Central nervous system virion detection in acute measles: histopathological, ultrastructural and pathogenetic aspects

Lancellotti, C.L.P.; Corbett, C.E.P.; Duarte, M.I.S.

doi:10.1590/S0036-46651995000200008

Abstracts

Histopathological and ultrastructural studies of 23 patients who died with clinical diagnosis of measles were carried out. In 12 cases viral nucleocapsids were searched by electron microscopy and detected in 100% of the cases in the lungs and in 50% of the cases in the central nervous system. They were mostly intranuclear. Histopathological changes associated to neurological alterations and the detection of virion are discussed in relation to acute and delayed clinical manifestations.

Measles; Virus; Central Nervous System; Pathology; Ultrastructure; Pathogenesis

Foram realizados estudos histopatológicos e ultraestruturais de 23 pacientes que morreram com diagnóstico clínico de sarampo. Presença de nucleo-capsides virais foi pesquisada em 12 casos e detectada em 50% destes casos no SNC. Eram, na maioria dos casos, intranucleares. As alterações histopatológicas associadas a manifestações neurológicas e à detecção do vírus são discutidas em relação às manifestações clínicas agudas e tardias.

VIROLOGY

Central nervous system virion detection in acute measles: histopathological, ultrastructural and pathogenetic aspects

Detecção de partículas virais no SNC no sarampo agudo: aspectos histopatológicos, ultraestruturais e patogenéticos

C.L.P. Lancellotti^I; C.E.P. Corbett^II; M.I.S. Duarte^II

^IInst. Infect. of Emilio Ribas and Faculty of Medical Science of Santa Casa of São Paulo - São Paulo, S. P., Brazil

^IILab. Path. Infect. Dis. - Univ. of São Paulo Medical School - São Paulo, S. P., Brazil

^{Correspondence to} Correspondence to: Prof. Dr. Carlos Eduardo Pereira Corbett Faculdade de Medicina da Universidade de São Paulo Av. Dr. Arnaldo, 455 - 1º andar - sala 26 01246-903 São Paulo, SP, Brasil

SUMMARY

Histopathological and ultrastructural studies of 23 patients who died with clinical diagnosis of measles were carried out. In 12 cases viral nucleocapsids were searched by electron microscopy and detected in 100% of the cases in the lungs and in 50% of the cases in the central nervous system. They were mostly intranuclear. Histopathological changes associated to neurological alterations and the detection of virion are discussed in relation to acute and delayed clinical manifestations.

Keywords: Measles; Virus; Central Nervous System; Pathology; Ultrastructure; Pathogenesis.

RESUMO

Foram realizados estudos histopatológicos e ultraestruturais de 23 pacientes que morreram com diagnóstico clínico de sarampo. Presença de nucleo-capsides virais foi pesquisada em 12 casos e detectada em 50% destes casos no SNC. Eram, na maioria dos casos, intranucleares. As alterações histopatológicas associadas a manifestações neurológicas e à detecção do vírus são discutidas em relação às manifestações clínicas agudas e tardias.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

ACKNOWLEDGEMENTS

We are grateful to Helio Correa, Shizie Fukasawa and Carla Pagliari for technical assistance, Maria Daisi de Morais for secretarial help and Marcio Carlos Baptista for the photography work. We thank Dr. H.F. Andrade Jr. for statistical analysis.

Recebido para publicação em 17/12/1993.

Aceito para publicação em 22/2/1995.

