, Volume 73, Issue 2, pp 131–158 | Cite as

Acute Viral Infections of the Central Nervous System in Immunocompetent Adults: Diagnosis and Management

  • Marie Studahl
  • Lars Lindquist
  • Britt-Marie Eriksson
  • Göran Günther
  • Malin Bengner
  • Elisabeth Franzen-Röhl
  • Jan Fohlman
  • Tomas Bergström
  • Elisabeth Aurelius
Therapy in Practice


Patients with viral infections of the central nervous system (CNS) may present with a variety of neurological symptoms, most commonly dominated by either encephalitis or meningitis. The aetiological panorama varies in different parts of the world as well as over time. Thus, virological first-line diagnostics must be adapted to the current epidemiological situation and to the individual patient history, including recent travels. This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective. Effective vaccines are available for viruses such as poliovirus and tick-borne encephalitis virus (TBEV) and for the childhood diseases morbilli (measles), rubella (German measles), parotitis (mumps) and varicella (chickenpox). However, cases do appear due to suboptimal immunization rates. In viral CNS infections, epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses. Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital. A positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) finding is usually reliable for aetiological diagnosis. The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease, hitherto sufficiently evaluated in herpes simplex encephalitis (HSE) and tick-borne encephalitis (TBE). Despite improved virological and differential diagnostic methods, aetiology remains unknown in about half of the cases with suspected viral encephalitis. Antiviral treatment is available chiefly for infections caused by herpesviruses, and acyclovir (aciclovir) is the drug of choice for empirical therapy in suspected viral encephalitis. However, randomized, controlled antiviral trials have only been conducted for HSE, while such studies are lacking in other viral CNS infections. Viral cytolysis and immune-mediated mechanisms may contribute to varying extents to neurological damage. Although the brain damage is believed to depend, to a varying degree, on the intrathecal host immune response, the use of corticosteroids in viral CNS infections is scarcely studied, as is specific treatment for neuroinflammation. Improved antiviral and immunomodulating treatment is desirable. Since neurological sequelae are still abundant, follow-up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan.



This work was supported by The Swedish Society of Infectious Diseases and the LUA Foundation of the Sahlgrenska University Hospital.


  1. 1.
    Rantalaiho T, Färkkilä M, Vaheri A, et al. Acute encephalitis from 1967 to 1991. J Neurol Sci. 2001;184(2):169–77.PubMedCrossRefGoogle Scholar
  2. 2.
    Davison KL, Crowcroft NS, Ramsay ME, et al. Viral encephalitis in England, 1989–1998: what did we miss? Emerg Infect Dis. 2003;9(2):234–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Kupila L, Vuorinen T, Vainionpää R, et al. Etiology of aseptic meningitis and encephalitis in an adult population. Neurology. 2006;66(1):75–80.PubMedCrossRefGoogle Scholar
  4. 4.
    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(3):254–60.PubMedCrossRefGoogle Scholar
  5. 5.
    McGrath N, Anderson NE, Croxson MC, et al. Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry. 1997;63(3):321–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Domingues RB, Tsanaclis AM, Pannuti CS, et al. Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples. Clin Infect Dis. 1997;25(1):86–91.PubMedCrossRefGoogle Scholar
  7. 7.
    Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet. 2008;371(9627):1861–71.PubMedCrossRefGoogle Scholar
  8. 8.
    Persson A, Bergström T, Lindh M, et al. Varicella zoster virus CNS disease: viral load, clinical manifestations and sequels. J Clin Virol. 2009;46(3):249–53.PubMedCrossRefGoogle Scholar
  9. 9.
    Franzen-Röhl E, Tiveljung-Lindell A, Grillner L, et al. Increased detection rate in diagnosis of herpes simplex virus type 2 meningitis by real-time PCR using cerebrospinal fluid samples. J Clin Microbiol. 2007;45(8):2516–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Mailles A, Stahl JP. Infectious encephalitis in France in 2007: a national prospective study. Clin Infect Dis. 2009;49(12):1838–47.PubMedCrossRefGoogle Scholar
  11. 11.
    Graneröd J, Ambrose HE, Davies NW, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10(12):835–44.PubMedCrossRefGoogle Scholar
  12. 12.
    Franzen-Röhl E, Larsson K, Skoog E, et al. High diagnostic yield by CSF-PCR for entero- and herpes simplex viruses and TBEV serology in adults with acute aseptic meningitis in Stockholm. Scand J Infect Dis. 2008;40(11–12):914–21.PubMedCrossRefGoogle Scholar
  13. 13.
    Studahl M, Hagberg, Rekabdar E, et al. Hematogenously spread herpesviruses are detected as frequently as neuronally spread herpesviruses in cerebrospinal fluid by polymerase chain reaction assay. Clin Infect Dis. 1999;29(1):216–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Weinberg A, Bloch KC, Li S, Tang YW, Palmer M, Tyler KL. Dual infections of the central nervous system with Epstein–Barr virus. J Infect Dis. 2005;191(2):234–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Kleines M, Schiefer J, Stienen A, et al. Expanding the spectrum of neurological disease associated with Epstein–Barr virus activity. Eur J Clin Microbiol Infect Dis. 2011;30(12):1561–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Martelius T, Lappalainen M, Palomäki M, et al. Clinical characteristics of patients with Epstein–Barr virus in cerebrospinal fluid. BMC Infect Dis. 2011;11:281.PubMedCrossRefGoogle Scholar
  17. 17.
    Leong HN, Tuke PW, Tedder RS, et al. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J Med Virol. 2007;79(1):45–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Ward KN, Leong HN, Thiruchelvam AD, et al. Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection differ from those due to chromosomal viral integration and have implications for diagnosis of encephalitis. J Clin Microbiol. 2007;45(4):1298–304.PubMedCrossRefGoogle Scholar
  19. 19.
    Forsgren M, Sköldenberg B, Jeansson S, et al. Serodiagnosis of herpes encephalitis by indirect enzyme-linked immunosorbent assay, experience from a Swedish trial. Serodiagn Immunother Infect Dis. 1989;3(4):259–71.CrossRefGoogle Scholar
  20. 20.
    Gunther G, Haglund M, Lindquist L, et al. Intrathecal IgM, IgA and IgG antibody response in tick-borne encephalitis: long-term follow-up related to clinical course and outcome. Clin Diagn Virol. 1997;8(1):17–29.PubMedCrossRefGoogle Scholar
  21. 21.
    Gregoire SM, van Pesch V, Goffette S, et al. Polymerase chain reaction analysis and oligoclonal antibody in the cerebrospinal fluid from 34 patients with varicella-zoster virus infection of the nervous system. J Neurol Neurosurg Psychiatry. 2006;77(8):938–42.PubMedCrossRefGoogle Scholar
  22. 22.
    Solomon T, Michael BD, Smith PE, Sanderson F, Davies NW, Hart IJ, et al. Management of suspected viral encephalitis in adults. Association of British Neurologists and British Infection Association National Guidelines. J Infect. 2012;64(4):347–73.PubMedCrossRefGoogle Scholar
  23. 23.
    Tunkel AR, Glaser CA, Bloch KC, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47(3):303–27.PubMedCrossRefGoogle Scholar
  24. 24.
    Aurelius E, Johansson B, Sköldenberg B, et al. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet. 1991;337(8735):189–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Aurelius E, Johansson B, Sköldenberg B, et al. 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(3):179–86.PubMedCrossRefGoogle Scholar
  26. 26.
    Guffond T, Dewilde A, Lopert PE, et al. Significance and clinical relevance of the detection of herpes simplex virus DNA by the polymerase chain reaction in cerebrospinal fluid from patients with presumed encephalitis. Clin Infect Dis. 1994;18(5):744–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Studahl M, Bergström T, Hagberg L. Acute viral encephalitis in adults: a prospective study. Scand J Infect Dis. 1998;30(3):215–20.PubMedCrossRefGoogle Scholar
  28. 28.
