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Forensic Pathology Reviews pp 169–186Cite as

Sudden, Unexpected Death Related to Viral Myocarditis

A Survey of Histological, Immunohistochemical, and Molecularpathological Methods for the Postmortem Diagnosis

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Part of the book series: Forensic Pathology Reviews ((FPR,volume 2))

Abstract

Sudden, unexpected deaths of previously healthy individuals without establishment of a definitive acute lethal event at autopsy represent a substantial proportion of forensic autopsy cases. It is well established that viral myocarditis can be associated with sudden, unexpected manifestation of death. Nevertheless, this diagnosis may present difficulties when there are no relevant histological findings using conventional histological stains. When applying a comprehensive combination of molecularpathological and immunohistochemical techniques, obviously a higher prevalence of viral myocarditis can be detected with regard to forensic pathological autopsy cases. Immunohistochemical methods include qualification and quantification of interstitial leukocytes including macrophages, T-lymphocytes, and the expression of adhesion molecules and cytokines as well as major histocompatibility complex class I and II molecules. Conventional histology may provide, when supplemented by immunohistochemistry, important clues regarding the underlying etiology of myocarditis. The actual demonstration of microorganisms in the myocardium or the elucidation of a previous administration of drugs or exposure to toxic substances are the only reliable means of establishing an etiological diagnosis of myocarditis. Molecularpathological techniques should be employed particularly for the detection of viral genome in the myocardium by reverse transcriptase polymerase chain reaction (rt-PCR) as already established regarding the investigation of endomyocardial biopsies. In combination with histological, immunohistochemical, and in situ hybridization, these techniques will enable the forensic pathologist or medical examiner, respectively, to clarify the cause of death in a higher number of cases of sudden, unexpected death that present otherwise without any relevant morphological findings.

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References

  1. Feldmann AM, McNamara D. Myocarditis. N Engl J Med 2000;343:1388–1398.

    Article  Google Scholar 

  2. Pankuweit S, Pratig I, Eckhardt H, Crombach M, Hufnagel G, Maisch B. Prevalence of viral genome in endomyocardial biopsies from patients with inflammatory heart muscle disease. Herz 2000;25:221–226.

    Article  PubMed  CAS  Google Scholar 

  3. Droroy TY, Hiss Y. Sudden unexpected death in persons less than 40 years of age. Am J Cardiol 1991; 68:1388–1392.

    Article  Google Scholar 

  4. Neuspiel DR, Kuller LH. Sudden unexpected natural death in childhood and adolescence. JAMA 1985;254: 1321–1325.

    Article  PubMed  CAS  Google Scholar 

  5. McCaffrey FM, Braden DS, Strong WB. Sudden cardiac death in young athletes. Am J Dis Child 1991; 145:177–183.

    PubMed  CAS  Google Scholar 

  6. Huber SA, Gauntt CJ, Sakkinen P. Enteroviruses and myocarditis: viral pathogenesis through replication, cytokine induction, and immunopathogenicity. Adv Vir Res 1999;51:35.

    Article  Google Scholar 

  7. Bowles NE. Detection of coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet 1986;1:1120–1123.

    Article  PubMed  CAS  Google Scholar 

  8. Muir P. Enteroviruses and heart disease. Br J Biomed Sci 1993;50:258–271.

    PubMed  CAS  Google Scholar 

  9. Phillips CA, Aronson MD, Tomkow J, Phillips ME. Enteroviruses in Vermont, 1969–1978: an important cause of illness throughout the year. J Infect Dis 1980;141:162–164.

    PubMed  CAS  Google Scholar 

  10. Mounts AW, Amr S, Jamshidi R, et al. A cluster of fulminant myocarditis cases in children, Baltimore, Maryland, 1997. Pediatr Cardiol 2001;22:34–39.

    Article  PubMed  CAS  Google Scholar 

  11. Kawai C, Matsumori A, Fujiwara H. Myocarditis and dilated cardiomyopathy. Ann Rev Med 1987;38: 221–239.

    Article  PubMed  CAS  Google Scholar 

  12. Haddad J, Gut J, Wendling M, et al. Enterovirus infections in neonates. A retrospective study of 21 cases. Eur J Med 1993;2:209–214.

