Skip to main content

Herpes Simplex Virus Infections of the Central Nervous System

  • Chapter
  • First Online:
Neuroinflammation and Neurodegeneration

Abstract

Herpes simplex virus infections of the central nervous system are associated with significant morbidity in spite of efficacious antiviral therapy. Herpes simplex virus, type 1 (HSV-1), causes focal neurologic findings that are characteristic of temporal lobe localization. Herpes simplex encephalitis occurs in a biphasic age distribution with one-third of the cases less than 20 and the majority of remaining cases over 50. The diagnostic test of choice is the detection of HSV DNA by PCR in the cerebrospinal fluid. Acyclovir is the treatment of choice and is administered for 14–21 days intravenously at a dose of 10 mg/kg every 8 h. Neonatal HSV infections are more frequently caused by HSV-2 than HSV-1, although the number of cases of the latter is increasing. Infection is most frequently acquired intrapartum by contact with infected maternal genital secretions. Approximately 50 % of all newborns with neonatal infection will have central nervous system involvement. Importantly, HSV-2 infections of the central nervous system in neonates have a poorer outcome than those attributable to HSV-1. Therapy of neonatal infection is achieved with high-dose acyclovir that is administered at 20 mg/kg/every 8 h for 14–21 days. Six months of oral acyclovir post-intravenous treatment has resulted in an improved neurologic outcome for children with central nervous system infection. Likely, in the future, combination antiviral approaches will be employed for both adult and pediatric disease in order to improve neurologic outcome.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover 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. Mettler C. History of medicine. New York, NY: McGraw-Hill (Blakiston); 1947.

    Google Scholar 

  2. Astruc J. De Morbis Venereis Libri Sex. editor. Paris: G. Cavelier; 1736, p. 365.

    Google Scholar 

  3. Gruter W. Das herpesvirus, seine atiologische und klinische bedeutung. Munch Med Wschr. 1924;71:1058.

    Google Scholar 

  4. Goodpasture E. The axis-cylinders of peripheral nerves as portals of entry to the central nervous system for the virus of herpes simplex encephalitis in man. Am J Pathol. 1925;I:11–28.

    Google Scholar 

  5. Commission M. Epidemic encephalitis: etiology, epidemiology, treatment. Report of a survey by the Mathewson Commission. New York, NY: Columbia University Press; 1929.

    Google Scholar 

  6. Smith MG, Lennette EH, Reames HR. Isolation of the virus of herpes simplex and the demonstration of intranuclear inclusions in a case of acute encephalitis. Am J Pathol. 1941;17:55–68.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Meyer Jr M, Johnson R, Crawford I, Dascomb H, Rogers N. Central nervous system syndromes of “viral” etiology. Am J Med. 1960;29:334–47.

    PubMed  Google Scholar 

  8. Zarafonetis CJD, Smodel MC, Adams JW, Haymaker V. Fatal herpes simplex encephalitis in man. Am J Pathol. 1944;20(3):429–45.

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Nahmias AJ, Dowdle WR. Antigenic and biologic differences in herpesvirus hominis. Prog Med Virol. 1968;10:110–59.

    CAS  PubMed  Google Scholar 

  10. Corey L, Spear P. Infections with herpes simplex viruses. N Engl J Med. 1986;314:686–91.

    CAS  PubMed  Google Scholar 

  11. Nahmias AJ, Roizman B. Infection with herpes simplex viruses 1 and 2. N Engl J Med. 1973;289:667–74. 719–25;81–89.

    CAS  PubMed  Google Scholar 

  12. Whitley RJ. Epidemiology of herpes simplex virus. In: Roizman B, editor. The herpesviruses. New York, NY: Plenum Publishing Company; 1985. p. 1–44.

    Google Scholar 

  13. Whitley RJ, Roizman B. Herpes simplex viruses. Lancet. 2001;357:1513–8.

    CAS  PubMed  Google Scholar 

  14. Boos J, Sporadic EMM, Encephalitis I. Viral encephalitis: pathology, diagnosis and management. Oxford: Blackwell Scientific Publishers; 1986. p. 55–93.

    Google Scholar 

  15. Boos J, Kim JH. Biopsy histopathology in herpes simplex encephalitis and in encephalitis of undefined etiology. Yale J Biol Med. 1984;57:751–5.

    Google Scholar 

  16. Kapur N, Barker S, Burrows EH, Ellison D, Brice J, Illis LS, et al. Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile. J Neurol Neurosurg Psychiatry. 1994;57:1334–42.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Garcia JH, Colon LE, Whitley RJ, Kichara J, Holmes FJ. Diagnosis of viral encephalitis by brain biopsy. Semin Diagn Pathol. 1984;1:71–80.

    CAS  PubMed  Google Scholar 

  18. Cook ML, Stevens JG. Pathogenesis of herpetic neuritis and ganglionitis in mice: evidence of intra-axonal transport of infection. Infect Immun. 1973;7:272–88.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Baringer JR. The biology of herpes simplex virus infection in humans. Surv Ophthalmol. 1976;21:171.

    CAS  PubMed  Google Scholar 

  20. Pagano JS. Diseases and mechanisms of persistent DNA virus infection: latency and cellular transformation. J Infect Dis. 1975;132:209–23.

    CAS  PubMed  Google Scholar 

  21. Roizman B. An inquiry into the mechanisms of recurrent herpes infections in man. In: Pollard M, editor. Perspectives in virology IV. New York, NY: Harper and Row Publishers; 1968. p. 283.

    Google Scholar 

  22. Roizman B, Sears A. An Inquiry into the mechanisms of herpes simplex virus latency. Annu Rev Microbiol. 1987;41:543–71.