    Puchhammer-Stöckl E, Presterl E, Aberle S, et al. Screening for possible failure of herpes simplex virus PCR in cerebrospinal fluid for the diagnosis of herpes simplex encephalitis. J Med Virol. 2001;64(4):531–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Weil AA, Glaser CA, Amad Z, et al. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis. 2002;34(8):1154–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Wald A, Zeh J, Selke S, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000;342(12):844–50.PubMedCrossRefGoogle Scholar
  31. 31.
    Kennedy PG. A retrospective analysis of forty-six cases of herpes simplex encephalitis seen in Glasgow between 1962 and 1985. Q J Med. 1988;68(255):533–40.PubMedGoogle Scholar
  32. 32.
    Sköldenberg B, Forsgren M, Alestig K, et al. Acyclovir versus vidarabine in herpes simplex encephalitis: randomised multicentre study in consecutive Swedish patients. Lancet. 1984;2(8405):707–11.PubMedCrossRefGoogle Scholar
  33. 33.
    Whitley RJ, Soong SJ, Linneman C, et al. Herpes simplex encephalitis: clinical assessment. JAMA. 1982;247(3):317–20.PubMedCrossRefGoogle Scholar
  34. 34.
    Utley TFM, Ogden JA, Gibb A, McGrath N, Anderson NE. The long-term neuro-psychological outcome of herpes simplex encephalitis in a series of unselected survivors. Neuropsychiatry Neuropsychol Behav Neurol. 1997;10:180–9.PubMedGoogle Scholar
  35. 35.
    Gordon B, Selnes OA, Hart J Jr, Hanley DF, Whitley RJ. Long-term cognitive sequelae of acyclovir-treated herpes simplex encephalitis. Arch Neurol. 1990;47:646–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Whitley RJ, Alford CA, Hirsch MS, et al. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med. 1986;314(3):144–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Hjalmarsson A, Blomqvist P, Sköldenberg B. Herpes simplex encephalitis in Sweden, 1990–2001: incidence, morbidity, and mortality. Clin Infect Dis. 2007;45(7):875–80.PubMedCrossRefGoogle Scholar
  38. 38.
    Dennett C, Cleator GM, Klapper PE. HSV-1 and HSV-2 in herpes simplex encephalitis: a study of sixty-four cases in the United Kingdom. J Med Virol. 1997;53(1):1–3.PubMedCrossRefGoogle Scholar
  39. 39.
    Vandvik B, Sköldenberg B, Forsgren M, et al. Long-term persistence of intrathecal virus-specific antibody responses after herpes simplex virus encephalitis. J Neurol. 1985;231(6):307–12.PubMedCrossRefGoogle Scholar
  40. 40.
    Domingues RB, Fink MC, Tsanaclis AM, et al. Diagnosis of herpes simplex encephalitis by magnetic resonance imaging and polymerase chain reaction assay of cerebrospinal fluid. J Neurol Sci. 1998;157(2):148–53.PubMedCrossRefGoogle Scholar
  41. 41.
    Schlesinger Y, Buller RS, Brunstrom JE, et al. Expanded spectrum of herpes simplex encephalitis in childhood. J Pediatr. 1995;126(2):234–41.PubMedCrossRefGoogle Scholar
  42. 42.
    Schmidbauer M, Podreka I, Winberger D, et al. SPECT and MR imaging in herpes simplex encephalitis. J Comput Assist Tomogr. 1991;15(5):811–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Schroth G, Gawehn J, Thron A, et al. Early diagnosis of herpes simplex encephalitis by MRI. Neurology. 1987;37(2):179–83.PubMedCrossRefGoogle Scholar
  44. 44.
    Hindmarsh T, Lindqvist M, Olding-Stenkvist E, et al. Accuracy of computed tomography in the diagnosis of herpes simplex encephalitis. Acta Radiol Suppl. 1986;369:192–6.PubMedGoogle Scholar
  45. 45.
    Bergey GK, Coyle PK, Krumholz A, et al. Herpes simplex encephalitis with occipital localization. Arch Neurol. 1982;39(5):312–3.PubMedCrossRefGoogle Scholar
  46. 46.
    Studahl M, Sköldenberg B. Herpes simplex encephalitis and other neurological syndromes caused by herpes simplex virus-1. In: Studahl M, Cinque P, Bergström T, editors. Herpes simplex viruses. New York: Taylor & Francis; 2006. p. 275–316.Google Scholar
  47. 47.
    Brodtkorb E, Lindqvist M, Jonsson M, et al. Diagnosis of herpes simplex encephalitis: a comparison between electro-encephalography and computed tomography findings. Acta Neurol Scand. 1982;66(4):462–71.PubMedCrossRefGoogle Scholar
  48. 48.
    Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. 2000;54(2):340–5.PubMedCrossRefGoogle Scholar
  49. 49.
    Schloss L, Falk KI, Skoog E, et al. 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(8):1432–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Cinque P, Cleator GM, Weber T, et al. The role of laboratory investigation in the diagnosis and management of patients with suspected herpes simplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis. J Neurol Neurosurg Psychiatry. 1996;61(4):339–45.PubMedCrossRefGoogle Scholar
  51. 51.
    National Institute of Allergy and Infectious Diseases (NIAID). Long term treatment of herpes simplex encephalitis (HSE) with valacyclovir [Clinicaltrials.gov identifier NCT00031486]. US National Institutes of Health, ClinicalTrials.gov. http://www.clinicaltrials.gov. Accessed 2 May 2012.
  52. 52.
    Stahl JP, Mailles A, De Broucker T, et al. Herpes simplex encephalitis and management of acyclovir in encephalitis patients in France. Epidemiol Infect. 2012;140(2):372–81.PubMedCrossRefGoogle Scholar
  53. 53.
    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(11):1544–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Martinez-Torres F, et al. Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933]. BMC Neurol. 2008;29(8):40.CrossRefGoogle Scholar
  55. 55.
    Sköldenberg B, Aurelius E, Hjalmarsson A, et al. Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults. J Neurol. 2006;253(2):163–70.PubMedCrossRefGoogle Scholar
  56. 56.
    Tedder DG, Ashley R, Tyler KL, et al. Herpes simplex virus infection as a cause of benign recurrent lymphocytic meningitis. Ann Intern Med. 1994;121(5):334–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Bergström T, Vahlne A, Alestig K, et al. Primary and recurrent herpes simplex virus type 2-induced meningitis. J Infect Dis. 1990;162(2):322–30.PubMedCrossRefGoogle Scholar
  58. 58.
    O’Sullivan CE, Aksamit AJ, Harrington JR, et al. Clinical spectrum and laboratory characteristics associated with detection of herpes simplex virus DNA in cerebrospinal fluid. Mayo Clin Proc. 2003;78(11):1347–52.PubMedCrossRefGoogle Scholar
  59. 59.
    Sköldenberg B, Jeansson S, Wolontis S. Herpes simplex virus type 2 and acute aseptic meningitis: clinical features of cases with isolation of herpes simplex virus from cerebrospinal fluids. Scand J Infect Dis. 1975;7(4):227–32.PubMedGoogle Scholar
  60. 60.
    Corey L, Adams HG, Brown ZA, et al. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med. 1983;98(6):958–72.PubMedCrossRefGoogle Scholar
  61. 61.
    Aurelius E, Forsgren M, Gille E, et al. Neurologic morbidity after herpes simplex virus type 2 meningitis: a retrospective study of 40 patients. Scand J Infect Dis. 2002;34(4):278–83.PubMedCrossRefGoogle Scholar
  62. 62.
    Terni M, Caccialanza P, Cassai E, et al. Aseptic meningitis in association with herpes progenitalis. N Engl J Med. 1971;285(9):503–4.PubMedCrossRefGoogle Scholar
  63. 63.