1. AARLI, J.A. - The immune system and the nervous system. J. Neurol. (Berl.), 229: 137-154, 1983.
2. ADAMS, J.M.; BAIRD, C. & FILLOY, L. - Inclusion bodies in measles encephalitis. J. Amer. med. Ass., 195: 290-298, 1966.
3. ANDERSON, J.R. - Viral encephalitis and its pathology. Curr. Top. Path., 76: 23-60, 1988.
4. BACZKO, K.; LIEBERT, U.G.; CATTANEO, R. et al. - Restriction of measles virus gene expression in measles inclusion body encephalitis. J. infect. Dis., 158: 144-150, 1988.
5. BROWN, H.R.; GOLLER, N.L.; THORMAR, H. et al. - Measles virus matrix protein gene expression in a subacute sclerosing panen-cephalitis patient brain and virus isolated demonstrated by cDNA hybridization and immunocytochemistry. Acta neuropath. (Berl.), 75: 123-130, 1987.
6. BUDKA, H.; LASSMAN, H. & POPOW-KRAUPP, Th. - Measles virus antigen in panencephalitis. An immunomorphological study. Stressing dendritic involvement in SSPE. Acta neuropath. (Berl.), 56: 52-62, 1982.
7. CERVOS-NAVARRO, J.; KANNUKI, S. & NAKAGAWA, Y. - Blood-Brain-Barrier (BBB). Review from morphological aspect. Histol. Histopath., 3: 203-213, 1988.
8. CHOPPIN, P.W. - Measles virus and chronic neurological diseases. Ann. Neurol., 9: 17-20, 1980.
9. DACHY, A. & THIRY, L. - Les affections neurologiques en rapport avec la rougeole. Considerations virologiques et immunologiques. Acta. paediat. belg., 24: 171-194, 1970.
10. FOURNIER, J.G.; PRIVATE, A. & BOUTEILLE, M. - Structural changes in the cell nucleus during measles virus infection in cerebellar explants. J. Ultrastruct. Res., 77: 319-328, 1981.
11. GENDELMAN, H.E.; WOLINSKY, J.S.; JOHNSON, R.J. et al. - Measles encephalitis: lack of evidence of viral invasion of the central nervous system and quantitative study of the nature of demyelination. Ann. Neurol., 15: 353-360, 1984.
12. GHADIALLY, F.N. - Ultrastructural pathology of the cell and matrix. London, Butterworths, 1982. p. 108-109.
13. GIBBS, F.A. & ROSENTHAL, I.M. - Eletroencephalographic in natural and attenuated measles. Amer. J. Dis. Child., 103: 395-400, 1962.
14. HAASE, A.T.; SWOVELAND, P.; STOWRING, L. et al. - Measles virus genome in infections of the central nervous system. J. infect. Dis., 144: 154-160, 1981.
15. HANKINS, R.W. & BLACK, F.L. - Western blot analysis measles virus antibody in normal persons and in patients with multiple sclerosis, subacute sclerosing panencephalitis, or atypical measles. J. clin. Microbiol., 24: 324-329, 1986.
16. HANNINEN, P.; ARSTILA, P.; LANG, H.; SALMI, A. & PANELIUS, M. - Involvement of the central nervous system in acute uncomplicated measles virus infection. J. clin. Microbiol., 11: 610- 613, 1980.
17. JOHNSON, R.T. - Viruses and chronic neurological diseases. Johns Hopk. med. J., 150: 132-140, 1982.
18. JOHNSON, R.T. - The pathogenesis of acute viral encephalitis and postinfectious encephalomyelitis. J. infect. Dis., 155: 359-365, 1987.
19. JOHNSON, R.T.; HIRSCH, R.L.; GRIFFIN, D.E. & WOLINSKY, J.S. - Clinical and immunological studies of measles encephalitis. Trans. Amer. Neurol. Ass., 106: 42-45, 1981.
20. JOHNSON, R.T.; GRIFFIN, D.E.; HIRSCH, R. & VAIBERG, A. - Measles encephalitis. Clin. exp. Neurol., 19: 13-16, 1983.
21. JOHNSON, R.T.; GRIFFIN, D.E.; HIRSCH, R.L. et al. - Measles encephalomyelitis - clinical and immunologic studies. New Engl. J. Med., 310: 137-141, 1984.
22. JOHNSON, R.T.; GRIFFIN, D.E. & MOENCH, T.R. - Pathogenesis of measles immunodeficiency and encephalomyelitis: parallels to AIDS. Microb. Pathogenesis, 4: 169-174, 1988.
