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Multiple Sclerosis 101: Understanding PML and the JC Virus

PML and the JC virus have been in the headlines a lot lately following the death of a person taking Tecfidera. Today I want to focus on PML, the JC virus, and how it effects those of us with MS. This is obviously one of the scariest medication side effects for us, and it is very important to know the what it is, it’s risk factors, and how it is detected.

PML stands for progressive multifocal leukoencephalopathy- ok lets just stop right there and breakdown that mouthful…

Progressive- steadily getting worse

Multifocal- in many areas

Leuko- white (in this case referring to white matter in the brain)

Encephalopathy- disorder or disease of the brain

So before even reading anything else you already know that this is a disease that afflicts multiple areas of white matter in the brain, and that it gets worse over time. But what causes it?

PML is in a category called “opportunistic infections”. These are infections that generally pose no threat to a person with a normal immune system, but love to rear their ugly heads in people with weakened immune systems. They are most frequently seen in chemotherapy patients or people with HIV because they are severely immunocompromised. Although it is much rarer, they can also occur in people with MS who are on drugs that weaken their immune systems. You may already know that Tysabri poses the greatest risk for developing PML. However, PML developed in one person taking Gilenya, and one person taking Tecfidera recently died of complications from a PML infection.

The JC virus (John Cunningham virus) is the infection that leads to PML. This virus behaves much like other common viral infections such as herpes and the chicken pox. When you get the chicken pox the virus never leaves your body, and later in life it may flare up again and cause a condition called shingles. Similarly, people who have been infected with herpes always have the virus lurking in their nervous systems. During times of stress it will become active and an outbreak of sores will occur, but unless an active outbreak is occurring there are no outward signs of the virus. The JC virus is fairly common, and is passed easily from person to person. However, since it’s an opportunistic infection healthy people never have any complications from it. When you introduce medications that weaken the immune system, like Tysabri does, your body no longer fights off viruses the way it used to. This gives the dormant JC virus the chance to become active. Once it is active there is a chance that it can cross through the blood-brain-barrier and cause PML. This causes severe damage to the white matter of the brain, and can even lead to death.

All of that information is fairly terrifying right? Well, here’s some good news! We can easily test to see if you have been exposed to the JC virus, which tells us if you are at risk for developing PML. A blood test called the JCV Antibody ELISA test is routinely done on anyone thinking about going on Tysabri. If you test negative, meaning you don’t carry the JC virus, we continue to test for it every 6 months while you are taking Tysabri because you can be exposed to the virus at any time. If you do test positive we also get an index value, which gives us even more information about how likely you are to get PML. A low index value indicates a very low risk, and a higher number indicates a greater risk. All that being said, PML is by no means a common side effect. However, when it does happen it is very serious, so we as providers aren’t willing to take any chances! During the first year of taking Tysabri your risk is very low, but it increases after two years. Additionally, being treated with immunosuppressants in the past puts you at a higher risk for developing PML. We look at all of these risk factors, and use that information to decide whether Tysabri is safe for you or not. The benefit of Tysabri is that it lowers relapse rates by 81%, and disability progression by 64% so we have to weigh its effectiveness against the relative risk of contracting PML, which I’ve summarized for you below:


Because PML attack the myelin, just like MS does, the symptoms should sound familiar. They include confusion, difficulty talking, weakness, memory loss, and loss of balance and coordination. If PML is suspected a MRI of the brain will be done, and a lumbar puncture can confirm the diagnosis. PML is treated in the hospital, and the goal of therapy is to remove all traces of the virus from your body.1-6

Picking medications is a very personal decision, and should be discusses in detail with your neurologist. It is imperative to weigh the risks versus benefits very carefully, and to understand the medications and their side effects. Being well informed is the first step to being your own best advocate!

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

  1. Consortium of Multiple Sclerosis Centers. Anti-JCV Antibody Index may further define PML. 2013.
  2. MSAA 2014 Tysabri Research Update.
  4. FDA Drug Safety Communication: FDA investigating rare brain infection in patient taking Gilenya (fingolimod).
  6. National Institutes of Health. NINDS Progressive Multifocal Leukoencephalopathy Information Page.
  7. Understanding PML, JCV, and the potential risks. Tysabri web page.
  8. Hutchinson, M., et. al. (2009). The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. Journal of Neurology, 256(3), 405-415.


  • Eduran
    1 year ago

    My sister recently died of PML and her main diagnosis was Lupus. Anyone know of any “like” medications patients with Lupus and MS take that might have caused it?

  • LoriJones
    8 months ago


    I am so sorry for the loss of your sister. I do hope that you have found some of the answers that you are looking for. Wish I could help. Lori

  • dudeman1961
    2 years ago

    Excellent primer.

  • @masbrautigam
    5 years ago

    Thanks for this article.I never understood it very well but your explanation mad it understandable,thanks

  • Adriann
    5 years ago

    I am so happy to have found this article while seeking out “New” Terminology .. I have been Dx’d now for 14 yrs. and these last two years seems I have been getting more relapses and odd things happening to my system more frequently ..

    Where I live in Florida , of course, there is no significant help as I am on Medicare/Medicaid and the MS Facilities are all hundreds of miles away ..

    I do have a question if it is not too late .. I have had most recently a case of what appeared to be Bell’s Palsy and had to go to the ER and followed up with my Neuro and an ENT ..

    No help they said even though my ear was stuffed up and had pain , still does .. My Vertigo got worse as well .. No Scans were done at this time .. Now I have a strange skin issue on the palms of my hands ..

    It broke out and turned into postules that I tries Hydrocortisone 2% which calmed them down , and a Pharmicist recommended trying my Foot Spray with micondrisol on my hands and that seemed to just turn the
    blisters red ..

    They are not going away .. It is frustrating as I am hounded by one issue each month after month and curious as to whether this could be the beginning of either of these Viruses .. I do not use any of the new Drugs on the market nor old ..

  • Lisa Emrich moderator
    5 years ago

    Excellent post, Stephanie. Thank you for breaking this down and helping us understand more clearly what the facts are surrounding PML and the JC Virus.

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