    PubMed  CAS  Google Scholar 

  13. Dettmeyer R, Baasner A, Winkelmann S, Graebe M, Madea B. Myocarditis and sudden death in infancy—immunohistochemical and molecularpathological investigations. J Perinat Med 2001;29(Suppl 2):25.

    Google Scholar 

  14. Dettmeyer R, Baasner A, Schlamann M, Haag C, Madea B. Coxsackie B3 myocarditis in 4 cases of suspected sudden infant death syndrome: diagnosis by immunohistochemical and molecular-pathologic investigations. Pathol Res Pract 2002;198:689–696.

    Article  PubMed  Google Scholar 

  15. Dettmeyer R, Kandolf R, Schmidt P, Schlamann M, Madea B. Lympho-monocytic enteroviral myocarditis: traditional, immunohistological and molecularpathological methods for diagnosis in a case of suspected sudden infant death syndrome (SIDS). Forensic Sci Int 2001;119:141–144.

    Article  PubMed  CAS  Google Scholar 

  16. Rambaud C, Cieuta C, Canioni D, et al. Cot death and myocarditis. Cardiol Young 1992;2:266–271.

    Google Scholar 

  17. Bajanowski T, Ortmann C, Teige K, et al. Pathological changes of the heart in sudden infant death. Int J Legal Med 2003;117:193–203.

    Article  PubMed  CAS  Google Scholar 

  18. Gold E, Carver DH, Heineberg H, Adelson L, Robbins FC. Viral infection. A possible cause of sudden unexpected death in infants. New Engl J Med 1961;264:53–60.

    Article  PubMed  CAS  Google Scholar 

  19. Jin O, Sole M, Butany JW, et al. Detection of enterovirus RNA in myocardial biopsies from patients with myocarditis and cardiomyopathy using gene amplification by polymerase chain reaction. Circulation 1990;82: 8–16.

    PubMed  CAS  Google Scholar 

  20. Lozinski GM, Davis GG, Krous HF, Billman GF, Shimizu H, Burns JC. Adenovirus myocarditis: retrospective diagnosis by gene amplification from formalin-fixed, paraffin-embedded tissues. Hum Pathol 1994;25: 831–834.

    Article  PubMed  CAS  Google Scholar 

  21. Hebert MM, Yu C, Towbin JA, Rogers BB. Fatal Epstein-Barr virus myocarditis in a child with repetitive myocarditis. Ped Pathol Lab Med 1995;15:805–812.

    CAS  Google Scholar 

  22. Bajanowski T, Rolf B, Jorch G, Brinkmann B. Detection of RNA viruses in sudden infant death (SID). Int J Legal Med 2003;117:237–240.

    Article  PubMed  CAS  Google Scholar 

  23. Maisch B, Schönian U, Crombach M, et al. Cytomegalovirus associated inflammatory heart muscle disease. Scand J Infect 1993;88(Suppl):135–148.

    CAS  Google Scholar 

  24. Murry CE, Jerome KR, Reichenbach DD. Fatal parvovirus myocarditis in a 5-yearold girl. Hum Pathol 2001;32:342–345.

    Article  PubMed  CAS  Google Scholar 

  25. Bültmann BD KK, Sotlar K, Bock TH, Baba HA, Sauter M, Kandolf R. Fatal parvovirus B19-associated myocarditis clinically mimicking ischemic heart disease: an endothelial cell-mediated disease. Hum Pathol 2003; 34:92–95.

    Article  PubMed  Google Scholar 

  26. Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol 1987;18:619–624.

    Article  PubMed  CAS  Google Scholar 

  27. Dettmeyer R, Schlamann M, Madea B. Immunohistochemical techniques improve the diagnosis of myocarditits in cases of suspected sudden infant death syndrome (SIDS). Forensic Sci Int 1999;105:83–94.

