ARTICLE IN PRESS

Risk of Stroke in Patients with Herpes Zoster: A Systematic

Review and Meta-Analysis

Sheng-Ye Yang, MM,*1 Hong-Xing Li, MM,†1 Xin-Hao Yi, MM,‡

Guang-Liang Han, MM,† Qiang Zong, MM,† Ming-Xing Wang, MM,† and
Xiao-Xiao Peng, MB,§

Background: Several observational studies suggest that herpes zoster (HZ) may
increase the risk of stroke, but the results are inconsistent. Our study was de-
signed to assess the association between HZ and the risk of stroke through a meta-
analysis of cohort studies. Methods: 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 re-
viewed to identify potential studies. The random-effects model and fixed-effects
model were used to calculate the summary relative risks (RRs) with 95% confi-
dence intervals (CIs). Results: Six cohort studies (251,076 HZ patients and 8462
cases of stroke) were identified in the study. The result showed that HZ was sig-
nificantly 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. Con-
clusion: Our study furnishes evidence of a positive association between HZ and
the risk of stroke. Key Words: Herpes zoster—stroke—risk factor—meta-analysis.
© 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Introduction worldwide.1-3 On average, every 40 seconds, someone has

Studies have reported that stroke is the second most
common cause of death and major cause of disability
From the *Department of Dermatology, Shengli Oilfield Central
Hospital, 31 Jinan Road, Dongying, Shandong 257000, China; †De-
partment of Neurosurgery, Shengli Oilfield Central Hospital, 31 Jinan
Road, Dongying, Shandong 257000, China; ‡Department of Central
Laboratory, Shengli Oilfield Central Hospital, 31 Jinan Road, Dongying,
Shandong 257000, China; and §Department of Intensive Care Unit
(ICU), Shengli Oilfield Central Hospital, 31 Jinan Road, Dongying,
Shandong 257000, China.
Received August 18, 2016; accepted September 13, 2016.
Address correspondence to Xiao-Xiao Peng, MB, Department of
Intensive Care Unit (ICU), Shengli Oilfield Central Hospital, 31 Jinan
Rd, Dongying, Shandong 257000, China. E-mail: luckpxx@sina.com.
1
These authors contributed equally to this work.
1052-3057/$ - see front matter
© 2016 National Stroke Association. Published by Elsevier Inc. All
rights reserved.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.09.021
a stroke and every 4 minutes, someone dies from stroke
in the United States.2,3 Although the incidence of stroke
has declined in many countries because of hypertension
management and reduced levels of smoking, the abso-
lute number of stroke was increasing due to an aging
population.4 Stroke is considered to be a multifactorial
disease that is caused by several factors such as diabetes,
hypertension, smoking, atrial fibrillation, and others. Primary
and secondary prevention should be a key public health
priority of stroke in the current society.5 Hence, risk factor
identification is crucial for the prevention of stroke.
Herpes zoster (HZ) is a common, painful disease caused
by a reactivation of the latent varicella zoster virus (VZV)
infection. HZ is a significant public health problem in
aging populations that affect millions of people every year
in developed countries.6,7 During the past decades, in-
creasing evidence suggested that HZ played a important
role in developing stroke,8-10 and numerous studies have

