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Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland

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Summary

Neuropathological changes were studied in a consecutive autopsy series of 135 cases, comprising 73% of all patients who died of AIDS in Switzerland between April 1981 and December 1987. Central nervous system involvement was found in 119 patients (88%), 19 of which had multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, encephalitis due toToxoplasma gondii was most frequent and occurred in 35 patients (26%), followed by central nervous system infection withCryptococcus neoformans, which was found in five patients (4%). Cytomegalovirus (CMV) encephalitis was present in 14 patients (10%). Disseminated microglial nodules without morphological or immunocytochemical evidence of CMV was encountered in 18 patients (13%). However, in all but two of these patients there was evidence of extracerebral CMV infection, suggesting that CMV was responsible for these nodular encephalitides. Nine patients (7%) had progressive multifocal leukoencephalopathy (PML); in five of these, demyelination was associated with extensive tissue destruction and cyst formation. HIV-associated encephalopathy was observed in 21 patients (16%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 13 cases and characterized by diffuse pallor and gliosis of the cerebral and cerebellar white matter with scattered multinucleated giant cells, but without significant inflammatory response. MGCE was found in eight patients and characterized by clusters of numerous multinucleated giant cells, rod cells, macrophages, lymphocytic infiltrates and occasional necroses. In our view, PDL and MGCE represent the two opposite variants of HIV-induced encephalopathies, with overlapping intermediate manifestations.

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References

  1. Anders KH, Guerra WF, Tomiyasu U, Verity MA, Vinters HV (1986) The neuropathology of AIDS: UCLA experience and review. Am J Pathol 124:537–558

    Google Scholar 

  2. Budka H (1986) Multinucleated giant cells in brain: a hallmark of the acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 69:253–258

    Google Scholar 

  3. Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L (1987) Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 cases. Acta Neuropathol (Berl) 75:185–198

    Google Scholar 

  4. Bundesamt für Gesundheitswesen (1988) AIDS Information. Bulletin des Schweizerischen Bundesamtes für Gesundheitswesen 3:30

    Google Scholar 

  5. Carlstrom G (1965) Virologic studies on cytomegalic inclusion disease. Acta Paediatr Scand 54:17–23

    Google Scholar 

  6. Centers for Disease Control (1986) Classification system for human T-lymphotropic virus type/III/lymphadenopathy-associated virus infections. JAMA 256:20–25

    Google Scholar 

  7. Cheng-Mayer C, Seto D, Tateno M, Levy JA (1988) Biologic features of HIV-1 that correlate with virulence in the host. Science 240:80–82

    Google Scholar 

  8. Conley FK, Jenkins KA, Remington JS (1981)Toxoplasma gondii infection of the central nervous system: use of the peroxidase-antiperoxidase method to demonstrate toxoplasma in formalin-fixed, paraffin-embedded tissue sections. Hum Pathol 12:690–698

    Google Scholar 

  9. de la Monte SM, Ho DD, Schooley RT, Hirsch MS, Richardson EP (1987) Subacute encephalitis of AIDS and its relation to HTLV-III infection. Neurology 37:562–569

    Google Scholar 

  10. Epstein LG, Sharer LR, Cho E-S, Meyenhofer MF, Navia BA, Price RW (1985) HTLV-III/LAV-like retrovirus particles in the brains of patients with AIDS encephalopathy. AIDS Res 1:447–451

    Google Scholar 

  11. Feldman HA (1968) Toxoplasmosis. N Engl J Med 279: 1431–1437

    Google Scholar 

  12. Gabuzda DH, Ho DD, de la Monte SM, Hirsch MS, Rota TR, Sobel RA (1986) Immunocytochemical identification of HTLV-III antigen in the brains of patients with AIDS. Ann Neurol 20:289–295

    Google Scholar 

  13. Gonzales MF, Davis RL (1988) Neuropathology of acquired immunodeficiency syndrome. Neuropathol Appl Neurobiol 14:345–360

    Google Scholar 

  14. Gyorkey F, Melnick JL, Gyorkey P (1987) Human immuno-deficiency virus in brain biopsies of patients with AIDS and progressive encephalopathy. J Infect Dis 155:870–876

    Google Scholar 

  15. 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 cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 313:1493–1497

    Google Scholar 

  16. Hurwitz E (1965) Die Toxoplasmose in der Schweiz. Schweiz Med Wochenschr 95:77–83

    Google Scholar 

  17. Kato T, Hirano A, Llena JF, Dembitzer HM (1987) Neuropathology of acquired immune deficiency syndrome (AIDS) in 53 autopsy cases with particular emphasis on microglial nodules and multinucleated giant cells. Acta Neuropathol (Berl) 73:287–294

