Skip to main content
Top
Published in: BMC Infectious Diseases 1/2012

Open Access 01-12-2012 | Research article

Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome

Authors: Julien Poissy, Karen Champenois, Anny Dewilde, Hugues Melliez, Hugues Georges, Eric Senneville, Yazdan Yazdanpanah

Published in: BMC Infectious Diseases | Issue 1/2012

Login to get access

Abstract

Background

Herpes simplex encephalitis (HSE) often leads to severe disability or death. Factors usually associated with outcome include Simplified Acute Physiology Score, age and delay of initiation of acyclovir treatment.
Our aim was to determine the impact of Herpes simplex virus (HSV) load in cerebrospinal fluid (CSF) upon HSE outcome.

Methods

We retrospectively determined HSV load in the CSF of 43 patients with confirmed HSE, hospitalized in northern France from 1998 to 2005, using CSF samples collected the day of hospital admission and stored at −20°C. We analyzed the association between HSV load and mortality/morbidity by the Glasgow Outcome Scale. Fisher’s exact test and Wilcoxon’s test were used for statistical analysis.

Results

The M/F sex ratio was 1.7 and median patient age was 61 years. Median HSV load in CSF was 2.0 log copies/μL (IQR 25-75=1.2-2.6). The mortality rate was 32.6% six months after HSE diagnosis. Higher age was associated with mortality (p=0.03). Longer delay in acyclovir initiation tended to be associated with higher mortality but did not reach statistical significance (p=0.08). Severe disability and death due to HSV were associated with a higher Knaus score (p=0.004), later acyclovir initiation (p=0.006), older age (p=0.04) and presence of red blood cells in CSF (p=0.05). HSV load in CSF was neither associated with mortality (p=1.00) nor with morbidity (p=0.90).

