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Herpes Zoster Attacks Increase Stroke Risk By 30%

  • Authors: News Author: Susan Jeffrey
    CME Author: Désirée Lie, MD, MSEd
  • CME Released: 10/20/2009
  • Valid for credit through: 10/20/2010
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Target Audience and Goal Statement

This article is intended for primary care clinicians, neurologists, infectious disease specialists, and other specialists who care for patients with varicella zoster virus infection.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Describe the risk for stroke after varicella zoster virus infection in adults.
  • Identify modifiers of stroke risk after herpes zoster infection in adults.


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  • Susan Jeffrey

    Susan Jeffrey is the news editor for Medscape Neurology & Neurosurgery. Susan has been writing principally for physician audiences for nearly 20 years. Most recently, she was news editor for and also wrote for; both of these Web sites have been acquired by WebMD. Prior to that, she spent 10 years covering neurology topics for a Canadian newspaper for physicians. She can be contacted at [email protected]


    Disclosure: Susan Jeffrey has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    is the News CME editor for Medscape Medical News.


    Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California


    Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

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Herpes Zoster Attacks Increase Stroke Risk By 30%

Authors: News Author: Susan Jeffrey CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME Released: 10/20/2009

Valid for credit through: 10/20/2010


October 20, 2009 — A new epidemiological study suggests that the risk for stroke, both ischemic and hemorrhagic, is increased by 30% after a herpes zoster attack. The risk is even higher, about 4-fold, if the attack involves the eye (herpes zoster ophthalmicus).

Herpes zoster infection, also known as shingles, has been shown in other studies to be associated with an increased risk for stroke, the researchers, with lead author Jiunn-Horng Kang, MD, from the Department of Physical Medicine and Rehabilitation and chair of the Sleep Physiological Lab at Taipei Medical University Hospital in Taiwan, point out. Their study is the first attempt to their knowledge to look at the exact risk and frequency of stroke after herpes zoster attacks.

There is still no established therapy to prevent herpes zoster vasculopathy and associated stroke, Dr. Kang told Medscape Neurology. Early antiviral medication could have an important role, he noted, but this role still needs to be studied.

"From the practical view, physicians should be aware of the potential elevated risk of stroke when they care [for] patients with acute herpes zoster attack," he said. "Furthermore, [careful] monitoring and management of the preexisting risk factors for stroke such as hypertension, hyperlipidemia, and diabetic mellitus could be helpful to reduce the risk for stroke."

The report was published online October 8 and will appear in the November issue of Stroke.

Large- and Small-Vessel VZV Vasculopathy

Primary varicella zoster virus (VZV) infection usually affects children and causes varicella or chicken pox, the researchers note. Although some children can have serious complications, varicella is usually benign and transient. The VZV then becomes inactive, sequestered in the sensory and autonomic ganglia. By mechanisms that are not entirely clear, the researchers note, spontaneous reactivation of VZV causes lesions with painful vesicles known as herpes zoster or shingles.

There have been numerous reports linking VZV vasculopathy and stroke syndrome after zoster attacks since the 1970s, the authors write, and VZV is the only recognized human virus able to replicate in cerebral arteries. "It is hypothesized to spread along the nerve fibers to the blood vessels, where it induces further inflammatory and thrombotic responses," Dr. Kang and colleagues note.

VZV vasculopathy can affect both the large and small vessels. In large-vessel VZV vasculopathy, vessels are damaged by inflammation induced by the virus, which can result in stroke. Small-vessel VZV vasculopathy, in contrast, can manifest as nonspecific symptoms including fever, headache, seizures, weakness, consciousness disturbances, and cognitive impairments, known as small-vessel encephalitis.

"To our knowledge, despite many case reports of conditions associated with VZV vasculopathy, large sample data regarding the exact frequency and risk of stroke occurring postherpes zoster attack are still lacking," the authors write.

In this study, the researchers used a data set released by the Taiwan National Health Research Institute in 2006, a representative sample of enrollees in Taiwan's National Health Insurance program. For this analysis, they identified a total of 7760 patients who received treatment for herpes zoster between 1997 and 2001 and matched them with 23,280 randomly selected subjects. The researchers then calculated the 1-year stroke-free survival for patients who received treatment for herpes zoster and for control subjects.

During the 1-year follow up, a total of 439 strokes occurred, 133 among those treated for herpes zoster (1.71%) and 306 from the control group (1.31%). The log rank test showed that those treated for herpes zoster had a significantly lower stroke-free survival rate (P < .001).

The risk for stroke after herpes zoster was increased by 31% compared with that for control patients and increased more than 4-fold for herpes zoster ophthalmicus.