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■ 1
 ARTICLE IN PRESS
2 S.-Y. YANG ET AL.
11-19
assessed the association of HZ with stroke risk ; however,
the association remains controversial. Some studies sug-
gested that HZ carries an increased risk of stroke,11,13-20
whereas the phenomenon has not been replicated in
another study.12 Recently, a large population-based cohort
study followed up 766,179 persons for 11 years and dem-
onstrated that HZ patients have a high risk of stroke.21
Therefore, a meta-analysis was carried out to investi-
gate the relationship between HZ and stroke risk.
Materials and Methods
Literature Search
Systematic literature searches for articles published
through Pubmed and Embase (date from database in-
ception to May 31, 2016) were performed. The following
keywords were used in our research strategy: “stroke,”
“cerebrovascular disease,” “cerebrovascular disorders,”
“cerebrovascular accident,” “cerebral infarct,” “ischemic
stroke,” “hemorrhage stroke,” “intracranial hemor-
rhage,” “intracranial artery disease,” and “herpes zoster,”
“herpes zoster virus,” “varicella zoster virus,” “chicken-
pox virus,” “herpes zoster ophthalmicus”. The reference
lists of the relevant articles were also reviewed to obtain
potential pertinent studies.
Inclusion and Exclusion Criteria
Studies will be included in the study if they met the
inclusion criteria: (1) cohort study design; (2) studies re-
searched the association between HZ and stroke; (3) stroke
as the outcome, and was diagnosed post-HZ; (4) relative
risk (RR), incidence rate ratio (IRR), odds ratio (OR), or
hazard ratio (HR), with their corresponding 95% confi-
dence interval (CI) (or could be calculated) were provided.
Case report, reviews, comments, and editorials were excluded.
Data Extraction
The following information was extracted from each
study: first author, year of publication, data source, study
location or period, sample size, gender, follow-up years,
age of subjects, adjustment factors, and the effect vari-
ables (RR, HR, OR, IRR, and 95% CI). The Newcastle–
Ottawa Scale (NOS) was used to assess the quality of
all included studies.22 Scores ranged from 0 to 9 stars,
and the high-quality study was defined as a study ≥7
stars.22 Literature search, study selection, data extrac-
tion, and quality assessment were conducted by two
investigators (S-Y.Y. and H-X.L.) independently, and any
disagreements were resolved through discussion.
Statistical Analysis
Our meta-analysis was performed and reported ac-
cording to the standard criteria of observational studies.23
STATA 12.0 (Stata Corporation, College Station, TX) was
used for all statistical analysis. RRs were pooled in our
study. Heterogeneity between studies was evaluated by
Cochran’s Q statistic24 and I2 statistic25 (I2 > 50% and P < .1
represented significant heterogeneity). RR was calcu-
lated using a random-effects model when significant
heterogeneity, otherwise fixed-effects model. If more than
10 studies were included in the meta-analysis, a publi-
cation bias will be evaluated, which was assessed using
Begg’s funnel plots and Egger’s regression test.26,27 Sen-
sitivity analysis was conducted to check the influence of
the single study to the overall results.28 All values were
two sided and P ≤ .05 was considered statistically significant.
Several subgroup analyses were conducted to probe the
potential heterogeneity as follows: risk period post-HZ
(0-3 months versus 0-12 months versus >12 months), gender
(male versus female), age (≥18 years versus 18-50 years),
and stroke type (ischemic versus hemorrhagic versus tran-
sient ischemic attack).
Results
Search Results and Study Characteristics
There were 729 articles identified in the initial screen-
ing. Most articles were excluded due to the following
reasons: (1) duplication studies; (2) irrelevant studies; (3)
no observational studies; and (4) the articles were case
report, reviews, letters, or editorials. By looking through
the titles and abstracts, 12 articles were selected for further
checking. After the full-text review, 6 articles were ex-
cluded for the following reasons: 3 studies were designed
by self-controlled case-series study (SCCS)11,13,20; 2 studies
researched herpesvirus but not HZ as a trigger for child-
hood stroke17,29; and one study assessed the stroke risk
associated with HZ in the general population by using
the time-dependent (dynamic) type.21 Eventually, 6 cohort
studies were identified that met the inclusion criteria.12,14-16,18,19
The flow chart of literature search is shown in Figure 1.
The main characteristics of the 6 studies are listed in
Table 1. A total of 251,076 HZ patients and 8462 cases
of stroke were included in these 6 studies between 2009
and 2015. Two studies were conducted in Taiwan,15,16
1 in Sweden,18 one in the United States,19 1 in the UK,12
and 1 in Denmark.14 Among the 6 studies, HR was used
in 3 studies to calculate risk estimates,12,15,16 IRR in 2
studies,14,18 and OR in 1 study.19 All studies were high
quality with Newcastle–Ottawa Scale score ≥7.
