecular mimicry:

T cell-mediated inflammation:

1. Priming and activation

2. Recruitment and effector phase and resulting into
• Infiltration of lymphocytes and macrophages in the small blood vessels of both white and grey matter
• Hyperemia
• Endothelial swelling
• Vessel wall invasion by inflammatory cells
• Perivascular edema
• Hemorrhage
• As the lesions become older, at a late stage of disease foci of fibrillary fibrosis can also be seen in adjacent brain tissue.

Clinical features

Initial Presentation

• Fever

• Headache

• Fatigue

• Meningismus

• Malaise

• Nausea

• Vomiting

Neurological Signs

1. Encephalopathy
The characteristic feature of ADEM develops rapidly.
Presents as
• Confusion
• Coma
• Irritability
• Acute cognitive dysfunction
• Behavioral changes

2. Other neurologic abnormalities:
• Ataxia
• Aphasia
• Nystagmus
• Optic neuritis
• Urinary retention
• Elevated intracranial pressure
• Extrapyramidal signs

Diagnostic Criteria

• Multifocal, clinical CNS event with a presumed inflammatory demyelinating cause

• Encephalopathy that cannot be explained by fever, systemic illness, or post-ictal fever

• No new clinical and MRI findings 3 months or more after the onset

• Brain MRI is abnormal with changes consistent with demyelination during the acute, 3-month phase.

Subtypes Of ADEM

• Monophasic ADEM
• single episode with no further demyelinating events more than 3 months after onset.

• Multiphasic ADEM
• Two episodes separated by at least 3 months in time. More than two episodes suggest an alternate disease process.

• ADEM-ON
• Any episode of ADEM plus one or more episodes of optic neuritis.

• Acute hemorrhagic encephalomyelitis (AHEM)
• Fulminant presentation associated with multifocal hemorrhages and necrosis.

Differential Diagnosis

• Aseptic meningitis

• Bell's palsy

• Brain metastasis

• Brucellosis

• Cardioembolic stroke

• Cauda equina and conus medullaris syndrome

• Cavernous sinus syndromes

• Central nervous system complications in HIV

• Cerebral venous thrombosis

• Churg-Strauss disease

ADEM and Multiple Sclerosis

Table 2: Differentiating Features of ADEM and Multiple Sclerosis

Derived from:Bickle, I. Acute disseminated encephalomyelitis. Case study, Radiopaedia.org. (accessed on 15 Oct 2021) https://radiopaedia.org/cases/37253

Derived from: Sorrentino, S. Multiple sclerosis. Case study, Radiopaedia.org. (accessed on 15 Oct 2021) https://radiopaedia.org/cases/15764

Figure 1: (Left) ADEM, showing bilateral enhancing lesions of variable size throughout both cerebral hemispheres in the deep white matter, juxta-cortical regions, and left thalamus. (Right) MS, showing periventricular hyper intensities typical of multiple sclerosis plaques.

Investigation

Non-specific

• Leucocytosis, predominately lymphocytosis

• Raised platelets

• Raised CRP and ESR

Viral cultures and serology

• Culture of throat, nasopharynx, stool, and CSF

• Serology testing for a variety of agents such as influenza, EBV, herpes, and mycoplasma, etc.

Cerebrospinal fluid

• Raise RBC and WBC

• Increase protein concentration

• Increase myelin basic protein

• Rarely elevated IgG index

• Oligoclonal bands in up to 29 % of cases

Imaging

MRI

• ADEM lesion characteristics
• Bilateral
• It may be symmetric or asymmetric
• Poorly marginated
• The periventricular area is spared (which is involved commonly in MS)
• Located in deep and subcortical and central white matter, cortical gray-white matter junction, and deep gray matter of the basal ganglia, thalami, cerebellum, brainstem.

• Best modality used in the diagnosis of ADEM and is best defined in T2, FLAIR &
• T2-weighted images
• Fluid-attenuated inversion recovery (FLAIR) sequences
• Proton density, or echo-planar trace diffusion techniques

CT scan

• most often unremarkable

• In later stages, ADEM may appear as focal or multifocal regions of white matter damage.

Electroencephalography

• Disturbed sleep pattern

• Focal or generalized slowing of electrical activity, typical of encephalopathy

• Seizure activity may also be noted

Management

Medical

Anti-microbial

• Antibiotic or Acyclovir until an infectious agent is ruled out

Corticosteroids

• High dose IV methylprednisolone 30 mg/kg/day up to a maximum dose of 1000 mg per day for 3-5 days

• Oral treatment at dose of 1-2 mg/kg/day is continued and gradually tapered over a period of 4-6 weeks to reduce risk of relapse

Intravenous immunoglobulin

• 1gm/kg/day IV for 2-5 days

Indication for IVIG use:

• Recommended for <1 year age

• No response to steroids in 48-72 hours
• Induction Dose up to 2 g/kg in 2 to 5 divided doses.
• Follow‐up Dose -1 g/kg followed by a second dose (if required) after 4 to 6 weeks for extended monophasic ADEM

• Recurrent cases
• Induction Dose up to 2 g/kg in 2–5 divided doses
• Maintenance Dose ‐ 1 g/kg, 4–6 weekly

• Acute hemorrhagic leucoencephalitis, AHLE

Plasmapheresis

• Recommended for patient not responding to both steroid and IVIG

Surgical

• Surgical intervention is indicated in cases of elevated intracranial pressure and hemorrhagic brain purpura as a result of AHLE by
• Lumboperitoneal shunt
• Bilateral optic nerve decompression
• Decompression of the intracranial fossae by unroofing of the cranium

Rehabilitation

• <5 years age show excellent recovery
• Early rehabilitation program is required in case of cognitive impairment, epilepsy, visual and motor deficits (weakness, spasticity, ataxia), and impairment in speech

Prognosis

• Children with ADEM show a slow and complete recovery in four to six weeks

• Adults with ADEM have increased rates of hospitalization, intensive care unit admission, and mortality compared to pediatric patients

• 60 % do not show any neurologic deficits.

• Neurologic deficits present in the form of transverse myelitis, behavioral problems, and cognitive impairment mostly in <5 years old.

Further Reading

1. Anilkumar AC, Foris LA, Tadi P. Acute Disseminated Encephalomyelitis. [Updated 2021 Jul 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430934/

2. Garg RK. Acute disseminated encephalomyelitis. Postgraduate Medical Journal 2003;79:11-17.

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