Research Article| Volume 26, ISSUE 2, P301-307, February 2017

Download started.


Risk of Stroke in Patients with Herpes Zoster: A Systematic Review and Meta-Analysis


      Several observational studies suggest that herpes zoster (HZ) may increase the risk of stroke, but the results are inconsistent. Our study was designed to assess the association between HZ and the risk of stroke through a meta-analysis of cohort studies.


      The electronic databases PubMed and EMBASE were searched from inception to May 31, 2016 to identify relevant cohort studies that assess the risk of stroke in patients with HZ. Reference lists were also reviewed to identify potential studies. The random-effects model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs).


      Six cohort studies (251,076 HZ patients and 8462 cases of stroke) were identified in the study. The result showed that HZ was significantly correlated with increased risk of stroke, and the pooled RR was 1.36 (95% confidence interval [CI]: 1.10, 1.67) (P = .004). In the subgroup analysis, the significant association was observed except for stroke type (hemorrhage group). In the sensitivity analysis, excluding 1 study, the pooled RR was 1.45 (95% CI: 1.17, 1.80) (P = .001) for HZ, and 4.42 (95% CI: 2.75, 7.11) (P = .000) for herpes zoster ophthalmicus. Considerable heterogeneity was observed in our study.


      Our study furnishes evidence of a positive association between HZ and the risk of stroke.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • World Health Organization (WHO)
        The top 10 causes of death.
        (World Health Organization; Available at:) (Accessed May 31, 2016)
        • Donnan G.A.
        • Fisher M.
        • Macleod M.
        • et al.
        Lancet. 2008; 371: 1612-1623
        • Mozaffarian D.
        • Benjamin E.J.
        • Go A.S.
        • et al.
        Heart disease and stroke statistics—2015 update: a report from the American Heart Association.
        Circulation. 2015; 131: e29-e322
        • World Health Organization (WHO)
        Global burden of stroke, the atlas of heart disease and stroke.
        (World Health Organisation; Available at:) (Accessed May 31, 2016)
        • van der Worp H.B.
        • van Gijn J.
        Clinical practice. Acute ischemic stroke.
        N Engl J Med. 2007; 357: 572-579
        • Johnson R.W.
        • Bouhassira D.
        • Kassianos G.
        • et al.
        The impact of herpes zoster and post-herpetic neuralgia on quality-of-life.
        BMC Med. 2010; 8: 37
        • Brisson M.
        • Edmunds W.J.
        • Law B.
        • et al.
        Epidemiology of varicella zoster virus infection in Canada and the United Kingdom.
        Epidemiol Infect. 2001; 127: 305-314
        • Ciccone S.
        • Faggioli R.
        • Calzolari F.
        • et al.
        Stroke after varicella-zoster infection: report of a case and review of the literature.
        Pediatr Infect Dis J. 2010; 29: 864-867
        • Sas A.M.
        • Niks E.H.
        • Lequin M.H.
        • et al.
        Herpes simplex virus type-1 encephalitis and occipital ischemic stroke.
        Pediatr Neurol. 2009; 41: 294-296
        • Joy J.L.
        • Colon H.F.
        • Velez-Borras J.R.
        The syndrome of cerebral infarction following herpes zoster ophthalmicus.
        Bol Asoc Med P R. 1989; 81: 24-25
        • Langan S.M.
        • Minassian C.
        • Smeeth L.
        • et al.
        Risk of stroke following herpes zoster: a self-controlled case-series study.
        Clin Infect Dis. 2014; 58: 1497-1503
        • Breuer J.
        • Pacou M.
        • Gautier A.
        • et al.
        Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK.
        Neurology. 2014; 83: e27-e33
        • Thomas S.L.
        • Minassian C.
        • Ganesan V.
        • et al.
        Chickenpox and risk of stroke: a self-controlled case series analysis.
        Clin Infect Dis. 2014; 58: 61-68
        • Sreenivasan N.
        • Basit S.
        • Wohlfahrt J.
        • et al.
        The short- and long-term risk of stroke after herpes zoster—a nationwide population-based cohort study.
        PLoS ONE. 2013; 8 (e69156)
        • Lin H.C.
        • Chien C.W.
        • Ho J.D.
        Herpes zoster ophthalmicus and the risk of stroke: a population-based follow-up study.
        Neurology. 2010; 74: 792-797
        • Kang J.H.
        • Ho J.D.
        • Chen Y.H.
        • et al.
