Epstein–Barr Virus and Cytomegalovirus Infections

Chapter
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)

Abstract

Epstein–Barr virus and cytomegalovirus are members of the human herpesviruses that have an extremely high seroprevalence in all populations studied. The initial infection is usually asymptomatic, or causes a febrile illness, but can rarely manifest itself neurologically. These viruses are increasingly important in the modern era of immunosuppression, whether due to AIDS or in the transplant or cancer chemotherapy population, and their reactivation gives rise to a wide spectrum of neurological diseases. The pathogenesis of these infections is not completely understood, but certainly multifaceted. In CMV lytic infection damages systemic tissues directly, whereas EBV involves an activated and distorted immune system. These diseases are treatable, but need to be recognized early in their course so that antiviral intervention can be effected promptly. The choice of therapeutic strategy can be counterintuitive: while CMV infections are conventionally managed with antiviral medications, EBV infections may demand a neoplastic treatment paradigm as an addition to (or alternative to) antiviral treatment.

Keywords

Cytomegalovirus Diagnostic virology Encephalitis Epstein-Barr virus Immunosuppression Lymphoproliferative disorder Myelitis Opportunistic infections Primary CNS lymphoma 

References

  1. Abul-Kasim K, Palm L, Maly P, Sundgren P (2009) Neuroanatomic localization of Epstein-Barr virus encephalitis may be a predictive factor for its clinical outcome: a case report and a review of 108 cases in 28 reports. J Child Neurol 24:720–726PubMedGoogle Scholar
  2. Adamson D, Gordon P (1992) Hemiplegia: a rare complication of acute Epstein-Barr virus (EBV) infection. Scand J Infect Dis 24:379–380PubMedGoogle Scholar
  3. Anduze-Fafri B, Fillet A, Gozlan J, Lancar R, Boukli N, Gasnault J et al (2000) Induction and maintenance therapy of CMV central nervous system infection in HIV infected patients. AIDS 14:517–524Google Scholar
  4. Anduze-Faris B, Fillet A, Gozlan J, Lancar R, Boukli N, Gasnault J et al (2000) Induction and maintenance therapy of CMV central nervous system infection in HIV infected patients. AIDS 14:517–524PubMedGoogle Scholar
  5. Angelini L, Bugiani M, Zibordi F, Cinque P, Bizzi A (2000) Brainstem encephalitis resulting from Epstein-Barr virus mimicking an infiltrating tumor in a child. Pediatr Neurol 22(2):130–132PubMedGoogle Scholar
  6. Applebaum F, Meyers J, Fefer A, Flourney N et al (1982) Nonbacterial nonfungal pneumonia following bone marrow transplantation in 100 identical twins. Transplantation 33:265–268PubMedGoogle Scholar
  7. Arribas J, Clifford D, Fichtenbaum C, Commons D et al (1995) Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS and CMV infection of the central nervous system. J Infect Dis 172:527–531PubMedGoogle Scholar
  8. Arribas J, Storch G, Clifford D, Tselis A (1996) Cytomegalovirus encephalitis. Ann Int Med 125:577–587PubMedGoogle Scholar
  9. Ashworth J, Motto S (1947) Infectious mononucleosis complicated by papilloretinal edema. N Engl J Med 237:544–545PubMedGoogle Scholar
  10. Back E, Hoglund C, Malmlund H (1977) Cytomegalovirus infection associated with severe encephalitis. Scand J Infect Dis 9:141–143PubMedGoogle Scholar
  11. Baker F, Kotchmar G, Foshee W, Sumaya C (1983) Acute hemiplegia of childhood associated with Epstein-Barr virus infection. Pediatr Infect Dis J 2:136–138Google Scholar
