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February 13, 2006

New Tune? Research Suggests Carotid Artery Stenting to Prevent Strokes May Offer Added Benefit of Improving Cognitive Function
By Dan Harvey
Radiology Today
Vol. 7 No. 3 P. 14

The toll strokes take on the U.S. population is tremendous. According to the American Stroke Association, each year nearly 700,000 Americans suffer a stroke. For 163,000 of those individuals, it proves fatal, making stroke the third-leading cause of death, behind heart disease and cancer. Further, if it is not deadly, it’s debilitating.

Approximately 25% of strokes are ischemic strokes, which are caused by arterial occlusion, or the narrowing of the carotid artery, which impedes blood flow to the brain. Ischemic strokes can be treated with surgery or angioplasty with stents. Until recently, surgery—or, more specifically, carotid endarterectomy, where a blockage is surgically removed from the carotid artery—has been the standard treatment to prevent stroke. However, more and more, stenting of the carotid artery is becoming the preferred procedure for preventing ischemic strokes and has proven a viable alternative. Like surgery, the procedure effectively reduces the risk of stroke by restoring blood flow to the brain, but is a much less invasive procedure.

In addition to the stroke prevention benefit, scientists are exploring another interesting benefit to stenting. Researchers in Germany have discovered that carotid artery stenting in the neck not only helps prevent stroke, it also appears to significantly improve cognitive function, or how quickly the brain processes information. At RSNA 2005, Iris Q. Grunwald, MD, a neuroradiologist and consultant with the Saarland University Clinic in Homburg, Germany, presented findings from that research. Grunwald reported on a study that combined neuropsychological testing with the perfusion imaging that screens for silent ischemic stroke events that can occur during a stenting procedure. She noted that it was the first time these two elements have been integrated in such a study so researchers could measure how well a subject’s brain functions after blood flow improves following stenting.

Removing Carotid Blockages
Stenting is an effective means of improving blood flow to the brain as it unblocks the carotid artery, the main blood vessel that transports the blood to the organ. During a stenting procedure, the physician inserts a catheter into a very small incision in the femoral artery in the leg. Then, guided by real-time x-ray imaging, the interventionalist maneuvers the catheter into the stenotic area of the carotid artery. A balloon expands the artery, which flattens the plaque, and the stent is then inserted to hold the blood vessel open, providing unimpeded blood flow.

On the surface, it would seem that such a procedure, with the increased blood flow to the brain, may have a positive impact on a patient’s mental capabilities, and that is what Grunwald and colleagues were seeking to validate. Grunwald says she and her colleagues had noticed that after patients receive a carotid stent, their memory function seemed to improve. “Patients have told us this as well,” she says.

The finding sent researchers back to literature on several studies involving cognitive function after carotid artery stenting. However, previous studies offered little that was definitive. “We found no consensus,” Grunwald says. “In some patients, there was improvement; in others, there wasn’t. Plus, the studies were so diverse. In some patients, the change came about in three days while in others it didn’t come until after six months. Also, the physicians did not check whether the patient had suffered a stroke.”

Grunwald and colleagues wanted to control the variables in their test for changes in cognitive performance after carotid artery stenting. While carotid artery stenting is an effective treatment for stroke prevention, not much was known about the effects it had on cognitive function. In addition, there has been concern that stenting could cause a silent ischemic stroke, which potentially impairs a patient’s cognitive function. Therefore, Grunwald and colleagues wanted to better understand the impact stenting had on both cognitive function and the procedure’s safety. As it turned out, their results indicated good news in both areas.

Homogenous Study
The researchers performed stenting on 26 patients who had carotid stenosis of 75% or higher as revealed by ultrasound. The stenting, Grunwald emphasized, was done, first and foremost, to prevent stroke—and not to improve cognitive function. Grunwald’s colleagues in the work included Wolfgang Reith, MD; Tillman Supprian, MD; Peter Falkai, MD; Christoph Krick, PhD; Tobias Struffert, MD; Kathrin Zercher; Verena Fedder; and Friederike Winnemann.

At least 24 hours before the stenting procedure, all patients were given a battery of neuropsychological tests to determine their memory function and how quickly their brains processed information. These tests included the Mini Mental Status Examination and subtests of the Consortium to Establish a Registry for Alzheimer’s Disease battery. The subtests involved a verbal fluency test, a connect-the-number test (CNT), a labyrinth test, a functional short-term (FST) memory test, and delayed recall. The tests were repeated three months after the stenting procedure. Patients were also screened for depression and dementia. Further, to achieve a homogeneity, all patients selected were right-handed. “This was the first study of this kind to use a homogenous group of patients,” says Grunwald.
Right-handedness is significant because that characteristic is involved with the side of the brain that processes speech and memory. “If someone is right-handed, the area related to speech will be on the left-hand side of the brain. Also, different functions will be on that side of the brain as well,” Grunwald says.