23. LANCELLOTTI, C.L.P. & ROSEMBERG, S. - As complicaçőes neurológicas pelo vírus do sarampo. Pediatria (S. Paulo), 6: 10-12, 1984.
24. LEBON, P. - Virus de la rougeole et systčme nerveux central. Ann. Pédiat., 34: 555-559, 1987.
25. LYON, G. - Viral encephalitis in children. Acta paediat. belg., 34: 143-150, 1981.
26. MALAMUD, N. - Encephalomyelitis complicating measles. Arch. Neurol. Psychiat. (Chic), 38: 1025-1038, 1937.
27. MALAMUD, N. - Sequelae of postmeasles encephalomyelitis: clinicopathologic study. Arch. Neurol. Psychiat. (Chic), 41: 943-954, 1939.
28. MEHTA, P.D.; PATRICK, B.A.; SOBCZYK, W. et al. - Immuno-globulin G subclass antibodies to measles virus in patients with subacute sclerosing panencephalitis or multiple sclerosis. J. clin. Microbiol., 27: 62-65, 1989.
29. MEULEN, V. ter; KATZ, M. & MULLER, D. - Subacute sclerosing panencephalitis: a review. Curr. Top. Microbiol. Immunol., 57: 1-38, 1972.
30. MEULEN, V. ter; MULLER, D.; KACKELLI, Y.; KATZ, M. & MYERMANN, R. - Isolation of infectious measles virus in measles encephalitis. Lancet, 2: 1172-1175, 1972a.
31. MEULEN, V. ter & HALL, W.W. - Slow virus infections of the nervous system: virological, immunological and pathogenetic considerations. J. gen. Virol., 41: 1-25, 1978.
32. MEULEN, V. ter & CARTER, M.J. - Measles virus persistency and disease. Progr. med. Virol., 30: 44-61, 1984.
33. MICCO, C. de & TOGA, M. - Le statut immunitaire du systéme nerveux central. Rev. neurol., 144: 776-788, 1988.
34. MICHENER, R.C. & HENLEY, W.L. - Focal convulsions associated with subclinical measles infection. Clin. Pediat. (Phila.), 22: 643-649, 1983.
35. MILLER, H.G.; STANTON, J.D. & GIBBONS, J.L. - Parainfectious encephalomyelitis and related syndromes. Quart. J. Med., 25: 427-505, 1956.
36. MOENCH, T.R.; GRIFFIN, D.E.; OBRIECHT, C.R.; VAISBERG, A.J. & JOHNSON, R.T. - Acute measles in patients with and without neurological involvement: distribution of measles virus antigen and RNA. J. infect. Dis., 58: 433-442, 1988.
37. NAKAI, M. & IMAGAWA, D.T. - Electron microscopy of measles virus replication. J. Virol., 3: 187-197, 1969.
38. OHUCHI, M.; CHUCHI, R.; MIFUNE, K.; ISHIHARA, T. & OGAWA, T. - Characterization of the measles virus isolated from the brain of a patient with immunosuppressive measles encephalitis. J. infect. Dis., 156: 436-441, 1987.
39. OJALA, A. - On changes in the cerebrospinal fluid during measles. Ann. Med. intern. Fenn., 36: 321-331, 1947.
40. OYANAGI, S.; MEULEN, V. ter; KATZ, M. & KOPROWSKI, H. - Comparison of subacute sclerosing panencephalitis and measles virus: an electron microscope study. J. Virol., 7: 176-187, 1971.
41. REINICKE, V.; MORDHORST, C.H. & INGERSLEV, N. - Central nervous system affection in connection with "ordinary" measles. Scand. J. infect. Dis., 6: 131-135, 1974.
42. RUSSELL, W.C. - Paramyxovirus and Morbillivirus infections and their relationship to neurological disease. Progr. Brain Res., 59: 113-132, 1983.
43. SCHADLICH, H.J.; KARENBERG, A.; NEKIC, M. & FELGENHAUER, K. - Acute encephalitis with intrathecal synthesis of measles antibodies. J. Neuroimmunol. (Amst.), 20: 171-172, 1988.
44. SCHADLICH, H.J.; KARENBERG, A.; NEKIC, M. & FELGENHAUER, K. - Acute encephalitis with intrathecal synthesis of measles antibodies. J. Neurol. (Berl.), 235: 248-251, 1988a.
45. WECHSLER, S.L. & MEISSNER, H.C. - Measles and SSPE viruses: similarities and differences. Progr. med. Virol., 28: 65-95, 1982.
46. WILD, T.F. - Measles virus and chronic infections. Path. et Biol., 29: 429-433, 1981.

