Skip to main content
Top
Published in: Journal of Neurology 2/2016

01-02-2016 | Original Communication

Predictors of outcome in HSV encephalitis

Authors: Tarun D. Singh, Jennifer E. Fugate, Sara Hocker, Eelco F. M. Wijdicks, Allen J. Aksamit Jr., Alejandro A. Rabinstein

Published in: Journal of Neurology | Issue 2/2016

Login to get access

Abstract

This study aims to explore the clinical features, radiological findings, management and the factors influencing prognosis in PCR-confirmed herpes simplex virus encephalitis (HSE). This is a retrospective review of consecutive patients diagnosed with HSE at Mayo Clinic, Rochester, MN, between January 1995 and December 2013. Only HSE cases confirmed by PCR were included. Univariate and multivariate analysis was used to identify factors associated with good (modified Rankin Scale of 0–2) or poor outcome (mRS of 3–6) at hospital discharge and 1-year follow-up. We identified 45 patients with HSE. Median age was 66 (IQR 53.5–78) years. HSE was caused by HSV-1 in 33 cases and by HSV-2 in 9. Nearly half had seizures upon admission or during hospitalization. The most common regions involved on MRI were the temporal lobe in 35 (87.5 %), insula in 28 (70.0 %), frontal lobe in 27 (67.5 %) and thalamus in 11 (27.5 %) patients. MRI pattern was quite homogeneous with HSV-1 infection, but much more heterogeneous with HSV-2. Good outcome at discharge and at 6–12 months was seen in 16 (35.6 %) and 27 (65.9 %) patients, respectively. On multivariate analyses, older age (p = 0.001), coma (p = 0.008), restricted diffusion on MRI (p = 0.005) and acyclovir started after the first day of admission (p = 0.050) were associated with poor outcome at discharge. Older age, development of coma, presence of restricted diffusion on brain MRI and delay in the administration of acyclovir portend poor outcome in HSE. Conversely, presence of seizures, focal neurological deficits, EEG abnormalities and location or extension of FLAIR/T2 abnormalities did not influence functional outcome.
Literature
1.
go back to reference Cinque P, Cleator GM, Weber T, Monteyne P, Sindic CJ, van Loon AM (1996) 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 61(4):339–345CrossRefPubMedPubMedCentral Cinque P, Cleator GM, Weber T, Monteyne P, Sindic CJ, van Loon AM (1996) 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 61(4):339–345CrossRefPubMedPubMedCentral
2.
go back to reference Aurelius E, Johansson B, Skoldenberg B, Forsgren M (1993) 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 39(3):179–186CrossRefPubMed Aurelius E, Johansson B, Skoldenberg B, Forsgren M (1993) 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 39(3):179–186CrossRefPubMed
3.
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(6):289–294. doi:10.1056/NEJM197708112970601 CrossRefPubMed 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(6):289–294. doi:10.​1056/​NEJM197708112970​601 CrossRefPubMed
4.
go back to reference 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):707–711CrossRefPubMed 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):707–711CrossRefPubMed
6.
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(8735):189–192CrossRefPubMed 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):189–192CrossRefPubMed
10.
go back to reference Hughes PS, Jackson AC (2012) Delays in initiation of acyclovir therapy in herpes simplex encephalitis. Can J Neurol Sci 39(5):644–648CrossRefPubMed Hughes PS, Jackson AC (2012) Delays in initiation of acyclovir therapy in herpes simplex encephalitis. Can J Neurol Sci 39(5):644–648CrossRefPubMed
11.
go back to reference Kapur N, Barker S, Burrows EH, Ellison D, Brice J, Illis LS, Scholey K, Colbourn C, Wilson B, Loates M (1994) Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile. J Neurol Neurosurg Psychiatry 57(11):1334–1342CrossRefPubMedPubMedCentral Kapur N, Barker S, Burrows EH, Ellison D, Brice J, Illis LS, Scholey K, Colbourn C, Wilson B, Loates M (1994) Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile. J Neurol Neurosurg Psychiatry 57(11):1334–1342CrossRefPubMedPubMedCentral