    Bachmeyer C, de la Blanchardière A, Lepercq J, et al. Recurring episodes of meningitis (Mollaret’s meningitis) with one showing an association with herpes simplex virus type 2. J Infect. 1996;32(3):247–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Kallio-Laine K, Seppänen M, Kautiainen H, et al. Recurrent lymphocytic meningitis positive for herpes simplex virus type 2. Emerg Infect Dis. 2009;15(7):1119–22.PubMedCrossRefGoogle Scholar
  65. 65.
    Aurelius E, Franzen-Röhl E, Glimåker M, et al. Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis: a double-blind, randomised, controlled trial. Clin Infect Dis. 2012;54(9):1304–13.PubMedCrossRefGoogle Scholar
  66. 66.
    Read S, Kurtz JB. Laboratory diagnosis of common viral infections of the central nervous system by using a single multiplex PCR screening assay. J Clin Microbiol. 1999;37(5):1352–5.PubMedGoogle Scholar
  67. 67.
    Brenton DW. Hypoglycorrhachia in herpes simplex type 2 meningitis. Arch Neurol. 1980;37(5):317.PubMedCrossRefGoogle Scholar
  68. 68.
    Sköldenberg B, Jeansson S, Wolontis S. Herpes simplex virus type 2 in acute aseptic meningitis. Br Med J. 1973;2(5866):611.PubMedCrossRefGoogle Scholar
  69. 69.
    Kupila L, Vainionpää R, Vuorinen T, et al. Recurrent lymphocytic meningitis: the role of herpesviruses. Arch Neurol. 2004;61(10):1553–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Aurelius E. Neurological disease in herpes simplex virus type 2 (HSV-2) infection. In: Studahl M, Cinque P, Bergström T, editors. Herpes simplex viruses. New York: Taylor & Francis; 2006. p. 317–38.Google Scholar
  71. 71.
    Lycke J, Malmeström C, Ståhle L. Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir. Antimicrob Agents Chemother. 2003;47(8):2438–41.PubMedCrossRefGoogle Scholar
  72. 72.
    Bergström T, Alestig K. Treatment of primary and recurrent herpes simplex virus type 2 induced meningitis with acyclovir. Scand J Infect Dis. 1990;22(2):239–40.PubMedCrossRefGoogle Scholar
  73. 73.
    Berger JR. Benign aseptic (Mollaret’s) meningitis after genital herpes. Lancet. 1991;115(1):19–21.Google Scholar
  74. 74.
    Koskiniemi M, Piiparinen H, Rantalaiho T, et al. Acute central nervous system complications in varicella zoster virus infections. J Clin Virol. 2002;25(3):293–301.PubMedCrossRefGoogle Scholar
  75. 75.
    Ziebold C, von Kries R, Lang R, et al. Severe complications of varicella in previously healthy children in Germany: a 1-year survey. Pediatrics. 2001;108(5):1–6.Google Scholar
  76. 76.
    Frenos S, Galli L, Chiappini E, et al. An increasing incidence of chickenpox central nervous system complications in children: what’s happening in Tuscany? J Clin Virol. 2007;38(4):358–61.PubMedCrossRefGoogle Scholar
  77. 77.
    Rack AL, Grote V, Streng A, et al. Neurologic varicella complications before routine immunization in Germany. Pediatr Neurol. 2010;42(1):40–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Glaser CA, Gilliam S, Schnurr D, et al. In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998–2000. Clin Infect Dis. 2003;36(6):731–42.PubMedCrossRefGoogle Scholar
  79. 79.
    Guess HA, Broughton DD, Melton LJ 3rd, et al. Population-based studies of varicella complications. Pediatrics. 1986;78(4Pt2):723–7.PubMedGoogle Scholar
  80. 80.
    Connolly AM, Dodson E, Prensky AL, et al. Course and outcome of acute cerebellar ataxia. Ann Neurol. 1994;35(6):673–9.Google Scholar
  81. 81.
    Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. 2001;71(2):149–54.PubMedCrossRefGoogle Scholar
  82. 82.
    Gilden D, Cohrs RJ, Mahalingam R, et al. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol. 2009;8(8):731–40.PubMedCrossRefGoogle Scholar
  83. 83.
    Ciccone S, Faggioli R, Calzolari F, et al. Stroke after varicella-zoster infection: report of a case and review of the literature. Pediatr Infect Dis J. 2010;29(9):864–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Sebire G, Meyer L, Chabrier S. Varicella as a risk factor for cerebral infarction in childhood: a case–control study. Ann Neurol. 1999;45(5):679–80.PubMedCrossRefGoogle Scholar
  85. 85.
    Nagel MA, Cohrs RJ, Mahalingam R, et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology. 2008;70(11):853–60.PubMedCrossRefGoogle Scholar
  86. 86.
    Hattori H, Higuchi Y, Tsuji M. Recurrent strokes after varicella. Ann Neurol. 2000;47(1):136.PubMedCrossRefGoogle Scholar
  87. 87.
    Berger TM, Caduff JH, Gebbers JO. Fatal varicella-zoster antigen-positive giant cell arteritis of the central nervous system. Pediatr Infect Dis J. 2000;19(7):653–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Okanishi T, Kondo A, Inoue T, Maegaki Y, Ohno K, Togari H. Bilateral middle cerebral artery infarctions following mild varicella infection: a case report. Brain Dev. 2009;31(1):86–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Hokkanen L, Launes J, Poutiainen E, et al. Subcortical type cognitive impairment in herpes zoster encephalitis. J Neurol. 1997;244(4):239–45.PubMedCrossRefGoogle Scholar
  90. 90.
    Aberle SW, Aberle JH, Steininger C, et al. Quantitative real time PCR detection of varicella zoster virus DNA in cerebrospinal fluid in patients with neurological disease. Med Microbiol Immunol. 2005;194(1–2):7–12.PubMedCrossRefGoogle Scholar
  91. 91.
    Mathiesen T, Linde A, Olding-Stenkvist E, et al. Antiviral IgM and IgG subclasses in varicella zoster associated neurological syndromes. J Neurol Neurosurg Psychiatry. 1989;52(5):578–82.PubMedCrossRefGoogle Scholar
  92. 92.
    Grahn A, Studahl M, Nilsson S, et al. Varicella-zoster virus (VZV) glycoprotein E is a serological antigen for detection of intrathecal antibodies to VZV in central nervous system infections, without cross-reaction to herpes simplex virus 1. Clin Vaccine Immunol. 2011;18(8):1336–42.PubMedCrossRefGoogle Scholar
  93. 93.
    Pahud BA, Glaser CA, Dekker CL, et al. Varicella zoster disease of the central nervous system: epidemiological, clinical, and laboratory features 10 years after the introduction of the varicella vaccine. J Infect Dis. 2011;203(3):316–23.PubMedCrossRefGoogle Scholar
  94. 94.
    Haanpää M, Dastidar P, Weinberg A, et al. CSF and MRI findings in patients with acute herpes zoster. Neurology. 1998;51(5):1405–11.PubMedCrossRefGoogle Scholar
  95. 95.
    Tien RD, Felsberg GJ, Osumi AK. Herpesvirus infections of the CNS: MR findings. Am J Roentgenol. 1993;161(1):167–76.CrossRefGoogle Scholar
  96. 96.
    Küker W. Cerebral vasculitis: imaging signs revisited. Neuroradiology. 2007;49(6):471–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Gnann JW, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. 2002;347(5):340–6.PubMedCrossRefGoogle Scholar
  98. 98.
    Gilden D. Varicella zoster virus and central nervous system syndromes. Herpes. 2004;11(Suppl 2):89A–94A.PubMedGoogle Scholar
  99. 99.
