Page 177 - AIDSBK23C

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demonstrated to contain HIV antigen and multinucleated giant cells are difficult to
find.[389,747]

MICROGLIAL NODULES.-- Microglial nodules may be seen in both grey and white
matter. About half of AIDS cases at autopsy will show these small focal areas, and there is a
propensity for these lesions to involve the brainstem, though they can be seen anywhere.
Microglial nodules are collections of cells, thought to arise from glial cells, that are mixed with
inflammatory cells, including plump reactive astrocytes and lymphocytes, though a variety of
inflammatory cell types may be present. They are often located near small capillaries that may
have plump endothelial cells with nearby hemosiderin-laden macrophages. Sometimes the
macrophages can give rise to multinucleated cells up to 25 microns in diameter with irregular
nuclei and scant cytoplasm. Most of the astroglial cells in the nodules have round to oblong
nuclei with scant cytoplasm. Small foci of necrosis may be seen in or near these nodules.
Microglial nodules are not specific for HIV infection and may be present with neoplasia,
traumatic focal necrosis, or infection from viral, protozoal or bacterial organisms.[756] HIV
and/or other infectious agents may be found. Specific etiologic agents in microglial nodules
demonstrated in routine tissue sections with hematoxylin-eosin staining most often include
cytomegalovirus and Toxoplasma gondii. Some microglial nodules have cells with
immunoreactivity for HIV by immunohistochemical staining. In a few cases, no infectious agent
can be demonstrated. Microglial nodules may be found in persons with asymptomatic HIV
infection as well as patients with AIDS at all stages.[761,763]

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY.-- Progressive
multifocal leukoencephalopathy (PML) results from human polyomavirus infection (designated
JC virus) affecting primarily the white matter of the brain. PML is seen most frequently in
patients with AIDS, though it also occurs in other immune compromised patients. PML is
diagnosed in about 5% of AIDS patients at autopsy.[758] Typical clinical findings may include
focal neurologic deficits, hemiparesis, cognitive impairment, dysarthria, gait imbalance,
headache, limb dystaxia, hemianopsia, cortical blindness, and seizures. Cerebrospinal fluid
analysis is typically normal, though some patients may have mild protein elevations along with
mononuclear cell pleocytosis. Oligoclonal bands may be found as well. Diagnosis can be
established definitively by brain biopsy, but less invasive techniques include PCR to detect JC
virus DNA in CSF or in blood.[764,765]
Computerized tomographic imaging studies show asymmetric focal zones of low
attenuation that involve the periventricular and subcortical white matter, compared with more
symmetric areas seen in HIV encephalopathy. There is no hemorrhage or mass effect. The
lesions tend to progress in number, size and lowered density over weeks to months. Magnetic
resonance imaging (MRI) scans are more sensitive than CT for detection of small PML lesions,
with extensive asymmetric white matter high signal areas on T2 (and low signal on T1) with
sparing of cortical grey matter. The involvement of the “U” fibers creates a sharp border with
the cortex. Lesions can be unilateral, bilateral, single, or multiple.[738,752]
Oligodendrocytes are targeted by the virus, leading to focal areas of white matter
granularity a few millimeters in size that may coalesce. Abnormalities of white matter range
from pallor to demyelination to necrosis. The grey-white matter junction is typically involved,
and adjacent cortical grey matter may be involved. White matter tracts in cerebellum, brain