Acute Disseminated Encephalomyelitis (ADEM) Causes, Symptoms, Diagnosis, Treatment

Acute Disseminated Encephalomyelitis (ADEM) Causes, Symptoms, Diagnosis, Treatment

What is Acute Disseminated Encephalomyelitis (ADEM)?

Acute disseminated encephalomyelitis (ADEM) is characterized by a brief but widespread attack of inflammation in the brain and spinal cord that damages myelin – the protective covering of nerve fibers.  ADEM often follows viral or bacterial infections, or less often, vaccination for measles, mumps, or rubella

The symptoms of ADEM appear rapidly, beginning with encephalitis-like symptoms such as fever, fatigue, headache, nausea and vomiting, and in the most severe cases, seizures and coma.  ADEM typically damages white matter (brain tissue that takes its name from the white color of myelin), leading to neurological symptoms such as visual loss (due to inflammation of the optic nerve) in one or both eyes, weakness even to the point of paralysis, and difficulty coordinating voluntary muscle movements (such as those used in walking).  ADEM is sometimes misdiagnosed as a severe first attack of multiple sclerosis (MS), since the symptoms and the appearance of the white matter injury on brain imaging may be similar.  

However, ADEM has several features which differentiate it from MS.  First, unlike MS patients, persons with ADEM will have rapid onset of fever, a history of recent infection or immunization, and some degree of impairment of consciousness, perhaps even coma; these features are not typically seen in MS. 

Children are more likely than adults to have ADEM, whereas MS is a rare diagnosis in children.  In addition, ADEM usually consists of a single episode or attack of widespread myelin damage, while MS features many attacks over the course of time. Doctors will often use imaging techniques, such as MRI (magnetic resonance imaging), to search for old and new lesions (areas of damage) on the brain.  The presence of older brain lesions on MRI suggest that the condition may be MS rather than ADEM, since MS can cause brain lesions before symptoms become obvious.  In rare situations, a brain biopsy may be necessary to differentiate between ADEM and some other diseases that involve inflammation and damage to myelin.

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What are the causes and/or risk factors associated with Acute Disseminated Encephalomyelitis (ADEM)?

We know that 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 (upper respiratory tract infection). Many different bacteria, viruses and other infections have been related to ADEM, but the disease does not appear to be caused by any one infectious agent. Most cases of ADEM begin about seven to 14 days after the infection.

On occasion, ADEM occurs after a vaccination. This is rare overall, but when it happens, it usually occurs after the measles, mumps, and rubella vaccination. In these cases, ADEM may occur up to three months after the vaccination.

ADEM appears to be an immune reaction to the infection. In this reaction, the immune system, instead of fighting off the infection, causes inflammation in the central nervous system. Inflammation is defined as the body’s complex biological response to harmful stimuli, such as infectious agents, damaged cells, or irritants. Inflammation is a protective attempt to remove the injurious stimuli and initiate the healing process. In the case of ADEM, the immune response is also responsible for demyelination, a process in which the myelin that covers many nerve fibers is stripped off.

What are the symptoms of Acute Disseminated Encephalomyelitis (ADEM)?

More than half of patients have an illness, usually an infection, two to four weeks before developing ADEM. Most of these illnesses are viral or bacterial, often no more than an upper respiratory tract infection. In children with ADEM, prolonged and severe headaches occur. In addition, the patient develops fevers during the ADEM course.

Along with this pattern, the patients usually get neurological symptoms which may include:

  • confusion, drowsiness, and even coma
  • unsteadiness and falling
  • visual blurring or double vision (occasionally)
  • trouble swallowing
  • weakness of the arms or legs
In adults with ADEM, motor (movement) and sensory (tingling, numbness) symptoms tend to be more common. Overall, what triggers a diagnosis of ADEM is a rapidly developing illness with neurological symptoms, often with fever and headache, usually following an upper respiratory tract infection, and which has significant MRI and spinal fluid findings consistent with ADEM.

Diagnosis for Acute Disseminated Encephalomyelitis (ADEM)

An accurate and early diagnosis of acute disseminated encephalomyelitis, or ADEM, is critical in the management of your child's disease and quality of life.

In making a diagnosis, your child's doctor will first conduct a thorough physical examination, asking about symptoms your child is experiencing, including when they started and how they've eased or progressed over time. Your child's doctor also will record a full medical history, including information about your immediate and extended family.

Next, a series of tests will be conducted, including magnetic resonance imaging (MRI) of the brain and spinal cord to look for lesions, or areas of damage that may indicate ADEM and rule out other disorders such as multiple sclerosis. An MRI scan is a non-invasive procedure that uses powerful magnets to construct clear, detailed pictures of the brain and spinal cord tissues.

Recent brain lesions are more typical in ADEM, but can also occur in multiple sclerosis.

Old "inactive" lesions usually indicate multiple sclerosis, which often causes brain lesions before symptoms become obvious.

Your child also may have a lumbar puncture or spinal tap to determine if there are abnormalities in the cerebrospinal fluid or CSF.

CSF is the fluid that bathes, cushions and protects the brain and spinal cord. It flows through the skull and spine in the subarachnoid space, which is the area inside the arachnoid membrane. Typically, in ADEM, a child's CSF contains elevated levels of white blood cells and protein.

A diagnosis of ADEM is based on an evaluation of your child's symptoms along with the physical exam and test results.

How is Acute Disseminated Encephalomyelitis (ADEM) treated?

ADEM is a rare disease, and so there are no well-designed clinical trials comparing one treatment with placebo, or one treatment with another. Everything we know about treatment in ADEM comes from small published series of cases, and there are no guidelines for treatment of ADEM yet.

At this time, intravenous methyl-prednisolone (for instance, Solu-Medrol®) or other steroid medications are the front-line treatment for ADEM. Usually these medications are given over a five- to seven-day course, followed by a tapering dose of oral steroids. The aim is to reduce inflammation and speed recovery from the disease.

Patients on steroids need to be monitored for increased blood glucose, low potassium, and sleep disturbance. There may be mood changes (irritability, crying, anxiety) when people are on steroid therapy. Other short-term complications of steroid therapy include weight gain, flushed cheeks, facial swelling, and a metallic taste (when using IV Solu-Medrol).

If a patient does not respond to IV methylprednisolone, the next line treatment may be intravenous immune globulin (IVIG). This is an intravenous treatment using a blood product which has been shown to reduce the activity in certain immune diseases, including ADEM. Treatment is usually given for a few hours daily over five days for ADEM. IVIG has the same risks as any blood product (allergic reaction, infection); it also sometimes causes shortness of breath due to fluid overload. Rarely, patients lack an antibody important to the system and may react more strongly to IVIG.

Another approach to treatment is a process called plasmapheresis. This is a treatment in which the blood is circulated through a machine that withdraws components of the immune system from the circulation, reducing immune activity. It is usually a process which takes a few hours and is done every other day for 10 to 14 days, often as part of a hospital stay. It may require the placement of a central venous catheter to allow for blood to be removed from the system rapidly. Risks of plasmapheresis include discomfort from taking blood, sometimes a tendency to bleed due to a reduction in platelets, and infections.

In very severe cases, chemotherapy may be necessary. Either cyclophosphamide or mitoxantrone can be used, but only if less toxic therapies are not effective.

What is the prognosis?

Corticosteroid therapy typically helps hasten recovery from most ADEM symptoms.  The long-term prognosis for individuals with ADEM is generally favorable.  For most individuals, recovery begins within days, and within six months the majority of ADEM patients will have total or near total recoveries.  Others may have mild to moderate lifelong impairment ranging from cognitive difficulties, weakness,  loss of vision, or numbness.  Severe cases of ADEM can be fatal but this is a very rare occurrence.  ADEM can recur, usually within months of the initial diagnosis, and is treated by restarting corticosteroids.  A small fraction of individuals who are initially diagnosed as having ADEM can go on to develop MS, but there is currently no method or known risk factors to predict whom those individuals will be.