Skip to main content
SpringerLink
Log in

Neurological Disorders Associated with Human Alphaherpesviruses

  • Chapter
  • First Online:
Human Herpesviruses

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1045))

Abstract

Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic fatal encephalitis worldwide, and central nervous system (CNS) involvement is observed in approximately one-third of neonatal HSV infections . In recent years, single-gene inborn errors of innate immunity have been shown to be associated with susceptibility to HSV encephalitis . Temporal lobe abnormalities revealed by magnetic resonance imaging—the most sensitive imaging method for HSV encephalitis—are considered strong evidence for the disease. Detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR) is the gold standard for the diagnosis of HSV encephalitis and neonatal meningoencephalitis. Intravenous acyclovir for 14−21 days is the standard treatment in HSV encephalitis. Neurological outcomes in neonates are improved by intravenous high-dose acyclovir for 21 days followed by oral acyclovir suppressive therapy for 6 months.

Varicella-zoster virus (VZV) causes a wide range of CNS manifestations. VZV encephalitis typically occurs after primary infection, and reactivation of VZV may cause encephalitis. On the other hand, VZV infection of cerebral arteries produces vasculopathy, which can manifest as ischemic stroke. Vasculopathy can occur after primary infection or reactivation of VZV. PCR detection of VZV DNA in the cerebrospinal fluid can be used for the diagnosis of encephalitis or vasculopathy. Although there are no controlled treatment trials to assess VZV treatments of encephalitis or vasculopathy, intravenous acyclovir is a common treatment.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
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

  • Aberle SW, Aberle JH, Steininger C, Puchhammer-Stockl E (2005) Quantitative real time PCR detection of Varicella-zoster virus DNA in cerebrospinal fluid in patients with neurological disease. Med Microbiol Immunol 194(1–2):7–12. https://doi.org/10.1007/s00430-003-0202-1

    Article  PubMed  CAS  Google Scholar 

  • Amlie-Lefond C, Kleinschmidt-DeMasters BK, Mahalingam R, Davis LE, Gilden DH (1995) The vasculopathy of varicella-zoster virus encephalitis. Ann Neurol 37(6):784–790. https://doi.org/10.1002/ana.410370612

    Article  PubMed  CAS  Google Scholar 

  • Andersen LL, Mork N, Reinert LS, Kofod-Olsen E, Narita R, Jorgensen SE, Skipper KA, Honing K, Gad HH, Ostergaard L, Orntoft TF, Hornung V, Paludan SR, Mikkelsen JG, Fujita T, Christiansen M, Hartmann R, Mogensen TH (2015) Functional IRF3 deficiency in a patient with herpes simplex encephalitis. J Exp Med 212(9):1371–1379. https://doi.org/10.1084/jem.20142274

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ando Y, Kimura H, Miwata H, Kudo T, Shibata M, Morishima T (1993) Quantitative analysis of herpes simplex virus DNA in cerebrospinal fluid of children with herpes simplex encephalitis. J Med Virol 41(2):170–173

    Article  PubMed  CAS  Google Scholar 

  • Armangue T, Leypoldt F, Malaga I, Raspall-Chaure M, Marti I, Nichter C, Pugh J, Vicente-Rasoamalala M, Lafuente-Hidalgo M, Macaya A, Ke M, Titulaer MJ, Hoftberger R, Sheriff H, Glaser C, Dalmau J (2014) Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol 75(2):317–323. https://doi.org/10.1002/ana.24083

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ashkar AA, Yao XD, Gill N, Sajic D, Patrick AJ, Rosenthal KL (2004) Toll-like receptor (TLR)-3, but not TLR4, agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA. J Infect Dis 190(10):1841–1849. https://doi.org/10.1086/425079

    Article  PubMed  CAS  Google Scholar 

  • Askalan R, Laughlin S, Mayank S, Chan A, MacGregor D, Andrew M, Curtis R, Meaney B, deVeber G (2001) Chickenpox and stroke in childhood: a study of frequency and causation. Stroke 32(6):1257–1262

