Herpetic brainstem encephalitis: report of a post-mortem case studied electron microscopically and immunohisiochemically

Pitella, José Eymard Homem; Leite, Virgínia Hora Rios; Lana-Peixoto, Marco Aurélio; Bacchi, Carlos Eduardo

doi:10.1590/S0004-282X1987000100006

Abstracts

A post-mortem examined case of herpetic brainstem encephalitis is presented. Clinically, the patient had cephalea followed by ataxia, drowsiness and multiple palsies of some cranial nerves, developing into death in eight days. The pathologic examination of the brain showed necrotizing encephalitis in multiple foci limited to the brainstem, more distinctly in the pons and medula oblongata. The technique of immunoperoxidase revealed rare glial cells with intranuclear immunoreactivity for herpes antigen. Rare viral particles with the morphological characteristics of the herpesvirus were identified in the nuclei of neurons in 10% formol fixed material. This is the second reported case of herpetic brainstem encephalitis confirmed by post-mortem examination. The pathway used by the virus to reach the central nervous system and its posterior dissemination to the oral cavity, the orbitofrontal region and the temporal lobes as well as to the brainstem, after a period of latency and reactivation, are discussed.

É apresentado um caso autopsiado de encefalite herpética do tronco encefalico. Clinicamente o paciente apresentou de início cefaléia, seguida de ataxia, sonolência e paralisias múltiplas de alguns nervos cranianos, evoluindo para a morte em 8 dias. O exame anatomopatológico do encéfalo mostrou encefalite necrosante em focos múltiplos limitada ao tronco encefálico, mais acentuada na ponte e bulbo. A técnica da imunoperoxidase revelou raras células gliais com imunorreatividade intranuclear para antígeno do herpes. Raras partículas virais com as características morfológicas do herpesvírus foram identificadas nos núcleos de células nervosas em material fixado em formol a 10%. Este caso é o segundo relatado de encefalite herpética do tronco do encéfalo confirmado pelo exame anatomopatológico. Comentam-se as vias de chegada do herpesvírus ao sistema nervoso central e sua posterior disseminação, após período de latência e reativação, para a cavidade oral, região órbito-frontal, lobos temporais e tronco encefálico.

Encefalite herpetica do tronco encefálico: relato de um caso autopsiado com estudo imuno-histoquímico e ao microscópio eletrônico

Herpetic brainstem encephalitis: report of a post-mortem case studied electron microscopically and immunohisiochemically

José Eymard Homem Pitella^I; Virgínia Hora Rios Leite^II; Marco Aurélio Lana-Peixoto^II; Carlos Eduardo Bacchi^III

^IProfessor Adjunto - Laboratório de Neuropatologia, Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais

^IIProfessor Assistente - Laboratório de Neuropatologia, Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais

^IIIProfessor Adjunto do Departamento de Patologia da Faculdade de Medicina da UNESP, Botucatu, SP - Laboratório de Neuropatologia, Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais

RESUMO

É apresentado um caso autopsiado de encefalite herpética do tronco encefalico. Clinicamente o paciente apresentou de início cefaléia, seguida de ataxia, sonolência e paralisias múltiplas de alguns nervos cranianos, evoluindo para a morte em 8 dias. O exame anatomopatológico do encéfalo mostrou encefalite necrosante em focos múltiplos limitada ao tronco encefálico, mais acentuada na ponte e bulbo. A técnica da imunoperoxidase revelou raras células gliais com imunorreatividade intranuclear para antígeno do herpes. Raras partículas virais com as características morfológicas do herpesvírus foram identificadas nos núcleos de células nervosas em material fixado em formol a 10%. Este caso é o segundo relatado de encefalite herpética do tronco do encéfalo confirmado pelo exame anatomopatológico. Comentam-se as vias de chegada do herpesvírus ao sistema nervoso central e sua posterior disseminação, após período de latência e reativação, para a cavidade oral, região órbito-frontal, lobos temporais e tronco encefálico.

SUMMARY

A post-mortem examined case of herpetic brainstem encephalitis is presented. Clinically, the patient had cephalea followed by ataxia, drowsiness and multiple palsies of some cranial nerves, developing into death in eight days. The pathologic examination of the brain showed necrotizing encephalitis in multiple foci limited to the brainstem, more distinctly in the pons and medula oblongata. The technique of immunoperoxidase revealed rare glial cells with intranuclear immunoreactivity for herpes antigen. Rare viral particles with the morphological characteristics of the herpesvirus were identified in the nuclei of neurons in 10% formol fixed material. This is the second reported case of herpetic brainstem encephalitis confirmed by post-mortem examination. The pathway used by the virus to reach the central nervous system and its posterior dissemination to the oral cavity, the orbitofrontal region and the temporal lobes as well as to the brainstem, after a period of latency and reactivation, are discussed.

