Category: Stroke

Stroke is the fourth leading cause of death and a common cause of long-term disability in the United States, but doctors have very few proven treatment methods. Now a new device that mechanically removes stroke-causing clots from the brain is being hailed as a game-changer.

In a recent clinical trial, the SOLITAIRE Flow Restoration Device dramatically outperformed the standard mechanical treatment. Findings from the trial, called SOLITAIRE With the Intention for Thrombectomy (SWIFT), are published online August 26 in the journal The Lancet and will also appear in a later print edition of the journal.

SOLITAIRE, which was approved by the U.S. Food and Drug Administration in March, is among an entirely new generation of devices designed to remove blood clots from blocked brain arteries in patients experiencing an ischemic stroke. It has a self-expanding, stent-like design, and once inserted into a blocked artery using a thin catheter tube, it compresses and traps the clot. The clot is then removed by withdrawing the device, reopening the blocked blood vessel.

"This new device is significantly changing the way we can treat ischemic stroke," said the study's lead author, Dr. Jeffrey L. Saver, director of the UCLA Stroke Center and a professor of neurology at the David Geffen School of Medicine at UCLA. "We are going from our first generation of clot-removing procedures, which were only moderately good in reopening target arteries, to now having a highly effective tool."

Results of the study showed that the device opened blocked vessels without causing symptomatic bleeding in or around the brain in 61 percent of patients. The standard FDA-approved mechanical device — a corkscrew-type clot remover called the MERCI Retriever — was effective in 24 percent of cases. The use of SOLITAIRE also led to better survival three months after a stroke. There was a 17.2 percent mortality rate with the new device, compared with a 38.2 percent rate with the older one.

About 87 percent of all strokes are caused by blood clots blocking a blood vessel supplying the brain. The stroke treatment that has received the most study is an FDA-approved clot-busting drug known as tissue plasminogen activator, but this drug must be given within four-and-a-half hours of the onset of stroke symptoms, and even more quickly in older patients.

When clot-busting drugs cannot be used or are ineffective, the clot can sometimes be mechanically removed during, or beyond, the four-and-a-half-hour window. The current study, however, did not compare mechanical clot removal to drug treatment.

For the trial, researchers randomly assigned 113 stroke patients at 18 hospitals to receive either SOLITAIRE or MERCI therapy within eight hours of stroke onset, between January 2010 and February 2011. The patients' average age was 67, and 68 percent were male. The time from the beginning of stroke symptoms to the start of the clot-retriever treatment averaged 5.1 hours. Forty percent of the patients had not improved with standard clot-busting medication prior to the study, while the remainder had not received it.

At the suggestion of a safety monitoring committee, the trial was ended nearly a year earlier than planned due to significantly better outcomes with the experimental device.

Other statistically significant findings included:

• 2 percent of SOLITAIRE-treated patients had symptoms of bleeding in the brain, compared with 11 percent of MERCI patients.

• At the 90-day follow-up, overall adverse event rates, including bleeding in the brain, were similar for the two devices.

• 58 percent of SOLITAIRE-treated patients had good mental/motor functioning at 90 days, compared with 33 percent of MERCI patients.

• The SOLITARE device also opened more vessels when used as the first treatment approach, necessitating fewer subsequent attempts with other devices or drugs.

The simple act of picking up a pencil requires the coordination of dozens of muscles: The eyes and head must turn toward the object as the hand reaches forward and the fingers grasp it. To make this job more manageable, the brain's motor cortex has implemented a system of shortcuts. Instead of controlling each muscle independently, the cortex is believed to activate muscles in groups, known as "muscle synergies." These synergies can be combined in different ways to achieve a wide range of movements.

A new study from MIT, Harvard Medical School and the San Camillo Hospital in Venice finds that after a stroke, these muscle synergies are activated in altered ways. Furthermore, those disruptions follow specific patterns depending on the severity of the stroke and the amount of time that has passed since the stroke.

The findings, published this week in the Proceedings of the National Academy of Sciences, could lead to improved rehabilitation for stroke patients, as well as a better understanding of how the motor cortex coordinates movements, says Emilio Bizzi, an Institute Professor at MIT and senior author of the paper.