    Article  PubMed  CAS  Google Scholar 

  • Audry M, Ciancanelli M, Yang K, Cobat A, Chang HH, Sancho-Shimizu V, Lorenzo L, Niehues T, Reichenbach J, Li XX, Israel A, Abel L, Casanova JL, Zhang SY, Jouanguy E, Puel A (2011) NEMO is a key component of NF-kappaB- and IRF-3-dependent TLR3-mediated immunity to herpes simplex virus. J Allergy Clin Immunol 128(3):610–617, e611–614. https://doi.org/10.1016/j.jaci.2011.04.059

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Aurelius E, Johansson B, Skoldenberg B, Staland A, Forsgren M (1991) Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet 337(8735):189–192

    Article  PubMed  CAS  Google Scholar 

  • Bajaj M, Mody S, Natarajan G (2014) Clinical and neuroimaging findings in neonatal herpes simplex virus infection. J Pediatr 165(2):404–407, e401. https://doi.org/10.1016/j.jpeds.2014.04.046

    Article  PubMed  Google Scholar 

  • Barnes DW, Whitley RJ (1986) CNS diseases associated with varicella zoster virus and herpes simplex virus infection. Pathogenesis and current therapy. Neurol Clin 4(1):265–283

    Article  PubMed  CAS  Google Scholar 

  • Barnett EM, Jacobsen G, Evans G, Cassell M, Perlman S (1994) Herpes simplex encephalitis in the temporal cortex and limbic system after trigeminal nerve inoculation. J Infect Dis 169(4):782–786

    Article  PubMed  CAS  Google Scholar 

  • Berkefeld J, Enzensberger W, Lanfermann H (2000) MRI in human immunodeficiency virus-associated cerebral vasculitis. Neuroradiology 42(7):526–528

    Article  PubMed  CAS  Google Scholar 

  • Bradford RD, Pettit AC, Wright PW, Mulligan MJ, Moreland LW, McLain DA, Gnann JW, Bloch KC (2009) Herpes simplex encephalitis during treatment with tumor necrosis factor-alpha inhibitors. Clin Infect Dis 49(6):924–927. https://doi.org/10.1086/605498

    Article  PubMed  PubMed Central  Google Scholar 

  • Britton PN, Khoury L, Booy R, Wood N, Jones CA (2016) Encephalitis in Australian children: contemporary trends in hospitalisation. Arch Dis Child 101(1):51–56. https://doi.org/10.1136/archdischild-2015-308468

    Article  PubMed  Google Scholar 

  • Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, Yang K, Alcais A, Picard C, Mahfoufi N, Nicolas N, Lorenzo L, Plancoulaine S, Senechal B, Geissmann F, Tabeta K, Hoebe K, Du X, Miller RL, Heron B, Mignot C, de Villemeur TB, Lebon P, Dulac O, Rozenberg F, Beutler B, Tardieu M, Abel L, Casanova JL (2006) Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314(5797):308–312. https://doi.org/10.1126/science.1128346

    Article  PubMed  CAS  Google Scholar 

  • Chow FC, Glaser CA, Sheriff H, Xia D, Messenger S, Whitley R, Venkatesan A (2015) Use of clinical and neuroimaging characteristics to distinguish temporal lobe herpes simplex encephalitis from its mimics. Clin Infect Dis 60(9):1377–1383. https://doi.org/10.1093/cid/civ051

    Article  PubMed  PubMed Central  Google Scholar 

  • Corey L, Wald A (2009) Maternal and neonatal herpes simplex virus infections. N Engl J Med 361(14):1376–1385. https://doi.org/10.1056/NEJMra0807633

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Corey L, Whitley RJ, Stone EF, Mohan K (1988) Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome. Lancet 1(8575–6):1–4

    Article  PubMed  CAS  Google Scholar 

  • De Tiege X, Heron B, Lebon P, Ponsot G, Rozenberg F (2003) Limits of early diagnosis of herpes simplex encephalitis in children: a retrospective study of 38 cases. Clin Infect Dis 36(10):1335–1339. https://doi.org/10.1086/374839