    Devriese PP, Moesker WH. The natural history of facial paralysis in herpes zoster. Clin Otolaryngol Allied Sci. 1988;13(4):289–98.PubMedCrossRefGoogle Scholar
  100. 100.
    Kinishi M, Amatsu M, Mohri M, et al. Acyclovir improves recovery rate of facial nerve palsy in Ramsay Hunt syndrome. Auris Nasus Larynx. 2001;28(3):223–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Furuta Y, Othani F, Mesuda Y, et al. Early diagnosis of zoster sine herpete and antiviral therapy for the treatment of facial palsy. Neurology. 2000;55(5):708–10.PubMedCrossRefGoogle Scholar
  102. 102.
    Murakami S, Hato N, Horiuchi J, et al. Treatment of Ramsay Hunt syndrome with acyclovir-prednisone: significance of early diagnosis and treatment. Ann Neurol. 1997;41(3):353–7.PubMedCrossRefGoogle Scholar
  103. 103.
    Uscategui T, Doree C, Chamberlain IJ, et al. Antiviral therapy for Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database Syst Rev. 2008;8(4):CD006851.Google Scholar
  104. 104.
    Uscategui T, Doree C, Chamberlain IJ, et al. Corticosteroids as adjuvant to antiviral treatment in Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database Syst Rev. 2008;16(3):CD006852.Google Scholar
  105. 105.
    Seward JF, Watson BM, Peterson CL, et al. Varicella disease after introduction of varicella vaccine in the United States, 1995–2000. JAMA. 2002;287(5):606–11.PubMedCrossRefGoogle Scholar
  106. 106.
    Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–84.PubMedCrossRefGoogle Scholar
  107. 107.
    Rafailidis PI, Mourtzoukou EG, Varbobitis IC, et al. Severe cytomegalovirus infection in apparently immuncompetent patients: a systematic review. Virol J. 2008;5:47.PubMedCrossRefGoogle Scholar
  108. 108.
    Arribas JR, Storch GA, Clifford DB, et al. Cytomegalovirus encephalitis. Ann Intern Med. 1996;125(7):577–87.PubMedCrossRefGoogle Scholar
  109. 109.
    Griffiths P. Cytomegalovirus infection of the central nervous system. Herpes. 2004;11(Suppl 2):95A–104A.PubMedGoogle Scholar
  110. 110.
    Koskiniemi M, Rantalaiho T, Piiparinen H, et al. Infections of the central nervous system of suspected viral origin: a collaborative study from Finland. J Neurovirol. 2001;7(5):400–8.PubMedCrossRefGoogle Scholar
  111. 111.
    Yao K, Honarmand S, Espinosa A, et al. Detection of human herpesvirus-6 in cerebrospinal fluid of patients with encephalitis. Ann Neurol. 2009;65(3):257–67.PubMedCrossRefGoogle Scholar
  112. 112.
    Ward KN, Leong HN, Nacheva EP, et al. Human herpes virus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles. J Clin Microbiol. 2006;44(4):1571–4.PubMedCrossRefGoogle Scholar
  113. 113.
    Volpi A. Epstein-Barr virus and human herpesvirus type 8 infections of the central nervous system. Herpes. 2004;11(Suppl 2):120A–7A.PubMedGoogle Scholar
  114. 114.
    Caserta MT, Hall CB, Schnabel K, et al. Neuroinvasion and persistence of human herpesvirus 6 in children. J Infect Dis. 1994;170(6):1586–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Hall CB, Long CE, Schnabel KC, et al. Human herpesvirus-6 infection in children: a prospective study of complications and reactivation. N Engl J Med. 1994;331(7):432–8.PubMedCrossRefGoogle Scholar
  116. 116.
    Ljungman P, Singh N. Human herpesvirus-6 infection in solid organ and stem cell transplant recipients. J Clin Virol. 2006;37(Suppl. 1):S87–91.PubMedCrossRefGoogle Scholar
  117. 117.
    McCullers JA, Lakeman FD, Whitley RJ. Human herpesvirus 6 is associated with focal encephalitis. Clin Infect Dis. 1995;21(3):571–6.PubMedCrossRefGoogle Scholar
  118. 118.
    Studahl M, Hagberg L, Rekabdar E, et al. Hematogenously spread herpesviruses are detected as frequently as neuronally spread herpesviruses in cerebrospinal fluid by polymerase chain reaction assay. Clin Infect Dis. 1999;29(1):216–8.PubMedCrossRefGoogle Scholar
  119. 119.
    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(1):82–7.PubMedCrossRefGoogle Scholar
  120. 120.
    Weber T, Beck R, Stark E, et al. Comparative analysis of intrathecal antibody synthesis and DNA amplification for the diagnosis of cytomegalovirus infection of the central nervous system in AIDS patients. J Neurol. 1994;241(7):407–14.PubMedCrossRefGoogle Scholar
  121. 121.
    Majid A, Galetta SL, Sweeney CJ, et al. Epstein–Barr virus myeloradiculitis and encephalomyeloradiculitis. Brain. 2002;125(Pt 1):159–65.PubMedCrossRefGoogle Scholar
  122. 122.
    Patnaik M, Peter JB. Intrathecal synthesis of antibodies to human herpesvirus 6 early antigen in patients with meningitis/encephalitis. Clin Infect Dis. 1995;21(3):715–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Abul-Kasim K, Palm L, Maly P, et al. The neuroanatomic localization of Epstein–Barr virus encephalitis may be a predictive factor for its clinical outcome: a case report and review of 100 cases in 28 reports. J Child Neurol. 2009;24(6):720–6.PubMedCrossRefGoogle Scholar
  124. 124.
    Mattes FM, Hainsworth EG, Geretti AM, et al. A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients. J Infect Dis. 2004;189(8):1355–61.PubMedCrossRefGoogle Scholar
  125. 125.
    Demey HE, Martin JJ, Leus RM, et al. Coma as a presenting sign of Epstein–Barr encephalitis. Arch Intern Med. 1988;148(6):1459–61.PubMedCrossRefGoogle Scholar
  126. 126.
    Dellemijn PL, Brandenburg A, Niesters HG, et al. Successful treatment with ganciclovir of presumed Epstein–Barr meningo-encephalitis following bone marrow transplant. Bone Marrow Transplant. 1995;16(2):311–2.PubMedGoogle Scholar
  127. 127.
    Straus SE, Cohen JI, Tosato G, et al. NIH conference. Epstein–Barr virus infections: biology, pathogenesis and management. Ann Intern Med. 1993;118(1):45–58.PubMedCrossRefGoogle Scholar
  128. 128.
    Troy SB, Blackburn BG, Yeom K, et al. Severe encephalomyelitis in an immunocompetent adult with chromosomally integrated human herpesvirus 6 and clinical response to treatment with foscarnet plus ganciclovir. Clin Infect Dis. 2008;47(12):e93–6.PubMedCrossRefGoogle Scholar
  129. 129.
    Birnbaum T, Padovan CS, Sporer B, et al. Severe meningoencephalitis caused by human herpesvirus 6 type B in an immunocompetent woman treated with ganciclovir. Clin Infect Dis. 2005;40(6):887–9.PubMedCrossRefGoogle Scholar
  130. 130.
    Zerr DM, Gupta D, Huang ML, et al. Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34(3):309–17.PubMedCrossRefGoogle Scholar
  131. 131.
    Pöhlmann C, Schetelig J, Reuner U, et al. Cidofovir and foscarnet for treatment of human herpesvirus 6 encephalitis in a neutropenic stem cell transplant recipient. Clin Infect Dis. 2007;44(12):e118–20.PubMedCrossRefGoogle Scholar
  132. 132.
    Astriti M, Zeller V, Boutolleau D, et al. Fatal HHV-6 associated encephalitis in an HIV-1 infected patient treated with cidofovir. J Infect. 2006;52(4):237–42.PubMedCrossRefGoogle Scholar
  133. 133.
