What is ADEM?
Acute disseminated encephalomyelitis (ADEM) is an inflammatory
disorder very similar to multiple sclerosis (MS). 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
immunizations. There is usually a latent period of days to two to three
weeks. Both ADEM and MS cause deterioration of the myelin sheath
surrounding nerve fibers in the brain and spinal cord. Because ADEM
usually occurs in children it is often confused with pediatric multiple sclerosis. Some researchers think that ADEM is a variant of MS that permanently resolves after one episode of illness.
This illness has been poorly understood and a variety of
terminologies used to describe it, these including post- infectious,
para-infectious or post-vaccinial.
Who is affected?
People of any age can develop ADEM although it is more likely to
occur in children. About 80 percent of all cases occur in children
younger than age 10 years and about 3 percent of all cases are reported
in adults. ADEM is known to occur after viral infections, particularly
measles, and after vaccinations, particularly those for rabies,
pertussis, and influenza. Among adolescents, ADEM is three times more
common than MS. Male children are affected slightly more often than
female children.
What are the Symptoms of ADEM?
The clinical presentation of ADEM despite different causes is
similar. The illness usually begins with non specific symptoms that
occur rapidly such as fever, headache, stiff neck, nausea, vomiting, and
anorexia. These are rapidly followed by gait disturbances, cranial
nerve palsies, irritability, changes in mental status, visual field
deficits, depression of consciousness in which the patient may become
confused, delirious and occasionally enter into a coma. Visual loss can
also occur if inflammation of the optic nerve develops. 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. A
particularly severe form of ADEM which causes hemorrhage is called
acute hemorrhagic leukoencephalopathy (AHLE)
Other Signs of ADEM
Both MS and ADEM cause perivenular-round cell inflammation with patchy demyelination of nerve fibers. The inflammatory exudates in these disorders contain predominantly microglial cells. In both MS and ADEM, there is evidence of T helper cells being sensitized to myelin proteins. Abnormalities in cytokine levels are similar in both disorders. The platelet count may be elevated in children with ADEM.
Prognosis of ADEM
ADEM is characterized by one or sometimes two episodes of symptoms that resolve. Usually, symptoms of ADEM persist for several weeks and then resolve although in about one third of all cases, symptoms can persist for up to one year. MS is characterized by a relapsing remitting condition of multiple disease flares. Children who develop ADEM before age 10 are known to very rarely develop multiple sclerosis in later life. However, there are no tests to tell if someone with ADEM will go on to develop MS.
Diagnosis
It is very important to differentiate encephalitis from other disorders that may cause similar neurological symptoms and which may have very different treatments. Disorders that mimic those of encephalitis include bacterial meningitis, stroke, brain tumors, drug reactions and metabolic disturbances. Symptoms alone often do not allow a doctor to distinguish between the many diseases that can mimic encephalitis and therefore a variety of hospital tests are required.
The following tests which can help confirm the diagnosis and rule out other disorders include:
Brain Scans Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) scans may show the extent of the inflammation in the brain and help differentiate encephalitis from other conditions. Brain scans can exclude stroke, brain tumours and aneurysms. In the early stages brain scans may show nothing abnormal with significant inflammatory changes only occurring later in the illness.
The lesions in ADEM may also show signs of hemorrhage. This does not occur in multiple sclerosis. By correlating the clinical history including previous viral illnesses and recent vaccines along with findings from imaging tests doctors can often differentiate MS from acute disseminated encephalomyelitis. However, the disorders may overlap and imaging tests alone should not be relied on.
Electroencephalogram (EEG), which records brain waves, can detect abnormal patterns of activity. Abnormal patterns found in encephalitis include slowing of brain activity as well as epileptic seizures. An electroencephalogram (EEG) also shows disturbances in the normal sleep rhythms in patients with ADEM. Focal or generalized slowing, the appearance of sharp waves, rhythmic delta, or spikes in the waking state are seen in the early stages of ADEM. The absence of these findings suggests MS.
Lumbar puncture (LP) allows a doctor to sample the cerebrospinal fluid (CSF), that surrounds the brain and spinal cord. CSF is produced within the brain and flows out at the base of the brain to surround and cushion the brain and spinal cord. It contains substances essential for normal activity of the brain but also takes waste products back to blood.
A lumbar puncture involves passing a needle, under local anaesthetic, between two of the back bones at the base of the spine. In an adult, several tablespoons full of fluid can be collected safely. Usually blood tests are taken at the same time as the LP in order to compare blood contents with that in CSF.
Approximately 10% of adult patients suffer from a mild headache after a LP. This headache is typically worsen when in an upright position and is better lying down. It usually improves with simple pain killers and good hydration.
A variety of laboratory tests are performed on CSF. Some tests give results within hours whereas others often take days.
Immediate tests are performed on CSF including an analysis under the microscope to assess the number and type of white blood cells present. A high number of white blood cells in CSF are indicative of inflammation within the brain, spinal cord, or lining of the brain (meninges). The types of white blood cells found help differentiate between viral or bacterial infections.
More complicated tests on CSF include culture for bacteria, antibody studies, or molecular tests to detect the genetic footprint of viruses or bacteria. The latter molecular tests include the polymerase chain reaction (PCR), which when applied to CSF is used most frequently to identify genetic material from herpes simplex virus, varicella zoster virus (chickenpox virus), and enteroviruses. PCR has significantly advanced the ability to diagnose viral encephalitis.
LP may have to be repeated during an individual’s illness.
Laboratory screening of blood, urine, as well as other body fluids can help detect and identify brain and/or spinal cord infection. Results from these tests can help exclude other diseases that mimic encephalitis.
The cause of the infection cannot always be determined. Research suggests that despite extensive testing, the infectious causes of encephalitis cannot be determinedin approximately 60% of cases.
For some individuals, their diagnosis of encephalitis will be diagnosis of exclusion based upon other diseases having been dismissed on the basis of laboratory tests. In most cases the type, either infectious or autoimmune/post-infectious will have been determined.
What causes ADEM?
ADEM usually follows an infection of some kind. In 50 percent to 75 percent of cases the beginning of the disease is preceded by a viral or bacterial infection, usually a sore throat or cough. Many different bacteria, viruses and other infections have been related to ADEM, but the disease does not appear to be caused by any particular infectious agent. Most cases of ADEM begin anywhere from seven to 14 days after the infection.
In some cases, ADEM occurs after a vaccination. This is rare overall, but when it happens, it usually occurs after the measles, mumps, and rubella vaccination. ADEM may occur up to three months after the vaccination.
ADEM appears to be an immune reaction to an infection. In this reaction, the immune system causes inflammation in the central nervous system instead of attacking the infection. The inflammation is the body’s protective attempt to remove the infection and initiate the healing process and in the case of ADEM, this immune response is also responsible for demyelination.
Treatment
The ideal form of treatment is immunomodulation to be instituted without delay once the diagnosis is made. High doses of corticosteroids can often lead to a very rapid resolution of symptoms with an excellent prognosis. Anticonvulsants are used in patients who present with seizures. If corticosteroids are stopped too soon, a relapse or second bout of ADEM can occur.
Overall the prognosis is good where the diagnosis is made early and the appropriate therapy instituted without delay.