"The cortex is responsible for motor learning and for controlling movement, so we want to understand what's going on there," says Bizzi, who is a member of the McGovern Institute for Brain Research at MIT. "How does the cortex translate an idea to move into a series of commands to accomplish a task?"

Coordinated control

One way to explore motor cortical functions is to study how motor patterns are disrupted in stroke patients who suffered damage to the motor areas.

In 2009, Bizzi and his colleagues first identified muscle synergies in the arms of people who had suffered mild strokes by measuring electrical activity in each muscle as the patients moved. Then, by utilizing a specially designed factorization algorithm, the researchers identified characteristic muscle synergies in both the stroke-affected and unaffected arms.

"To control, precisely, each muscle needed for the task would be very hard. What we have proven is that the central nervous system, when it programs the movement, makes use of these modules," Bizzi says. "Instead of activating simultaneously 50 muscles for a single action, you will combine a few synergies to achieve that goal."

In the 2009 study, and again in the new paper, the researchers showed that synergies in the affected arms of patients who suffered mild strokes in the cortex are very similar to those seen in their unaffected arms even though the muscle activation patterns are different. This shows that muscle synergies are structured within the spinal cord, and that cortical stroke alters the ability of the brain to activate these synergies in the appropriate combinations.

However, the new study found a much different pattern in patients who suffered more severe strokes. In those patients, synergies in the affected arm merged to form a smaller number of larger synergies. And in a third group of patients, who had suffered their stroke many years earlier, the muscle synergies of the affected arm split into fragments of the synergies seen in the unaffected arm.

This phenomenon, known as fractionation, does not restore the synergies to what they would have looked like before the stroke. "These fractionations appear to be something totally new," says Vincent Cheung, a research scientist at the McGovern Institute and lead author of the new PNAS paper. "The conjecture would be that these fragments could be a way that the nervous system tries to adapt to the injury, but we have to do further studies to confirm that."

This is the first time that fractionation of muscle synergies identified by factorization has been seen in chronic stroke patients, says Simon Giszter, a professor of neurobiology and anatomy at Drexel University. "It raises the question of how this occurs and if it's a compensatory process. If it is, we can use this measurement to study how the recovery process can be accelerated," says Giszter, who was not involved in this study.

Toward better rehabilitation

The researchers believe that these patterns of synergies, which are determined by both the severity of the deficit and the time since the stroke occurred, could be used as markers to more fully describe individual patients' impaired status. "In some of the patients, we see a mixture of these patterns. So you can have severe but chronic patients, for instance, who show both merging and fractionation," Cheung says.

The findings could also help doctors design better rehabilitation programs. The MIT team is now working with several hospitals to establish new therapeutic protocols based on the discovered markers.

About 700,000 people suffer strokes in the United States every year, and many different rehabilitation programs exist to treat them. Choosing one is currently more of an art than a science, Bizzi says. "There is a great deal of need to sharpen current procedures for rehabilitation by turning to principles derived from the most advanced brain research," he says. "It is very likely that different strategies of rehabilitation will have to be used in patients who have one type of marker versus another."

The research was funded by the National Institutes of Health and the Italian Ministry of Health.

---

Journal Reference:

1. Vincent C. K. Cheung, Andrea Turolla, Michela Agostini, Stefano Silvoni, Caoimhe Bennis, Patrick Kasi, Sabrina Paganoni, Paolo Bonato, and Emilio Bizzi. Muscle synergy patterns as physiological markers of motor cortical damage. PNAS, August 20, 2012 DOI: 10.1073/pnas.1212056109

Aspirin combined with the antiplatelet drug clopidogrel is no better than aspirin alone for stroke prevention in people with a history of lacunar strokes, and the combination carries a greater risk of gastrointestinal bleeding, according to results of a trial funded by the National Institutes of Health. Lacunar strokes occur due to chronic high blood pressure and typically produce small lesions deep within the brain.

The trial results also point to an overall improvement in stroke management during the past decade. Regardless of whether patients received aspirin alone or the dual therapy, their stroke risk was reduced more than three-fold from what it was 10 years ago.

Antiplatelet drugs such as aspirin are routinely prescribed to help prevent new strokes in people with a history of lacunar stroke. The Secondary Prevention of Small Subcortical Strokes (SPS3) trial was designed to determine if adding clopidogrel to aspirin would offer better protection than aspirin alone. The results appear in the Aug. 30th New England Journal of Medicine.* They show that the aspirin-clopidogrel combination was about equal to aspirin in reducing the risk of any type of stroke, but it almost doubled the risk of gastrointestinal bleeding.

"For all stroke therapeutics, there is a need to balance the potential benefits against the risks. The SPS3 findings establish that for lacunar stroke, dual therapy with aspirin and clopidogrel carries significant risk and minimal benefit," said Walter Koroshetz, M.D., deputy director of National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

The SPS3 trial is funded by NINDS and led by Oscar R. Benavente, M.D., research director of the Stroke and Cerebrovascular Health program at the University of British Columbia in Vancouver, British Columbia.

In addition to comparing dual antiplatelet therapy with aspirin, the trial was designed to test two levels of blood pressure control. After an interim data analysis in August 2011, the antiplatelet component of the trial was stopped. NIH also issued a clinical alert, warning that there was "little likelihood of benefit in favor of aspirin plus clopidogrel [for] recurrent stroke should the study continue to conclusion." The blood pressure component of the trial is ongoing, and the trial participants have been encouraged to continue taking aspirin without clopidogrel.

Strokes occur when blood vessels that supply the brain rupture or become blocked, such as by a blood clot. Antiplatelet drugs interfere with the formation of blood clots.

Lacunar strokes occur due to chronic high blood pressure, which in turn leads to progressive narrowing and finally blockage of small arteries that supply deep brain structures. They account for up to one-fifth of all strokes and are especially common among African-Americans, Hispanics and people with diabetes. Although lacunar strokes tend to produce relatively small lesions, they can cause disability depending on where they occur in the brain.

The SPS3 trial involves more than 3,000 participants at 82 clinical centers in North and South America and in Spain. The participants are age 30 and older, and all had a recent history of lacunar stroke prior to enrollment. About 52 percent are white, 31 percent Hispanic and 17 percent black.

For the antiplatelet component of the trial, about half of the participants received 325 milligrams of aspirin and 75 milligrams of clopidogrel daily, and the other half received aspirin and placebo. The participants were also randomly assigned to receive either standard control of systolic blood pressure (less than 130 mm Hg) or aggressive control (130-149 mm Hg).

After eight years of study, the annual risk of recurrent stroke was 2.7 percent in the aspirin-only group and 2.5 percent in the aspirin plus clopidogrel group. Most of the recurrent strokes in both groups were lacunar strokes. The rate of serious or life-threatening internal bleeding was 1.1 percent in the aspirin group and 2.1 percent in the dual therapy group. The difference was due mostly to a higher number of gastrointestinal bleeds in the dual therapy group. The percentage of brain bleeds in the two groups was not significantly different. Deaths from any cause were also higher in the aspirin-clopidogrel group.

For both groups, stroke recurrence was lower than the investigators had expected. When the SPS3 trial began in 2003, another large trial that tested warfarin vs. aspirin for stroke prevention had just ended. Warfarin is an anticoagulant, another class of drugs that interferes with blood clotting. That trial, called the Warfarin vs. Aspirin Recurrent Stroke Study (WARSS), found that patients with a history of lacunar strokes who took aspirin had an annual stroke recurrence rate of about 7 percent. (Warfarin and aspirin were about equal.)

This reflects a common trend, Dr. Benavente said. "What we see more and more often in stroke prevention trials is a significant decrease in stroke risk, compared to data from 10 years ago. We have better medications now to control stroke risk factors such as high blood pressure and cholesterol, and these are clearly having an impact."