Conclusion

In this study, HSV load in CSF was not found to be associated with poor outcome in patients with HSE. These data do not support measurement of HSV load at admission in patients with HSE.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Whitley RJ: Herpes simplex encephalitis: adolescents and adults. Antiviral Res. 2006, 71 (2–3): 141-148.CrossRefPubMed Whitley RJ: Herpes simplex encephalitis: adolescents and adults. Antiviral Res. 2006, 71 (2–3): 141-148.CrossRefPubMed
3.
go back to reference Gordon B, Selnes OA, Hart J, Hanley DF, Whitley RJ: Long-term cognitive sequelae of acyclovir-treated herpes simplex encephalitis. Arch Neurol. 1990, 47 (6): 646-647. 10.1001/archneur.1990.00530060054017.CrossRefPubMed Gordon B, Selnes OA, Hart J, Hanley DF, Whitley RJ: Long-term cognitive sequelae of acyclovir-treated herpes simplex encephalitis. Arch Neurol. 1990, 47 (6): 646-647. 10.1001/archneur.1990.00530060054017.CrossRefPubMed
4.
go back to reference Kapur N, Barker S, Burrows EH, Ellison D, Brice J, Illis LS, Scholey K, Colbourn C, Wilson B, Loates M: Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile. J Neurol Neurosurg Psychiatry. 1994, 57 (11): 1334-1342. 10.1136/jnnp.57.11.1334.CrossRefPubMedPubMedCentral Kapur N, Barker S, Burrows EH, Ellison D, Brice J, Illis LS, Scholey K, Colbourn C, Wilson B, Loates M: Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile. J Neurol Neurosurg Psychiatry. 1994, 57 (11): 1334-1342. 10.1136/jnnp.57.11.1334.CrossRefPubMedPubMedCentral
5.
go back to reference Raschilas F, Wolff M, Delatour F, Chaffaut C, De Broucker T, Chevret S, Lebon P, Canton P, Rozenberg F: Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis. 2002, 35 (3): 254-260. 10.1086/341405.CrossRefPubMed Raschilas F, Wolff M, Delatour F, Chaffaut C, De Broucker T, Chevret S, Lebon P, Canton P, Rozenberg F: Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis. 2002, 35 (3): 254-260. 10.1086/341405.CrossRefPubMed
6.
go back to reference Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, Hanley D, Nahmias AJ, Soong SJ: Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med. 1986, 314 (3): 144-149. 10.1056/NEJM198601163140303.CrossRefPubMed Whitley RJ, Alford CA, Hirsch MS, Schooley RT, Luby JP, Aoki FY, Hanley D, Nahmias AJ, Soong SJ: Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med. 1986, 314 (3): 144-149. 10.1056/NEJM198601163140303.CrossRefPubMed
7.
go back to reference Nahmias AJ, Whitley RJ, Visintine AN, Takei Y, Alford CA: Herpes simplex virus encephalitis: laboratory evaluations and their diagnostic significance. J Infect Dis. 1982, 145 (6): 829-836. 10.1093/infdis/145.6.829.CrossRefPubMed Nahmias AJ, Whitley RJ, Visintine AN, Takei Y, Alford CA: Herpes simplex virus encephalitis: laboratory evaluations and their diagnostic significance. J Infect Dis. 1982, 145 (6): 829-836. 10.1093/infdis/145.6.829.CrossRefPubMed
8.
go back to reference 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, 36 (8): 2229-2234.PubMedPubMedCentral 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, 36 (8): 2229-2234.PubMedPubMedCentral
9.
go back to reference Revello MG, Baldanti F, Sarasini A, Zella D, Zavattoni M, Gerna G: Quantitation of herpes simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis by the polymerase chain reaction. Clin Diagn Virol. 1997, 7 (3): 183-191. 10.1016/S0928-0197(97)00269-9.CrossRefPubMed Revello MG, Baldanti F, Sarasini A, Zella D, Zavattoni M, Gerna G: Quantitation of herpes simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis by the polymerase chain reaction. Clin Diagn Virol. 1997, 7 (3): 183-191. 10.1016/S0928-0197(97)00269-9.CrossRefPubMed
10.
go back to reference Wildemann B, Ehrhart K, Storch-Hagenlocher B, Meyding-Lamade U, Steinvorth S, Hacke W, Haas J: Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis. Neurology. 1997, 48 (5): 1341-1346. 10.1212/WNL.48.5.1341.CrossRefPubMed Wildemann B, Ehrhart K, Storch-Hagenlocher B, Meyding-Lamade U, Steinvorth S, Hacke W, Haas J: Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis. Neurology. 1997, 48 (5): 1341-1346. 10.1212/WNL.48.5.1341.CrossRefPubMed
11.
go back to reference Ruzek D, Piskunova N, Zampachova E: High variability in viral load in cerebrospinal fluid from patients with herpes simplex and varicella-zoster infections of the central nervous system. Clin Microbiol Infect. 2007, 13 (12): 1217-1219. 10.1111/j.1469-0691.2007.01831.x.CrossRefPubMed Ruzek D, Piskunova N, Zampachova E: High variability in viral load in cerebrospinal fluid from patients with herpes simplex and varicella-zoster infections of the central nervous system. Clin Microbiol Infect. 2007, 13 (12): 1217-1219. 10.1111/j.1469-0691.2007.01831.x.CrossRefPubMed
12.
go back to reference Jennett B, Bond M: Assessment of outcome after severe brain damage. Lancet. 1975, 1 (7905): 480-484.CrossRefPubMed Jennett B, Bond M: Assessment of outcome after severe brain damage. Lancet. 1975, 1 (7905): 480-484.CrossRefPubMed
13.
go back to reference Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974, 2 (7872): 81-84.PubMed Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974, 2 (7872): 81-84.PubMed
14.
go back to reference Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE: APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med. 1981, 9 (8): 591-597. 10.1097/00003246-198108000-00008.CrossRefPubMed Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE: APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med. 1981, 9 (8): 591-597. 10.1097/00003246-198108000-00008.CrossRefPubMed