    CAS  PubMed  Google Scholar 

  23. Stevens JC. Latent herpes simplex virus and the nervous system. Curr Top Immunol. 1975;70:31–50.

    CAS  Google Scholar 

  24. Terni M. Infections due to herpes simplex virus, recurrent disease and problem of latency. G Maln Infett Parassit. 1971;23:433–67.

    CAS  Google Scholar 

  25. Baringer JR, Swoveland P. Recovery of herpes simplex virus from human trigeminal ganglions. N Engl J Med. 1973;288:648–50.

    CAS  PubMed  Google Scholar 

  26. Bastian FO, Rabson AS, Yee CL. Herpesvirus hominis: isolation from human trigeminal ganglion. Science. 1972;178:306.

    CAS  PubMed  Google Scholar 

  27. Hill TJ. Mechanisms involved in recurrent herpes simplex. In: Nahmias A, Dowdle WR, Schinazi R, editors. The human herpesvirus: an interdisciplinary perspective. Amsterdam: Elsevier/North-Holland; 1981. p. 241.

    Google Scholar 

  28. Nesburn AB, Cook ML, Stevens JG. Latent herpes simplex virus isolation from rabbit trigeminal ganglia between episodes of recurrent ocular infection. Arch Ophthalmol. 1972;88:412–7.

    CAS  PubMed  Google Scholar 

  29. Stevens JG, Cook ML. Latent herpes simplex virus in spinal ganglia. Science. 1971;173:843–5.

    CAS  PubMed  Google Scholar 

  30. Stevens JG, Cook ML. Latent herpes simplex virus in sensory ganglia. Perspect Virol. 1974;8:171.

    Google Scholar 

  31. Warren KG, Brown SM, Wrobelwska A, Gilden D, Koprowski H, Subak-Sharpe J. Isolation of latent herpes simplex virus from the superior cervical and vagus ganglions of human beings. N Engl J Med. 1978;298:1068–9.

    CAS  PubMed  Google Scholar 

  32. Cushing H. Surgical aspects of major neuralgia of trigeminal nerve: report of 20 cases of operation upon the Gasserian ganglion with anatomic and physiologic notes on the consequences of its removal. JAMA. 1905;44:773–3379. 860–865, 920–929, 1002–8.

    Google Scholar 

  33. Goodpasture EW. Herpetic infections with special reference to involvement of the nervous system. Medicine. 1929;8:223–43.

    Google Scholar 

  34. Carlton CA, Kilbourne ED. Activation of latent herpes simplex by trigeminal sensory-root section. N Engl J Med. 1952;246:172.

    Google Scholar 

  35. Pazin GJ, Ho M, Jannetta PJ. Reactivation of herpes simplex virus after decompression of the trigeminal nerve root. J Infect Dis. 1978;138:405–9.

    CAS  PubMed  Google Scholar 

  36. Pazin GJ, Armstrong JA, Lam MT, Tarr GC, Jannetta PJ, Ho M. Prevention of reactivation of herpes simplex virus infection by human leukocyte interferon after operation on the trigeminal route. N Engl J Med. 1979;301:225–30.

    CAS  PubMed  Google Scholar 

  37. Ellison SA, Carlton CA, Rose HM. Studies of recurrent herpes simplex infections following section of the trigeminal nerve. J Infect Dis. 1959;105:161.

    CAS  PubMed  Google Scholar 

  38. Walz MA, Price RW, Nortkins AL. Latent ganglionic infections with herpes simplex virus types 1 and 2: viral reactivation in vivo after neurectomy. Science. 1974;184:1185–7.

    CAS  PubMed  Google Scholar 

  39. Kibrick S, Gooding GW. Pathogenesis of infection with special reference to nervous tissue. Slow, latent and temperate virus infections. NINBD monograph no. 2; 1965. pp 143–54.

    Google Scholar 

  40. Hill TJ, Field HJ, Roome APC. Intra-axonal location of herpes simplex virus particles. J Gen Virol. 1972;15:233–5.

    CAS  PubMed  Google Scholar 

  41. Rector JT, Lausch RN, Oakes JE. Use of monoclonal antibodies for analysis of antibody-dependent immunity to ocular herpes simplex virus type 1 infection. Infect Immun. 1982;38:168–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Segal AL, Katcher AH, Brightman VJ, Miller MF. Recurrent herpes labialis, recurrent aphthous ulcers and the menstrual cycles. J Dent Res. 1974;53:797–803.

    CAS  PubMed  Google Scholar 

  43. Hill TJ. Herpes simplex virus latency. In: Roizman B, editor. The herpesviruses. New York, NY: Plenum Publishing; 1985. p. 175–240.

    Google Scholar 

  44. Baringer JR. Recovery of herpes simplex virus from human sacral ganglions. N Engl J Med. 1974;291:828.

    CAS  PubMed  Google Scholar 

  45. Cabrera CV, Wholenberg C, Openshaw H, Rey-Mendez M, Puga A, Notkins AL. Herpes simplex virus DNA sequences in the CNS of latently infected mice. Nature. 1980;288:288–90.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Selling B, Kibrick S. An outbreak of herpes simplex among wrestlers (herpes gladiatorum). N Engl J Med. 1964;270:979–82.

    CAS  PubMed  Google Scholar 

  48. Warren KG, Gilden DH, Brown SM. Isolation of herpes simplex virus from human trigeminal ganglia, including ganglia from one patient with multiple sclerosis. Lancet. 1977;2:637–9.

    CAS  PubMed  Google Scholar 

  49. Nahmias AJ, Whitley RJ, Visintine AN, Takei Y, Alford Jr CA. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Herpes simplex encephalitis: laboratory evaluations and their diagnostic significance. J Infect Dis. 1982;145:829–36.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  51. Johnson RT, Olson LC, Buescher EL. Herpes simplex virus infections of the nervous system. Problems in laboratory diagnosis. Arch Neurol. 1968;18(3):260–4.

