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Neuronal density in the superior frontal and temporal gyri does not correlate with the degree of human immunodeficiency virus-associated dementia

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Abstract

Human immune deficiency virus (HIV) disease may be associated, neuropathologically, with significant neuronal loss and clinically with a severe dementia. However, the significance of neuronal loss in the development of dementia has not been established. In this study we have undertaken a stereological determination of the neuronal numerical density and neuronal volumes in post mortem tissue from the superior frontal and superior temporal gyri in 32 patients who died of acquired immune deficiency syndrome (AIDS). All were prospectively clinically characterized, with dementia identified or excluded, and antiretroviral medication documented. This study combines morphometric techniques with prospective clinical assessment of dementia. As previously demonstrated, all patients dying with AIDS showed neuronal loss, but this was not related to the presence of HIV-associated dementia.

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References

  1. American Academy of Neurology AIDS Taskforce (1991) Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Neurology 41: 778–785

    Google Scholar 

  2. Brenneman DE, Westbrook GL, Fitzgerald SP, Ennist DL, Elkins KL, Ruff MR, Pert CB (1988) Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive peptide. Nature 335: 639–642

    Google Scholar 

  3. Budka H, Wiley CA, Kleihues P, Artigas J, Asbury AK, Cho ES, Cornblath DR, Dal Canto MC, DeGirolami U, Dickson D, Epstein LG, Esiri MM, Giangaspero F, Gosztonyi G, Gray F, Griffin JW, Henin D, Iwasaki Y, Janssen RS, Johnson RT, Lantos PL, Lyman WD, McArthur JC, Nagashima K, Peress N, Petito CK, Price RW, Rhodes RH, Rosenblum M, Said G, Scaravilli F, Sharer LR, Vinters HV (1991) HIV-associated disease of the nervous system and proposal for neuropathology-based terminology. Brain Pathol 1: 143–152

    Google Scholar 

  4. Ciardi A, Sinclair E, Scaravilli F, Harcourt-Webster NJ, Lucas S (1990) The involvement of the cerebral cortex in human immunodeficiency virus encephalopathy: a morphological and immunohistochemical study. Acta Neuropathol 81: 51–59

    Google Scholar 

  5. Davies J, Everall I, Bell J, Esiri M, Lucas S, Harrison M, Scaravilli F, Lantos P (1993) Does azidothymidine after HIV-associated neuropathology. Clin Neuropathol 12: S9

  6. Dreyer EB, Kaiser PK, Offermann JT, Lipton SA (1990) HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 248: 364–367

    Google Scholar 

  7. Everall IP, Luthert PJ, Lantos PL (1991) Neuronal loss in the frontal cortex in HIV infection. Lancet 337: 1119–1121

    Google Scholar 

  8. Everall IP, Luthert PJ, Lantos PL (1993) Neuronal number and volume alterations in the neocortex in HIV-infected individuals. J Neurol Neurosurg Psychiatry 56: 481–486

    Google Scholar 

  9. Everall I, Barnes H, Spargo E, Lantos P (1993) Evidence for selective neuronal loss in the putamen in HIV-infected patients using spatial analysis. Clin Neuropathol 12: S10

  10. Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14: 60–67

    Google Scholar 

  11. Glass JD, Wesselingh SL, Selnes OA, McArthur JC (1993) Clinical-neuropathologic correlation in HIV associated dementia. Neurology 43: 2230–2237

    Google Scholar 

  12. Grauss F, Ribalta T, Abos J, Alom J, Cruz-Sanchez F, Mallolas J, Miro M, Cardesa A, Tolosa E (1990) Subacute cerebellar syndrome as the first manifestation of AIDS dementia complex. Acta Neurol Scand 81: 118–120

    Google Scholar 

  13. Gray F, Geny C, Dournon E, Fenelon G, Lionnet F, Gherardi R (1991) Neuropathological evidence that zidovudine reduces incidence of HIV infection of brain. Lancet 337: 852–853

    Google Scholar 

  14. Gundersen HJG (1986) Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson. J Microsc 143: 3–45

    Google Scholar 

  15. Gundersen HJG (1988) The nucleator. J Microsc 138: 291–310

    Google Scholar 

  16. Gundersen HJG, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, West MJ (1988) The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. Acta Pathol Microbiol Immunol Scand 96: 857–881

    Google Scholar 

  17. Heyes MP, Brew BJ, Martin A, Price RW, Salazar AM, Sidtis JJ, Yergey JA, Mourdain MM, Sadler AE, Kelip J, Rubinow D, Markey SP (1991) Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. Ann Neurol 29: 202–209

    Google Scholar 

  18. Hill JM, Mervis RF, Avidor R, Moody TW, Brenneman DE (1993) HIV envelope protein-induced neuronal damage and retardation of behavioural development in rat neonates. Brain Res 603: 222–233

    Google Scholar 

  19. Ketzler S, Weis S, Haug H, Budka H (1990) Loss of neurons in the frontal cortex in AIDS brains. Acta Neuropathol 80: 92–94

    Google Scholar 

  20. Lipton SA (1991) HIV-related neurotoxicity. Brain Pathol 1: 193–199

    Google Scholar 

  21. Maehlen J, Dunlop O, Dobloug JH, Liestol K, Torvik A (1993) Brain lesions in AIDS patients in Norway 1983–1992. Unexplained changes with time and opposing effects of length of survival and AZT treatment. Clin Neuropathol 12: S12

  22. Masliah E, Achim CL, Ge N, DeTeresa R, Terry RD, Wiley CA (1992) Spectrum of human immunodeficiency virus-associated neocortical damage. Ann Neurol 32: 321–329

