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Neuropathological studies in the brains of AIDS patients with opportunistic diseases

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Summary

The brains of 70 fatal cases with AIDS were studied by means of immunohistochemistry and in-situ hybridization in a consecutive autopsy series (1985–July 1992). In addition, the neuropathological changes were correlated with the neurological and neuroimaging findings. Opportunistic infections included toxoplasmosis (15 cases), cytomegalovirus (CMV)-encephalitis (6), progressive multifocal leucoencephalopathy (2) and fungal infections (3). Malignant lymphomas were found in 7 patients; 6 involved primarily the CNS, one was metastatic. In 14 cases the neuropathological changes were consistent with HIV encephalitis and HIV leucoencephalopathy. Non-specific lesions occurred in 31 cases. The clinical diagnosis in patients with opportunistic diseases (n = 27) diverged in 15 cases (55%) from the underlying pathology. Toxoplasma gondii, CMV and JC viruses were identified by immunohistochemistry and in-situ hybridization on serial paraffin sections. In addition, antibodies against lymphocyte subsets, tissue macrophages, the glial fibrillary acid protein (GFAP) and myelin basic protein were used to characterize the phenotype of cells and to highlight the degree of gliosis and demyelination. Our results show that the distribution and degree of morphological changes might be helpful for the differential diagnosis antemortem. Since neurological complications may represent the first or sole manifestation of AIDS and risk factors for AIDS are often not known, it should be taken into account that CNS manifestations of AIDS may contribute to a sudden and unexpected death or accident. Opportunistic diseases should be considered as a possible differential diagnosis in cases mimicking the clinical picture of apoplexia or dementia. Furthermore, CNS lesions may be detected postmortem in patients who were not known to suffer from Neuro-Aids during life, indicating that CNS involvement is more widespread than assumed.

Zusammenfassung

Die Gehirne von 70 verstorbenen AIDS-Patienten wurden mit Hilfe von Immunhistochemie und in-situ-Hybridisierung in einer systematischen Autopsie-Serie (1985–Juli 1992) untersucht. Die neuropathologischen Befunde wurden mit den neurologischen und neuroradiologischen Untersuchungsergebnissen korreliert. Opportunistische Infektionen umfaßten Toxoplasmose (15 Fälle), Cytomegalievirus (CMV)-Encephalitis (6), progressive multifokale Leukoencephalopathie (2) und Pilzinfektionen (3). Maligne Lymphome fanden sich bei 7 Patienten; 6 davon waren primäre ZNS-Lymphome, eines eine metastatische Absiedelung. In 14 Fällen waren die Befunde vereinbar mit einer HIV-Encephalitis bzw. HIV-Leukoencephalopathie. In 31 Fällen fanden sich unspezifische Veränderungen. Bei den Patienten mit opportunistischen Infektionen zeigte sich in 15 Fällen (55%) keine Übereinstimmung zwischen klinischer und pathologischer Diagnose. An Paraffin-Serienschnitten wurden Toxoplasmen, CMV und JC-Virus mit Immunhistochemie und in-situ-Hybridisierung identifiziert. Mit Hilfe von Antikörpern gegen Lymphozyten-Subtypen, Gewebsmakrophagen, saures Gliafaserprotein und basisches Myelin-protein wurden die Phänotypen der Zellen charakterisiert und das Ausmaß von Gliose und Demyelinisierung quantifiziert. Unsere Ergebnisse zeigen, daß Ausmaß und Verteilung der morphologischen Veränderungen bereits zu Lebzeiten der Patienten hilfreich für die Differentialdiagnose sein können. Da neurologische Komplikationen die erste oder einzige Manifestation von AIDS darstellen können und Risikofaktoren häufig nicht bekannt sind, kann eine ZNS-Beteiligung bei AIDS Mitursache eines plötzlichen, unerwarteten Todes oder Unfalls sein. Opportunistische Erkrankungen sollten bei klinischem Bild eines Apoplex oder einer Demenz differentialdiagnostisch ausgeschlossen werden. Darüberhinaus können ZNS-Läsionen post-

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This work was supported by the Heinz-Ansmann-Stiftung für AIDS-Forschung, Düsseldorf mortal bei Patienten gefunden werden, bei denen keine neurologische Beteiligung zu Lebzeiten bekannt war. Eine ZNS-Beteiligung im Rahmen von AIDS scheint somit verbreiteter zu sein als bisher angenommen.

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Neuen-Jacob, E., Figge, C., Arendt, G. et al. Neuropathological studies in the brains of AIDS patients with opportunistic diseases. Int J Leg Med 105, 339–350 (1993). https://doi.org/10.1007/BF01222119

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