Herpes Simplex Encephalitis Questions & Answers

1. Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res. 2006 Sep. 71(2-3):141-8. [QxMD MEDLINE Link].

2. Whitley RJ, Kimberlin DW. Herpes simplex encephalitis: children and adolescents. Semin Pediatr Infect Dis. 2005 Jan. 16(1):17-23. [QxMD MEDLINE Link].

3. Tyler KL. Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's. Herpes. 2004 Jun. 11 Suppl 2:57A-64A. [QxMD MEDLINE Link].

4. Whitley RJ, Cobbs CG, Alford CA Jr, Soong SJ, Hirsch MS, Connor JD, et al. Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group. JAMA. 1989 Jul 14. 262(2):234-9. [QxMD MEDLINE Link].

5. Whitley RJ, Soong SJ, Linneman C Jr, Liu C, Pazin G, Alford CA. Herpes simplex encephalitis. Clinical Assessment. JAMA. 1982 Jan 15. 247(3):317-20. [QxMD MEDLINE Link].

6. Tan IL, McArthur JC, Venkatesan A, Nath A. Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology. 2012 Nov 20. 79(21):2125-32. [QxMD MEDLINE Link]. [Full Text].

7. Lakeman FD, Whitley RJ. 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. 1995 Apr. 171(4):857-63. [QxMD MEDLINE Link].

8. Cinque P, Cleator GM, Weber T, Monteyne P, Sindic CJ, van Loon AM. 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 Oct. 61(4):339-45. [QxMD MEDLINE Link]. [Full Text].

9. Wasay M, Mekan SF, Khelaeni B, Saeed Z, Hassan A, Cheema Z, et al. Extra temporal involvement in herpes simplex encephalitis. Eur J Neurol. 2005 Jun. 12(6):475-9. [QxMD MEDLINE Link].

10. Aurelian L. HSV-induced apoptosis in herpes encephalitis. Curr Top Microbiol Immunol. 2005. 289:79-111. [QxMD MEDLINE Link].

11. DeBiasi RL, Kleinschmidt-DeMasters BK, Richardson-Burns S, Tyler KL. Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis. J Infect Dis. 2002 Dec 1. 186(11):1547-57. [QxMD MEDLINE Link].

12. Esiri MM. Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain. J Neurol Sci. 1982 May. 54(2):209-26. [QxMD MEDLINE Link].

13. Cinque P, Vago L, Marenzi R, Giudici B, Weber T, Corradini R, et al. Herpes simplex virus infections of the central nervous system in human immunodeficiency virus-infected patients: clinical management by polymerase chain reaction assay of cerebrospinal fluid. Clin Infect Dis. 1998 Aug. 27(2):303-9. [QxMD MEDLINE Link].

14. Fodor PA, Levin MJ, Weinberg A, Sandberg E, Sylman J, Tyler KL. Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF. Neurology. 1998 Aug. 51(2):554-9. [QxMD MEDLINE Link].

15. Osih RB, Brazie M, Kanno M. Multifocal herpes simplex virus type 2 encephalitis in a patient with AIDS. AIDS Read. 2007 Feb. 17(2):67-70. [QxMD MEDLINE Link].

16. Baringer JR, Pisani P. Herpes simplex virus genomes in human nervous system tissue analyzed by polymerase chain reaction. Ann Neurol. 1994 Dec. 36(6):823-9. [QxMD MEDLINE Link].

17. Mitchell BM, Stevens JG. Neuroinvasive properties of herpes simplex virus type 1 glycoprotein variants are controlled by the immune response. J Immunol. 1996 Jan 1. 156(1):246-55. [QxMD MEDLINE Link].

18. Geiger KD, Nash TC, Sawyer S, Krahl T, Patstone G, Reed JC, et al. Interferon-gamma protects against herpes simplex virus type 1-mediated neuronal death. Virology. 1997 Nov 24. 238(2):189-97. [QxMD MEDLINE Link].

19. Zhang SY, Abel L, Casanova JL. Mendelian predisposition to herpes simplex encephalitis. Handb Clin Neurol. 2013. 112:1091-7. [QxMD MEDLINE Link].

20. Menasria R, Boivin N, Lebel M, Piret J, Gosselin J, Boivin G. Both TRIF and IPS-1 adaptor proteins contribute to the cerebral innate immune response against HSV-1 infection. J Virol. 2013 Apr 17. [QxMD MEDLINE Link].

21. Cathomas R, Pelosi E, Smart J, Murray N, Simmonds P. Herpes simplex encephalitis as a complication of adjuvant chemotherapy treatment for breast cancer. Clin Oncol (R Coll Radiol). 2005 Jun. 17(4):292-3. [QxMD MEDLINE Link].

