Herpes Zoster Attacks Increase Stroke Risk By 30%

Susan Jeffrey

October 08, 2009

October 8, 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.