Mark Gudesblatt, MD

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Understanding theComplexities ofJCV and PMLCONTENTSAn Overview of JC Virusand Progressive MultifocalLeukoencephalopathy ..................................S3Mark Gudesblatt, MDThe Epidemiology ofProgressive MultifocalLeukoencephalopathy ................................S10John F. Foley, MDProgressive MultifocalLeukoencephalopathy:Survival Statistics ............................................S17Moti L. Chapagain, PhDSUPPLEMENT EDITORMark Gudesblatt, MDFACULTYMark Gudesblatt, MDJohn F. Foley, MDMoti L. Chapagain, PhDS2 July 2011 • Clinical Reviews of JCV and PML
An Overview of JC Virusand Progressive MultifocalLeukoencephalopathyMark Gudesblatt, MDChief of Neurology, Brookhaven MemorialHospital Medical Center, Brookhaven, NY,and South Shore Neurologic Associates, PC,Bay Shore, New York.Dr. Gudesblatt is a consultant for Biogen Idec,Teva Neuroscience, Medtronic, Inc, and Lundbeck Inc.IntroductionThe risk of progressive multifocal leukoencephalopathy(PML) has been traced to an otherwiseinnocuous acquisition of the JC virus (JCV). Afteran asymptomatic primary infection, JCV, ahuman polyomavirus, typically persists in a quiescentstate without clinical consequences. 1 Thegenesis of PML, a rare complication of JCV, is dependenton a series of events that permit the virusto become active within the central nervous system(CNS). 2 Although JCV was isolated in 1971, 3much of the progress in understanding the pathophysiologyof PML was subsequent to the steepincrease in cases associated with the epidemic ofhuman immunodeficiency virus (HIV). 2 Recentattention to the causes and prevention of PMLis driven by a small but accumulating number ofcases associated with the use of immunomodulatingdrugs prescribed for such indications as organtransplant or chronic autoimmune diseases. 1 Theinfrequency of PML even in the most vulnerablepopulations suggests that the complex molecularroute from asymptomatic JCV infection to a fulminantCNS disease is potentially modifiable. 4While increased survival has been seen with somebiological therapies, such as natalizumab formultiple sclerosis (MS), risk stratification prior toinitiating immunosuppressive drugs may furtherreduce PML cases. 5JCV: Biological PropertiesJCV, named from the initials of the first patient inwhom the virus was isolated, is a 5.1-Kb doublestrandedDNA virus with only 5100 base pairs buta large coding region, representing 90% of its viralgenome. 6 Like the BK virus, another polyomavi-Clinical Reviews of JCV and PML • July 2011 S3
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Page 5 and 6: cation. Although PML is generally c
Page 7 and 8: JCV exposure than those who are not
Page 9 and 10: 39. Weber F, Goldmann C, Krämer M,
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Page 14: tainment of JCV in the CNS as well
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Page 21 and 22: characteristic brain changes on mag
Page 23 and 24: with HIV-associated PML, recent stu
Page 25 and 26: Natalizumab, the first monoclonal a
Page 27: 22. Lebwohl M, Tyring SK, Hamilton

Mark Gudesblatt, MD

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