ADEM Management

Dr Roopchand PS

Senior Resident Academic

Department of Neurology

Introduction:• Uncommon monophasic idiopathic

inflammatory demyelinating disease.

• Pleiotropic clinical manifestations.• Usually include encephalopathy.

• Often considered in the differential diagnosis of

a clinicallyisolated (demyelinating) syndrome

(CIS).

• The hallmark of ADEM is its monophasic

course.

• The annual incidence of ADEM is reported to

be 0.4–0.8 per 100,000

• ADEM should be considered when one or more

of the following are present:

• Multifocal, polysymptomatic initial

presentation.

• Age younger than 10 years.

• Signs and symptoms of meningoencephalitis.

• Encephalopathy.

• Bilateral ON.

• Cerebrospnal fluid (CSF) pleocytosis without

oligoclonal bands.

• Magnetic resonance imaging (MRI)-detected

lesions involving structures not typically

affected in MS such as the deep gray matter

or cortex.

• MRI-detected lesions that are large and

exhibit indistinct borders and enhancement

following gadoli nium administration.

• There are no accepted, prospective, or

pathologically verified clinical diagnostic criteria

for ADEM.

• Mikaeloff et al definition:• The occurrence in a previously healthy child of

acute symptoms associating the following at onset:

more than one neurological deficit

(‘‘polysymptomatic’’ onset); change in mental state;

and any combination of alterations seen on MRI,

providing that these included white matter lesions.

• Most restricted definition of ADEM to date• In Pediatric age group.

• 18 % relapsed.

• IPMSSG criteria under evaluation.

• Encephalopathy is the most specific clinical

feature of ADEM.

• Encephalopathy can be seen in fulminant MS.

• Pathophysiology:• Pathological hallmark of ADEM is perivenular

inflammation with limited sleeves of demyelination.

• Acute hemorrhagic leukoencephalitis - additionally

exhibits petechial hemorrhage and venular

necrosis.

• Activation of autoreactive T-cell clones.

Clinical Findings:

• Winter and spring seasonal peaks- suggests viral

etiology.

• Molecular mimicry may produce immune mediated

attack.

• There is a unique immune-mediated CNS process

with a distinct pathophysiology that is

independent of the immune trigger.

• A history of antecedent infection or vaccination may

increase the likelihood of ADEM.

ANTECEDENT INFECTION AND

VACCINATION

• ADEM is more frequent in children.

• Five percent of MS patients present at an age

younger than 16 years.

• Several clinical symptoms of

meningoencephalitis are consistently

associated with ADEM.

• Encephalopathy, seizures, fever, headache,and

meningeal signs.

• More common in pediatric age group and less

common in adults.

• Encephalitis can also cause these symptoms.

• A change in level of consciousness is more

suggestive.

• 23% of 40 patients diagnosed with ADEM

presented with bilateral ON(Dale et al).

• Unilateral ON is associated with MS.

• NMO can present with B/L ON.

• Suspected ADEM patients with B/L ON should

be also evaluated for NMO.

• Typical ADEM is poly symptomatic.

• Restricted forms : ON, Transverse myelitis,

Cerebellitis, Brain stem encephalitis.

Investigations:

• Infection must be excluded by CSF analysis

and culture.

• CSF can be normal or can show lymphocytic

pleocytosis.

• 58% of adult and 29% of pediatric cases with

ADEM have OCBs.

• OCBs resolve in ADEM.

• Persistent OCB points towards MS.

MRI

• Useful in diagnosing ADEM and excluding other conditions.

• MRI will show : multifocal areas of increased T2-weighted (T2W) signal abnormalities in the CNS white matter, with or without gray matter involvement.

• Gadolinium enhancement is less or not seen in ADEM.

• ADEM suggestive: symmetric bilateral disease, relative sparing of the periventricular white matter, or deep gray matter involvement.

• MRI features alone may not be able to

differentiate MS.

• MRI negative ADEM has been reported.

• Single large focal lesion can be compatible with

ADEM..

• Diffusion Tensor imaging and Magnetization

Transfer Imaging can identify abnormalities in

apparently normal appearing white matter.

• ADEM can recurr : 10 to 18%

• Possibility of MS cannot be completely ruled

out.

• Expert opinion: A case is ‘‘recurrent’’ if a

subsequent attack is stereotypical of the first

attack and there is no evidence of involvement

of a different part of the CNS clinically or by

MRI.

TREATMENT

• Spontaneous recovery can occur.

• Recovery is incomplete in patients who have not

received immunomodulation.

• Use of high-dose steroids, plasma exchange,

and intravenous immunoglobulin are based on

the analogy of pathogenesis of ADEM with that

of MS.

• (1) supportive

• (2) specific—high-dose intravenous methyl

prednisolone, intravenous immunoglobulin

(IVIg), and plasma paresis

• (3) physical and rehabilitation therapy

• Supportive care : management of ventilation,

dyselectrolemias, seizures, maintenance of BP.

Methyl Prednisolone:

• Intravenous methyl prednisolone is the first-line

drug (10–30 mg/kg/day, up to a maximum of 1

g/day) for 3–5 days are being used (Class IV).

• Full recovery has been reported in 50%–80% of

patients.

• Oral corticosteroid treatment is continued with

gradual tapering over 6 weeks to reduce the

risk of relapses.

• Any type of vaccination should be avoided

during the first 6 months following recovery.

PLEx

• Plasma exchange is indicated if corticosteroid

therapy fails.

• There is Class Ib evidence for PE.

• A course of 4–6 PEs have been shown to be

associated with moderate to marked and

sustained improvement.

• Predictors associated with improvement include

male sex, preserved reflexes, and early

initiation of treatment.

IvIg:

• Intravenous immunoglobulin (IVIg) (0.4

gm/kg/day for 5 days) is another option.

• High cost of treatment and the evidence for this

modality of treatment in ADEM is Class IV.

• The improvement is seen within 2–3 days.

• The choice of IvIg vs PLEx depends upon

availability and clinical situation.

• Methyl prednisolone along with IVIg has been

successfully used in patients with atypical

features and could be tried for fulminant,

aggressive, and atypical disease.

Prognosis

• Early studies showed mortality rate of 20% with

a high incidence of neurologic sequelae (

especially postmeasles).

• Prolonged altered mental state was associated

with both mortality and morbidity.

• Multiple or single extensive lesions on MRI

lesions may be associated with disability.

• The prognosis of nonmeasles cases is

favorable and most studies report a full

recovery in 50%–75% of patients.

• Recovery period : 1 to 6 months.