22. Kohl S. Herpes Simplex Virus. In: Behrman RE, Kliegman RM, Jenson HB. Behrman: Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders; 2004.

23. Kimberlin D. Herpes simplex virus, meningitis and encephalitis in neonates. Herpes. 2004 Jun. 11 Suppl 2:65A-76A. [QxMD MEDLINE Link].

24. Whitley RJ, Soong SJ, Dolin R, Galasso GJ, Ch'ien LT, Alford CA. Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med. 1977 Aug 11. 297(6):289-94. [QxMD MEDLINE Link].

25. Utley TF, Ogden JA, Gibb A, McGrath N, Anderson NE. The long-term neuropsychological outcome of herpes simplex encephalitis in a series of unselected survivors. Neuropsychiatry Neuropsychol Behav Neurol. 1997 Jul. 10(3):180-9. [QxMD MEDLINE Link].

26. Elbers JM, Bitnun A, Richardson SE, Ford-Jones EL, Tellier R, Wald RM, et al. A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease?. Pediatrics. 2007 Feb. 119(2):e399-407. [QxMD MEDLINE Link].

27. Shelley BP, Raniga SB, Al-Khabouri J. An unusual late complication of intracerebral haematoma in herpes encephalitis after successful acyclovir treatment. J Neurol Sci. 2007 Jan 31. 252(2):177-80. [QxMD MEDLINE Link].

28. Marschitz I, Rödl S, Gruber-Sedlmayr U, Church A, Giovannoni G, Zobel G, et al. Severe chorea with positive anti-basal ganglia antibodies after herpesencephalitis. J Neurol Neurosurg Psychiatry. 2007 Jan. 78(1):105-7. [QxMD MEDLINE Link]. [Full Text].

29. Sköldenberg B, Aurelius E, Hjalmarsson A, Sabri F, Forsgren M, Andersson B, et al. Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults. J Neurol. 2006 Feb. 253(2):163-70. [QxMD MEDLINE Link].

30. Ku A, Lachmann EA, Nagler W. Selective language aphasia from herpes simplex encephalitis. Pediatr Neurol. 1996 Sep. 15(2):169-71. [QxMD MEDLINE Link].

31. McGrath NM, Anderson NE, Hope JK, Croxson MC, Powell KF. Anterior opercular syndrome, caused by herpes simplex encephalitis. Neurology. 1997 Aug. 49(2):494-7. [QxMD MEDLINE Link].

32. Mondal G, Kumar R, Ghosh JK, Basu K, Chatterjee S. Basal ganglia involvement in a child with herpes simplex encephalitis. Indian J Pediatr. 2009 Jul. 76(7):749-50. [QxMD MEDLINE Link].

33. Li JZ, Sax PE. HSV-1 encephalitis complicated by cerebral hemorrhage in an HIV-positive person. AIDS Read. 2009 Apr. 19(4):153-5. [QxMD MEDLINE Link].

34. Benetó A, Gómez E, Rubio P, Sobrino R, Esparza A, Gil M, et al. [Periodical EEG pattern modifications in herpetic encephalitis treated with acyclovir]. Rev Neurol. 1996 Jul. 24(131):829-32. [QxMD MEDLINE Link].

35. Mook-Kanamori B, van de Beek D, Wijdicks EF. Herpes simplex encephalitis with normal initial cerebrospinal fluid examination. J Am Geriatr Soc. 2009 Aug. 57(8):1514-5. [QxMD MEDLINE Link].

36. Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E. Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol. 2009 Aug. 81(8):1432-7. [QxMD MEDLINE Link].

37. Domingues RB, Lakeman FD, Mayo MS, Whitley RJ. Application of competitive PCR to cerebrospinal fluid samples from patients with herpes simplex encephalitis. J Clin Microbiol. 1998 Aug. 36(8):2229-34. [QxMD MEDLINE Link]. [Full Text].

38. Wildemann B, Ehrhart K, Storch-Hagenlocher B, Meyding-Lamadé U, Steinvorth S, Hacke W, et al. Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis. Neurology. 1997 May. 48(5):1341-6. [QxMD MEDLINE Link].

39. Weil AA, Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis. 2002 Apr 15. 34(8):1154-7. [QxMD MEDLINE Link].

40. Benson PC, Swadron SP. Empiric acyclovir is infrequently initiated in the emergency department to patients ultimately diagnosed with encephalitis. Ann Emerg Med. 2006 Jan. 47(1):100-5. [QxMD MEDLINE Link].

