Skip to main content
SpringerLink
Log in

Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 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

    Google Scholar 

  2. Baley RO, Baltch AL, Venkatesh R, Singh JK, Bishop MB (1988) Sensory motor neuropathy associated with AIDS. Neurology 38: 886–891

    Google Scholar 

  3. 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

    Google Scholar 

  4. 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

    Google Scholar 

  5. 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

    Google Scholar 

  6. Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38: 794–796

    Google Scholar 

  7. 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

    Google Scholar 

  8. 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

    Google Scholar 

  9. Eidelberg D, Sotrel A, Vogel H, Walker P, Kleenfield J, Crumpacker CS (1986) Progressive polyradiculopathy in acquired immune deficiency syndrome. Neurology 36: 912–916

    Google Scholar 

  10. Epstein LG, Gendelman HE (1993) Human immunodeficiency virus type 1 infection of the nervous system: pathogenetic mechanism. Ann Neurol 33: 429–436

    Google Scholar 

  11. 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

    Google Scholar 

  12. Fuller GN, Jacobs JM, Guilloff RJ (1989) Association of painful peripheral neuropathy in AIDS with cytomegalovirus infection. Lancet 21: 937–941

    Google Scholar 

  13. Fuller GN, Jacobs JM, Guiloff RJ (1990) Axonal atrophy in the painful peripheral neuropathy in AIDS. Acta Neuropathol 81: 198–203

    Google Scholar 

  14. Fuller GN, Jacobs JM, Guilloff RJ (1993) Nature and incidence of peripheral nerve syndromes in HIV infection. J Neurol Neurosurg Psychiatry 56: 372–381

    Google Scholar 

  15. 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

    Google Scholar 

  16. 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

    Google Scholar 

  17. Griffin JW, George R, Ho T (1993) Macrophage systems in peripheral nerves. A review. J Neuropathol Exp Neurol 52: 553–560

    Google Scholar 

  18. 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

    Google Scholar 

  19. 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

    Google Scholar 

  20. Morgello S, Simpson DM (1994) Multifocal cytomegalovirus demyelinative polyneuropathy associated with AIDS. Muscle Nerve 17: 176–182

    Google Scholar 

  21. 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

    Google Scholar 

  22. 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

    Google Scholar 

  23. 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

    Google Scholar 

  24. 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

    Google Scholar 

  25. 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

    Google Scholar 

  26. 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

    Google Scholar 

  27. 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

    Google Scholar 

  28. 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

    Google Scholar 

  29. 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

    Google Scholar 

  30. 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

    Google Scholar 

  31. 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

    Google Scholar 

  32. 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

    Google Scholar 

  33. 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

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurological and Visual Sciences, Section of Neurology, University of Verona, Verona, Italy

    Nicolo Rizzuto, Tiziana Cavallaro, Salvatore Monaco, Michela Morbin, Bruno Bonetti, Sergio Ferrari, Sandra Galiazzo-Rizzuto, Giampietro Zanette & Laura Bertolasi

  2. Section of Neurology, Department of Neurological and Visual Sciences, University of Verona, Policlinico di Borgo Roma, 1-37134, Verona, Italy

    Nicolo Rizzuto

Authors
  1. Nicolo Rizzuto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiziana Cavallaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Salvatore Monaco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michela Morbin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bruno Bonetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sergio Ferrari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sandra Galiazzo-Rizzuto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giampietro Zanette
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Laura Bertolasi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00296507

Key words

Search

Navigation