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HIV infection and
neurological complications of AIDS
AIDS is now the fourth leading cause of death in the world, according
to figures released by WHO. Despite the introduction of antiretroviral
medications, the epidemics remain out of control and in many countries,
AIDS constitutes a major public health problem. UNAIDS estimates that
new infections by HIV are increasing by at least 6 million each year.
Involvement of the central and peripheral nervous systems are frequent
and associated with neurological disorders such as dementia, neuropathy
and opportunistic infections.
Our Studies
- HIV dementia
Of all neurological complications of AIDS, perhaps the most feared and
debilitating is HIV dementia (HIV-D). This unique, dementing illness,
recognized soon after the initial description of AIDS, has been referred
to variously as subacute encephalitis, AIDS dementia complex, HIV encephalopathy
and HIV-associated major cognitive/motor disorder. The essential features
of HIV-D are disabling cognitive impairment, usually accompanied by
motor dysfunction, and behavioral changes. Cognitive impairment has
been estimated to occur in approximately 30% of people with advanced
AIDS and frank dementia in 15% to 20%. HIV-D has major impact on quality
of life, and is clearly predictive of poor survival. Our research focuses
on the role of immune mediated mechanisms and neuroglia dysfunction
in the pathogenesis of HIV-D.
- HIV neuropathy
With recent declines in the incidence rates of HIV-associated dementia
and CNS opportunistic infections, sensory neuropathies (HIV-SN) have
become the mos common neurological disorders associated with AIDS. These
include distal sensory polyneuropathy (DSP) and antiretroviral toxic
neuropathy (ATN) and affect up to 30% of patients with advanced HIV
disease. The most prominent symptom is pain in the feet, but the underlying
pathophysiological mechanisms remain undefined. HIV-SN is associated
with distal degeneration of long axons. This pattern is often termed
"dying back," a term which implies that the distal regions of fibers
degenerate first, with centripetal progression. Pathological changes
in the dorsal root ganglia (DRG) have been also described in patients
with HIV-N. Whether HIV infection occurs in DRG neurons remains controversial.
The most consistent pathology in the DRG, however, appears to be perineuronal
inflammation which leads to damage to DRG neurons. Our own preliminary
data have demonstrated a reduction of DRG neurons and significant infiltration
by CD68+ and CD14+ macrophages. The presence of proinflammatory cytokines
including TNF-α, IFN-γ, IL-6, and nitric oxide, have consistently
been demonstrated in DRG's in AIDS. We suggest that this aberrant inflammatory
response plays a critical role in damaging or sensitizing DRG neurons,
and axons, and subsequently affecting the inputs to central pain pathways.
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