Abstract
We report the results of a clinical, electrophysiological and pathological study conducted in 18 AIDS patients presenting a distal symmetrical predominantly sensory polyneuropathy (DSPN) characterized by painful dysesthesias as main complaint. Onset of the neuropathy was at CDC (Center for Disease Control) stage II in 2 patients, at CDC stage III in 5 patients and at CDC stage IV in the remainder. Electrophysiological 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 axonal degeneration with macrophagic activation. The expression of monocyte-macrophage markers and of major histocompatibily complex class II antigens appeared up-regulated in endoneurial ramified cells, while expression of CR3, a complement receptor involved in the process of phagocytosis, 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. Storage of the virus inside macrophages may act both as a reservoir for the virus and as a putative cause of nerve damage, probably through release of cytotoxins and/or interaction with trophic factors.
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Accolla RS, Sekali RP, McDonald AP (1982) Demonstration at single cell level of the existence of distinct clusters of epitopes in two predefined human Ia molecular subsets. Eur J Immunol 12: 166–173
Baley RO, Baltch AL, Venkatesh R, Singh JK, Bishop MB (1988) Sensory motor neuropathy associated with AIDS. Neurology 38: 886–891
Bonetti B, Monaco S, Giannini C, Ferrari S, Zanusso GL, Rizzuto N (1993) Human peripheral nerve macrophages in normal and pathological conditions. J Neurol Sci 118: 158–168
Cavallaro T, Martone RL, Dwork AJ, Schon EA, Herbert J (1990) The retinal pigment epithelium is the unique site of transthyretin synthesis in the rat eye. Invest Ophthalmol Vis Sci 81: 497–501
Chaunu MP, Ratinahirana H, Raphael M, Henin D, Leport C, Brun-Vezinet F, Leger JM, Brunet P, Hauw JJ (1989) The spectrum of changes on 20 nerve biopsies in patients with HIV infection. Muscle Nerve 12: 452–459
Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38: 794–796
Cornford ME, Ho HW, Vinters HV (1992) Correlation of neuromuscular pathology in acquired immune deficiency syndrome patients with cytomegalovirus infection and zidovudine treatment. Acta Neuropathol 84: 516–529
Dickson DW, Mattiace LA, Kure K, Hutchins K, Lyman WD, Brosnan CF (1991) Microglia in human disease, with an emphasis on acquired immune deficiency syndrome. Lab Invest 64: 135–156
Eidelberg D, Sotrel A, Vogel H, Walker P, Kleenfield J, Crumpacker CS (1986) Progressive polyradiculopathy in acquired immune deficiency syndrome. Neurology 36: 912–916
Epstein LG, Gendelman HE (1993) Human immunodeficiency virus type 1 infection of the nervous system: pathogenetic mechanism. Ann Neurol 33: 429–436
Esiri MM, Morris CS, Millard PR (1993) Sensory and sympathetic ganglia in HIV-1 infection: immunocytochemical demonstration of HIV-1 viral antigens, increased MHC class II antigen expression and mild reactive inflammation. J Neurol Sci 114: 178–187
Fuller GN, Jacobs JM, Guilloff RJ (1989) Association of painful peripheral neuropathy in AIDS with cytomegalovirus infection. Lancet 21: 937–941
Fuller GN, Jacobs JM, Guiloff RJ (1990) Axonal atrophy in the painful peripheral neuropathy in AIDS. Acta Neuropathol 81: 198–203
Fuller GN, Jacobs JM, Guilloff RJ (1993) Nature and incidence of peripheral nerve syndromes in HIV infection. J Neurol Neurosurg Psychiatry 56: 372–381
Gherardi R, Lebargy F, Gaulard P, Mhiri C, Bernaurdin JF, Gray F (1989) Necrotizing vasculitis and HIV replication in peripheral nerve (letter). N Engl J Med 321: 685–686
Gibbels E, Diederich (1988) Human immunodeficiency virus (HIV)-related chronic relapsing inflammatory demyelinating polyneuropathy with multifocal unusual onion bulbs in sural nerve biopsy. Acta Neuropathol (Berl) 75: 529–534
