Acute disseminated

encephalomyelitis
(ADEM)

Vimalesh Praveen Gnanasekaran,

Group 10, Semester 12, TSMU.

Introduction
● Acute disseminated encephalomyelitis (ADEM) is a central demyelinating disorder
of childhood
● The belief was that ADEM was a monophasic immunological reaction to a viral
illness because fever is an initial feature. This belief is incor-rect on two counts. First,
consider the fever as part of the ADEM and not evidence of prior infection; second,
ADEM often is not monophasic, but the first attack of a recurring disorder similar to
multiple sclerosis.
● An immune-mediated mechanism is the presumed pathophysiology
Etiology
● All forms of acute disseminated encephalomyelitis (ADEM) presumably result from a cross-
reactive immune response to the infectious agent or vaccine that then triggers an inflammatory
demyelinating response
(1) Environmental ● Associated with viral infections
o Measles, Mumps, Rubella (MMR)
o In rare cases, follows immunization from MMR vaccine
● Mycoplasma pneumoniae
● Streptococcus β-hemolyticus
(2) Genetic
● There may be susceptibility genes present but not yet known or documented
● More common in children than in adults
Etiology
● Most commonly associated organisms include cytomegalovirus, Epstein-Barr virus,
herpes simplex virus, human herpes-virus-6, influenza virus, hepatitis A, human
immunodeficiency virus, and mycoplasma pneumonia – though, in the majority of
cases, the causative pathogen is not identified. Additional associated bacterial
infections include Leptospira, beta-hemolytic streptococci, and Borrelia burgdorferi
● Rabies vaccine has been the earliest reported vaccine associated with ADEM. It is
seen in both adults and children approximately eight to 21 days following
immunization. Other less commonly associated vaccines include those for measles,
pertussis, tetanus, influenza, hepatitis B, diphtheria, rubella, pneumococcus, varicella,
smallpox, human papillomavirus, and poliomyelitis.
Epidemiology
● Although it is a rare illness, there is an estimated 1 in 125,000-250,000 individuals
affected by ADEM each year. Though most cases occur in children (majority
younger than age ten, and the remainder between the ages ten to 20), ADEM has
been documented in adults ranging from ages 18-82 as well. The disease occurs more
commonly in males than in females (male to female ratio 1.3:1), and more often
seasonally in the winter and spring (historically, the colder months of the year).
● All ethnic groups are susceptible to developing ADEM, and the condition occurs
worldwide.
● In 50% - 75% of cases, ADEM is associated with either a preceding infection or
vaccination, and the majority of cases follow a viral or bacterial infection (although
the causative pathogen is not always identified).
Pathophysiology
● The exact mechanism of ADEM is not completely understood, It has been proposed that
either a cell-mediated response or antibodies produced in response to an environmental
trigger cross-react with myelin autoantigens (e.g., myelin basic protein, myelin
oligodendrocyte protein, proteolipid protein) in the CNS, resulting in the demyelination
characteristically seen in ADEM.
● An alternatively proposed mechanism suggests that ADEM may occur as a result of increased
vascular permeability and congestion in the CNS due to the inf l ammation and circulating
immune complexes that follow vaccination or infection. Mononuclear inf i ltration of the
vasculature of the CNS is thought to result in edema surrounding vessels and, at times,
hemorrhage causing damage to surrounding neuronal cells (e.g., demyelination, necrosis or
gliosis) and ultimately, the variety of possible clinical presentations and prognoses seen in
individuals with ADEM
Pathophysiology
Pathophysiology summary
Summary of events:
● Increased cell adhesion molecule expression
● Vasodilation
● Increased capillary permeability
● Chemotaxis
● Stimulation of macrophages
● Increase in antibody production
● Phagocytosis of oligodendrocytes and myelin sheaths
● “Plaque” formation
Clinical features
● One-time event ● In severe cases, there is an abrupt onset and the disease progress rapidly (hours to days)
(1) Fever, headache, nausea
● In postinfectious ADEM, the immune system is activated and cytokine production (IL-1, IL-6, TNF-α) will
be triggered.
These cytokines will act on the hypothalamus which will then trigger prostaglandin E2 production which
resets the hypothalamic thermostat.
As a result, there will be an increase in body temperature.
(2) Optic neuritis
● Optic nerve [Cranial nerve (CN) II] is inflamed affecting the visual pathway
● CN II involvement is generally bilateral and transverse myelopathy complete
● ↓ Visual acuity
● Color vision abnormalities
Clinical features
(3) Pseudobulbar palsy
● The oligodendrocytes that myelinate the axons of the corticobulbar tract are destroyed;
upper motor neuron (UMN) lesion
● Trigeminal nerve (CN V) o Decreased chewing o Jaw jerk reflex will be brisk or
hyperactive
● Facial nerve (CN VII) o Absent facial expression
● Glossopharyngeal, Vagus, and Accessory nerves (CN IX, X, XI) o Dysphonia, dysphagia
● Hypoglossal nerve (CN XII) o Dysarthria
Clinical features
(4) Altered mental status (Encephalopathy)
o There is a lot of demyelination of higher order brain centers
o Important for differentiation o Very irritable and confused
(5) Decreased level of consciousness
o Demyelinated axons of the reticular formation
o Arousal of the central nervous system is affected
o Worst case leads to comatose
6) Ataxia
● Demyelinated axons of the cerebellum
o Seizures happens if there is involvement of a lot of cortical neurons
Spinal cord involvement
● ↓ Dorsal column sensation: o Proprioception, fine touch, discriminative
touch, and vibration sense are affected

● UMN lesion: o Injury to the corticospinal tract, upper motor neuron that
gives fibers that go the lower motor neuron (LMN) in the anterior horn o
Weakness, increased tone, increased deep tendon reflex (hyperreflexia,
positive Babinski sign

● Anterior spinothalamic tract: o Demyelination of the axons causes

decreased crude touch and pressure sensation

● Lateral spinothalamic tract: o Demyelination of the axons causes

decreased pain and temperature sensation

● LMN lesion: o Injury to the anterior gray horn o Weakness o Hypotonia

o Hyporeflexia o Fasciculations
Diagnosis
(1) Magnetic Resonance Imaging (MRI)

● First line

● MRI of the brain and spinal cord with and without contrast

● A lot of lesions in the cerebral cortex, the brainstem, and spinal

cord can be seen, just like in MS

o In the supratentorial region, there are a lot of demyelination which

is asymmetric in character, called multifocal

o T1 – presents as hypointense (dark) when there is demyelination

o T2 – presents as hyperintense (bright) when there is demyelination

o Contrast enhances acute lesions

Diagnosis
(2) Lumbar puncture
● Obtain cerebrospinal fluid o CSF protein is modestly elevated (0.5-1.5 g/L)
● Increase in IgG antibodies
● Pleocytosis o Lymphocytic pleocytosis (200 cells/µL or greater) occurs in 80% of patients
● Can be subjected to culture for identification of S. β-hemolyticus, Mycoplasma
● Viral panel for measles, mumps, Rubella
Although there are no set diagnostic criteria for ADEM in adults, for children, a diagnosis is
made based on the presence of both encephalopathy and multifocal CNS involvement. Children
with ADEM have also been found to have an elevated sedimentation rate and a slightly elevated
platelet count
Treatment
(A) ACUTE TREATMENT
● First line: High dose IV corticosteroids
o The drug will decrease the activity or function of the cytokines
o Depending on the response, medication may need to be continued for 8 weeks
● Second line: o Plasmapheresis
● IVIg Will bind to IgG antibodies and hinder it form being able to bind to the
oligodendrocytes in the myelin
(B) EMPIRIC THERAPHY
● Start with antibiotics and antiviral medications until the result of culture comes back. These
should be discontinued if the result is clear of any infectious agent.
● Mortality rate of 5-20% ● Survivors have permanent neurologic sequelae
Treatment
● Treatment with intravenous high-dose methylprednisolone (20–30 mg/kg/day, up to 1
g) helps in about 50% of cases.
● Intravenous immunoglobulin (IVIg) (2 g/kg divided into 2–5 days) and plasma
exchange may benefit children who fail to respond to corticosteroids.
● Decompressive craniectomy may be needed to treat high intracranial pressure
Prognosis
● The prognosis for most individuals with ADEM is good. The recovery process may
take place over four to six weeks, but the majority of those with ADEM make a fairly
significant recovery. Between 60 to 90 percent are left with no neurological deficits.
● In rare instances, ADEM can be fatal.
THANK YOU !
Vimalesh Praveen Gnanasekaran,
Group 10, Semester 12, TSMU.