    Google Scholar 

  18. Kleihues P, Lang W, Burger PC, Budka H, Vogt M, Maurer R, Lüthy R, Siegenthaler W (1985) Progressive diffuse leukoencephalopathy in patients with acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 68:333–339

    Google Scholar 

  19. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS (1986) Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233:1089–1093

    Google Scholar 

  20. Koyanagi Y, Miles S, Mitsuyasu RT, Merrill JE, Vinters HV, Chen ISY (1987) Dual infection of the central nervous system by AIDS viruses with distinct cellular tropism. Science 236:819–822

    Google Scholar 

  21. Krech UH (1971) Epidemiology. In: Krech UH, Jung M, Jung F (eds) Cytomegalovirus infections in man. Karger, Basel, pp 26–32

    Google Scholar 

  22. Laskin OH, Stahl-Bayliss M, Morgello S (1987) Concomitant herpes simplex virus type 1 and cytomegalovirus ventriculoencephalitis in acquired immunodeficienct syndrome. Arch Neurol 44:843–847

    Google Scholar 

  23. Levy JA, Shimabukuro J, Hollander H, Miller J, Kaminsky L (1985) Isolation of AIDS-associated retrovirus from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet II:586–588

    Google Scholar 

  24. Levy RM, Bredesen DE, Rosenblum ML (1985) Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J Neurosurg 62:475–495

    Google Scholar 

  25. Luft BJ, Remington JS (1983) Toxoplasmosis. In: Hoeprich PD (ed) Infectious diseases, 3rd edn. Harper and Row, Philadelphia, pp 1133–1145

    Google Scholar 

  26. Luft BJ, Brooks RG, Conley FK, McCabe RE, Remington JS (1984) Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome. JAMA 252:913–917

    Google Scholar 

  27. Morgello S, Cho E-S, Nielsen S, Devinsky O, Petito CK (1987) Cytomegalovirus encephalitis in patients with acquired immunodeficiency syndrome: an autopsy study and review of the literature. Hum Pathol 18:289–297

    Google Scholar 

  28. Moskowitz LB, Gregorios JB, Hensley GT, Berger JR (1984) Cytomegalovirus-induced demyelination associated with acquired immune deficiency syndrome. Arch Pathol Lab Med 108:873–877

    Google Scholar 

  29. Moskowitz LB, Hensley GT, Chan JC, Gregorios J, Conley FK (1984) The neuropathology of acquired immune deficiency syndrome. Arch Pathol Lab Med 108:867–872

    Google Scholar 

  30. National Cancer Institute (1982) The Non-Hodgkin lymphoma pathology classification project: summary and description of a working formulation for clinical usage. Cancer 49:2112–2135

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  33. Navia BA, Petito CK, Gold JWM, Cho E-S, Jordan BD, Price RW (1986) Cerebral toxoplasmosis complicating the acquired immune deficiency syndrome: Clinical and neuropathological findings in 27 patients. Ann Neurol 19:224–238

    Google Scholar 

  34. Nielsen SL, Petito CK, Urmacher CD, Posner JB (1984) Subacute encephalitis in acquired immune deficiency syndrome: a postmortem study. Am J Clin Pathol 82:678–682

    Google Scholar 

  35. 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 312:874–879

    Google Scholar 

  36. Petito CK, Cho E-S, Lehmann W, Navia BA, Price RW (1986) Neuropathology of acquired immunodeficiency syndrome (AIDS): an autopsy review. J Neuropathol Exp Neurol 45:635–646

    Google Scholar 

  37. Price RW, Brew B, Sidtis S, Rosenblum M, Scheck AC, Cleary P (1988) The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586–592

    Google Scholar 

  38. Pumarola-Sune T, Navia BA, Cordon-Cardo C, Cho E-S, Price RW (1987) HIV antigen in the brains of patients with the AIDS dementia complex. Ann Neurol 21:490–496

    Google Scholar 

  39. Resnick L, diMarzo-Veronese F, Schüpbach J, Tourtelotte WW, Ho DD, Müller F, Shapshak P, Vogt M, Groopman JE, Markham PD, Gallo RC (1985) Intra-blood-brain-barrier synthesis of HTLV-III-specific IgG in patients with neurologic symptoms associated with AIDS or AIDS-related complex. N Engl J Med 313:1498–1503

