Posts tagged stroke

ScienceDaily (July 17, 2012) — A stroke can weaken one side of the body, raising the dangerous possibility of unstable walking and debilitating falls. Physical therapy can help patients learn to shift their body weight slightly to the weaker, stroke-affected side to help regain balance, but for some patients, the weakness returns after their therapy ends.

University of Illinois at Chicago physical therapy professor Alexander Aruin has developed an inexpensive, simple way to deal with the problem, training the brain to rebalance body weight using a simple shoe insole he calls a “compelled body weight shift.” It slightly lifts and tilts the body toward the stroke-affected side, restoring balance without the patient having to think about it.

Aruin along with colleagues at UIC and Marianjoy Rehabilitation Hospital in Wheaton, Ill., studied two patient groups: one group at UIC who just had strokes, and one at Marianjoy who had strokes over a year ago.

"We tried a purely biomechanical approach," Aruin said. "We mechanically lifted the healthy side so the patient cannot resist. The mechanics force body weight to where it is distributed almost 50/50. When patients ambulate in such a condition, they learn how to bear weight equally through both extremities. It’s quite simple."

The two test groups followed slightly different protocols and were tested for various lengths of time. Their results were measured against those of control groups, who did not get the small therapeutic shoe insole, which measures less than half an inch thick. patients in all groups also received standard post-stroke physical therapy.

After the testing period ended, patients stopped using the insole. About three months afterward they were tested again to see if they retained the ability to keep their balance. Aruin and his colleagues found that physical therapy helped both the insole-user and control groups, but the insole group got an added boost.

"They showed more symmetrical body weight distribution and bore more weight on their affected side, and their gait velocity improved," he said. "The outcome looks promising. The technique is very simple and inexpensive and has potential, which is exciting."

Aruin hopes other physical therapists use the simple devices on stroke patients to see if they too benefit from it. His associates are also considering ways to use the insole to improve posture in post-stroke patients.

Source: Science Daily

July 10, 2012

The ability for substances to pass through the blood-brain barrier is increased after adult stroke, but not after neonatal stroke, according to a new study the UCSF that will be published July 11 in the Journal of Neuroscience.

The blood-brain barrier is selectively permeable and blocks unwanted molecules from entering into the brain. The selectivity is achieved through fine coordination in function of many transporting systems in endothelial cells, which line the interior of blood vessels, and communication between endothelial cells and several types of cells in the brain. When blood flow in an artery to the brain is blocked by a blood clot, as occurs in arterial stroke, brain energy metabolism is compromised, and ion and other transporting systems malfunction, leading to blood-brain disruption.

The new finding suggests, the researchers said, that drugs used to treat stroke need to be tailored to the specific makeup of the neonate blood-brain barrier.

"How the blood-brain barrier responds to stroke in adults and neonates currently is poorly understood,” said senior author Zinaida Vexler, PhD, director of research at the Neonatal Brain Disorders Center at the Department of Neurology at UCSF.

"The assumption has been that at birth the blood-brain barrier is immature and thus permeable and that a neonatal brain responds in the same way to injury as an adult brain. This would mean that, after a stroke, the blood-brain barrier is an open gate and different molecules could go in and out, like a floodgate,” she said. “But in neonatal stroke the situation is very different, and this study shows that the neonatal brain has the ability to protect itself by limiting blood-brain barrier permeability.”

In the study, the scientists examined the structural and functional aspects of the blood-brain barrier in live rats that had acute stroke, and found that the blood-brain barrier was markedly more intact in neonatal rats than in adult rats.

The study compared vascular responses to injury in an adult arterial stroke model and an age-appropriate model of neonatal arterial stroke using several blood-brain barrier permeability procedures. Injected molecules that remained in blood vessels under normal conditions leaked into the injured tissue of the adult rats, but the same molecules remained in vessels of neonatal injured rats within 24 hours after injury.

Importantly, the vessels remained intact for molecules of various sizes. The study also showed a different composition of several barrier structural proteins in neonates versus adults, as well as a differential response to stroke at both ages, findings that likely are to contribute to the higher resistance of the neonatal blood-brain barrier after stroke. The study also showed age-related differences in communication between circulating white blood cells and the blood-brain barrier. Neutrophils — a subtype of leukocytes — stuck to injured vasculature and entered the adult brain shortly after stroke, releasing toxic molecules and reactive oxidants and producing damage. In contrast, only a few neutrophils were able to enter the injured neonatal brain. However, pharmacological change – in communication of neutrophils with injured vessels in the neonate made injury worse.