In prior studies, antiplatelet drugs including aspirin or clopidogrel alone, or a combination of aspirin and dipyridamole, have been shown to reduce stroke risk in patients with heart disease or prior stroke. In one trial, aspirin combined with clopidogrel was more effective than aspirin alone at reducing stroke risk in patients with atrial fibrillation, a type of abnormal heart rhythm. However, other trials involving broader stroke populations found no added benefit from combining aspirin and clopidogrel. Therefore, current practice guidelines recommend aspirin alone, clopidogrel alone, or aspirin plus dipyridamole for secondary prevention after most types of stroke. The SPS3 results are consistent with those guidelines.

Researchers continue to investigate whether the clopidogrel-aspirin combination might be beneficial for patients with other types of stroke, such as transient ischemic attack (TIA). This is a type of stroke in which symptoms fade away in less than 24 hours; it is also a warning that a more damaging stroke may be imminent. The Platelet-Oriented Inhibition in New TIA (POINT) trial is testing whether aspirin plus clopidogrel are effective at preventing major strokes when given within 12 hours of a TIA. That trial is also funded by NINDS.

Eating a moderate amount of chocolate each week may be associated with a lower risk of stroke in men, according to a new study published in the August 29, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology. "While other studies have looked at how chocolate may help cardiovascular health, this is the first of its kind study to find that chocolate, may be beneficial for reducing stroke in men," said study author Susanna C. Larsson, PhD, with the Karolinska Institute in Stockholm, Sweden.

For the study, 37,103 Swedish men ages 49 to 75 were given a food questionnaire that assessed how often they consumed various foods and drinks and were asked how often they had chocolate. Researchers then identified stroke cases through a hospital discharge registry. Over 10 years, there were 1,995 cases of first stroke.

Men in the study who ate the largest amount of chocolate, about one-third of a cup of chocolate chips (63 grams) per week, had a lower risk of stroke compared to those who did not consume any chocolate. Those eating the highest amount of chocolate had a 17-percent lower risk of stroke, or 12 fewer strokes per 100,000 person-years compared to those who ate no chocolate. Person-years is the total number of years that each participant was under observation.

In a larger analysis of five studies that included 4,260 stroke cases, the risk of stroke for individuals in the highest category of chocolate consumption was 19 percent lower compared to non-chocolate consumers. For every increase in chocolate consumption of 50 grams per week, or about a quarter cup of chocolate chips, the risk of stroke decreased by about 14 percent.

"The beneficial effect of chocolate consumption on stroke may be related to the flavonoids in chocolate. Flavonoids appear to be protective against cardiovascular disease through antioxidant, anti-clotting and anti-inflammatory properties. It's also possible that flavonoids in chocolate may decrease blood concentrations of bad cholesterol and reduce blood pressure," said Larsson.

"Interestingly, dark chocolate has previously been associated with heart health benefits, but about 90 percent of the chocolate intake in Sweden, including what was consumed during our study, is milk chocolate," Larsson added.

The study was supported by the Swedish Council for Working Life and Social Research, the Swedish Research Council/Committee for Infrastructure and the Karolinska Institute.

The risk of ischemic stroke one year after acute myocardial infarction (AMI) dropped by 21% over a ten year period, according to research presented at ESC Congress 2012. The analysis of data from two Swedish registries was presented by Dr Anders Ulvenstam, and suggests that the reduction is due to improvements in AMI care.

Ischemic stroke is a well known, relatively rare but potentially devastating complication following myocardial infarction. It can lead to severe neurological handicap and death for the patient and it is associated with great costs for society.

"The risk of ischemic stroke after myocardial infarction has been studied previously, but there are many questions that remain unanswered," said Dr Ulvenstam. "Many studies have been conducted within clinical trials but these trials tend to focus on a particular patient group. Few, if any, studies have been done on the broader group of patients seen in day to day clinical practice. We based our analysis on two registries which include all AMI patients in Sweden."

"Great variation in the incidence of ischemic stroke after AMI has been found in previous studies, which tells us that we do not have a realistic estimate of the risk of suffering from ischemic stroke after myocardial infarction," he added.

