Herpes And Stroke: Is There A Link?

Herpes zoster is a common viral disease, in which the most debilitating complication is post-herpetic neuralgia, which can have a very large negative impact on quality of life. The aim of this study was to investigate whether stroke increases the risk of herpes zoster.

Herpes zoster is a risk factor for stroke and TIA: A retrospective cohort study in the UK

Herpes zoster is a risk factor for stroke and TIA. A retrospective cohort study in the UK found that patients with herpes zoster had a 15% increased risk of TIA and a 10% increased risk of MI. The study also found that the risk of stroke, TIA, and MI was higher in patients whose herpes zoster occurred when they were younger than 40 years old.

The relationship between herpes zoster and stroke

Varicella zoster virus (VZV) infects more than 95% of the world population. Typically, varicella (chickenpox) results from primary infection. The virus then becomes latent in ganglionic neurons along the entire neuraxis. In immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), pain, and rash in 1–2 dermatomes.

Multiple case reports showed a link between stroke and zoster, and recent studies have emerged which reveal that VZV infection of the cerebral arteries directly causes pathological vascular remodelling and stroke (VZV vasculopathy). In the past few years, several large epidemiological studies in Taiwan, Denmark, and the U.K. demonstrated that zoster is a risk factor for stroke and that antiviral therapy may reduce this risk.

Ischemic and hemorrhagic stroke after zoster results from cerebral arterial infection by VZV (VZV vasculopathy). The average time between zoster and onset of focal neurological deficits is 4 months. Brain MRI is abnormal in 97% of cases, frequently revealing lesions at the junction of the gray and white matter, and angiography demonstrates involvement of large and small arteries in nearly 70% of cases.

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, during the first month after HZ infection. After pooling the results, an increased stroke risk was observed (RR: 1.32; 95% CI, 1.13–1.54) within 3 months after herpes zoster.

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, herpes zoster correlated positively with the stroke. With respect to hemorrhagic stroke, the association between was not significant except within 3 months after a herpes zoster infection.

Herpes zoster (HZ) infectious outbreaks, also called shingles, are caused by the reactivation of the varicella-zoster virus (VZV). Primary infection with VZV in childhood manifests as chickenpox, and then VZV enters a dormant period in the dorsal root ganglia. After VZV reactivates, it travels along sensory nerve endings and causes neuronal damage to the corresponding dermatome of the skin, where it is characterized by a vesicular rash. Spontaneous reactivation of VZV may occur in the elderly and individuals with compromised cell-mediated immunity; therefore, the risk of an HZ outbreak substantially increases with age and immunosuppression. Accumulating evidence has shown that more than 95% of adults worldwide are infected with VZV, and approximately 30% will develop HZ in their lifetime, with this proportion increasing to 50% in those aged at least 85 years.

Stroke is one of the leading causes of deaths and disability throughout the world, and it is a multifactorial disease resulting from interactions between many risk factors. Previous studies have found that infection appears to be an important trigger that precedes up to a third of ischemic strokes and can cause stroke on a background of potential mechanisms. Strokes after HZ infections were initially reported in the early 1970s. Since then, numerous epidemiologic studies have investigated the association between HZ and risk of stroke. VZV is the only recognized human virus that can replicate in cerebral arteries, and it is hypothesized to spread along the nerve fibers to the blood vessels, where it induces further inflammatory and thrombotic responses. Although the short-term and long-term risk of different subtypes of stroke after HV infection have been studied extensively, the results remain controversial. In addition, a quantitative analysis has not been performed to examine the specific association between HZ and stroke risk. Therefore, a systematic review of the published literature was conducted to evaluate the association between HZ and stroke risk.

Overall, the incidence of ischemic stroke is significantly higher in the short term after herpes zoster, whereas a significant relationship was not observed in the long term after HZ infection. With respect to hemorrhagic stroke, herpes zoster correlated positively with the stroke. With respect to hemorrhagic stroke, the association between was not significant except within 3 months after a herpes zoster infection.

Our systemic review quantitatively summarized the current literature and analyzed 8 studies to determine the short-term and long-term stroke risk after HZ infection.

Our review shows an increased stroke risk following zoster and suggests that recent infection or reactivation of other herpesviruses increases stroke risk, although better evidence is needed. Herpesviruses are common and potentially preventable; these findings may have implications for reducing stroke burden.

Does Herpes Zoster Increase the Risk of Stroke and Myocardial Infarction? A Comprehensive Review

Herpes zoster (HZ) is a serious health problem due to its abundance and complications. It is caused by the reactivation of the varicella-zoster virus (VZV) from its latent state in the sensory ganglia. HZ is characterised by a vesicular rash of unilateral distribution that can also cause multiple complications, such as post-herpetic neuralgia, ophthalmic zoster, and other neurological issues.

VZV can increase the risk of cerebrovascular and cardiac events, such as stroke and myocardial infarction (MI). This is due to VZV's ability to cause inflammatory vasculopathy, which can lead to haemorrhagic or ischemic complications.