"This study is a very critical step towards developing therapeutics, but these findings are a tip of the iceberg and a lot is still to be learned," said Vexler. "We’re moving to characterize the potential for neonatal repair. Some brain damage can’t be diagnosed early, but might show up later. Now we are experimenting with postponing certain treatments or tweaking some signaling mechanisms to see if we can enhance the capacity of the immature brain to repair itself."

Provided by University of California, San Francisco

Source: medicalxpress.com

July 9, 2012

A study of patients with stroke admitted to English National Health Service public hospitals suggests that patients who were hospitalized on weekends were less likely to receive urgent treatments and had worse outcomes, according to a report published Online First by Archives of Neurology.

Studies from other countries have suggested higher mortality in patients who were admitted to the hospital on weekends for a variety of medical conditions, a phenomenon known as “the weekend effect.” However, other studies have not identified an association between the day of admission and mortality rates due to stroke, so the debate over “the weekend effect” continues, according to the study background.

William L. Palmer, M.A., M.Sc., of Imperial College and the National Audit Office, and colleagues conducted a study of patients admitted to hospitals with stroke from April 2009 through March 2010, accounting for 93,621 admissions.

Performance across five of six measures was lower on weekends, with one of the largest disparities seen in rates of same-day brain scans (43.1 percent on weekends compared with 47.6 percent on weekdays). Also, the rate of seven-day, in-hospital mortality for Sunday admissions was 11 percent compared with a mean (average) of 8.9 percent for weekday admissions, according to study results.

"We calculated that approximately 350 potentially avoidable in-hospital deaths occur within seven days each year and that an additional 650 people could be discharged to their usual place of residence within 56 days if the performance seen on weekdays was replicated on weekends," the authors comment.

Provided by JAMA and Archives Journals

Source: medicalxpress.com

July 4, 2012

(Medical Xpress) — Researchers at the UCL Institute of Neurology have found that giving the drug rotigotine as a skin patch can improve inattention in some stroke patients.

Hemi-spatial neglect, a severe and common form of inattention that can be caused by brain damage following a stroke, is one of the most debilitating symptoms, frequently preventing patients from living independently. When the right side of the brain has suffered damage, the patient may have little awareness of their left-hand side and have poor memory of objects that they have seen, leaving them inattentive and forgetful. Currently there are few treatment options.

The randomised control trial took 16 patients who had suffered a stroke on the right-hand side of their brain and assessed to see whether giving the drug rotigotine improved their ability to concentrate on their left-hand side. The results showed that even with treatment for just over a week, patients who received the drug performed significantly better on attention tests than when they received the placebo treatment.

Rotigotine acts by stimulating receptors on nerve cells for dopamine, a chemical normally produced within the brain.

Professor Masud Husain who led the study at the Institute of Neurology at UCL says: “Inattention can have a devastating effect on stroke patients and their families. It impacts on all aspects of their lives. If the results of our clinical trial are replicated in further, larger studies, we will have overcome a major hurdle towards providing a new treatment for this important consequence of stroke.

“Milder forms of inattention occur in other brain disorders, across all ages - from ADHD (attention deficit hyperactivity disorder) to Parkinson’s disease. Our findings show that it is possible to alter attention by using a drug that acts at specific receptors in the brain, and therefore have implications for understanding the mechanisms that might cause inattention in conditions other than stroke.”

Provided by University College London

Source: medicalxpress.com

July 2, 2012

After stroke, patients often suffer from dysphagia, a swallowing disorder that results in greater healthcare costs and higher rates of complications such as dehydration, malnutrition, and pneumonia. In a new study published in the July issue of Restorative Neurology and Neuroscience, researchers have found that transcranial direct current stimulation (tDCS), which applies weak electrical currents to the affected area of the brain, can enhance the outcome of swallowing therapy for post-stroke dysphagia.