    Article  PubMed  Google Scholar 

  • Dennett C, Klapper PE, Cleator GM (1996) Polymerase chain reaction in the investigation of “relapse” following herpes simplex encephalitis. J Med Virol 48(2):129–132. https://doi.org/10.1002/(SICI)1096-9071(199602)48:2<129::AID-JMV2>3.0.CO;2-B

    Article  PubMed  CAS  Google Scholar 

  • Dhawan A, Kecskes Z, Jyoti R, Kent AL (2006) Early diffusion-weighted magnetic resonance imaging findings in neonatal herpes encephalitis. J Paediatr Child Health 42(12):824–826. https://doi.org/10.1111/j.1440-1754.2006.00986.x

    Article  PubMed  Google Scholar 

  • Domingues RB, Tsanaclis AM, Pannuti CS, Mayo MS, Lakeman FD (1997) Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples. Clin Infect Dis 25(1):86–91

    Article  PubMed  CAS  Google Scholar 

  • Domingues RB, Fink MC, Tsanaclis AM, de Castro CC, Cerri GG, Mayo MS, Lakeman FD (1998) Diagnosis of herpes simplex encephalitis by magnetic resonance imaging and polymerase chain reaction assay of cerebrospinal fluid. J Neurol Sci 157(2):148–153

    Article  PubMed  CAS  Google Scholar 

  • Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, Yang K, Chapgier A, Eidenschenk C, Eid P, Al Ghonaium A, Tufenkeji H, Frayha H, Al-Gazlan S, Al-Rayes H, Schreiber RD, Gresser I, Casanova JL (2003) Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet 33(3):388–391. https://doi.org/10.1038/ng1097

    Article  PubMed  CAS  Google Scholar 

  • Egan KP, Wu S, Wigdahl B, Jennings SR (2013) Immunological control of herpes simplex virus infections. J Neurovirol 19(4):328–345. https://doi.org/10.1007/s13365-013-0189-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Eidelberg D, Sotrel A, Horoupian DS, Neumann PE, Pumarola-Sune T, Price RW (1986) Thrombotic cerebral vasculopathy associated with herpes zoster. Ann Neurol 19(1):7–14. https://doi.org/10.1002/ana.410190103

    Article  PubMed  CAS  Google Scholar 

  • Elbers JM, Bitnun A, Richardson SE, Ford-Jones EL, Tellier R, Wald RM, Petric M, Kolski H, Heurter H, MacGregor D (2007) A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease? Pediatrics 119(2):e399–e407. https://doi.org/10.1542/peds.2006-1494

    Article  PubMed  Google Scholar 

  • Fonseca-Aten M, Messina AF, Jafri HS, Sanchez PJ (2005) Herpes simplex virus encephalitis during suppressive therapy with acyclovir in a premature infant. Pediatrics 115(3):804–809. https://doi.org/10.1542/peds.2004-0777

    Article  PubMed  Google Scholar 

  • Gaensbauer JT, Birkholz M, Pfannenstein K, Todd JK (2014) Herpes PCR testing and empiric acyclovir use beyond the neonatal period. Pediatrics 134(3):e651–e656. https://doi.org/10.1542/peds.2014-0294

    Article  PubMed  Google Scholar 

  • Gantt S, Muller WJ (2013) The immunologic basis for severe neonatal herpes disease and potential strategies for therapeutic intervention. Clin Dev Immunol 2013:369172. https://doi.org/10.1155/2013/369172

    Article  PubMed  PubMed Central  Google Scholar 

  • Gilden DH, Kleinschmidt-DeMasters BK, Wellish M, Hedley-Whyte ET, Rentier B, Mahalingam R (1996) Varicella zoster virus, a cause of waxing and waning vasculitis: the New England Journal of Medicine case 5-1995 revisited. Neurology 47(6):1441–1446

