Skip to main content

Advertisement

SpringerLink
Log in

Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome: Explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

In the era of the AIDS pandemic, progressive multifocal leukoencephalopathy (PML) has ceased being a rare disease. Prevalence estimates from clinical and pathological series suggest that up to 5% of all HIV-infected persons will develop PML. The extraordinary frequency with which PML attends HIV infection vastly exceeds its appearance in association with other predisposing conditions and has resulted in it no longer being considered a rare disorder. Why PML appears to be far more common with AIDS than with other underlying immunosuppressive conditions remains unexplained. Potential explanations include an alteration of the CNS milieu by HIV facilitating JC viral entry into the brain and activation of the JCV by HIV proteins, e.g., tat, and by inflammatory byproducts of HIV infection. It is quite likely that multiple diverse mechanisms are at play.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Antinori A, Ammassari A, et al (2001). Epidemiology and prognosis of AIDS-associated progressive multifocal leukoencephalopathy in the HAART era. J NeuroVirol 7: 323–328.

    Article  PubMed  CAS  Google Scholar 

  • Astrom K, Mancall E, et al (1958). Progressive multifocal leukoencephalopathy. Brain 81: 93–127.

    Article  PubMed  CAS  Google Scholar 

  • Bedri J, Weinstein W, et al (1983). Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome. N Engl J Med 309: 492–493.

    Article  PubMed  CAS  Google Scholar 

  • Berger JR, Chauhan A, et al (2001). Epidemiological evidence and molecular basis of interactions between HIV and JC virus. J NeuroVirol 7: 329–338.

    Article  PubMed  CAS  Google Scholar 

  • Berger JR, Kaszovitz B, et al (1987). Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases. Ann Intern Med 107: 78–87.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Bernick C, Gregorios JB (1984). Progressive multifocal leukoencephalopathy in a patient with acquired immune deficiency syndrome. Arch Neurol 41: 780–782.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Centers for Disease Control and Prevention (CDC) (1997). Update: trends in AIDS incidence—United States, 1996. MMWR Morb Mortal Wkly Rep 46: 861–867.

    Google Scholar 

  • CDC (2002). U.S. HIV and AIDS cases reported through June 2001. HIV/AIDS Surveillance Rep 13: 1–41.

    Google Scholar 

  • Chi D, Henry J, et al (2000). The effects of HIV infection on endothelial function. Endothelium 7: 223–242.

    PubMed  CAS  Google Scholar 

  • Couraud PO (1998). Infiltration of inflammatory cells through brain endothelium. Pathol Biol (Paris) 46: 176–180.

    CAS  Google Scholar 

  • Dubois V, Moret H, et al (1998). Prevalence of JC virus viraemia in HIV-infected patients with or without neurological disorders: a prospective study. J NeuroVirol 4: 539–544.

    Article  PubMed  CAS  Google Scholar 

  • Dworkin MS, Wan PC, et al (1999). Progressive multifocal leukoencephalopathy: improved survival of human immunodeficiency virus-infected patients in the protease inhibitor era. J Infect Dis 180: 621–625.

    Article  PubMed  CAS  Google Scholar 

  • Gillespie SM, Chang Y, et al (1991). Progressive multifocal leukoencephalopathy in persons infected with human immunodeficiency virus, San Francisco, 1981–1989. Ann Neurol 30: 597–604.

    Article  PubMed  CAS  Google Scholar 

  • Ho JL, Poldre PA, et al (1984). Acquired immunodeficiency syndrome with progressive multifocal leukoencephalopathy and monoclonal B-cell proliferation. Ann Intern Med 100: 693–696.

    PubMed  CAS  Google Scholar 

  • Holman RC, Janssen RS, et al (1991). Epidemiology of progressive multifocal leukoencephalopathy in the United States: analysis of national mortality and AIDS surveillance data [see comments]. Neurology 41: 1733–1736.

    PubMed  CAS  Google Scholar 

  • Ives NJ, Gazzard BG, et al (2001). The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART) in a London clinic. J Infect 42: 134–139.

    Article  PubMed  CAS  Google Scholar 

  • Janssen RS (1997). Epidemiology and neuroepidemiology of human immunodeficiency virus infection. In: AIDS and the nervous system. Berger JR, Levy RM (eds). Lippincott-Raven: Philadelphia, PA, pp 13–37.

    Google Scholar 

  • Katz DA, Berger JR, et al (1994). Progressive multifocal leukoencephalopathy complicating Wiskott-Aldrich syndrome. Report of a case andreview of the literature of progressive multifocal leukoencephalopathy with other inherited immunodeficiency states. Arch Neurol 51: 422–426.

    PubMed  CAS  Google Scholar 

  • Kure K, Llena JF, et al (1991). Human immunodeficiency virus-1 infection of the nervous system: an autopsy study of 268 adult, pediatric, and fetal brains. Hum Pathol 22: 700–710.

    Article  PubMed  CAS  Google Scholar 

  • Kurtzke J, Kurland L (1983). The epidemiology of neurologic disease. In: Clinical Neurology. Harper & Row: Philadelphia, PA, pp 1–14.

    Google Scholar 

  • Lane JH, Sasseville VG, et al (1996). Neuroinvasion by simian immunodeficiency virus coincides with increased numbers of perivascular macrophages/microglia and intrathecal immune activation. J Neuro-Virol 2: 423–432.

    CAS  Google Scholar 

  • Maschke M, Kastrup O, et al (2000). Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). J Neurol Neurosurg Psychiatry 69: 376–380.

    Article  PubMed  CAS  Google Scholar 

  • Messite J, Stillman S (1996). Accuracy of death certificate completion. JAMA 275: 794–796.

    Article  PubMed  CAS  Google Scholar 

  • Miller JR, Barrett RE, et al (1982). Progressive multifocal leukoencephalopathy in a male homosexual with T-cell immune deficiency. N Engl J Med 307: 1436–1438.

    Article  PubMed  CAS  Google Scholar 

  • Nath A (November 11, 2002). Personal communication regarding the absence of adhesion molecule expression in AIDS-associated PML brain sections.

  • Persidsky Y (1999). Model systems for studies of leukocyte migration across the blood-brain barrier. J NeuroVirol 5: 579–590.

    Article  PubMed  CAS  Google Scholar 

  • Sacktor N, RH Lyles, et al (2001). HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology 56: 257–260.

    PubMed  CAS  Google Scholar 

  • Tate LG (1994). Personal communication regarding PML in the Broward Medical Examiner’s office.

  • Tornatore C, Berger JR, et al (1992). Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy. Ann Neurol 31: 454–462.

    Article  PubMed  CAS  Google Scholar 

  • Williams KC, Hickey WF (1995). Traffic of hematogenous cells through the central nervous system. Curr Top Microbiol Immunol 202: 221–245.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, University of Kentucky College of Medicine, Kentucky Clinic L-445, 40536-0284, Lexington, Kentucky, USA

    Joseph R. Berger

Authors
  1. Joseph R. Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph R. Berger.

Additional information

This work has been reported in the Proceedings of the Basic, Clinical and Epidemiological Studies of Progressive Multifocal Leukoencephalopathy: Implications for Therapy Meeting, sponsored by the National Institute of Mental Health, National Institute of Neurological Diseases and Stroke, and the Office of Rare Diseases, July 25–26, 2002, Portland, Maine, USA.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berger, J.R. Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome: Explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions. Journal of NeuroVirology 9 (Suppl 1), 38–41 (2003). https://doi.org/10.1080/13550280390195261

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280390195261

Keywords

Search

Navigation