The researchers also used a proximal protection device to diminish thromboembolic events. “That is another important element involved with stenting: whether to use a protection device,” says Grunwald. “I’m sure there will be a lot to follow on this.”

They found that cognitive speed improved after stent placement. “So now we wanted to know why it improved,” says Grunwald.

Diffusion/Perfusion Imaging
That led researchers to try something never done before. “We looked at perfusion in the brain,” says Grunwald. Researchers obtained diffusion- and perfusion-weighted MRIs before and after the stenting. Examinations were performed at baseline and three months after treatment to identify the perfusion deficit, confirm that a patient hadn’t suffered a stroke during the stent placement procedure, and assess poststenting reperfusion.

Diffusion-weighted imaging would have revealed a stroke. “So, we found the patients were asymptomatic, before and after placement of the stent,” says Grunwald. “This was another unique thing we did. In the previous studies, researchers hadn’t checked if a patient had a stroke.”

Results not only showed that carotid stenting significantly improved cognitive speed function, but that the improvement was unaffected by the patient’s age, site of stenosis, or degree of stenosis. Also, the researchers found a correlation between the degree of vessel stenosis and perfusion deficit (decreased blood flow) in the brain area on the side of the stenosis. Increasing the blood flow with stenting clearly improved cognitive speed for patients with perfusion deficit.

Significant Statistics
So, with the patients receiving the imaging before and after stent placement, researchers were able to ascertain that patients with a large perfusion deficit, where the blood took a long time to reach the brain, improved most, says Grunwald. “Conversely, patients with hardly any deficit didn’t demonstrate a great deal of improvement,” she adds. “So what we think is that there is a correlation between the amount of perfusion deficit a patient had and the amount of cognitive improvement afterward.”

Statistics were significant, as patients showed improvement in the CNT (3%), labyrinth (5.4%), and FST (5.6%) tests. Improvements were related to the speed with which the tests were completed. Increase in cognitive speed was at a strong P value of 0.02. “That indicates more than a 98% confidence level,” says Grunwald.

She adds that while all patients improved in cognitive function, there was no measurable effect on memory function, as only a tendency was demonstrated. The P value was not significant. “The tendency was there, but the statistics were not,” she says. “We hope to learn more about that with bigger samples and more refined testing.”

Future Studies
The researchers concluded that carotid stenting is not only a safe way to treat stenosis in that artery, but that it offers more than just reduced stroke risk, particularly in patients with perfusion to the brain that has been impaired by the stenosis. But Grunwald emphasized that the main purpose for placing a stent is to prevent stroke. Improved cognitive function is only a side effect and more research is needed, she points out. Findings of the study were only preliminary, and it only involved a small number of patients. Future studies should involve more patients to provide better statistical reliability. Further, such studies should employ different time intervals. “This is really just the beginning,” comments Grunwald.

Indeed, future studies appear inevitable. Grunwald says there was a great deal of positive reaction to the recent study and its findings. “I was amazed,” she remarked. “So many people want to do more studies, not only in the United States, but in Italy and Germany, too.”

In addition to further work with stenting and memory function, Grunwald also plans on performing more studies involving the drug Viagra, which in addition to its approved indication can also increase blood flow to the brain and improve cognitive function. “After our study, we wondered what we could do with these results as, up until now, it was only a side effect. So, the next thing we did was to check if increasing the brain perfusion by using Viagra, which also increases perfusion, improves cognitive speed. And, it does.”

As far as the potential for treatment that her studies with stenting and Viagra suggest, Grunwald indicated that it appears significant. However, stenting would not be performed only for the purpose of improving cognitive function. “If an increase in brain perfusion can also increase cognitive function, then there is a potential to improve that function through medication, for instance,” she says.

Physicians wouldn’t try to improve cognitive function if the stenosis wasn’t high enough, because of the risk involved, she indicates. “But you could be able to do it through other means,” she adds. “If impaired cognitive function is due to impaired brain perfusion, then you can try and change that.

“At least for the moment, we can say that with stenting, cognitive function seems to increase,” she concluded.

— Dan Harvey is a freelance writer based in Wilmington, Del., and a frequent contributor to Radiology Today.

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