    CAS  PubMed  Google Scholar 

  52. Dinn JJ. Transolfactory spread of virus in herpes simplex encephalitis. Br Med J. 1980;281:1392.

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Ojeda VJ, Archer M, Robertson TA, Bucens MR. Necropsy study of olfactory portal of entry in herpes simplex encephalitis. Med J Aust. 1983;1:79–81.

    CAS  PubMed  Google Scholar 

  54. Twomey JA, Barker CM, Robinson G, Howell DA. Olfactory mucosa in herpes simplex encephalitis. J Neurol Neurosurg Psychiatry. 1979;42:983–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Whitley RJ. Therapeutic advances for severe and life-threatening herpes simplex virus infections. In: Lopez C, Roizman B, editors. Human herpesvirus infections. New York, NY: Raven; 1986. p. 153–64.

    Google Scholar 

  56. Schlitt M, Lakeman FD, Wilson ER, To A, Acoff R, Harsh GR, et al. A rabbit model of focal herpes simplex encephalitis. J Infect Dis. 1986;153:732–5.

    CAS  PubMed  Google Scholar 

  57. Stroop WG, Schaefer DC. Production of encephalitis restricted to the temporal lobes by experimental reactivation of herpes simplex virus. J Infect Dis. 1986;153:721–31.

    CAS  PubMed  Google Scholar 

  58. Rock DL, Frasher NW. Detection of HSV-1 genome in central nervous system of latently infected mice. Nature. 1983;302:523–31.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  60. Griffith JR, Kibrick S, Dodge PR, Richardson EP. Experimental herpes simplex encephalitis: electroencephalographic, clinical, virologic, and pathologic observations in the rabbit. Electroencephalogr Clin Neurophysiol. 1967;23:263–7.

    CAS  PubMed  Google Scholar 

  61. Barnes DW, Whitley RJ. CNS disease associated with varicella-zoster virus and herpes simplex virus infection. Neurol Clin. 1986;4(1):265–83.

    CAS  PubMed  Google Scholar 

  62. Casanova JL, Tardieu M, Abel L. Genetic predisposition to herpetic meningo-encephalitis in children. Bull Acad Natl Med. 2010;194(6):915–22. Epub 2011/04/26. Predisposition genetique a l'encephalite herpetique chez l'enfant.

    CAS  PubMed  Google Scholar 

  63. Whitley RJ. Herpes simplex viruses. In: Fields BN, Knipe DM, Chanock R, Hirsch M, Melnick J, Monath T, et al., editors. Fields virology. 2nd ed. New York, NY: Raven; 1990. p. 1843–87.

    Google Scholar 

  64. Fife KH, Corey L. Herpes simplex virus. In: Holmes KK, Mardh PA, Sparling PF, Wiesner PJ, Cates W, Lemon SM, et al., editors. Sexually transmitted diseases. 2nd ed. New York, NY: McGraw-Hill Publishers; 1990. p. 941–52.

    Google Scholar 

  65. Whitley RJ. Herpes simplex virus. In: Knipe DM, Howley RM, Grriffin D, Lamb R, Martin M, Straus SE, editors. Fields virology. 4th ed. New York: Lippincott Williams & Wilkins; 2001. p. 2461–509.

    Google Scholar 

  66. Black FL. Infectious diseases in primitive societies. Science. 1975;187:515–8.

    CAS  PubMed  Google Scholar 

  67. Burnet FM, Williams SW. Herpes simplex: new point of view. Med J Aust. 1939;1:637–40.

    Google Scholar 

  68. Dodd K, Johnston LM, Buddingh GJ. Herpetic stomatitis. J Pediatr. 1938;12:95.

    Google Scholar 

  69. Buddingh GH, Schrum DI, Lanier JC, Guidy DJ. Studies of the natural history of herpes simplex infections. Pediatrics. 1953;11:595.

    CAS  PubMed  Google Scholar 

  70. Juretic M. Natural history of herpetic infection. Helv Paediatr Acta. 1966;21:356.

    CAS  PubMed  Google Scholar 

  71. Cesario TC, Poland JD, Wulff H, Chin TD, Wenner HA. Six years experiences with herpes simplex virus in a children’s home. Am J Epidemiol. 1969;90:416–22.

    CAS  PubMed  Google Scholar 

  72. Douglas Jr RG, Couch RB. A prospective study of chronic herpes simplex virus infection and recurrent herpes labialis in humans. J Immunol. 1970;104:289–95.

    CAS  PubMed  Google Scholar 

  73. Kloene W, Bang FB, Chakroborty SM, Cooper MR, Kulemann H, Shah KV, et al. A two year respiratory virus survey in four villages in West Bengal, India. Am J Epidemiol. 1970;92:307–20.

    CAS  PubMed  Google Scholar 

  74. Komorous JM, Wheeler CE, Briggaman RA, Caro L. Intrauterine herpes simplex infections. Arch Dermatol. 1977;113:918–22.

    CAS  PubMed  Google Scholar 

  75. Lindgren KM, Douglas Jr RG, Couch RB. Significance of herpesvirus hominis in respiratory secretions of man. N Engl J Med. 1968;276:517–23.

    Google Scholar 

  76. Overall Jr JC. Antiviral chemotherapy of oral and genital herpes simplex virus infections. In: Nahmias AJ, Dowdle WR, Schinazi RE, editors. The human herpesviruses: an interdisciplinary perspective. Amsterdam: Elsevier/North-Holland; 1980. p. 447–65.

    Google Scholar 

  77. Stern H, Elek SD, Miller DM, Anderson HF. Herpetic Whitlow, a form of cross-infection in hospitals. Lancet. 1959;2:871.

    CAS  PubMed  Google Scholar 

  78. Young SK, Rowe NH, Buchanan RA. A clinical study for the control of facial mucocutaneous herpes virus infections. I Characterization of natural history in a professional school population. Oral Surg Oral Med Oral Pathol. 1976;41:498–507.