    Google Scholar 

  23. Masliah E, Ge N, Achim CL, Hansen LA, Wiley CA (1992) Selective neuronal vulnerabiluty in HIV encephalitis. J Neuropathol Exp Neurol 51: 585–593

    Google Scholar 

  24. Masliah E, Ge N, Morey M, DeTeresa R, Terry RD, Wiley CA (1992) Cortical dendritic pathology in human immunodeficiency virus encephalitis. Lab Invest 66: 285–291

    Google Scholar 

  25. McArthur JC, Hoover DR, Bacellar H, Miller EN, Cohen BA, Becker JT, Graham NMH, McArthur JH, Selnes OA, Jacobsen LP, Visscher BR, Concha M, Saah A (1993) Dementia in AIDS patients. Neurology 43: 2245–2252

    Google Scholar 

  26. Merrill JE, Koyanagi JZ, Thomas L, Martin F, Chen ISY (1992) Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1. J Virol 66: 2217–2225

    Google Scholar 

  27. Navia BA, Jordan BD, Price RW (1986) The AIDS-dementia complex. I. Clinical features. Ann Neurol 19: 517–524

    Google Scholar 

  28. Navia BA, Cho E-S, Petito CK, Price RW (1986) The AIDS-dementia complex. II. Neuropathology. Ann Neurol 19: 525–535

    Google Scholar 

  29. Price RW, Brew BJ (1988) The AIDS dementia complex. J Infect Dis 158: 1079–1083

    Google Scholar 

  30. Pulliam L, Herndier BG, Tang NM, McGrath MS (1991) Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neutrochemical alterations in cultured human brains. J Clin Invest 87: 503–512

    Google Scholar 

  31. Reyes MG, Faraldi F, Senseng CS, Flowers C, Fariello R (1991) Nigral degeneration in acquired immune deficiency syndrome (AIDS). Acta Neuropathol 82: 39–44

    Google Scholar 

  32. Schmitt FA, Bigley JW, McKinnis R, Logue PE, Evans RW, Drucker JL (1988) Neuropsychological outcome of zidovudine (AZT) treatment of patients with AIDS and AIDS-related complex. N Engl J Med 319: 889–896

    Google Scholar 

  33. Seilhean D, Duyckaerts C, Vazeux R, Bolgert F, Brunet P, Katlama C, Gentilini M, Hauw J-J (1993) HIV-1-associated cognitive/motor complex. Neurology 43: 1492–1499

    Google Scholar 

  34. Sidtis JJ, Gatsonis C, Price RW, Singer EJ, Collier AC, Richman DD, Hirsch MJ, Schaerf FW, Fischl MA, Kieburtz K, Simpson D, Koch MA, Feinberg J, Dafni O (1993) Zidovudine treatment of the AIDS dementia complex: results of a placebo controlled trial. Ann Neurol 33: 343–349

    Google Scholar 

  35. Sterio DC (1984) The unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 134: 127–136

    Google Scholar 

  36. Swingler S, Easton A, Morris A (1992) Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells. AIDS Res Hum Retroviruses 8: 487–493

    Google Scholar 

  37. Tornatore C, Nath A, Amemiya K, Major EO (1991) Persistent human immunodeficiency virus type-1 infection in human fetal glial cells reactivated by T-cell factors or by cytokines tumor necrosis factor alpha and interleukin-1 beta. J Virol 65: 6094–6100

    Google Scholar 

  38. Tyor WR, Glass JD, Griffin JW, Becker SP, McArthur JC, Bezman L, Griffen DE (1992) Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol 31: 349–360

    Google Scholar 

  39. Weis S, Haug H, Budka H (1993) Neuronal damage in the cerebral cortex of AIDS brains: a morphometric study. Acta neuropathol 85: 185–189

    Google Scholar 

  40. Wiley CA, Masliah E, Morey M, Lemere C, DeTeresa R, Grafe M, Hansen L, Terry R (1991) Neocortocal damage during HIV infection. Ann Neurol 29: 651–657

    Google Scholar 

  41. Williams RW, Rakic P (1988) Three-dimensional counting: an accurate and direct method to estimate numbers of cells in sectioned material. J Comp Neurol 278: 344–352

    Google Scholar 

  42. Yarchoan R, Brouwers P, Spitzer AR, Grafman J, Safai B, Perno CF, Larson SM, Berg G, Fischl MA, Wichman A, Thoman RV, Brunetti A, Schmidt PJ, Myers CE, Broder S (1987) Response of human immunodeficiency virus associated neurological disease to 3‘-azido-3’-deoxythymidine. Lancet I: 132–135

    Google Scholar 

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Authors and Affiliations

  1. Department of Neuropathology, Institute of Psychiatry, DeCrespigny Park, SE5 8AF, London, UK

    Ian P. Everall, Edward Spargo & Peter Lantos

  2. Department of Pathology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, USA

    Jonathan D. Glass

  3. Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, USA

    Justin McArthur

  4. Department of Neuropathology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, USA

    Edward Spargo & Peter Lantos

Authors
  1. Ian P. Everall
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  2. Jonathan D. Glass
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  3. Justin McArthur
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  4. Edward Spargo
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  5. Peter Lantos
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Additional information

Supported by the Medical Research Council (I.P.E.) and the National Institutes of Health (NS 26643, AI3, RR00722). The work was carried out at the correspondence address

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Everall, I.P., Glass, J.D., McArthur, J. et al. Neuronal density in the superior frontal and temporal gyri does not correlate with the degree of human immunodeficiency virus-associated dementia. Acta Neuropathol 88, 538–544 (1994). https://doi.org/10.1007/BF00296490

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  • DOI: https://doi.org/10.1007/BF00296490

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