Skip to main content

Advertisement

Log in

Herpes simplex encephalitis in patients with cancer

  • Clinical Study – Patient Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Case reports and animal models suggest that chemotherapy, corticosteroids and radiotherapy (RT) may increase the risk of herpes simplex encephalitis (HSE). We retrospectively examined cases of HSE at an academic hospital devoted to cancer care. Patients were identified by positive herpes simplex virus (HSV) polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) or by brain pathology. There were seven patients with HSE over a 12 year period, four of whom had received cranial RT. During this time, a total of 997 patients were treated with cranial RT, suggesting a greater incidence than the expected risk of two to four cases per million people per year in the general population. Five patients had recently received chemotherapy and three were on dexamethasone. MRI findings were typical; four patients had bilateral anterior temporal lesions and three had unilateral-temporal lesions. Four patients had a normal CSF white blood cell count, three of whom had prior RT and dexamethasone. Four patients were positive for HSV-1, and two for HSV-2. One patient had a negative CSF PCR for HSV, but autopsy confirmed active HSE. Though still rare, the risk of HSE may be increased in patients with cancer, especially in those receiving cranial RT. MRI findings were typical, but CSF white blood cell count was normal in four patients and one had negative CSF testing, suggesting that CSF results may be misleading in this population.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hjalmarsson A, Blomqvist P, Skoldenberg B (2007) Herpes simplex encephalitis in Sweden, 1990–2001: incidence, morbidity and mortality. Clin Infect Dis 45:875–880

    Article  PubMed  Google Scholar 

  2. Mailles A, Stahl JP (2009) Infectious encephalitis in France in 2007: a national prospective study. Clin Infect Dis 49:1838–1847

    Article  PubMed  Google Scholar 

  3. Puchhammer-Stockl E, Presterl E, Croy C et al (2001) Screening for possible failure of herpes simplex PCR in cerebrospinal fluid for the diagnosis of herpes simplex encephalitis. J Med Virol 64:531–536

    Article  PubMed  CAS  Google Scholar 

  4. Schiff D, Rosenblum MK (1998) Herpes simplex encephalitis (HSE) and the immunocompromised. Hum Pathol 29:215–222

    Article  PubMed  CAS  Google Scholar 

  5. Jacobs DH (1999) Herpes simplex virus encephalitis following corticosteroids and cranial irradiation. Neurology 52:1108–1109

    PubMed  CAS  Google Scholar 

  6. Spacca B, Mallucci C, Riordan A et al (2007) HSV encephalitis in a child with brain stem glioma: a rare complication of therapy: case report and review of the neurosurgical literature. Childs Nerv Syst 23:1347–1350

    Article  PubMed  Google Scholar 

  7. Patchell RA, White CL, Clark AW et al (1985) Neurologic complications of bone marrow transplantation. Neurology 35:300–306

    PubMed  CAS  Google Scholar 

  8. Kocher M, Kunze S, Eich HT et al (2005) Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma. Strahlenther Onkol 181:157–163

    Article  PubMed  Google Scholar 

  9. https://a816healthpsi.nyc.gov/epiquery/EpiQuery/CDSS/index.html. Accessed 14 Feb 2011

  10. Stroop WG, Schaefer DC (1986) Production of encephalitis restricted to the temporal lobes by experimental reactivation of herpes simplex virus. J Inf Dis 153:721–731

    Article  CAS  Google Scholar 

  11. Oakley C, Epstein JB, Sherlock CH (1997) Reactivation of oral herpes simplex virus: implications for clinical management of herpes simplex virus recurrence during radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84:272–278

    Article  PubMed  CAS  Google Scholar 

  12. Aldea S, Joly LM, Roujeau T et al (2003) Postoperative herpes simplex virus encephalitis after neurosurgery: case report and review of the literature. Clin Infect Dis 36:e96–e99

    Article  PubMed  Google Scholar 

  13. Sergerie Y, Boivin G, Gosselin D et al (2007) Delayed but not early glucocorticoid treatment protects the host during experimental herpes simplex virus encephalitis in mice. J Infect Dis 195:817–825

    Article  PubMed  CAS  Google Scholar 

  14. Sancho-Shimizu V, Zhang SY, Abel L, Tardieu M, Rozenberg F, Jouanguy E, Casanova JL (2008) Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans. Curr Opin Allergy Clin Immunol 7:495–505

    Article  Google Scholar 

  15. McCoy CE, Carpenter S, Palsson-McDermott EM, Gearing LJ, O’Neill LAJ (2008) Glucocorticoids inhibit IRF3 phosphorylation in response to toll-like receptor-3 and -4 by targeting TBK1 activation. J Biol Chem 283:14277–14285

    Article  PubMed  CAS  Google Scholar 

  16. Turrin NP, Plante M-M, Lessard M, Rivest S (2007) Irradiation does not compromise or exacerbate the innate immune response in the brains of mice that were transplanted with bone marrow stem cells. Stem Cells 25:3165–3172

    Article  PubMed  Google Scholar 

  17. Roses RE, Xu M, Koski GK, Czerniecki BJ (2008) Radiation therapy and toll-like receptor signaling: implications for the treatment of cancer. Oncogene 27:200–207

    Article  PubMed  CAS  Google Scholar 

  18. Martinez-Torres F, Menon S, Pristch M et al (2008) Protocol for German trial of acyclovir and corticosteroids in Herpes-Simplex-Encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial. BMC Neurol 8:40