Several studies have found an association between HZ and subsequent acute strokes or MI. Individuals exposed to HZ or herpes zoster ophthalmicus had 1.3 to 4-fold increased risks of cerebrovascular events. Higher risks were noted among younger patients (age <40 years) within one year after an HZ episode. The elevated risk of cardiovascular events (CVEs) diminished gradually according to age and length of time after an HZ episode.

The Potential Mechanism of VZV-Associated Vascular Events

VZV vasculopathy caused by the productive virus infection of the cerebral arteries can cause pathological vascular remodelling, resulting in clinical ischemic or haemorrhagic stroke. HZ induces vasculopathy via the following mechanisms:

• Induction of the production of prothrombotic autoimmune antibodies, such as IgM and IgG anticardiolipin antibodies.
• Autoimmune phenomenon caused by circulating immune complexes.
• Disruption of the internal elastic lamina, intimal hyperplasia, and decreased smooth muscle cells in the tunica medial layer.

There is a significant association between HZ and stroke or MI. The risk of CVEs is highest in the first week after an HZ episode, then gradually decreases over time. The risk is also greater for younger patients and those with herpes zoster ophthalmicus.

Higher risk of herpes zoster in stroke patients

Herpes zoster, also known as shingles, is a reactivation of the varicella-zoster virus (VZV) that causes chickenpox. The virus lies dormant in the body after the initial infection and can reactivate later in life, causing herpes zoster.

Several studies have found a link between stroke and herpes zoster, with recent studies showing that VZV infection of the cerebral arteries can directly cause pathological vascular remodelling and stroke.

Risk factors

Risk factors for herpes zoster include:

• Female gender
• Mechanical trauma
• Genetic susceptibility
• Interleukin 10 gene polymorphism
• Weakened immune system due to ageing, comorbidities, drug exposure, or nutritional deficiencies
• Depression, which is a common complication after stroke and can have neuro-endocrine and immunological/inflammatory effects
• Ageing, as older age is the most important attributable factor in stroke and herpes zoster

Studies on stroke patients

A 2020 study from Taiwan found that stroke patients had a 25.27 times higher risk of developing herpes zoster compared to the general population over a 1-year follow-up period and a 3.44 times higher risk over a 5-year follow-up period. Both hemorrhagic and ischemic strokes were significantly associated with an increased risk of herpes zoster.

A 2014 UK-based study found that herpes zoster was a risk factor for stroke, with the risk being highest in the first four weeks after the herpes zoster episode and decreasing over time.

A 2013 Danish study of 4.6 million adults found that stroke risk increased by 126% in the first two weeks after a herpes zoster episode and by 5% overall when compared to patients who did not receive antiviral treatment.

The available evidence suggests that stroke patients are at a significantly higher risk of developing herpes zoster, especially in the first year after the stroke. This risk is present for both hemorrhagic and ischemic strokes and is higher for ophthalmic-distribution herpes zoster. Antiviral therapy may help reduce this risk.

The Relationship Between Herpes Zoster and Stroke

Varicella zoster virus (VZV) infects over 95% of the world population. Typically, the primary infection results in chickenpox, after which the virus becomes latent in ganglionic neurons. In immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), pain, and a rash.

Multiple case reports have shown a link between stroke and herpes zoster. Recent studies have revealed that VZV infection of the cerebral arteries directly causes pathological vascular remodelling and stroke (VZV vasculopathy). Epidemiological studies have also demonstrated that zoster is a risk factor for stroke, and that antiviral therapy may reduce this risk.

The onset of stroke after herpes zoster due to VZV reactivation was described as early as 1896. Since then, several case reports of contralateral hemiplegia have been documented, as well as other neurological complications such as cranial neuropathies, meningitis, encephalitis, and transient ischemic attacks.

Ischemic and hemorrhagic stroke after zoster results from cerebral arterial infection by VZV (VZV vasculopathy). The average time between zoster and the onset of focal neurological deficits is 4 months. Brain MRI is abnormal in 97% of cases, and angiography demonstrates involvement of large and small arteries in nearly 70% of cases.

The definitive diagnosis of VZV vasculopathy is made by the detection of anti-VZV IgG antibody in the CSF, which is more often positive than the presence of amplifiable VZV DNA in the CSF. Interestingly, about 30% of patients with VZV vasculopathy have no history of earlier zoster, indicating that VZV can reactivate from the ganglia and travel centrally to infect the cerebral arteries without peripheral spread to the skin.

Mechanisms of VZV vasculopathy have been studied using virus-infected cerebral and temporal arteries from subjects who died of VZV vasculopathy. These studies have revealed that VZV infection of the cerebral arteries leads to pathological vascular remodelling, resulting in a thickened intima that contributes to vascular occlusion and ischemia, and with a disruption of the media contributing to aneurysm formation and hemorrhage.

Given that VZV reactivates to cause zoster in about one-half of individuals by 85 years of age, with approximately 1 million zoster cases yearly in the USA alone, VZV vasculopathy is not uncommon. Epidemiological studies from Asia, Europe, and the UK have revealed that zoster is a significant risk factor for stroke, especially ophthalmic-distribution zoster, and that treatment with antiviral agents may reduce this risk.

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