Introduction
Progressive multifocal leukoencephalopathy (PML) is a progressive infection of the brain by reactivation of the JC virus that manifests clinically as a subacute decline in neurologic function in the setting of significant immune suppression. It was first named in 1958 after histological definition of autopsy cases. All patients suffered underlying lymphoproliferative disorders (Astrom et al. 1958). PML has since continued to be a rarely occurring complication of these diseases, such as myelodysplastic syndrome, chronic lymphocytic leukemia, and Hodgkin disease. Reviewing the world’s publications through 1984 and adding cases from their own extensive experience, Brooks and Walker were only able to identify 230 cases (Brooks and Walker 1984). With the emergence of the HIV pandemic, PML became exponentially more common, typically emerging in the HIV-infected when CD4 counts waned below 200 cells/μL. In fact, it was diagnosed in 4% of the HIV-infected population (Berger et...
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References
Aksamit Jr AJ. Progressive multifocal leukoencephalopathy. Continuum (Minneap Minn). 2012;18(6 Infectious Disease):1374–91.
Altschuler EL, Kast RE. The atypical antipsychotic agents ziprasidone [correction of zisprasidone], risperdone and olanzapine as treatment for and prophylaxis against progressive multifocal leukoencephalopathy. Med Hypotheses. 2005;65(3):585–6.
Amend KL, Turnbull B, et al. Incidence of progressive multifocal leukoencephalopathy in patients without HIV. Neurology. 2010;75(15):1326–32.
Antinori A, Cingolani A, et al. Clinical implications of HIV-1 drug resistance in the neurological compartment. Scand J Infect Dis Suppl. 2003a;106:41–4.
Antinori A, Cingolani A, et al. Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: data from the Italian Registry Investigative Neuro AIDS (IRINA). J Neurovirol. 2003b;9 Suppl 1:47–53.
Astrom KE, Mancall EL, et al. Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease. Brain. 1958;81(1):93–111.
Axthelm MK, Koralnik IJ, et al. Meningoencephalitis and demyelination are pathologic manifestations of primary polyomavirus infection in immunosuppressed rhesus monkeys. J Neuropathol Exp Neurol. 2004;63(7):750–8.
Balduzzi A, Lucchini G, et al. Polyomavirus JC-targeted T-cell therapy for progressive multiple leukoencephalopathy in a hematopoietic cell transplantation recipient. Bone Marrow Transplant. 2011;46(7):987–92.
Beltrami S, Gordon J. Immune surveillance and response to JC virus infection and PML. J Neurovirol. 2013;20(2):137–49.
Berger JR. Steroids for PML-IRIS. A double-edged sword? Neurology. 2009;72:1454–5.
Berger JR. Progressive multifocal leukoencephalopathy and newer biological agents. Drug Saf. 2010;33(11):969–83.
Berger JR, Khalili K. The pathogenesis of progressive multifocal leukoencephalopathy. Discov Med. 2011;12(67):495–503.
Berger JR, Kaszovitz B, et al. Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases. Ann Intern Med. 1987;107(1):78–87.
Berger JR, Levy RM, et al. Predictive factors for prolonged survival in acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy. Ann Neurol. 1998a;44(3):341–9.
Berger JR, Pall L, et al. Progressive multifocal leukoencephalopathy in patients with HIV infection. J Neurovirol. 1998b;4(1):59–68.
Berger JR, Aksamit AJ, et al. PML diagnostic criteria: consensus statement from the AAN neuroinfectious disease section. Neurology. 2013a;80(15):1430–8.
Berger JR, Houff SA, et al. JC virus antibody status underestimates infection rates. Ann Neurol. 2013b;74(1):84–90.
Bloomgren G, Richman S, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870–80.
Brickelmaier M, Lugovskoy A, et al. Identification and characterization of mefloquine efficacy against JC virus in vitro. Antimicrob Agents Chemother. 2009;53(5):1840–9.
Brooks BR, Walker DL. Progressive multifocal leukoencephalopathy. Neurol Clin. 1984;2(2):299–313.
Buckanovich RJ, Liu G, et al. Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin’s lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy. Ann Hematol. 2002;81(7):410–3.
Casado JL, Corral I, et al. Continued declining incidence and improved survival of progressive multifocal leukoencephalopathy in HIV/AIDS patients in the current era. Eur J Clin Microbiol Infect Dis. 2013;33(2):179–87.
Cavanagh JB, Greenbaum D, et al. Cerebral demyelination associated with disorders of the reticuloendothelial system. Lancet. 1959;2(7102):524–9.