    CAS  PubMed  Google Scholar 

  79. Scott TF, Steigman AJ, Convey JH. Acute infectious gingivostomatitis: etiology, epidemiology, and clinical pictures of a common disorder caused by the virus of herpes simplex. JAMA. 1941;117:999.

    Google Scholar 

  80. Stavaraky NM, Rawls WE, Chiavetta J, Donner AP, Wanklin JM. Sexual and socioeconomic factors affecting the risk of past infections with herpes simplex virus type 2. Am J Epidemiol. 1983;118:109–21.

    Google Scholar 

  81. Templeton AC. Generalized herpes simplex in malnourished children. J Clin Pathol. 1970;23:24–30.

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Rawls WE, Campione-Piccardo J. Epidemiology of herpes simplex virus type 1 and 2. In: Nahmias A, Dowdle W, Schinazi R, editors. The human herpesviruses: an interdisciplinary perspective. Amsterdam: Elsevier/North-Holland; 1981. p. 137–52.

    Google Scholar 

  83. Bader C, Crumpacker CS, Schnipper LE, Ransel B, Clark JE, Arndt K, et al. The natural history of recurrent facial-oral infection with herpes simplex virus. J Infect Dis. 1978;138:897–905.

    CAS  PubMed  Google Scholar 

  84. Black FL, Hierholzer WJ, Pinheiro F, Evans AS, Woodall JP. Evidence for persistence of infectious agents in isolated human populations. Am J Epidemiol. 1974;100:230–50.

    CAS  PubMed  Google Scholar 

  85. Nahmias AJ, Josey WE, Naib ZM, Luce C, Duffey C. Antibodies to herpesvirus hominis type 1 and 1 in humans. I Patients with genital herpetic infections. Am J Epidemiol. 1970;91:539–46.

    CAS  PubMed  Google Scholar 

  86. Nahmias AJ, Josey WE, Naib ZM, Luce CF, Fuest B. Antibodies to herpesvirus hominis types 1 and 2 in humans. II Women with cervical cancer. Am J Epidemiol. 1970;91:547–52.

    CAS  PubMed  Google Scholar 

  87. Rawls WE, Tompkins WA, Melnick JL. The association of herpesvirus type 2 and carcinoma of the uterine cervix. Am J Epidemiol. 1969;89:547–54.

    CAS  PubMed  Google Scholar 

  88. Sawanabori S. Acquisition of herpes simplex virus infection in Japan. Acta Paediatr Jpn Overseas Ed. 1973;15:16.

    Google Scholar 

  89. Wentworth BB, Alexander ER. Seroepidemiology of infections due to members of herpesvirus group. Am J Epidemiol. 1971;94:496–507.

    CAS  PubMed  Google Scholar 

  90. Glezen WP, Fernald GW, Lohr JA. Acute respiratory disease of university students with special references to the etiologic role of herpesvirus hominis. Am J Epidemiol. 1975;101:111–21.

    CAS  PubMed  Google Scholar 

  91. Gibson JJ, Hornung CA, Alexander GR, Lee FK, Potts WA, Nahmias AJ. A cross-sectional study of herpes simplex virus types 1 and 2 in college students: occurrence and determinants of infection. J Infect Dis. 1990;162:306–12.

    CAS  PubMed  Google Scholar 

  92. Evans AS, Dick EC. Acute pharyngitis and tonsillitis in University of Wisconsin students. JAMA. 1964;190:699–708.

    CAS  PubMed  Google Scholar 

  93. Corey L, Adams HG, Brown ZA, Holmes KK. Genital herpes simplex virus infections: clinical manifestations, course and complications. Ann Intern Med. 1983;98:958–72.

    CAS  PubMed  Google Scholar 

  94. Kalinyak JE, Fleagle G, Docherty JJ. Incidence and distribution of herpes simplex virus types 1 and 2 from genital lesions in college women. J Med Virol. 1977;1:175–81.

    CAS  PubMed  Google Scholar 

  95. Smith IW, Peutherer JR, Robertson DH. Virological studies in genital herpes. Lancet. 1977;2:1089–90.

    Google Scholar 

  96. Wolontis S, Jeansson S. Correlation of herpes simplex virus types 1 and 2 with clinical features of infection. J Infect Dis. 1977;135:28–33.

    CAS  PubMed  Google Scholar 

  97. Bernstein DI, Bellamy AR, Hook 3rd EW, Levin MJ, Wald A, Ewell MG, et al. Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women. Clin Infect Dis. 2013;56(3):344–51. Epub 2012/10/23.

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Armstrong GL, Schillinger J, Markowitz L, Nahmias AJ, Johnson RE, McQuillan GM, et al. Incidence of herpes simplex virus type 2 infection in the United States. Am J Epidemiol. 2001;153:912–20.

    CAS  PubMed  Google Scholar 

  99. Institute of Medicine, Committee on issues and priorities for new vaccine development. Appendix I. Prospects for immunizing against Herpes Simplex Virus 1 and 2. New vaccine development establishing priorities: disease of importance in the United States. Washington, DC: National Academy Press; 1985. pp. 280–312.

    Google Scholar 

  100. Corey L, Holmes K, Benedetti J, Critchlow C. Clinical course of genital herpes: Implications for therapeutic trials. In: Nahmias A, Dowdle WR, Schinazi R, editors. The human herpesviruses: an interdisciplinary perspective. Amsterdam: Elsevier/North Holland; 1981. p. 496–502.

    Google Scholar 

  101. Magder LS, Nahmias AJ, Johnson RE, Lee FK, Brooks C, Snowden C. The prevalence and distribution of herpes simplex virus type 1 and 2 antibodies in the United States population. N Engl J Med. 1989;321:7–12.