41. Rathmann K, Scott SA. Acyclovir. Undefined. In: Drug Evaluation Monographs. Micromedex:2005.

42. Stone KM, Reiff-Eldridge R, White AD, Cordero JF, Brown Z, Alexander ER, et al. Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999. Birth Defects Res A Clin Mol Teratol. 2004 Apr. 70(4):201-7. [QxMD MEDLINE Link].

43. James SH, Kimberlin DW, Whitley RJ. Antiviral therapy for herpesvirus central nervous system infections: neonatal herpes simplex virus infection, herpes simplex encephalitis, and congenital cytomegalovirus infection. Antiviral Res. 2009 Sep. 83(3):207-13. [QxMD MEDLINE Link]. [Full Text].

44. National Institute of Allergy and Infectious Diseases. A Phase III Double-Blind, Placebo-Controlled Trial of Long Term Therapy of Herpes Simplex Encephalitis (HSE): An Evaluation of Valacyclovir (CASG-204). ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct/show/NCT00031486?order=1. Accessed: August 8, 2007.

45. Glenny AM, Fernandez Mauleffinch LM, Pavitt S, Walsh T. Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer. Cochrane Database Syst Rev. 2009 Jan 21. CD006706. [QxMD MEDLINE Link].

46. Sergerie Y, Boivin G, Gosselin D, Rivest S. Delayed but not early glucocorticoid treatment protects the host during experimental herpes simplex virus encephalitis in mice. J Infect Dis. 2007 Mar 15. 195(6):817-25. [QxMD MEDLINE Link].

47. 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 Feb. 6(1):25-32. [QxMD MEDLINE Link].

48. Kamei S, Sekizawa T, Shiota H, Mizutani T, Itoyama Y, Takasu T, et al. Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry. 2005 Nov. 76(11):1544-9. [QxMD MEDLINE Link]. [Full Text].

49. Martinez-Torres F, Menon S, Pritsch M, Victor N, Jenetzky E, Jensen K, 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 Oct 29. 8:40. [QxMD MEDLINE Link]. [Full Text].

50. Pérez de Diego R, Mulvey C, et al. The proteome of Toll-like receptor 3-stimulated human immortalized fibroblasts: implications for susceptibility to herpes simplex virus encephalitis. J Allergy Clin Immunol. 2013 Apr. 131(4):1157-66. [QxMD MEDLINE Link]. [Full Text].

51. Schleede L, Bueter W, Baumgartner-Sigl S, Opladen T, Weigt-Usinger K, Stephan S, et al. Pediatric herpes simplex virus encephalitis: a retrospective multicenter experience. J Child Neurol. 2013 Mar. 28(3):321-31. [QxMD MEDLINE Link].

Shaheen E Lakhan, MD, PhD, MS, MEd, FAAN Clinical Professor of Neurology, Western University of Health Sciences

Shaheen E Lakhan, MD, PhD, MS, MEd, FAAN is a member of the following medical societies: American Academy of Neurology, American Medical Association, International Association for the Study of Pain

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cleveland Clinic; UCLA; MGH; California University of Science and Medicine; Carilion Clinic; Sage Therapeutics; The Learning Corp; Zogenix; Fern Health; Thriveworks; Click Therapeutics; Neurocrine; NeuroSport; SpineThera; Shaheen E. Lakhan, MD.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK life science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Eisai, Jazz, LivaNova, Neurelis, SK life science, Stratus, Sunovion, UCB<br/>Received research grant from: Cerevel Therapeutics, Ovid Therapeutics, Neuropace, Greenwich Jazz, SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Neuroelectrics Corporation, Longboard, Janssen, Equilibre Biopharmaceuticals.

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM Adjunct Associate Professor of Neurology, University of Missouri-Columbia School of Medicine; Medical Director of St Mary's Stroke Program, SSM Neurosciences Institute, SSM Health

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Headache Society

Disclosure: Nothing to disclose.

Wayne E Anderson, DO, FAHS, FAAN Assistant Professor of Internal Medicine/Neurology, College of Osteopathic Medicine of the Pacific Western University of Health Sciences; Clinical Faculty in Family Medicine, Touro University College of Osteopathic Medicine; Clinical Instructor, Departments of Neurology and Pain Management, California Pacific Medical Center

Wayne E Anderson, DO, FAHS, FAAN is a member of the following medical societies: American Academy of Neurology, American Headache Society, California Medical Association, California Neurology Society, International Headache Society, San Francisco Medical Society, San Francisco Neurological Society

Disclosure: Nothing to disclose.

Ramon Diaz-Arrastia, MD, PhD Professor, Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director, North Texas TBI Research Center, Comprehensive Epilepsy Center, Parkland Memorial Hospital

Ramon Diaz-Arrastia, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, New York Academy of Sciences, Phi Beta Kappa

Disclosure: Nothing to disclose.

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