TAG: "Stroke"

Brain’s iconic seat of speech goes silent when we actually talk


UC Berkeley discovery has implications for diagnoses, treatments of stroke, epilepsy.

New findings will better help map out the brain’s speech regions (Photo courtesy of Adeen Flinker)

By Yasmin Anwar, UC Berkeley

For 150 years, the iconic Broca’s area of the brain has been recognized as the command center for human speech, including vocalization. Now, scientists at UC Berkeley and Johns Hopkins University in Maryland are challenging this long-held assumption with new evidence that Broca’s area actually switches off when we talk out loud.

The findings, reported today (Feb. 16) in the Proceedings of the National Academy of Sciences journal, provide a more complex picture than previously thought of the frontal brain regions involved in speech production. The discovery has major implications for the diagnoses and treatments of stroke, epilepsy and brain injuries that result in language impairments.

“Every year millions of people suffer from stroke, some of which can lead to severe impairments in perceiving and producing language when critical brain areas are damaged,” said study lead author Adeen Flinker, a postdoctoral researcher at New York University who conducted the study as a UC Berkeley Ph.D. student. “Our results could help us advance language mapping during neurosurgery as well as the assessment of language impairments.”

Flinker said that neuroscientists traditionally organized the brain’s language center into two main regions: one for perceiving speech and one for producing speech.

“That belief drives how we map out language during neurosurgery and classify language impairments,” he said. “This new finding helps us move towards a less dichotomous view where Broca’s area is not a center for speech production, but rather a critical area for integrating and coordinating information across other brain regions.”

In the 1860s, French physician Pierre Paul Broca pinpointed this prefrontal brain region as the seat of speech. Broca’s area has since ranked among the brain’s most closely examined language regions in cognitive psychology. People with Broca’s aphasia are characterized as having suffered damage to the brain’s frontal lobe and tend to speak in short, stilted phrases that often omit short connecting words such as “the” and “and.”

Specifically, Flinker and fellow researchers have found that Broca’s area — which is located in the frontal cortex above and behind the left eye — engages with the brain’s temporal cortex, which organizes sensory input, and later the motor cortex, as we process language and plan which sounds and movements of the mouth to use, and in what order. However, the study found, it disengages when we actually start to utter word sequences.

“Broca’s area shuts down during the actual delivery of speech, but it may remain active during conversation as part of planning future words and full sentences,” Flinker said.

The study tracked electrical signals emitted from the brains of seven hospitalized epilepsy patients as they repeated spoken and written words aloud. Researchers followed that brain activity – using event-related causality technology – from the auditory cortex, where the patients processed the words they heard, to Broca’s area, where they prepared to articulate the words to repeat, to the motor cortex, where they finally spoke the words out loud.

In addition to Flinker, other co-authors and researchers on the study are Robert Knight and Avgusta Shestyuk at the Helen Wills Neuroscience Institute at UC Berkeley, Nina Dronkers at the Center for Aphasia and Related Disorders at the Veterans Affairs Northern California Health Care System, and Anna Korzeniewska, Piotr Franaszczuk and Nathan Crone at Johns Hopkins School of Medicine.

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Paramedics may be best first lineof defense in treating stroke patients


First-of-its-kind study, led by UCLA, offers hope for faster, more effective care.

By Kim Irwin, UCLA

A consortium led by UCLA physicians has found that paramedics can safely start providing people with medication in the first minutes after the onset of a stroke instead of waiting for them to receive treatment at a hospital.

Although the drug tested, magnesium sulfate, did not improve patient outcomes, the research points to a new method for treating stroke patients quickly.

For people who have suffered a stroke, immediate treatment is key — the more time that passes before the restoration of blood flow, the higher the likelihood that stroke victims will suffer irreversible brain damage.

The study findings indicate that paramedics can give intravenous medications to stroke patients within the “golden hour,” the window during which treatments are most likely to help patients survive and avoid debilitating, long-term neurological damage. That finding is a game-changer, said Dr. Jeffrey Saver, the study’s co-principal investigator and director of the UCLA Stroke Center.

“The trial succeeded in its goal of devising a means to deliver promising drugs to stroke patients in the first minutes, when there’s the greatest amount of brain to save. We have opened a new therapeutic window that is now being used to test other compounds and deliver clot-busting drugs to patients in the field,” said Saver, who also is a professor of neurology at the David Geffen School of Medicine at UCLA. “Stroke is a true emergency condition. Time lost is brain lost — for every minute that goes by without restoration of blood flow, 2 million nerve cells are lost.”

The study appears in today’s (Feb. 5) issue of the New England Journal of Medicine.

The phase 3 Field Administration of Stroke Therapy–Magnesium (FAST–MAG) clinical trial involved collaboration among 315 ambulances, 40 emergency medical service agencies, 60 receiving hospitals, 715 emergency physicians, 210 neurologists, 26 neurosurgeons and 2,988 paramedics in Los Angeles and Orange counties. In the study, half of the 1,700 patients had the study drug administered within 45 minutes, while 74 percent were treated within the golden hour.

“This study involved an unprecedented cooperative effort of paramedics in the field and emergency physicians serving as investigators,” said Dr. Sidney Starkman, co-principal investigator and co-director of the UCLA Stroke Center.

“Through this study we were able to instill permanently in everyone’s mind the idea that ‘time is brain.’ We believe this represents a paradigm shift in the treatment of stroke and potentially numerous other neurological conditions,” said Starkman, who also is professor of emergency medicine and neurology at the Geffen School. “We demonstrated that paramedics not only are eager to provide the best possible patient care, but also are capable of being invaluable partners in an intense, time-dependent clinical trial.”

Today, the only ways to treat strokes caused by blocked blood vessels are to reopen the arteries with tissue plasminogen activator, a clot-busting drug, or to use catheters to remove the clot. But, in general, neither can be done until the patient arrives at the hospital and undergoes a CT scan to rule out bleeding in the brain. Additional treatments can only be offered after that, by which time substantial brain injury may already have occurred.

The FAST–MAG trial used magnesium because in animal studies it dilated blood vessels and increased blood flow in the brain. Magnesium also countered the damaging calcium buildup that occurs when cells are deprived of oxygen. It had been already approved for use in humans, it had a good safety profile and paramedics were familiar with it.

“Now we are tasked with finding a different agent or combination of agents that can improve stroke outcomes within that golden hour,” Saver said. “The ambulance treatment platform can be used around the world to test promising agents.”

Dr. Bill Koenig, medical director of the Los Angeles County Emergency Medical Service Agency, worked closely with Saver and Starkman on the FAST-MAG study.

“To assist paramedic recognition of stroke victims, the nationally recognized Los Angeles Pre-hospital Stroke Screen was developed,” Koenig said. “FAST-MAG also served as an impetus to create the Los Angeles County System of Stroke Hospitals, which every year treats over 10,000 stroke victims. When the day comes that a medication can successfully treat stroke in its early stages, this novel system in Los Angeles will be well positioned to immediately apply the treatment to our patients. I am confident that with the dedicated investigators, along with a finely tuned EMS system, that discovery will be sooner rather than later.”

Dr. Walter Koroshetz, acting director of the National Institute of Neurological Disorders and Stroke, said this study shows that it is possible to get treatments to stroke patients even before they arrive at a hospital.

“Because a blocked blood vessel causes brain damage over minutes to hours, this pre-hospital approach to treatment is sure to be adopted and refined in clinical research studies,” Koroshetz said. “Ultra-early brain salvage in stroke patients will someday surely reduce the tremendous burden of disability and death due to stroke.”

Saver said clinical trials currently being conducted in the U.S., Canada and England are testing new compounds using the early treatment infrastructure created by the FAST–MAG study.

Stroke is the fifth leading cause of death in the U.S. and is a major cause of adult disability. About 800,000 people in the U.S. have strokes each year, and one person dies from a stroke every four minutes, on average.

The study was funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health.

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UC San Diego to host region’s first camp for stroke survivors, caregivers


Therapeutic retreat offers support, education and a bit of fun.

Alexander Khalessi, UC San Diego

By Jackie Carr, UC San Diego

On Jan. 23-25, more than 15 stroke survivors and their caregivers will go on a mini-vacation in La Jolla as part of a therapeutic retreat for those whose lives have been affected – sometimes turned upside down – by stroke. The 50s-themed stroke camp is being co-hosted by UC San Diego Health System, which has one of the nation’s first certified Comprehensive Stroke Centers.

“Stroke camp is part of UC San Diego’s larger commitment to the care of neurovascular patients and their families,” said Alexander Khalessi, M.D., director of endovascular neurosurgery and surgical director of neurocritical care at UC San Diego Health System. “Beyond receiving the best possible neurological care or developing new therapies, we support patients through their recovery and get them back to their lives.”

The camp will be the first Refresh & Retreat Stroke Camp in California, with the flare of an American Bandstand theme, complete with an invitation to bring “your letter sweaters, poodle skirts and dancing shoes.” The event is sponsored with Covidien, a global health care leader.

Stroke care has advanced rapidly in recent years, but strokes still involve some permanent loss of healthy brain tissue due to either a lack of blood flow or bleeding within the brain itself. As a result, many stroke survivors require significant time to recover and rehabilitate. During this healing process, it is the caregivers – often a spouse or family member – who may suddenly find themselves overwhelmed and socially isolated by their new responsibilities.

“Stroke camp is about pampering the caregivers and recognizing the toll strokes take on them,” said Julie Jurf, R.N., stroke care coordinator, UC San Diego Health System. “The camp’s aim is to bring fun, respite and renewal to stroke survivors, their families and caregivers.”

Jurf will volunteer at the retreat to assist caregivers.

“I will be pushing a wheelchair, standing in line for food, or doing whatever needs to be done so that my caregiver can go for a swim or relax,” she said. “Even just a two-day break can go a long way to bring renewal to people’s life.”

Khalessi added that stroke camp provides patients with support and encouragement, offers a welcome rest for their caregivers, and provides an opportunity to bond with other stroke survivors.

Over three days, attendees will be invited to participate in a variety of camp-like activities, including drum circles, craft-time and 50’s bingo, as well as survivor and caregiver break-out discussion sessions that allow attendees to vent, share and console as needed.

In addition, Khalessi, a national expert in catheter-based and open cranial neurosurgeries for stroke, aneurysms and other blood vessel disorders of the brain, will lead a tour of the Center for the Future of Surgery at the UC San Diego School of Medicine. This facility is a national destination for developing and refining new life-saving stroke treatments, now transforming the standard of care for stroke patients.

“Stroke is a disease that had no solutions 30 years ago. It is now a treatable medical and neurosurgical emergency. Even five years ago, stroke care involved a single drug and supporting patients through their new disabilities,” Khalessi said. “We now have catheter-based procedures and devices that allow for rapid and safe restoration of blood flow in the most severe forms of stroke, involving large vessels of the brain,” a procedure known as stent thrombectomy that in a recent study published in the New England Journal of Medicine greatly improved stroke patients’ prognoses.

“We have phenomenal new treatments for hemorrhagic stroke, or bleeds within the brain, due to cerebral aneurysms or high blood pressure, using minimally invasive surgical or catheter-based techniques,” he said. “These strokes are no less devastating and were a death sentence a decade ago.”

The designation of a Comprehensive Stroke Center at UC San Diego Health System is formal recognition of its ability to receive and treat the most complex stroke cases around the clock, every day of the year, with a multidisciplinary team of neurologists, neurosurgeons, cardiologists and rehabilitation specialists.

Approximately 680,000 American’s each year survive a stroke, making stroke the nation’s leading cause of disability. A patient’s ability to benefit from the latest in stroke-care technologies hinges upon a third party recognizing stroke and ensuring that the patient is brought to a hospital where comprehensive stroke care can be provided.

About Retreat & Refresh Stroke Camp
Retreat & Refresh Stroke Camp is a nonprofit based in Peoria, Illinois. It has sponsored 105 stroke camps nationwide since 2004. The nonprofit’s founder and executive director, Marylee Nunley, is caregiver to her husband John, who had a stroke in 2001. For more information, visit http://strokecamp.org.

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UCLA honored for stroke care


Receives Get With The Guidelines award for implementing quality improvement measures.

The UCLA Comprehensive Stroke Center at Ronald Reagan UCLA Medical Center has received a Get With The Guidelines – Stroke award for implementing specific quality improvement measures outlined by the American Heart Association/American Stroke Association for the treatment of stroke patients.

Get With The Guidelines – Stroke helps hospital teams provide the most up-to-date, research-based guidelines with the goal of speeding recovery and reducing death and disability for stroke patients. UCLA earned the Gold-Plus Quality Achievement Award award for measures that include aggressive use of medications and risk-reduction therapies aimed at reducing death and disability and improving the lives of stroke patients.

UCLA also received the association’s Target: Stroke Honor Roll for meeting stroke quality measures that reduce the time between hospital arrival and treatment with the clot-buster tPA, the only drug approved by the U.S. Food and Drug Administration to treat ischemic stroke. People who suffer a stroke who receive the drug within three hours of the onset of symptoms may recover quicker and are less likely to suffer severe disability.

“At the UCLA Comprehensive Stroke Center, we are dedicated to improving the quality of stroke care, and The American Heart Association/American Stroke Association’s Get With The Guidelines–Stroke helps us achieve that goal,” said Dr. Jeffrey Saver, director of the UCLA Stroke Center and professor of neurology at the David Geffen School of Medicine at UCLA. “With this award, our hospital demonstrates our commitment to ensure that our patients receive care based on internationally-respected clinical guidelines.”

“We are pleased to recognize UCLA for their commitment and dedication to stroke care,” said Dr. Deepak L. Bhatt, national chairman of the Get With The Guidelines steering committee and executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School. “Studies have shown that hospitals that consistently follow Get With The Guidelines quality improvement measures can reduce patients’ length of stays and 30-day readmission rates and reduce disparity gaps in care.”

Get With The Guidelines–Stroke also helps UCLA’s staff implement prevention measures, which include educating stroke patients to manage their risk factors and to be aware of warning signs for stroke, and ensuring they take their medications properly. Hospitals can make customized patient education materials available upon discharge, based on the patients’ individual risk profiles. The take-away materials are written in an easy-to-understand format in either English or Spanish.

According to the American Heart Association/American Stroke Association, stroke is the number four cause of death and a leading cause of adult disability in the United States. On average, someone suffers a stroke every 40 seconds; someone dies of a stroke every four minutes; and 795,000 people suffer a new or recurrent stroke each year.

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Young adults not too young to be at risk for stroke


Knowing symptoms and getting immediate attention is crucial.

Jennifer Reilly was 28 years old when she began experiencing some odd symptoms. Half of her left hand went numb. She could move her fingers, but she couldn’t feel anything on the outer part of that hand.

Because she was so young, Reilly assumed it was nothing. She was wrong.

She was having a stroke.

The numbness recurred off and on for several days. Then one night she had a piercing headache, an uncommon event for her. She mentioned her symptoms to a work colleague, who urged her to see a doctor.

“I didn’t know I was having a stroke at the time,” said Reilly, now 35. “I just assumed I was a healthy, normal 28-year-old.”

Reilly saw several doctors and finally landed at UCLA in the neurology department, where she saw Dr. David Liebeskind, professor of neurology and director of outpatient stroke and neurovascular programs. After a battery of tests, Reilly was diagnosed with Moyamoya disease — a rare, progressive cerebrovascular disorder caused by blocked arteries at the base of the brain, which cuts off blood flow. One of the first symptoms of Moyamoya is recurrent transient ischemic attacks, or TIAs, commonly referred to as “mini-strokes,” which are exactly what Reilly was experiencing.

She had no idea the danger she was in, said Liebeskind, who is also director of the neurovascular imaging research core at UCLA.

“The worst and a very likely possibility is that she would have had a significant stroke,” he said, one that could have been extremely debilitating or even fatal.

Reilly was referred to Dr. Neil Martin, chair of neurosurgery at Ronald Reagan UCLA Medical Center and head of the neurovascular surgery section.

“He told me I needed to be admitted into the hospital immediately, and that I would be in surgery within 24 hours,” she said. “It was such a shock. I can’t fathom what my parents must have been going through. We had a few tears, and they stayed very strong for me.”

Dr. Nestor Gonzalez, an associate professor of neurosurgery and radiology, performed two nine-hour brain surgeries on Reilly to reroute arteries that normally bring blood to the scalp to instead supply blood to her brain. Over time, the arteries formed new branches and restored blood supply to the brain.

Gonzalez highlighted the importance of Reilly acting quickly after her symptoms began.

“The good thing is that she sought attention when she started having those symptoms and we were able to diagnose her condition very early,” he said. “We were able to avert a stroke that could have devastated her life.”

It’s a common misconception that strokes only affect older people, Gonzalez said.

“A stroke is not a disease limited to elder individuals,” he said. “It is a condition that can affect younger individuals, even kids. The moment someone feels any of the symptoms of a stroke, they need to seek immediate emergency attention.”

Liebeskind said the most common signs of stroke include sudden onset of weakness, sudden onset of numbness, difficulty speaking, difficulty seeing and difficulty interacting with other individuals.

It’s been nearly six years since her mini strokes and surgeries and today Reilly is embracing life. She got married and will celebrate her third wedding anniversary next June.

“Since my recovery I have an absolutely newfound perspective on life,” she said. “I really try to stop and appreciate that I was given a second chance.”

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Researchers find promising new treatment approach for ischemic stroke


‘Sonic hedgehog’ plays key role in reducing size of stroke, promoting nerve regeneration.

(From left) Peter Bannerman, Olga Chechneva and Wenbin Deng, UC Davis

A team of UC Davis scientists has found that administering a small molecule – purmorphamine – in animal models after a stroke results in multiple protective effects, including reducing the size of the stroke, decreasing inflammation and increasing markers for nerve regeneration. The findings, which may offer a new approach to treating ischemic stroke — the disruption of blood flow in the brain from a blood clot — are published online in the journal Cell Death and Disease.

“We have revealed a previously unrecognized role of a developmental pathway that, when stimulated with a small molecule drug, leads to neuroprotection, regeneration and functional recovery following ischemic stroke,” said Wenbin Deng, associate professor in the UC Davis Department of Biochemistry and Molecular Medicine, and principal investigator of the study. “This is an important conceptual advance that could lead to a novel treatment approach, paving the way for new medicines in the treatment of a variety of neurological and neurodegenerative diseases.”

Deng added that the neuroprotective small molecule compound has broad in vitro and in vivo activities and offers new opportunities for studying neurological diseases and injuries as well as developmental and degenerative diseases in other tissues sharing common mechanisms. He and his research team focused on the humorously named “sonic hedgehog” signaling pathway, which plays a fundamental role in the early development of the central nervous system, regulating the generation and survival of neurons and other brain cells. It is also activated in response to an injury to the nervous system and has been shown to have beneficial effects in animal models of various conditions including stroke, multiple sclerosis and amyotrophic lateral sclerosis (ALS).

A key component of the sonic hedgehog pathway is the so-called Smoothened protein, a receptor that when stimulated promotes activation of the pathway. Purmorphamine is a small molecule that was developed to be a stimulator (also called an agonist) of the Smoothened protein.

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Colds may temporarily increase stroke risk in kids


Study shows colds, flu can create short-lived increased stroke risk in vulnerable children.

A new study suggests that colds and other minor infections may temporarily increase stroke risk in children. The study found that the risk of stroke was increased only within a three-day period between a child’s visit to the doctor for signs of infection and having the stroke.

The study was led by researchers at UCSF Benioff Children’s Hospital San Francisco in collaboration with the Kaiser Permanente Division of Research.

“These findings suggest that infection has a powerful but short-lived effect on stroke risk,” said senior author Heather Fullerton, M.D., a pediatric vascular neurologist and medical director of the Pediatric Brain Center at UCSF Benioff Children’s Hospital San Francisco.

“We’ve seen this increase in stroke risk from infection in adults, but until now, an association has not been studied in children.”

Strokes are extremely rare in children, affecting just 5 out of 100,000 kids per year. “The infections are acting as a trigger in children who are likely predisposed to stroke,” said Fullerton. “Infection prevention is key for kids who are at risk for stroke, and we should make sure those kids are getting vaccinated against whatever infections – such as flu – that they can.”

The study appears in today’s (Aug. 20) online issue of Neurology.

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Coalition teams to help reduce heart attacks, strokes in San Diego County


UC San Diego part of regional project awarded $5.8M Health Care Innovation grant.

Approximately 84 million people in the United States suffer from some form of cardiovascular disease, and about 720,000 Americans have a heart attack every year, which works out to one every 44 seconds. To address these alarming statistics, the Be There San Diego Initiative has been awarded a $5.8 million Health Care Innovation grant for a coalition project to help reduce heart attacks and strokes in San Diego County.

The initiative’s program, San Diego: A Heart Attack and Stroke Free Zone, is a regional collaboration of health care organizations and stakeholders to improve health care delivery and patient outcomes.

The goal during the three year project is to enroll 4,000 high-risk patients and lower their blood pressure and cholesterol levels through evidence-based practices and a better understanding of the importance of treatment adherence. The project will also promote heart attack and stroke prevention measures, test novel, cost-effective technology solutions and provide educational opportunities both for patients and within the physician community.

Partners in the Be There Initiative include UC San Diego Health System, Arch Health Partners, Scripps Health, Sharp HealthCare, Kaiser Permanente, Palomar Medical Center, Naval Medical Center, Veterans Administration, the San Diego County Medical Society Foundation, the County of San Diego Health and Human Services Agency, community clinics and others. UC San Diego Health System serves as the fiscal agent for the project.

“Health organizations that are competitive in the market will be working together for the benefit of San Diego patients,” said Anthony DeMaria, M.D., principal investigator of the Heart Attack and Stroke Free Zone program and cardiologist at UC San Diego Health System. “This approach will decrease our community’s risk for cardiovascular disease and could result in saving millions in the county by preventing half of the heart attacks and strokes that would have otherwise occurred in the participating patient population.”

Patients will be educated about the program, consented and enrolled through their physician’s office beginning later this year. Participants will also receive blood pressure cuffs to monitor levels at home and work closely with a health care coach.

“Because it’s a silent condition, we find that many patients are unaware of having hypertension, and only about 40 percent of patients diagnosed with high blood pressure take their medication, which can directly lead to cardiovascular disease. We hope through the Heart Attack and Stroke Free Zone program, we can increase this to 80 percent,” said Katherine Bailey, executive director of the Be There Initiative.

The Health Care Innovation grant supporting the project is made possible by the Centers for Medicare and Medicaid Services (CMS) through the Affordable Care Act and is part of an ongoing effort to advance innovative solutions in delivering and improving patient care across the nation.

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UC Davis honored with quality achievement for stroke care


Medical center earns Gold Plus award.

UC Davis Medical Center has received the Get With The Guidelines-Stroke Gold-Plus Quality Achievement Award for using measures developed by the American Heart Association/American Stroke Association to improve care and quality of life for stroke patients.

UC Davis earned the award for implementing diagnostic and treatment guidelines — including specific medications and risk-reduction therapies — that can reduce deaths and disabilities and speed recovery from stroke.

“This award demonstrates our commitment to using the latest evidence-based clinical approaches to improve outcomes for patients,” said Ann Madden Rice, chief executive officer of UC Davis Medical Center. “We owe this recognition to the multidisciplinary team of physicians, nurses, imaging specialists, educators and rehabilitation therapists in our stroke program and their determination to make sure our patients have access to the most current care and resources.”

The UC Davis Medical Center Stroke Program includes a designated team of stroke specialists who provide acute inpatient hospital care as well as outpatient management of cerebrovascular disease. Patients receive aggressive medical care and treatment, including thrombolytic therapy, interventional neuroradiologic techniques and new medications under clinical investigation.

“We are pleased to recognize the team at UC Davis Medical Center for their commitment and dedication to stroke care,” said Deepak L. Bhatt, national chairman of the Get With The Guidelines steering committee. “Studies show that hospitals that consistently follow Get With The Guidelines quality improvement measures can reduce patients’ length of stays and 30-day readmission rates and reduce disparity gaps in care.”

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Stroke treatment, outcomes improve at hospitals taking part in UCLA-led initiative


Study finds jump in patients receiving clot-busting drug within “golden hour.”

Gregg Fonarow, UCLA

Administering a clot-dissolving drug to stroke victims quickly — ideally within the first 60 minutes after they arrive at a hospital emergency room — is crucial to saving their lives, preserving their brain function and reducing disability.

Given intravenously, tPA (tissue plasminogen activator) is currently the only Food and Drug Administration–approved therapy shown to improve outcomes for patients suffering acute ischemic stroke, which affects some 800,000 Americans annually.

Now, a UCLA-led study demonstrates that hospitals participating in the “Target: Stroke” national quality-improvement program have markedly increased the speed with which they treat stroke patients with tPA. Researchers looked at more than 1,000 hospitals participating in the initiative, which was conceived by UCLA faculty and is conducted in collaboration with the American Heart Association/American Stroke Association.

The findings of the study are published in today’s (April 23) issue of JAMA, the Journal of the American Medical Association.

The researchers report that at participating hospitals, the average time it took to deliver tPA to patients fell from 74 minutes to 59 minutes. This speedier treatment, they said, was accompanied by improved outcomes, including reduced mortality, fewer treatment complications and a greater likelihood that patients would go home after leaving the hospital instead of being referred to a skilled nursing facility for advanced rehabilitation.

“These findings reinforce the importance and clinical benefits of faster administration of intravenous tPA. Through this national initiative, more patients were able to be treated with this beneficial therapy and in a safer, more effective fashion,” said first author Dr. Gregg C. Fonarow, UCLA’s Eliot Corday Professor of Cardiovascular Medicine and Science and director of the Ahmanson–UCLA Cardiomyopathy Center at the David Geffen School of Medicine at UCLA.

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Study IDs new cause of brain bleeding immediately after stroke


Research by UC Irvine, Salk Institute points to novel therapies for minimizing damage.

Dritan Agaliu, UC Irvine

By discovering a new mechanism that allows blood to enter the brain immediately after a stroke, researchers at UC Irvine and the Salk Institute have opened the door to new therapies that may limit or prevent stroke-induced brain damage.

 A complex and devastating neurological condition, stroke is the fourth-leading cause of death and primary reason for disability in the U.S. The blood-brain barrier is severely damaged in a stroke and lets blood-borne material into the brain, causing the permanent deficits in movement and cognition seen in stroke patients.

Dritan Agalliu, assistant professor of developmental & cell biology at UC Irvine, and Axel Nimmerjahn of the Salk Institute for Biological Studies developed a novel transgenic mouse strain in which they use a fluorescent tag to see the tight, barrier-forming junctions between the cells that make up blood vessels in the central nervous system. This allows them to perceive dynamic changes in the barrier during and after strokes in living animals.

While observing that barrier function is rapidly impaired after a stroke (within six hours), they unexpectedly found that this early barrier failure is not due to the breakdown of tight junctions between blood vessel cells, as had previously been suspected. In fact, junction deterioration did not occur until two days after the event.

Instead, the scientists reported dramatic increases in carrier proteins called serum albumin flowing directly into brain tissue. These proteins travel through the cells composing blood vessels – endothelial cells – via a specialized transport system that normally operates only in non-brain vessels or immature vessels within the central nervous system. The researchers’ work indicates that this transport system underlies the initial failure of the barrier, permitting entry of blood material into the brain immediately after a stroke (within six hours).

“These findings suggest new therapeutic directions aimed at regulating flow through endothelial cells in the barrier after a stroke occurs,” Agalliu said, “and any such therapies have the potential to reduce or prevent stroke-induced damage in the brain.”

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Bone marrow stem cells show promise in stroke treatment


UC Irvine analysis reveals that they trigger repair mechanisms, limit inflammation.

Steven Cramer, UC Irvine

Stem cells culled from bone marrow may prove beneficial in stroke recovery, scientists at UC Irvine’s Sue & Bill Gross Stem Cell Research Center have learned.

In an analysis of published research, neurologist Dr. Steven Cramer and biomedical engineer Weian Zhao identified 46 studies that examined the use of mesenchymal stromal cells – a type of multipotent adult stem cells mostly processed from bone marrow – in animal models of stroke. They found MSCs to be significantly better than control therapy in 44 of the studies.

Importantly, the effects of these cells on functional recovery were robust regardless of the dosage, the time the MSCs were administered relative to stroke onset or the method of administration. (The cells helped even if given a month after the event and whether introduced directly into the brain or injected via a blood vessel.)

“Stroke remains a major cause of disability, and we are encouraged that the preclinical evidence shows [MSCs’] efficacy with ischemic stroke,” said Cramer, a professor of neurology and leading stroke expert. “MSCs are of particular interest because they come from bone marrow, which is readily available, and are relatively easy to culture. In addition, they already have demonstrated value when used to treat other human diseases.”

He noted that MSCs do not differentiate into neural cells. Normally, they transform into a variety of cell types, such as bone, cartilage and fat cells. “But they do their magic as an inducible pharmacy on wheels and as good immune system modulators, not as cells that directly replace lost brain parts,” he said.

In an earlier report focused on MSC mechanisms of action, Cramer and Zhao reviewed the means by which MSCs promote brain repair after stroke. The cells are attracted to injury sites and, in response to signals released by these damaged areas, begin releasing a wide range of molecules. In this way, MSCs orchestrate numerous activities: blood vessel creation to enhance circulation, protection of cells starting to die, growth of brain cells, etc. At the same time, when MSCs are able to reach the bloodstream, they settle in parts of the body that control the immune system and foster an environment more conducive to brain repair.

“We conclude that MSCs have consistently improved multiple outcome measures, with very large effect sizes, in a high number of animal studies and, therefore, that these findings should be the foundation of further studies on the use of MSCs in the treatment of ischemic stroke in humans,” said Cramer, who is also clinical director of the Sue & Bill Gross Stem Cell Research Center.

The analysis appears in the April 8 issue of Neurology. Quynh Vu, Kate Xie and Mark Eckert of UC Irvine contributed to the project, which received support from UC Irvine’s Institute for Clinical & Translational Science through the National Center for Research Resources (grant 5M011 RR-00827-29) and the National Institutes of Health (grants K24HD074722 and R01 NS059909).

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