        Increased risk of stroke after a herpes zoster attack: a population-based follow-up study.
        Stroke. 2009; 40: 3443-3448
        • Sebire G.
        • Meyer L.
        • Chabrier S.
        Varicella as a risk factor for cerebral infarction in childhood: a case-control study.
        Ann Neurol. 1999; 45: 679-680
        • Sundström K.
        • Weibull C.E.
        • Soderberg-Lofdal K.
        • et al.
        Incidence of herpes zoster and associated events including stroke—a population-based cohort study.
        BMC Infect Dis. 2015; 15: 488
        • Yawn B.P.
        • Wollan P.C.
        • Nagel M.A.
        • et al.
        Risk of stroke and myocardial infarction after herpes zoster in older adults in a us community population.
        Mayo Clin Proc. 2016; 91: 33-44
        • Minassian C.
        • Thomas S.L.
        • Smeeth L.
        • et al.
        Acute cardiovascular events after herpes zoster: a self-controlled case series analysis in vaccinated and unvaccinated older residents of the United States.
        PLoS Med. 2015; 12 (e1001919)
        • Kwon S.U.
        • Yun S.C.
        • Kim M.C.
        • et al.
        Risk of stroke and transient ischaemic attack after herpes zoster.
        Clin Microbiol Infect. 2016; 22: 542-548
        • Stang A.
        Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.
        Eur J Epidemiol. 2010; 25: 603-605
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • et al.
        Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.
        JAMA. 2000; 283: 2008-2012
        • Higgins J.P.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • et al.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Begg C.B.
        • Mazumdar M.
        Operating characteristics of a rank correlation test for publication bias.
        Biometrics. 1994; 50: 1088-1101
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • et al.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Copas J.
        • Shi J.Q.
        Meta-analysis, funnel plots and sensitivity analysis.
        Biostatistics. 2000; 1: 247-262
        • Elkind M.S.
        • Hills N.K.
        • Glaser C.A.
        • et al.
        Herpesvirus infections and childhood arterial ischemic stroke: results of the VIPS study.
        Circulation. 2016; 133: 732-741
        • Chen W.H.
        • Chui C.
        • Yin H.L.
        Zoster sine herpete, vertebral artery stenosis, and ischemic stroke.
        J Stroke Cerebrovasc Dis. 2013; 22: e234-e237
        • de Broucker T.
        • Verollet D.
        • Schoindre Y.
        • et al.
        Cerebral vasculitis with aneurysms caused by varicella-zoster virus infection during AIDS: a new clinicoangiographical syndrome.
        Rev Neurol (Paris). 2008; 164: 61-71
        • Kalita J.
        • Das M.
        • Misra U.K.
        Herpes zoster ophthalmicus leading to middle cerebral artery infarction: a case report.
        Int J Angiol. 2004; 13: 51-53
        • Dalton C.M.
        • Jager H.R.
        • Losseff N.A.
        • et al.
        Neurological picture. Varicella zoster virus and intracranial dolichoectasia in a late adult cancer survivor.
        J Neurol Neurosurg Psychiatry. 2008; 79: 573
        • Gonzalez-Suarez I.
        • Fuentes-Gimeno B.
        • Ruiz-Ares G.
        • et al.
        Varicella-zoster virus vasculopathy. A review description of a new case with multifocal brain hemorrhage.
        J Neurol Sci. 2014; 338: 34-38
        • Nagel M.A.
        • Gilden D.
        The relationship between herpes zoster and stroke.
        Curr Neurol Neurosci Rep. 2015; 15: 16
        • Frid M.G.
        • Brunetti J.A.
        • Burke D.L.
        • et al.
        Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage.
        Am J Pathol. 2006; 168: 659-669
        • Stenmark K.R.
        • Yeager M.E.
        • El Kasmi K.C.
        • et al.
        The adventitia: essential regulator of vascular wall structure and function.
        Annu Rev Physiol. 2013; 75: 23-47
        • Feller L.
        • Jadwat Y.
        • Bouckaert M.
        Herpes zoster post-herpetic neuralgia.
        SADJ. 2005; 60 (436-437): 432
        • Daniel H.C.
        • Narewska J.
        • Serpell M.
        • et al.
        Comparison of psychological and physical function in neuropathic pain and nociceptive pain: implications for cognitive behavioral pain management programs.
        Eur J Pain. 2008; 12: 731-741