Progressive Multifocal Leukoencephalopathy

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What is progressive multifocal leukoencephalopathy?

Progressive multifocal leukoencephalopathy (PML) is a disease of the white matter of the brain, caused by a virus infection (polyomavirus JC) that targets cells that make myelin—the material that insulates nerve cells (neurons). Polyomavirus JC (often called JC virus) is carried by a majority of people and is harmless except among those with lowered immune defenses.

PML is rare and occurs in people undergoing chronic corticosteroid or immunosuppressive therapy for organ transplant, or individuals with cancer (such as Hodgkin's disease or lymphoma). Individuals with autoimmune conditions such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus—some of whom are treated with biological therapies that allow JC virus reactivation—are at risk for PML as well. PML is most common among individuals with HIV-1 infection. 

Studies estimate that prior to effective antiretroviral therapy (ART), as many as five percent of people living with HIV-1 eventually develop PML, which is an AIDS-defining illness. However, current HIV therapy using ART—which effectively restores immune system function—allows as many as half of all people with HIV-PML to survive, although they may sometimes have an inflammatory reaction in the regions of the brain affected by PML. 

The symptoms of PML, which vary according to the location and amount of damage in the brain, may evolve over the course of several weeks to months. The most prominent symptoms are:

  • Clumsiness
  • Progressive weakness
  • Visual, speech, and sometimes personality changes

The progression of deficits leads to life-threatening disability and (frequently) death. 

A diagnosis of PML can be made following brain biopsy or by combining observations of a progressive course of the disease, consistent white matter lesions visible on a magnetic resonance imaging (MRI) scan, and the detection of the JC virus in spinal fluid.

Currently, the best available therapy is reversal of the immune-deficient state, since there are no effective drugs that block virus infection without toxicity. Reversal may be achieved by using plasma exchange to accelerate the removal of the therapeutic agents that put people at risk for PML. 

In the case of HIV-associated PML, immediately beginning ART will benefit most individuals. Several new drugs that laboratory tests found effective against infection are being used in people with PML with special permission of the U.S. Food and Drug Administration (FDA).

The outlook for individuals with PML depends on the severity of the underlying disease and treatment received. In general, PML has a mortality rate of 30 to 50 percent in the first few months following diagnosis. Those who survive the disease may be left with severe neurological disabilities.

Learn About Clinical Trials
Clinical trials are studies that allow us to learn more about disorders and improve care. They can help connect patients with new and upcoming treatment options.

How can I or my loved one help improve care for people with progressive multifocal leukoencephalopathy?

Consider participating in a clinical trial so clinicians and scientists can learn more about PML and related disorders. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with PML at

Where can I find more information about progressive multifocal leukoencephalopathy?

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