Acta Neuropathologica

, Volume 78, Issue 5, pp 497–503

Vacuolar myelopathy with multinucleated giant cells in the acquired immune deficiency syndrome (AIDS)

Light and electron microscopic distribution of human immunodeficiency virus (HIV) antigens
  • H. Maier
  • H. Budka
  • H. Lassmann
  • P. Pohl
Regular Papers


Vacuolar myelopathy (VM) is a frequent neurological complication of the acquired immune deficiency syndrome (AIDS). A suspected connection between VM and human immunodeficiency virus (HIV) has been based only on HIV isolation from affected spinal cord tissue. We report here an AIDS patient dying after 14 months of progressive dementia, including 3 months of spinal signs and symptoms. At autopsy, the brain revealed moderate diffuse damage of the white matter compatible with HIV-induced progressive diffuse leukoencephalopathy. The spinal cord showed VM mainly in the lateral and the posterior columns. Mono- and multinucleated macrophages were localized within intramyelinic and periaxonal vacuoles. Light and electron microscopic immunocytochemistry revealed the presence of HIV antigens restricted to mono- and multinucleated macrophages within the spongy lesions. Productive HIV infection is documented for the first time within VM lesions of this case. Therefore, VM should be included among HIV-induced lesions of the central nervous system. The intimate relation of infected macrophages to vacuolar myelinopathy could suggest secretion of a myelinotoxic factor by macrophages productively infected by HIV. Immune electron microscopy appears as promising tool to detect HIV in tissue even when the density of virus may be low.

Key words

Acquired immune deficiency syndrome (AIDS) Human immunodeficiency virus (HIV) Immunocytochemistry Vacuolar myelopathy Demyelination 


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  1. 1.
    Anders KH, Guerra WF, Tomiyasu U, Verity MA, Vinters HV (1986) The neuropathology of AIDS. UCLA experience and review. Am J Pathol 124:537–558Google Scholar
  2. 2.
    Budka H (1986) Multinucleated giant cells in brain: a hall-mark of the acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 69:253–258Google Scholar
  3. 3.
    Budka H (1989) Human immunodeficiency virus (HIV)-induced disease of the central nervous system: pathology and implications for pathogenesis. Acta Neuropathol (Berl) 77:225–236Google Scholar
  4. 4.
    Budka H (1989) CNS distribution of human immunodeficiency virus (HIV) antigens in AIDS. J Neuropathol Exp Neurol 48:384 [abstr]Google Scholar
  5. 5.
    Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L (1987) Brain pathology induced by infections with the human immunodeficiency virus (HIV). Acta Neuropathol (Berl) 75:185–198Google Scholar
  6. 6.
    Budka H, Maier H, Pohl P (1988) Human immunodeficiency virus in vacuolar myelopathy of the acquired immune deficiency syndrome (letter). N Engl J Med 319:1667–1668Google Scholar
  7. 7.
    Goldstick L, Mandybur TI, Bode R (1985) Spinal cord degeneration in AIDS. Neurology 35:103–106Google Scholar
  8. 8.
    Gray F, Gherardi R, Keohane C, Favolini M, Sobel A, Poirier J (1988) Pathology of the central nervous system in 40 cases of the acquired immune deficiency syndrome (AIDS). Neuropathol Appl Neurobiol 14:365–380Google Scholar
  9. 9.
    Gray F, Gherardi R, Scaravilli F (1988) The neuropathology of the acquired immune deficiency syndrome (AIDS). A review. Brain 111:245–266Google Scholar
  10. 10.
    Ho DD, Rota TR, Schooley RT, Kaplan JC, Allan JD, Groopman JE, Resnick L, Felsenstein D, Andrews CA, Hirsch M (1985) Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 311:1493–1497Google Scholar
  11. 11.
    Kleihues P, Lang W, Burger PC, Budka H, Vogt M, Maurer R, Lüthy R, Siegenthaler W (1985) Progressive diffuse leucoencephalopathy in patients with acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 68:333–339Google Scholar
  12. 12.
    Monte SM de la, Moore T, Hedley-Whyte ET (1986) Vacuolar encephalopathy of AIDS. N Engl J Med 315:1549–1550Google Scholar
  13. 13.
    Monte SM de la, Ho DD, Schooley RT, Hirsch MS, Richardson EP Jr (1987) Subacute encephalomyelitis of AIDS and its relation to HTLV-III infection. Neurology 37:562–569Google Scholar
  14. 14.
    Navia BA, Jordan BD, Price RW (1986) The AIDS dementia complex. I. Clinical features. Ann Neurol 19:517–524Google Scholar
  15. 15.
    Navia BA, Cho E-S, Petito CK, Price RW (1986) The AIDS dementia complex. II. Neuropathology. Ann Neurol 19:525–535Google Scholar
  16. 16.
    Petito CK, Navia BA, Cho E-S, Jordan BD, George DC, Price RW (1985) Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. N Engl J Med 312:874–879Google Scholar
  17. 17.
    Petito CK, Cho E-S, Lemann W, Navia BA, Price RW (1986) Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review. J Neuropathol Exp Neurol 45:635–646Google Scholar
  18. 18.
    Popovic M, Sarngadharan MG, Read E, Gallo RC (1984) Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497–500Google Scholar
  19. 19.
    Price RW, Sidtis JJ, Navia BA, Pumarola-Sune T, Ornitz DB (1986) The AIDS dementia complex. In: Rosenblum ML, Levy RM, Bredesen DE (eds) AIDS and the nervous system. Raven Press, New York, pp 203–219Google Scholar
  20. 20.
    Schmidbauer M, Budka H, Ambros P (1988) Comparison of in situ DNA hybridization (ISH) and immunocytochemistry for diagnosis of herpes simplex virus (HSV) encephalitis in tissue. Virchows Arch [A] 414:39–43Google Scholar
  21. 21.
    Selmaj KW, Raine CS (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 23:339–346Google Scholar
  22. 22.
    Sharer LR, Epstein LG, Cho E-S, Petito CK (1986) HTLV-III and vacuolar myelopathy. N Engl J Med 315:62–63Google Scholar
  23. 23.
    Smith KJ, Hall SM (1988) Peripheral demyelination and remyelination initiated by the calcium-selective ionophore ionomycin: in vivo observations. J Neurol Sci 83:37–53Google Scholar
  24. 24.
    Vanguri P, Shin MI (1988) Hydrolysis of myelin basic protein in human myelin sheaths by terminal complement complexes. J Biol Chem 263:7228–7234Google Scholar
  25. 25.
    Vass K, Lassmann H, Wekerle H, Wisniewski HM (1986) The distribution of Ia antigen in the lesions of rat acute experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 70:149–160Google Scholar
  26. 26.
    Westland K, Pollard JD (1988) Proteinase-induced demyelination. An electrophysiological and histological study. J Neurol Sci 82:41–54Google Scholar

Copyright information

© Springer-Verlag GmbH & Co. KG 1989

Authors and Affiliations

  • H. Maier
    • 1
    • 2
  • H. Budka
    • 2
  • H. Lassmann
    • 2
  • P. Pohl
    • 3
  1. 1.Institut für PathologieUniversität InnsbruckInnsbruckAustria
  2. 2.Neurologisches InstitutUniversität WienWienAustria
  3. 3.Neurologische UniversitätsklinikInnsbruckAustria

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