Skip to main content

Acute Viral Encephalitis: Herpesviruses and Enteroviruses

  • Chapter
  • First Online:
CNS Infections

Abstract

Acute encephalitis is a syndrome of diverse etiology, mostly viral, which varies according to the time of the year and the geographic location. Etiology remains unidentified in many cases. The current outcome of viral encephalitis remains unsatisfactory with high mortality and morbidity rates in adults and children. Worldwide, herpes simplex type 1 encephalitis is the most common cause of sporadic encephalitis. Viral encephalitis represents a medical emergency that requires prompt diagnosis and therapy and a high index of suspicion. Early initiation of antiviral therapy is crucial while diagnostic test are being performed. Supportive care should be directed at the prevention and treatment of secondary complications, including cerebral edema and epilepsy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kupila L, Vuorinen T, Vainionpaa R, Hukkanen V, Marttila RJ, Kotilainen P. Etiology of aseptic meningitis and encephalitis in an adult population. Neurology. 2006;66:75–80.

    Article  CAS  PubMed  Google Scholar 

  2. Glaser CA, Honarmand S, Anderson LJ, et al. Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis. 2006;43:1565–77.

    Article  CAS  PubMed  Google Scholar 

  3. Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res. 2006;71:141–8.

    Article  CAS  PubMed  Google Scholar 

  4. Olson LC, Buescher EL, Artenstein MS, Parkman PD. Herpesvirus infections of the human central nervous system. N Engl J Med. 1967;277:1271–7.

    Article  CAS  PubMed  Google Scholar 

  5. Hjalmarsson A, Blomqvist P, Skoldenberg B. Herpes simplex encephalitis in Sweden, 1990-2001: incidence, morbidity, and mortality. Clin Infect Dis. 2007;45:875–80.

    Article  PubMed  Google Scholar 

  6. Huppatz C, Durrheim DN, Levi C, et al. Etiology of encephalitis in Australia, 1990-2007. Emerg Infect Dis. 2009;15:1359–65.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Huppatz C, Kelly PM, Levi C, Dalton C, Williams D, Durrheim DN. Encephalitis in Australia, 1979-2006: trends and aetiologies. Commun Dis Intell Q Rep. ;33:192–7.

    Google Scholar 

  8. Whitley RJ, Kimberlin DW. Herpes simplex encephalitis: children and adolescents. Semin Pediatr Infect Dis. 2005;16:17–23.

    Article  PubMed  Google Scholar 

  9. Solomon T, Michael BD, Smith PE, et al. Management of suspected viral encephalitis in adults – Association of British Neurologists and British Infection Association National Guidelines. J Infect. 2012;64:347–73.

    Article  CAS  PubMed  Google Scholar 

  10. Nahmias AJ, Lee FK, Beckman-Nahmias S. Sero-epidemiological and -sociological patterns of herpes simplex virus infection in the world. Scand J Infect Dis Suppl. 1990;69:19–36.

    CAS  PubMed  Google Scholar 

  11. Steiner I, Kennedy PG. Herpes simplex virus latent infection in the nervous system. J Neurovirol. 1995;1:19–29.

    Article  CAS  PubMed  Google Scholar 

  12. Davis LE, Johnson RT. An explanation for the localization of herpes simplex encephalitis? Ann Neurol. 1979;5:2–5.

    Article  CAS  PubMed  Google Scholar 

  13. Fraser NW, Lawrence WC, Wroblewska Z, Gilden DH, Koprowski H. Herpes simplex type 1 DNA in human brain tissue. Proc Natl Acad Sci U S A. 1981;78:6461–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Whitley R, Lakeman AD, Nahmias A, Roizman B. Dna restriction-enzyme analysis of herpes simplex virus isolates obtained from patients with encephalitis. N Engl J Med. 1982;307:1060–2.

    Article  CAS  PubMed  Google Scholar 

  15. Koelle DM, Corey L. Recent progress in herpes simplex virus immunobiology and vaccine research. Clin Microbiol Rev. 2003;16:96–113.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Kapoor AK, Buckmaster A, Nash AA, Field HJ, Wildy P. Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice. Immunol Lett. 1982;5:259–65.

    Article  CAS  PubMed  Google Scholar 

  17. Sancho-Shimizu V, Zhang SY, Abel L, et al. Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans. Curr Opin Allergy Clin Immunol. 2007;7:495–505.

    Article  CAS  PubMed  Google Scholar 

  18. Rozenberg F. Acute viral encephalitis. Handb Clin Neurol. 2013;112:1171–81.

    Article  CAS  PubMed  Google Scholar 

  19. Casrouge A, Zhang SY, Eidenschenk C, et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science. 2006;314:308–12.