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Departamento de Anatomía Patológica e Medicina Legal, Faculdade de Medicina da UFMG - Av. Alfredo Balena, 190 - 30130, Belo Horizonte, MO - Brasil

1 AL-DIN, A.N.; ANDERSON, M. ; BICKERSTAFF, E.R. & HARVEY, I. - Brainstem encephalitis and the syndrome of Miller Fisher: a clinical study. Brain 105:481, 1982.
2. BARINGER, J.R. & SWOVELAND, P. - Recovery of Herpes simplex virus from human trigeminal ganglions. N. Engl. J. Med. 288:648, 1973.
3. BICKERSTAFF, E.R. - Brainstem encephalitis: further observations on a grave syndrome with benign prognosis. Brit. Med. J. 1:1384, 1957.
4. BICKERSTAFF, E.R. & CLOAKE, P.C.P. - Mesencephalitis and rhombencephalitis. Brit. Med. J. 2:77, 1951.
5. BUDDINGH, G.J. ; SCHRUM, D.I. ; LAINER, J.C. & GUIDRY, D.J. - Studies on the natural history of Herptes simplex infections. Pediatrics 11:595, 1953.
6. BURNETT, F.M. & WILLIAMS, S.W. - Herpes simplex: a new point of view. Med. J. Aust. 1:637, 1939.
7. BUYSE, G. ; FLAMENT-DURAND, J. & RAPPEL, M. - Recurrent brain stem encephalitis: a clinico-pathological report. Acta neurol. belg. 71:253, 1971.
8. COSTA, J.C. & RABSON, A.S. - Latent infection by Herpes simplex virus. Pathologica Ann. 2:61, 1979.
9. DAVIS, L.E. & JOHNSON, R.T. - An explanation for the localization of Herpes simplex encephalitis? Ann. Neurol. 5:2, 1979.
tO. DAYAN, A.D.; GOODY, W. ; HARRISON, M.J.G. & RUDGE, P. - Brain stem encephalitis caused by Herpesvirus hominis. Brit. Med. J. 4:405, 1972.
11. ELLISON, P.H. & HANSON, P.A. - Herpes simplex: a possible cause of brainstem encephalitis. Pediatrics 59:240, 1977.
12. FENTON, T.R. ; MARSHALL, P.C.; CAVANAGH, N. ; WILSON, J. & MARSHALL, W.C. - Herpes simplex infection presenting as brainstem encephalitis. Lancet 2:977, 1977.
13. GOODPASTURE, E.W. & TEAGUE, O. - Transmission of the virus of Herpes febrilis along nerves in experimentally infected rabbits. J. med. Res. 44:139, 1923.
14. IIZUKA, R. - Tiber Hirnstammencephalitis mit eigenartigem chronischem klinischen Verlauf: ein Beitrag zu atypischen, sporadischen, primaren Encephalitiden. Acta neuropathologica 4:1, 1964.
15. JOHNSON, R.T. - The pathogenesis of herpes virus encephalitis: I. Virus pathways to the nervous system of suckling mice demonstrated by fluorescent antibody staining. J. exp. Med. 119:343, 1964.
16. KINDLEY, A.D. ; HARRIS, F. & BUSH, G.H. - Herpes simplex infection presenting as brainstem encephalitis. Lancet 1:212, 1978.
17. KRISTENSSON, K. ; VAHLNE, A.; PERSSON, L.A. & LYCKE, E. - Neural spread of Herpes simplex virus types 1 and 2 in mice after corneal or subcutaneous (footpad) inoculation. J. neurol. Sci. 35:331, 1978.
1.8. LYON, G. ; GORCE, F. & THIEFFRY, St. - Encéphalite du tronc cérébral chez l'enfant. Arch, franc. Péd. 24:1113, 1967.
19. MARINESCO, G. & DRAGANESCO, S. - Recherches expérimentales sur le neurotropisme du virus herpétique. Ann. Inst. Pasteur 37:753, 1923.
20. MARSAL, J. - Étude anatomo-clinique d'un cas d'encéphalite du tronc cérébral. Rev. neurol. 116:141, 1967.
21. MINAUF, M. & TATEISHI, J. - Sporadische «Hirnstammencephalitiden». Arch. Psychiat. Nervenkr. 212:200, 1969.
22. MÖLLER, F. & NENZELIUS, C. - Acute focal brain-stem lesions with favourable course («brain stem encephalitis»). Acta neurol. scand. 57:297, 1961.
23. ROMAN-CAMPOS, G. & TORO, G. - Herpetic brainstem encephalitis. Neurology 30:981, 1980.
24. RUTIGIAN, R. ; SMULOW, J.B. ; TYE, M.; GIBSON, W.A. & SHINDELL, E. - Studies on latent infection of skin and oral mucosa in individuals with recurrent Herpes simplex. J. Invest. Dermatol. 47:218, 1966.
25. SCADDING, J.G. - Disseminated focal pneumonia. Brit. Med. J. 2:956, 1937.
26. SCHAIN, R.J. & WILSON, G. - Brainstem encephalitis with radiographic evidence of medullary enlargement. Neurology 21:537, 1971.
27. STERNBERGER, L.A. ; HARDY, P.H., Jr.; CUCULIS, J.J. & MEYER, H.G. - The unlabeled antibody enzime method of immunohistochemistry : preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J. Histochem. Cytochem. 18:315, 1970.
28. STEVENS, J.G. & COOK, M.L. - Latent Herpes simplex virus in spinal ganglia of mice. Science 173:843, 1971.
29. STEVENS, J.G. ; NESBURN, A.B. & COOK, M.L. - Latent Herpes simplex virus from trigeminal ganglia of rabbits with recurrent eye infection. Nature new Biol. 235:216, 1972.
30. UENO, T. & TAKAHATA, N. - Chronic brainstem encephalitis with mental symptoms and ataxia: report of three cases with necropsy. J. Neurol. Neurosurg. Psychiat. 41:516, 1978.
31. WARREN K.G. ; BROWN, S.M. ; WROBLEWSKA, Z. ; GILDEN, D. ; KOPROWSKI, H. & SUBAK-SHARPE, J. - Isolation of latent Herpes simplex virus from the superior cervical and vagus ganglions of human beings. N. Engl. J. Med. 298:1068, 1978.
32. WAXMAN, S.G. ; SABIN, T.D. & EMBREE, L.J. - Subacute brain-stem encephalitis. J. Neurol. Neurosurg. Psychiat. 37:811, 1974.
33. WENTWORTH, B.B. & ALEXANDER, E.R. - Seroepidemiology of infections due to members of the herpesvirus group. Amer. J. Epidemiol. 94:4%, 1971.
34. YALAZ, K. & TINAZTEPE, K. - Brain stem encephalitis. Acta paediat. scand. 63:235, 1974.

