Progressive Multifocal Leukoencephalopathy (PML)

What is progressive multifocal leukoencephalopathy?

Progressive multifocal leukoencephalopathy (PML) is an infection that affects the brain when the immune system is weak. PML is caused by infection with the JC virus (JCV). The virus damages cells that produce myelin, the protective covering around nerve fibers in the brain.

Even though most healthy people are infected with JCV, very few develop PML because the condition almost always happens in people with a weakened immune system. Examples of conditions that can weaken the immune system are AIDS (acquired immunodeficiency syndrome) and certain blood cancers like lymphoma or chronic lymphocytic leukemia. Some medicines used to treat autoimmune disease can also lower the ability to fight infections and increase the risk for PML.          

Symptoms of PML

PML is very rare, but it’s serious and life-threatening. It can cause these symptoms, which get worse over weeks to months:     

• Changes in thinking or memory
• Clumsiness
• Weakness 
• Changes in vision
• Trouble speaking or swallowing

Who is more likely to get progressive multifocal leukoencephalopathy?

 People may be at risk of PML if they: 

• Have an HIV (human immunodeficiency virus) infection or AIDS
• Have a blood cancer such as lymphoma or chronic lymphocytic leukemia 
• Were born with a condition that weakens the immune system (genetic immune deficiency)
• Have had an organ transplant
• Take medicines that weaken the immune system, such as some used to treat multiple sclerosis (MS), rheumatoid arthritis, or other autoimmune diseases

How is progressive multifocal leukoencephalopathy diagnosed and treated?

Diagnosing PML

A doctor may test for PML if a person with a weakened immune system has neurological symptoms that are getting worse . They may use an MRI (magnetic resonance imaging) scan of the brain and test spinal fluid for JCV. Sometimes doctors need to remove a small sample of brain tissue (brain biopsy) to make the diagnosis. 

Learn more about neurological diagnostic tests and procedures.

Treating PML

There is no cure for PML. Treatment aims to help a person’s immune system get stronger so it can fight the JCV infection. For people with HIV, this means starting HIV medicines (antiretroviral therapy). For people taking medicines that weaken the immune system, doctors may stop those medicines. As the immune system starts to strengthen, symptoms can sometimes get worse because of a serious reaction called IRIS (immune reconstitution inflammatory syndrome). This can happen when the body responds too strongly and leads to inflammation in the brain. Doctors may treat IRIS with steroids if needed.

What are the latest updates on progressive multifocal leukoencephalopathy?

The National Institutes of Health (NIH), which includes NINDS, is the leading federal funder of research on the brain and nervous system, including disorders such as PML. NIH supports new research to better understand, diagnose, and treat PML.      

Several NIH-funded research projects are studying how JCV causes PML. Researchers are learning  how healthy cells block JCV and how it gets into the brain and causes disease. Other researchers are studying the disease in mice to better understand how PML develops in humans.

NIH-funded scientists are also working to improve how doctors diagnose PML. Some are developing better ways to detect JCV in patient samples. Others are using information from exams and lab tests to make diagnosis faster and more accurate.

NIH-funded researchers are also looking for new treatments for PML. Some are studying an experimental treatment called virus-specific T-cell (VST) therapy, which uses human immune cells called T-cells from healthy donors to target JCV and fight the infection. Early studies have shown encouraging results, but VST therapy is still experimental and is available only at a limited number of centers worldwide. Researchers have also studied medicines called checkpoint inhibitors, which remove some of the brakes on the immune system so it can better fight the virus.

NIH-funded clinical studies are monitoring people with PML over time to learn how the disease changes and affects them. Scientists are also using brain scans to detect and measure PML changes or response to treatment. Brain scans can also help doctors look for complications such as IRIS.

For more information on research about PML, check NIH RePORTER, a searchable database of current and past research projects funded by NIH and other federal agencies. RePORTER also has links to publications and resources from these projects. 

For research articles and summaries on PML, search PubMed, which contains citations from medical journals and other sites.

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 with human study participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

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

The NINDS PML Clinic at the NIH Clinical Center offers full evaluations, including exams, lab tests, and brain imaging, as part of ongoing research and treatment trials for PML. Visit the NINDS Clinics and Patient Research page to contact a coordinator and find out if you qualify.

For information about participating in clinical research, visit the NINDS Clinical Trials site and NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with PML at ClinicalTrials.gov, a searchable database of current and past clinical studies and research results.

Learn about related topics

• Neurological Complications of HIV
• Multiple Sclerosis (MS)