    Article  PubMed  Google Scholar 

  19. Stranska R, Schuurman R, Nienhuis E et al (2005) Survey of acyclovir-resistant herpes simplex virus in the Netherlands: prevalence and characterization. J Clin Virol 32:7–18

    Article  PubMed  CAS  Google Scholar 

  20. Silvano G, Lzazzari G, Resta F et al (2007) A herpes simplex virus-1 fatal encephalitis following chemo-radiotherapy, steroids and prophylactic cranial irradiation in a small cell lung cancer patient. Lung Cancer 57:243–246

    Article  PubMed  CAS  Google Scholar 

  21. Peng T, Blakely J, Cingolani E et al (2007) Herpes simplex encephalitis in a patient with recurrent pituitary adenoma receiving radiation therapy. Am J Clin Oncol 30:664–665

    Article  PubMed  Google Scholar 

  22. Manz HJ, Phillips TM, McCullough DC (1979) Herpes simplex type 2 encephalitis concurrent with known cerebral metastases. Acta Neuropathol 47:237–240

    Article  PubMed  CAS  Google Scholar 

  23. Suzuki HI, Hangaishi A, Hosoya N et al (2008) Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma. Int J Hematol 87:538–541

    Article  PubMed  Google Scholar 

  24. Tohyama Y, Sako K, Daita G et al (1997) Dissociation of 99mTc-ECD and 99mTc-HMPAO distributions in herpes simplex encephalitis. Childs Nerv Syst 13:352–355

    Article  PubMed  CAS  Google Scholar 

  25. Molloy S, Allcutt D, Brennan P, Farrell MA, Perryman R, Brett FM (2000) Herpes simplex encephalitis occurring after chemotherapy, surgery, and stereotactic radiotherapy for medulloblastoma. Arch Pathol Lab Med 124:1809–1812

    PubMed  CAS  Google Scholar 

  26. Riel-Romero RM, Baumann RJ (2003) Herpes simplex encephalitis and radiotherapy. Pediatr Neurol 29:69–71

    Article  PubMed  Google Scholar 

  27. Koudriavtseva T, Onesti E, Tonachella R et al (2010) Fatal herpetic encephalitis during brain radiotherapy in a cerebral metastasized breast cancer patient. J Neurooncol 100:137–140

    Article  PubMed  Google Scholar 

  28. Dragoje S, Tolnay M, Dalquen P et al (1995) Brain irradiation and antioedematous dexamethasone treatment-risk factors for herpes simplex encephalitis. Schweiz Arch Neurol Psychiatr 146:277–280

    PubMed  CAS  Google Scholar 

  29. Saran F, Baumert BG, Creak AL et al (2008) Hypofractionated stereotactic radiotherapy in the management of recurrent or residual medulloblastoma/PNET. Pediatr Blood Cancer 50:554–560

    Article  PubMed  Google Scholar 

  30. Cathomas E, Pelosi E, Smart J (2005) Herpes simplex encephalitis as a complication of adjuvant chemotherapy treatment for breast cancer. Clin Oncol (R Coll Radiol) 17:292–293

    Article  CAS  Google Scholar 

  31. Nolan RC, Van Gessel H, Byrne M (2004) An unusual complication of chemotherapy: herpes simplex meningoencephalitis and bilateral acute retinal necrosis. Clin Oncol 16:81–82

    Article  CAS  Google Scholar 

  32. Graber JJ, Rus H, Zivin-Tutela T et al (2009) Herpes encephalitis in monoclonal gammopathy. Infect Med 26(3):78–81

    Google Scholar 

  33. Rommee R, Brunstein CG, Wiesdorf DJ et al (2010) Herpes simplex virus encephalitis after allogeneic transplantation: an instructive case. Bone Marrow Transpl 45:776–778

    Article  Google Scholar 

  34. McDermott SS, McDermott PF, Skare J et al (2000) Positive CSF HSV PCR in patients with GBM: a note of caution. Neurology 54:746–749

    PubMed  CAS  Google Scholar 

  35. Calderoni A, Aebi S (2002) Combination chemotherapy with high-dose methotrexate and cytarabine with or without brain irradiation for primary central nervous system lymphomas. J Neurooncol 59:227–230

    Article  PubMed  Google Scholar 

  36. Schütt P, Ebeling P, Buttkereit U et al (2005) Thalidomide in combination with dexamethasone for pretreated patients with multiple myeloma: serum level of soluble interleukin-2 receptor as a predictive factor for response rate and for survival. Ann Hematol 84:594–600

    Article  PubMed  Google Scholar 

  37. Klingelhöfer J, Prange HW, Schipper HI (1984) Herpes simplex encephalitis and plasmacytoma: chance coincidence or causal relation (in German). Nervenarzt 55:86–89

    PubMed  Google Scholar 

  38. Chim CS, Ho PL, Yuen KY et al (1999) Herpes simplex encephalitis in multiple myeloma. Aust N Z J Med 29:381–382

    Article  PubMed  CAS  Google Scholar 

  39. Schmidt-Hieber M, Schwender J, Heinz WJ et al (2011) Viral encephalitis after allogeneic stem cell transplantation: a rare complication with distinct characteristics of causative agents. Haematalogica 96:142–149

    Article  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Galina Yusim for her able assistance with data collection for this project, Dr. Peter Mead for his helpful advice and Judith Lampron for her tireless editorial expertise.

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lisa M. DeAngelis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Graber, J.J., Rosenblum, M.K. & DeAngelis, L.M. Herpes simplex encephalitis in patients with cancer. J Neurooncol 105, 415–421 (2011). https://doi.org/10.1007/s11060-011-0609-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-011-0609-2

Keywords

Navigation