HZ and Stroke Risk
All studies were included to assess the association
between HZ and stroke risk. The combined RR was 1.36
(95% confidence interval [CI]: 1.10, 1.67) (P = .004), which
determined that patients with HZ had a 36% higher risk
of developing stroke compared with non-HZ. There were
significant heterogeneity found between these studies
(I2 = 87.8%, P = .000). For herpes zoster ophthalmicus
 ARTICLE IN PRESS
STROKE RISK IN HZ PATIENTS
Figure 1. Flow chart of studies included in the meta-analysis.
(HZO), 3 studies12,15,16 were included and the pooled
risk estimates RR was 2.62 (95% CI: .85, 8.06) (P = .092),
with high heterogeneity (I2 = 92.3%, P = .000). The forest
plot of the stroke risk in HZ and HZO is shown in
Figure 2.
Stratified Analysis
Several subgroup analyses of stroke risk with HZ were
performed, and the results are listed in Table 2.
In the stratified analysis by risk period post-HZ, 2 studies
were included.14,19 The pooled RR for 0-3 months was 1.94
(95% CI: 1.33, 2.84) (P = .001), for 0-12 months was 1.17
(95% CI: 1.10, 1.25) (P = .000), and for >12 months was
1.05 (95% CI: 1.02, 1.09) (P = .004). These results suggest
that HZ patients have a higher risk of stroke within a
short term (3 months).
In the stratified analysis by gender, 3 studies were
included.14,16,18 Similar results were achieved for both male
and female patients, with the combined RR as 1.31 (95%
CI: 1.13, 1.53) (P = .000) for male and 1.31 (95% CI: 1.15,
1.51) (P = .000) for female.
As per stratification by age, 6 and 4 studies provided
enough information for age ≥18 years and age 18-50 years
subgroups, respectively. The summary RR was 1.36 (95%
CI: 1.10, 1.68) (P = .004) for age ≥18 years, and 1.64 (95%
CI: 1.18, 2.28) (P = .003) for age 18-50 years.
For stratification by stroke type, the data showed that
a significant association was detected for ischemic stroke
in patients with HZ, and the pooled RR was 1.99 (95%
CI: 1.04, 3.81) (P = .037). Nevertheless, no significant cor-
relation was observed between hemorrhagic stroke and
HZ (RR = 1.86; 95% CI: .76-4.54; P = .173).
3
Sensitivity Analysis and Publication Bias
For the sensitivity analysis, we deleted 1 study at each
time from the overall pooled analysis to investigate the
influence of a single study on the overall RRs. For HZ,
the combined RR was 1.45 (95% CI: 1.17, 1.80) (P = .001)
after excluding the study by Breuer et al,12 and 4.42 (95%
CI: 2.75, 7.11) (P = .000) for HZO. These results revealed
that HZO carries an increased risk of stroke, but not robust.
Owing to a small number studies included, neither
Begg’s funnel plots nor Egger’s regression test was used
to evaluate the publication bias.
Discussion
As far as we know, this study is the first comprehen-
sive meta-analysis to evaluate the association of the stroke
risk and HZ to date. The meta-analysis of 6 cohort studies
involving 251,076 HZ patients and 8462 cases of stroke
demonstrated that patients with HZ may increase the risk
of stroke. Subgroup analysis also found an association
between HZ and the risk of stroke no matter the strat-
ification factors, with an exception of the hemorrhagic
stroke group.
Subgroup analysis by stroke type identified that HZ
was strongly associated with ischemic stroke (RR = 1.99;
95% CI: 1.04-3.81; P = .037), but not hemorrhagic stroke
(RR = 1.86; 95% CI: .76-4.54; P = .173). Lin et al found that
HZ may be a significant risk factor for ischemic stroke
but not for hemorrhagic stroke.15 However, another study
showed that there were no differences between cases and
controls in incidence by stroke type.12 Moreover, Kang
et al reported that the patients with HZ both increased
the risk of hemorrhagic and ischemic stroke, but the risk
was higher for hemorrhagic stroke.16 Previous studies have
shown that VZV could lead to a series of clinical mani-
festations, including vertebral artery stenosis,30 aneurysm,31
infarctions,32 arterial dolichoectasia,33 hemorrhagic stroke.34
In the meantime, high heterogeneity was observed in the
current analysis. Although the random-effects model was
used to estimate the accumulated effect in the study, the
results were not robust. Therefore, further exploration into
this matter was suggested.
Heterogeneity is a factor of concern in a meta-
analysis. Substantial evidence of heterogeneity was observed
in our study. This is not surprising because the in-
cluded studies were different with regard to study design,
geographic area, characteristic of populations, and ad-
justment for confounding factors. Although the included
studies in our meta-analysis were cohort studies, some
were 1-year follow-up 1 year whereas others 6-7 years
of follow-up. In our meta-analysis, the identified studies
were conducted in different geographic regions—
European, Asian, and North American—where people have
different living habits, work style,s and genetic back-
grounds, which may affect the results. Hence, the random-
effects model was used in these analyses, which was
 4
Table 1. Study characteristics of HZ and the risk of stroke