    Article  PubMed  CAS  Google Scholar 

  • Gnann JW Jr, Skoldenberg B, Hart J, Aurelius E, Schliamser S, Studahl M, Eriksson BM, Hanley D, Aoki F, Jackson AC, Griffiths P, Miedzinski L, Hanfelt-Goade D, Hinthorn D, Ahlm C, Aksamit A, Cruz-Flores S, Dale I, Cloud G, Jester P, Whitley RJ, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (2015) Herpes simplex encephalitis: lack of clinical benefit of long-term valacyclovir therapy. Clin Infect Dis 61(5):683–691. https://doi.org/10.1093/cid/civ369

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grahn A, Studahl M (2015) Varicella-zoster virus infections of the central nervous system – prognosis, diagnostics and treatment. J Infect 71(3):281–293. https://doi.org/10.1016/j.jinf.2015.06.004

    Article  PubMed  Google Scholar 

  • Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, Cunningham R, Zuckerman M, Mutton KJ, Solomon T, Ward KN, Lunn MP, Irani SR, Vincent A, Brown DW, Crowcroft NS, Group UKHPAAoES (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10(12):835–844. https://doi.org/10.1016/S1473-3099(10)70222-X

    Article  PubMed  Google Scholar 

  • Heiner L, Demaerel P (2003) Diffusion-weighted MR imaging findings in a patient with herpes simplex encephalitis. Eur J Radiol 45(3):195–198

    Article  PubMed  CAS  Google Scholar 

  • Herman M, Ciancanelli M, Ou YH, Lorenzo L, Klaudel-Dreszler M, Pauwels E, Sancho-Shimizu V, Perez de Diego R, Abhyankar A, Israelsson E, Guo Y, Cardon A, Rozenberg F, Lebon P, Tardieu M, Heropolitanska-Pliszka E, Chaussabel D, White MA, Abel L, Zhang SY, Casanova JL (2012) Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood. J Exp Med 209(9):1567–1582. https://doi.org/10.1084/jem.20111316

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hjalmarsson A, Blomqvist P, Skoldenberg B (2007) Herpes simplex encephalitis in Sweden, 1990–2001: incidence, morbidity, and mortality. Clin Infect Dis 45(7):875–880. https://doi.org/10.1086/521262

    Article  PubMed  Google Scholar 

  • Hudson SJ, Dix RD, Streilein JW (1991) Induction of encephalitis in SJL mice by intranasal infection with herpes simplex virus type 1: a possible model of herpes simplex encephalitis in humans. J Infect Dis 163(4):720–727

    Article  PubMed  CAS  Google Scholar 

  • Huppatz C, Durrheim DN, Levi C, Dalton C, Williams D, Clements MS, Kelly PM (2009) Etiology of encephalitis in Australia, 1990–2007. Emerg Infect Dis 15(9):1359–1365. https://doi.org/10.3201/eid1509.081540

    Article  PubMed  PubMed Central  Google Scholar 

  • Jones CA, Raynes-Greenow C, Isaacs D, Neonatal HSVSI, Contributors to the Australian Paediatric Surveillance U (2014) Population-based surveillance of neonatal herpes simplex virus infection in Australia, 1997–2011. Clin Infect Dis 59(4):525–531. https://doi.org/10.1093/cid/ciu381

    Article  PubMed  CAS  Google Scholar 

  • Kamei S, Sekizawa T, Shiota H, Mizutani T, Itoyama Y, Takasu T, Morishima T, Hirayanagi K (2005) Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry 76(11):1544–1549. https://doi.org/10.1136/jnnp.2004.049676

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kang JH, Ho JD, Chen YH, Lin HC (2009) Increased risk of stroke after a herpes zoster attack: a population-based follow-up study. Stroke 40(11):3443–3448. https://doi.org/10.1161/STROKEAHA.109.562017

    Article  PubMed  CAS  Google Scholar 

  • Kato K, Hara S, Kawada J, Ito Y (2015) Recurrent neonatal herpes simplex virus infection with central nervous system disease after completion of a 6-month course of suppressive therapy: case report. J Infect Chemother 21(12):879–881. https://doi.org/10.1016/j.jiac.2015.08.005

    Article  PubMed  Google Scholar 

  • Kawada J, Kimura H, Ito Y, Ando Y, Tanaka-Kitajima N, Hayakawa M, Nunoi H, Endo F, Morishima T (2004a) Evaluation of systemic inflammatory responses in neonates with herpes simplex virus infection. J Infect Dis 190(3):494–498. https://doi.org/10.1086/422325

    Article  PubMed  Google Scholar 

  • Kawada J, Kimura H, Ito Y, Hoshino Y, Tanaka-Kitajima N, Ando Y, Futamura M, Morishima T (2004b) Comparison of real-time and nested PCR assays for detection of herpes simplex virus DNA. Microbiol Immunol 48(5):411–415

    Article  PubMed  CAS  Google Scholar 

  • Kielian T (2009) Overview of toll-like receptors in the CNS. Curr Top Microbiol Immunol 336:1–14. https://doi.org/10.1007/978-3-642-00549-7_1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kimberlin DW (2007) Herpes simplex virus infections of the newborn. Semin Perinatol 31(1):19–25. https://doi.org/10.1053/j.semperi.2007.01.003

    Article  PubMed  Google Scholar 

  • Kimberlin DW, Lakeman FD, Arvin AM, Prober CG, Corey L, Powell DA, Burchett SK, Jacobs RF, Starr SE, Whitley RJ (1996) 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 174(6):1162–1167

    Article  PubMed  CAS  Google Scholar 

  • Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Corey L, Gruber WC, Rathore M, Bradley JS, Diaz PS, Kumar M, Arvin AM, Gutierrez K, Shelton M, Weiner LB, Sleasman JW, de Sierra TM, Weller S, Soong SJ, Kiell J, Lakeman FD, Whitley RJ, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (2001) Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics 108(2):230–238

    Article  PubMed  CAS  Google Scholar 

  • Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A, Palmer A, Sanchez PJ, Jacobs RF, Bradley JS, Robinson JL, Shelton M, Dennehy PH, Leach C, Rathore M, Abughali N, Wright P, Frenkel LM, Brady RC, Van Dyke R, Weiner LB, Guzman-Cottrill J, CA MC, Griffin J, Jester P, Parker M, Lakeman FD, Kuo H, Lee CH, Cloud GA, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (2011) Oral acyclovir suppression and neurodevelopment after neonatal herpes. N Engl J Med 365(14):1284–1292. https://doi.org/10.1056/NEJMoa1003509

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kimura H, Futamura M, Kito H, Ando T, Goto M, Kuzushima K, Shibata M, Morishima T (1991) Detection of viral DNA in neonatal herpes simplex virus infections: frequent and prolonged presence in serum and cerebrospinal fluid. J Infect Dis 164(2):289–293

    Article  PubMed  CAS  Google Scholar 

  • Kimura H, Ito Y, Futamura M, Ando Y, Yabuta Y, Hoshino Y, Nishiyama Y, Morishima T (2002) Quantitation of viral load in neonatal herpes simplex virus infection and comparison between type 1 and type 2. J Med Virol 67(3):349–353. https://doi.org/10.1002/jmv.10084

    Article  PubMed  Google Scholar 

  • Kleinschmidt-DeMasters BK, Gilden DH (2001) Varicella-Zoster virus infections of the nervous system: clinical and pathologic correlates. Arch Pathol Lab Med 125(6):770–780. https://doi.org/10.1043/0003-9985(2001)125<0770:VZVIOT>2.0.CO;2

    Article  PubMed  CAS  Google Scholar 

  • Kneen R, Jakka S, Mithyantha R, Riordan A, Solomon T (2010) The management of infants and children treated with aciclovir for suspected viral encephalitis. Arch Dis Child 95(2):100–106. https://doi.org/10.1136/adc.2008.144998

    Article  PubMed  Google Scholar 

  • Kneen R, Michael BD, Menson E, Mehta B, Easton A, Hemingway C, Klapper PE, Vincent A, Lim M, Carrol E, Solomon T, National Encephalitis Guidelines D, Stakeholder G (2012) Management of suspected viral encephalitis in children – Association of British Neurologists and British Paediatric Allergy, Immunology and Infection Group national guidelines. J Infect 64(5):449–477. https://doi.org/10.1016/j.jinf.2011.11.013

