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Published in: Journal of Neurology 8/2009

01-08-2009 | Original Communication

Prognostic value of intrathecal antibody production and DNA viral load in cerebrospinal fluid of patients with herpes simplex encephalitis

Authors: Anders Hjalmarsson, Fredrik Granath, Marianne Forsgren, Maria Brytting, Paul Blomqvist, Birgit Sköldenberg

Published in: Journal of Neurology | Issue 8/2009

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Abstract

Herpes simplex encephalitis is a devastating disease. In the early 1980s our group conducted a nationwide clinical trial of acyclovir versus vidarabine in patients with herpes simplex encephalitis in whom intrathecal herpes simplex virus (HSV) antibodies were assayed. The purpose of this study was to investigate if antibody levels and viral load correlate with outcome in herpes simplex encephalitis. We have analysed the prognostic value of HSV antibody levels in serum and cerebrospinal fluid (CSF) at the start of antiviral treatment in the 53 included patients. Frozen samples from a subset of patients were analysed with quantitative polymerase chain reaction (PCR) to assess the prognostic value of the viral load in CSF. IgG-levels in CSF at presentation were significantly higher in vidarabine-treated patients with a favourable outcome than in those treated with vidarabine but with an unfavourable outcome. The intrathecal viral load at presentation showed no correlation with outcome. However, the duration of positive HSV-PCR in CSF was longer in vidarabine-treated than in acyclovir-treated patients. These findings indicate that the B-cell response is important in the pathogenetic process of herpes simplex encephalitis. However, neither antibody levels nor viral load at presentation are useful as prognostic markers for the individual patient in this study.
Literature
1.
go back to reference Aurelius E, Forsgren M, Skoog E, Skoldenberg B (1989) Serodiagnosis of herpes simplex encephalitis by antibody capture enzyme-linked immunosorbent assay. Serodiagnosis and immunotherapy in infectious disease 3:249–258CrossRef Aurelius E, Forsgren M, Skoog E, Skoldenberg B (1989) Serodiagnosis of herpes simplex encephalitis by antibody capture enzyme-linked immunosorbent assay. Serodiagnosis and immunotherapy in infectious disease 3:249–258CrossRef
2.
go back to reference 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 337:189–192PubMedCrossRef 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 337:189–192PubMedCrossRef
3.
go back to reference Aurelius E, Forsgren M, Skoldenberg B, Strannegard O (1993) Persistent intrathecal immune activation in patients with herpes simplex encephalitis. J Infect Dis 168:1248–1252PubMed Aurelius E, Forsgren M, Skoldenberg B, Strannegard O (1993) Persistent intrathecal immune activation in patients with herpes simplex encephalitis. J Infect Dis 168:1248–1252PubMed
4.
go back to reference Aurelius E, Andersson B, Forsgren M, Skoldenberg B, Strannegard O (1994) Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis. J Infect Dis 170:678–681PubMed Aurelius E, Andersson B, Forsgren M, Skoldenberg B, Strannegard O (1994) Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis. J Infect Dis 170:678–681PubMed
5.
go back to reference Bai X, Hosler G, Rogers B, Dawson D, Scheuermann R (1997) Quantitative polymerase chain reaction for human herpesvirus diagnosis and measurement of Epstein–Barr virus burden in posttransplant lymphoproliferative disorder. Clin Chem 43:1843–1849PubMed Bai X, Hosler G, Rogers B, Dawson D, Scheuermann R (1997) Quantitative polymerase chain reaction for human herpesvirus diagnosis and measurement of Epstein–Barr virus burden in posttransplant lymphoproliferative disorder. Clin Chem 43:1843–1849PubMed
6.
go back to reference Casrouge A, Zhang SY, Eidenschenk C et al (2006) Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314:308–312PubMedCrossRef Casrouge A, Zhang SY, Eidenschenk C et al (2006) Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314:308–312PubMedCrossRef
7.
go back to reference Domingues RB, Lakeman FD, Mayo MS, Whitley RJ (1998) Application of competitive PCR to cerebrospinal fluid samples from patients with herpes simplex encephalitis. J Clin Microbiol 36:2229–2234PubMed Domingues RB, Lakeman FD, Mayo MS, Whitley RJ (1998) Application of competitive PCR to cerebrospinal fluid samples from patients with herpes simplex encephalitis. J Clin Microbiol 36:2229–2234PubMed
8.
go back to reference Forsgren M, Skoldenberg B, Jeansson S et al (1989) Serodiagnosis of herpes encephalitis by indirect enzyme-linked immunosorbent assay, experience from a Swedish antiviral trial. Serodiagnosis and immunotherapy in infectious disease 3:259–271CrossRef Forsgren M, Skoldenberg B, Jeansson S et al (1989) Serodiagnosis of herpes encephalitis by indirect enzyme-linked immunosorbent assay, experience from a Swedish antiviral trial. Serodiagnosis and immunotherapy in infectious disease 3:259–271CrossRef
9.
go back to reference Hjalmarsson A, Blomqvist P, Sköldenberg B (2007) Herpes simplex encephalitis in Sweden, 1990–2001: incidence, morbidity, and mortality. Clin Infect Dis 45:875–880PubMedCrossRef Hjalmarsson A, Blomqvist P, Sköldenberg B (2007) Herpes simplex encephalitis in Sweden, 1990–2001: incidence, morbidity, and mortality. Clin Infect Dis 45:875–880PubMedCrossRef
10.
