Scientists confirm correlation between malignant hyperthermia and exertional heat stroke

New research published online in The FASEB Journal may ultimately help athletes and trainers better understand who may be more at risk for heat stroke. In the report, scientists use animals to show that there is a link between the susceptibility to malignant hyperthermia (MH) and exertional heat stroke.

“Global warming and increasing frequency of heat waves, which are particularly dangerous in large urban areas, in future years will represent a reason of concern for human health,” said Feliciano Protasi, Ph.D., a researcher involved in the work at the Department of Neuroscience, Imaging and Clinical Sciences, University G. d’Annunzio, Chieti, Italy. “However, in spite of the increased incidence, severity and life-threatening nature of heat stroke, there are currently no safe and effective drug interventions to protect or reverse this deadly syndrome. We hope that our study will contribute to develop preventive measures and/or acute treatments for heat stroke caused by environmental heat and physical exertion.”

Scientists used three groups of mice to reach their conclusion. The first two groups (RYR1Y522S/WT and CASQ1-null mice) had altered genes that made them susceptible to lethal hyperthermic crises when exposed to anesthetics, while the third group was normal (wild-type mice). When the three sets of mice were exposed to a protocol of exertional stress (incremental running at 34 degrees Celsius and 40 percent humidity) the MH-susceptible mice (but not the normal mice) suffered lethal overheating episodes.

“This work addresses a dangerous, often lethal, physiological maladjustment that animals and humans can undergo,” said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal. “The door now stands open to finding effective preventative drugs.”

New Study Finds Cardiac PET/CT Imaging Effective In Detecting Calcium Blockages, Assessing Heart Attack Risk

Many people who experience chest pain but don’t have a heart attack breathe a big sigh of relief when a stress test comes back negative for blockages in their blood vessels.

But a new study by cardiac researchers at the Intermountain Medical Center Heart Institute in Salt Lake City found they may not be off the hook after all.

Researchers studied 658 men and women between the ages of 57 and 77 who passed a stress test for blocked arteries and who were later found to have calcium in their arteries after being screened by imaging technology that measured their total coronary artery calcification.

They found that five percent of patients who passed their stress test and later tested high for calcium in their arteries — 31 of 658 patients — went on to have an adverse cardiac event within one year. Such events included death, heart attack and stroke.
Researchers say there is something more doctors can do to assess a patient’s risk of future heart attack: check the calcium — a sign of plaque buildup — in a patient’s arteries.

“We now have the ability to better measure coronary artery calcification,” says Viet Le, MPAS, PA-C, lead author of the Intermountain Medical Center Heart Institute study, who will deliver results at the American Heart Association Scientific Session in New Orleans on Nov 14, at 10:45 am, CST.

“People say, ‘I’m good. They gave me a stress test,’” said Le. “But it doesn’t tell the whole story. The story it tells is that on that day your engine — your heart — passed the test. Some of these people die within a year from a heart attack.”
Cardiac experts have known for years that calcium left by plaque is a good marker of heart disease, but there was not good imaging technology to measure it without exposing the patient to too much radiation, Le said. That changed about five years ago.
PET/CT, an advanced nuclear imaging technology that combines positron emission tomography (PET) and computed tomography (CT) in one machine, allows physicians doing a chemical stress test to also measure coronary artery calcification.

Calcification cannot be reversed, but the plaque that causes it can be reduced or stabilized with proper medication, diet and exercise.

Researchers found that 33 patients in the study, or five percent, had no or mild calcification, and they had no cardiac events. But there was a significant correlation between the amount of calcium and the occurrence of cardiac events in the remainder of the patients.

Twelve of 309 (3.88 percent) patients with moderate calcification had a cardiac event within a year, 10 of 190 (5.26 percent) with severe calcification had a cardiac event within a year, and nine of 126 (7.14 percent) with very severe calcification had a cardiac event within a year. In total, 16.28 percent of calcified patients in the study had a heart event.

The results confirmed for Le the value of assessing calcification in patients suspected of having clogged arteries.

“Right now, it’s a neglected tool that should better be utilized,” he said.

Neighborhoods Important Factor In Risk Of Stroke For All Races

A higher neighborhood advantage, or socioeconomic status, of where a person lives contributes to a lower risk of having a stroke no matter the person’s race, according to findings published in the Oct. 14 online issue of Neurology®, the medical journal of the American Academy of Neurology.

The report from the University of Alabama at Birmingham REasons for Geographic And Racial Differences in Stroke study shows this effect is the same for black and white adults, both men and women.

“More blacks than whites in the United States have strokes and die from strokes,” saidVirginia Howard, Ph.D., lead author of the study and professor in the UAB School of Public Health Department of Epidemiology. “More people who live in the Southeastern area known as the stroke belt have stroke and die from stroke compared to those who live in the rest of the United States.”

This study showed that residents in more disadvantaged neighborhoods had greater stroke risk than those who lived in more advantaged neighborhoods. The neighborhood index is composed of six factors, including a higher value of housing units and higher proportion of residents employed in professional occupations. A higher score in all of these categories leads to a higher advantaged neighborhood.

The observation was true even after adjustment for age, race, sex and region of the country. But after adjustment for other stroke risk factors, there was no association between the level of the neighborhood advantage and stroke risk, suggesting that those living in more disadvantaged neighborhoods are more likely to develop risk factors including hypertension, diabetes and smoking. Because of being more likely to develop these risk factors, they are at higher risk of stroke.

“These results are consistent with other evidence showing that factors associated with living in more disadvantaged neighborhoods contribute to stroke risk. However, it is difficult to separate the influence of neighborhood characteristics from characteristics of the individuals living in the neighborhood,” Howard said. “Many social and behavioral risk factors, such as smoking and physical inactivity, are more prevalent in the less advantaged neighborhoods. Greater attention needs to be paid to risk factor management strategies in disadvantaged neighborhoods in order to make a difference in preventing stroke on an individual level.”

The current study looked at measures of the neighborhood advantage where people live to determine whether these factors contributed to future stroke risk. Data came from the REGARDS study, a national random sample of the general population with more people selected from the stroke belt and about half black, half white.

The study involved 24,875 people with an average age of 65 who had not had a stroke at the start of the study. The participants were divided into four neighborhood groups, ranging from lowest level of advantage to the highest. The participants were followed for an average of seven and a half years. During that time, 929 people had a stroke.

This study has advantages over other studies in that it includes individuals of low, middle, upper-middle and high individual wealth across 1,833 urban and rural counties in the United States, and a large number of both blacks and whites. Other stroke risk factors were measured prior to the stroke.

New Hope For Recovery Of Hand Movement For Stroke Patients

Stroke patients are starting a trial of a new electronic device to recover movement and control of their hand.

Neuroscientists at Newcastle University have developed the device, the size of a mobile phone, which delivers a series of small electrical shocks followed by an audible click to strengthen brain and spinal connections.

The experts believe this could revolutionise treatment for patients, providing a wearable solution to the effects of stroke.

Following successful work in primates and healthy human subjects, the Newcastle University team are now working with colleagues at the prestigious Institute of Neurosciences, Kolkata, India, to start the clinical trial. Involving 150 stroke patients, the aim of the study is to see whether it leads to improved hand and arm control.

Stuart Baker, Professor of Movement Neuroscience at Newcastle University who has led the work said: “We were astonished to find that a small electric shock and the sound of a click had the potential to change the brain’s connections. However, our previous research in primates changed our thinking about how we could activate these pathways, leading to our study in humans.”

Recovering hand control

Publishing today in the Journal of Neuroscience, the team report on the development of the miniaturised device and its success in healthy patients at strengthening connections in the reticulospinal tract, one of the signal pathways between the brain and spinal cord.

This is important for patients as when people have a stroke they often lose the major pathway found in all mammals connecting the brain to spinal cord. The team’s previous work in primates showed that after a stroke they can adapt and use a different, more primitive pathway, the reticulospinal tract, to recover.

