CEREBRAL WHITE-MATTER CHANGES IN ACQUIRED-IMMUNODEFICIENCY-SYNDROME DEMENTIA - ALTERATIONS OF THE BLOOD-BRAIN-BARRIER

The cause of acquired immunodeficiency syndrome (AIDS) dementia, which is a frequent late manifestation of human immunodeficiency virus (HIV ) infection, is unknown but radiological and pathological studies have implicated alterations in subcortical white matter. To investigate th e pathological basis of these white matter abnormalities, we performed an immunocytochemical and histological analysis of subcortical white matter from AIDS patients with and without dementia, from pre-AIDS pat ients (asymptomatic HIV-seropositive patients), and from HIV-seronegat ive control subjects. Reduced intensity of Luxol fast blue staining, d esignated ''diffuse myelin pallor,'' was detected in 8 of 15 AIDS deme ntia patients, 3 of 13 AIDS nondemented patients, and none of the pre- AIDS patients (n = 2) or control subjects (n = 9). In contrast to Luxo l fast blue staining, sections stained immunocytochemically for myelin proteins did not show decreased staining intensities in regions of di ffuse myelin pallor. In addition, neither demyelinated axons nor activ e demyelination were detected in light and electron micrographs of sub cortical white matter from brains of patients with AIDS dementia. An i ncrease in the number of perivascular macrophages and hypertrophy of a strocytes and microglia occurred in brain sections from HIV-infected p atients. These changes were not specific to dementia or regions of dif fuse myelin pallor and they occurred in both gray and white matter. In contrast to the lack of myelin pathology in AIDS dementia brains, sig nificant accumulations of serum proteins in white matter glia were det ected in the brains of 12 of 12 patients with AIDS dementia and 6 of 1 2 AIDS patients without dementia. Serum protein-immunopositive cortica l neurons were detected in the frontal cortex of 11 of 12 patients wit h AIDS dementia and 3 of 12 nondemented AIDS patients. Seronegative co ntrol subjects showed minimal serum protein immunoreactivity in both c ortex and white matter. We conclude therefore that alterations in the blood-brain barrier and not demyelination contribute to the developmen t of AIDS dementia.