Research: Spotting PML

R
Blair et al. Natalizumab-associated PML identified in the presymptomatic phase using MRI surveillance.Neurology. 2012 Feb [Epub]

Natalizumab, a humanized monoclonal antibody that binds to the cellular adhesion molecule α4-integrin, prevents leukocytes from crossing the blood-brain barrier. It is effective in multiple sclerosis (MS), but its use is limited by the potential risk of progressive multifocal leukoencephalopathy.



This person had MS for a few years and after 24 months of tysabri on a brain scan, there were abnormalities suggestive of PML (where infection with JC virus leads to brain damage because the immune system in not present because of tysabri treatment), but the person was asymptomatic. They rapidly had there plasma replaced to get rid of the tysabri, but after about two months the person got IRIS (and Immune reconstitution symdrome that occurs because there is JC virus in the brain and once tysabri wears off, then white blood cells reenter the brain and then destroy virally-infected cells. The person got steroids and the symptoms stabilized for a significant period of time. This suggests that with some surveliance it may be possible to catch PML before it becomes a clinical reality, which carriers a 20% of fatality. With the apparent risk of PML after 24 months of treatment, if you are JC virus positive and have had previous immunosuppression, one route is to have “drug holiday” but you need to discuss this with your neuro.

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11 comments

  • This person was lucky to have the MRI scan at the right moment to catch PML. It isnt possible to get scanned often enough to ensure this always happens. A JC- status can change to JC+ at any time.

    What do you recommend for MRI freauency and repeating the JC antibody test?

  • Even though the patient had PML, she/he was asymptomatic. Symptoms appeared once the immune system was allowed to do its job. That is, the symptoms were a manifestation of the immune response, not the damage done by the JC virus.

    Here, we do not consider the immune reaction abnormal. But in MS relapses, we do. What makes the difference?

  • Re: "What do you recommend for MRI freauency and repeating the JC antibody test?"

    Annually; the main reason is to re-baseline MS'ers on Natalizumab. Once you go onto Natalizumab MS lesions may shrink and even disappear.

    You can also have early PML without obvious MRI changes. One of the early cases reported from Sweden with PML had an initial MRI that showed no new lesions.

    You are correct frequent MRI is not the way to monitor for PML.

  • Re: "Here, we do not consider the immune reaction abnormal. But in MS relapses, we do. What makes the difference?"

    Not necessarily true. The immune response in MS could be an immune response to a causative virus! In fact I think this is the most likely explanation for focal inflammatory events. The real question is why do these reduce with time?

  • Re "The immune response in MS could be an immune response to a causative virus!"

    If this is true then we should support the immune system and not suppress it, right?

  • Re: "If this is true then we should support the immune system and not suppress it, right?"

    Only if we have a treatment to address the virus. An analogy is hepatitis B; the immune response to the virus causes most of the damage (chronic active hepatitis), but if you suppress the inflammation and leave the virus unchecked it still causes damage (chronic persistent hepatitis).

    Please note this is a hypothesis, we have not yet found a virus in the MS lesion. So all this discussion may be irrelevant.

    At least IFN-beta is an anti-viral, a lot of us believe it is working as an antiviral. What we need is evidence to back-up this belief. Dr M's paper on EBV in the brain is some of evidence underpinning this hypothesis. Which is why we have to keep her in our group to take this work forward.

  • Even though the patient had PML, she/he was asymptomatic. Symptoms appeared once the immune system was allowed to do its job.

    The person was asymptomatic because they had a low viral load,if the viral load had increased then it would have caused symptomatic problems

    By the time IRIS developed there was a detectable viral load in the cerebrospinal fluid, it was not detectable at the time of detection of the MRI lesions.

  • Shouldn't JCV antibody status be checked more often than once a year? Monthly may too much but why not every quarter?

  • Re: "Shouldn't JCV antibody status be checked more often than once a year? Monthly may too much but why not every quarter?"

    The sero-conversion rate from negative to positive is 0.5%; i.e. 1 in 200. The risk of PML in the first 12 months of treatment and hence in the first 12 months after sero-conversion will be very low. Hence the 12 months. Why consume resource if you don't have to? We are constantly being reminded of the need to be practice efficient, i.e. cost-efficient, healthcare. So let's start with saving on unnecessary JCV testing.

    • Hi, I could do with some advice please, my mum has got pml and I wonderd if a treatment would be possible

    • Dear Jamie
      I am very sorry to hear this. As far as I know there are no treatments for the JC virus. One this is to try and get rid of the tysabri, if this is what has caused the problems. But we can't really offer any advice on the blog about specifics, and without knowing the full history this would be ill advised.

      However,maybe ProfG will tell us what he plans in this scenario. I am sure that he has thought about this a lot.

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