    Article  PubMed  CAS  Google Scholar 

  28. Cioc AM, Nuovo GJ. Histologic and in situ viral findings in the myocardium in cases of sudden, unexpected death. Mod Pathol 2002;15:914–922.

    Article  PubMed  Google Scholar 

  29. Drescher J ZP, Verhagen W, Flik J, Milbradt H. Recent influenza virus A infections in forensic cases of sudden unexplained death. Arch Virol 1987;92:63–76.

    Article  PubMed  CAS  Google Scholar 

  30. Morens DM. Enteroviral disease in infancy. J Pediatr 1978;92:374–377.

    Article  PubMed  CAS  Google Scholar 

  31. Friman G, Fohlman J. The epidemiology of viral heart disease. Scand J Infect Dis 1993;88(Suppl): 7–10.

    CAS  Google Scholar 

  32. Fairley CK, Ryan M, Wall PG, Weinberg J. The organisms reported to cause infective myocarditis and pericarditis in England and Wales. J Infect 1996;32:223–225.

    Article  PubMed  CAS  Google Scholar 

  33. Martino TA, Liu P, Sole MJ. Viral infection and the pathogenesis of dilated cardiomyopathy. Circ Res 1994;74:182–188.

    PubMed  CAS  Google Scholar 

  34. Kawai C. From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death. Circulation 1999;99:1091–1100.

    PubMed  CAS  Google Scholar 

  35. Aretz HT, Billingham ME, Edwards W, et al. Myocarditis: a histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1:5–14.

    Google Scholar 

  36. Shanes JG, Ghali J, Billingham ME, et al. Interobserver variability in the pathologic interpretation of endomyocardial biopsy results. Circulation 1987;75:401–405.

    PubMed  CAS  Google Scholar 

  37. Strauer B, Kandolf R, Mall G, et al. Myokarditis-Kardiomyopathie. Update 2001. Med Klin 2001;96: 608–625.

    CAS  Google Scholar 

  38. Kandolf R, Klingel K, Zell R, et al. Molecular mechanisms in the pathogenesis of enteroviral heart disease: acute and persistent infections. Clin Immunol Immunopathol 1993;68:153–158.

    Article  PubMed  CAS  Google Scholar 

  39. Heusch A, Kühl U, Rammos S, Krogmann ON, Schultheiss HP, Bourgeois M. Complete AV-block in two children with immunohistological proven myocarditis. Eur J Pediatr 1996;155:633–636.

    Article  PubMed  CAS  Google Scholar 

  40. Wojnicz R, Nowalany-Kozielska E, Wodniecki J. Immunohistological diagnosis of myocarditis. Eur Heart J 1998;19:1564–1572.

    Article  PubMed  CAS  Google Scholar 

  41. Schnitt SJ, Ciano PS, Schoen FJ. Quantification of lymphocytes in endomyocardial biopsies. Hum Pathol 1987;18:796–800.

    Article  PubMed  CAS  Google Scholar 

  42. Chow LH, Ye Y, Linder J, McManus BM. Phenotypic analysis of infiltrating cells in human myocarditis. Arch Pathol Lab Med 1989;113:1357–1362.

    PubMed  CAS  Google Scholar 

  43. Steenbergen C, Kolbeck PC, Wolfe JA, Anthony RM, Sanfilippo FP, Jennings RB. Detection of lymphocytes in endomyocardium using immunohistochemical techniques. Relevance to evaluation of endomyocardial biopsies in suspected cases of lymphocytic myocarditis. J Appl Cardiol 1986;1:63–73.

    Google Scholar 

  44. Southern J, Kaynor B, Howard CA, Bain KM, Palcios IF, Fallon JT. Is immunoperoxidase staining of endomyocardial biopsies for interstitial inflammatory cells helpful in the diagnosis of myocarditis? Eur Heart J 1987;8:195–197.

    Google Scholar 

  45. Forcada P, Beigelman J, Milei J. Inapparent myocarditis and sudden death in pediatrics. Diagnosis by immunohistochemical staining. Int J Cardiol 1996;56:93–97.

