Etiology of microglial nodules in brains of patients with acquired immunodeficiency syndrome

Microglial nodules associated with opportunistic and HIV-related lesions ar e frequently found in the brains of AIDS patients. However, in many cases, the causative agent is only presumptively suspected. We reviewed 199 brains of AIDS patients with micronodular lesions to clarify their etiology by im munohistochemistry (to Toxoplasma gondii, cytomegalovirus, herpes simplex v irus I/II, varicella tester virus and HIV-p24 core protein), PCR (for herpe tic viruses and Mycobacterium tuberculosis) and electron microscopy. Produc tive HN infection was observed in 110 cases (55.1%): 30 cases with Toxoplas ma gondii encephalitis, 30 with cytomegalovirus encephalitis, eight with mu ltiple cerebral diseases, while in the remaining 42 cases HIV was the only pathogenetic agent. Multinucleated giant cells (hallmark of HIV infection) were found in the MGNs of 85/110 cases with HIV-related lesions; the remain ing 25 cases had only p24 positive cells but no multinucleated giant cells. In these latter cases the micronodular lesions had been initially attribut ed to the main opportunistic agent found in the brain, or defined as subacu te encephalitis. Individual microglial nodules positive for an opportunisti c pathogen were generally negative for HIV antigens, In 13 cases no opportu nistic agent or HIV productive infection was found. In these cases, PCR and electron microscopy examination for HIV and other viral infections were ne gative. Our data suggest that HIV-immunohistochemistry should be used far t he etiological diagnosis of micronodular lesions in AIDS brains, even in th e presence of other pathogens. After extensive search, the etiology of the microglial nodules remains unknown in only a small percentage of cases.