    PubMed  Google Scholar 

  102. Ng ABP, Reagin JW, Yen SS. Herpes genitalis–clinical and cytopathologic experience with 256 patients. Obstet Gynecol. 1970;36:645.

    CAS  PubMed  Google Scholar 

  103. Ekwo E, Wong YW, Myers M. Asymptomatic cervicovaginal shedding of herpes simplex virus. Am J Obstet Gynecol. 1979;134:102–3.

    CAS  PubMed  Google Scholar 

  104. Rattray MC, Corey L, Reeves WC, Vontver LA, Holmes KK. Recurrent genital herpes among women: symptomatic versus asymptomatic viral shedding. Br J Vener Dis. 1978;54:262–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  105. Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000;342(12):844–50.

    CAS  PubMed  Google Scholar 

  106. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis. 2002;185:45–52.

    PubMed  Google Scholar 

  107. Adam E, Kaufman RH, Mirkovic RR, Melnick JL. Persistence of virus shedding in asymptomatic women after recovery from herpes genitalis. Obstet Gynecol. 1979;54:171–3.

    CAS  PubMed  Google Scholar 

  108. Naib ZM, Nahmias AJ, Josey WE, Zaki SA. Relation of cytohistopathology of genital herpesvirus infection to cervical anaplasia. Cancer. 1973;33:1452–63.

    CAS  Google Scholar 

  109. Becker WB. The epidemiology of herpesvirus infection in three racial communities in Cape Town. S Afr Med J. 1966;40:109–11.

    Google Scholar 

  110. IHMF Monograph, editor. Herpesvirus infections in pregnancy. Management Strategies Workshop and 7th Annual Meeting; 1999; Seville, Spain.

    Google Scholar 

  111. Rawls WE, Adam E, Melnick JL. Geographical variation in the association of antibodies to herpesvirus type 2 and carcinoma of the cervix. In: Biggs PM, de The G, Payne LN, editors. Oncogenesis and herpesviruses. Lyon: Scientific Publication II, International Agency for Research on Cancer; 1972. p. 424–7.

    Google Scholar 

  112. IHMF. Strategies for interrupting the transmission of genital and neonatal HSV infection. Herpes. 2004;11(Supplement 3):129A–86.

    Google Scholar 

  113. Rawls WE, Gardner HL. Herpes genitalis: venereal aspects. Clin Obstet Gynecol. 1972;15:912–8.

    Google Scholar 

  114. Rawls WE, Gardner HL, Flanders RW, Lowry SP, Kaufman RH, Melnick JL. Genital herpes in two social groups. Am J Obstet Gynecol. 1971;110:682–9.

    CAS  PubMed  Google Scholar 

  115. Rawls WE, Garfield CH, Seth P, Adam E. Serological and epidemiological considerations of the role of herpes simplex virus type 2 in cervical cancer. Cancer Res. 1976;36:829–35.

    CAS  PubMed  Google Scholar 

  116. Chang TW, Fiumara NJ, Weinstein L. Genital herpes: some clinical and laboratory observations. JAMA. 1974;229:544–5.

    CAS  PubMed  Google Scholar 

  117. Reeves WC, Corey L, Adams HG, Vontver LA, Holmes KK. Risk of recurrence after first episodes of genital herpes: relation to HSV type and antibody response. N Engl J Med. 1981;305:315–9.

    CAS  PubMed  Google Scholar 

  118. Choi NW, Shettigara PT, Abu-Zeid HA, Nelson NA. Herpesvirus infection and cervical anaplasia: a seroepidemiological study. Int J Cancer. 1977;19:167–71.

    CAS  PubMed  Google Scholar 

  119. Lafferty WE, Coombs RW, Benedetti J, Critchlow C, Corey L. Recurrences after oral and genital herpes simplex virus infection. Influence of site of infection and viral type. N Engl J Med. 1987;316:1444–9.

    CAS  PubMed  Google Scholar 

  120. Corey L, Ashley R, Benedetti J, Selke S, editors. The effect of prior HSV-1 infection on the subsequent natural history of genital HSV-2. 28th interscience conference on antimicrobial agents and chemotherapy, 23–26 Oct 1988, Los Angeles, CA.

    Google Scholar 

  121. Longson M. The general nature of viral encephalitis in the United Kingdom. In: Ellis LS, editor. Viral diseases of the central nervous system. London: Bailliere Tindall; 1984. p. 19–31.

    Google Scholar 

  122. Skoldenberg B, Forsgren M, Alestig K, Bergstrom T, Burman L, Dahlqvist E, et al. Acyclovir versus vidarabine in herpes simplex encephalitis: a randomized multicentre study in consecutive Swedish patients. Lancet. 1984;2:707–11.

    CAS  PubMed  Google Scholar 

  123. Corey L, Spear P. Infections with herpes simplex viruses. N Engl J Med. 1986;314:749–57.

    CAS  PubMed  Google Scholar 

  124. Straus S, Rooney JF, Sever JL, Seilding M, Nusinoff-Lehrman S, Cremer K. Herpes simplex virus infection: biology. Treatment and prevention. Ann Intern Med. 1985;103:404–19.

    CAS  PubMed  Google Scholar 

  125. Khetsuriani N, Holman RC, Anderson LJ. Burden of encephalitis-associated hospitalizations in the United States, 1988–1997. Clin Infect Dis. 2002;35:175–82.

    PubMed  Google Scholar 

  126. Whitley RJ, Soong SJ, Linneman Jr C, Liu C, Pazin G, Alford CA. Herpes simplex encephalitis. Clinical assessment. JAMA. 1982;247(3):317–20.

    CAS  PubMed  Google Scholar 

  127. Boston Interhospital Virus Study Group and the NIAID Sponsored Cooperative Antiviral Clinical Study, Chien LT, Whitley RJ, et al. Failure of high dose 5-deoxyuridine in the therapy of herpes simplex virus encephalitis: evidence of unacceptable toxicity. N Engl J Med. 1975;292:600–3.