Correspondence to:

Prof. Dr. Carlos Eduardo Pereira Corbett

Faculdade de Medicina da Universidade de São Paulo

Av. Dr. Arnaldo, 455 - 1º andar - sala 26

01246-903 São Paulo, SP, Brasil

Publication Dates

Publication in this collection
22 Feb 2007
Date of issue
Apr 1995

History

Accepted
22 Feb 1995
Received
17 Dec 1993

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. AARLI, J.A. - The immune system and the nervous system. J. Neurol. (Berl.), 229: 137-154, 1983.

[2] 2. ADAMS, J.M.; BAIRD, C. & FILLOY, L. - Inclusion bodies in measles encephalitis. J. Amer. med. Ass., 195: 290-298, 1966.

[3] 3. ANDERSON, J.R. - Viral encephalitis and its pathology. Curr. Top. Path., 76: 23-60, 1988.

[4] 4. BACZKO, K.; LIEBERT, U.G.; CATTANEO, R. et al. - Restriction of measles virus gene expression in measles inclusion body encephalitis. J. infect. Dis., 158: 144-150, 1988.

[5] 5. BROWN, H.R.; GOLLER, N.L.; THORMAR, H. et al. - Measles virus matrix protein gene expression in a subacute sclerosing panen-cephalitis patient brain and virus isolated demonstrated by cDNA hybridization and immunocytochemistry. Acta neuropath. (Berl.), 75: 123-130, 1987.

[6] 6. BUDKA, H.; LASSMAN, H. & POPOW-KRAUPP, Th. - Measles virus antigen in panencephalitis. An immunomorphological study. Stressing dendritic involvement in SSPE. Acta neuropath. (Berl.), 56: 52-62, 1982.

[7] 7. CERVOS-NAVARRO, J.; KANNUKI, S. & NAKAGAWA, Y. - Blood-Brain-Barrier (BBB). Review from morphological aspect. Histol. Histopath., 3: 203-213, 1988.

[8] 8. CHOPPIN, P.W. - Measles virus and chronic neurological diseases. Ann. Neurol., 9: 17-20, 1980.

[9] 9. DACHY, A. & THIRY, L. - Les affections neurologiques en rapport avec la rougeole. Considerations virologiques et immunologiques. Acta. paediat. belg., 24: 171-194, 1970.

[10] 10. FOURNIER, J.G.; PRIVATE, A. & BOUTEILLE, M. - Structural changes in the cell nucleus during measles virus infection in cerebellar explants. J. Ultrastruct. Res., 77: 319-328, 1981.

[11] 11. GENDELMAN, H.E.; WOLINSKY, J.S.; JOHNSON, R.J. et al. - Measles encephalitis: lack of evidence of viral invasion of the central nervous system and quantitative study of the nature of demyelination. Ann. Neurol., 15: 353-360, 1984.

[12] 12. GHADIALLY, F.N. - Ultrastructural pathology of the cell and matrix. London, Butterworths, 1982. p. 108-109.

[13] 13. GIBBS, F.A. & ROSENTHAL, I.M. - Eletroencephalographic in natural and attenuated measles. Amer. J. Dis. Child., 103: 395-400, 1962.

[14] 14. HAASE, A.T.; SWOVELAND, P.; STOWRING, L. et al. - Measles virus genome in infections of the central nervous system. J. infect. Dis., 144: 154-160, 1981.

[15] 15. HANKINS, R.W. & BLACK, F.L. - Western blot analysis measles virus antibody in normal persons and in patients with multiple sclerosis, subacute sclerosing panencephalitis, or atypical measles. J. clin. Microbiol., 24: 324-329, 1986.

[16] 16. HANNINEN, P.; ARSTILA, P.; LANG, H.; SALMI, A. & PANELIUS, M. - Involvement of the central nervous system in acute uncomplicated measles virus infection. J. clin. Microbiol., 11: 610- 613, 1980.

[17] 17. JOHNSON, R.T. - Viruses and chronic neurological diseases. Johns Hopk. med. J., 150: 132-140, 1982.

[18] 18. JOHNSON, R.T. - The pathogenesis of acute viral encephalitis and postinfectious encephalomyelitis. J. infect. Dis., 155: 359-365, 1987.

[19] 19. JOHNSON, R.T.; HIRSCH, R.L.; GRIFFIN, D.E. & WOLINSKY, J.S. - Clinical and immunological studies of measles encephalitis. Trans. Amer. Neurol. Ass., 106: 42-45, 1981.

[20] 20. JOHNSON, R.T.; GRIFFIN, D.E.; HIRSCH, R. & VAIBERG, A. - Measles encephalitis. Clin. exp. Neurol., 19: 13-16, 1983.

[21] 21. JOHNSON, R.T.; GRIFFIN, D.E.; HIRSCH, R.L. et al. - Measles encephalomyelitis - clinical and immunologic studies. New Engl. J. Med., 310: 137-141, 1984.

[22] 22. JOHNSON, R.T.; GRIFFIN, D.E. & MOENCH, T.R. - Pathogenesis of measles immunodeficiency and encephalomyelitis: parallels to AIDS. Microb. Pathogenesis, 4: 169-174, 1988.

[23] 23. LANCELLOTTI, C.L.P. & ROSEMBERG, S. - As complicaçőes neurológicas pelo vírus do sarampo. Pediatria (S. Paulo), 6: 10-12, 1984.

[24] 24. LEBON, P. - Virus de la rougeole et systčme nerveux central. Ann. Pédiat., 34: 555-559, 1987.

