Acta Neuropathologica

, Volume 77, Issue 4, pp 379–390 | Cite as

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

  • W. Lang
  • J. Miklossy
  • J. P. Deruaz
  • G. P. Pizzolato
  • A. Probst
  • T. Schaffner
  • E. Gessaga
  • P. Kleihues
Regular Papers


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.

Key words

Acquired immune deficiency syndrome (AIDS) Neuropathology HIV encephalopathy Opportunistic infections 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  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 hallmark of the acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 69:253–258Google Scholar
  3. 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) 75:185–198Google Scholar
  4. 4.
    Bundesamt für Gesundheitswesen (1988) AIDS Information. Bulletin des Schweizerischen Bundesamtes für Gesundheitswesen 3:30Google Scholar
  5. 5.
    Carlstrom G (1965) Virologic studies on cytomegalic inclusion disease. Acta Paediatr Scand 54:17–23Google Scholar
  6. 6.
    Centers for Disease Control (1986) Classification system for human T-lymphotropic virus type/III/lymphadenopathy-associated virus infections. JAMA 256:20–25Google Scholar
  7. 7.
    Cheng-Mayer C, Seto D, Tateno M, Levy JA (1988) Biologic features of HIV-1 that correlate with virulence in the host. Science 240:80–82Google Scholar
  8. 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 12:690–698Google Scholar
  9. 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 37:562–569Google Scholar
  10. 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 1:447–451Google Scholar
  11. 11.
    Feldman HA (1968) Toxoplasmosis. N Engl J Med 279: 1431–1437Google Scholar
  12. 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 20:289–295Google Scholar
  13. 13.
    Gonzales MF, Davis RL (1988) Neuropathology of acquired immunodeficiency syndrome. Neuropathol Appl Neurobiol 14:345–360Google Scholar
  14. 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 155:870–876Google Scholar
  15. 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 313:1493–1497Google Scholar
  16. 16.
    Hurwitz E (1965) Die Toxoplasmose in der Schweiz. Schweiz Med Wochenschr 95:77–83Google Scholar
  17. 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) 73:287–294Google Scholar
  18. 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) 68:333–339Google Scholar
  19. 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 233:1089–1093Google Scholar
  20. 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 236:819–822Google Scholar
  21. 21.
    Krech UH (1971) Epidemiology. In: Krech UH, Jung M, Jung F (eds) Cytomegalovirus infections in man. Karger, Basel, pp 26–32Google Scholar
  22. 22.
    Laskin OH, Stahl-Bayliss M, Morgello S (1987) Concomitant herpes simplex virus type 1 and cytomegalovirus ventriculoencephalitis in acquired immunodeficienct syndrome. Arch Neurol 44:843–847Google Scholar
  23. 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:586–588Google Scholar
  24. 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 62:475–495Google Scholar
  25. 25.
    Luft BJ, Remington JS (1983) Toxoplasmosis. In: Hoeprich PD (ed) Infectious diseases, 3rd edn. Harper and Row, Philadelphia, pp 1133–1145Google Scholar
  26. 26.
    Luft BJ, Brooks RG, Conley FK, McCabe RE, Remington JS (1984) Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome. JAMA 252:913–917Google Scholar
  27. 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 18:289–297Google Scholar
  28. 28.
    Moskowitz LB, Gregorios JB, Hensley GT, Berger JR (1984) Cytomegalovirus-induced demyelination associated with acquired immune deficiency syndrome. Arch Pathol Lab Med 108:873–877Google Scholar
  29. 29.
    Moskowitz LB, Hensley GT, Chan JC, Gregorios J, Conley FK (1984) The neuropathology of acquired immune deficiency syndrome. Arch Pathol Lab Med 108:867–872Google Scholar
  30. 30.
    National Cancer Institute (1982) The Non-Hodgkin lymphoma pathology classification project: summary and description of a working formulation for clinical usage. Cancer 49:2112–2135Google Scholar
  31. 31.
    Navia BA, Cho E-S, Petito CK, Price RW (1986) The AIDS dementia complex: II. Neuropathology. Ann Neurol 19:525–535Google Scholar
  32. 32.
    Navia BA, Jordan BD, Price RW (1986) The AIDS dementia complex: I. Clinical features. Ann Neurol 19:517–524Google Scholar
  33. 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 19:224–238Google Scholar
  34. 34.
    Nielsen SL, Petito CK, Urmacher CD, Posner JB (1984) Subacute encephalitis in acquired immune deficiency syndrome: a postmortem study. Am J Clin Pathol 82:678–682Google Scholar
  35. 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 312:874–879Google Scholar
  36. 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 45:635–646Google Scholar
  37. 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 239:586–592Google Scholar
  38. 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 21:490–496Google Scholar
  39. 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 313:1498–1503Google Scholar
  40. 40.
    Rosemberg S, Lopes MBS, Tsanaclis AM (1986) Neuropathology of acquired immunodeficiency syndrome (AIDS)-Analysis of 22 Brazilian cases. J Neurol Sci 76:187–198Google Scholar
  41. 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 17:271–284Google Scholar
  42. 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 227:177–182Google Scholar
  43. 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 14:403–418Google Scholar
  44. 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 20:566–572Google Scholar
  45. 45.
    Sternberger L (1979) Immunocytochemistry, 2nd edn. Wiley, New York, pp 104–130Google Scholar
  46. 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 256:2360–2364Google Scholar
  47. 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 83:2271–2275Google Scholar
  48. 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 126:403–410Google Scholar
  49. 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 127:199–205Google Scholar
  50. 50.
    WHO collaborating centre on AIDS (1987) AIDS surveillance in Europe. WHO report 13:1–25Google Scholar
  51. 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 45:127–139Google Scholar
  52. 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 830:7089–7093Google Scholar
  53. 53.
    Wiley CA, Grafe M, Kennedy C, Nelson JA (1988) HIV and JC virus in AIDS patients with progressive multifocal leukoencephalopathy. Acta Neuropathol 76:338–346Google Scholar
  54. 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 100:36–42Google Scholar
  55. 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 311:565–570Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • W. Lang
    • 1
  • J. Miklossy
    • 2
  • J. P. Deruaz
    • 2
  • G. P. Pizzolato
    • 3
  • A. Probst
    • 4
  • T. Schaffner
    • 5
  • E. Gessaga
    • 6
  • P. Kleihues
    • 1
  1. 1.Division of Neuropathology, Institute of PathologyUniversity of ZürichZürichSwitzerland
  2. 2.Division de NeuropathologieCentre Hospitalier Universitaire VaudoisLausanneSwitzerland
  3. 3.Unité de NeuropathologieCentre Medical UniversitaireGenèveSwitzerland
  4. 4.Division of Neuropathology, Institute of PathologyUniversity of BaselBaselSwitzerland
  5. 5.Institute of PathologyUniversity of BernBernSwitzerland
  6. 6.Institute of PathologyKantonsspital AarauAarauSwitzerland

Personalised recommendations