    Google Scholar 

  128. Longson M. Le defi des encephalitis herpetiques. Ann Microbiol (Paris). 1979;130:5.

    Google Scholar 

  129. Longson MM, Bailey AS, Klapper P. Herpes encephalitis. In: Waterson AP, editor. Recent advances in clinical virology. New York, NY: Churchill Livingston; 1980. p. 147–57.

    Google Scholar 

  130. Whitley RJ, Soong S-J, Dolin R, Galasso GJ, Chien LT, Alford Jr CA, et al. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis: National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study. N Engl J Med. 1977;297:289–94.

    CAS  PubMed  Google Scholar 

  131. Whitley RJ, Soong S-J, Hirsch MS, Karchmer AW, Dolin R, Galasso G, et al. Herpes simplex encephalitis: vidarabine therapy and diagnostic problems. N Engl J Med. 1981;304:313–8.

    CAS  PubMed  Google Scholar 

  132. Whitley RJ. Herpes virus of the central nervous system. International Herpes Management Forum Management Strategies Workshop, Paris. 2003.

    Google Scholar 

  133. Chien LT, Boehm RM, Robinson H, Liu C, Frenkel LD. Characteristic early electroencephalographic changes in herpes simplex encephalitis. Arch Neurol. 1977;34:361–4.

    CAS  Google Scholar 

  134. Miller JHD, Coey A. The EEG in necrotizing encephalitis. Electroencephalogr Clin Neurophysiol. 1959;2:582–5.

    Google Scholar 

  135. Radermecker J. Significant electroencephalographic patterns in the detection and follow-up of cranio-cerebral traumas and encephalatides. Electroencephalogr Clin Neurophysiol. 1970;29(1):98.

    CAS  PubMed  Google Scholar 

  136. Smith JB, Westmoreland BF, Reagan TJ, Sandok BA. A distinctive clinical EEG profile in herpes simplex encephalitis. Mayo Clin Proc. 1975;50:469–74.

    CAS  PubMed  Google Scholar 

  137. Enzmann DR, Ransom B, Norman D. Computed tomography of herpes simplex encephalitis. Radiology. 1978;129:419–25.

    CAS  PubMed  Google Scholar 

  138. Zimmerman RD, Russell EJ, Leeds NE, Kaufman D. CT in the early diagnosis of herpes simplex encephalitis. Am J Roentgenol. 1980;134:61–6.

    CAS  Google Scholar 

  139. Schlesinger Y, Buller RS, Brunstrom JE, Moran CJ, Storch GA. Expanded spectrum of herpes simplex encephalitis in childhood. J Pediatr. 1995;126:234–41.

    CAS  PubMed  Google Scholar 

  140. Rowley A, Lakeman F, Whitley R, Wolinsky S. Rapid detection of herpes simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis. Lancet. 1990;335:440–1.

    CAS  PubMed  Google Scholar 

  141. Kimura H, Aso K, Kuzushima K, Hanada N, Shibata M, Morishima T. Relapse of herpes simplex encephalitis in children. Pediatrics. 1992;89:891–4.

    CAS  PubMed  Google Scholar 

  142. Aurelius E, Johansson B, Skoldenberg B, Staland A, Forsgren M. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet. 1991;337(8735):189–92.

    CAS  PubMed  Google Scholar 

  143. 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.

    CAS  PubMed  Google Scholar 

  144. Puchhammer-Stockl E, Heinz FX, Kundi M, Popow-Kraupp T, Grimm G, Millner MM, et al. Evaluation of the polymerase chain reaction for diagnosis of herpes simplex virus encephalitis. J Clin Microbiol. 1993;31:146–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Shoji H, Koga M, Kusuhara T, Kaji M, Ayabe M, Hino H, et al. Differentiation of herpes simplex virus 1 and 2 in cerebrospinal fluid of patients with HSV encephalitis and meningitis by stringent hybridization of PCR-amplified DNAs. J Neurol. 1994;241:526–30.

    CAS  PubMed  Google Scholar 

  146. Sakrauski A, Weber B, Kessler HH, Pierer K, Doerr HW. Comparison of two hybridization assays for the rapid detection of PCR amplified HSV genome sequences from cerebrospinal fluid. J Virol Methods. 1994;50:175–84.

    CAS  PubMed  Google Scholar 

  147. Lakeman FD, Whitley RJ. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Diagnosis of herpes simplex encephalitis: Application of polymerase chain reaction to cerebrospinal fluid from brain biopsied patients and correlation with disease. J Infect Dis. 1995;172:857–63.

    Google Scholar 

  148. Whitley RJ, Cobbs CG, Alford CA, Soong SJ, Morawetz R, Benton JW, et al. Diseases that mimic herpes simplex encephalitis: diagnosis, presentation and outcome. JAMA. 1989;5:33–40.

    Google Scholar 

  149. Whitley RJ, Alford Jr CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, et al. Vidarabine versus acyclovir therapy of herpes simplex encephalitis. N Engl J Med. 1986;314:144–9.

    CAS  PubMed  Google Scholar 

  150. Davis LE, McLaren LE. Relapsing herpes simplex encephalitis following antiviral therapy. Ann Neurol. 1983;13:192–5.

    CAS  PubMed  Google Scholar 

  151. Dix RD, Baringer JR, Panitch HS, Rosenberg SH, Hagedorn J, Whaley J. Recurrent herpes simplex encephalitis: recovery of virus after Ara-A treatment. Ann Neurol. 1983;13:196–200.

    CAS  PubMed  Google Scholar 

  152. Wang HS, Kuo MF, Huang SC, Chou ML. Choreoathetosis as an initial sign of relapsing of herpes simplex encephalitis. Pediatr Neurol. 1994;11:341–5.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  154. Zuelzer WW, Wolf W, Stulbery CS. Herpes simplex virus as the cause of fulminating visceral disease and hepatitis in infancy. Am J Dis Child. 1952;83:421–39.