    Gunther G, Haglund M, Lindquist L, et al. Tick-bone encephalitis in Sweden in relation to aseptic meningo-encephalitis of other etiology: a prospective study of clinical course and outcome. J Neurol. 1997;244(4):230–8.PubMedCrossRefGoogle Scholar
  134. 134.
    Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994–98: a prospective study of 656 patients. Brain. 1999;122(Pt 11):2067–78.PubMedCrossRefGoogle Scholar
  135. 135.
    Mickiene A, Laiskonis A, Gunther G, et al. Tickborne encephalitis in an area of high endemicity in Lithuania: disease severity and long-term prognosis. Clin Infect Dis. 2002;35(6):650–8.PubMedCrossRefGoogle Scholar
  136. 136.
    Ecker M, Allison SL, Meixner T, et al. Sequence analysis and genetic classification of tick-borne encephalitis viruses from Europe and Asia. J Gen Virol. 1999;80(Pt 1):179–85.PubMedGoogle Scholar
  137. 137.
    Holzmann H, Vorobyova MS, Ladyzhenskaya IP, et al. Molecular epidemiology of tick-borne encephalitis virus: cross-protection between European and Far Eastern subtypes. Vaccine. 1992;10(5):345–9.PubMedCrossRefGoogle Scholar
  138. 138.
    Holmgren EB, Forsgren M. Epidemiology of tick-borne encephalitis in Sweden 1956–1989: a study of 1116 cases. Scand J Infect Dis. 1990;22(3):287–95.PubMedCrossRefGoogle Scholar
  139. 139.
    Haglund M, Forsgren M, Lindh G, et al. A 10-year follow-up study of tick-borne encephalitis in the Stockholm area and a review of the literature: need for a vaccination strategy. Scand J Infect Dis. 1996;28(3):217–24.PubMedCrossRefGoogle Scholar
  140. 140.
    Puchhammer-Stockl E, Kunz C, Mandl CW, et al. Identification of tick-borne encephalitis virus ribonucleic acid in tick suspensions and in clinical specimens by a reverse transcription-nested polymerase chain reaction assay. Clin Diagn Virol. 1995;4(4):321–6.PubMedCrossRefGoogle Scholar
  141. 141.
    Saksida A, Duh D, Lotric-Furlan S, et al. The importance of tick-borne encephalitis virus RNA detection for early differential diagnosis of tick-borne encephalitis. J Clin Virol. 2005;33(4):331–5.PubMedCrossRefGoogle Scholar
  142. 142.
    Andersson CR, Vene S, Insulander M, et al. Vaccine failures after active immunisation against tick-borne encephalitis. Vaccine. 2010;28(16):2827–31.PubMedCrossRefGoogle Scholar
  143. 143.
    Stiasny K, Holzmann H, Heinz FX. Characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs. Vaccine. 2009;27(50):7021–6.PubMedCrossRefGoogle Scholar
  144. 144.
    Lorenzl S, Pfister HW, Padovan C, et al. MRI abnormalities in tick-borne encephalitis. Lancet. 1996;347(9002):698–9.PubMedCrossRefGoogle Scholar
  145. 145.
    Marjelund S, Tikkakoski T, Tuisku S, et al. Magnetic resonance imaging findings and outcome in severe tick-borne encephalitis: report of four cases and review of the literature. Acta Radiol. 2004;45(1):88–94.PubMedCrossRefGoogle Scholar
  146. 146.
    Waldvogel K, Bossart W, Huisman T, et al. Severe tick-borne encephalitis following passive immunisation. Eur J Pediatr. 1996;155(9):775–9.PubMedCrossRefGoogle Scholar
  147. 147.
    Broker M, Kollaritsch H. After a tick bite in a tick-borne encephalitis virus endemic area: current positions about post-exposure treatment. Vaccine. 2008;26(7):863–8.PubMedCrossRefGoogle Scholar
  148. 148.
    Stefanoff P, Polkowska A, Giambi C, et al. Reliable surveillance of tick-borne encephalitis in European countries is necessary to improve the quality of vaccine recommendations. Vaccine. 2011;29(6):1283–8.PubMedCrossRefGoogle Scholar
  149. 149.
    Heinz FX, Holzmann H, Essl A, et al. Field effectiveness of vaccination against tick-borne encephalitis. Vaccine. 2007;25(43):7559–67.PubMedCrossRefGoogle Scholar
  150. 150.
    Weinberger B, Keller M, Fischer KH, et al. Decreased antibody titers and booster responses in tick-borne encephalitis vaccinees aged 50–90 years. Vaccine. 2010;28(20):3511–5.PubMedCrossRefGoogle Scholar
  151. 151.
    Hainz U, Jenewein B, Asch E, et al. Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine. 2005;23(25):3232–5.PubMedCrossRefGoogle Scholar
  152. 152.
    Loew-Baselli A, Poellabauer EM, Pavlova BG, et al. Seropersistence of tick-borne encephalitis antibodies, safety and booster response to FSME-IMMUN 0.5 ml in adults aged 18–67 years. Hum Vaccin. 2009;5(8):551–6.PubMedCrossRefGoogle Scholar
  153. 153.
    Loew-Baselli A, Konior R, Pavlova BG, et al. Safety and immunogenicity of the modified adult tick-borne encephalitis vaccine FSME-IMMUN: results of two large phase 3 clinical studies. Vaccine. 2006;24(24):5256–63.PubMedCrossRefGoogle Scholar
  154. 154.
    Zent O, Jilg W, Plentz A, et al. Kinetics of the immune response after primary and booster immunization against tick-borne encephalitis (TBE) in adults using the rapid immunization schedule. Vaccine. 2003;21(32):4655–60.PubMedCrossRefGoogle Scholar
  155. 155.
    Beran J, Douda P, Gniel D, et al. Long-term immunity after vaccination against tick-borne encephalitis with encepur using the rapid vaccination schedule. In J Med Microbiol. 2004;293(Suppl 37):130–3.Google Scholar
  156. 156.
    Schöndorf I, Beran J, Cizkova D, et al. Tick-borne encephalitis (TBE) vaccination: applying the most suitable vaccination schedule. Vaccine. 2007;25(8):1470–5.PubMedCrossRefGoogle Scholar
  157. 157.
    Stiasny K, Aberle JH, Keller M, et al. Age affects quantity but not quality of antibody responses after vaccination with an inactivated flavivirus vaccine against tick-borne encephalitis. PLoS One. 2012;7(3):e34145.PubMedCrossRefGoogle Scholar
  158. 158.
    Lee BE, Davies HD. Aseptic meningitis. Curr Opin Infect Dis. 2007;20(3):272–7.PubMedCrossRefGoogle Scholar
  159. 159.
    Ropka SL, Jubelt B. Enteroviruses. In: Nath A, Berger JR, editors. Clinical neurovirology. New York: Marcel-Dekker; 2003. p. 359–77.Google Scholar
  160. 160.
    Sawyer MH, Rotbart HA. Viral meningitis and aseptic meningitis syndrome. In: Scheld WM, Whitley RJ, Marra CM, editors. Infections of the central nervous system. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 75–93.Google Scholar
  161. 161.
    Rotbart HA. Enteroviral infections of central nervous system. Clin Infect Dis. 1995;20(4):971–81.PubMedCrossRefGoogle Scholar
  162. 162.
    Polio Global Eradication Initiative. Wild poliovirus weekly update. http://www.polioeradication.org/. Accessed 8 Feb 2012.
  163. 163.
    Ho M. Enterovirus 71: the virus, its infections and outbreaks. J Microbiol Immunol Infect. 2000;33(4):205–16.PubMedGoogle Scholar
  164. 164.
