Biological Plausibility of a Link Between Arterial Ischemic Stroke and Infection With Varicella-Zoster Virus or Herpes Simplex Virus

Grose, Charles

doi:10.1161/circulationaha.116.021459

Cited by 16 publications

(13 citation statements)

References 19 publications

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“…This latter group included mostly postherpetic neuralgia and other nonspecific designations. The rationale for this segregation relates to the known capacity of varicella to establish latency in cranial nerve ganglia, especially cranial nerve V, and spread retrograde via sensory nerve fibers to the cerebral circulation .…”

Section: Discussionmentioning

confidence: 99%

Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases

Calabrese

Xie

Yun

et al. 2017

Arthritis & Rheumatology

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Background Herpes zoster (HZ) is an opportunistic infection caused by varicella zoster virus (VZV), and observed with increasing frequency in patients on immunosuppressive therapies. Prior literature has suggested that the risk of stroke may increase shortly after herpes zoster, but little is known about this association for patients with autoimmune (AI) diseases, who are at increased risk both for zoster and stroke. Methods Medicare data (2006–2013) was used to identify patients with autoimmune diseases. The outcome of interest was hospitalized stroke. The hypothesis tested was that the incidence of stroke immediately following HZ was increased compared to the incidence of stroke at later time points. Secondary analysis included assessment of the impact of antiviral therapy on subsequent stroke as well as the influence of VZV-related complications on stroke incidence. Results The crude incidence of stroke ranged from a high of 2.30 (0.96–5.52) per 100 patient years within 90 days of HZ in patients who had HZ-related cranial nerve complications and did not receive treatment to a low of 0.87 (0.75–1.02) per 100py (>1 year after uncomplicated HZ). After multivariable adjustment for multiple stroke-related factors, the incidence rate ratio (IRR) for stroke in the first 90 days after HZ was 1.36 (1.10–1.68) compared to stroke >1 year after HZ. The risk was greater for patients with zoster with cranial nerve complications (IRR 2.08, 95%CI 0.99–4.36). Prompt antiviral therapy was associated with lower incidence of subsequent stroke (IRR 0.83, 95% CI 0.70–0.98). Conclusion In patients with autoimmune diseases, incident HZ was associated with up to a two-fold increased risk for stroke in the subsequent few months. These data provide urgency for developing strategies to reduce the risk of VZV.

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Section: Discussionmentioning

confidence: 99%

Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases

Calabrese

Xie

Yun

et al. 2017

Arthritis & Rheumatology

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“…The reactivation of VZV in the trigeminal ganglion leads not only to zoster ophthalmicus but also to VZV replication along the cerebral arteries. VZV replication adjacent to an artery in turn leads to inflammation in the artery and subsequent thrombosis and stroke [17]. Therefore, viral replication directly damages and weakens the cerebral artery walls, which results in thrombosis, occlusions, infarctions, aneurysms and haemorrhages [16].…”

Section: Discussionmentioning

confidence: 99%

Risk of stroke and transient ischaemic attack after herpes zoster

Kwon

Yun

Kim

et al. 2016

Clinical Microbiology and Infection

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We assessed the association of herpes zoster (HZ) with stroke/transient ischaemic attack (TIA) in the general population according to age with controlling risk factors for stroke, using a nationwide representative cohort. The study was based on a prospective dynamic cohort consisting of 1 million Koreans representing all age groups, genders and geographical areas in the Korea Health Insurance Database. New events of stroke/TIA and HZ were identified using the diagnostic codes in the International Classification of Diseases, tenth revision. The risk for stroke/TIA after HZ was compared with HZ-free stroke/TIA individuals according to age group. A total of 766 179 adults were followed up for 11 years from 2003. The incidence of the first-diagnosed HZ cases was 9.40 per 1000 person-years, and that of the first-diagnosed stroke/TIA cases was 9.77 per 1000 person-years. The risk for stroke/TIA was higher in patients who had previous HZ episodes than in those who had never experienced HZ (incidence rate ratio 1.90; 95% CI 1.85-1.95). In addition, this risk persisted for several years after HZ. The risk of stroke/TIA after HZ gradually decreased with age; adjusted hazard ratio (HR) 2.04 in 18- to 30-year-olds, HR 1.74 in 30- to 40-year-olds, HR 1.43 in 40- to 50-year-olds, HR 1.23 in 50- to 60-year-olds, HR 1.24 in 60- to 70-year-olds, and HR 1.29 in those >70 years old, after controlling risk factors for stroke/TIA. Our findings provide evidence that HZ carries an increased risk of stroke or TIA and that the effect of HZ on stroke decreases with increasing age.

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“…As virus replicate in cerebral arteries where infection spread along nerve fibers to blood vessels, thrombotic responses are evoked[ 26 ]. Another possible factor is that varicella zoster virus replication adjacent to an artery induces inflammation in the artery and thus increases risk of thrombosis and stroke [ 27 ]. In this situation, it is also possible that herpes zoster itself or post-herpetic neuralgia raises sympathetic status and cacoethic emotional reactions, which theoretically increases stroke risk[ 28 ].…”

Section: Discussionmentioning

confidence: 99%

The Short- and Long-Term Risk of Stroke after Herpes Zoster: A Meta-Analysis

et al. 2016

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BackgroundAccumulating evidence indicates that stroke risk may be increased following herpes zoster. The aim of this study is to perform a meta-analysis of current literature to systematically analyze and quantitatively estimate the short and long-term effects of herpes zoster on the risk of stroke.MethodsEmbase, PubMed and Cochrane library databases were searched for relevant studies up to March 2016. Studies were selected for analysis based on certain inclusion and exclusion criteria. Relative risks with 95% confidence interval (CI) were extracted to assess the association between herpes zoster and stroke.ResultsA total of 8 articles were included in our analysis. The present meta-analysis showed that the risks of stroke after herpes zoster were 2.36 (95% CI: 2.17–2.56) for first 2 weeks, 1.56 (95% CI: 1.46–1.66) for first month, 1.17 (95% CI: 1.13–1.22) for first year, and 1.09 (95% CI: 1.02–1.16) for more than 1 year, respectively.ConclusionThe results of our study demonstrated that herpes zoster was associated with a higher risk of stroke, but the risks decreased along with the time after herpes zoster.

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Biological Plausibility of a Link Between Arterial Ischemic Stroke and Infection With Varicella-Zoster Virus or Herpes Simplex Virus

Cited by 16 publications

References 19 publications

Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases

Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases

Risk of stroke and transient ischaemic attack after herpes zoster

The Short- and Long-Term Risk of Stroke after Herpes Zoster: A Meta-Analysis

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