PML With Natalizumab Despite Recent JCV- Test

[Marco]

A case of progressive multifocal leukoencephalopathy (PML) associated with natalizumab (Tysabri, Biogen) therapy has been reported in a patient with multiple sclerosis (MS) who had tested negative for JC virus (JCV) antibodies just 2 weeks before symptoms developed.


Commenting on the case for Medscape Medical News, Jeffrey Cohen, MD, Cleveland Clinic, Ohio, said this case illustrates two important points. "First, although negative JCV serology is reassuring and lessens the risk of PML, there is a low but finite false-negative rate," he said. "Second, any new MRI lesion or apparent relapse in a patient on Tysabri is suspicious, particularly with prolonged treatment."


Please continue to get monitored and talk to your neurologist about your current risk(s) factor(s).



http://www.medscape.com/viewarticle/857293


**Link requires a membership to Medscape to view**

[Seasha]

Marco, because this leads to a login page, perhaps you could copy and paste the article and post again. I'm sure many would want to read this.

Thanks!

[Marco]

Marco, because this leads to a login page, perhaps you could copy and paste the article and post again. I'm sure many would want to read this.

Thanks!

Sure! It was my understanding we were not supposed to post entire article, but I would be happy to oblige.

[Marco]

A case of progressive multifocal leukoencephalopathy (PML) associated with natalizumab (Tysabri, Biogen) therapy has been reported in a patient with multiple sclerosis (MS) who had tested negative for JC virus (JCV) antibodies just 2 weeks before symptoms developed.

The case, published online (http://www.neurology.org/content/ear...00002330.short) in Neurology on January 6, was reported by Marie-Sarah Gagne Brosseau, MD, and colleagues from University of Washington, Seattle.

Because the first sign of PML was seen in MRI findings, the authors emphasize the value of surveillance MRIs in patients receiving natalizumab.

"This case exemplifies the risk of delay in PML diagnosis for initial misdiagnosis of MS exacerbation, reiterating that a natalizumab-treated patient with any new MRI lesion or neurologic symptoms could have PML, independent of JCV antibody status," they conclude. "Short-term clinical and MRI reassessment, repeat anti-JCV antibody testing, and CSF [cerebrospinal fluid] testing may be warranted, depending on the level of clinical suspicion."

Commenting on the case for Medscape Medical News, Jeffrey Cohen, MD, Cleveland Clinic, Ohio, said this case illustrates two important points.

"First, although negative JCV serology is reassuring and lessens the risk of PML, there is a low but finite false-negative rate," he said. "Second, any new MRI lesion or apparent relapse in a patient on Tysabri is suspicious, particularly with prolonged treatment."

The authors note that as of March 2015, Biogen had reported 541 cases of natalizumab-related PML. Of 278 cases with available data, only 2 were negative for anti-JCV antibodies and these patients had tests dating from 8 and 9 months before diagnosis.

"The notable finding in this patient is the 2-week timespan between the most recent negative anti-JCV antibody test result and the onset of PML symptoms," they write.

The patient in this case, a 70-year-old woman with MS, had been taking natalizumab since January 2010, had never received immunosuppressants, and had had several negative JCV antibody test results, the most recent of which was just 2 weeks before the onset of PML symptoms.

The patient was discovered to have new right-hand weakness at an urgent follow-up visit prompted by a routine annual brain MRI in June 2014, which showed two new nonenhancing lesions in the subcortical left precentral gyrus and the left insula. The radiologist thought these represented MS progression.

After two short courses of intravenous methylprednisolone failed to improve the symptoms of weakness in the hand, which had by this time spread to involve the arm, repeat MRI in August 2014 raised concern for PML. The left precentral and insular nonenhancing lesions had progressed, with increasing U-fiber involvement. At this time, natalizumab was stopped and the result of a CSF JCV polymerase chain reaction test proved positive. The result of an anti-JCV antibody test was also now positive.

The researchers note that patients with negative JCV antibody results are still at risk for PML because of the potential for de novo infection as well as the possibility of false-negative test results, which may be as high as 3%.

They say that they cannot exclude de novo infection with seroconversion in this case, although a latent infection with too-low peripheral viral activity to reach threshold is more likely, considering the low viral load in the patient's CSF.

No targeted funding for was reported. Dr Gagne Brosseau has disclosed no relevant financial relationships. Disclosures for coauthors appear in the paper. Neurology. Published online January 6, 2016. Excerpt

[Seasha]

Sure! It was my understanding we were not supposed to post entire article, but I would be happy to oblige.

Hi Marco! It's perfectly OK to post articles as long as they are related in some way to MS and there are credible references (ie. URL addresses) to back them up. Sometimes, if the article is too lengthy, it may be best to insert a paragraph or two and back them up with a URL. In your original post, the direct link was removed b/c it led to a login page instead of the actual article.

We always look forward to reading the articles you post, Marco. They keep us all well informed and up to date. Keep them coming!

[LL60]

Thank you so much for the post. I have printed it out.

A hard to choice for people to make on what treatment to follow. I certainly hope this women recovers. The new numbers are out and the death rate still stands at 23% and I just wonder why there continues to be no treatment once PML is found. Maybe the disability numbers are going down. Who knows. They make it so hard to find information. So we all do rely on sharing. It is so important.

I feel like I have found a cure, for me it has just been so dramatic. But, I would never encourage anyone one way or the other, although at times in posts it may seen I am yelling it's virtues. It works. No side effects. It's easy. Way expensive, but the last two years I have had help with that. I have had 6 1/2 years of my life back. I would never regret my decision.

But......how sad when someone is trying to make an informed medical decision for themselves and they end up losing their life.......or worse.

[jreagan70]

I just wonder why there continues to be no treatment once PML is found.

There is treatment for Tysabri patients after PML is found (presuming their doctors know what to do and act quickly enough). Patients undergo a series of plasma exchange, followed by IV steroids if they develop immune reconstitution inflammatory syndrome (IRIS). Treatment, though, doesn't necessarily mean recovery, and IRIS can cause its own serious damage.

I haven't looked into what's being done for patients with other diseases, who are taking other medications, who develop PML.

[Myoak]

There have been 3 cases of PML reported in those who were negative for anti-JCV antibodies (above article). Two of those tested negative 8 and 9 months before diagnosis. Obviously, they converted from – to + at some point. The third tested negative only two weeks before diagnosis; that was unique, reported only once, thankfully.

On PML risk charts widely available, the risk of PML being tested as JCV negative is always listed as 1 in 10,000. However, we have 3 (above) reported cases in 142,000 (as of August 31, 2015) who have taken Tysabri. The risk of PML if you test anti-JCV antibody negative appears to be less than 1 in 10,000.

Also, it is worth keeping in mind that even if you are JCV positive, the JC virus must mutate into a neurotropic form to develop PML.

“Most slow, or delayed, viral infections of the brain that result from being infected by common viruses are caused by mutant strains of the virus. For, example subacute sclerosing panencephalitis (SSPE) is due to a mutant measles virus. Similarly, a mutant strain of the John Cunningham Virus (JCV) causes progressive multifocal leukoencephalopathy (PML).”

That quote is from a post on a research website which can be found by Googling, “EBV and MS disease clusters” look for CrowdSpeak and ResearchSpeak: EBV and disease clusters.