    Kelly H, Brussen KA, Lawrence A, et al. Polioviruses and other enteroviruses isolated from faecal samples of patients with acute flaccid paralysis in Australia, 1996–2004. J Paediatr Child Health. 2006;42(6):370–6.PubMedCrossRefGoogle Scholar
  165. 165.
    Glimåker M, Johansson B, Olcen P, et al. Detection of enteroviral RNA by polymerase chain reaction in cerebrospinal fluid from patients with aseptic meningitis. Scand J Infect Dis. 1993;25(5):547–57.PubMedCrossRefGoogle Scholar
  166. 166.
    Mohamed N, Elfaitouri A, Fohlman J, et al. A sensitive and quantitative single-tube real-time reverse transcriptase-PCR for detection of enteroviral RNA. J Clin Virol. 2004;30(2):150–6.PubMedCrossRefGoogle Scholar
  167. 167.
    Sato M, Hosoya M, Honzumi K, et al. Cytokine and cellular inflammatory sequence in enteroviral meningitis. Pediatrics. 2003;112(5):1103–7.PubMedCrossRefGoogle Scholar
  168. 168.
    King RL, Lorch SA, Cohen DM, et al. Routine cerebrospinal fluid enterovirus polymerase chain reaction testing reduces hospitalization and antibiotic use for infants 90 days of age or younger. Pediatrics. 2007;120(3):489–96.PubMedCrossRefGoogle Scholar
  169. 169.
    Nigrovic LE, Chiang VW. Cost analysis of enteroviral polymerase chain reaction in infants with fever and cerebrospinal fluid pleocytosis. Arch Pediatr Adolesc Med. 2000;154(8):817–21.PubMedCrossRefGoogle Scholar
  170. 170.
    Ninove L, Tan C, Nougairede A, et al. Impact of diagnostic procedures on patient management and hospitalization cost during the 2000 and 2005 enterovirus epidemics in Marseilles, France. Clin Microbiol Infect. 2010;16(6):651–6.PubMedCrossRefGoogle Scholar
  171. 171.
    Fauquet C, Mayo M, Maniloff J, et al., editors. Virus taxonomy: eighth report of the International Committee on Taxonomy of Viruses. San Diego: Elsevier Inc.; 2005.Google Scholar
  172. 172.
    ICTVdB management. 00.052. Picornaviridae. In: Büchen-Osmond C, editor. ICTVdB: the universal virus database, version 4. New York: Columbia University; 2006.Google Scholar
  173. 173.
    Glimåker M, Samuelson A, Magnius L, et al. Early diagnosis of enteroviral meningitis by detection of specific IgM antibodies with a solid-phase reverse immunosorbent test (SPRIST) and m-capture EIA. J Med Virol. 1992;36(3):193–201.PubMedCrossRefGoogle Scholar
  174. 174.
    Elfaitouri A, Mohamed N, Fohlman J, et al. Quantitative PCR-enhanced immunoassay for measurement of enteroviral immunoglobulin M antibody and diagnosis of aseptic meningitis. Clin Diagn Lab Immunol. 2005;12(2):235–41.PubMedGoogle Scholar
  175. 175.
    Desmond RA, Accortt NA, Talley L, et al. Enteroviral meningitis: natural history and outcome of pleconaril therapy. Antimicrob Agents Chemother. 2006;50(7):2409–14.PubMedCrossRefGoogle Scholar
  176. 176.
    Abzug MJ, Cloud G, Bradley J, Sánchez PJ, Romero J, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, et al. Double blind placebo-controlled trial of pleconaril in infants with enterovirus meningitis. Pediatr Infect Dis J. 2003;22(4):335–41.PubMedGoogle Scholar
  177. 177.
    Li ZH, Li CM, Ling P, et al. Ribavirin reduces mortality in enterovirus 71-infected mice by decreasing viral replication. J Infect Dis. 2008;197(6):854–7.PubMedCrossRefGoogle Scholar
  178. 178.
    Quartier P, Foray S, Casanova JL, et al. Enteroviral meningoencephalitis in X-linked agammaglobulinemia: intensive immunoglobulin therapy and sequential viral detection in cerebrospinal fluid by polymerase chain detection. Pediatr Infect Dis J. 2000;19(11):1106–8.PubMedCrossRefGoogle Scholar
  179. 179.
    Abzug MJ, Keyserling HL, Lee ML, et al. Neonatal enterovirus infection: virology, serology, and effects of intravenous immune globulin. Clin Infect Dis. 1995;20(5):1201–6.PubMedCrossRefGoogle Scholar
  180. 180.
    Wang SM, Lei HY, Huang MC, et al. Modulation of cytokine production by intravenous immunoglobulin in patients with enterovirus 71-associated brainstem encephalitis. J Clin Virol. 2006;37(1):47–52.PubMedCrossRefGoogle Scholar
  181. 181.
    McMinn PC. Recent advances in the molecular epidemiology and control of human enterovirus 71 infection. Curr Opin Virol. 2012;2(2):199–205.PubMedCrossRefGoogle Scholar
  182. 182.
    Mizuguchi M, Abe J, Mikkaichi K, et al. Acute necrotising encephalopathy of childhood: a new syndrome presenting with multifocal, symmetric brain lesions. J Neurol Neurosurg Psychiatry. 1995;58(5):555–61.PubMedCrossRefGoogle Scholar
  183. 183.
    Kirton A, Busche K, Ross C, et al. Acute necrotizing encephalopathy in caucasian children: two cases and review of the literature. J Child Neurol. 2005;20(6):527–32.PubMedGoogle Scholar
  184. 184.
    Mastroyianni SD, Gionnis D, Voudris K, et al. Acute necrotizing encephalopathy of childhood in non-Asian patients: report of three cases and literature review. J Child Neurol. 2006;21(10):872–9.PubMedCrossRefGoogle Scholar
  185. 185.
    Fasano A, Natoli GF, Cianfoni A, et al. Acute necrotizing encephalopathy: a relapsing case in a European adult. J Neurol Neurosurg Psychiatry. 2008;79(2):227–8.PubMedCrossRefGoogle Scholar
  186. 186.
    Amin R, Ford-Jones E, Richardson SE, et al. Acute childhood encephalitis and encephalopathy associated with influenza: a prospective 11-year review. Pediatr Infect Dis J. 2008;27(5):390–5.PubMedCrossRefGoogle Scholar
  187. 187.
    Fowler A, Stödberg T, Eriksson M, et al. Childhood encephalitis in Sweden: etiology, clinical presentation and outcome. Eur J Paediatr Neurol. 2008;12(6):484–90.PubMedCrossRefGoogle Scholar
  188. 188.
    Surana P, Tang S, McDougall M, et al. Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review. Eur J Pediatr. 2011;170(8):1007–15.PubMedCrossRefGoogle Scholar
  189. 189.
    Studahl M, Linde A. Influenza and CNS complications. In: Nath A, Berger JR, editors. Clinical neurovirology. 1st ed. New York: Marcel-Dekker; 2003. p. 453–68.Google Scholar
  190. 190.
    Fujimoto S, Kobayashi M, Uemura O, et al. PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis. Lancet. 1998;352(9131):873–5.PubMedCrossRefGoogle Scholar
  191. 191.
    Kimura S, Ohtuki N, Nezu A, et al. Clinical and radiological variability of influenza-related encephalopathy or encephalitis. Acta Paediatr Jpn. 1998;40(3):264–70.PubMedCrossRefGoogle Scholar
  192. 192.
    Takanashi J. Two newly proposed infectious encephalitis/encephalopathy syndromes. Brain Dev. 2009;31(7):521–8.PubMedCrossRefGoogle Scholar
  193. 193.
    Studahl M. Influenza virus and CNS manifestations. J Clin Virol. 2003;28(3):225–32.PubMedCrossRefGoogle Scholar
  194. 194.