    Article  PubMed  CAS  Google Scholar 

  • Kollmann TR, Levy O, Montgomery RR, Goriely S (2012) Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity 37(5):771–783. https://doi.org/10.1016/j.immuni.2012.10.014

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kurt-Jones EA, Chan M, Zhou S, Wang J, Reed G, Bronson R, Arnold MM, Knipe DM, Finberg RW (2004) Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A 101(5):1315–1320. https://doi.org/10.1073/pnas.0308057100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lakeman FD, Whitley RJ (1995) Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis 171(4):857–863

    Article  PubMed  CAS  Google Scholar 

  • Levitz RE (1998) Herpes simplex encephalitis: a review. Heart Lung 27(3):209–212

    Article  PubMed  CAS  Google Scholar 

  • Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A (2003) Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 198(3):513–520. https://doi.org/10.1084/jem.20030162

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Manco-Johnson MJ, Nuss R, Key N, Moertel C, Jacobson L, Meech S, Weinberg A, Lefkowitz J (1996) Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis. J Pediatr 128(3):319–323

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Torres F, Menon S, Pritsch M, Victor N, Jenetzky E, Jensen K, Schielke E, Schmutzhard E, de Gans J, Chung CH, Luntz S, Hacke W, Meyding-Lamade U, Investigators G (2008) 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 8:40. https://doi.org/10.1186/1471-2377-8-40

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McCabe K, Tyler K, Tanabe J (2003) Diffusion-weighted MRI abnormalities as a clue to the diagnosis of herpes simplex encephalitis. Neurology 61(7):1015–1016

    Article  PubMed  Google Scholar 

  • Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, Safdieh JE, Kamenkovich E, Ostrow LW, Levy M, Greenberg B, Russman AN, Katzan I, Gardner CJ, Hausler M, Nau R, Saraya T, Wada H, Goto H, de Martino M, Ueno M, Brown WD, Terborg C, Gilden DH (2008) The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 70(11):853–860. https://doi.org/10.1212/01.wnl.0000304747.38502.e8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nahmias AJ, Whitley RJ, Visintine AN, Takei Y, Alford CA Jr (1982) Herpes simplex virus encephalitis: laboratory evaluations and their diagnostic significance. J Infect Dis 145(6):829–836

    Article  PubMed  CAS  Google Scholar 

  • Pahud BA, Glaser CA, Dekker CL, Arvin AM, Schmid DS (2011) 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 203(3):316–323. https://doi.org/10.1093/infdis/jiq066

    Article  PubMed  PubMed Central  Google Scholar 

  • Perez de Diego R, Sancho-Shimizu V, Lorenzo L, Puel A, Plancoulaine S, Picard C, Herman M, Cardon A, Durandy A, Bustamante J, Vallabhapurapu S, Bravo J, Warnatz K, Chaix Y, Cascarrigny F, Lebon P, Rozenberg F, Karin M, Tardieu M, Al-Muhsen S, Jouanguy E, Zhang SY, Abel L, Casanova JL (2010) Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis. Immunity 33(3):400–411. https://doi.org/10.1016/j.immuni.2010.08.014

    Article  PubMed  CAS  Google Scholar 

  • Persson A, Bergstrom T, Lindh M, Namvar L, Studahl M (2009) Varicella-zoster virus CNS disease—Viral load, clinical manifestations and sequels. J Clin Virol 46(3):249–253. https://doi.org/10.1016/j.jcv.2009.07.014

    Article  PubMed  CAS  Google Scholar 

  • Pinninti SG, Kimberlin DW (2014) Management of neonatal herpes simplex virus infection and exposure. Arch Dis Child Fetal Neonatal Ed 99(3):F240–F244. https://doi.org/10.1136/archdischild-2013-303762

    Article  PubMed  Google Scholar 

  • Piret J, Boivin G (2015) Innate immune response during herpes simplex virus encephalitis and development of immunomodulatory strategies. Rev Med Virol 25(5):300–319. https://doi.org/10.1002/rmv.1848

