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      Herpes zoster and the risk of ischemic and hemorrhagic stroke: A systematic review and meta-analysis

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          Abstract

          Background

          Herpes zoster infection and stroke are highly prevalent in the general population; however, reports have presented inconsistent findings regarding the relationship between herpes zoster infection and stroke. In this meta-analysis, we aimed to clarify this association.

          Material and methods

          The PubMed and Embase databases were searched for studies published from their inception to January 2016. Two investigators independently extracted the data. The pooled relative risk (RR) was calculated using a random effects model.

          Results

          A total of 8 studies met the inclusion criteria. During the first 1 month after herpes zoster infection, the pooled RRs for ischemic stroke and hemorrhagic stroke were 1.55 (95% CI, 1.46–1.65) and 1.70 (95% CI, 0.73–3.96), respectively, and within 3 months after infection, the corresponding RRs were 1.17 (95% CI, 1.12–1.23) and 2.05 (95% CI, 1.17–3.60), respectively. At 1 year and more than 1 year after herpes zoster infection, a significant relationship was not observed between herpes zoster infection and the incidence of ischemic and hemorrhagic stroke. Publication bias was not observed.

          Conclusion

          The accumulated evidence generated from this systematic review indicates that an increased risk for ischemic stroke occurred in the short term after herpes zoster infection, whereas a significant relationship was not observed in the long term after infection. With respect to hemorrhagic stroke, the association was not significant. With respect to hemorrhagic stroke, the association between was not significant except within 3 months after a herpes zoster infection.

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          Most cited references16

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          A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction.

          P Wollan, Barbara P. Yawn, Irwin Kurland … (2007)
          To establish accurate, up-to-date, baseline epidemiological data for herpes zoster (HZ) before the introduction of the recently licensed HZ vaccine. Using data from January 1, 1996, to October 15, 2005, we conducted a population-based study of adult residents (Greater than or equal to 22 years) of Olmsted County, MN, to determine (by medical record review) the incidence of HZ and the rate of HZ-related complications. Incidence rates were determined by age and sex and adjusted to the US population. A total of 1669 adult residents with a confirmed diagnosis of HZ were identified between January 1, 1996, and December 31, 2001. Most (92%) of these patients were immunocompetent and 60% were women. When adjusted to the US adult population, the incidence of HZ was 3.6 per 1000 person-years (95% confidence interval, 3.4-3.7), with a temporal increase from 3.2 to 4.1 per 1000 person-years from 1996 to 2001. The incidence of HZ and the rate of HZ-associated complications increased with age, with 68% of cases occurring in those aged 50 years and older. Postherpetic neuralgia occurred in 18% of adult patients with HZ and in 33% of those aged 79 years and older. Overall, 10% of all patients with HZ experienced 1 or more nonpain complications. Our population-based data suggest that HZ primarily affects immunocompetent adults older than 50 years; 1 in 4 experiences some type of HZ-related complication.
          Article 0 comments Cited 166 times – based on 0 reviews     Review now
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            Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment.

            Don Gilden, Randall Cohrs, Ravi Mahalingam … (2009)
            Vasculopathies caused by varicella zoster virus (VZV) are indicative of a productive virus infection in cerebral arteries after either reactivation of VZV (shingles) or primary infection (chickenpox). VZV vasculopathy can cause ischaemic infarction of the brain and spinal cord, as well as aneurysm, subarachnoid and cerebral haemorrhage, carotid dissection, and, rarely, peripheral arterial disease. VZV vasculopathy in immunocompetent or immunocompromised individuals can be unifocal or multifocal with deep-seated and superficial infarctions. Lesions at the grey-white matter junction on brain imaging are a clue to diagnosis. Involvement of both large and small arteries is more common than that of either alone. Most patients have a mononuclear cerebrospinal fluid pleocytosis, often with red blood cells. Cerebrospinal fluid pleocytosis and rash are absent in about a third of cases. Anti-VZV IgG antibody in the cerebrospinal fluid is found more frequently than VZV DNA. In recent years, the number of recognised VZV vasculopathies has grown, and accurate diagnosis is important for the effective treatment of these disorders.
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              The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features.

              B Forghani, E Kamenkovich, C. Terborg … (2008)
              Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities. We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both. Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis. Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers.
              Article 0 comments Cited 109 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Ilhem Messaoudi: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 8 February 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 2
                Electronic Location Identifier: e0171182
                Affiliations
                [1 ]Department of case administration, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China
                [2 ]Department of Oro-maxillofacial Head and Neck oncology, Ninth People’s Hospital College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
                [3 ]Health Management Center, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China
                [4 ]Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, China
                University of California Riverside, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: YL YZ RSD.

                • Data curation: YL FT.

                • Formal analysis: FT.

                • Funding acquisition: FT.

                • Investigation: YL FT BY.

                • Methodology: YL FT.

                • Project administration: RSD.

                • Resources: YZ.

                • Software: YL.

                • Supervision: RSD.

                • Validation: RSD.

                • Visualization: YZ.

                • Writing – original draft: YL YZ.

                • Writing – review & editing: YL YZ RSD.

                Author information
                http://orcid.org/0000-0002-0679-2403
                Article
                Publisher ID: PONE-D-16-16685
                DOI: 10.1371/journal.pone.0171182
                PMC ID: 5298244
                PubMed ID: 28178287
                SO-VID: 5c6bada0-bb3d-4e40-859b-941477170dc3
                Copyright © © 2017 Lian et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 28 April 2016
                Date accepted : 17 January 2017
                Page count
                Figures: 6, Tables: 1, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100007129, Natural Science Foundation of Shandong Province;
                Award ID: ZR2015HL102
                Award Recipient :
                This work was supported by Shandong provincial Natural Science Foundation (nos.ZR2015HL102). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Cerebrovascular Diseases
                Subject: Stroke
                Subject: Ischemic Stroke
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Stroke
                Subject: Ischemic Stroke
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Cerebrovascular Diseases
                Subject: Stroke
                Subject: Hemorrhagic Stroke
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Stroke
                Subject: Hemorrhagic Stroke
                Subject: Medicine and Health Sciences
                Subject: Infectious Diseases
                Subject: Viral Diseases
                Subject: Shingles
                Subject: Research and Analysis Methods
                Subject: Mathematical and Statistical Techniques
                Subject: Statistical Methods
                Subject: Meta-Analysis
                Subject: Physical Sciences
                Subject: Mathematics
                Subject: Statistics (Mathematics)
                Subject: Statistical Methods
                Subject: Meta-Analysis
                Subject: Research and Analysis Methods
                Subject: Research Design
                Subject: Cohort Studies
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Cerebrovascular Diseases
                Subject: Stroke
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Stroke
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Vaccination and Immunization
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Vaccination and Immunization
                Subject: Medicine and Health Sciences
                Subject: Public and Occupational Health
                Subject: Preventive Medicine
                Subject: Vaccination and Immunization
                Subject: Research and Analysis Methods
                Subject: Database and Informatics Methods
                Subject: Database Searching
                Custom metadata
                Data Availability All relevant data are in the paper and Supporting Information files.

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