15.
go back to reference Mac Cabe W, Jackson W: Gram negative bacteriema: etiology and ecology. Arch Intern Med. 1962, 110: 83-91. 10.1001/archinte.1962.03620190085013.CrossRef Mac Cabe W, Jackson W: Gram negative bacteriema: etiology and ecology. Arch Intern Med. 1962, 110: 83-91. 10.1001/archinte.1962.03620190085013.CrossRef
16.
go back to reference Poissy J, Wolff M, Dewilde A, Rozenberg F, Raschilas F, Blas M, Georges H, Chaffaut C, Yazdanpanah Y: Factors associated with delay to acyclovir administration in 184 patients with herpes simplex virus encephalitis. Clin Microbiol Infect. 2009, 15 (6): 560-564. 10.1111/j.1469-0691.2009.02735.x.CrossRefPubMed Poissy J, Wolff M, Dewilde A, Rozenberg F, Raschilas F, Blas M, Georges H, Chaffaut C, Yazdanpanah Y: Factors associated with delay to acyclovir administration in 184 patients with herpes simplex virus encephalitis. Clin Microbiol Infect. 2009, 15 (6): 560-564. 10.1111/j.1469-0691.2009.02735.x.CrossRefPubMed
17.
go back to reference Whitley R, Arvin A, Prober C, Burchett S, Corey L, Powell D, Plotkin S, Starr S, Alford C, Connor J, et al: A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med. 1991, 324 (7): 444-449. 10.1056/NEJM199102143240703.CrossRefPubMed Whitley R, Arvin A, Prober C, Burchett S, Corey L, Powell D, Plotkin S, Starr S, Alford C, Connor J, et al: A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. N Engl J Med. 1991, 324 (7): 444-449. 10.1056/NEJM199102143240703.CrossRefPubMed
18.
go back to reference 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, 297 (6): 289-294. 10.1056/NEJM197708112970601.CrossRefPubMed 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, 297 (6): 289-294. 10.1056/NEJM197708112970601.CrossRefPubMed
19.
go back to reference Hjalmarsson A, Granath F, Forsgren M, Brytting M, Blomqvist P, Skoldenberg B: Prognostic value of intrathecal antibody production and DNA viral load in cerebrospinal fluid of patients with herpes simplex encephalitis. J Neurol. 2009, 256 (8): 1243-1251. 10.1007/s00415-009-5106-6.CrossRefPubMed Hjalmarsson A, Granath F, Forsgren M, Brytting M, Blomqvist P, Skoldenberg B: Prognostic value of intrathecal antibody production and DNA viral load in cerebrospinal fluid of patients with herpes simplex encephalitis. J Neurol. 2009, 256 (8): 1243-1251. 10.1007/s00415-009-5106-6.CrossRefPubMed
20.
go back to reference Kamei S, Takasu T, Morishima T, Mizutani T: Serial changes of intrathecal viral loads evaluated by chemiluminescence assay and nested PCR with aciclovir treatment in herpes simplex virus encephalitis. Intern Med. 2004, 43 (9): 796-801. 10.2169/internalmedicine.43.796.CrossRefPubMed Kamei S, Takasu T, Morishima T, Mizutani T: Serial changes of intrathecal viral loads evaluated by chemiluminescence assay and nested PCR with aciclovir treatment in herpes simplex virus encephalitis. Intern Med. 2004, 43 (9): 796-801. 10.2169/internalmedicine.43.796.CrossRefPubMed
21.
go back to reference Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E: Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol. 2009, 81 (8): 1432-1437. 10.1002/jmv.21563.CrossRefPubMed Schloss L, Falk KI, Skoog E, Brytting M, Linde A, Aurelius E: Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real-time PCR in patients with herpes simplex encephalitis. J Med Virol. 2009, 81 (8): 1432-1437. 10.1002/jmv.21563.CrossRefPubMed
22.
go back to reference Kurt-Jones EA, Belko J, Yu C, Newburger PE, Wang J, Chan M, Knipe DM, Finberg RW: The role of toll-like receptors in herpes simplex infection in neonates. J Infect Dis. 2005, 191 (5): 746-748. 10.1086/427339.CrossRefPubMed Kurt-Jones EA, Belko J, Yu C, Newburger PE, Wang J, Chan M, Knipe DM, Finberg RW: The role of toll-like receptors in herpes simplex infection in neonates. J Infect Dis. 2005, 191 (5): 746-748. 10.1086/427339.CrossRefPubMed
23.
go back to reference Kurt-Jones EA, Chan M, Zhou S, Wang J, Reed G, Bronson R, Arnold MM, Knipe DM, Finberg RW: Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A. 2004, 101 (5): 1315-1320. 10.1073/pnas.0308057100.CrossRefPubMedPubMedCentral Kurt-Jones EA, Chan M, Zhou S, Wang J, Reed G, Bronson R, Arnold MM, Knipe DM, Finberg RW: Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A. 2004, 101 (5): 1315-1320. 10.1073/pnas.0308057100.CrossRefPubMedPubMedCentral
24.
go back to reference Jerome KR, Huang ML, Wald A, Selke S, Corey L: Quantitative stability of DNA after extended storage of clinical specimens as determined by real-time PCR. J Clin Microbiol. 2002, 40 (7): 2609-2611. 10.1128/JCM.40.7.2609-2611.2002.CrossRefPubMedPubMedCentral Jerome KR, Huang ML, Wald A, Selke S, Corey L: Quantitative stability of DNA after extended storage of clinical specimens as determined by real-time PCR. J Clin Microbiol. 2002, 40 (7): 2609-2611. 10.1128/JCM.40.7.2609-2611.2002.CrossRefPubMedPubMedCentral
Metadata
Title
Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome
Authors
Julien Poissy
Karen Champenois
Anny Dewilde
Hugues Melliez
Hugues Georges
Eric Senneville
Yazdan Yazdanpanah
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2012
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-12-356

Other articles of this Issue 1/2012

BMC Infectious Diseases 1/2012 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.