This paper was prepared by Dr Clive Hawkins Consultant Neurologist / Senior Lecturer
Royal Infirmary, Stoke on Trent
Acute disseminated encephalomyelitis (ADEM) accounts for up to one third of all
known cases of encephalitis. This illness usually follows in the wake of exanthema
or after other viral infections or immunisations. There is usually a latent
period of days to two to three weeks. This illness was first described 250
years ago by the distinguished English physician, Clifton who noted that it occurred
occasionally in patients who had smallpox. The white matter of the brain is
predominantly affected and under the microscope it can be seen that there is invasion
around small veins by white blood cells from the blood. Where these cells
accumulate myelin is destroyed. The illness has been poorly understood and
a variety of terminologies used to describe it, these including post infectious,
parainfectious or post vaccinial.
Clinical Presentation
The clinical presentation of ADEM despite different causes is similar. The
illness usually begins with non specific symptoms such as fever, headache, stiff
neck, vomiting and anorexia. These are rapidly followed by depression of consciousness
in which the patient may become confused, stuporous, delirious and occasionally
entering into coma. During this early period neurological examination usually
shows focal neurological signs such as bilateral optic neuritis, ataxia of the limbs,
clumsiness in walking, paralysis down one side and seizures may occur. The
duration of these symptoms is variable, some cases lasting a few weeks to a month,
and other fatal cases having a rapid progressive course over a number of days.
The clinical sign that correlates most closely with the prognosis is the level of
consciousness. The illness usually has monophasic course i.e. once it is over,
further attacks rarely develop. Recently long term studies of patients with
ADEM have shown that a small number later on develop multiple sclerosis.
Investigations
The cerebrospinal fluid is frequently abnormal showing an increase in white cells
and protein. The electroencephalogram is abnormal in most cases showing diffuse
slowing. Magnetic resonance imaging typically shows multiple areas of abnormality
in the white matter of the brain.
Differential Diagnosis
The differential diagnoses of ADEM include acute meningitis, acute viral encephalitis
and acute multiple sclerosis. Differentiation of these diseases is not easy,
certainly in the early stages. In viral encephalitis the CSF is often abnormal
and a rise in specific viral antibody may occur. To distinguish ADEM from
multiple sclerosis in the initial phases may be more difficult. Magnetic resonance
imaging and CSF examination may help.
Pathology
The brain at post mortem may appear entirely normal or may show the signs of congestion.
Histologically the basic lesions consist of infiltrations of mononuclear cells from
the blood which occur around small veins in the white matter. Demyelination
occurs and is limited to the area of the perivenous cellular cuff. These are
different from the lesions found in multiple sclerosis.
Evidence for an Immunological aetiology
There is general agreement that a causative organism cannot be isolated from the
central nervous system of patients with ADEM. The association of the disease
with an antecedent infection or immunisation suggests an immunological process and
detailed laboratory studies involving measurement of anti-brain antibodies and of
cellular immune responses to specific myelin antigens have shown that these patients
indeed have mounted an allergic response against their own brain constituents.
Treatment
The ideal form of treatment is immunomodulation to be instituted without delay once
the diagnosis is made. High doses of steroids can often lead to a very rapid
resolution of symptoms with an excellent prognosis. Overall the prognosis
is good where the diagnosis is made early and the appropriate therapy instituted
without delay.
Last modified: March 2008