    Article  PubMed  CAS  Google Scholar 

  46. Hufnagel G, Maisch B. Expression of MHC class I and II antigens and the IL-2 receptor in rejection, myocarditis and dilated cardiomyopathy. Eur Heart J 1991;12(Suppl D):137–140.

    PubMed  Google Scholar 

  47. Daar AS, Fuggle SV, Fabre JW, Ting A, Morris PJ. The detailed distribution of MHC class II antigens in normal human organs. Transplantation 1984;38:293–298.

    Article  PubMed  CAS  Google Scholar 

  48. Daar AS, Fuggle SV, Fabre JW, Ting A, Morris J. The detailed distribution of HLA-A, B, C antigens in normal human organs. Transplantation 1984;38:287–292.

    PubMed  CAS  Google Scholar 

  49. Thorsby E. Structure and function of HLA molecules. Transplant Proceed 1987;19:29–35.

    CAS  Google Scholar 

  50. Henke A, Nain M, Stelzner A, Gemsa D. Induction of cytokine release from human monocytes by coxsackievirus infection. Eur Heart J 1991;12(Suppl D):134–136.

    PubMed  Google Scholar 

  51. Ino T, Kishiro M, Okubo M, et al. Late, persistent expressions of ICAM-1 and VCAM-1 on myocardial tissue in children with lymphocytic myocarditis. Cardiovasc Res 1997;34:323–328.

    Article  PubMed  CAS  Google Scholar 

  52. Noutsias M, Seeberg B, Schultheiss HP, Kühl U. Expression of cell adhesion molecules in dilated cardiomyopathy. Evidence for endothelial activation in inflammatory cardiomyopathy. Circulation 1999;99: 2124–2131.

    PubMed  CAS  Google Scholar 

  53. Seko Y, Takahashi N, Ishiyama S, et al. Expression of costimulatory molecules B7-1, B7-2, and CD40 in the heart of patients with acute myocarditis and dilated cardiomyopathy. Circulation 1998;97:637–639.

    PubMed  CAS  Google Scholar 

  54. Li Y, Bourlet T, Andreoletti L, Mosnier JF, Peng T, Yang Y, et al. Enteroviral capsid protein is present in myocardial tissues from some patients with myocarditis or dilated cardiomyopathy. Circulation 2000;101: 231–234.

    PubMed  CAS  Google Scholar 

  55. Yousef GE, Mann GF, Brown IN, Mowbray JF. Clinical and research application of an enterovirus group-reactive monoclonal antibody. Intervirology 1987;28:199–205.

    PubMed  CAS  Google Scholar 

  56. Edwards WD, Holmes DR, Reeder GS. Diagnosis of active lymphocytic myocarditis by endomyocardial biopsy. Quantitative criteria for light microscopy. Mayo Clin Proc 1982;57:419–425.

    PubMed  CAS  Google Scholar 

  57. Linder J, Cassling RS, Rogler WC, et al. Immunohistochemical characterization of lymphocytes in uninflamed ventricular myocardium. Arch Pathol Lab Med 1985;109:917–920.

    PubMed  CAS  Google Scholar 

  58. Cassling RS, Linder J, Sears TD, et al. Quantitative evaluation of inflammation in biopsy specimen from idiopathically failing or irritable hearts: experience in 80 pediatric and adult patients. Am Heart J 1985; 110:713–720.

    Article  PubMed  CAS  Google Scholar 

  59. Martin AB, Webber S, Fricker FJ, et al. Acute myocarditits: rapid diagnosis by PCR in children. Circulation 1994;90:330–339.

    PubMed  CAS  Google Scholar 

  60. Severini GM, Mestroni L, Falaschi A, Camerini F, Giacca M. Nested polymerase chain reaction for high-sensitivity detection of enteroviral RNA in biological samples. J Clin Microbiol 1993;31:1345–1349.

    PubMed  CAS  Google Scholar 

  61. Bendig JWA, O’Brien PS, Muir P, Porter HJ, Caul EO. Enterovirus sequences resembling coxsackievirus A2 detected in stool and spleen from a girl with fatal myocarditis. J Med Virol 2001;64:482–486.