Risk for Stroke After Herpes Zoster Attack vs Control During 1-Year Follow-up

Group Adjusted Hazard Ratio 95% Confidence Interval P
Herpes zoster 1.31 1.06 – 1.60 <.05
Herpes zoster ophthalmicus 4.28 2.01 – 9.03 <.001

The risk was increased for both ischemic and hemorrhagic stroke, and in both men and women, but only for those subjects who were 45 years of age or older, not for younger subjects.

Risk for Stroke After Herpes Zoster Attack vs Control by Stroke Type, Sex, and Age

Group Adjusted Hazard Ratio 95% Confidence Interval P
Ischemic stroke 1.31 1.07 – 1.65 .009
Intracerebral or subarachnoid hemorrhage 2.79 1.69 – 4.61 <.001
Men 1.32 1.01 – 1.75 <.05
Women 1.30 1.01 – 1.75 <.05
Age ≥ 45 years 1.31 1.06 – 1.63 <.05

"Although varicella zoster virus vasculopathy is a well-documented complication that may induce a stroke postherpes zoster attack, it does not fully account for the unexpectedly high risk of stroke in these patients," the authors conclude.

Asked to speculate on the potential mechanisms involved, Dr. Kang told Medscape Neurology that they think the most likely explanation is direct invasion of the cerebral vessels by the herpes zoster virus.

"Previous studies have shown that VZV can replicate and damage the vessel and induce an inflammatory process," he noted. "The vasculopathy results in further occlusion or rupture of involved vessels, manifested as ischemic or hemorrhagic stroke."

In addition, factors including postherpetic neuralgia, systemic diseases, general health status, or preexisting atherosclerosis could also contribute to the occurrence of stroke.

The authors have disclosed no relevant financial relationships.

Stroke. Published online October 8, 2009.

Clinical Context

VZV infection is an important stroke risk in children, with a 3-fold increase in the risk for ischemic stroke after the infection. However, data on stroke frequency after VZV infection are lacking despite reports of VZV-induced vasculopathy associated with large- and small-vessel disease and leading to angiitis and stroke.

This is a prospective database study of patients from Taiwan with VZV infection who were observed for 1 year and compared vs control subjects without VZV infection to examine the risk for stroke after VZV infection and factors modifying that risk.

Study Highlights

  • The database of the Taiwan National Health Research Institute was used to extract cases of VZV infection from 1997 to 2001.
  • This database consists of 1 million individuals randomly selected from a population of 25 million enrollees representing 98% of the country's population.
  • Claims data were used to identify adults 18 years or older with VZV infection by use of the International Classification of Diseases, Ninth Revision, code.
  • Excluded were patients with a previous stroke and those younger than 18 years.
  • 7760 patients with VZV were identified, and 23,280 from the database without VZV and without a history of stroke or VZV infection before 2001 were used as age- and sex-matched control subjects.
  • The first ambulatory visit during 2001 was determined to be the index visit for the comparison group.
  • Both cohorts were tracked for 1 year, with the primary outcome of stroke.
  • Mean age of the patients was 46.7 years, slightly more than 2% had diabetes, 5% had hypertension, and more than two thirds were from northern Taiwan.
  • Patients with herpes zoster were more likely to have comorbidities including hypertension, diabetes, coronary artery disease, renal disease, heart failure, and peripheral artery disease at the time of presentation with VZV infection.
  • At the 1-year follow up period, 1.41% of patients had a stroke.
  • 1.71% of cases of stroke were from the herpes zoster group, and 1.31% were from the control group.
  • Patients from the herpes zoster group had significantly lower 1-year stroke-free survival rates vs the comparison cohort (P < .001).
  • After adjustment for age and comorbidities, the hazard ratio (HR) for the development of stoke during the 1-year follow up period was 1.31 (P < .05) for patients with herpes zoster vs the comparison cohort.
  • For patients with herpes zoster ophthalmicus, the HR for stroke was 4.28.
  • When analyzed by stroke type, the HR for ischemic stroke was 1.31, and the HR for intracerebral or subarachnoid hemorrhage was 2.79 vs the comparison cohort.
  • The adjusted HR was similar for men and women (1.32 and 1.30, respectively).
  • The risk was 1.31 for patients 45 years and older but was not increased in those younger than 45 years vs the comparison cohort.
  • The authors concluded that herpes zoster infection in adults was associated with increased stroke risk and that this risk is influenced by age, type of stroke, and presence of ophthalmic complication but not by sex.
  • They also noted the higher cardiovascular comorbidity burden among those with stroke and suggested that the herpes virus infection could accelerate atherosclerosis development as well as increase risk through vasculopathy.

Clinical Implications

  • Herpes zoster infection is associated with increased stoke risk in adults.
  • The risk for stroke associated with herpes zoster is in patients 45 years and older, is similar for men and women, and is higher for ischemic vs hemorrhagic stroke.

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