Progressive Multifocal Leukoencephalopathy (PML)

Overview

What is progressive multifocal leukoencephalopathy (PML)?

Progressive multifocal leukoencephalopathy (PML) is a rare brain infection. PML causes the cells that produce myelin to break down. Myelin is a substance in the brain that protects nerve cells.

How does progressive multifocal leukoencephalopathy (PML) affect the body?

PML causes brain damage. This damage can lead to mental impairment, visual symptoms and difficulty moving.

Because PML is a progressive disorder, it will get worse over time. Some people can slow the disease’s progression with timely treatment.

Who might get progressive multifocal leukoencephalopathy (PML)?

PML typically only occurs in people who have severely weakened immune systems. You may be at risk of developing PML if you have:

How common is progressive multifocal leukoencephalopathy (PML)?

Progressive multifocal leukoencephalopathy is rare. It affects about 1 in every 200,000 people.

Symptoms and Causes

What causes progressive multifocal leukoencephalopathy (PML)?

PML occurs because of the JC virus (JCV) — named after the initials of the first patient identified with it. Up to 85% of all adults have the JC virus. Experts aren’t certain how people contract JCV. There is evidence that children may pick it up through food or water.

In most people, JCV remains inactive and causes no symptoms. But in people with a weak immune system, the virus may progress into PML.

What are the symptoms of progressive multifocal leukoencephalopathy (PML)?

For most people, PML symptoms start subtly. The symptoms may vary depending on which part of your brain has the infection.

Early symptoms may include:

  • Clumsiness or lack of coordination.
  • Difficulty speaking.
  • Weakness.

As the infection progresses, people may experience:

Some people may experience headaches or epilepsy, although these symptoms are rare. Eventually, PML usually progresses. The condition is often fatal, but the outlook varies according to the underlying condition and response to treatment.

Diagnosis and Tests

How is progressive multifocal leukoencephalopathy (PML) diagnosed?

Your healthcare provider can diagnose PML with tests that evaluate your brain and spinal cord. You may have:

  • MRI to take images of the brain.
  • Spinal tap to sample and evaluate your cerebrospinal fluid (fluid that surrounds tissue in your brain and spinal cord).

Management and Treatment

How is progressive multifocal leukoencephalopathy (PML) treated?

Treatment for PML focuses on strengthening your immune system. For example, if you have AIDS, you may take antiretroviral therapy (drugs to reduce HIV in your body). This treatment can restore some of your immune system’s function.

Other people may benefit from plasma exchange. This treatment involves removing some immunosuppressant drugs from your blood. The treatment may increase your immune system’s function so it can fight the JC virus more effectively. Speak with your healthcare provider about the benefits and risks of plasma exchange.

Prevention

How do I know if I’m at risk for progressive multifocal leukoencephalopathy (PML)?

If you have a condition that weakens your immune system, ask your healthcare provider about your risk for PML.

Do other conditions put me at higher risk of progressive multifocal leukoencephalopathy (PML)?

People who have multiple sclerosis (MS) or Crohn’s disease may also have a blood test to look for conditions like HIV that predispose you to JCV infection. Providers often prescribe the drug natalizumab (Tysabri®) to treat MS or Crohn’s disease. This medication can increase risks for PML.

If you have JCV that is not active or causing symptoms, you may still be able to take natalizumab. But it’s important to talk with your provider about the risks and benefits.

Outlook / Prognosis

What is the outlook for people with progressive multifocal leukoencephalopathy (PML)?

The outlook for people with PML varies depending on the cause and severity of the infection. Some people already have advanced PML by the time they receive diagnosis. In these cases, life expectancy is often around six to 12 months.

What is the outlook for people who undergo plasma exchange?

If PML symptoms began because of an immunosuppressant, your symptoms may improve if you stop the medication. You may also have plasma exchange to remove some immunosuppressant drugs from your body. The goal of plasma exchange is to increase your immune system’s function. For some people, plasma exchange may slow the progression of PML and slightly increase their life expectancy, but the benefits are uncertain.

Even after stopping a medication or having plasma exchange, many people experience lingering PML symptoms. Others may develop neurological disabilities. And there are other risks to stopping a medication. Be sure to make decisions about your medicine with your healthcare provider.

Living With

What else should I ask my doctor?

You may ask your healthcare provider:

  • What is my risk of PML?
  • Can I do anything to minimize my risk?
  • What PML symptoms should I watch for?
  • What are the risks of immunosuppressant medications?
  • Are there other treatments for my condition?
  • What are the risks and benefits of the treatment options?

A note from Cleveland Clinic

Progressive multifocal leukoencephalopathy is a rare brain infection. It occurs when something triggers a common virus, JCV. PML primarily affects people with weakened immune systems. The disease is progressive, meaning it gets worse over time. Timely treatments such as initiating antiretroviral therapy in HIV patients and withdrawing immunosuppressive drugs may slow disease progression.

Last reviewed by a Cleveland Clinic medical professional on 05/26/2021.

References

  • Merck Manuals. Progressive Multifocal Leukoencephalopathy (PML). (https://www.merckmanuals.com/home/brain,-spinal-cord,-and-nerve-disorders/brain-infections/progressive-multifocal-leukoencephalopathy-pml) Accessed 6/29/2021.
  • Nanda T. Progressive Multifocal Leukoencephalopathy in a HIV Negative, Immunocompetent Patient. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978838/#:~:text=Progressive%20multifocal%20leukoencephalopathy%20(PML%29%20is,life%20expectancy%20of%206%20months) Case Report Neurol Med. 2016:7050613. Accessed 6/29/2021.
  • National Institute of Neurological Disorders and Stroke. Progressive Multifocal Leukoencephalopathy Information Page. (https://www.ninds.nih.gov/Disorders/All-Disorders/Progressive-Multifocal-Leukoencephalopathy-Information-Page) Accessed 6/29/2021.
  • National Organization for Rare Disorders. Progressive Multifocal Leukoencephalopathy. (https://rarediseases.org/rare-diseases/progressive-multifocal-leukoencephalopathy/) Accessed 6/29/2021.

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