[25] 25. LYON, G. - Viral encephalitis in children. Acta paediat. belg., 34: 143-150, 1981.

[26] 26. MALAMUD, N. - Encephalomyelitis complicating measles. Arch. Neurol. Psychiat. (Chic), 38: 1025-1038, 1937.

[27] 27. MALAMUD, N. - Sequelae of postmeasles encephalomyelitis: clinicopathologic study. Arch. Neurol. Psychiat. (Chic), 41: 943-954, 1939.

[28] 28. MEHTA, P.D.; PATRICK, B.A.; SOBCZYK, W. et al. - Immuno-globulin G subclass antibodies to measles virus in patients with subacute sclerosing panencephalitis or multiple sclerosis. J. clin. Microbiol., 27: 62-65, 1989.

[29] 29. MEULEN, V. ter; KATZ, M. & MULLER, D. - Subacute sclerosing panencephalitis: a review. Curr. Top. Microbiol. Immunol., 57: 1-38, 1972.

[30] 30. MEULEN, V. ter; MULLER, D.; KACKELLI, Y.; KATZ, M. & MYERMANN, R. - Isolation of infectious measles virus in measles encephalitis. Lancet, 2: 1172-1175, 1972a.

[31] 31. MEULEN, V. ter & HALL, W.W. - Slow virus infections of the nervous system: virological, immunological and pathogenetic considerations. J. gen. Virol., 41: 1-25, 1978.

[32] 32. MEULEN, V. ter & CARTER, M.J. - Measles virus persistency and disease. Progr. med. Virol., 30: 44-61, 1984.

[33] 33. MICCO, C. de & TOGA, M. - Le statut immunitaire du systéme nerveux central. Rev. neurol., 144: 776-788, 1988.

[34] 34. MICHENER, R.C. & HENLEY, W.L. - Focal convulsions associated with subclinical measles infection. Clin. Pediat. (Phila.), 22: 643-649, 1983.

[35] 35. MILLER, H.G.; STANTON, J.D. & GIBBONS, J.L. - Parainfectious encephalomyelitis and related syndromes. Quart. J. Med., 25: 427-505, 1956.

[36] 36. MOENCH, T.R.; GRIFFIN, D.E.; OBRIECHT, C.R.; VAISBERG, A.J. & JOHNSON, R.T. - Acute measles in patients with and without neurological involvement: distribution of measles virus antigen and RNA. J. infect. Dis., 58: 433-442, 1988.

[37] 37. NAKAI, M. & IMAGAWA, D.T. - Electron microscopy of measles virus replication. J. Virol., 3: 187-197, 1969.

[38] 38. OHUCHI, M.; CHUCHI, R.; MIFUNE, K.; ISHIHARA, T. & OGAWA, T. - Characterization of the measles virus isolated from the brain of a patient with immunosuppressive measles encephalitis. J. infect. Dis., 156: 436-441, 1987.

[39] 39. OJALA, A. - On changes in the cerebrospinal fluid during measles. Ann. Med. intern. Fenn., 36: 321-331, 1947.

[40] 40. OYANAGI, S.; MEULEN, V. ter; KATZ, M. & KOPROWSKI, H. - Comparison of subacute sclerosing panencephalitis and measles virus: an electron microscope study. J. Virol., 7: 176-187, 1971.

[41] 41. REINICKE, V.; MORDHORST, C.H. & INGERSLEV, N. - Central nervous system affection in connection with "ordinary" measles. Scand. J. infect. Dis., 6: 131-135, 1974.

[42] 42. RUSSELL, W.C. - Paramyxovirus and Morbillivirus infections and their relationship to neurological disease. Progr. Brain Res., 59: 113-132, 1983.

[43] 43. SCHADLICH, H.J.; KARENBERG, A.; NEKIC, M. & FELGENHAUER, K. - Acute encephalitis with intrathecal synthesis of measles antibodies. J. Neuroimmunol. (Amst.), 20: 171-172, 1988.

[44] 44. SCHADLICH, H.J.; KARENBERG, A.; NEKIC, M. & FELGENHAUER, K. - Acute encephalitis with intrathecal synthesis of measles antibodies. J. Neurol. (Berl.), 235: 248-251, 1988a.

[45] 45. WECHSLER, S.L. & MEISSNER, H.C. - Measles and SSPE viruses: similarities and differences. Progr. med. Virol., 28: 65-95, 1982.

[46] 46. WILD, T.F. - Measles virus and chronic infections. Path. et Biol., 29: 429-433, 1981.