FREQUENCY AND TOPOGRAPHICAL DISTRIBUTION OF CD68-POSITIVE MACROPHAGESAND HIV-1 CORE PROTEINS IN HIV-ASSOCIATED BRAIN-LESIONS

We report the neuropathological and immunohistochemical findings in th e brains of 14 AIDS patients with HIV-related encephalopathy. Clinical ly, half of the patients presented with severe AIDS dementia complex i ncluding advanced psychomotor retardation and behavioural dysfunction. These features correlated with striking cerebral atrophy and subcorti cal lesions visible in CT and/or MRI scans. In 7 cases early signs of impaired memory and concentration and/or psychomotor slowing were appa rent accompanied by subcortical lesions in MRI scans and normal CCTs. In order to investigate the topographical distribution of HIV-1-associ ated features, in every case tissue samples from the frontal, temporal , parietal, occipital cortex and subcortical white matter, the hippoca mpus, basal ganglia, midbrain, pons, medulla oblongata and cerebellum were studied. In all patients histological examination disclosed the t ypical cellular constituents of HIV encephalitis (n = 12) or leukoence phalopathy (n = 2). Antibodies against lymphocyte subsets, CD68 antige n, myelin basic protein and GFAP were used to characterize the phenoty pe of cells and to highlight the white matter gliosis. The distributio n and degree of pathological features were analysed in a semiquantitat ive scale, based on the number of CD68-positive cells, and disclosed g reat interindividual differences concerning the affected brain regions which only in part correlated with the severity of the clinical pictu re. It is noteworthy, that the deep gray matter, in particular putamen and thalamus, was involved in every case, independant from the stage of the disease. In addition, quantity and topographical distribution o f HIV-1 core protein p24 were studied by use of two monoclonal antibod ies. It is noteworthy, that the number of immunoreactive multinucleate d giant cells and microglial cells decreased gradually from the deep g ray matter, especially putamen and thalamus, and deep white matter to corpus callosum, cerebellar white matter and subcortical cerebral whit e matter. The topographical predilection of the deep gray matter even in cases with early cognitive decline indicates that the basal ganglia are affected early in the course of the disease. This observation clo sely resembles the results of highly sensitive quantitative neuropsych ological tests which disclosed slowing and impaired coordination of ra pid extremity movements indicating basal ganglia lesions even in early stages of HIV dementia.