    CAS  Google Scholar 

  155. Whitley RJ. Herpes simplex virus infections of the central nervous system in children. Semin Neurol. 1982;2:87–97.

    Google Scholar 

  156. Baldwin S, Whitley RJ. Intrauterine herpes simplex virus infection. Teratology. 1989;39:1–10.

    CAS  PubMed  Google Scholar 

  157. Florman AL, Gershon AA, Blackett RP, Nahmias AJ. Intrauterine infection with herpes simplex virus: resultant congenital malformation. JAMA. 1973;225:129–32.

    CAS  PubMed  Google Scholar 

  158. Hutto C, Arvin A, Jacobs R, Steele R, Stagno S, Lyrene R, et al. Intrauterine herpes simplex virus infections. J Pediatr. 1987;110:97–101.

    CAS  PubMed  Google Scholar 

  159. South MA, Tompkins WA, Morris CR, Rawls WE. Congenital malformation of the central nervous system associated with genital type (type 2) herpesvirus. J Pediatr. 1969;75:13–8.

    CAS  PubMed  Google Scholar 

  160. Whitley RJ, Hutto C. Neonatal herpes simplex virus infections. Pediatr Rev. 1985;7:119–26.

    Google Scholar 

  161. Whitley RJ. Herpes simplex virus infections. In: Remington J, Klein J, editors. Infectious diseases of the fetus and newborn infants. 3rd ed. Philadelphia, PA: W. B. Saunders Company; 1990. p. 282–305.

    Google Scholar 

  162. Stagno S, Whitley RJ. Herpesvirus infections of pregnancy. II Herpes simplex virus and varicella-zoster virus infections. N Engl J Med. 1985;313:1327–30.

    CAS  PubMed  Google Scholar 

  163. Corey L. The diagnosis and treatment of genital herpes. JAMA. 1982;248:1041–9.

    CAS  PubMed  Google Scholar 

  164. Nahmias AJ, Keyserling HL, Kerrick GM. Herpes simplex. In: Remington JS, Klein JO, editors. Infectious diseases of the fetus and newborn infant. Philadelphia, PA: W. B. Saunders Company; 1983. p. 636–78.

    Google Scholar 

  165. Prober CG, Sullender WM, Yasukawa LL, Au DS, Yeager AS, Arvin AM. Low risk of herpes simplex virus infections in neonates exposed to the virus at the time of vaginal delivery to mothers with recurrent genital herpes simplex virus infections. N Engl J Med. 1987;316:240–4.

    CAS  PubMed  Google Scholar 

  166. Yeager AS, Arvin AM, Urbani LJ, Kemp III JA. Relationship of antibody to outcome in neonatal herpes simplex infections. Infect Immun. 1980;29:532–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  167. Kaye EM, Dooling EC. Neonatal herpes simplex meningoencephalitis associated with fetal monitor scalp electrodes. Neurology. 1981;31:1045–7.

    CAS  PubMed  Google Scholar 

  168. Parvey LS, Chien LT. Neonatal herpes simplex virus infection introduced by fetal monitor scalp electrode. Pediatrics. 1980;65:1150–3.

    CAS  PubMed  Google Scholar 

  169. Brown ZA, Wald A, Morrow RM, 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.

    PubMed  Google Scholar 

  170. Kohl S, West MS, Prober CG, Sullender WM, Loo LS, Arvin AM. Neonatal antibody-dependent cellular cytoxic antibody levels are associated with the clinical presentation of neonatal herpes simplex virus infection. J Infect Dis. 1989;160:770–6.

    CAS  PubMed  Google Scholar 

  171. Dunkle LM, Schmidt RR, O'Connor DM. Neonatal herpes simplex infection possibly acquired via maternal breast milk. Pediatrics. 1979;63:250–1.

    CAS  PubMed  Google Scholar 

  172. Kibrick S. Herpes simplex virus in breast milk. Pediatrics. 1979;64:390–1.

    CAS  PubMed  Google Scholar 

  173. Sullivan-Bolyai JZ, Fife KH, Jacobs RF, Miller Z, Corey L. Disseminated neonatal herpes simplex virus type 1 from a maternal breast lesion. Pediatrics. 1983;71:455–7.

    CAS  PubMed  Google Scholar 

  174. Yeager AS, Ashley RL, Corey L. Transmission of herpes simplex virus from father to neonate. J Pediatr. 1983;103:905–7.

    CAS  PubMed  Google Scholar 

  175. Douglas J, Schmidt O, Corey L. Acquisition of neonatal HSV-1 infection from a paternal source contact. J Pediatr. 1983;103:908–10.

    CAS  PubMed  Google Scholar 

  176. Linnemann Jr CC, Buchman TG, Light IJ, Ballard JL, Roizman B. Transmission of herpes simplex virus type-1 in a nursery for the newborn: identification of viral species isolated by DNA fingerprinting. Lancet. 1978;1:964–6.

    PubMed  Google Scholar 

  177. Light IJ. Postnatal acquisition of herpes simplex virus by the newborn infant: a review of the literature. Pediatrics. 1979;63:480–2.

    CAS  PubMed  Google Scholar 

  178. Hammerberg O, Watts J, Chernesky M, Luchsinger I, Rawls W. An outbreak of herpes simplex virus type 1 in an intensive care nursery. Pediatr Infect Dis. 1983;2:290–4.

    CAS  PubMed  Google Scholar 

  179. Nahmias AJ, Josey WE, Naib ZM, Freeman MG, Fernandez RJ, Wheeler JH. Perinatal risk associated with maternal genital herpes simplex virus infection. Am J Obstet Gynecol. 1971;110:825–36.