12.
go back to reference McGrath N, Anderson NE, Croxson MC, Powell KF (1997) Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry 63(3):321–326CrossRefPubMedPubMedCentral McGrath N, Anderson NE, Croxson MC, Powell KF (1997) Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry 63(3):321–326CrossRefPubMedPubMedCentral
13.
go back to reference Pleumpanupat P, Danchaivijitr N, Danchaivijitr C (2009) Retrospective study of patients with herpes simplex encephalitis and positive CSF PCR. J Med Assoc Thai 92(Suppl 2):S95–100PubMed Pleumpanupat P, Danchaivijitr N, Danchaivijitr C (2009) Retrospective study of patients with herpes simplex encephalitis and positive CSF PCR. J Med Assoc Thai 92(Suppl 2):S95–100PubMed
14.
go back to reference 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. doi:10.1086/341405 CrossRefPubMed 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. doi:10.​1086/​341405 CrossRefPubMed
15.
go back to reference Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ (2008) The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 47(3):303–327. doi:10.1086/589747 CrossRefPubMed Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ (2008) The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 47(3):303–327. doi:10.​1086/​589747 CrossRefPubMed
16.
go back to reference Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA (2013) Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 57(8):1114–1128. doi:10.1093/cid/cit458 CrossRefPubMedPubMedCentral Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA (2013) Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 57(8):1114–1128. doi:10.​1093/​cid/​cit458 CrossRefPubMedPubMedCentral
18.
go back to reference 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. doi:10.1093/cid/civ051 PubMedPubMedCentral 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. doi:10.​1093/​cid/​civ051 PubMedPubMedCentral
21.
go back to reference Okanishi T, Yamamoto H, Hosokawa T, Ando N, Nagayama Y, Hashimoto Y, Maihara T, Goto T, Kubota T, Kawaguchi C, Yoshida H, Sugiura K, Itomi S, Ohno K, Takanashi J, Hayakawa M, Otsubo H, Okumura A (2015) Diffusion-weighted MRI for early diagnosis of neonatal herpes simplex encephalitis. Brain Dev 37(4):423–431. doi:10.1016/j.braindev.2014.07.006 CrossRefPubMed Okanishi T, Yamamoto H, Hosokawa T, Ando N, Nagayama Y, Hashimoto Y, Maihara T, Goto T, Kubota T, Kawaguchi C, Yoshida H, Sugiura K, Itomi S, Ohno K, Takanashi J, Hayakawa M, Otsubo H, Okumura A (2015) Diffusion-weighted MRI for early diagnosis of neonatal herpes simplex encephalitis. Brain Dev 37(4):423–431. doi:10.​1016/​j.​braindev.​2014.​07.​006 CrossRefPubMed
23.
go back to reference Poissy J, Wolff M, Dewilde A, Rozenberg F, Raschilas F, Blas M, Georges H, Chaffaut C, Yazdanpanah Y (2009) Factors associated with delay to acyclovir administration in 184 patients with herpes simplex virus encephalitis. Clin Microbiol Infect 15(6):560–564. doi: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 (2009) Factors associated with delay to acyclovir administration in 184 patients with herpes simplex virus encephalitis. Clin Microbiol Infect 15(6):560–564. doi:10.​1111/​j.​1469-0691.​2009.​02735.​x CrossRefPubMed
24.
go back to reference 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 (2015) Herpes simplex encephalitis: lack of clinical benefit of long-term valacyclovir therapy. Clin Infect Dis. doi:10.1093/cid/civ369 PubMedCentral 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 (2015) Herpes simplex encephalitis: lack of clinical benefit of long-term valacyclovir therapy. Clin Infect Dis. doi:10.​1093/​cid/​civ369 PubMedCentral
Metadata
Title
Predictors of outcome in HSV encephalitis
Authors
Tarun D. Singh
Jennifer E. Fugate
Sara Hocker
Eelco F. M. Wijdicks
Allen J. Aksamit Jr.
Alejandro A. Rabinstein
Publication date
01-02-2016
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 2/2016
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-015-7960-8

Other articles of this Issue 2/2016

Journal of Neurology 2/2016 Go to the issue