However, their recovery tends to be imbalanced with more connections made to flexors, the muscles that close the hand, than extensors, those that open the hand. This imbalance is also seen in stroke patients as typically, even after a period of recuperation, they find that they still have weakness of the extensor muscles preventing them opening their fist which leads to the distinctive curled hand.

Partial paralysis of the arms, typically on just one side, is common after stroke, and can affect someone’s ability to wash, dress or feed themselves. Only about 15% of stroke patients spontaneously recover the use of their hand and arm, with many people left facing the rest of their lives with a severe level of disability.

Senior author of the paper, Professor Baker added: “We have developed a miniaturised device which delivers an audible click followed by a weak electric shock to the arm muscle to strengthen the brain’s connections. This means the stroke patients in the trial are wearing an earpiece and a pad on the arm, each linked by wires to the device so that the click and shock can be continually delivered to them.

“We think that if they wear this for 4 hours a day we will be able to see a permanent improvement in their extensor muscle connections which will help them gain control on their hand.”

Improving connections

The techniques to strengthen brain connections using paired stimuli are well documented, but until now this has needed bulky equipment, with a mains electric supply.

The research published today is a proof of concept in human subjects and comes directly out of the team’s work on primates. In the paper they report how they pair a click in a headphone with an electric shock to a muscle to induce the changes in connections either strengthening or weakening reflexes depending on the sequence selected. They demonstrated that wearing the portable electronic device for seven hours strengthened the signal pathway in more than half of the subjects (15 out of 25).

Professor Stuart Baker added: “We would never have thought of using audible clicks unless we had the recordings from primates to show us that this might work. Furthermore, it is our earlier work in primates which shows that the connections we are changing are definitely involved in stroke recovery.”

The work has been funded through a Milstein Award from the Medical Research Council and the Wellcome Trust.

The clinical trial is just starting at the Institute of Neurosciences, Kolkata, India. The country has a higher rate of stroke than Western countries which can affect people at a younger age meaning there is a large number of patients. The Institute has strong collaborative links with Newcastle University enabling a carefully controlled clinical trial with results expected at the end of this year.

Biomarkers May Help Better Predict Who Will Have a Stroke

People with high levels of four biomarkers in the blood may be more likely to develop a stroke than people with low levels of the biomarkers, according to a study published in the August 24, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“Identifying people who are at risk for stroke can help us determine who would benefit most from existing or new therapies to prevent stroke,” said study author Ashkan Shoamanesh, MD, of McMaster University in Hamilton, Canada, and a member of the American Academy of Neurology. “Future research could also investigate whether lowering the levels of these biomarkers or blocking their action could be a way to prevent strokes. However, our study does not provide evidence that these markers are validated well enough to be implemented in clinical practice.”

For the study, researchers from the Boston University Schools of Medicine and Public Health measured the levels of 15 biomarkers associated with inflammation in the blood of people from the Framingham Heart Study Offspring Cohort who had never had a stroke. The 3,224 participants were an average age of 61 at the start of the study and were followed for an average of nine years. During that time, 98 people had a stroke.

Of the 15 biomarkers, four were associated with an increased risk of stroke. People with elevated homocysteine were 32 percent more likely to have a stroke. Those with high vascular endothelial growth factor were 25 percent more likely; those with high ln-C reactive protein were 28 percent more likely; and those with high ln-tumor necrosis factor receptor 2 were 33 percent more likely to have a stroke during the study.

Adding these four biomarkers to an existing method of predicting a person’s stroke risk based on factors such as age, sex, cholesterol and blood pressure, called the Framingham Stroke Risk Profile, improved the ability to predict who would develop a stroke.
Shoamanesh noted that the study was observational. It shows a relationship between high levels of the biomarkers and stroke; it does not establish that the high levels cause stroke. He also noted that the biomarkers were measured only once and researchers did not account for infections, chronic diseases or other conditions that could have affected the results. In addition, study participants are mainly of European ancestry and the results may not apply to other populations.

The study was supported by Framingham Heart Study’s National Heart, Lung, and Blood Institute contract, National Institute of Neurological Disorders and Stroke, National Institute on Aging and National Institutes of Health.