Publication Dates

Publication in this collection
22 June 2011
Date of issue
Mar 1987

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

[1] 1 AL-DIN, A.N.; ANDERSON, M. ; BICKERSTAFF, E.R. & HARVEY, I. - Brainstem encephalitis and the syndrome of Miller Fisher: a clinical study. Brain 105:481, 1982.

[2] 2. BARINGER, J.R. & SWOVELAND, P. - Recovery of Herpes simplex virus from human trigeminal ganglions. N. Engl. J. Med. 288:648, 1973.

[3] 3. BICKERSTAFF, E.R. - Brainstem encephalitis: further observations on a grave syndrome with benign prognosis. Brit. Med. J. 1:1384, 1957.

[4] 4. BICKERSTAFF, E.R. & CLOAKE, P.C.P. - Mesencephalitis and rhombencephalitis. Brit. Med. J. 2:77, 1951.

[5] 5. BUDDINGH, G.J. ; SCHRUM, D.I. ; LAINER, J.C. & GUIDRY, D.J. - Studies on the natural history of Herptes simplex infections. Pediatrics 11:595, 1953.

[6] 6. BURNETT, F.M. & WILLIAMS, S.W. - Herpes simplex: a new point of view. Med. J. Aust. 1:637, 1939.

[7] 7. BUYSE, G. ; FLAMENT-DURAND, J. & RAPPEL, M. - Recurrent brain stem encephalitis: a clinico-pathological report. Acta neurol. belg. 71:253, 1971.

[8] 8. COSTA, J.C. & RABSON, A.S. - Latent infection by Herpes simplex virus. Pathologica Ann. 2:61, 1979.

[9] 9. DAVIS, L.E. & JOHNSON, R.T. - An explanation for the localization of Herpes simplex encephalitis? Ann. Neurol. 5:2, 1979.

[10] tO. DAYAN, A.D.; GOODY, W. ; HARRISON, M.J.G. & RUDGE, P. - Brain stem encephalitis caused by Herpesvirus hominis. Brit. Med. J. 4:405, 1972.

[11] 11. ELLISON, P.H. & HANSON, P.A. - Herpes simplex: a possible cause of brainstem encephalitis. Pediatrics 59:240, 1977.

[12] 12. FENTON, T.R. ; MARSHALL, P.C.; CAVANAGH, N. ; WILSON, J. & MARSHALL, W.C. - Herpes simplex infection presenting as brainstem encephalitis. Lancet 2:977, 1977.