  12. Bazan C, Jackson C, Jinkins J, Barohn R (1991) Gadolinium enhanced MRI in a case of cytomegalovirus polyradiculopathy. Neurology 41:1522–1523PubMedGoogle Scholar
  13. Bennett D, Peters H (1961) Acute cerebellar syndrome secondary to infectious mononucleosis in a fifty-two year old man. Ann Intern Med 55(1):147–149Google Scholar
  14. Bergen D, Grossman H (1975) Acute cerebellar ataxia of childhood associated with infectious mononucleosis. J Pediatr 87:832–833PubMedGoogle Scholar
  15. Bernstein T, Wolfe H (1950) Involvement of the nervous system in infectious mononucleosis. Ann Intern Med 33:1120–1138PubMedGoogle Scholar
  16. Biebl A, Webersinke C, Traxler B, Povysil B, Furthner D, Schmitt K (2009) Fatal Epstein-Barr virus encephalitis in a 12 year old child: an underappreciated neurological complication? Nature Clin Pract Neurol 5:171–174Google Scholar
  17. Blaustein A, Caccavo A (1950) Infectious mononucleosis complicated by bilateral papilloretinal edema. Arch Ophthalmol 43:853–856Google Scholar
  18. Bonynge T, Van Hagen K (1952) Severe optic neuritis in infectious mononucleosis. J Am Med Assoc 145:933–934Google Scholar
  19. Caruso J, Tung G, Gascon G, Rogg J, Davis L, Brown W (2000) Persistent preceding focal neurologic deficits in children with Epstein-Barr encephalitis. J Child Neurol 15:791–796PubMedGoogle Scholar
  20. Chalaupka Devetag F, Boscariolo L (2000) Cytomegalovirus meningoencephalitis with paroxysmal course in immunocompetent adults: a new nosographical entity. Clinical, diagnostic, and therapeutic correlations and pathogenetic hpothesis. Eur Neurol 44:242–247Google Scholar
  21. Chin W, Magoffin R, Frierson J, Lennette E (1973) Cytomegalovirus infection: a case with meningoencephalitis. JAMA 225:740–741PubMedGoogle Scholar
  22. Cleary T, Henle W, Pickering L (1980) Acute cerebellar ataxia associated with Epstein-Barr virus infection. J Am Med Assoc 243:148–149Google Scholar
  23. Clevenbergh R, Brohee P, Velu T, Jacobs E, Liesnard C, Deneft E, Thys J (1997) Infectious mononucleosis complicated by transverse myelitis: detection of the viral genome by polymerase chain reaction in the cerebrospinal fluid. J Neurol 244:592–594PubMedGoogle Scholar
  24. Copperman S (1977) “Alice in Wonderland” syndrome as a presenting symptom of infectious mononucleosis in children. Clin Pediatr 16:143–146Google Scholar
  25. Cotton P, Webb-Peploe M (1966) Acute transverse myelitis as a complication of glandular fever. Br Med J 1:654–655PubMedGoogle Scholar
  26. Dimova P, Bojinova V, Georgiev D, Milanov I (2006) Acute reversible parkinsonism in Epstein-Barr virus-related encephalitis lethargica-like illness. Mov Disord 21:564–566PubMedGoogle Scholar
  27. Dorfman L (1973) Cytomegalovirus encephalitis in adults. Neurology 23:136–144PubMedGoogle Scholar
  28. Egan R (1960) Facial diplegia in infectious mononucleosis in the absence of Landry–Guillain–Barre syndrome. N Engl J Med 262(23):1178–1179PubMedGoogle Scholar
  29. Eshel G, Eyov A, Lahat E, Brauman A (1987) Alice in Wonderland syndrome, a manifestation of acute Epstein-Barr virus infection. Pediatr Infect Dis J 6:68PubMedGoogle Scholar
  30. Foss H, Herbst H, Hummel M, Araujo I, Latza U, Rancso C, Dallenbach F, Stein H (1994) Patterns of cytokine gene expression in infectious mononucleosis. Blood 83:707–712PubMedGoogle Scholar
