title: Progressive multifocal leukoencephalopathy (PML) in AIDS and in the pre-AIDS era. A neuropathological comparison using immunocytochemistry and in situ DNA hybridization for virus detection.
abstract: Twenty-five brains with definite, and three brains with possible, progressive multifocal leukoencephalopathy (PML), including six brains of AIDS patients, were studied with special regard to the detection of papovaviruses. Formalin-fixed serial paraffin sections were immunostained with monospecific anti-JC virus (JCV) and genus-specific anti-simian virus (SV) 40 antisera, and hybridized in situ with DNA probes for JCV and SV 40, respectively. Immunocytochemistry (ICC) and in situ hybridization (ISH) were similarly sensitive in detecting virus in classical PML lesions. In all but one definite PML cases at least one method detected virus (96%). Possible PML tissue was never labeled. Labeling patterns were generally similar in ICC and ISH: mainly oligodendroglia and, less frequently, astroglia harbored virus, whereas labeling of neurons and endothelia was absent. Bizarre giant astrocytes were occasionally labeled by ICC and ISH. Burnt-out lesions harbored JCV DNA but not virus antigens. SV 40 DNA was never detectable. PML morphology in AIDS cases did not usually differ from the disease process seen in the pre-AIDS era. However, two AIDS brains presented extremely extended and, in one case, unusually necrotizing PML damage; in the latter case, PML lesions contained large amounts not only of JCV, but also of human immunodeficiency virus (HIV) antigens. We conclude that ICC and ISH are methods of comparable sensitivity for detection of papovavirus in fluorishing PML lesions. In burnt-out PML lesions only ISH may detect virus. The possibility of an exceptional non-JCV (e.g., SV 40) etiology of PML could be neither confirmed nor disproved. In AIDS, massive coinfection by HIV of PML lesions may increase damage to tissue, resulting in unusually extended and necrotizing PML.
authors.affiliation: Neurologisches Institut, Universität Wien, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Schmidbauer
authors.forename: H
authors.initials: H
authors.lastname: Budka
authors.forename: K V
authors.initials: KV
authors.lastname: Shah
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D001921:Brain / Q000382:microbiology / Q000473:pathology*; D015342:DNA Probes; D004279:DNA, Viral / Q000032:analysis; D015488:HIV Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D012189:Retrospective Studies
chemical_list: D015342:DNA Probes; D004279:DNA, Viral; D015488:HIV Antigens