    Wang GF, Li W, Li K. Acute encephalopathy and encephalitis caused by influenza virus infection. Curr Opin Neurol. 2010;23(3):305–11.PubMedCrossRefGoogle Scholar
  195. 195.
    Falagas ME, Koletsi PK, Vouloumanou EK, et al. Effectiveness and safety of neuraminidase inhibitors in reducing influenza complications: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2010;65(7):1330–46.PubMedCrossRefGoogle Scholar
  196. 196.
    Jhee SS, Yen M, Ereshefsky L, et al. Low penetration of oseltamivir and its carboxylate into cerebrospinal fluid in healthy Japanese and Caucasian volunteers. Antimicrob Agents Chemother. 2008;52(10):3687–93.PubMedCrossRefGoogle Scholar
  197. 197.
    Kornhuber J, Quack G, Danysz W, et al. Therapeutic brain concentration of the NMDA receptor antagonist amantadine. Neuropharmacology. 1995;34(7):713–21.PubMedCrossRefGoogle Scholar
  198. 198.
    Munakata M, Kato R, Yokoyama H, et al. Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy. Brain Dev. 2000;22(6):373–7.PubMedCrossRefGoogle Scholar
  199. 199.
    Jefferson T, Di Pietrantonj C, Rivetti A, et al. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2010;7:CD001269.PubMedGoogle Scholar
  200. 200.
    Sugaya N, Takeuchi Y. Mass vaccination of schoolchildren against influenza and its impact on the influenza-associated mortality rate among children in Japan. Clin Infect Dis. 2005;41(7):939–47.PubMedCrossRefGoogle Scholar
  201. 201.
    Miller HG, Stanton JB, Gibbons JL. Para-infectious encephalomyelitis and related syndromes: a critical review of the neurological complications of certain specific fevers. Q J Med. 1956;25(100):427–505.PubMedGoogle Scholar
  202. 202.
    Baba Y, Tsuboi Y, Inoue H, et al. Acute measles encephalitis in adults. J Neurol. 2006;253(1):121–4.PubMedCrossRefGoogle Scholar
  203. 203.
    Aicardi J, Goutieres F, Arsenio-Nunes ML, et al. Acute measles encephalitis in children with immunosuppression. Pediatrics. 1977;59(2):232–9.PubMedGoogle Scholar
  204. 204.
    Norrby E, Kristensson K. Measles virus in the brain. Brain Res Bull. 1997;44(3):213–20.PubMedCrossRefGoogle Scholar
  205. 205.
    Gutierrez J, Issacson RS, Koppel BS. Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol. 2010;52(10):901–7.PubMedCrossRefGoogle Scholar
  206. 206.
    Hviid A, Rubin S, Mühlemann K. Mumps. Lancet. 2008;371(9616):932–44.PubMedCrossRefGoogle Scholar
  207. 207.
    Koskiniemi M, Donner M, Pettay O. Clinical appearance and outcome in mumps encephalitis in children. Acta Paediatr Scand. 1983;72(4):603–9.PubMedCrossRefGoogle Scholar
  208. 208.
    Griffin DE. Measles and rubella. In: Scheld WM, Whitley RJ, Marra CM, editors. Infections of the central nervous system. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 111–22.Google Scholar
  209. 209.
    Nath A. Rubella. In: Nath A, Berger JR, editors. Clinical neurovirology. 1st ed. London: Taylor and Francis; 2003. p 447–52.Google Scholar
  210. 210.
    Weissbrich B, Schneider-Schaulies J, ter Meulen V. Measles and its neurological complications. In: Nath A, Berger JR, editors. Clinical neurovirology. 1st ed. London: Taylor and Francis; 2003. p 401–30.Google Scholar
  211. 211.
    Health Protection Agency UK. Investigation of viral encephalitis and meningitis. National Standard Method QSOP. 2004;48(2):1–29.Google Scholar
  212. 212.
    Garg RK. Subacute sclerosing panencephalitis. J Neurol. 2008;255(12):1861–71.PubMedCrossRefGoogle Scholar
  213. 213.
    Baum SG, Litman N. Mumps virus. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill-Livingstone; 2000. p. 1776–81.Google Scholar
  214. 214.
    Lau KK, Lai ST, Lai JY, et al. Acute encephalitis complicating rubella. Hong Kong Med J. 1998;4(3):325–8.PubMedGoogle Scholar
  215. 215.
    Bosma TJ, Corbett KM, O′Shea S, et al. PCR for detection of rubella virus RNA in clinical samples. J Clin Microbiol. 1995;33(5):1075–9.PubMedGoogle Scholar
  216. 216.
    Schneider-Schaulies J, ter Meulen V, Schneider-Schaulies S. Measles infection of the central nervous system. J Neurovirol. 2003;9(2):247–52.Google Scholar
  217. 217.
    Sugita K, Ando M, Minamitani K, et al. Magnetic resonance imaging in a case of mumps postinfectious encephalitis with asymptomatic optic neuritis. Eur J Pediatr. 1991;150(11):773–5.PubMedCrossRefGoogle Scholar
  218. 218.
    Liebert UG. Measles virus infections of the central nervous system. Intervirology. 1997;40(2–3):176–84.PubMedCrossRefGoogle Scholar
  219. 219.
    Wetzel K, Asholt I, Herrmann E, et al. Good cognitive outcome of patients with herpes zoster encephalitis: a follow-up study. J Neurol. 2002;249(11):1612–4.PubMedCrossRefGoogle Scholar
  220. 220.
    Adour KK. Otological complications of herpes zoster. Ann Neurol. 1994;35 Suppl:S62–4.Google Scholar
  221. 221.
    Wagstaff AJ, Faulds D, Goa KL, et al. Aciclovir: a reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1994;47(1):153–205.PubMedCrossRefGoogle Scholar
  222. 222.
    Gnann JW Jr. Varicella zoster virus: atypical presentations and unusual complications. J Infect Dis. 2002;186(Suppl. 1):S91–8.PubMedCrossRefGoogle Scholar
  223. 223.
    Wood MJ, Kay R, Dworkin RH, et al. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo-controlled trials. Clin Infect Dis. 1996;2282:341–7.CrossRefGoogle Scholar
  224. 224.
    Wood MJ, Shukla S, Fiddian AP, et al. Treatment of acute herpes zoster: effect of early (<48 h) versus late (48–72 h) therapy with acyclovir and valacyclovir on prolonged pain. J Infect Dis. 1998;178(Suppl. 1):S81–4.PubMedCrossRefGoogle Scholar
  225. 225.
    Gilden DH, Mahalingam R, Cohrs RJ, et al. Herpesvirus infections of the central nervous system. Nat Clin Pract Neurol. 2007;3(2):82–94.PubMedCrossRefGoogle Scholar
  226. 226.
    Sekiyama T, Hatsua S, Tanaka Y, et al. Synthesis and antiviral activity of novel acyclic nucleosides: discovery of a cyclopropyl nucleoside with potent inhibitory activity against herpesviruses. J Med Chem. 1998;41(8):1284–98.PubMedCrossRefGoogle Scholar
  227. 227.
    Kimberlin DW, Lin CY, Jacobs RF, et al. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics. 2001;108(2):230–8.PubMedCrossRefGoogle Scholar
  228. 228.
    Bean B, Aeppli D. Adverse effects of high-dose intravenous acyclovir in ambulatory patients with acute herpes zoster. J Infect Dis. 1985;151(2):362–5.PubMedCrossRefGoogle Scholar
  229. 229.
    Perazella MA. Crystal-induced acute renal failure. Am J Med. 1999;106(4):45–65.CrossRefGoogle Scholar
  230. 230.
    Hellden A, Lycke J, Vander T, et al. The acyclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during acyclovir and valaciclovir treatment. J Antimicrob Chemother. 2006;57(5):945–9.PubMedCrossRefGoogle Scholar
  231. 231.