  31. Friedland R, Yahr M (1977) Meningoencephalopathy secondary to infectious mononucleosis unusual presentation with stupor and chorea. Arch Neurol 34:186–188PubMedGoogle Scholar
  32. Fujimoto J, Asaoka J, Imaizumi T, Ayabe M, Shoji H, Kaji M (2003) Epstein-Barr virus infection of the central nervous system. Intern Med 42:33–40PubMedGoogle Scholar
  33. Garamendi I, Montejo M, Cancelo L, Lopez L et al (2002) Encephalitis caused by Epstein-Barr virus in a renal transplant recipient. Clin Infect Dis 34:287–288PubMedGoogle Scholar
  34. Gilbert J, Culebras A (1972) Cerebellitis in infectious mononucleosis. J Am Med Assoc 220(5):727Google Scholar
  35. Greenberg D, Weinkle D, Aminoff M (1982) Periodic EEG complexes in infectious mononucleosis encephalitis. J Neurol Neurosurg Psychiatry 45:648–651PubMedGoogle Scholar
  36. Goodpasture E, Talbot F (1921) Concerning the nature of “protozoan-like” cells in certain lesions of infancy. Am J Dis Child 21:415–421Google Scholar
  37. Grose C, Feorino P (1973) Epstein-Barr virus and transverse myelitis. Lancet 1:892PubMedGoogle Scholar
  38. Grose C, Feorino P, Dye L, Rand J (1973) Bell's palsy and infectious mononucleosis. Lancet 2:231–232PubMedGoogle Scholar
  39. Henle G, Henle W, Diehl V et al (1968) Relation of Burkitt’s tumor-associated herpes-type virus to infectious mononucleosis. Proc Natl Acad Sci 59:94–101PubMedGoogle Scholar
  40. Henle W, Henle G, Horwitz C (1974) Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Hum Pathol 5:551–565PubMedGoogle Scholar
  41. Ho M (2008) The history of cytomegalovirus and its diseases. Med Microbiol Immunol 197:65–73PubMedGoogle Scholar
  42. Hochberg F, Miller G, Schooley R, Hirsch M, Feorino P, Henle G (1983) Central nervous system lymphoma related to Epstein-Barr virus. N Engl J Med 309:745–748PubMedGoogle Scholar
  43. Holland N, Power C, Mathews V, Glass J et al (1994) CMV encephalitis in acquired immunodeficiency syndrome. Neurology 44:507–514PubMedGoogle Scholar
  44. Hotson J, Pedley T (1976) The neurological complications of cardiac transplantation. Brain 99:673–694PubMedGoogle Scholar
  45. Hummel M, Abecassis M (2002) A model for reactivation of CMV from latency. J Clin Virol 25:s123–s136PubMedGoogle Scholar
  46. Hurt C, Tammaro D (2007) Diagnostic evaluation of mononucleosis-like illness. Amer J Med 120:911.e911–911.e918Google Scholar
  47. Janowicz D, Johnson R, Gupta S (2005) Successful treatment of CMV ventriculitis immune reconstitution syndrome. J Neurol Neurosurg Psychiatry 76:691–692Google Scholar
  48. Jesionek A, Kiolemenoglou R (1904) Uber einen Befund von protoenartigan…. Muench Med Wochenschr 51:1905–1907Google Scholar
  49. Jones K, Rivera C, Sgadari C, Franklin J, Max E, Bhatia KG, Tosato G (1995) Infection of human endothelial cells with Epstein-Barr virus. J Exp Med 182:1213–1221PubMedGoogle Scholar
  50. Johansen A (1931) Serous meningitis and infectious mononucleosis. Acta Med Scand 76:269Google Scholar
  51. Kalayjian R, Cohen M, Bonomo R, Flanigan T (1993) Cytomegalovirus ventriculoencephalitis in AIDS: a syndrome with distinct clinical and pathological features. Medicine 72:67–77PubMedGoogle Scholar
  52. Khattab M, Eslam M, Abd-eelfattah E (2009) Encephalitis, acute renal failure, and acute hepatitis caused by a viral infection in an immunocompetent young adult: a case report. J Med Case Rep 3:9289PubMedGoogle Scholar
  53. Klemola E, Kaariainen L (1965) Cytomegalovirus as a possible cause of a disease resembling infectious mononucleosis. Br Med J 2:1099–1102PubMedGoogle Scholar
  54. Klemola E, Weckman N, Haltia K, Kaariainen L (1967) The Guillain-Barre syndrome associated with acquired cytomegalovirus infection. Acta Med Scand 181:603–607PubMedGoogle Scholar
  55. Kuo Y, Chiu N, Shen C et al (1998) Cerebral perfusion in children with Alice in Wonderland syndrome. J Child Neurol 19:105–108Google Scholar
  56. Lahat E, Berkovitch M, Barr J, Peret G, Barzilai A (1999) Abnormal visual evoked potentials in children in “Alice in Wonderland” syndrome due to infectious mononucleosis. J Child Neurol 14:732–735PubMedGoogle Scholar
  57. Larocca L, Capello D, Rinelli A, Nori S, Antinori A et al (1998) The molecular and phenotypic profile of primary central nervous system lymphoma identifies distinct categories of the disease and is consistent with histogenetic derivation from germinal center-related B-cells. Blood 92:1011–1019PubMedGoogle Scholar
  58. Lascelles R, Johnson P, Longson M, Chiang A (1973) Infectious mononucleosis presenting as acute cerebellar syndrome. Lancet 2:707–709PubMedGoogle Scholar
  59. Leavell R, Ray CG, Ferry P, Minnich LL (1986) Unusual acute neurological presentations with Epstein-Barr virus infection. Arch Neurol 43:186–188PubMedGoogle Scholar
  60. Ljungman P (2002) Beta-Herpesvirus challenges in the transplant recipient. J Infect Dis 186:S99–S109PubMedGoogle Scholar
  61. McKendall R, Sadiq S, Calverley J (1990) Unusual manifestations of Epstein-Barr virus encephalomyelitis. Infection 18(1):33–35PubMedGoogle Scholar
  62. Miles C, Hoffman W, Lai C-W, Freeman J (1993) Cytomegalovirus-associated transverse myelitis. Neurology 43:2143–2145PubMedGoogle Scholar
  63. Mischler M, Fleming G, Shanley T, Madden L, Levine J, Castle V, Filipovich A, Cornell T (2006) Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease: a mimicker of sepsis in the pediatric intensive care unit. Pediatrics 119:e1212–e1218Google Scholar
  64. Mizuno T, Takanashi Y, Onodera H et al (2003) A case of lymphomatoid granulomatosis/angiocentric immunoproliferative lesion with long clinical course and diffuse brain involvement. J Neurol Sci 213:67–76PubMedGoogle Scholar
  65. Morgello S, Simpson D (1994) Multifocal cytomegalovirus demyelinative polyneuropathy associated with AIDS. Muscle Nerve 17:176–182PubMedGoogle Scholar
  66. Morgello S, Cho E-S, Nielsen S, Devinsky O, Petito C (1987) Cytomegalovirus encephalitis in patients with acquired immunodeficiency syndrome: an autopsy study of 30 cases and a review of the literature. Hum Pathol 18:289–297PubMedGoogle Scholar
  67. Niederman J, McCollum R, Henle G, Henle W (1968) Infectious mononucleosis clinical manifestations in relation to EB virus antibodies. JAMA 203:139–142Google Scholar
  68. North K, de Silva L, Procopis P (1993) Brain-stem encephalitis caused by Epstein-Barr virus. J Child Neurol 8:40–42PubMedGoogle Scholar
  69. Paul J, Bunnell W (1932) The presence of heterophile antibodies in infectious mononucleosis. Am J Med Sci 183:191–194Google Scholar
  70. Perham T, Caul E, Clarke S, Gibson A (1971) Cytomegalovirus meningoencephalitis. Br Med J 2:50PubMedGoogle Scholar
  71. Philips C, Fanning L, Gump D, Phillips C (1977) Cytomegalovirus encephalitis in immunologically normal adults: successful treatment with vidarabine. JAMA 238:2299–2300Google Scholar
  72. Phowthongkum P, Phantumchinda K, Jutivorakool K, Suankratay C (2007) Basal ganglia and brainstem encephalitis, optic neuritis, and radiculomyelitis in Epstein-Barr virus infection. J Infect 54:e141–e144PubMedGoogle Scholar
  73. Reddy S et al (2010) CMV central nervous system disease in stem-cell transplant recipients: an increasing complication of drug-resistant CMV infection and protracted immunodeficiency. Bone Marrow Transplant 45:979–984PubMedGoogle Scholar
  74. Richert J, Potolicchio S, Garagusi V, Manz H, Cohan S, Hartmann D, Johnson R (1987) Cytomegalovirus encephalitis associated with episodic neurologic deficits and OKT-8+ pleocytosis. Neurology 37:149–152PubMedGoogle Scholar
  75. Riley H Jr (1997) History of the cytomegalovirus. South Med J 90:184–190PubMedGoogle Scholar
  76. Roselli F, Russo I, Fraddosio A, Aniello M, De Mari M, Lamberti P, Livrea P, Defazio G (2006) Reversible parkinsonian syndrome associated with anti-neuronal antibodies in acute EBV encephalitis: a case report. Parkinsonism Relat Disord 12:257–260PubMedGoogle Scholar
  77. Roullet E, Assuerus V, Gozlan J, Ropert A, Said G, Baudriment M et al (1994) Cytomegalovirus multifocal neuropathy in AIDS: analysis of 15 consecutive cases. Neurology 44:2174–2182PubMedGoogle Scholar
  78. Russell J, Fisher M, Zivin J, Sullivan J, Drachman D (1985) Status epilepticus and Epstein-Barr virus encephalopathy diagnosis by modern serologic techniques. Arch Neurol 42:789–792PubMedGoogle Scholar
  79. Rowe W, Hartley J, Waterman S, Al E (1956) Cytopathogenic agent resembling human salivary gland virus recovered from tissue cultures of human adenoids. Proc Soc Exp Biol Med 92:418–424Google Scholar
  80. Schmahmann J (2004) Plasmapheresis improves outcome in postinfectious cerebellitis induced by Epstein-Barr virus. Neurology 62:1443PubMedGoogle Scholar
  81. Schmitz H, Enders G (1977) Cytomegalovirus as a frequent cause of Guillain Barre syndrome. J Med Virol 1:21–27PubMedGoogle Scholar
  82. Schneck S (1965) Neuropathologic features of human organ transplantation I. Probable cytomegalovirus infection. J Neuropathol Exp Neurol 24:415–429Google Scholar
  83. Schober R, Herman M (1973) Neuropathology of cardiac transplantation. Survey of 31 cases. Lancet 1:962–967PubMedGoogle Scholar
  84. Seo S, Regan A, Cihlar T, Lin D, Boulad F, George D, Prasad V, Kiehn T, Polsky B (2001) Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance. Clin Infect Dis 33:e105–e109PubMedGoogle Scholar
  85. Shian W, Chi C (1994) Fatal brainstem encephalitis caused by Epstein-Barr virus. Pediatr Radiol 24:596–597PubMedGoogle Scholar
  86. Shoji H, Goto Y, Yanase Y, Sato Y, Nakashima K, Natori H, Kaji M (1983) Recurrent cerebellitis. A case report of a possible relationship with Epstein-Barr virus infection. Kurume Med J 30:23–26PubMedGoogle Scholar
  87. Siegman-Igra Y, Michaeli D, Doron A, Weinberg M, Heilbrun Y (1984) Cytomegalovirus encephalitis in a noncompromised host. Isr J Med Sci 20:163–166PubMedGoogle Scholar
  88. Silverstein A, Steinberg G, Nathanson M (1972) Nervous system involvement in infectious mononucleosis. The heralding and/or major manifestation. Arch Neurol 26:353–358PubMedGoogle Scholar
  89. Sinzger C, Grefte A, Plachter B, Gouw A, The T, Jahn G (1995) Fibroblasts, epithelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol 76:741–750PubMedGoogle Scholar
  90. Smith M (1956) Propagation in tissue cultures of a cytopathic virus from human salivary gland virus (SGV) disease. Proc Soc Exp Biol Med 92:242–430Google Scholar
