ADEM

INTRODUCTION

ADEM is an inflammatory, demyelinating event

of early childhood presenting with an acute

onset of polyfocal neurologic deficits,

accompanied by encephalopathy and changes

compatible with demyelination on brain MRI

Epidemiology

Although ADEM can occur at any age, most series reporta mean

age of between 5 and 8 yr with a slight male predominance. The

reported incidence ranges from 0.1-0.6 per 100,000 per year in the

pediatric population. ADEM is usualy monophasic, but recurrence

can occur; if the recurrence is 3 mo or longer after the first

episode, the condition is termed multiphasic disseminated

encephalomyelitis (MDEM). Up to 50% of cases of ADEM have

been found to be associated with MOG-Ab (Myelin oligodendrocyte

glycoprotien) positivity in the serum, and almost all cases of MDEM

are MOG-Ab positive; there is thus a strong likelihood that as

MOG-Ab testing becomes more available, cases of non-MOGAb

positive MDEM will become exceptionally rare. An episode of

ADEM can also be followed by non-ADEM demyelination in a new

location. In this scenario, if the MOG-Ab is negative, MS may be

diagnosed. If ADEM is followed by a relapse in a specific location,

such as the optic nerve (ON), then ADEM-ON is diagnosed. If the

ON and spinal cord are involved, then NMOSD (neuromyelitis

optica spectrum disorder); the latter two are frequently associated

with MOG-Ab positivity.

Pathogenesis

Molecular mimicry induced by infectious exposure or

vaccine has been thought to trigger production of CNS

autoantigens, although causality has never been proven.

Many patients experience a transient febrile illness in the

month prior to ADEM onset. Preceding infections

associated with ADEM include influenza, Epstein-Barr virus,

cytomegalovirus, varicella, enterovirus, measles, mumps,

rubella, herpes simplex, and Mycoplasma pneumoniae.

Postvaccination ADEM has been reported following

immunizations for rabies, smallpox, measles, mumps,

rubella, Japanese encephalitis B, pertussis, diphtheria

polio-tetanus, and influenza, although the risk of ADEM

Dostvaccination is significantly lower than following the

infection itself.

ADEM Produces multiple infImamatory lesion

in the brain & spinal cord particularly in the

white matter .Usually these are found in the

subcortical, central white matter &cortical

gray white junction of both cerebral

hemisphere, cerebellum brainstem, spinal cord

but periventicular white matter &gray matter

of cortex,thalami &basal ganglia may also be

involved

Clinical Manifestations

Initial symptoms of ADEM may include:

lethargy, fever, headache, vomiting, meningeal signs, and

seizures, including status epilepticus. Encephalopathy is the

hallmarkof ADEM, ranging from changes in behavior and

persistent irritability to coma.

Focal neurologic deficits can be difficult to ascertain in the

obtunded or very young child, but common neurologic

signs in ADEM include visual loss, cranial neuropathies,

ataxia, and motor and sensory deficits, plus bladder/bowel

dysfunction with concurrent spinal cord demyelination. The

clinical course is usually rapidly progressive over days.

Intensive care unit admission may be required, particularly

for patients with brainstem dysfunction or raised

intracranial pressure.

INVESTIGATIONS

Neuroimaging

Head CT scanning may be normal or show hypodense regions.

Cranial MRI, the imaging study of choice, typically exhibits bilateral,

large, multifocal, and sometimes confluent, edematous mass-like T2

lesions with variable enhancement within white and gray matter of

the cerebral hemispheres, cerebellum, and brainstem. Deep gray

matter structures (e.g., thalami, basal ganglia) are often involved,

although this may not be specific to ADEM . The spinal cord may

have an abnormal T2 signal or enhancement, with or without

clinical signs of myelitis. MRI lesions of ADEM typically appear to be

of similar age, but their evolution may lag behind the clinical

presentation. Serial MRI imaging 3-12 mo following ADEM shows

improvement and often complete resolution of T2 abnormalities,

although residual gliosis may remain.

MATFRM 17

Fig: boy 5 yr of age diagnosed with adem presenting with encephalopathy,atixa &

motor deficits following mild viral infection MRI T2 weighted axilal image shows

bilateral,diffuse, poorly demarcated lesions ,Gray matter involvement

Severe involvement may progress to an acute

hemorrhagic leukoencephalopathy (Weston

Hurst disease) with large lesions, edema, mass

affect, and a polymorphonucleated cell

pleocytosis (in contrast to lymphocytic

pleocytosis in the CSF noted in typical ADEM)

Laboratory Findings

There is no biologic marker for ADEM, and

laboratory findings can vary widely. CSF studies

are often normal or can exhibit pleocytosis with

lymphocytic or monocytic predominance. CSF

protein can be elevated, especially on repeat

studies. Elevated CSF immune globulin

production can be present, but true 0CB

positivity is rare. Electroencephalograms often

show generalized slowing, consistent with

encephalopathy, although polyregional

demyelination of ADEM can also cause focal

slowing or epileptiform discharges.

Differential Diagnosis

ADEM is a clinical diagnosis supported by MRI,

CSF, and serum findings. The differential

diagnosis for ADEM is broad, and empirical

antibiotic and antiviral treatment should be

considered while infectious evaluations are

pending. Follow-up MRI examinations 3-12 mo

after ADEM should show improvement; new or

enlarging T2 lesions should prompt reevaluation

for other etiologies, such as MS, antibody

associated disorders, leukodystrophies, tumor,

vasculitis, or mitochondrial, metabolic, or

rheumatologic disorders

Feature that may distinguiash adem from a first attack of MS

ADEM Wwith or MS

withoutMOG-AB

Age <10 yr(boys and giris are >10 yr Female are

equal) preponderanc

Seizures +

Encephalopathy

Fever/vomiting +

Family history No 20%

Optic neuritis Bllateral unilaterl

CSF study Pleocytosis(lymphocytosis)0 Acellular

CBS negative(oligoconal OCBS positive

bands)

MRI Large,fluffy, poorly Ovoid T2 lesions involving

demarcated T2 lesions juxtacortical, periverntricular,

involving white & gray mtter or infratentorial areas or

spinal lesions; T1

hypointense lesions

MRI Follow up after 30 days

No new lesions

New lesions seen

Treatment

Although there are no randomized controlled trials to

compare acute treatments for ADEM or other

demyelinating disorders of childhood, high-dose

intravenous steroids (typically, methylprednisolone 20

30 mg/kg per day for 5 days with a maximum dose of

1000 mg per day) followed by an oral prednisolone

taper of 1-2 mg/kg/day (maximum 40-60 mg/day) over

4-6 wk. Other treatment options include intravenous

immunoglobulin (usually 2 g/kg administered over 2-5

days) or plasmapheresis (typically 5-7 exchanges

administered every other day) for refractory or severe

cases.After given methylprednisolone 2dose

Prognosis

Most children experience full motor

recovery(50-70%) after ADEM, but residual

defects can be seen, and cognitive deficits or

behavioral changes are not uncommon.

Recovery starts within days to weeks&average

time to recoveris 1-6 month but symptoms

can fluctuate.

Mortality rate may be high 5%

Slightly fluctuate