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Redefining Asymptomatic A study’s findings suggest that carotid artery stenting to restore blood flow to the brain significantly reduces depressive symptoms. Some wonder whether reduced symptoms reflect a halo effect that the procedure went well and the patient’s stroke risk is reduced. Every 45 seconds, someone in the United States has a stroke. Approximately 25% of those who have a stroke die from it or the complications it causes each year. A leading cause of stroke is atherosclerosis of the carotid arteries in the neck. If the arteries are severely blocked with plaque—at least 70%—the gold standard therapy has been endarterectomy, where the fatty buildup or plaque is surgically removed. In the past 10 years, however, endarterectomy has been competing with minimally invasive carotid artery stenting, which is done under local anesthesia. To perform the stenting procedure, a physician uses a fluoroscopic imaging system in an angiography suite to guide a wire and catheter to reach the site of the narrowing in the artery. At the site, the physician uses a tiny balloon to expand the artery and inserts a stent to hold the artery open. A filterlike mechanical protection device is inserted above the stent to prevent plaque and debris from breaking off and going into the brain. This new addition has made the procedure considerably safer. “Nowadays, carotid artery stenting is widely accepted, especially in the treatment of patients for whom surgery is high risk and for patients who are symptomatic,” says Wolfgang Mlekusch, MD, specialist of clinical angiology and internal medicine at Vienna General Hospital and Medical School in Vienna, Austria. In Europe, patients with narrowed carotid arteries who do not have respective neurological symptoms may be treated with carotid stenting as well, Mlekusch says. However, in the United States, the Centers for Medicare & Medicaid Services approves reimbursement for carotid stenting only in symptomatic patients—those patients with focal neurological symptoms corresponding to the site of stenosis. In the August issue of Radiology, Mlekusch and colleagues published a study that provides a reason to consider treating such patients, including those who are neurologically asymptomatic, with carotid stenting. Measurable Improvement David C. Steffens, MD, MHS, professor of geriatric psychiatry at Duke University Medical Center in Durham, N.C., says the Austrians’ study underscores the need to monitor depression symptoms in patients with carotid arteries who are considered asymptomatic. “It raises the question of whether we need to rethink our definition of asymptomatic because in these patients, depression may be a sign that they have significant stenosis as well as cerebrovascular disease,” he says. “For clinicians taking care of patients with suspected carotid [artery] stenosis, it points to the need to do a depression screen.” Rodney Raabe, MD, director of radiology at Sacred Heart Medical Center in Spokane, Wash., agrees: the Austrians’ study is significant because it challenges the thinking about not treating asymptomatic patients with carotid stenting. Carotid stenting has been shown to reduce a patient’s stroke risk by 50% compared with medical therapy, Raabe says. This study shows that carotid stenting may also improve brain function, which could be reason to consider it for stenosis patients even if they have not had a stroke or transient ischemic attack. “Papers like this demonstrate that there are more benefits for treating stenosis that we are starting to measure,” Raabe says. Further Study At the Society of Interventional Radiology meeting in Toronto earlier this year, Raabe reported interim results of a study that found that increasing blood flow to the brain with carotid artery stenting improves cognition in at-risk stroke patients. The 51 patients in the trial who either had a stroke or were at high risk for a stroke had showed improved memory, executive function, and reading and auditory-verbal learning skills that continued to be significant six months after the stenting procedure. The Austrian researchers wanted to see whether clinically important depressive symptoms in patients with CAS improved after successful endovascular revascularization therapy. So they studied 143 patients (91 men and 52 women with an interquartile range of 63 and 76 years) who were undergoing carotid artery stenting because of a narrowing of at least 80%. Patients were excluded if they were permanently disabled by a stroke or had dementia. They chose as their control group 102 patients (64 men and 38 women with an interquartile range of 63 to 73 years) who had been hospitalized because of peripheral artery disease (PAD) and who were scheduled to undergo percutaneous transluminal angioplasty (PTA), an alternative to open vascular surgery to restore blood flow in the lower limbs. The control group did not have narrowed carotid arteries. The researchers chose this control group because patients with advanced PAD who require peripheral revascularization also frequently exhibit coronary and cerebrovascular atherosclerosis, Mlekusch says. “These patients with generalized atherosclerosis seem to be at a particularly high risk for depressive symptoms and therefore may be a reasonable control group for the study purpose.” Evaluating Depression The highest score on each of the 21 questions is three—making the highest possible score 63 and the lowest zero. A patient who scores 10 or