    Article  PubMed  Google Scholar 

  • Poissy J, Champenois K, Dewilde A, Melliez H, Georges H, Senneville E, Yazdanpanah Y (2012) Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome. BMC Infect Dis 12:356. https://doi.org/10.1186/1471-2334-12-356

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pollak L, Dovrat S, Book M, Mendelson E, Weinberger M (2012) Varicella zoster vs. herpes simplex meningoencephalitis in the PCR era. A single center study. J Neurol Sci 314(1–2):29–36. https://doi.org/10.1016/j.jns.2011.11.004

    Article  PubMed  Google Scholar 

  • Pouplin T, Pouplin JN, Van Toi P, Lindegardh N, Rogier van Doorn H, Hien TT, Farrar J, Torok ME, Chau TT (2011) Valacyclovir for herpes simplex encephalitis. Antimicrob Agents Chemother 55(7):3624–3626. https://doi.org/10.1128/AAC.01023-10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pruss H, Finke C, Holtje M, Hofmann J, Klingbeil C, Probst C, Borowski K, Ahnert-Hilger G, Harms L, Schwab JM, Ploner CJ, Komorowski L, Stoecker W, Dalmau J, Wandinger KP (2012) N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 72(6):902–911. https://doi.org/10.1002/ana.23689

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ramos-Estebanez C, Lizarraga KJ, Merenda A (2014) A systematic review on the role of adjunctive corticosteroids in herpes simplex virus encephalitis: is timing critical for safety and efficacy? Antivir Ther 19(2):133–139. https://doi.org/10.3851/IMP2683

    Article  PubMed  CAS  Google Scholar 

  • Raschilas F, Wolff M, Delatour F, Chaffaut C, De Broucker T, Chevret S, Lebon P, Canton P, Rozenberg F (2002) Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis 35(3):254–260. https://doi.org/10.1086/341405

    Article  PubMed  Google Scholar 

  • Sancho-Shimizu V, Perez de Diego R, Lorenzo L, Halwani R, Alangari A, Israelsson E, Fabrega S, Cardon A, Maluenda J, Tatematsu M, Mahvelati F, Herman M, Ciancanelli M, Guo Y, AlSum Z, Alkhamis N, Al-Makadma AS, Ghadiri A, Boucherit S, Plancoulaine S, Picard C, Rozenberg F, Tardieu M, Lebon P, Jouanguy E, Rezaei N, Seya T, Matsumoto M, Chaussabel D, Puel A, Zhang SY, Abel L, Al-Muhsen S, Casanova JL (2011) Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency. J Clin Invest 121(12):4889–4902. https://doi.org/10.1172/JCI59259

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schleede L, Bueter W, Baumgartner-Sigl S, Opladen T, Weigt-Usinger K, Stephan S, Smitka M, Leiz S, Kaiser O, Kraus V, van Baalen A, Skopnik H, Hartmann H, Rostasy K, Lucke T, Schara U, Hausler M (2013) Pediatric herpes simplex virus encephalitis: a retrospective multicenter experience. J Child Neurol 28(3):321–331. https://doi.org/10.1177/0883073812471428

    Article  PubMed  Google Scholar 

  • Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E (2009) 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 81(8):1432–1437. https://doi.org/10.1002/jmv.21563

    Article  PubMed  CAS  Google Scholar 

  • Skoldenberg B, Forsgren M, Alestig K, Bergstrom T, Burman L, Dahlqvist E, Forkman A, Fryden A, Lovgren K, Norlin K et al (1984) Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet 2(8405):707–711

    Article  PubMed  CAS  Google Scholar 

  • Solomon T, Michael BD, Smith PE, Sanderson F, Davies NW, Hart IJ, Holland M, Easton A, Buckley C, Kneen R, Beeching NJ, National Encephalitis Guidelines D, Stakeholder G (2012) Management of suspected viral encephalitis in adults—Association of British Neurologists and British Infection Association National Guidelines. J Infect 64(4):347–373. https://doi.org/10.1016/j.jinf.2011.11.014