Cettomai D, McArthur JC. Mirtazapine use in human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy. Arch Neurol. 2009;66(2):255–8.
Chapagain ML, Nerurkar VR. Human polyomavirus JC (JCV) infection of human B lymphocytes: a possible mechanism for JCV transmigration across the blood-brain barrier. J Infect Dis. 2010;202(2):184–91.
Christakis PG, Okin D, et al. Progressive multifocal leukoencephalopathy in an immunocompetent patient. J Neurol Sci. 2013;326(1–2):107–10.
Clifford DB, Nath A, et al. A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes. J Neurovirol. 2013;19(4):351–8.
Dang X, Koralnik IJ. A granule cell neuron-associated JC virus variant has a unique deletion in the VP1 gene. J Gen Virol. 2006;87(Pt 9):2533–7.
Dang X, Wuthrich C, et al. JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant. PLoS One. 2012;7(4):e35793.
Deeks SG, Lewin SR, et al. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013;382(9903):1525–33.
Diotti RA, Nakanishi A, et al. JC polyomavirus (JCV) and monoclonal antibodies: friends or potential foes? Clin Dev Immunol. 2013;2013:967581.
Ermis U, Weis J, et al. PML in a patient treated with fumaric acid. N Engl J Med. 2013;368(17):1657–8.
Ferenczy MW, Marshall LJ, et al. Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev. 2012;25(3):471–506.
Gheuens S, Pierone G, et al. Progressive multifocal leukoencephalopathy in individuals with minimal or occult immunosuppression. J Neurol Neurosurg Psychiatry. 2010;81(3):247–54.
Giacomini PS, Rozenberg A, et al. Maraviroc and JC virus-associated immune reconstitution inflammatory syndrome. N Engl J Med. 2014;370(5):486–8.
Goldberg SL, Pecora AL, et al. Unusual viral infections (progressive multifocal leukoencephalopathy and cytomegalovirus disease) after high-dose chemotherapy with autologous blood stem cell rescue and peritransplantation rituximab. Blood. 2002;99(4):1486–8.
Hall CD, Dafni U, et al. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS clinical trials group 243 team. N Engl J Med. 1998;338(19):1345–51.
Hirsch HH, Kardas P, et al. The human JC polyomavirus (JCPyV): virological background and clinical implications. APMIS. 2013;121(8):685–727.
Kato A, Kitamura T, et al. Detection of the archetypal regulatory region of JC virus from the tonsil tissue of patients with tonsillitis and tonsilar hypertrophy. J Neurovirol. 2004;10(4):244–9.
Kaufman GP, Aksamit AJ, et al. Progressive multifocal leukoencephalopathy: a rare infectious complication following allogeneic hematopoietic cell transplantation (HCT). Eur J Haematol. 2014;92(1):83–7.
Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005;353(4):369–74.
Koralnik IJ, Boden D, et al. JC virus DNA load in patients with and without progressive multifocal leukoencephalopathy. Neurology. 1999;52(2):253–60.
Koralnik IJ, Wuthrich C, et al. JC virus granule cell neuronopathy: a novel clinical syndrome distinct from progressive multifocal leukoencephalopathy. Ann Neurol. 2005;57(4):576–80.
Kuchelmeister K, Gullotta F, et al. Progressive multifocal leukoencephalopathy (PML) in the acquired immunodeficiency syndrome (AIDS). A neuropathological autopsy study of 21 cases. Pathol Res Pract. 1993;189(2):163–73.
Laghi L, Randolph AE, et al. JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci U S A. 1999;96(13):7484–9.
Lang W, Miklossy J, et al. Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland. Acta Neuropathol. 1989;77(4):379–90.
Langer-Gould A, Atlas SW, et al. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005;353(4):375–81.
Lanzafame M, Ferrari S, et al. Mirtazapine in an HIV-1 infected patient with progressive multifocal leukoencephalopathy. Infez Med. 2009;17(1):35–7.
Major EO, Frohman E, et al. JC viremia in natalizumab-treated patients with multiple sclerosis. N Engl J Med. 2013;368(23):2240–1.
Marshall LJ, Major EO. Molecular regulation of JC virus tropism: insights into potential therapeutic targets for progressive multifocal leukoencephalopathy. J Neuroimmune Pharmacol. 2010;5(3):404–17.
Mateen FJ, Muralidharan R, et al. Progressive multifocal leukoencephalopathy in transplant recipients. Ann Neurol. 2011;70(2):305–22.