"Our pilot study demonstrated that ten daily sessions of tDCS over the affected esophageal motor cortex of the brain hemisphere affected by the stroke, combined with swallowing training, improved post-stroke dysphagia. We observed long-lasting effects of anodal tDCS over three months,” reports lead investigator Nam-Jong Paik, MD, PhD, of the Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Sixteen patients with acute post-stroke dysphagia were enrolled in the trial. They showed signs of swallowing difficulties such as reduced tongue movements, coughing and choking during eating, and vocal cord palsy. Patients underwent ten 30-minute sessions of swallowing therapy and were randomly assigned to a treatment or control group. Both groups were fitted with an electrode on the scalp, on the side of the brain affected by the stroke, and in the region associated with swallowing. For the first 20 minutes of their sessions, tDCS was administered to the treatment group and then swallowing training alone continued for the remaining 10 minutes. In the control group, the direct current was tapered down and turned off after thirty seconds. Outcomes were measured before the experiment, just after the experiment, and again three months after the experiment. A patient from each group underwent a PET scan at before and just after the treatment to view the effect of the treatment on metabolism.

All patients underwent interventions without any discomfort or fatigue. There were no significant differences in age, sex, stroke lesion site, or extent of brain damage. Evaluation just after the conclusion of the sessions found that dysphagia improved for all patients, without much difference between the two groups. However, at the three month follow-up, the treatment group showed significantly greater improvement than the control group.

In the PET study, there were significant differences in cerebral metabolism between the first PET scan and the second PET scan in the patient who had received tDCS. Increased glucose metabolism was observed in the unaffected hemisphere, although tDCS was only applied to the affected hemisphere, indicating that tDCS might activate a large area of the cortical network engaged in swallowing recovery rather than just the areas stimulated under the electrode.

"The results indicate that tDCS can enhance the outcome of swallowing therapy in post-stroke dysphagia," notes Dr. Paik. "As is always the case in exploratory research, further investigation involving a greater number of patients is needed to confirm our results. It will be important to determine the optimal intensity and duration of the treatment to maximize the long-term benefits."

Provided by IOS Press

Source: medicalxpress.com

ScienceDaily (June 22, 2012) — The gene p53 is the most commonly mutated gene in cancer. p53 is dubbed the “guardian of the genome” because it blocks cells with damaged DNA from propagating and eventually becoming cancerous. However, new research led by Ute M. Moll, M.D., Professor of Pathology at Stony Brook University School of Medicine, and colleagues, uncovers a novel role for p53 beyond cancer in the development of ischemic stroke. The research team identified an unexpected critical function of p53 in activating necrosis, an irreversible form of tissue death, triggered during oxidative stress and ischemia.

Dr. Ute Moll, Professor of Pathology, has uncovered a novel role for p53 in the development of ischemic stroke. (Credit: Image courtesy of Stony Brook Medicine)

The findings are detailed online in Cell.

Ischemia-associated oxidative damage leads to irreversible necrosis which is a major cause of catastrophic tissue loss. Elucidating its signaling mechanism is of paramount importance. p53 is a central cellular stress sensor that responds to multiple insults including oxidative stress and is known to orchestrate apoptotic and autophagic types of cell death. However, it was previously unknown whether p53 can also activate oxidative stress-induced necrosis, a regulated form of cell death that depends on the mitochondrial permeability transition pore (PTP) pore.

"We identified an unexpected and critical function of p53 in activating necrosis: In response to oxidative stress in normal healthy cells, p53 accumulates in the mitochondrial matrix and triggers the opening of the PTP pore at the inner mitochondrial membrane, leading to collapse of the electrochemical gradient and cell necrosis," explains Dr. Moll. "p53 acts via physical interaction with the critical PTP regulator Cyclophylin D (CypD). This p53 action occurs in cultured cells and in ischemic stroke in mice. "

Of note, they found in their model that when the destructive p53-CypD complex is blocked from forming by using Cyclosporine-A type inhibitors, the brain tissue is strongly protected from necrosis and stroke is prevented.

"The findings fundamentally expand our understanding of p53-mediated cell death networks," says Dr. Moll. "The data also suggest that acute temporary blockade of the destructive p53-CypD complex with clinically well-tolerated Cyclosporine A-type inhibitors may lead to a therapeutic strategy to limit the extent of an ischemic stroke in patients."

"p53 is one of the most important genes in cancer and by far the most studied," says Yusuf A. Hannun, M.D., Director of the Stony Brook University Cancer Center, Vice Dean for Cancer Medicine, and the Joel Kenny Professor of Medicine at Stony Brook. "Therefore, this discovery by Dr. Moll and her colleagues in defining the mechanism of a new p53 function and its importance in necrotic injury and stoke is truly spectacular."