"Furthermore, many of the earlier studies were done before modern AMI care -with different drugs and interventional procedures- was established, which is why we do not know how this has affected the risk over time. There is also conflicting data regarding independent predictors of stroke risk."

The study presented at ESC Congress 2012 was based on 173,233 Swedish AMI patients between 1998-2008, from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). In order to identify which of these AMI patients suffered an ischemic stroke within one year, the RIKS-HIA database was merged with the Swedish National Registry, which contains diagnoses for all patients at discharge from hospital care.

Dr Ulvenstam said: "Based on this patient information we were able to answer the questions raised above, regarding the incidence, time trends and independent predictors of ischemic stroke at one year after AMI."

The researchers found that during 1998-2008 the average risk of ischemic stroke one year after AMI was 4.1%. This was nearly twice as high as the incidence found in an important meta-analysis performed by Witt et al. in 2006 which showed an average risk of 2.1% (1). Dr Ulvenstam said: "The higher incidence in our study could be explained by the fact that we have such an unselected patient group. The registries used exclude very few AMI patients which means that there are more potential stroke victims."

A second finding from the study was that the risk of ischemic stroke one year after AMI fell by 21% over a ten year period, from 4.7% in 1998-2000 to 3.8% in 2007-2008. "We are the first to show that the risk of suffering from stroke after AMI seems to be diminishing," said Dr Ulvenstam. "This is probably a direct result of the great improvement in AMI care which has taken place during the last two decades. For the first time we can see the impact of different drugs and interventional procedures on stroke risk after AMI."

The researchers also conducted an analysis of independent predictors of stroke risk. Multiple regression analysis showed for the first time that each of the following factors independently reduced stroke risk: reperfusion therapy with percutaneous coronary intervention (PCI), blood clot dissolving therapy (fibrinolysis), thrombocyte aggregation inhibitors (aspirin and P2Y12-inhibitors) and statins. Dr Ulvenstam said: "The finding that PCI actually reduces stroke risk is somewhat surprising, being an invasive procedure. It has traditionally been associated with an increased stroke risk. We speculate that early reperfusion of the myocardium reduces infarction size and thereby leads to a reduced burden of atrial fibrillation and heart failure and in turn, reduced stroke risk."

He concluded: "The risk of stroke after myocardial infarction is higher than previously thought, but seems to be decreasing with the modernization of coronary care. We predict that this risk will continue to decline if clinicians treat their AMI patients with the recommended drugs and interventions."

Patients who resume smoking after a stroke increase their risk of death by three-fold, according to research presented at ESC Congress 2012 by Professor Furio Colivicchi from San Filippo Neri Hospital. The researchers also found that the earlier patients resume smoking, the greater their risk of death with one year.

"It is well established that smoking increases the risk of having a stroke," said Professor Colivicchi. "Quitting smoking after an acute ischemic stroke may be more effective than any medication in reducing the risk of further adverse events. However, on the other hand, our study shows that stroke patients resuming active smoking after leaving the hospital can raise their risk of dying by as much as three-fold."

The purpose of the study was to gauge the effects of resuming smoking after a stroke, and to see how many patients are likely to relapse. Cardiologists from S. Filippo Neri Hospital in Rome, in collaboration with neurologists from the Santa Lucia Foundation of Rome, tracked 921 patients (584 men and 337 women, mean age 67 ± 16 years) who reported being regular smokers before they were hospitalized with acute ischemic stroke.

All patients ceased smoking while in the hospital and declared themselves motivated to continue abstaining once they were discharged. In addition, all patients attended brief smoking cessation counseling sessions while in the hospital, but no nicotine replacement or other smoking cessation help was provided after they left the hospital.

Patients were interviewed about their smoking status at one, six, and 12 months after their release from the hospital and by the end of the first year 493 (53%) had resumed regular smoking. Older patients and women were more likely to relapse.

Within a year 89 patients died, which equates to a one-year probability of death of 9.6%. After adjusting for patient ages and other clinical variables such as stroke severity, presence of diabetes, hypertension or coronary artery disease, the researchers found that resuming smoking raised a person's risk of death by about three-fold compared to patients who didn't relapse. Moreover, the earlier a patient relapsed, the more likely he or she was to die within a year. "In fact, those who resumed smoking within 10 days of leaving the hospital were five times more likely to die within a year than those who continued to abstain," said Professor Colivicchi.

