Skip to main content
SpringerLink
Log in

Comorbidity: Progressive Multifocal Leukoencephalopathy

  • Reference work entry
  • First Online:
Encyclopedia of AIDS

  • 67 Accesses

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...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,099.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,599.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aksamit Jr AJ. Progressive multifocal leukoencephalopathy. Continuum (Minneap Minn). 2012;18(6 Infectious Disease):1374–91.

    Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Amend KL, Turnbull B, et al. Incidence of progressive multifocal leukoencephalopathy in patients without HIV. Neurology. 2010;75(15):1326–32.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Beltrami S, Gordon J. Immune surveillance and response to JC virus infection and PML. J Neurovirol. 2013;20(2):137–49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Berger JR. Steroids for PML-IRIS. A double-edged sword? Neurology. 2009;72:1454–5.

    Article  PubMed  Google Scholar 

  • Berger JR. Progressive multifocal leukoencephalopathy and newer biological agents. Drug Saf. 2010;33(11):969–83.

    Article  CAS  PubMed  Google Scholar 

  • Berger JR, Khalili K. The pathogenesis of progressive multifocal leukoencephalopathy. Discov Med. 2011;12(67):495–503.

    PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Berger JR, Pall L, et al. Progressive multifocal leukoencephalopathy in patients with HIV infection. J Neurovirol. 1998b;4(1):59–68.

    Article  CAS  PubMed  Google Scholar 

  • Berger JR, Aksamit AJ, et al. PML diagnostic criteria: consensus statement from the AAN neuroinfectious disease section. Neurology. 2013a;80(15):1430–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Berger JR, Houff SA, et al. JC virus antibody status underestimates infection rates. Ann Neurol. 2013b;74(1):84–90.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bloomgren G, Richman S, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870–80.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brooks BR, Walker DL. Progressive multifocal leukoencephalopathy. Neurol Clin. 1984;2(2):299–313.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Cavanagh JB, Greenbaum D, et al. Cerebral demyelination associated with disorders of the reticuloendothelial system. Lancet. 1959;2(7102):524–9.

    Article  CAS  PubMed  Google Scholar 

  • Cettomai D, McArthur JC. Mirtazapine use in human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy. Arch Neurol. 2009;66(2):255–8.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Christakis PG, Okin D, et al. Progressive multifocal leukoencephalopathy in an immunocompetent patient. J Neurol Sci. 2013;326(1–2):107–10.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Dang X, Wuthrich C, et al. JC virus encephalopathy is associated with a novel agnoprotein-deletion JCV variant. PLoS One. 2012;7(4):e35793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deeks SG, Lewin SR, et al. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013;382(9903):1525–33.

    Article  PubMed  PubMed Central  Google Scholar 

  • Diotti RA, Nakanishi A, et al. JC polyomavirus (JCV) and monoclonal antibodies: friends or potential foes? Clin Dev Immunol. 2013;2013:967581.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ermis U, Weis J, et al. PML in a patient treated with fumaric acid. N Engl J Med. 2013;368(17):1657–8.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Giacomini PS, Rozenberg A, et al. Maraviroc and JC virus-associated immune reconstitution inflammatory syndrome. N Engl J Med. 2014;370(5):486–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Hirsch HH, Kardas P, et al. The human JC polyomavirus (JCPyV): virological background and clinical implications. APMIS. 2013;121(8):685–727.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Koralnik IJ, Boden D, et al. JC virus DNA load in patients with and without progressive multifocal leukoencephalopathy. Neurology. 1999;52(2):253–60.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Lanzafame M, Ferrari S, et al. Mirtazapine in an HIV-1 infected patient with progressive multifocal leukoencephalopathy. Infez Med. 2009;17(1):35–7.

    CAS  PubMed  Google Scholar 

  • Major EO, Frohman E, et al. JC viremia in natalizumab-treated patients with multiple sclerosis. N Engl J Med. 2013;368(23):2240–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mateen FJ, Muralidharan R, et al. Progressive multifocal leukoencephalopathy in transplant recipients. Ann Neurol. 2011;70(2):305–22.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Padgett BL, Walker DL, et al. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet. 1971;1(7712):1257–60.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Tan IL, McArthur JC, et al. Immune reconstitution inflammatory syndrome in natalizumab-associated PML. Neurology. 2011;77(11):1061–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walker DL, Padgett BL, et al. Human papovavirus (JC): induction of brain tumors in hamsters. Science. 1973;181(4100):674–6.

    Article  CAS  PubMed  Google Scholar 

  • Westwood, et al. Eur J Radiol. 2013;82(8):e374–9. PMID 23578921.

    Google Scholar 

  • White MK, Khalili K. Pathogenesis of progressive multifocal leukoencephalopathy – revisited. J Infect Dis. 2011;203(5):578–86.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wuthrich C, Dang X, et al. Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neurons. Ann Neurol. 2009;65(6):742–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yousry TA, Pelletier D, et al. Magnetic resonance imaging pattern in natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol. 2012;72(5):779–87.

    Article  CAS  PubMed  Google Scholar 

  • Zaheer F, Berger JR. Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps. Ther Adv Drug Saf. 2012;3(5):227–35.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Division of Neurological Infections and Inflammatory Diseases, Brigham and Women’s Hospital and Harvard Medical School, 40 Fenwood Rd, Boston, MA, 02115, USA

    Jennifer L. Lyons

  2. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Joseph R. Berger

Authors
  1. Jennifer L. Lyons
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph R. Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jennifer L. Lyons .

Editor information

Editors and Affiliations

  1. Department of Cell and Molecular Biology, Northwestern University, Robert H. Lurie Medical Research Center, Chicago, IL, USA

    Thomas J. Hope

  2. VA San Diego Healthcare System and University of California San Diego, La Jolla, CA, USA

    Douglas D. Richman

  3. Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA

    Mario Stevenson

Section Editor information

  1. University of Pennsylvania, 415 Curie Blvd.; 280C Clinical Research Building, 19104/6146, Philadelphia, PA, USA

    Dennis L Kolson

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media LLC

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

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

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7101-5_280

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-7100-8

  • Online ISBN: 978-1-4939-7101-5

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation