ROLE OF HIV IN THE PATHOGENESIS OF DISTAL SYMMETRICAL PERIPHERAL NEUROPATHY

We report the results of a clinical, electrophysiological and patholog ical study conducted in 18 AIDS patients presenting a distal symmetric al predominantly sensory polyneuropathy (DSPN) characterized by painfu l dysesthesias as main complaint. Onset of the neuropathy was at CDC ( Center for Disease Control) stage II in 2 patients, at CDC stage III i n 5 patients and at CDC stage IV in the remainder. Electrophysiologica l investigation confirmed the presence of-an axonal alteration in the sensory nerves, but also revealed motor involvement in all cases. The neuropathological features of sensory nerves were fiber loss and axona l degeneration with macrophagic activation. The expression of monocyte -macrophage markers and of major histocompatibily complex class II ant igens appeared up-regulated in endoneurial ramified cells, while expre ssion of CR3, a complement receptor involved in the process of phagocy tosis, was down-regulated. In six nerve biopsy samples and in two out of five DSPN dorsal root ganglia we found HIV-related mRNA and protein located in scattered cells of the endoneurium which we presume to be macrophages. These data suggest that: (a) DSPN may occur early in the course of the disease and is not limited to later stages; (b) DSPN is not a ganglionitis but is actually a sensory-motor neuropathy; (c) the virus enters the peripheral nervous system and induces changes in the immunocompetent cell population with activation of macrophages. Stora ge of the virus inside macrophages may act both as a reservoir for the virus and as a putative cause of nerve damage, probably through relea se of cytotoxins and/or interaction with trophic factors.