This document discusses the treatment and prognosis of acute disseminated encephalomyelitis (ADEM) in children. It recommends high-dose intravenous glucocorticoids as the primary treatment, with options for intravenous immunoglobulin or plasma exchange for patients who do not respond to glucocorticoids. Most children with ADEM fully recover, though some studies found 10-40% of patients had minor residual symptoms. The prognosis is generally good, but worse for rare hemorrhagic variants of the disease.

1. Dr Mohamed elsayed gharbia
Acute disseminated encephalomyelitis
in children:
Treatment and prognosis

2. 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.

3. TREATMENT
Children withADEM 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.

4. Lines of treatment
1. high-dose intravenous glucocorticoids .
2. intravenous immune globulin .
3. plasma exchange .
 However, the effectiveness of these treatments forADEM
has not been definitively confirmed, as there are no
prospective clinical trial data to determine optimal
treatment, including dose or duration.

5. 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 ofADEM 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 .

6. 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.

7. 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 withADEM who were treated with shorter ( ≤ 3
weeks) compared with longer glucocorticoid tapers, but this
finding was not statistically significant .

8. Recommendation
We recommend immunosuppressive treatment forADEM 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.

9. 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.

10. Intravenous immune globulin
Data from small case series and case reports suggest that
intravenous immune globulin (IVIG) is beneficial as rescue
therapy in patients withADEM 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 .

11. Intravenous immune globulin
No studies have compared IVIG treatment with
glucocorticoids or plasma exchange .
We suggest IVIG for patients withADEM 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.

12. Plasma exchange
 Limited 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 withADEM
associated with myelopathy .

13. 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.

14. 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 ofADEM .
 The development of relapses with new lesions on MRI is not compatible
with a diagnosis of monophasicADEM, and suggests that the correct
diagnosis is either multiphasicADEM or multiple sclerosis, depending on
the clinical and imaging features.

15. 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
ofADEM
 to confirm the absence of new inflammatory demyelinating
lesions .

16. PROGNOSIS
Most children withADEM 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 ofADEM in children report little or
no mortality, earlier studies suggested that the mortality of
postinfectiousADEM was as high as 5 %.
The extent and site of lesions on the initial MRI do not predict
the clinical outcome

17. outcome
the following case series illustrate the range of outcomes for children
with ADEM:
The largest study included 84 children fromArgentina 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.

18. outcome
In a report fromAustralia, 31 children withADEM 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.

19. outcome
In a study from the United Kingdom, 28 children withADEM
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.

20. 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
typicalADEM .
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.