    CAS  PubMed  Google Scholar 

  180. Arvin AM, Yeager AS, Bruhn FW, Grossman M. Neonatal herpes simplex infection in the absence of mucocutaneous lesions. J Pediatr. 1982;100:715–21.

    CAS  PubMed  Google Scholar 

  181. Whitley RJ, Nahmias AJ, Visitine AM, Fleming CL, Alford Jr CA. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. The natural history of herpes simplex virus infection of mother and newborn. Pediatrics. 1980;66:489–94.

    CAS  PubMed  Google Scholar 

  182. Yeager AS, Arvin AM. Reasons for the absence of a history of recurrent genital infections in mothers of neonates infected with herpes simplex virus. Pediatrics. 1984;73:188–93.

    CAS  PubMed  Google Scholar 

  183. Mizrahi EM, Tharp BR. A unique electroencephalogram pattern in neonatal herpes simplex virus encephalitis. Neurology. 1981;31:164.

    Google Scholar 

  184. Whitley RJ, Nahmias AJ, Soong S-J, Galasso GG, Fleming CL, Alford Jr CA, et al. Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics. 1980;66:495–501.

    CAS  PubMed  Google Scholar 

  185. Guttman LT, Wilfert CM, Eppes S. Herpes simplex virus encephalitis in children: analysis of cerebrospinal fluid and progressive neurodevelopmental deterioration. J Infect Dis. 1986;154:415–21.

    Google Scholar 

  186. Nahmias AJ, Visitine A, Caldwell A, Wilson C. Eye infections with herpes simplex viruses in neonates. Surv Ophthalmol. 1976;21:100–5.

    CAS  PubMed  Google Scholar 

  187. Nahmias A, Hagler W. Ocular manifestations of herpes simplex in the newborn. Int Ophthalmol Clin. 1972;12:191–213.

    CAS  PubMed  Google Scholar 

  188. Reested P, Hansen B. Chorioretinitis of the newborn with herpes simplex type 1: report of a case. Acta Ophthalmol. 1979;57:1096–100.

    Google Scholar 

  189. Cibis A, Burde RM. Herpes simplex virus induced congenital cataracts. Arch Ophthalmol. 1971;85:220–3.

    CAS  PubMed  Google Scholar 

  190. Kimberlin DW, Lakeman FD, Arvin AM, Prober CG, Corey L, Powell DA, et al. Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis. 1996;174(6):1162–7. Epub 1996/12/01.

    CAS  PubMed  Google Scholar 

  191. Corey L. Laboratory diagnosis of herpes simplex virus infections. Principles guiding the development of rapid diagnostic tests. Diagn Microbiol Infect Dis. 1986;4(3 Suppl):111S–9. Epub 1986/03/01.

    CAS  PubMed  Google Scholar 

  192. Boehm FH, Estes W, Wright PE, Growdon Jr JF. Management of genital herpes simplex virus infection occurring during pregnancy. Am J Obstet Gynecol. 1980;141:735–40.

    Google Scholar 

  193. International Herpes Management Forum. Strategies for interrupting the transmission of genital and neonatal HSV infection. Herpes. 2004;11 Suppl 3:A129–86.

    Google Scholar 

  194. Kimberlin D, Powell D, Gruber W, Diaz P, Arvin A, Kumar M, et al. Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial. Pediatr Infect Dis J. 1996;15(3):247–54. Epub 1996/03/01.

    CAS  PubMed  Google Scholar 

  195. Hardy DA, Arvin AM, Yasukawa LL, Bronzan RN, Lewinsohn DM, Hensleigh PA, et al. Use of polymerase chain for successful identification of asymptomatic genital infection with herpes simplex virus in pregnant women in delivery. J Infect Dis. 1990;162:1031–5.

    CAS  PubMed  Google Scholar 

  196. Whitley RJ, Corey L, Arvin A, Lakeman FD, Sumaya CV, Wright PF, et al. Changing presentation of herpes simplex virus infection in neonates. J Infect Dis. 1988;158:109–16.

    CAS  PubMed  Google Scholar 

  197. Whitley RJ. Herpes simplex virus infections of the central nervous system: a review. Am J Med. 1988;85:61–7.

    CAS  PubMed  Google Scholar 

  198. Whitley RJ, Yeager A, Kartus P, Bryson Y, Connor JD, Alford Jr CA, et al. Neonatal herpes simplex virus infection: follow-up evaluation of vidarabine therapy. Pediatrics. 1983;72:778–85.

    CAS  PubMed  Google Scholar 

  199. Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Corey L, Gruber WC, 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. Epub 2001/08/03.

    CAS  PubMed  Google Scholar 

  200. Whitley RJ, Arvin A, Prober C, Burchett S, Corey L, Powell D, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. N Engl J Med. 1991;324:444–9.

    CAS  PubMed  Google Scholar 

  201. Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Frenkel LM, Gruber WC, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics. 2001;108(2):223–9. Epub 2001/08/03.

    CAS  PubMed  Google Scholar 

  202. Whitley RJ, Arvin A, Prober C, Corey L, Burchett S, Plotkin S, et al. Predictors of morbidity and mortality in neonates with herpes simplex virus infections. N Engl J Med. 1991;324:450–4.

    CAS  PubMed  Google Scholar 

  203. Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A, et al. Oral acyclovir suppression and neurodevelopment after neonatal herpes. N Engl J Med. 2011;365(14):1284–92. Epub 2011/10/14.

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Some or all of the research reported in this chapter was supported by the National Center for Advancing Translational Research of the National Institutes of Health through the UAB Center for Clinical and Translational Science under award number UL1TR00165.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard J. Whitley M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Whitley, R.J. (2014). Herpes Simplex Virus Infections of the Central Nervous System. In: Peterson, P., Toborek, M. (eds) Neuroinflammation and Neurodegeneration. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1071-7_13

Download citation

Publish with us

Policies and ethics