    Article  CAS  PubMed  Google Scholar 

  20. Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev. 2004;17:1–13.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA. 2003;289:203–9.

    Article  PubMed  Google Scholar 

  22. Kimura H, Futamura M, Kito H, et al. Detection of viral DNA in neonatal herpes simplex virus infections: frequent and prolonged presence in serum and cerebrospinal fluid. J Infect Dis. 1991;164:289–93.

    Article  CAS  PubMed  Google Scholar 

  23. Fisher CM. Hypomanic symptoms caused by herpes simplex encephalitis. Neurology. 1996;47:1374–8.

    Article  CAS  PubMed  Google Scholar 

  24. Fodor PA, Levin MJ, Weinberg A, Sandberg E, Sylman J, Tyler KL. Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF. Neurology. 1998;51:554–9.

    Article  CAS  PubMed  Google Scholar 

  25. Solomon T, Hart IJ, Beeching NJ. Viral encephalitis: a clinician’s guide. Pract Neurol. 2007;7:288–305.

    Article  PubMed  Google Scholar 

  26. Steiner I. Herpes simplex virus encephalitis: new infection or reactivation? Curr Opin Neurol. 2011;24:268–74.

    Article  PubMed  Google Scholar 

  27. Grover D, Newsholme W, Brink N, Manji H, Miller R. Herpes simplex virus infection of the central nervous system in human immunodeficiency virus-type 1-infected patients. Int J STD AIDS. 2004;15:597–600.

    Article  CAS  PubMed  Google Scholar 

  28. Tan IL, McArthur JC, Venkatesan A, Nath A. Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology. 2012;79:2125–32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Steiner I, Budka H, Chaudhuri A, et al. Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol. 2010;17:999–e57.

    Article  CAS  PubMed  Google Scholar 

  30. Corey L, Wald A. Maternal and neonatal herpes simplex virus infections. N Engl J Med. 2009;361:1376–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Whitley R, Arvin A, Prober C, et al. Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med. 1991;324:450–4.

    Article  CAS  PubMed  Google Scholar 

  32. De Tiege X, Heron B, Lebon P, Ponsot G, Rozenberg F. Limits of early diagnosis of herpes simplex encephalitis in children: a retrospective study of 38 cases. Clin Infect Dis. 2003;36:1335–9.

    Article  PubMed  Google Scholar 

  33. Elbers JM, Bitnun A, Richardson SE, et al. A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease? Pediatrics. 2007;119:e399–407.

    Article  PubMed  Google Scholar 

  34. De Tiege X, Rozenberg F, Burlot K, Gaudelus J, Ponsot G, Heron B. Herpes simplex encephalitis: diagnostic problems and late relapse. Dev Med Child Neurol. 2006;48:60–3.

    Article  PubMed  Google Scholar 

  35. Garcia-Ribes A, Martinez-Gonzalez MJ, Prats-Vinas JM. Suspected herpes encephalitis and opercular syndrome in childhood. Pediatr Neurol. 2007;36:202–6.

    Article  PubMed  Google Scholar 

  36. De Tiege X, Rozenberg F, Heron B. The spectrum of herpes simplex encephalitis in children. Eur J Paediatr Neurol. 2008;12:72–81.

    Article  PubMed  Google Scholar 

  37. Sabah M, Mulcahy J, Zeman A. Herpes simplex encephalitis. BMJ. 2012;344:e3166.

    Article  PubMed  Google Scholar 

  38. Lai CW, Gragasin ME. Electroencephalography in herpes simplex encephalitis. J Clin Neurophysiol. 1988;5:87–103.

    Article  CAS  PubMed  Google Scholar 

  39. Misra UK, Tan CT, Kalita J. Viral encephalitis and epilepsy. Epilepsia. 2008;49 Suppl 6:13–8.

    Article  PubMed  Google Scholar 

  40. Tuzun E, Dalmau J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist. 2007;13:261–71.

    Article  PubMed  Google Scholar 

  41. Raschilas F, Wolff M, Delatour F, et al. Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis. 2002;35:254–60.

    Article  PubMed  Google Scholar 

  42. Bell DJ, Suckling R, Rothburn MM, et al. Management of suspected herpes simplex virus encephalitis in adults in a U.K. teaching hospital. Clin Med. 2009;9:231–5.

