The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex.
ABSTRACT Infection with human immunodeficiency virus type 1 (HIV-1) is frequently complicated in its late stages by the AIDS dementia complex, a neurological syndrome characterized by abnormalities in cognition, motor performance, and behavior. This dementia is due partially or wholly to a direct effect of the virus on the brain rather than to opportunistic infection, but its pathogenesis is not well understood. Productive HIV-1 brain infection is detected only in a subset of patients and is confined largely or exclusively to macrophages, microglia, and derivative multinucleated cells that are formed by virus-induced cell fusion. Absence of cytolytic infection of neurons, oligodentrocytes, and astrocytes has focused attention on the possible role of indirect mechanisms of brain dysfunction related to either virus or cell-coded toxins. Delayed development of the AIDS dementia complex, despite both early exposure of the nervous system to HIV-1 and chronic leptomeningeal infection, indicates that although this virus is "neurotropic," it is relatively nonpathogenic for the brain in the absence of immunosuppression. Within the context of the permissive effect of immunosuppression, genetic changes in HIV-1 may underlie the neuropathological heterogeneity of the AIDS dementia complex and its relatively independent course in relation to the systemic manifestations of AIDS noted in some patients.
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ABSTRACT: The advent of highly active antiretroviral therapy has prolonged the life expectancy of HIV patients and decreased the number of adults who progress to AIDS and HIV-associated dementia. However, neurocognitive deficits remain a pronounced consequence of HIV/AIDS. HIV-1 infection targets the central nervous system in subcortical brain areas and leads to high rates of delirium, depression, opportunistic central nervous system infections, and dementia. Long-term HIV replication in the brain occurs in astrocytes and microglia, allowing the virus to hide from antiviral medication and later compromise neuronal function. The associated cognitive disturbance is linked to both viral activity and inflammatory and other mediators from these immune cells that lead to the damage associated with HIV-associated neurocognitive disorders, a general term given for these disturbances. We review the severity and prevalence of the neuropsychiatric complications of HIV including delirium, neurobehavioral impairments (depression), minor cognitive-motor dysfunction, and HIV-associated dementia.
Article: Cerebrovascular disease in AIDS[Show abstract] [Hide abstract]
ABSTRACT: The autopsy records of adult patients dying with AIDS between 1983 and 1987 at a large, metropolitan, university-affiliated hospital were reviewed to determine the incidence and spectrum of cerebrovascular and associated cardiovascular disease. The clinical records of those patients with AIDS with cerebrovascular disease were retrospectively examined in detail. All autopsied patients between the ages of 20 and 50 years dying without AIDS in 1986 and 1987 served as the control group. At autopsy, 13 (8%) of 154 adult patients with AIDS had evidence of recent cerebrovascular disease. In comparison, 25 (23%) of the 111 control patients dying without AIDS had recent cerebrovascular disease (P < 0.04). The spectrum of cerebrovascular diseases was similar in patients both with and without AIDS; however, cerebral vasculitis was observed only in the former. Thirty-nine (40%) of 97 patients with AIDS had significant cardiac disease, and cerebral emboli were demonstrated in four of the 13 patients with stroke. Stroke must be considered in the differential diagnosis of neurological disease in patients with AIDS, although it does not appear to be more common in this group than in a control population of young adults with other terminal illnesses. The causes of stroke occurring with AIDS are diverse and include cerebral emboli secondary to cardiac disease, cerebral hemorrhage secondary to thrombocytopenia, and cerebral vasculitis.AIDS 01/1990; 4(3):239-244. DOI:10.1097/00002030-199003000-00010 · 6.56 Impact Factor
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ABSTRACT: Objective: To assess the effect of zidovudine on productive HIV infection of the brain. Design: To correlate the incidence of HIV-specific neuropathology with zidovudine therapy. Patients: We examined 192 AIDS cases neuropathologically; 97 had never been treated with zidovudine, 72 had received zidovudine for over 3 months and until death, 23 had their treatment terminated more than 1 month before death. Results: The incidence of HIV encephalitis/HIV leukoencephalopathy (HIVE/HIVL) and of multinucleated giant cells (MGC) was significantly lower in patients who had received zidovudine than in those who had never received zidovudine. The yearly incidence of HIVE/HIVL increased between 1982 and 1987 probably because of improved survival, and decreased between 1987 and 1990 although the percentage of patients treated with zidovudine increased. Since 1991 the incidence of HIVE/HIVL and of MCC increased slightly. The percentage of patients treated with zidovudine until death decreased and that of patients whose treatment was terminated increased concomitantly. In 1989 and 1990, most patients whose treatment was terminated had MGC and HIVE/HIVL. In 1991 and 1992 this incidence decreased markedly, coinciding with the introduction of dideoxyinosine therapy. Conclusion: Zidovudine treatment significantly reduces the occurence of productive HIV infection of the brain in AIDS. Discontinuing zidovudine therapy may favour the occurrence of HIV encephalitis. Substitution therapy with dideoxyinosine also appears to protect against HIV-specific brain pathology.AIDS 01/1994; 8(4):489-494. DOI:10.1097/00002030-199404000-00011 · 6.56 Impact Factor