Abstract
There is a need for consistent definition of human immunodeficiency virus (HIV)-associated cases of progressive multifocal leukoencephalopathy (PML), especially following the profound disease changes that have resulted from the use of highly active antiretroviral therapy (HAART). According to the criteria used for diagnosis, PML cases should be either referred to as “histology-confirmed,” with evidence of JC virus (JCV) infection in brain, “laboratory-confirmed,” with detection of JCV DNA in cerebrospinal fluid (CSF), or “possible,” in the presence of typical clinical and radiological picture, but no demonstration of JCV infection. Disease outcome should be defined by the evidence or lack of evidence of disease activity, rather than using survival or other variables. Disease activity should be based on clinical (scored neurological examination), radiological (magnetic resonance imaging), and virological (JCV DNA levels in CSF) indicators, to be assessed regularly, e.g., every 3 months until evidence of disease arrest or death. Furthermore, parallel assessments of other HIV-associated manifestations, including CD4+ cell counts and viral load, are required. A standard patient classification would be helpful for clinical management of PML patients, for their inclusion in clinical studies, and also will increase our current knowledge of PML and its evolution in relation with HAART.
Similar content being viewed by others
References
Antinori A, Ammassari A, De Luca A, Cingolani A, Murri R, Scoppettuolo G, Fortini M, Tartaglione T, Larocca LM, Zannoni G, Cattani P, Grillo R, Roselli R, Iacoangeli M, Scerrati M, Ortona L (1997). Diagnosis of AIDS-related focal brain lesions: a decision-making analysis based on clinical and neuroradiologic characteristics combined with polymerase chain reaction assays in CSF. Neurology 48: 687–694.
Astrom KE, Mancall EL, Richardson EP Jr (1958). Progressive multifocal leukoencephalopathy. Brain 81: 93–127.
Berger JR, Levy RM, Flomenhoft D, Dobbs M (1998). Predictive factors for prolonged survival in acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy. Ann Neurol 44: 341–349.
Cinque P, Scarpellini P, Vago L, Linde A, Lazzarin A (1997). Diagnosis of central nervous system complications in HIV-infected patients: cerebrospinal fluid analysis by the polymerase chain reaction. AIDS 11: 1–17.
Clifford DB, Yiannoutsos C, Glicksman M, Simpson DM, Singer EJ, Piliero PJ, Marra CM, Francis GS, McArthur JC, Tyler KL, Tselis AC, Hyslop NE (1999). HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy. Neurology 52: 623–625.
Corral I, Quereda C, Hellin T, Navas E, Garcia-Villanueva M (2002). Relapsing and remitting leukoencephalopathy associated with chronic HIV infection. Eur Neurol 481: 39–41.
De Luca A, Giancola ML, Ammassari A, Grisetti S, Paglia MG, Gentile M, Cingolani A, Murri R, Liuzzi G, Monforte AD, Antinori A (2000). The effect of potent antiretroviral therapy and JC virus load in cerebrospinal fluid on clinical outcome of patients with AIDS-associated progressive multifocal leukoencephalopathy. J Infect Dis 182: 1077–1083.
Dorries K (2002). Human polyomavirus infection in peripheral blood. Presented at the meeting Basic, Clinical and Epidemiologic Studies of Progressive Multifocal Leukoencephalopathy: Implications for Therapy, July 25–26, 2002, Portland, Maine.
Dworkin MS, Wan PC, Hanson DL, Jones JL (1999). Progressive multifocal leukoencephalopathy: improved survival of human immunodeficiency virus-infected patients in the protease inhibitor era. J Infect Dis 180: 621–625.
Eggers C, Stellbrink HJ, Buhk T, Dorries K (1999). Quantification of JC virus DNA in the cerebrospinal fluid of patients with human immunodeficiency virus-associated progressive multifocal leukoencephalopathy—a longitudinal study. J Infect Dis 180: 1690–1694.
Ferrante P, Omodeo-Zorini E, Caldarelli-Stefano R, Mediati M, Fainardi E, Granieri E, Caputo D (1998). Detection of JC virus DNA in cerebrospinal fluid from multiple sclerosis patients. Mult Scler 4: 49–54.
Garcia de Viedma D, Alonso R, Miralles P, Berenguer J, Rodriguez-Creixems M, Bouza E (1999). Dual qualitative-quantitative nested PCR for detection of JC virus in cerebrospinal fluid: high potential for evaluation and monitoring of progressive multifocal leukoencephalopathy in AIDS patients receiving highly active antiretroviral therapy. J Clin Microbiol 37: 724–728.
Gasnault J, Kousignian P, Kahraman M, Rahoiljaon J, Matheron S, Delfraissy JF, Taoufik Y (2001). Cidofovir in AIDS-associated progressive multifocal leukoencephalopathy: a monocenter observational study with clinical and JC virus load monitoring. J Neurovirol 7: 375–381.
Geschwind MD, Skolasky RI, Royal WS, McArthur JC (2001). The relative contributions of HAART and alphainterferon for therapy of progressive multifocal leukoencephalopathy in AIDS. J NeuroVirol 7: 353–357.