    Weller S, Blum R, Doucette M, et al. Pharmacokinetics of the acyclovir prodrug valacyclovir after escalating single-and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993;54(6):595–605.PubMedCrossRefGoogle Scholar
  232. 232.
    Pouplin T, Pouplin JN, Van Toi P, et al. Valacyclovir for herpes simplex encephalitis. Antimicrob Agents Chemother. 2011;55(7):3624–6.PubMedCrossRefGoogle Scholar
  233. 233.
    Frank KB, Chiou JF, Cheng YC. Interaction of herpes simplex virus-induced DNA polymerase with 9-(1,3-dihydroxy-2-propoxymethyl) guanine triphosphate. J Biol Chem. 1984;259(3):1566–9.PubMedGoogle Scholar
  234. 234.
    Russler SK, Tapper MA, Carrigan DR. Susceptibility of human herpesvirus 6 to acyclovir and ganciclovir. Lancet. 1989;2(8659):382.PubMedCrossRefGoogle Scholar
  235. 235.
    Crumpacker CS. Ganciclovir. N Engl J Med. 1996;335(10):721–9.PubMedCrossRefGoogle Scholar
  236. 236.
    Cinque P, Cleator GM, Weber T, et al. Diagnosis and clinical management of neurological disorders caused by cytomegalovirus in AIDS patients. J Neurovirol. 1998;4(1):120–32.PubMedCrossRefGoogle Scholar
  237. 237.
    Brown F, Banken L, Saywell K, et al. Pharmacokinetics of valganciclovir and ganciuclovir following multiple oral dosages of valganciclovir in HIV-and CMV-seropositive volunteers. Clin Pharmacokinet. 1999;37(2):161–76.CrossRefGoogle Scholar
  238. 238.
    Martin DF, Sierra-Mader J, Walmsley S, et al. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med. 2002;346(15):1119–26.PubMedCrossRefGoogle Scholar
  239. 239.
    Gerard L, Salmon-Ceron D. Pharmacology and clinical use of foscarnet. Int J Antimicrob Agents. 1995;5(4):209–17.PubMedCrossRefGoogle Scholar
  240. 240.
    Jabs DA, Enger C, Forman M, The cytomegalovirus retinitis and viral resistance study group, et al. Incidence of foscarnet resistance and cidofovir resistance in patients treated for cytomegalovirus retinitis. Antimicrob Agents Chemother. 1998;42(9):2240–4.Google Scholar
  241. 241.
    Peters M, Timm U, Schürmann D, et al. Combined and alternating ganciclovir and foscarnet in acute and maintenance therapy of human immunodeficiency virus-related cytomegalovirus encephalitis refractory to ganciclovir alone: a case report and review of the literature. Clin Invest. 1992;70(5):456–8.CrossRefGoogle Scholar
  242. 242.
    Peavear DC, Tull TM, Seipel ME, et al. Activity of pleconaril against enteroviruses. Antimicrob Agents Chemother. 1999;43(9):2109–15.Google Scholar
  243. 243.
    L′Huillier AG, Lorenzini KI, Crisinel PA, et al. Polymorphisms and neuropsychiatric adverse events in oseltamivir-treated children during influenza H1N1/09 pandemia. Pharmacogenomics. 2011;12(10):1493–501.PubMedCrossRefGoogle Scholar
  244. 244.
    Field HJ, Darby G, Wildy P. Isolation and characterization of acyclovir resistant mutants of herpes simplex virus. J Gen Virol. 1980;49(1):115–24.PubMedCrossRefGoogle Scholar
  245. 245.
    Pottage JC Jr, Kessler HA. Herpes simplex virus resistance to acyclovir: clinical relevance. Infect Agents Dis. 1995;4(3):115–24.PubMedGoogle Scholar
  246. 246.
    Biron KK, Fyfe JA, Noblin JE, et al. Selection and preliminary characterization of acyclovir resistant mutants of varicella zoster virus. Am J Med. 1982;73(1A):383–6.PubMedCrossRefGoogle Scholar
  247. 247.
    Bacon TH, Boon RJ, Schultz M, et al. Surveillance for antiviral-agent-resistant herpes simplex virus in the general population with recurrent herpes labialis. Antimicrob Agents Chemother. 2002;46:3042–4.PubMedCrossRefGoogle Scholar
  248. 248.
    Grey F, Sowa M, Collins P, et al. Characterization of a neurovirulent acyclovir-resistant variant of herpes simplex virus. J Gen Virol. 2003;84:1403–10.PubMedCrossRefGoogle Scholar
  249. 249.
    Schulte EC, Sauerbrei A, Hoffman D, et al. Acyclovir resistance in herpes simplex encephalitis. Ann Neurol. 2010;67(6):830–3.PubMedCrossRefGoogle Scholar
  250. 250.
    Kakiuchi S, Nonoyama S, Wakamatsu H, et al. Neonatal herpes encephalitis caused by a virologically confirmed acyclovir resistant herpes simplex virus type 1. J Clin Microbiol. 2013;51(1):356–9.Google Scholar
  251. 251.
    Brink AA, van Gelder M, Wolffs PF, et al. Compartmentalization of acyclovir-resistant varicella zoster virus: implications for sampling in molecular diagnostics. Clin Infect Dis. 2011;52(8):982–7.PubMedCrossRefGoogle Scholar
  252. 252.
    Aurelius E, Forsgren M, Sköldenberg B, et al. Persistent intrathecal immune activation in patients with herpes simplex encephalitis. J Infect Dis. 1993;168(5):1248–52.PubMedCrossRefGoogle Scholar
  253. 253.
    Aurelius E, Andersson B, Forsgren M, et al. Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis. J Infect Dis. 1994;170(3):678–81.PubMedCrossRefGoogle Scholar
  254. 254.
    Thompson KA, Blessing WW, Wesselingh SL. Herpes simplex replication and dissemination is not increased by corticosteroid treatment in a rat model of focal Herpes encephalitis. J Neurovirol. 2000;6(1):25–32.PubMedCrossRefGoogle Scholar
  255. 255.
    Meyding-Lamade UK, Oberlinner C, Rau PR, et al. Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities. J Neurovirol. 2003;9(1):118–25.PubMedGoogle Scholar
  256. 256.
    Mailles A, De Broucker T, Costanzo P, et al. Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France. Clin Infect Dis. 2012;54(10):1455–64.PubMedCrossRefGoogle Scholar
  257. 257.
    De Broucker T, Mailles A, Chabrier S, et al. Acute varicella zoster encephalitis without evidence of primary vasculopathy in a case series of 20 patients. Clin Microbiol Infect. 2012;18(8):808–19.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Marie Studahl
    • 1
    • 7
  • Lars Lindquist
    • 2
  • Britt-Marie Eriksson
    • 3
  • Göran Günther
    • 3
  • Malin Bengner
    • 4
  • Elisabeth Franzen-Röhl
    • 8
  • Jan Fohlman
    • 5
  • Tomas Bergström
    • 6
  • Elisabeth Aurelius
    • 8
  1. 1.Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
  2. 2.Institution of Medicine, Huddinge, Unit for Infectious Diseases, Karolinska Institutet, Karolinska University HospitalStockholmSweden
  3. 3.Section of Infectious Diseases, Department of Medical SciencesUppsala UniversityUppsalaSweden
  4. 4.Infectious Diseases, Ryhov County HospitalJönköpingSweden
  5. 5.R & D Centre and Department of Infectious DiseasesCentral HospitalVäxjöSweden
  6. 6.Department of VirologyUniversity of GothenburgGothenburgSweden
  7. 7.Department of Infectious DiseasesSahlgrenska University HospitalGöteborgSweden
  8. 8.Institution of Medicine, Solna, Unit for Infectious Diseases, Karolinska Institutet, Karolinska University HospitalStockholmSweden

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