Dr. Moll has studied p53 for 20 years in her Stony Brook laboratory. Her research has led to numerous discoveries about the function of p53 and two related genes. For example, previous to this latest finding regarding p53 and stroke, Dr. Moll identified that p73, a cousin to p53, steps in as a tumor suppressor gene when p53 is lost and can stabilize the genome. She found that p73 plays a major developmental role in maintaining the neural stem cell pool during brain formation and adult learning. Her work also helped to identify that another p53 cousin, called p63, has a critical surveillance function in the male germ line and likely contributed to the evolution of humans and great apes, enabling their long reproductive periods.

Source: Science Daily

ScienceDaily (June 11, 2012) — Researchers at the University of Missouri have demonstrated the effectiveness of a potential new therapy for stroke patients in an article published in the journal Molecular Neurodegeneration. Created to target a specific enzyme known to affect important brain functions, the new compound being studied at MU is designed to stop the spread of brain bleeds and protect brain cells from further damage in the crucial hours after a stroke.

In a model of induced stroke in mice, MU researchers have shown the success of a treatment in stopping further bleeding in the brain after a stroke (above). The outlined area shows the stroke damage. (Credit: Image courtesy of University of Missouri School of Medicine)

Stroke is a leading cause of death in the U.S. with more than 800,000 deaths occurring each year from stroke and other cardiac events. Other than surgery, existing emergency treatments for stroke victims such as the use of a tissue plasminogen activator (tPA) must be administered within hours of the stroke onset because of the risk for brain hemorrhaging. The injectable medication can only be used to treat the most common type of stroke that occurs when blood clots block blood flow to the brain, called ischemic stroke.

"For a stroke victim, time is a matter of life and death. While we are still in the research phase for this type of compound, we believe it could be combined with tPA in the future to buy ischemic stroke patients a longer window of time to receive emergency treatment," said Zezong Gu, MD, PhD, the article’s corresponding author and assistant professor of pathology and anatomical sciences at the MU School of Medicine. The new compound being studied also has potential for use in patients experiencing hemorrhagic stroke, which is a less common type of stroke caused by bleeding within the brain, Gu said.

MU researchers collaborated with a team at the University of Notre Dame to study the effects of the new compound, a thiirane class of gelatinase selective inhibitors, on the function of a type of matrix metalloproteinase (MMP) enzyme, particularly MMP-9. MMP-9 is part of a group of more than 20 enzymes or MMPs that are known to contribute to many key pathological events in the brain after stroke, traumatic brain injury and other neurodegenerative events.

In 2005, Gu served as a lead author on a research paper published in the Journal of Neuroscience that identified MMP-9 as a promising target for development of therapeutic drugs for stroke patients. Since then, his lab at MU medical school’s Center for Translational Neuroscience has been studying the function of MMP enzymes and how to inhibit the harmful effects of MMP-9.

"MMPs play a role in the structure of blood vessels in the brain and are also needed in the interactions between cells during development and tissue remodeling," Gu said. "Unregulated, the activity of these enzymes contributes to neurological disorders and stroke. With this compound, we’ve now confirmed a potential method to rescue the blood vessels from the damaging effects of MMP-9 and protect neurons at the same time."

MU researchers successfully used a model of ischemic stroke in mice and studied the effects of the MMP-9 inhibitor compound on brain activity after a stroke.

"Our lab at the Center for Translational Neuroscience is one of only a few in the United States that has successfully induced a blood clot in the brains of mice," said Jiankun Cui, MD, the article’s lead author and assistant professor of pathology and anatomical sciences at the MU School of Medicine. "To be able to study the effectiveness of this potential new treatment under these conditions provides us with a highly unique set of data showing this compound can disrupt key harmful pathological events that occur after a stroke."

Source: Science Daily

June 5, 2012

Researchers studying stroke patients have found a strong association between impairments in a network of the brain involved in emotional regulation and the severity of post-stroke depression. Results of the study are published online in the journal Radiology.

"A third of patients surviving a stroke experience post-stroke depression (PSD),” said lead researcher Igor Sibon, M.D., Ph.D., professor of neurology at the University of Bordeaux in Bordeaux, France. “However, studies have failed to identify a link between lesions in the brain caused by ischemia during a stroke and subsequent depression.”