[13] 13. GOODPASTURE, E.W. & TEAGUE, O. - Transmission of the virus of Herpes febrilis along nerves in experimentally infected rabbits. J. med. Res. 44:139, 1923.

[14] 14. IIZUKA, R. - Tiber Hirnstammencephalitis mit eigenartigem chronischem klinischen Verlauf: ein Beitrag zu atypischen, sporadischen, primaren Encephalitiden. Acta neuropathologica 4:1, 1964.

[15] 15. JOHNSON, R.T. - The pathogenesis of herpes virus encephalitis: I. Virus pathways to the nervous system of suckling mice demonstrated by fluorescent antibody staining. J. exp. Med. 119:343, 1964.

[16] 16. KINDLEY, A.D. ; HARRIS, F. & BUSH, G.H. - Herpes simplex infection presenting as brainstem encephalitis. Lancet 1:212, 1978.

[17] 17. KRISTENSSON, K. ; VAHLNE, A.; PERSSON, L.A. & LYCKE, E. - Neural spread of Herpes simplex virus types 1 and 2 in mice after corneal or subcutaneous (footpad) inoculation. J. neurol. Sci. 35:331, 1978.

[18] 1.8. LYON, G. ; GORCE, F. & THIEFFRY, St. - Encéphalite du tronc cérébral chez l'enfant. Arch, franc. Péd. 24:1113, 1967.

[19] 19. MARINESCO, G. & DRAGANESCO, S. - Recherches expérimentales sur le neurotropisme du virus herpétique. Ann. Inst. Pasteur 37:753, 1923.

[20] 20. MARSAL, J. - Étude anatomo-clinique d'un cas d'encéphalite du tronc cérébral. Rev. neurol. 116:141, 1967.

[21] 21. MINAUF, M. & TATEISHI, J. - Sporadische «Hirnstammencephalitiden». Arch. Psychiat. Nervenkr. 212:200, 1969.

[22] 22. MÖLLER, F. & NENZELIUS, C. - Acute focal brain-stem lesions with favourable course («brain stem encephalitis»). Acta neurol. scand. 57:297, 1961.

[23] 23. ROMAN-CAMPOS, G. & TORO, G. - Herpetic brainstem encephalitis. Neurology 30:981, 1980.

[24] 24. RUTIGIAN, R. ; SMULOW, J.B. ; TYE, M.; GIBSON, W.A. & SHINDELL, E. - Studies on latent infection of skin and oral mucosa in individuals with recurrent Herpes simplex. J. Invest. Dermatol. 47:218, 1966.

[25] 25. SCADDING, J.G. - Disseminated focal pneumonia. Brit. Med. J. 2:956, 1937.

[26] 26. SCHAIN, R.J. & WILSON, G. - Brainstem encephalitis with radiographic evidence of medullary enlargement. Neurology 21:537, 1971.

[27] 27. STERNBERGER, L.A. ; HARDY, P.H., Jr.; CUCULIS, J.J. & MEYER, H.G. - The unlabeled antibody enzime method of immunohistochemistry : preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J. Histochem. Cytochem. 18:315, 1970.

[28] 28. STEVENS, J.G. & COOK, M.L. - Latent Herpes simplex virus in spinal ganglia of mice. Science 173:843, 1971.

[29] 29. STEVENS, J.G. ; NESBURN, A.B. & COOK, M.L. - Latent Herpes simplex virus from trigeminal ganglia of rabbits with recurrent eye infection. Nature new Biol. 235:216, 1972.

[30] 30. UENO, T. & TAKAHATA, N. - Chronic brainstem encephalitis with mental symptoms and ataxia: report of three cases with necropsy. J. Neurol. Neurosurg. Psychiat. 41:516, 1978.

[31] 31. WARREN K.G. ; BROWN, S.M. ; WROBLEWSKA, Z. ; GILDEN, D. ; KOPROWSKI, H. & SUBAK-SHARPE, J. - Isolation of latent Herpes simplex virus from the superior cervical and vagus ganglions of human beings. N. Engl. J. Med. 298:1068, 1978.

[32] 32. WAXMAN, S.G. ; SABIN, T.D. & EMBREE, L.J. - Subacute brain-stem encephalitis. J. Neurol. Neurosurg. Psychiat. 37:811, 1974.

[33] 33. WENTWORTH, B.B. & ALEXANDER, E.R. - Seroepidemiology of infections due to members of the herpesvirus group. Amer. J. Epidemiol. 94:4%, 1971.

[34] 34. YALAZ, K. & TINAZTEPE, K. - Brain stem encephalitis. Acta paediat. scand. 63:235, 1974.