He added: "The results of this study suggest that healthcare providers should take smoking cessation interventions more seriously, as recommended treatments are not making their way into practice. A successful programme to help stroke patients quit smoking should take a comprehensive long-term approach, including individual counseling, post-discharge support and pharmacological treatment."

Tests to screen for "silent" neck artery narrowing in a bid to curb the risk of a stroke result in many unnecessary and costly surgical procedures, and ultimately save very few lives, concludes an editorial in the Journal of NeuroInterventional Surgery.

In 2-6% of European men aged 60 plus, the major arteries supplying the brain (carotid arteries) are narrowed by 50-99%. This condition, termed carotid stenosis or atherosclerosis, accounts for 10-15% of strokes (data not in paper).

Carotid atherosclerosis is commonest in those with mild peripheral arterial disease in their legs, a condition known as claudication.

In this group the prevalence of silent carotid atherosclerosis is 15%. As they are already under the care of a vascular specialist, they are considered ideal candidates to test for silent carotid atherosclerosis.

But debate rages as to whether to screen for carotid atherosclerosis to stave off a stroke: the Royal College of Physicians does not currently recommend it, but the US Society for Vascular Surgery strongly backs testing in selected groups.

Those found to have severe (70-99%) carotid narrowing on screening are offered surgical treatment (endarterectomy).

But 133 people with claudication would need to be tested to pick up 20 patients eligible for surgery, and this would only prevent a single stroke, at a cost of around £76, 000, say the authors.

If this policy were to be introduced into England and Wales at age 60 for those with mild peripheral arterial disease, it would cost £17.5 million a year, on the basis that around 669 000 would be eligible for an ultrasound scan, 4600 of whom would then require surgery.

But all this effort would still only prevent 231 strokes, even in this high risk group, equivalent to around 0.2% of all 110,000 strokes sustained in 2010, say the authors.

"The hazards of overdiagnosis have recently been highlighted, and perhaps it is time to realise why it has been recommended that we stop testing for asymptomatic carotid atherosclerosis in the UK," they conclude.

A new study shows that people who have three or more alcoholic drinks per day may be at higher risk for experiencing a stroke almost a decade and a half earlier in life than those who do not drink heavily. The research is published in the September 11, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.

"Heavy drinking has been consistently identified as a risk factor for this type of stroke, which is caused by bleeding in the brain rather than a blood clot," said study author Charlotte Cordonnier, MD, PhD, with the University of Lille Nord de France in Lille, France. "Our study focuses on the effects of heavy alcohol use on the timeline of stroke and the long-term outcome for those people."

For the study, 540 people with an average age of 71 who had a type of stroke called intracerebral hemorrhage were interviewed about their drinking habits. Doctors also interviewed the participants or the caregivers or relatives about the participants' drinking habits. A total of 137 people, or 25 percent, were heavy drinkers, which was defined as having three or more drinks per day, or about 1.6 ounces per day of "pure" alcohol.

Participants also underwent CT brain scans and their medical records were reviewed.

The study found that heavy drinkers experienced a stroke at an average age of 60, 14 years before the average age of their non-heavy drinking counterparts. Among people younger than 60 who had a stroke that occurred in the deep part of the brain, heavy drinkers were more likely to die within two years of the study follow-up than non-heavy drinkers.

"It's important to keep in mind that drinking large amounts of alcohol contributes to a more severe form of stroke at a younger age in people who had no significant past medical history," said Cordonnier.

The study was supported by the University of Lille Nord de France and the Association for the Development of Research and Innovation the North Pas de Calais (ADRINORD).

Group yoga can improve balance in stroke survivors who no longer receive rehabilitative care, according to new research in the American Heart Association journal Stroke.

 Shift work is associated with an increased risk of major vascular problems, such as heart attacks and strokes, concludes a study published on the website of the British Medical Journal.