HIV neuropathy: Insights in the pathology of HIV peripheral nerve disease

HIV-associatecl neuropathies (HIV-N) have become the most frequent neurolog ical disorder associated with HIV infection. The most common forms of HIV-N are the distal sensory polyneuropathy (DSP) and antiretroviral toxic neuro pathies (ATN), disorders characterized mostly by sensory symptoms that incl ude spontaneous or evoked pain that follow a subacute or chronic course. Th e main pathological features that characterize DSP and ATN include "dying b ack" axonal degeneration of long axone in distal regions, loss of unmyelina ted fibers, and variable degree of macrophage infiltration in peripheral ne rves and dorsal root ganglia. Marked activation of macrophages as well as t he effect of proinflammatory cytokines appear to be the main immunopathogen ic factors in DSP. Interference with DNA synthesis and mitochondrial abnorm alities produced by nucleoside anti-retrovirals have been hypothesized as p athogenic factors involved in ATN. The use of skin biopsy has become a usef ul tool in the evaluation of HIV-N. Reduction in fiber density, increased f requency of fiber varicosities and fiber fragmentation are prominent featur es of skin biopsies from patients with HIV-N. Other forms of HIV-N include acute or chronic inflammatory polyneuropathies, uncommon disorders that may ocur during seroconversion or early stages of HIV infection. Opportunisiti c infections, mostly associated with cytomegalovirus or herpes tester virus infection occur in late stages of AIDS and produce characteristic clinical features such as mononeuritis multiple or radiculopathies.