higher is generally considered to have clinically important depressive symptoms, Mlekusch says. The BDI tests were administered within three days of the planned treatment and four weeks after treatment. As they hypothesized, the researchers found that patients with high-grade internal CAD more frequently demonstrated depressive symptoms than the control subjects. Forty-eight (33.6%) of those with narrowed carotid arteries had symptoms of depression while only 17 patients (16.7%) with PAD appeared depressed. The first 27 patients were treated without the use of a mechanical cerebral protection device while the remaining patients were treated with the use of a filter-type cerebral protection device, Mlekusch says. All the carotid artery stenting procedures were technically successful. Five patients suffered procedure-related strokes—two were major and three were minor. CAS patients had a significant reduction in depressive symptoms after successful carotid recanalization while PTA patients had no change in the frequency of their depressive symptoms, Mlekusch says. After the stenting procedure, only 9.8% of the patients with CAS exhibited depressive symptoms while 13% of the patients who had undergone PTA did. No patient in either group exhibited significant worsening of depressive symptoms after the procedure, Mlekusch says. The findings suggest that opening the carotid artery and restoring blood flow to the brain via a minimally invasive technique under local anesthesia can significantly reduce depressive symptoms, Mlekusch says. “We were able to demonstrate a clear neuropsychological benefit to patients after carotid stenting.” A few other researchers have studied whether depressive symptoms among CAS patients improve with endarterectomy, Mlekusch says. However, so far they have not reported a significant improvement of depressive symptoms with endarterectomy. It could be, Mlekusch says, that endarterectomy requires the administration of general anesthesia, which has been known to decrease mental functions in patients. “In contrast, our findings suggest that improvement of cerebral profusion by removing the stenosis with a minimally invasive technique with the use of a local anesthetic is associated with significant improvement of depressive symptoms.” What Does It Mean? One criticism of Mlekusch’s study is that the follow-up period was fairly short. However, Mlekusch says it seemed long enough to document a positive effect on the course of depressive symptoms in patients who underwent CAS compared with those who underwent PTA. “By reviewing other articles describing the neuropsychological course of patients after recanalizing procedures of the carotid arteries, you can see that most of the studies retested four to six weeks after intervention and long-term follow-up investigations were rarely performed,” Mlekusch says. Besides, BDI scores were available for 29 of the patients after four months and they showed no significant changes compared with their scores at four weeks, Mlekusch notes. Another criticism is the choice of patients with PAD as a control group. Benjamin T. Mast, PhD, associate professor of psychological and brain sciences at the University of Louisville in Kentucky, believes the researchers chose a good comparison group in those with PAD. However, he suggests that they could have improved the study by including another comparison group such as those who had a similar level of CAS but were waiting for treatment or had elected to undergo treatments other than stenting. Some have also questioned whether the stenosis patients’ mood improved after stenting simply because their risky situation was successfully treated. Michael D. Dake, MD, chairman of the department of radiology at the University of Virginia Health System in Charlottesville, says it’s possible that the patients were depressed because of their diagnosis and fear they would suffer a debilitating stroke. Their mood may have improved after stenting because they realized they were OK and had not had a stroke. Halo Effect? Mast also believes in the euphoric effect of a successful procedure. However, he does not believe the patients’ concerns over their condition would be enough to explain the differences in the rates of depression between those with CAS and those with PAD. “Still,” Mast says, “it would be helpful to know how stable the depression was prior to stenting or if it was associated with stress concerning the procedure.” Mlekusch says the issue of surgical risk and mood was one reason they chose patients with PAD as controls. Those patients with PAD did not show any improved depressive symptoms, although they were successfully treated and had not lost their legs, he says. While carotid stenting is valuable for relieving depression caused by narrowing neck arteries, it should not be considered as a treatment for depression caused by other triggers, Mlekusch says. Further studies are in the works, Mlekusch says. “Another study is currently under review, describing the cognitive course with regard to frontal lobe functioning in patients after carotid stenting.” Dake says the Mlekusch study is intriguing and “piques the interest of a lot of investigators to further explore the depression issue and examine it.” — Beth W. Orenstein is a freelance medical
writer and a regular contributor to Radiology Today.
She writes from her home in Northampton, Pa.
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September
11, 2006
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