    Article  PubMed  Google Scholar 

  43. Marchbank ND, Howlett DC, Sallomi DF, Hughes DV. Magnetic resonance imaging is preferred in diagnosing suspected cerebral infections. BMJ. 2000;320:187–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Kuker W, Nagele T, Schmidt F, Heckl S, Herrlinger U. Diffusion-weighted MRI in herpes simplex encephalitis: a report of three cases. Neuroradiology. 2004;46:122–5.

    Article  CAS  PubMed  Google Scholar 

  45. McCabe K, Tyler K, Tanabe J. Diffusion-weighted MRI abnormalities as a clue to the diagnosis of herpes simplex encephalitis. Neurology. 2003;61:1015–6.

    Article  PubMed  Google Scholar 

  46. Hinson VK, Tyor WR. Update on viral encephalitis. Curr Opin Neurol. 2001;14:369–74.

    Article  CAS  PubMed  Google Scholar 

  47. Bradford RD, Pettit AC, Wright PW, et al. Herpes simplex encephalitis during treatment with tumor necrosis factor-alpha inhibitors. Clin Infect Dis. 2009;49:924–7.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Razavi B, Razavi M. Herpes simplex encephalitis – an atypical case. Infection. 2001;29:357–8.

    Article  CAS  PubMed  Google Scholar 

  49. DeBiasi RL, Kleinschmidt-DeMasters BK, Weinberg A, Tyler KL. Use of PCR for the diagnosis of herpesvirus infections of the central nervous system. J Clin Virol. 2002;25 Suppl 1:S5–11.

    Article  CAS  PubMed  Google Scholar 

  50. Davies NW, Brown LJ, Gonde J, et al. Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections. J Neurol Neurosurg Psychiatry. 2005;76:82–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E. Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol. 2009;81:1432–7.

    Article  CAS  PubMed  Google Scholar 

  52. Aurelius E, Johansson B, Skoldenberg B, Forsgren M. Encephalitis in immunocompetent patients due to herpes simplex virus type 1 or 2 as determined by type-specific polymerase chain reaction and antibody assays of cerebrospinal fluid. J Med Virol. 1993;39:179–86.

    Article  CAS  PubMed  Google Scholar 

  53. Whitley RJ, Cobbs CG, Alford Jr CA, et al. Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group. JAMA. 1989;262:234–9.

    Article  CAS  PubMed  Google Scholar 

  54. Sobel RA, Collins AB, Colvin RB, Bhan AK. The in situ cellular immune response in acute herpes simplex encephalitis. Am J Pathol. 1986;125:332–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Esiri MM. Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain. J Neurol Sci. 1982;54:209–26.

    Article  CAS  PubMed  Google Scholar 

  56. Lellouch-Tubiana A, Fohlen M, Robain O, Rozenberg F. Immunocytochemical characterization of long-term persistent immune activation in human brain after herpes simplex encephalitis. Neuropathol Appl Neurobiol. 2000;26:285–94.

    Article  CAS  PubMed  Google Scholar 

  57. Skoldenberg B, Forsgren M. Acyclovir versus vidarabine in herpes simplex encephalitis. Scand J Infect Dis Suppl. 1985;47:89–96.

    CAS  PubMed  Google Scholar 

  58. Whitley RJ, Alford CA, Hirsch MS, et al. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med. 1986;314:144–9.

    Article  CAS  PubMed  Google Scholar 

  59. Dennett C, Klapper PE, Cleator GM. Polymerase chain reaction in the investigation of “relapse” following herpes simplex encephalitis. J Med Virol. 1996;48:129–32.

    Article  CAS  PubMed  Google Scholar 

  60. VanLandingham KE, Marsteller HB, Ross GW, Hayden FG. Relapse of herpes simplex encephalitis after conventional acyclovir therapy. JAMA. 1988;259:1051–3.

    Article  CAS  PubMed  Google Scholar 

  61. Valencia I, Miles DK, Melvin J, et al. Relapse of herpes encephalitis after acyclovir therapy: report of two new cases and review of the literature. Neuropediatrics. 2004;35:371–6.

    Article  CAS  PubMed  Google Scholar 

  62. Leypoldt F, Titulaer MJ, Aguilar E, et al. Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report. Neurology. 2013;81:1637–9.

    Article  PubMed  Google Scholar 

  63. Lycke J, Malmestrom C, Stahle L. Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir. Antimicrob Agents Chemother. 2003;47:2438–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Hollinger P, Matter L, Sturzenegger M. Normal MRI findings in herpes simplex virus encephalitis. J Neurol. 2000;247:799–801.

    Article  CAS  PubMed  Google Scholar 

  65. Pacheco LR, Tavares HM, Moyses Neto M, et al. Acute renal failure related to intravenous acyclovir. Rev Assoc Med Bras. 2005;51:275–8.