  91. Sprunt T, Evans F (1920) Mononuclear leucocytosis in reaction to acute infections (“infectious mononucleosis”). Johns Hopkins Hospital Bulletin 357:410–416Google Scholar
  92. Studahl M, Ricksten A, Sandburg T, Burgstrom T (1992) Cytomegalovirus encephalitis in four immunocompetent patients. Lancet 340:1045–1046PubMedGoogle Scholar
  93. Talpos D, Tien R, Hesselink J (1991) Magnetic resonance imaging of AIDS-related polyradiculopathy. Neurology 41:1996–1997Google Scholar
  94. Taylor L, Parsons-Smith G (1969) Infectious mononucleosis, deafness and facial paralysis. J Laryngol Otol 83:613–616PubMedGoogle Scholar
  95. Toorkey C, Carrigan D (1989) Immunohistochemical detection of an immediate early antigen of human cytomegalovirus in normal tissues. J Infect Dis 160:741–751PubMedGoogle Scholar
  96. Tselis A, Lavi E (2000) Cytomegalovirus in the adult nervous system. Infectious diseases of the nervous System LE Davis and PGE Kennedy. Butteworth–Heinemann, BostonGoogle Scholar
  97. Tselis A, Duman R, Storch G, Lisak R (1997) Epstein-Barr virus encephalomyelitis diagnosed by polymerase chain reaction: detection of the genome in the CSF. Neurology 48:1351–1355PubMedGoogle Scholar
  98. Tunkel A, Glaser C, Bloch K, Sejvar J, Marra C, Roos K, Hartman H, Kaplan S, Scheld W, Whitley R (2008) The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 47:303–327PubMedGoogle Scholar
  99. Tyler K, Gross R, Cascino G (1986) Unusual viral causes of transverse myelitis: hepatitis A and cytomegalovirus. Neurology 36:855–858PubMedGoogle Scholar
  100. Verma A, Brozman B (2002) Opsoclonus-myoclonus syndrome following Epstein-Barr virus infection. Neurology 58:1131–1132PubMedGoogle Scholar
  101. Von Glahn W, Pappenheimer A (1925) Intranuclear inclusions in visceral disease. Am J Pathol 1:445–465Google Scholar
  102. Waris E, Rasanen O, Kreus K-E, Kreus R (1972) Fatal cytomegalovirus disease in a previously healthy adult. Scand J Infect Dis 4:61–67PubMedGoogle Scholar
  103. Weinberg A, Li S, Palmer M, Tyler K (2002) Quantitative CSF PCR in Epstein-Barr virus infections of the central nervous system. Ann Neurol 52:543–548PubMedGoogle Scholar
  104. Weinberg A, Bloch K, Li S, Tang Y, Palmer M, Tyler K (2005) Dual infections of the central nervous system with Epstein-Barr virus. J Infect Dis 191:234–237PubMedGoogle Scholar
  105. Weller T, Macauley J, Craig J, Wirth P (1957) Isolation of intranuclearinclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease. Proc Soc Exp Biol Med 94:4–12Google Scholar
  106. Weller T (1970) Cytomegalovirus. The difficult years. J Infect Dis 122:532–539PubMedGoogle Scholar
  107. Weller T (2000) Cytomegalovirus: a historical perspective. Herpes 7:66–69PubMedGoogle Scholar
  108. Wyatt J, Saxton J, Lee R, Al E (1950) Generalized cytomegalic inclusion disease. J Pediat 36:271–294Google Scholar
  109. Zaganas I, Prinianakis G, Xirouchaki N, Mavridis M (2007) Opsoclonus-myoclonus syndrome associated with cytomegalovirus encephalitis. Neurology 68:1636PubMedGoogle Scholar
  110. Zaidi A, Kampalath B, Peltier W, Viesole D (2004) Successful treatment of systemic and central nervous system lymphomatoid granulomatosis with rituximab. Leuk Lymphoma 45:777–780PubMedGoogle Scholar

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© Springer Basel 2013

Authors and Affiliations

  1. 1.Department of NeurologyWayne State UniversityDetroitUSA

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