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       #Post#: 1068--------------------------------------------------
       PML w/Tysabri despite recent negative JCV test result
       By: agate Date: January 14, 2016, 6:36 pm
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       From Medscape Medical News, January 14, 2016:
       [quote]PML With Natalizumab Despite Recent Negative JCV Test
       Result
       Sue Hughes
       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 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[/quote]
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