Abstract
The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus (VZV) in patients older than 65 years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65 years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out. The study included 280 patients. The disease was considered to be caused by a VZV infection in 32 patients (11.4%), of which 23 cases were virologically confirmed (detection of VZV DNA in CSF). The most frequent diagnosis of the patients with VZV CNS infection was encephalitis (83.3%), followed by meningitis (13.3%) and cerebellitis (3.3%). The mean annual incidence of VZV CNS infection was 3.0 cases per 100,000 inhabitants. VZV was the most common cause of encephalitis and viral meningitis, ahead of herpes simplex virus (n = 9). At the time of discharge, 12 (40%) patients showed neurological sequelae. Five patients (20%) died during hospitalization, all with encephalitis. Patients with a fatal outcome had significantly higher median age and longer delay before initiating acyclovir. In conclusion, VZV was the first cause of encephalitis in our elderly population. Despite acyclovir treatment, there was a high rate of case fatality and sequelae at discharge.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aberle SW, Aberle JH, Steininger C, Puchhammer-Stöckl E (2005) Quantitative real time PCR detection of varicella-zoster virus DNA in cerebrospinal fluid in patients with neurological disease. Med Microbiol Immunol 194:7–12
Becerra JC, Sieber R, Martinetti G, Costa ST, Meylan P, Bernasconi E (2013) Infection of the central nervous system caused by varicella zoster virus reactivation: a retrospective case series study. Int J Infect Dis 17:e529–e534
Blein C, Gavazzi G, Paccalin M, Baptiste C, Berrut G, Vainchtock A (2015) Burden of herpes zoster: the direct and comorbidity costs of herpes zoster events in hospitalized patients over 50 years in France. BMC Infect Dis 15:350
Burke BL, Steele RW, Beard OW, Wood JS, Cain TD, Marmer DJ (1982) Immune responses to varicella-zoster in the aged. Arch Intern Med 142:291–293
Centers for Disease Control and Prevention (CDC) (1996) Prevention of varicella. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 45:1–36
Cunningham AL, Lal H, Kovac M, Chlibek R, Hwang SJ, Díez-Domingo J et al (2016) Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med 375:1019–1032
De Broucker T, Mailles A, Chabrier S, Morand P (2012) Stahl JP; steering committee and investigators group. Acute varicella zoster encephalitis without evidence of primary vasculopathy in a case-series of 20 patients. Clin Microbiol Infect 18:808–819
de Ory F, Avellón A, Echevarría JE, Sánchez-Seco MP, Trallero G, Cabrerizo M et al (2013) Viral infections of the central nervous system in Spain: a prospective study. J Med Virol 85:554–562
Esteban-Vasallo MD, Domínguez-Berjón MF, Gil-Prieto R, Astray-Mochales J, Gil de Miguel Á (2015) Temporal trends in herpes zoster-related hospitalizations in Madrid (Spain), 2003-2013. J Infect 71:85–92
Gil A, San-Martín M, Carrasco P, González A (2004) Epidemiology of severe varicella-zoster virus infection in Spain. Vaccine 22:3947–3951
Grahn A, Studahl M (2015) Varicella-zoster virus infections of the central nervous system—prognosis, diagnostics and treatment. J Infect 71:281–293
Grahn A, Hagberg L, Nilsson S, Blennow K, Zetterberg H, Studahl M (2013) Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections. J Neurol 260:1813–1821
Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D et al (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10:835–844
Kadambari S, Okike I, Ribeiro S, Ramsay ME, Heath PT, Sharland M et al (2014) Seven-fold increase in viral meningo-encephalitis reports in England and Wales during 2004-2013. J Infect. 69:326–332
Kaewpoowat Q, Salazar L, Aguilera E, Wootton SH, Hasbun R (2016) Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes. Infection 44:337–345
Kawai K, Gebremeskel BG, Acosta CJ (2014) Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open 4(6):e004833
Mailles A, Stahl JP (2009) Steering Committee and Investigators Group. Infectious encephalitis in France in 2007: a national prospective study. Clin Infect Dis 49:1838–1847
Miller AE (1980) Selective decline in cellular immune response to varicella-zoster in the elderly. Neurology 30:582–587
Nagel MA, Gilden D (2014) Neurological complications of varicella zoster virus reactivation. Curr Opin Neurol 27:356–360
Nagel MA, Forghani B, Mahalingam R, Wellish MC, Cohrs RJ, Russman AN et al (2007) The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 68:1069–1073
Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD et al (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271–2284
Pahud BA, Glaser CA, Dekker CL, Arvin AM, Schmid DS (2011) Varicella zoster disease of the central nervous system: epidemiological, clinical, and laboratory features 10 years after the introduction of the varicella vaccine. J Infect Dis 203:316–323
Parisi SG, Basso M, Del Vecchio C, Andreis S, Franchin E, Dal Bello F et al (2016) Viral infections of the central nervous system in elderly patients: a retrospective study. Int J Infect Dis 44:8–10
Persson A, Bergström T, Lindh M, Namvar L, Studahl M (2009) Varicella-zoster virus CNS disease—viral load, clinical manifestations and sequels. J Clin Virol 46:249–253
Rottenstreich A, Oz ZK, Oren I (2014) Association between viral load of varicella zoster virus in cerebrospinal fluid and the clinical course of central nervous system infection. Diagn Microbiol Infect Dis 79:174–177
Studahl M, Petzold M, Cassel T (2013) Disease burden of herpes zoster in Sweden—predominance in the elderly and in women—a register based study. BMC Infect Dis 13:586
Weil AA, Glaser CA, Amad Z, Forghani B (2002) Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymersae chain reaction result. Clin Infect Dis 34:1154–1157
Yawn BP, Gilden D (2013) The global epidemiology of herpes zoster. Neurology 81:928–930
Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS (2007) A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc 82:1341–1349
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The study was approved by the Ethics Committee of the Hospital Universitario Donostia.
Conflict of interest
All authors declare that they have no conflict of interest.
Funding
No funding was received to perform this study.
Rights and permissions
About this article
Cite this article
Arruti, M., Piñeiro, L., Salicio, Y. et al. Incidence of varicella zoster virus infections of the central nervous system in the elderly: a large tertiary hospital-based series (2007–2014). J. Neurovirol. 23, 451–459 (2017). https://doi.org/10.1007/s13365-017-0519-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13365-017-0519-y