Giudici B, Vaz B, Bossolasco S, Casari S, Brambilla AM, Luke W, Lazzarin A, Weber T, Cinque P (2000). Highly active antiretroviral therapy and progressive multifocal leukoencephalopathy: effects on cerebrospinal fluid markers of JC virus replication and immune response. Clin Infect Dis 30: 95–99.
Hall CD, Dafni U, Simpson D, Clifford D, Wetherill PE, Cohen B, McArthur J, Hollander H, Yainnoutsos C, Major E, Millar L, Timpone J (1998). Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team. N Engl J Med 338: 1345–1351.
Hallervorden J (1930). Eigennartige und nicht rubriziebare Prozesse. In: Handbuch der Geiteskranheiten, vol 2. Die anatomie der Psychosen. Bumke O (ed). Springer, Berlin, pp 1063–1107.
Holloway RG, Mushlin AI (1996). Intracranial mass lesions in acquired immunodeficiency syndrome: using decision analysis to determine the effectiveness of stereotactic brain biopsy. Neurology 46: 1010–1015.
Koralnik IJ, Du Pasquier RA, Kuroda MJ, Schmitz JE, Dang X, Zheng Y, Lifton M, Letvin NL (2002). Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope. J Immunol 168: 499–504.
Kurtzke JF (1983). Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33: 1444–1452.
Levy RM, Russell E, Yungbluth M, Hidvegi DF, Brody BA, Dal Canto MC (1992). The efficacy of image-guided stereotactic brain biopsy in neurologically symptomatic acquired immunodeficiency syndrome patients. Neurosurgery 30: 186–189; discussion, 189–190.
Marra CM, Rajicic N, Barker DE, Cohen BA, Clifford D, Donovan Post MJ, Ruiz A, Bowen BC, Huang ML, Queen-Baker J, Andersen J, Kelly S, Shriver S (2002). A pilot study of cidofovir for progressive multifocal leukoencephalopathy in AIDS. AIDS 16: 1791–1797.
Padgett BL, ZuRhein GM, Walker D, Echroade R, Dessel B (1971). Cultivation of papova-like virus from human barin with progressive multifocal leukoencephalopathy. Lancet 1: 1257–1260.
Price RW, Nielsen S, Horten B, Rubino M, Padgett B, Walker D (1983). Progressive multifocal leukoencephalopathy: a burnt-out case. Ann Neurol 13: 485–490.
Silverman L, Rubinstein LJ (1965). Electron microscopic observations on case of progressive multifocal leukoencephalopathy. Acta Neuropathol (Berl) 5: 215–224.
Sweeney BJ, Manji H, Miller RF, Harrison MJ, Gray F, Scaravilli F (1994). Cortical and subcortical JC virus infection: two unusual cases of AIDS associated progressive multifocal leukoencephalopathy. J Neurol Neurosurg Psychiatry 57: 994–997.
Tassie JM, Gasnault J, Bentata M, Deloumeaux J, Boue F, Billaud E, Costagliola D (1999). Survival improvement of AIDS-related progressive multifocal leukoencephalopathy in the era of protease inhibitors. Clinical Epidemiology Group. French Hospital Database on HIV. AIDS 13: 1881–1887.
Thurnher MM, Post MJ, Rieger A, Kleibl-Popov C, Loewe C, Schindler E (2001). Initial and follow-up MR imaging findings in AIDS-related progressive multifocal leukoencephalopathy treated with highly active antiretroviral therapy. AJNR Am J Neuroradiol 22: 977–984.
Vinters HV, Tomiyasu U, Anders KH (1989). Neuropathologic complications of infection with the human immunodeficiency virus (HIV). Prog AIDS Pathol 1: 101–130.
Weber T, Klapper PE, Cleator GM, Bodemer M, Luke W, Knowles W, Cinque P, Van Loon AM, Grandien M, Hammarin AL, Ciardi M, Bogdanovic G (1997). Polymerase chain reaction for detection of JC virus DNA in cerebrospinal fluid: a quality control study. European Union Concerted Action on Viral Meningitis and Encephalitis. J Virol Methods 69: 231–237.
Yiannoutsos CT, Major EO, Curman B, Jensen PN, Gravell M, Hou J, Clifford DB, Hall CD (1999). Relation of JC virus DNA in the cerebrospinal fluid to survival in acquired immunodeficiency syndrome patients with biopsy-proven progressive multifocal leukoencephalopathy. Ann Neurol 45: 816–820.
ZuRhein GM, Chou SM (1965). Particles resembling paopvavirus in human cerebral demyelinating disease. Science 148: 1477–1479.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cinque, P., Koralnik, I.J. & Clifford, D.B. The evolving face of human immunodeficiency virus-related progressive multifocal leukoencephalopathy: Defining a consensus terminology. Journal of NeuroVirology 9 (Suppl 1), 88–92 (2003). https://doi.org/10.1080/13550280390195298
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1080/13550280390195298