Page 174 - AIDSBK23C

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predominantly subcortical brain involvement. These features include increasing forgetfulness,
difficulty with concentration, loss of libido, apathy, inertia, and waning interest in work and
hobbies. ADC is characterized by social withdrawal and a blunting of emotional responsiveness.
Short-term memory is impaired. Motor problems are often mild and include poor handwriting,
poor balance, gait difficulties, and a tendency to drop things easily. As the dementia progresses,
learning and memory deteriorate. There is a reduced output of spontaneous speech. Eventually,
late in the course of the disease there is global impairment with severe psychomotor retardation
and mutism.[746]
The neurologic examination is often normal early in the course of ADC. Focal
neurologic deficits are more likely to be found with CNS opportunistic infections. Subtle
findings can include impairments of raid eye and limb movements and diffuse hyperreflexia.
Progression of the disease results in an increased muscle tone, particularly of the lower
extremities. This is usually associated with tremor, clonus, frontal release signs, and hyperactive
reflexes. In some cases, myelopathy may be more severe than cognitive impairment. There can
be spastic paraparesis with variable sensory ataxia and bladder involvement. Retinal cotton-
wool spots may be found on funduscopy in 60% of cases. Generalized seizures may occur.[746]
Encephalopathy results from direct infection by HIV of microglial cells, monocytes, and
macrophages, which then produce indirect immunopathologic effects upon the CNS via release
of neurotoxins or elaboration of cytokines that promote inflammation and glial proliferation.
Neurons are not directly infected by HIV. Instead, cytokines and viral factors lead to neuronal
damage and dropout. The neurotoxin quinolinic acid is produced by macrophages. The highest
concentrations of HIV occur in basal ganglia, subcortical regions, and frontal cortex. There is
wide variability HIV genotype, viral production by macrophages, and toxin production in AIDS
patients, which may explain the variability in neuropathologic findings between individuals and
even between different areas of the brain in the same individual.[747,748]
Though the severity of AIDS dementia does not correlate with neuronal loss, viral load,
or CD4 cell count, dementia has a significant correlation with greater numbers of macrophages
present within the brain, but there is only a borderline correlation with the numbers of HIV-
infected cells (by immunohistochemical staining with antibody to gp41) in the brain.[747,749]
A possible mechanism of injury to the brain may result from increased nitric oxide (NO)
production. The presence of HIV has been shown to increase the amount of inducible nitric
oxide synthetase (ions) in cell cultures with macrophages and with astrocytes. The number of
astrocytes infected with HIV appears to be increased with HIV-associated dementia. A
prolonged, high-level production of NO may account for the neurologic damage seen in HIV-
infected persons.[750,751]
Examination of body fluids, including cerebrospinal fluid (CSF), reveals no specific
findings for ADC. The CSF is usually acellular or demonstrates a mild lymphocytic pleocytosis.
The total protein is elevated in about two thirds of cases. The IgG is increased in up to 80% of
cases. Oligoclonal bands may be found in the CSF in a third of cases, but the myelin basic
protein is usually not elevated. Although the levels of HIV-1 RNA in the CSF are not useful for
diagnosis of ADC, the levels are predictive of the severity of dementia when it is present. In
some cases, the HIV-1 RNA is high in the CSF even when the plasma level has been suppressed,
and this is known as “CNS escape.” This may be due to prolonged use of antiretroviral therapy,
poor compliance, and viral sequestration in the CNS.[746]
Radiologic features of ADC include diffuse cortical atrophy as well as periventricular and
deep white matter abnormalities, with confluent areas of high signal intensity and sparing of