Instead of looking for dysfunction in a specific area of the brain following a stroke, Dr. Sibon’s study was designed to assess a group of brain structures organized in a functional network called the default-mode network (DMN). Modifications of connectivity in the DMN, which is associated with internally generated thought processes, has been observed in depressive patients.

"The default-mode network is activated when the brain is at rest," Dr. Sibon said. "When the brain is not actively involved in a task, this area of the brain is engaged in internal thoughts involving self-related memory retrieval and processing.”

In the study, 24 patients between the ages of 18 and 80 underwent resting-state functional magnetic resonance imaging (fMRI) 10 days after having mild to moderate ischemic stroke. An fMRI imaging study measures metabolic changes in specific areas of the brain. Although many fMRI exams are designed to measure brain changes while a patient performs a specific task, during a resting-state fMRI exam, patients lie motionless.

The patients, which included 19 men and five women, were also clinically evaluated 10 days and three months post-stroke to determine the presence and severity of depression and anxiety symptoms. At three months post-stroke, patients were evaluated for depression using the DSM-IV diagnostic classification system.

Using the DSM-IV criteria, 10 patients had minor to moderate depression, and 14 patients had no depression. Results of the fMRI exams revealed an association between modifications of connectivity in the DMN 10 days after stroke and the severity of depression three months post-stroke.

"We found a strong association between early resting-state network modifications and the risk of post-stroke mood disorders," Dr. Sibon said. "These results support the theory that functional brain impairment following a stroke may be more critical than structural lesions."

According to Dr. Sibon, the widespread chemical changes that result from a stroke may lead to the modification of connectivity in brain networks such as the DMN. He said results of his study may contribute to the clinical management of stroke patients by providing an opportunity to investigate the effects of a variety of treatments on patients whose fMRI results immediately post-stroke indicate impaired connectivity in the DMN.

Provided by Radiological Society of North America

Source: medicalxpress.com

May 24, 2012

(Medical Xpress) — Patients given a clot-busting drug within six hours of a stroke are more likely to make a better recovery than those who do not receive the treatment, new research has found.

The trial was set up in 2000 by the University of Sydney’s Professor Richard Lindley, while he was employed at the University of Edinburgh.

The study of more than 3000 patients is the world’s largest trial of the drug rt-PA and was coordinated at the University of Edinburgh. Since coming to Sydney Medical School in 2003, Professor Lindley has continued as the co-principal investigator of the research.

The findings of the study are published today in The Lancet, alongside an analysis of all other trials of the drug carried out in the past 20 years.

The trial found that following treatment with the drug rt-PA, which is given intravenously to patients who have suffered an acute ischaemic stroke, more patients were able to look after themselves.

"The trial results, together with the updated review, mean that rt-PA can now be offered to a much wider group of patients presenting with stroke", Professor Lindley said.

A patient’s chances of making a complete recovery within six months of a stroke were also increased.

An ischaemic stroke happens when the brain’s blood supply is interrupted by a blood clot. The damage caused can be permanent or fatal.

Researchers now know that for every 1000 patients given rt-PA within three hours of stroke, 80 more will survive and live without help from others than if they had not been given the drug.

The benefits of using rt-PA do come at a price, say researchers. Patients are at risk of death within seven days of treatment because the drug can cause a secondary bleed in the brain. The research team concluded that the benefits were seen in a wide variety of patients, despite the risks.

Stroke experts stress that these mortality figures need to be viewed in the context of deaths from stroke. Without treatment, one third of people who suffer a stroke die, with another third left permanently dependent and disabled.

Researchers say the threat of death and disability means many stroke patients are prepared to take the early risks of being treated with rt-PA to avoid being disabled.

The authors conclude that for those who do not experience bleeding, the drug improves patients’ longer term recovery.

About half of those who took part in the trial were over 80.

"The trial underlines the benefits of treating patients with the drug as soon as possible and provides the first reliable evidence that treatment is effective for those aged 80 and over," Professor Lindley said.

The study also found no reason to restrict use of rt-PA - also known as alteplase - on the basis of how severe a patient’s stroke has been.

Chief investigator Professor Peter Sandercock of the University of Edinburgh’s Centre for Clinical Brain Sciences said: “Our trial shows that it is crucial that treatment is given as fast as possible to all suitable patients.”

Provided by University of Sydney

Source: medicalxpress.com