Acute Disseminated Encephalomyelitis
Acute Disseminated Encephalomyelitis
National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Acute Disseminated Encephalomyelitis is not the name you expected.
Acute disseminated encephalomyelitis (ADEM) is a neurological, immune-mediated disorder in which widespread inflammation of the brain and spinal cord damages tissue known as white matter. White matter is tissue composed of nerve fibers, many of which are covered by a collection of fats and proteins known as myelin. Myelin, which collectively may be referred to as the myelin sheath, protects the nerve fibers, acts as an insulator and increases the speed of transmission of nerve signals. Damage to the myelin sheath (demyelination) affects the nerve's ability to transmit information and potentially can cause a wide range of neurological symptoms. The specific symptoms and severity of ADEM can vary from one individual to another. In some cases, ADEM is preceded by a viral infection or vaccination. The exact cause the disorder is unknown although it is believed that an improper response of the immune system plays a role its development. ADEM must be differentiated from other demyelinating disorders such as multiple sclerosis.
A variety of different terms have been used to describe ADEM in the medical literature creating confusion. The International Pediatric MS Study Group proposed three specific terms to describe the disorder. ADEM, which describes individuals who develop the initial illness that characterizes the disorder; recurrent disseminated encephalomyelitis (RDEM); which describes a new occurrence of ADEM, three or more months after the initial occurrence, that has the same clinical presentation and affects the same areas of the central nervous system; and multiphasic disseminated encephalomyelitis (MDEM), which describes one or more relapses of ADEM, at least three months after the initial occurrence and involving new areas of the central nervous system. Some researchers argue that it is unclear whether cases of RDEM or MDEM represent recurrent or multiphasic cases of ADEM or are actually other conditions such as multiple sclerosis. More research is necessary to accurately and definitively define acute disseminated encephalomyelitis.
In some cases, a viral infection precedes the development of symptoms by two days to four weeks. Less often, the disorder may follow a vaccination. However, a preceding event is not always identified and some cases appear to occur spontaneously. Typically, ADEM is considered a monophasic disorder, which is a disorder that has a single occurrence or one phase in a particular individual. However, recurrent or multiphasic forms of ADEM have been described in the medical literature as well but are controversial.
The progression and severity of ADEM varies from one person to another. Some individuals may have mild, self-limited forms of the disorders; others may develop more severe symptoms and, in the most severe cases, life-threatening complications such as respiratory failure may occur.
Initial symptoms usually develop rapidly and may include various symptoms common to many different illnesses (nonspecific symptoms) including fever, headaches, irritability, fatigue, lethargy, a general feeling of ill health (malaise), unintended weight loss and abdominal complaints including nausea and vomiting. In some cases, these symptoms may be followed by mental status changes such as confusion, stupor, delirium and, potentially, coma.
Additional neurological symptoms can develop in some cases. The specific symptoms vary from one person to another based upon the exact locations of the lesions within the central nervous system. It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.
Neurological symptoms that can potentially develop in ADEM include including an inability to coordinate voluntary movements (ataxia), paralysis of one side of the body (hemiplegia), seizures, slurred speech, cranial nerve paralysis (palsy), numbness on one side of the body (hemiparesthesia). Inflammation of the optic nerve (optic neuritis) may develop and can cause vision loss. Disease affecting the nerves outside of the central nervous system (peripheral nervous system disorders) has been reported in adults with ADEM, but appears to be a rare occurrence in children. Peripheral nervous system disorders can cause weakness, pain, numbness or a burning or tingling sensation in the extremities. In some cases, additional symptoms may develop including involuntary movements, amnesia, personality changes and depression.
The symptoms of ADEM may also be affected by age of onset. Seizures are common in children and adults. Long-lasting fevers and headaches are more common in children than adults. Sensory deficits predominately affect adults.
The exact cause of ADEM is not known. However, most clinical investigators agree that the disorder is most likely the result of an abnormal immune system response to an infection or other trigger. Many researchers suggest that ADEM may represent an abnormal immune reaction directed against the body's own tissues (autoimmune disorder). In autoimmune disorders, the body's natural defenses (e.g., antibodies, lymphocytes) against substances that are perceived as foreign (antigens) inappropriately begin to attack healthy tissues, for unknown reasons.
ADEM often develops following an upper respiratory tract infection, usual of viral cause. Specific agents that have been identified as resulting in ADEM include influenza, measles, mumps, rubella, varicella-zoster, Epstein Barr virus, cytomegalovirus, and herpes simplex virus. Some bacterial agents can also bring about ADEM.
Less often, ADEM may develop following a vaccination. Certain antirabies vaccinations have been linked to the development of the disorder. Other vaccinations that are believed to potentially result in the development of ADEM include the smallpox vaccination and certain older measles vaccinations. In rare cases, immunizations against pertussis (whooping cough) and influenza have been linked to ADEM. In extremely rare cases, ADEM has occurred following an organ transplant. The risk of developing ADEM is extremely low and should not preclude routine vaccinations as recommended.
A variety of factors in addition to immunologic ones may play a role in the development of ADEM potentially including genetic and environmental ones. More research is necessary to determine the exact causes and underlying mechanisms that ultimately cause ADEM.
ADEM can develop at any age, but is much more frequent in children than adults. Males and females are affected in equal numbers, although a slight male preponderance was seen in a couple pediatric studies. In children, the mean at presentation is between 5-8 years old. The exact incidence of ADEM in the general population is unknown. One study conducted in San Diego, California estimated the incidence of ADEM in persons under 20 years of age at .4 per 100,000. ADEM seems to peak in the winter and spring months in studies conducted in the United States.
Symptoms of the following disorders can be similar to those of ADEM. Comparisons may be useful for a differential diagnosis.
Multiple sclerosis is a chronic neuroimmunologic (both the nervous system and the immunological system are involved) disorder of the central nervous system involving the brain, spinal chord and optic nerves. By means of a mechanism not clearly understood, the protective fatty, insulating substance called myelin sheath that covers the nerve is destroyed. The inflammatory attacks that produce the characteristic scarring (plaques or patches) of the myelin sheath occur randomly and vary in intensity and are found at multiple sites. The course of the disease may advance, relapse, remit, or stabilize. The randomness of the location of plaques or patches affects the nerve's ability to transmit information (neurotransmission) and causes a wide range of neurological symptoms, which may vary from person to person. Some researchers believe that multiple sclerosis and ADEM are part of a continuum of disease. (For more information on this disorder, choose "multiple sclerosis" as your search term in the Rare Disease Database.)
Neuromyelitis optica, also known as Devic disease (DD), is a chronic disorder of nerve tissue characterized by inflammation of the optic nerve (optic neuritis) and inflammation of the spinal cord (myelitis). There appear to be two forms of this disease. In the classical, but less common type, there is a series of attacks over a short period of time (days or weeks) but, after the initial outburst, there are seldom repeat incidents. The second form is more common and is characterized by repeated attacks separated by periods of remission. In this form, the interval between attacks may be weeks, months or years. Neuromyelitis optica can cause pain and vision loss of the eyes and weakness, numbness, and sometimes paralysis of the arms and legs. Neuromyelitis optica is believed to be an autoimmune disorder. (For more information on this disorder, choose "neuromeylitis optica" as your search term in the Rare Disease Database.)