Griffin JW, George R, Ho T (1993) Macrophage systems in peripheral nerves. A review. J Neuropathol Exp Neurol 52: 553–560
Ho DD, Rota TR, Schooley RT, Kaplan JC, Allan JD, Groopman JE, Resnick L, Felsenstein D, Andrews CA, Hirsch MS (1985) Isolation of HTLV-III from cerebral fluid and neuronal tissue of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 313: 1493–1497
Mah V, Vartavarian LM, Akers MA, Vinters HV (1988) Abnormalities of peripheral nerve in patients with human immunodeficiency virus infection. Ann Neurol 24: 713–717
Morgello S, Simpson DM (1994) Multifocal cytomegalovirus demyelinative polyneuropathy associated with AIDS. Muscle Nerve 17: 176–182
Nelson AJ, Fleckenstein B, Jahn G, Galloway DA, McDougall JK (1984) Structure of the transforming region of humean cytomegalovirus AD169. J Virol 49: 109–115
Peudenier S, Hery C, Montagnier L, Tardieu M (1991) Human microglial cells: characterization in cerebral tissue and in primary culture, and study of their susceptibility to HIV-1 infection. Ann Neurol 29: 152–161
Rance NE, McArthur JC, Cornblath DR, Landstrom DL, Griffin JW, Price DL (1988) Gracile tract degeneration in patients with sensory neuropathy and AIDS. Neurology 38: 265–271
Ratner L, Haseltine W, Patraca R, Livak KJ, Starcich B, Josephs SF, Doron ER, Ratalski JA, Whitehorn EA, Baumeister K, Ivanoff L, Petteway SR Jr, Pearson ML, Lautenberger JH, Papas TS, Ghrayeb J, Chand NT, Gallo RC, Wong-Staal F (1985) Complete nucleotide sequence of the AIDS virus. HTLV-III. Nature 313: 277–284
Sabourin JC, Florea-Strat A, Gray F, Gherardi RK (1994) Cytokines expression in the nerve of patients with various HIV-associated peripheral neuropathies (abstract). Brain Pathol 4: 486
Said G, Lacroix P, Chemouilli P, Goulon-Goeau C, Roullet E, Penaud D, Broucker T de, Maduri G, Vincent D, Torchet M, Vittcoq D, Leport C, Vilde JL (1991) Cytomegalovirus neuropathy in acquired immunodeficiency syndrome: a clinical and pathological study. Ann Neurol 29: 139–146
Scaravilli F, Sinclair E, Arango JC, Manji H, Lucas S, Harrison MJG (1992) The pathology of the posterior root ganglia in AIDS and its relationship to the pallor of the gracile tract. Acta Neuropathol 84: 163–170
So YT, Holtzman DM, Abrams DI, Olney RK (1988) Peripheral neuropathy associated with acquired immunodeficiency syndrome. Prevalence and clinical features from a population-based survey. Arch Neurol 45: 495–498
Soelder BM, Reisinger EC, Koefler D, Bitterlich G, Wacther H, Dierich MP (1989) Complement receptors: another port of entry for HIV (letter). Lancet II: 271–272
Sommer C, Schroder JM (1995) HLA-DR expression in peripheral neuropathies: the role of Schwann cells, resident and hematogenous macrophages, and endoneurial fibroblasts. Acta Neuropathol 89: 63–71
Tyor WR, Glass JD, Baumrind N, McArthur JC, Griffin JW, Becker PS, Griffin DE (1993) Cytokines expression of macrophages in HIV-1-associated vacuolar myelopathy. Neurology 43: 1002–1009
Vital A, Beylot M, Vital C, Delors B, Bloch B Julien J (1992) Morphological findings on peripheral nerve biopsies in 15 patients with human immunodeficiency virus infection. Acta Neuropathol 83: 618–623
Wesselingh SL, Power C, Glass JD, Tyor WR, McArthur JC, Farber JM, Griffin JW, Griffin DE (1993) Intracerebral cytokines messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann Neurol 33: 576–582
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Rizzuto, N., Cavallaro, T., Monaco, S. et al. Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy. Acta Neuropathol 90, 244–250 (1995). https://doi.org/10.1007/BF00296507
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DOI: https://doi.org/10.1007/BF00296507