    Google Scholar 

  40. Rosemberg S, Lopes MBS, Tsanaclis AM (1986) Neuropathology of acquired immunodeficiency syndrome (AIDS)-Analysis of 22 Brazilian cases. J Neurol Sci 76:187–198

    Google Scholar 

  41. Sharer LP, Epstein LG, Cho E-S, Joshi VV, Meyenhofer MF, Rankin LF, Petito CK (1986) Pathologic features of AIDS encephalopathy in children: evidence for LAV/HTLV-III infection of brain. Hum Pathol 17:271–284

    Google Scholar 

  42. Shaw GM, Harper ME, Hahn BH, Epstein LG, Gajdusek DC, Price RW, Navia BA, Petito CK, O'Hara CJ, Groopman JE, Cho E-S, Oleske JM, Wong-Staal F, Gallo RC (1985) HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science 227:177–182

    Google Scholar 

  43. Snider WD, Simpson DM, Nielsen S, Gold JWM, Metroka CE, Posner JB (1983) Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann Neurol 14:403–418

    Google Scholar 

  44. So YT, Beckstead JH, Davis RL (1986) Primary central nervous system lymphoma in acquired immune deficiency syndrome: a clinical and pathological study Ann Neurol 20:566–572

    Google Scholar 

  45. Sternberger L (1979) Immunocytochemistry, 2nd edn. Wiley, New York, pp 104–130

    Google Scholar 

  46. Stoler MH, Eskin TA, Benn S, Angerer RC, Angerer LM (1986) Human T-cell lymphotropic virus type III infection of the central nervous system. A preliminary in situ analysis. JAMA 256:2360–2364

    Google Scholar 

  47. Stoner GL, Ryschkewitsch C, Walker DL, deFWebster H (1986) JC papovavirus large tumor (T)-antigen expression in brain tissue of acquired immune deficiency syndrome (AIDS) and non-AIDS patients with progressive multifocal leukoencephalopathy. Proc Natl Acad Sci USA 83:2271–2275

    Google Scholar 

  48. Vazeux R, Brousse N, Jarry A, Henin D, Marche C, Vedrenne C, Mikol J, Wolff M, Michon C, Rozenbaum W, Bureau JF, Montagnier L, Brahic M (1987) AIDS subacute encephalitis. Identification of HIV-infected cells. Am J Pathol 126:403–410

    Google Scholar 

  49. Ward JM, O'Leary TJ, Baskin GB, Benveniste R, Harris CA, Nara PL, Rhodes RH (1987) Immunohistochemical localization of human and simian immunodeficiency viral antigens in fixed tissue sections. Am J Pathol 127:199–205

    Google Scholar 

  50. WHO collaborating centre on AIDS (1987) AIDS surveillance in Europe. WHO report 13:1–25

    Google Scholar 

  51. Wiley CA, Schrier RD, Denaro FJ, Nelson JA, Lampert PW (1986) Localization of cytomegalovirus proteins and genome during fulminant central nervous system infection in an AIDS patient. J Neuropathol Exp Neurol 45:127–139

    Google Scholar 

  52. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MBA (1986) Cellular localization of LAV/HTLV-III/ARV infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 830:7089–7093

    Google Scholar 

  53. Wiley CA, Grafe M, Kennedy C, Nelson JA (1988) HIV and JC virus in AIDS patients with progressive multifocal leukoencephalopathy. Acta Neuropathol 76:338–346

    Google Scholar 

  54. Wong B, Gold JWM, Brown, AE, Lange M, Fried R, Grieco M, Milvan D, Giron J, Tapper ML, Lerner CW, Armstrong D (1984) Central nervous system toxoplasmosis in homosexual men and parenteral drug abusers. Ann Int Med 100:36–42

    Google Scholar 

  55. Ziegler JL, Beckstead JA, Volberding PA, Abrams DI, Levine AM, Lukes RJ, Gill PS, Burkes RL, Meyer PR, Metroka CE, Mouradian J, Moore A, Riggs SA, Butler JJ, Cabanillas FC, Hersh E, Newell GR, Laubenstein LJ, Knowles D, Odajnyk C, Raphael B, Koziner B, Urmacher C, Clarkson BD (1984) Non-Hodgkin's lymphoma in 90 homosexual men: relation to generalized lymphadenopathy and the acquired immune deficiency syndrome. N Engl J Med 311:565–570

    Google Scholar 

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Lang, W., Miklossy, J., Deruaz, J.P. et al. Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland. Acta Neuropathol 77, 379–390 (1989). https://doi.org/10.1007/BF00687372

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