Transverse myelitis is a neurological disorder of the spine caused by inflammation across the spinal cord. It is sometimes associated with the term myelopathy, which refers to any disorder of the spinal cord. However, transverse myelitis is a more specific term for inflammation (myelitis) across the width of the spinal cord (transverse) that results in changed function below this level while function remains normal above. Symptoms are related to movement and sensory functions. This disorder occurs in both adults and children, and typically begins with a rather rapid development of symptoms over the course of several hours, days, or weeks. Symptoms may include lower back pain, weakness in the legs and arms, sensory disturbance, spasms leading to gradual paralysis, and bowel or bladder dysfunction. In most cases, this is a disorder that occurs on a single occasion, although a small number of individuals may experience recurrence. The initial occurrence may be followed, over a period of several weeks or months, by a period of recovery, although this does not happen in all cases. There is considerable variability in the degree of recovery achieved. Transverse myelitis may occur following viral or bacterial infections, especially those associated with a rash, spinal cord injuries, or immune reactions. (For more information on this disorder, choose "transverse myelitis" as your search term in the Rare Disease Database.)
Acute hemorrhagic leukoencephalitis (AHL) is believed to be a severe, hyperacute form of ADEM. This variant is associated with the rapid onset of fever, headaches, vomiting neck stiffness, seizures and various neurological signs, usually following a viral infection or vaccination. AHL is often associated with rapid deterioration and life-threatening complications such as fluid accumulation within the brain (brain edema) as soon as one week after onset. Despite the severe, rapid course, there have been reports within the medical literature of favorable neurological outcomes in individuals treated promptly and aggressively.
A variety of additional disorders can present with signs and symptoms that are similar to those found in ADEM. Such disorders including other inflammatory, demyelinating disorders of the central nervous system (in addition to multiple sclerosis and neuromyelitis optica) including Behcet's disease and neurosarcoidosis; vascular disorders affecting the central nervous system such as promthrombotic conditions, antiphospholipid antibody syndrome, sickle cell anemia, Susac syndrome and CADASIL; certain malignancies such as central nervous system lymphoma or glioblastoma multiforme; and a variety of toxic, nutritional and metabolic disorders including vitamin B12 deficiency, folate deficiency, mercury poisoning, Marchiafava-Bignami disease, the organic acidurias, and the inherited leukodystrophies. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
A diagnosis of ADEM is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including imaging techniques such as magnetic resonance imaging (MRI). An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues and can demonstrate characteristic brain lesions in individuals with ADEM. Additional tests to exclude other conditions may also be performed. Such tests may include infectious, immunologic, and metabolic tests.
No standard therapy for ADEM has been established. Most therapies that have been used to treat ADEM have some effect of suppressing the activity of the immune system (immunosuppressive therapy). Such therapies include corticosteroids, immunoglobulin (IVIg) therapy, or plasmapheresis.
High dose regimens of corticosteroids have commonly been used to treat individuals with ADEM and generally are considered the mainstay of treatment. Corticosteroids have led to an improvement of symptoms in many cases. Corticosteroids are the most widely reported therapy for individuals with ADEM. Methylprednisone is a specific corticosteroid that is commonly used for ADEM. However, there is great variation in the specific forms, manner of administration, dosage and tapering schedule in treating affected individuals with corticosteroids. In addition, high dose regimens of corticosteroids can be associated with significant side effects in some people.
Intravenous immunoglobuin (IVIg) has been used to treat some individuals with ADEM such as those who do not respond or cannot tolerate corticosteroid therapy. IVIg is a concentrated solution of antibodies that have been extracted from the blood of healthy donors. IVIg is used to treat a variety of autoimmune disorders because it can neutralize the effects of autoantibodies, which are antibodies that mistakenly attack healthy tissue.
Plasmapheresis has been used to treat individuals who do not respond to other forms of therapy. However, its use has only been described in random case reports. Plasmapheresis is a procedure is a method for removing unwanted substances (toxins, metabolic substances and plasma parts) from the blood. Blood is removed from the patient and blood cells are separated from plasma. The patient's plasma is then replaced with other human plasma and the blood is retransfused into the patient.
Controlled, randomized clinical trials evaluating the various therapies for children and adults with ADEM have not been done. These studies are necessary to determine the optimal therapeutic options for treating individuals with ADEM.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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