Cytomegalovirus (CMV) disease of the brain in AIDS and connatal infection: a comparative study by histology, immunocytochemistry and in situ DNA hybridization

Abstract

Brain tissues from 45 patients with AIDS and two brains with connatal cytomegalic inclusion body disease were investigated for a cytomegalovirus (CMV) etiology of encephalitic lesions. Nineteen brains showed evidence of CMV infection by histology, immunocytochemistry (ICC) using two different antibodies (mono- and polyclonal), and in situ hybridization (ISH). Fourteen cases with typical cytomegalic cells in conventional histology [eight with focally necrotizing encephalitis/ventriculitis including the two connatal infections and six with nodular encephalitis (NE)] revealed CMV with any method. In 5 of 15 AIDS cases of NE without cytomegalic cells, CMV infection was established by ISH, whereas ICC remained negative in these cases. Typical lesions of human immunodeficiency virus (HIV)-induced multi-focal giant cell encephalitis (HIV encephalitis) in 13 brains were never labeled for CMV. In necrotizing encephalitis/ventriculitis, cell types which labeled for CMV, with and without cytomegalic change, comprised neurons, astrocytes, oligodendrocytes, ependyma, choroid plexus, endothelia, and cells in peri- and endoneurium, and in leptomeninges. Both ISH and ICC were able to detect widespread non-cytomegalic CMV-infected cells in normal parenchyma, well beyond the necrotizing lesions, in two AIDS cases. Labeling patterns of nuclei versus cytoplasms varied between the three methods for CMV detection. We conclude that in CNS tissues with cytomegalic cells, ICC and ISH are of comparable sensitivity; however, a diagnosis of CMV disease is possible in such cases by conventional histology. For an in situ diagnosis of CMV infection in NE without cytomegalic cells in AIDS, ISH is the method of choice. A selective vulnerability to CMV infection of any specific cell type of the human CNS is absent.(ABSTRACT TRUNCATED AT 250 WORDS)