Molloy ES, Calabrese LH. Progressive multifocal leukoencephalopathy: a national estimate of frequency in systemic lupus erythematosus and other rheumatic diseases. Arthritis Rheum. 2009;60(12):3761–5.
Monaco MC, Jensen PN, et al. Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection. J Virol. 1998;72(12):9918–23.
Monaco MC, Sabath BF, et al. JC virus multiplication in human hematopoietic progenitor cells requires the NF-1 class D transcription factor. J Virol. 2001;75(20):9687–95.
Netravathi M, Mahadevan A, et al. Progressive multifocal leukoencephalopathy (PML) associated with HIV Clade C – is not uncommon. J Neurovirol. 2013;19(3):198–208.
Padgett BL, Walker DL, et al. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet. 1971;1(7712):1257–60.
Pohlmann C, Hochauf K, et al. Chlorpromazine combined with cidofovir for treatment of a patient suffering from progressive multifocal leukoencephalopathy. Intervirology. 2007;50(6):412–7.
Przepiorka D, Jaeckle KA, et al. Successful treatment of progressive multifocal leukoencephalopathy with low-dose interleukin-2. Bone Marrow Transplant. 1997;20(11):983–7.
Pugnet G, Pagnoux C, et al. Progressive multifocal encephalopathy after cyclophosphamide in granulomatosis with polyangiitis (Wegener) patients: case report and review of literature. Clin Exp Rheumatol. 2013;31(1 Suppl 75):S62–4.
Ricciardiello L, Laghi L, et al. JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Gastroenterology. 2000;119(5):1228–35.
Ryschkewitsch CF, Jensen PN, et al. Multiplex qPCR assay for ultra sensitive detection of JCV DNA with simultaneous identification of genotypes that discriminates non-virulent from virulent variants. J Clin Virol. 2013;57(3):243–8.
Sahraian MA, Radue EW, et al. Progressive multifocal leukoencephalopathy: a review of the neuroimaging features and differential diagnosis. Eur J Neurol. 2012;19(8):1060–9.
Stoner GL, Ryschkewitsch CF. Capsid protein VP1 deletions in JC virus from two AIDS patients with progressive multifocal leukoencephalopathy. J Neurovirol. 1995;1(2):189–94.
Tan IL, McArthur JC, et al. Immune reconstitution inflammatory syndrome in natalizumab-associated PML. Neurology. 2011;77(11):1061–7.
Tan CS, Broge Jr TA, et al. Detection of JC virus-specific immune responses in a novel humanized mouse model. PLoS One. 2013;8(5):e64313.
Telenti A, Marshall WF, et al. Detection of JC virus by polymerase chain reaction in cerebrospinal fluid from two patients with progressive multifocal leukoencephalopathy. Eur J Clin Microbiol Infect Dis. 1992;11(3):253–4.
Terrier B, Hummel A, et al. Progressive multifocal leukoencephalopathy in a non-AIDS patient: high efficiency of combined cytarabine and cidofovir. Rev Med Interne. 2007;28(7):488–91.
Van Assche G, Van Ranst M, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med. 2005;353(4):362–8.
Vendrely A, Bienvenu B, et al. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol. 2005;109(4):449–55.
Vulliemoz S, Lurati-Ruiz F, et al. Favourable outcome of progressive multifocal leucoencephalopathy in two patients with dermatomyositis. J Neurol Neurosurg Psychiatry. 2006;77(9):1079–82.
Walker DL, Padgett BL, et al. Human papovavirus (JC): induction of brain tumors in hamsters. Science. 1973;181(4100):674–6.
Westwood, et al. Eur J Radiol. 2013;82(8):e374–9. PMID 23578921.
White MK, Khalili K. Pathogenesis of progressive multifocal leukoencephalopathy – revisited. J Infect Dis. 2011;203(5):578–86.
Wuthrich C, Dang X, et al. Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neurons. Ann Neurol. 2009;65(6):742–8.
Yoon JH, Bang OY, Kim HS. J Clin Neurol. 2007;3(4):200–3. https://doi.org/10.3988/jcn.2007.3.4.200. PMID 19513133.
Yousry TA, Pelletier D, et al. Magnetic resonance imaging pattern in natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol. 2012;72(5):779–87.
Zaheer F, Berger JR. Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps. Ther Adv Drug Saf. 2012;3(5):227–35.
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Lyons, J.L., Berger, J.R. (2018). Comorbidity: Progressive Multifocal Leukoencephalopathy. In: Hope, T.J., Richman, D.D., Stevenson, M. (eds) Encyclopedia of AIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7101-5_280
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