Page 175 - AIDSBK23C

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subcortical U fibers. In contrast, lesions of opportunistic infections are more likely to be focal
and have a mass effect. In children, calcifications of the basal ganglia can be seen with
computed tomographic (CT) scans. The degree of cerebral atrophy may not correlate with the
severity of disease. White matter hyperintensities that are small and ill-defined are seen with
magnetic resonance imaging (MRI) scans, or attenuation can be seen on CT scans, and these
findings suggest that HIV leukoencephalopathy may be present. Other findings with MRI
include focal caudate nucleus atrophy and diffuse grey matter atrophy. Positron emission
tomography (PET) scans show subcortical hypermetabolism in the early stages of
ADC.[746,747,752]
Gross examination of the brain and spinal cord at autopsy rarely reveals specific lesions
with ADC. Subcortical lesions are most prominent in lobar white matter and deep gray nuclei
such as the thalamus, and atrophy can be mild to marked, with hydrocephalus ex vacuo.
Therefore, multiple areas must be sampled for histologic examination.[746]
Microscopic findings with ADC may demonstrate increased macrophages and
multinucleated giant cells. Diffuse myelin pallor may also be seen. However, up to half of
patients with a history of ADC may have no histopathologic findings.[745,746] Areas of active
HIV encephalitis contain abundant HIV RNA and DNA localized to macrophages and microglia,
but not neurons. Areas with minimal or no inflammation have minimal proviral HIV.[753]
The differential diagnosis for ADC depends upon many factors. Injection drug users may
have infarcts from previous bouts of endocarditis with embolization of thrombi. Patients with
bacterial infections may show a purulent meningitis or localized vasculitis producing
hemorrhage. Cryptococcosis may also produce meningitis. Toxoplasmosis may produce
abscesses. However, lesions from most opportunistic agents are subtle in appearance and may be
characterized only by focal demyelination or hemorrhage. Malignant lymphomas can present as
mass lesions that are grey to white, but they may also be diffuse or metastasize within the
ventricles or along the meninges.[745]
The onset and severity of ADC may be increased with drugs of abuse, including cocaine,
marijuana, and methamphetamine. Exposure to most drugs of abuse can increase brain levels of
dopamine, which has been implicated in the pathogenesis of HIV-associated neurologic damage.
HIV-infected macrophages and microglial cells within the CNS leads to release of HIV proteins
such as gp120 and Tat that can bind to and impair dopamine transporter functions, leading to
elevated levels of dopamine in the dopaminergic synapses in the early asymptomatic stage of
HIV infection. Use of cocaine and methamphetamine further increases synaptic levels of
dopamine. The synaptic dopamine can diffuse out and activate microglia through binding to
dopamine receptors. The activation of microglia may result in increased HIV replication as well
as increased production of inflammatory cytokines including tumor necrosis factor-alpha. The
combination of increased viral load and cytokine release can cause apoptosis of dopaminergic
neurons, leading to a dopamine deficit that may exacerbate ADC.[754]
No specific therapy is available for ADC. However, antiretroviral therapy has been
shown to be effective in delaying onset or even restoring cognitive function. Patients treated
with antiretroviral therapy are less likely to develop ADC and have fewer CNS lesions at
autopsy. Since ADC is more common in the late stages of AIDS, survival from the time of
diagnosis may be limited.[745,746] The N-methyl-D-aspartate receptor antagonist memantine
may help protect against excitotoxic injury.[747]
Other CNS lesions may demonstrate a specific opportunistic infectious agent or neoplasm
associated with AIDS, while others may result from immunologic or hypersensitivity phenomena