go back to reference 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 171:857–863PubMed 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 171:857–863PubMed
11.
go back to reference Maccallum FO, Potter JM, Edwards DH (1964) Early diagnosis of herpes-simplex encephalitis by brain biopsy. Lancet 14:332–334CrossRef Maccallum FO, Potter JM, Edwards DH (1964) Early diagnosis of herpes-simplex encephalitis by brain biopsy. Lancet 14:332–334CrossRef
12.
go back to reference Norberg P, Bergstrom T, Liljeqvist JA (2006) Genotyping of clinical herpes simplex virus type 1 isolates by use of restriction enzymes. J Clin Microbiol 44:4511–4514PubMedCrossRef Norberg P, Bergstrom T, Liljeqvist JA (2006) Genotyping of clinical herpes simplex virus type 1 isolates by use of restriction enzymes. J Clin Microbiol 44:4511–4514PubMedCrossRef
13.
go back to reference Raschilas F, Wolff M, Delatour F et al (2002) Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis 35:254–260PubMedCrossRef Raschilas F, Wolff M, Delatour F et al (2002) Outcome of and prognostic factors for herpes simplex encephalitis in adult patients: results of a multicenter study. Clin Infect Dis 35:254–260PubMedCrossRef
14.
go back to reference Revello M, Baldanti F, Sarasini A, Zella D, Zavattoni M, Gerna G (1997) Quantitation of herpes simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis by the polymerase chain reaction. Clin Diagn Virol 7(3):183–191PubMedCrossRef Revello M, Baldanti F, Sarasini A, Zella D, Zavattoni M, Gerna G (1997) Quantitation of herpes simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis by the polymerase chain reaction. Clin Diagn Virol 7(3):183–191PubMedCrossRef
15.
go back to reference Rosler A, Pohl M, Braune HJ, Oertel WH, Gemsa D, Sprenger H (1998) Time course of chemokines in the cerebrospinal fluid and serum during herpes simplex type 1 encephalitis. J Neurol Sci 157:82–89PubMedCrossRef Rosler A, Pohl M, Braune HJ, Oertel WH, Gemsa D, Sprenger H (1998) Time course of chemokines in the cerebrospinal fluid and serum during herpes simplex type 1 encephalitis. J Neurol Sci 157:82–89PubMedCrossRef
16.
go back to reference Sabri F, Granath F, Hjalmarsson A, Aurelius E, Skoldenberg B (2006) Modulation of sFas indicates apoptosis in human herpes simplex encephalitis. J Neuroimmunol 171:171–176PubMedCrossRef Sabri F, Granath F, Hjalmarsson A, Aurelius E, Skoldenberg B (2006) Modulation of sFas indicates apoptosis in human herpes simplex encephalitis. J Neuroimmunol 171:171–176PubMedCrossRef
17.
go back to reference Skoldenberg B (1996) Herpes simplex encephalitis. Scand J Infect Dis Suppl 100:8–13PubMed Skoldenberg B (1996) Herpes simplex encephalitis. Scand J Infect Dis Suppl 100:8–13PubMed
18.
go back to reference Skoldenberg B, Forsgren M, Alestig K et al (1984) Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet 2:707–711PubMedCrossRef Skoldenberg B, Forsgren M, Alestig K et al (1984) Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet 2:707–711PubMedCrossRef
19.
go back to reference Studahl M, Rosengren L, Gunther G, Hagberg L (2000) Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction. J Neurol 247:636–642PubMedCrossRef Studahl M, Rosengren L, Gunther G, Hagberg L (2000) Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction. J Neurol 247:636–642PubMedCrossRef
20.
go back to reference Tyler KL (2004) Update on herpes simplex encephalitis. Rev Neurol Dis 1:169–178PubMed Tyler KL (2004) Update on herpes simplex encephalitis. Rev Neurol Dis 1:169–178PubMed
21.
22.
go back to reference Whitley RJ (1991) Herpes simplex virus infections of the central nervous system. Encephalitis and neonatal herpes. Drugs 42:406–427PubMedCrossRef Whitley RJ (1991) Herpes simplex virus infections of the central nervous system. Encephalitis and neonatal herpes. Drugs 42:406–427PubMedCrossRef
23.
go back to reference Whitley RJ (2006) Herpes simplex encephalitis: adolescents and adults. Antiviral Res 71(2–3):141–148PubMedCrossRef Whitley RJ (2006) Herpes simplex encephalitis: adolescents and adults. Antiviral Res 71(2–3):141–148PubMedCrossRef
24.
go back to reference Whitley RJ, Soong SJ, Dolin R, Galasso GJ, Ch’ien LT, Alford CA (1977) Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med 297:289–294PubMedCrossRef Whitley RJ, Soong SJ, Dolin R, Galasso GJ, Ch’ien LT, Alford CA (1977) Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. N Engl J Med 297:289–294PubMedCrossRef
25.
go back to reference Whitley RJ, Alford CA, Hirsch MS et al (1986) Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 314:144–149PubMed Whitley RJ, Alford CA, Hirsch MS et al (1986) Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med 314:144–149PubMed
26.
go back to reference Wildemann B, Ehrhart K, Storch-Hagenlocher B et al (1997) Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis. Neurology 48:1341–1346PubMed Wildemann B, Ehrhart K, Storch-Hagenlocher B et al (1997) Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis. Neurology 48:1341–1346PubMed
Metadata
Title
Prognostic value of intrathecal antibody production and DNA viral load in cerebrospinal fluid of patients with herpes simplex encephalitis
Authors
Anders Hjalmarsson
Fredrik Granath
Marianne Forsgren
Maria Brytting
Paul Blomqvist
Birgit Sköldenberg
Publication date
01-08-2009
Publisher
D. Steinkopff-Verlag
Published in
Journal of Neurology / Issue 8/2009
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-009-5106-6

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