Mark Gudesblatt, MD

was employed, the patient developed PMLseveral months after natalizumab discontinuationand, on biopsy, had substantial inflammatorychanges in the brain, suggesting thatPML-IRIS can occur even when therapy withplasma exchange is not instituted.In a more recent series of natalizumabassociatedPML, Vermersch and colleagues 11reported an identical survival rate (71%) tothat found in the analysis by Clifford et al. 10Of the 35 cases analyzed, nonfatal cases (n =25) were younger, had less disability prior toPML and more localized PML on MRI, andwere diagnosed more quickly following onsetof PML symptoms than the fatal cases. WidespreadPML was detected on MRI in 7 of the10 fatal cases, and survival rates varied widelyby geographic region: 22 of the 24 patients(94%) seen in Europe survived, versus only 3of 11 (27%) in the United States. Natalizumabwas discontinued in all cases, and plasma exchangeor immunoabsorption was given tomost patients to achieve rapid clearance ofthe monoclonal antibody. Most of the patients(91%) experienced IRIS, which was usuallytreated with high-dose corticosteroids. Notingthat natalizumab-associated PML has a bettersurvival rate than the disease has in other patientpopulations, the investigators concludedthat earlier diagnosis and aggressive managementof both PML and PML-IRIS may improveoutcomes significantly.In essence, while the incidence of HIV/AIDS-associated PML has declined and survivalhas improved significantly after introductionof cART, immune-modulating monoclonalantibody–associated PML has emergedas a new threat in recent years. However,prompt diagnosis and appropriate managementhave dramatically improved patientsurvival. In the future, deliberate attempts topromptly identify individuals at risk of developingPML after monoclonal antibody treatmentis warranted. References1. 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JC virus persistence followingprogressive multifocal leukoencephalopathyin multiple sclerosis patientstreated with natalizumab. Ann Neurol.2010;68(3):384-391.8. Tan CS, Koralnik IJ. Progressive multifocalleukoencephalopathy and otherdisorders caused by JC virus: clinical featuresand pathogenesis. Lancet Neurol.2010;9(4):425-437.9. Lima MA, Bernal-Cano F, Clifford DB, et al.Clinical outcome of long-term survivorsof progressive multifocal leukoencephalopathy.J Neurol Neurosurg Psychiatry.2010;81(11):1288-1291.10. Clifford DB, De Luca A, Simpson DM, et al.Natalizumab-associated progressive multifocalleukoencephalopathy in patientswith multiple sclerosis: lessons from 28cases. Lancet Neurol. 2010;9(4):438-446.11. Vermersch P, Kappos L, Gold R, et al. Clinicaloutcomes of natalizumab-associatedprogressive multifocal leukoencephalopathy.Neurology. 2011;76(20):1697-1704.12. Richardson EP Jr, Webster HD. Progressivemultifocal leukoencephalopathy: itspathological features. Prog Clin Biol Res.1983;105:191-203.13. Sabath BF, Major EO. Traffic of JC virus fromsites of initial infection to the brain: thepath to progressive multifocal leukoencephalopathy.J Infect Dis. 2002;186(Suppl2):S180-S186.14. Berger JR. The basis for modeling progressivemultifocal leukoencephalopathypathogenesis. Curr Opin Neurol. 2011;24(3):262-267.15. Matos A, Duque V, Beato S, et al. Characterizationof JC human polyomavirus infectionin a Portuguese population. J MedVirol. 2010;82(3):494-504.16. Monaco MC, Atwood WJ, Gravell M, et al.JC virus infection of hematopoietic progenitorcells, primary B lymphocytes, andtonsillar stromal cells: implications for virallatency. J Virol. 1996;70(10):7004-7012.17. Warnke C, Smolianov V, Dehmel T, et al.CD34+ progenitor cells mobilized by natalizumabare not a relevant reservoir forJC virus. Mult Scler. 2011;17(2):151-156.18. Ransohoff RM. Natalizumab and PML. NatNeurosci. 2005;8(10):127519. Chen Y, Bord E, Tompkins T, et al. Asymptomaticreactivation of JC virus in patientstreated with natalizumab. N Engl J Med.2009;361(11):1067-1074.20. Rudick RA, O’Connor PW, Polman CH, et al.Assessment of JC virus DNA in blood andurine from natalizumab-treated patients.Ann Neurol. 2010;68(3):304-310.21. Rice GP, Hartung HP, Calabresi PA. Anti-alpha4integrin therapy for multiple sclerosis:mechanisms and rationale. Neurology.2005;64(8):1336-1342.S26 July 2011 • Clinical Reviews of JCV and PML