No. of stroke Adjusted risk

Data case/HZ Follow-up estimate with
References Location period source patients Gender (Y) Age (Y) HZ variables assessed and adjustment (95% CI)

Sundström Sweden VGC 111/13,269 M; F; 1 >0 Stroke, age, sex; adjusted for age and sex 1.34 (1.12, 1.62)
et al18 2008-2010 MF
Yawn USA REP 562/4862 MF 7.1 (Mean) ≥50 Stroke, age, risk period after HZ; adjusted for 1.21 (.98, 1.51)
et al19 January 1986- 68.1 (Mean) age, sex, hypertension, coronary artery
October 2011 disease, diabetes, depression
Breuer UK THIN 2727/106,601 MF 6.3 (Mean) ≥18 Stroke, TIA, ischemic and hemorrhagic 1.02 (.98, 1.07)

ARTICLE IN PRESS
et al12 2002-2010 57.8 (Mean) stroke, HZO, age; adjusted for sex, age,
obesity, smoking status, history of
cholesterol, hypertension, diabetes,
ischemic heart disease, atrial fibrillation,
intermittent arterial claudication, carotid
stenosis, and valvular heart disease
Sreenivasan Denmark CRS; 4,876/117,926 M; F; ≥1 ≥18 Stroke, age, risk period after HZ, antiviral 1.35 (1.09, 1.67)
et al14 January 1995- NRMPS; MF treatment, gender; adjusted for age, sex,
December 2008 NPR and calendar period
Lin et al15 Taiwan NHIRD 53/658 MF 1 ≥18 Stroke, HZO, no antiviral treatment, ischemic 4.52 (2.45, 8.33)
January 2003- 56.9 (Mean) and hemorrhagic stroke, risk period after
December 2004 HZ; adjusted for age, gender, hypertension,
diabetes, hyperlipidemia, coronary heart
disease, chronic rheumatic heart disease,
other forms of heart disease, and
medication habits
Kang Taiwan NHIRD 133/7760 M; F; 1 ≥18 Stroke, age, HZO, sex, age, ischemic and 1.31 (1.06, 1.60)
et al16 January 1997- MF 46.7 (Mean) hemorrhagic stroke; adjusted for sex, age,
December 2001 hypertension, diabetes, coronary heart
disease, hyperlipidemia, renal disease, atrial
fibrillation, heart failure, heart valve/
myocardium disease, carotid/peripheral
vascular disease, monthly income,

S.-Y. YANG ET AL.

urbanization level, and geographical region

Abbreviations: CI, confidence interval; CRS, Danish Civil Registration System; F, female; HZ, herpes zoster; HZO, herpes zoster ophthalmicus; M, male; MF, male and female; NHIRD, Taiwan
National Health Insurance Research Database; NPR, National Patient Registry; NRMPS, Danish National Register of Medicinal Product Statistics; REP, The Rochester Epidemiology Project; THIN,
The Health Improvement Network; TIA, transient ischemic attack; VGC, Västra Götaland County; Y, year.
 ARTICLE IN PRESS
STROKE RISK IN HZ PATIENTS 5

Figure 2. Forest plot of stroke risk with herpes zoster and herpes zoster ophthalmicus. (Herpes zoster: studies that have the overall data. Herpes zoster
ophthalmicus: studies that have the data of herpes zoster ophthalmicus.) Abbreviation: RR, relative risk.