    Article  PubMed  Google Scholar 

  66. Chen Y, Scieux C, Garrait V, et al. Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation. Clin Infect Dis. 2000;31:927–35.

    Article  CAS  PubMed  Google Scholar 

  67. Cundy KC. Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. Clin Pharmacokinet. 1999;36:127–43.

    Article  CAS  PubMed  Google Scholar 

  68. Kamei S, Sekizawa T, Shiota H, et al. Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry. 2005;76:1544–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Yan HJ. Herpes simplex encephalitis: the role of surgical decompression. Surg Neurol. 2002;57:20–4.

    Article  PubMed  Google Scholar 

  70. Lo WB, Wilcock DJ, Carey M, Albanese E. Herpes encephalitis complicated by cerebral haemorrhage. J Neurol Neurosurg Psychiatry. 2013;84(12):1404–6.

    Google Scholar 

  71. Rodriguez-Sainz A, Escalza-Cortina I, Guio-Carrion L, et al. Intracerebral hematoma complicating herpes simplex encephalitis. Clin Neurol Neurosurg. 2013;115:2041–5.

    Article  PubMed  Google Scholar 

  72. Riancho J, Delgado-Alvarado M, Sedano MJ, Polo JM, Berciano J. Herpes simplex encephalitis: clinical presentation, neurological sequelae and new prognostic factors. Ten years of experience. Neurol Sci. 2013;34(10):1879–81.

    Google Scholar 

  73. Whitley RJ. Viral encephalitis. N Engl J Med. 1990;323:242–50.

    Article  CAS  PubMed  Google Scholar 

  74. Arciniegas DB, Anderson CA. Viral encephalitis: neuropsychiatric and neurobehavioral aspects. Curr Psychiatry Rep. ;6:372–9.

    Google Scholar 

  75. Gordon B, Selnes OA, Hart Jr J, Hanley DF, Whitley RJ. Long-term cognitive sequelae of acyclovir-treated herpes simplex encephalitis. Arch Neurol. 1990;47:646–7.

    Article  CAS  PubMed  Google Scholar 

  76. Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol. 2009;8:731–40.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Nagel MA, Gilden D. The challenging patient with varicella-zoster virus disease. Neurol Clin Pract. 2013;3:109–17.

    Article  PubMed Central  PubMed  Google Scholar 

  78. Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, Mahalingam R, Cohrs RJ. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med. 2000;342:635–45.

    Article  CAS  PubMed  Google Scholar 

  79. Cohen EJ. Prevention of herpes zoster: we need to do better. JAMA Ophthalmol. 2013;131:396–8.

    Article  PubMed  Google Scholar 

  80. Cohen JI. Clinical practice: herpes zoster. N Engl J Med. 2013;369:255–63.

    Article  CAS  PubMed  Google Scholar 

  81. Torgovnick J, Arsura EL, Lala D. Cytomegalovirus ventriculoencephalitis presenting as a Wernicke’s encephalopathy-like syndrome. Neurology. 2000;55:1910–3.

    Article  CAS  PubMed  Google Scholar 

  82. Ho M, Chen ER, Hsu KH, et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med. 1999;341:929–35.

    Article  CAS  PubMed  Google Scholar 

  83. Chang LY, Huang LM, Gau SS, et al. Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med. 2007;356:1226–34.

    Article  CAS  PubMed  Google Scholar 

  84. Rust RS. Human arboviral encephalitis. Semin Pediatr Neurol. 2012;19:130–51.

    Article  PubMed  Google Scholar 

  85. Huang C, Chatterjee NK, Grady LJ. Diagnosis of viral infections of the central nervous system. N Engl J Med. 1999;340:483–4.

    Article  CAS  PubMed  Google Scholar 

  86. Sonneville R, Klein IF, Wolff M. Update on investigation and management of postinfectious encephalitis. Curr Opin Neurol. 2010;23:300–4.

    Article  PubMed  Google Scholar 

  87. Garcia-Monco JC, Cortina IE, Ferreira E, et al. Reversible splenial lesion syndrome (RESLES): what’s in a name? J Neuroimaging. 2011;21:e1–14.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José Luis Sánchez-Menoyo MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

Sánchez-Menoyo, J.L., Ruiz-Ojeda, J. (2014). Acute Viral Encephalitis: Herpesviruses and Enteroviruses. In: García-Moncó, J. (eds) CNS Infections. Springer, London. https://doi.org/10.1007/978-1-4471-6401-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-6401-2_5

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-6400-5

  • Online ISBN: 978-1-4471-6401-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics