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as a result of HIV infection of CNS cells directly. Microglial and glial cell activation by HIV
infection can lead to cytokine production, oxidative stress, and resultant neuronal apoptosis. The
infection of monocyte/macrophage/microglial cells by HIV is the mechanism by which the
pathologic changes are mediated in the CNS.[755,756,757]

HIV ENCEPHALITIS.-- Microscopic examination of the brain at autopsy in AIDS may
reveal a subacute encephalitis consisting of multiple foci with mononuclear cells typical of small
macrophages, microglia, and multinucleated giant cells in 5 to 10% of cases.[758] These are
often seen near small blood vessels, most often in the basal ganglia, in deep cerebral white
matter, and brainstem. They appear less commonly scattered in the grey matter or
leptomeninges. The multinucleated giant cells are the hallmark of HIV infection involving the
CNS. HIV can be demonstrated in their cytoplasm. Thus, the central nervous system remains an
important reservoir for HIV infection, even with aggressive antiretroviral therapy.[304]
Sometimes multinucleated cells can be quite numerous. Cerebral atrophy with multinucleated
giant cells has been reported with HIV-associated subacute encephalitis in over 25% of AIDS
patients. In some cases of HIV encephalitis, multinucleated giant cells are not found, but large
amounts of HIV antigen may be found in macrophages and microglia.[755,756]
Radiologic MR imaging may show multiple sclerosis-like plaques from demyelination
and gliosis accompanying more florid HIV encephalitis. The white matter plaques are typically
nonenhancing, hypodense foci on CT imaging, compared with periventricular high signal areas
on T2 weighting and FLAIR MRI.[759]
Laboratory methods are available to aid in diagnosis of HIV encephalitis. In tissues,
immunohistochemical methods for detection of HIV with antibody to p24, gp41, or gp120 can be
performed.[760] The occurrence of HIV encephalitis appears to be unrelated to the stage of
AIDS. Perivascular or leptomeningeal lymphocytic infiltration may be seen even in persons with
asymptomatic HIV infection.[761] In cerebrospinal fluid samples, an increasing level of HIV-1
RNA correlates with the presence of HIV encephalitis, though plasma HIV-1 RNA levels may
not.[762]

HIV LEUKOENCEPHALOPATHY.-- HIV leukoencephalopathy may be seen in about
5% of AIDS patients at autopsy.[758] It produces diffuse bilateral damage to cerebral white
matter that can be seen on magnetic resonance imaging (MRI). Occasionally the cerebellum is
also involved. There is myelin loss involving mainly the deep white matter, with a tendency to
spare the subcortical U fibers and the more compact myelin bundles of corpus callosum, internal
capsules, optic radiations, and descending tracts in the brainstem. Grossly, the lesions are similar
to multiple sclerosis plaques. By light microscopy, the predominantly perivascular lesions
demonstrate myelin debris in macrophages, reactive astrocytosis, hemosiderin in macrophages,
multinucleated giant cells, and little or no inflammation. Vacuolar myelin swellings can appear,
as well as axonal damage. Oligodendroglial cells appear normal. Without the presence of
multinucleated giant cells, the diagnosis depends upon the finding of HIV antigen in
macrophages.[747]
The pathologic findings of HIV leukoencephalopathy and HIV encephalitis may overlap
in a third of cases. A multifocal pontine leukoencephalopathy may rarely be seen in AIDS
patients in which necrosis involves corticospinal tracts and crossing fibers. In one third of AIDS
patients with dementia, histologic findings are minimal.[755] Pediatric AIDS encephalopathy
(progressive neurologic disease) has similar findings, except that fewer cells can be