Table 2. Results of meta-analysis for HZ and risk of stroke

Group No. of studies RR (95% CI) P value I2 (%) P heterogeneity Analysis model

HZ 6 1.36 (1.10, 1.67) .004 87.8 .000 Random-effects model

HZO 3 2.62 (.85, 8.06) .092 92.3 .000 Random-effects model
Risk period post-HZ (months)
0-3 2 1.94 (1.33, 2.84) .001 63.0 .027 Random-effects model
0-12 2 1.17 (1.10, 1.25) .000 .0 .770 Fixed-effects model
>12 2 1.05 (1.02, 1.09) .004 .0 .945 Fixed-effects model
Gender
Male 3 1.31 (1.13, 1.53) .000 .0 .996 Fixed-effects model
Female 3 1.31 (1.15, 1.51) .000 .0 .895 Fixed-effects model
Age (years)
≥18 6 1.36 (1.10, 1.68) .004 87.5 .000 Random-effects model
18-50 4 1.64 (1.18, 2.28) .003 14.1 .312 Fixed-effects model
Stroke type
Ischemic stroke 3 1.99 (1.04, 3.81) .037 95.6 .000 Random-effects model
Hemorrhagic stroke 3 1.86 (.76, 4.53) .173 89.5 .000 Random-effects model
TIA 1 1.15 (1.09, 1.21) — — — —

