Definition
Progressive multifocal leukoencephalopathy is a rare, fatal disease of the white matter of the brain that almost solely strikes individuals who already have weakened immune systems.
Description
In progressive multifocal leukoencephalopathy, myelin (the substance that wraps around nerve fibers, providing insulation and speeding nerve transmission) is progressively destroyed. Although the disease is caused by a very prevalent virus (called JC virus), it only develops in individuals who are immunocompromised (have weakened immune systems).
Multiple areas of the brain are affected by the demyelination associated with progressive multifocal leukoencephalopathy. Additionally, other abnormalities and bizarre cells take up residence within the brain, causing destruction of normal brain tissue and impairing normal function.
Demographics
The causative virus in progressive multifocal leukoencephalopathy, JC virus, is extremely common. It is thought to be present in upwards of 85% of all children before the age of nine, and probably is present in an even greater percentage of adults. However, the JC virus does not actually cause any symptoms or disease, except in individuals who have severely compromised immune systems. About 62.2% of all progressive multifocal leukoencephalopathy cases occur in individuals with lymphatic cancers (lymphoproliferative disease, such as Hodgkin's disease and other lymphomas); 6.5% occur in individuals with cancer of bone marrow cells (myeloproliferative disease or leukemias); 2.2% occur in individuals with carcinomatous disease (cancers that affect the lining of tissues or organs of the body); and 10% occur in individuals with any of a number of acquired immunodeficiency states (such as systemic lupus erthematosus, sarcoidosis, and organ transplant survivors). Among patients with Acquired Immunodeficiency Syndrome (AIDS), about 10% of patients develop progressive multifocal leukoencephalopathy. Only 5.6% of all cases of progressive multifocal leukoencephalopathy occur in individuals with no other underlying source of immunocompromise.
Causes and symptoms
Although much is left to be defined about the mechanism whereby progressive multifocal leukoencephalopathy affects an individual, researchers believe that the JC virus resides in the kidneys of most individuals. In normal, nonimmunocompromised individuals, the virus stays within the kidneys, doing no harm. In immunocompromised individuals, the virus is reactivated, travels through the circulatory system to the brain, and selectively destroys myelinated nerve cells.
Patients with progressive multifocal leukoencephalopathy experience a range of symptoms that grow gradually worse over time, including headache and difficulties with speech, thinking, walking, weakness, vision problems (even blindness), memory problems, confusion, slowness of movement, paralysis of half of the body, and seizures. Eventually, patients lapse into a coma and die, usually within just months of the onset of their initial symptoms.
Diagnosis
Diagnosis is usually suggested by a patient's characteristic symptoms of progressive multifocal leukoencephalopathy, in combination with evidence of white matter destruction visualized on CT or MRI scanning of the brain. Specialized tests on cerebrospinal fluid (called polymerase chain reactions) may demonstrate the presence of JC virus DNA. However, only brain biopsy can result in an absolutely definitive diagnosis.
Treatment team
Patients with progressive multifocal leukoencephalopathy are usually seen by neurologists, as well as by hematologist/oncologists for patients with lymphoma or leukemia, infectious disease specialists for patients with AIDS, and a rheumatologist for individuals with specific autoimmune disease.
Treatment
There are no treatments available to cure progressive multifocal leukoencephalopathy. Some degree of slowing of the relentless progression of the disease has been noted in certain patients treated with the AIDS drug AZT.
Prognosis
Progressive multifocal leukoencephalopathy is uniformly fatal, usually within one to four months of the initial symptoms. A few patients have had brief remissions in the disease progression, and have lived for several years beyond diagnosis.
Resources
BOOKS
Berger, Joseph R., and Avindra Nath. "Progressive Multifocal Leukoencephalopathy." In Cecil Textbook of InternalMedicine, edited by Lee Goldman, et al. Philadelphia: W. B. Saunders Company, 2000.
Roos, Karen L. "Viral Infections." In Textbook of Clinical Neurology, edited by Christopher G. Goetz. Philadelphia: W. B. Saunders Company, 2003.
Tyler, Kenneth L. "Viral Meningitis and Encephalitis." In Harrison's Principles of Internal Medicine, edited by Eugene Braunwald, et al. NY: McGraw-Hill Professional, 2001.
PERIODICALS
Pruitt, A. A. "Nervous System Infections in Patients with Cancer." Neurol Clin 21, no. 1 (February 1, 2003): 193–219
WEBSITES
National Institute of Neurological Disorders and Stroke (NINDS). NINDS Progressive Multifocal Leukoencephalopathy Information Page. May 29, 2002. (June 4, 2004). http://www.ninds.nih.gov/health_and_medical/disorders/pml_doc.htm.
Rosalyn Carson-DeWitt, MD