    Article  PubMed  CAS  Google Scholar 

  • VanLandingham KE, Marsteller HB, Ross GW, Hayden FG (1988) Relapse of herpes simplex encephalitis after conventional acyclovir therapy. JAMA 259(7):1051–1053

    Article  PubMed  CAS  Google Scholar 

  • Vossough A, Zimmerman RA, Bilaniuk LT, Schwartz EM (2008) Imaging findings of neonatal herpes simplex virus type 2 encephalitis. Neuroradiology 50(4):355–366. https://doi.org/10.1007/s00234-007-0349-3

    Article  PubMed  Google Scholar 

  • Westman G, Studahl M, Ahlm C, Eriksson BM, Persson B, Ronnelid J, Schliamser S, Aurelius E (2016) N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis. Clin Microbiol Infect 22(11):934–940. https://doi.org/10.1016/j.cmi.2016.07.028

    Article  PubMed  CAS  Google Scholar 

  • Whitley R, Arvin A, Prober C, Burchett S, Corey L, Powell D, Plotkin S, Starr S, Alford C, Connor J et al (1991) A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med 324(7):444–449. https://doi.org/10.1056/NEJM199102143240703

    Article  PubMed  CAS  Google Scholar 

  • Whitley R, Kimberlin DW, Prober CG (2007) Pathogenesis and disease. In: Arvin A, Campadelli-Fiume G, Mocarski E et al (eds) Human herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge University Press, Cambridge

    Chapter  Google Scholar 

  • Whitley RJ (1990) Viral encephalitis. N Engl J Med 323(4):242–250. https://doi.org/10.1056/NEJM199007263230406

    Article  PubMed  CAS  Google Scholar 

  • Whitley RJ (2006) Herpes simplex encephalitis: adolescents and adults. Antivir Res 71(2–3):141–148. https://doi.org/10.1016/j.antiviral.2006.04.002

    Article  PubMed  CAS  Google Scholar 

  • Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, Hanley D, Nahmias AJ, Soong SJ (1986) Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 314(3):144–149. https://doi.org/10.1056/NEJM198601163140303

    Article  PubMed  CAS  Google Scholar 

  • Whitley RJ, Nahmias AJ, Soong SJ, Galasso GG, Fleming CL, Alford CA (1980) Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics 66(4):495–501

    PubMed  CAS  Google Scholar 

  • Yamada S, Kameyama T, Nagaya S, Hashizume Y, Yoshida M (2003) Relapsing herpes simplex encephalitis: pathological confirmation of viral reactivation. J Neurol Neurosurg Psychiatry 74(2):262–264

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segal D, Sancho-Shimizu V, Lorenzo L, Puel A, Picard C, Chapgier A, Plancoulaine S, Titeux M, Cognet C, von Bernuth H, Ku CL, Casrouge A, Zhang XX, Barreiro L, Leonard J, Hamilton C, Lebon P, Heron B, Vallee L, Quintana-Murci L, Hovnanian A, Rozenberg F, Vivier E, Geissmann F, Tardieu M, Abel L, Casanova JL (2007) TLR3 deficiency in patients with herpes simplex encephalitis. Science 317(5844):1522–1527. https://doi.org/10.1126/science.1139522

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Jun-ichi Kawada

Authors
  1. Jun-ichi Kawada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun-ichi Kawada .

Editor information

Editors and Affiliations

  1. Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan

    Yasushi Kawaguchi

  2. Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

    Yasuko Mori

  3. Department of Virology, Nagoya University Graduation School of Medicine, Nagoya, Aichi, Japan

    Hiroshi Kimura

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kawada, Ji. (2018). Neurological Disorders Associated with Human Alphaherpesviruses. In: Kawaguchi, Y., Mori, Y., Kimura, H. (eds) Human Herpesviruses. Advances in Experimental Medicine and Biology, vol 1045. Springer, Singapore. https://doi.org/10.1007/978-981-10-7230-7_5

Download citation

Publish with us

Policies and ethics

Search

Navigation