Dr Mohamed elsayed gharbia

Acute disseminated encephalomyelitis

in children:

Treatment and prognosis

INTRODUCTION

Acute disseminated encephalomyelitis (ADEM), also known

as postinfectious encephalomyelitis,

is a demyelinating disease of the central nervous system that

typically presents as a monophasic disorder associated with

multifocal neurologic symptoms and disability.

TREATMENT

Children with ADEM typically present with fever,

meningeal signs, acute encephalopathy, and evidence of

inflammation in blood and cerebrospinal fluid.

Thus, consideration should be given to treatment with

broad-spectrum antibiotics and acyclovir until an infectious

etiology is excluded.

Lines of treatment

1. high-dose intravenous glucocorticoids .

2. intravenous immune globulin .

3. plasma exchange .

However, the effectiveness of these treatments for ADEM

has not been definitively confirmed, as there are no

prospective clinical trial data to determine optimal

treatment, including dose or duration.

Glucocorticoids

The mainstay of treatment for ADEM is high-dose iv glucocorticoids .

Glucocorticoids may be started at the time of the patient's

presentation and can be used concurrently with antibiotics

and acyclovir.

in several small observational studies, treatment of ADEM with

iv methylprednisolone (10 -30 mg/kg /day, maximum 1000 mg

daily) or

dexamethasone (1 mg/kg /day) for 3-5 days, followed by oral

glucocorticoid taper over 4-6 weeks, was associated with full

recovery in approximately 60 to 90 % of patients .

Which glucocorticoid is preferred ?

In the only study that compared these two treatments for

ADEM intravenous methylprednisolone (n=21) was associated with a modestly

better outcome, as measured by the median Expanded Disability Status

Scale, than

intravenous dexamethasone (n=25), and the difference was statistically

significant .

The strength of this result is limited by small patient

numbers, lack of randomization, and lack of blinded

treatment or assessment.

Tapering of glucocorticoid !!! ??

There is no convincing evidence that the use or duration of a

tapering oral glucocorticoid regimen after iv glucocorticoid

therapy influences outcome.

Two small observational studies reported higher relapse rates in

children with ADEM who were treated with shorter ( ≤ 3

weeks) compared with longer glucocorticoid tapers, but this

finding was not statistically significant .

Recommendation

We recommend immunosuppressive treatment for ADEM in

children, and suggest high-dose iv glucocorticoids as initial

therapy.

Although there is no consensus regarding glucocorticoid

regimens, we use methylprednisolone (30 mg/kg / day, up to

a maximum dose of 1000 mg / day) for 5 days.

Recommendation

We use an oral prednisone taper only in children who

continue to show clinical symptoms after completion of the

high dose iv glucocorticoid treatment.

We begin the taper with oral prednisone 1 mg/kg / day up to

a maximum of 60 mg / day and then reduce the dose by 10

mg every 5 days to allow for a total tapering duration of 4 - 6

weeks.

Intravenous immune globulin

Data from small case series and case reports suggest that

intravenous immune globulin (IVIG) is beneficial as rescue

therapy in patients with ADEM who fail to respond to

methylprednisolone or as initial therapy .

Dosing of IVIG in these studies ranged from 1- 2 g/kg given

either as a single dose or divided over 3 – 5 days .

Intravenous immune globulin

No studies have compared IVIG treatment with

glucocorticoids or plasma exchange .

We suggest IVIG for patients with ADEM who have an

insufficient response to i.v glucocorticoid treatment.

Our preferred regimen is a total of 2 g/kg given in divided

doses over 3 days.

Plasma exchangeLimited data suggest that plasma exchange is beneficial in children with

ADEM who fail treatment with IVIG and/or methylprednisolone .

The largest series was retrospective and reported improvement following plasma exchange in six children with ADEM who did not respond to initial treatment with glucocorticoids followed by IVIG .

In another retrospective study, plasma exchange demonstrated some benefit for patients with idiopathic transverse myelitis when used in combination with iv glucocorticoids.

Therefore, it may be of particular benefit for patients with ADEM associated with myelopathy .

We suggest treatment with plasma exchange for children with ADEM who have longitudinally extensive transverse myelitis and who fail treatment with glucocorticoids.

Plasma exchange also should be considered for other patients with ADEM who fail to respond to treatment with glucocorticoids and IVIG.

Our preferred regimen is a total of six exchanges, one every other day, with each exchange consisting of 1 - 1.5 plasma volumes.

EXTENDED FOLLOW-UP Follow-up MRI shows complete or partial resolution of abnormalities in

the majority of ADEM cases However, residual gliosis and demyelination

persist in some.

Long-term clinical follow-up and sequential imaging by MRI are usually

required to confirm the diagnosis of ADEM .

The development of relapses with new lesions on MRI is not compatible

with a diagnosis of monophasic ADEM, and suggests that the correct

diagnosis is either multiphasic ADEM or multiple sclerosis, depending on

the clinical and imaging features.

Do we need to repeat MRI ??

Although no consensus exists, some experts suggest

obtaining at least two additional MRIs after the 1st normal

MRI,

over a period of at least 5 years from the initial episode

of ADEM

to confirm the absence of new inflammatory demyelinating

lesions .

PROGNOSIS

Most children with ADEM make a full recovery, usually slowly

over 4 – 6 weeks.

At follow-up, approximately 60 - 90 % have minimal or no

neurologic deficits .

Although modern studies of ADEM in children report little or

no mortality, earlier studies suggested that the mortality of

postinfectious ADEM was as high as 5 %.

The extent and site of lesions on the initial MRI do not predict

the clinical outcome

outcomethe following case series illustrate the range of outcomes for children

with ADEM:

The largest study included 84 children from Argentina with ADEM.

At a mean follow-up of 6.6 years, the neurologic examination was either normal or detected minor abnormalities but no associated disability in 75 children (89 %).

Residual deficits in the remaining children included : mild to severe hemiparesis,

mild paraparesis,

partial epilepsy,

reduced visual acuity, and

mental handicap.

outcome

In a report from Australia, 31 children with ADEM were followed

for an average of 18 months .

Complete recovery occurred in 25 (81 %).

Mild abnormalities were detected in the remaining 6 patients;

these included

recurrent headaches,

behavioral problems,

esotropia,

subtle hemiparesis, and

minor gross motor abnormalities.

outcome

In a study from the United Kingdom, 28 children with ADEM

were followed for a mean of 5.8 years .

A complete recovery occurred in 20 (57 %).

Of the remainder, 6 patients four had motor disabilities, which were severe in three

four had visual impairment;

four had cognitive impairment;

four had behavior problems; and

two had persistent limb paresthesia.

outcome

The prognosis for survival and recovery of neurologic

function is worse for the hyperacute hemorrhage variants of

ADEM, such as acute hemorrhagic leukoencephalitis, than for

typical ADEM .

Brain edema and subsequent death may occur within a week

of the onset of encephalopathy in these uncommon variants.

However, immunosuppressive treatment may be associated

with improved outcome.