Abbreviations: CI, confidence interval; HZ, herpes zoster; HZO, herpes zoster ophthalmicus; RR, relative risk; TIA, transient ischemic
attack.
 ARTICLE IN PRESS
6 S.-Y. YANG ET AL.
considered as a conservative way to estimate the cumu-
lative effect.
The potential mechanisms of HZ that may contribute
to stroke have been researched. VZV is a herpes virus
that, after its reactivation from nerve ganglia, could cause
HZ. VZV reactivates and travels to infect the cerebral ar-
teries, wherein inflammation response leads to pathological
vascular remodeling. VZV infection arteries cause vessel-
thickened intima that contributes to vascular occlusion
and ischemia, and disrupt the vessel media that lead to
aneurysm formation and hemorrhage.35-37 On the other
hand, patients with HZ may experience postherpetic
neuralgia, and the chronic pain may increase the cere-
brovascular disease risk.38,39
Our study has several important strengths. Firstly, our
study is the first meta-analysis to evaluate the associa-
tion between HZ and stroke risk. Secondly, a large number
of HZ patients and stroke cases were involved in our study,
which enhanced the statistical power to detect the sig-
nificant association. Thirdly, several subgroup analyses
were carried out in our meta-analysis. In addition, all the
original studies were cohort study design, which greatly
reduced the likelihood of recall and selection biases. All
these measures led to our robust results.
Several limitations should also be addressed in our study.
First, a small number of studies (n = 6) was included in
the study. Second, when sensitivity analysis was con-
ducted, we found 1 group (HZO group) that was not
robust, which needed further research. Third, the obser-
vation in our study to the heterogeneity of moderate to
high may be inevitable, because the methodological dif-
ferences and confounding factors from the original research
are unavoidable.
Conclusions
In summary, HZ was associated with an increased risk
of stroke. Further studies are needed to demonstrate
whether effective treatment of HZ or zoster vaccination
could reduce the risk of stroke.
References
1. World Health Organization (WHO). The top 10 causes
of death. World Health Organization. Available at:
http://www.who.int/mediacentre/factsheets/fs310/
en/. Accessed May 31, 2016, 2016.
2. Donnan GA, Fisher M, Macleod M, et al. Stroke. Lancet
2008;371:1612-1623.
3. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease
and stroke statistics—2015 update: a report from the
American Heart Association. Circulation 2015;131:e29-e322.
4. World Health Organization (WHO). Global burden of
stroke, the atlas of heart disease and stroke. World Health
Organisation. Available at: http://www.who.int/
cardiovascular_diseases/en/cvd_atlas_15_burden
_stroke.pdf?ua=1. Accessed May 31, 2016, 2016.
5. van der Worp HB, van Gijn J. Clinical practice. Acute
ischemic stroke. N Engl J Med 2007;357:572-579.
6. Johnson RW, Bouhassira D, Kassianos G, et al. The impact
of herpes zoster and post-herpetic neuralgia on quality-
of-life. BMC Med 2010;8:37.
7. Brisson M, Edmunds WJ, Law B, et al. Epidemiology of
varicella zoster virus infection in Canada and the United
Kingdom. Epidemiol Infect 2001;127:305-314.
8. 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.
9. Sas AM, Niks EH, Lequin MH, et al. Herpes simplex
virus type-1 encephalitis and occipital ischemic stroke.
Pediatr Neurol 2009;41:294-296.
10. Joy JL, Colon HF, Velez-Borras JR. The syndrome of
cerebral infarction following herpes zoster ophthalmicus.
Bol Asoc Med P R 1989;81:24-25.
11. Langan SM, 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.
12. 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.
13. Thomas SL, Minassian C, Ganesan V, et al. Chickenpox
and risk of stroke: a self-controlled case series analysis.
Clin Infect Dis 2014;58:61-68.
14. 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.
15. Lin HC, Chien CW, Ho JD. Herpes zoster ophthalmicus
and the risk of stroke: a population-based follow-up study.
Neurology 2010;74:792-797.
16. Kang JH, Ho JD, Chen YH, et al. Increased risk of stroke
after a herpes zoster attack: a population-based follow-up
study. Stroke 2009;40:3443-3448.
17. 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.
18. Sundström K, Weibull CE, 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.
19. Yawn BP, Wollan PC, Nagel MA, 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.
20. Minassian C, Thomas SL, 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.
21. Kwon SU, Yun SC, Kim MC, et al. Risk of stroke and
transient ischaemic attack after herpes zoster. Clin
Microbiol Infect 2016;22:542-548.
22. 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.
23. Stroup DF, Berlin JA, Morton SC, 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.
24. Higgins JP, Thompson SG. Quantifying heterogeneity in
a meta-analysis. Stat Med 2002;21:1539-1558.
25. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring
inconsistency in meta-analyses. BMJ 2003;327:557-560.
26. Begg CB, Mazumdar M. Operating characteristics of a
rank correlation test for publication bias. Biometrics
1994;50:1088-1101.
 ARTICLE IN PRESS
STROKE RISK IN HZ PATIENTS
27. Egger M, Davey Smith G, Schneider M, et al. Bias in
meta-analysis detected by a simple, graphical test. BMJ
1997;315:629-634.
28. Copas J, Shi JQ. Meta-analysis, funnel plots and sensitivity
analysis. Biostatistics 2000;1:247-262.
29. Elkind MS, Hills NK, Glaser CA, et al. Herpesvirus
infections and childhood arterial ischemic stroke: results
of the VIPS study. Circulation 2016;133:732-741.
30. Chen WH, Chui C, Yin HL. Zoster sine herpete, vertebral
artery stenosis, and ischemic stroke. J Stroke Cerebrovasc
Dis 2013;22:e234-e237.
31. 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.
32. Kalita J, Das M, Misra UK. Herpes zoster ophthalmicus
leading to middle cerebral artery infarction: a case report.
Int J Angiol 2004;13:51-53.
33. Dalton CM, Jager HR, Losseff NA, et al. Neurological
picture. Varicella zoster virus and intracranial
dolichoectasia in a late adult cancer survivor. J Neurol
Neurosurg Psychiatry 2008;79:573.
7
34. 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.
35. Nagel MA, Gilden D. The relationship between herpes
zoster and stroke. Curr Neurol Neurosci Rep 2015;15:
16.
36. Frid MG, Brunetti JA, Burke DL, 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.
37. Stenmark KR, Yeager ME, El Kasmi KC, et al. The
adventitia: essential regulator of vascular wall structure
and function. Annu Rev Physiol 2013;75:23-47.
38. Feller L, Jadwat Y, Bouckaert M. Herpes zoster post-
herpetic neuralgia. SADJ 2005;60:432, 436-437.
39. Daniel HC, 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.