    Article  PubMed  CAS  Google Scholar 

  62. Druyts-Voets E, van Renterghem L, Gerniers S. Coxsackie B virus epidemiology and neonatal infection in Belgium. J Infect 1993;27:311–316.

    Article  PubMed  CAS  Google Scholar 

  63. Singer DB. Infections of fetuses and neonates. In: Wigglesworth JS, Singer DB, eds. Textbook of Fetal and Perinatal Pathology. Blackwell Scientific Publications, Boston, 1991, pp. 554,555.

    Google Scholar 

  64. Leipner C, Grün K, Borchers M, Stelzner A. The outcome of coxsackievirus B3-(CVB3-) induced myocarditis is influenced by the cellular immune status. Herz 2000;25:245–248.

    Article  PubMed  CAS  Google Scholar 

  65. Shimizu H, Rambaud C, Cheron G, et al. Molecular identification of viruses in sudden infant death associated with myocarditis and pericarditis. Ped Infect Dis J 1995;14:584–588.

    Article  CAS  Google Scholar 

  66. Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science 1997;275:1320–1323.

    Article  PubMed  CAS  Google Scholar 

  67. Schwimmbeck PL, Rohn G, Wrusch A, et al. Enteroviral and immune mediated myocarditis in SCID mice. Herz 2000;25:240–244.

    Article  PubMed  CAS  Google Scholar 

  68. Klingel K, Selinka HC, Huber M, Sauer M, Leube M, Kandolf R. Molecular pathology and structural features of enteroviral replication. Toward understanding the pathogenesis of viral heart disease. Heart 2000;25: 216–220.

    CAS  Google Scholar 

  69. McManus BM, Chow LH, Wilson JE, et al. Direct myocardial injury by enterovirus: a central role in the evolution of murine myocarditits. Clin Immunol Immunopathol 1993;68:159–169.

    Article  PubMed  CAS  Google Scholar 

  70. Badorff C, Berkely N, Mehrotra S, Talhouk JW, Rhoads RE, Knowlton KU. Enteroviral protease 2A directly cleaves dystrophin and is inhibited by a dystrophinbased substrate analogue. J Biol Chem 2000;275: 1191–1197.

    Article  Google Scholar 

  71. Badorff C, Lee GH, Knowlton KU. Enteroviral cardiomypathy: bad news for the dystrophin-glycoprotein-complex. Herz 2000;25:227–232.

    Article  PubMed  CAS  Google Scholar 

  72. Dettmeyer R, Kandolf R, Baasner A, Banaschak S, Eis-Hübinger AM, Madea B. Fatal parvovirus B19 myocarditis in an 8-year-old boy. J Forensic Sci 2003;48:183–186.

    PubMed  Google Scholar 

  73. Arola A, Jokinen E, Ruuskanen O, et al. Epidemiology of idiopathic cardiomyopathies in children and adolescents. A nationwide study in Finland. Am J Epidemiol 1997;146:385–393.

    PubMed  CAS  Google Scholar 

  74. Pauschinger M, Meissner G, Preis S, et al. Detection of enteroviral RNA by polymerase chain reaction in patients with myocarditis and dilated cardiomyopathy. JACC 1994;1994:880.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Forensic Medicine, Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany

    Reinhard Dettmeyer MD & Burkhard Madea MD

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  1. Reinhard Dettmeyer MD
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  2. Burkhard Madea MD
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  1. Institute of Legal Medicine, University of Hamburg, Hamburg, Germany

    Michael Tsokos MD

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Dettmeyer, R., Madea, B. (2005). Sudden, Unexpected Death Related to Viral Myocarditis. In: Tsokos, M. (eds) Forensic Pathology Reviews. Forensic Pathology Reviews, vol 2. Humana Press. https://doi.org/10.1385/1-59259-872-2:169

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  • DOI: https://doi.org/10.1385/1-59259-872-2:169

  • Publisher Name: Humana Press

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