The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with 30,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

To learn more about stroke, please visit http://www.aan.com/patients.

Stroke-Like Brain Damage Is Reduced In Mice Injected With Omega-3s

Researchers from Columbia University Medical Center (CUMC) found that omega-3 fatty acids reduced brain damage in a neonatal mouse model of stroke.

Findings from the study were published recently in PLOS ONE.

The researchers treated 10-day-old mice that had incurred hypoxic-ischemic brain injury (caused by a decrease in blood flow and oxygen to the brain, as occurs during a stroke) with a fat emulsion containing either DHA or EPA—omega-3 fatty acids that are found in certain foods and in supplements. The researchers evaluated the mice’s neurological function 24 hours and 8 to 9 weeks after the brain injury.

EPA and DHA are bioactive omega-3 fatty acids that are found in oils extracted from cold-water fish. The CUMC researchers and other scientists have shown that these fish-oil fatty acids protect organs and cells in numerous ways after oxygen deprivation, reducing inflammation and cell death.

At 24 hours, mice treated with DHA, but not EPA, had a significant reduction in brain injury. In the following weeks, the DHA group also had significantly better results in multiple brain functions compared to the EPA-treated mice and untreated (control) mice.
The researchers also discovered that these mice had increased concentrations of DHA in their brain mitochondria, energy-producing structures in cells that can be injured by free radicals when blood flow is restored to the brain after a stroke. This process, known as reperfusion injury, is a common cause of brain damage following the oxygen and nutrient deprivation that occurs after a stroke.
“Our findings suggest that injecting the omega-3 fatty acid DHA after a stroke-like event has the ability to protect brain mitochondria against the damaging effects of free radicals,” said senior co-author, Vadim S. Ten, MD, PhD, associate professor of pediatrics at CUMC.

Interruption of blood flow and oxygen supply to the brain during or shortly after birth is a major cause of brain damage in newborns, causing life-long neurological impairments in more than 25 percent of those affected. Many of the pathways involved in this type of brain damage are similar to those in an adult stroke.

“Clinical trials are needed to determine if administering lipid emulsions containing DHA shortly after a stroke-like brain injury offers the same neuroprotective effects in babies and adults, as seen in mice. If successful, such trials could lead to the development of a novel therapy for stroke in newborns, children, and adults, addressing a major medical need,” said senior co-author Richard J. Deckelbaum, MD, CM, the Robert R. Williams Professor of Nutrition (in Pediatrics) and Professor of Epidemiology and director of the Institute of Nutrition at CUMC.

Implanted Neuroprosthesis Improves Walking Ability in Stroke Patient

A surgically implanted neuroprosthesis—programmed to stimulate coordinated activity of hip, knee, and ankle muscles—has led to substantial improvement in walking speed and distance in a patient with limited mobility after a stroke, according to a single-patient study in the American Journal of Physical Medicine & Rehabilitation, the official journal of the Association of Academic Physiatrists. The journal is published by Wolters Kluwer.

“An implanted stimulation system for multi-joint control is a promising intervention to provide assistance to stroke survivors during daily walking,” write Nathaniel S. Makowski, PhD, and colleagues of the Louis Stokes Cleveland Veterans Affairs Medical Center. With technical refinements and further research, such implanted neuroprosthesis systems might help to promote walking ability for at least some patients with post-stroke disability.

Initial Experience Shows ‘Clinically Relevant Improvements in Gait’
The researchers report their experience with an implanted neuroprosthesis in a 64-year-old man with impaired motion and sensation of his left leg and foot after a hemorrhagic (bleeding) stroke. After thorough evaluation, he underwent surgery to place an implanted pulse generator and intramuscular stimulating electrodes in seven muscles of the hip, knee, and ankle.

Dr. Makowski and colleagues then created a customized electrical stimulation program to activate the muscles, with the goal of restoring a more natural gait pattern. The patient went through extensive training in the researchers’ laboratory for several months after neuroprosthesis placement.

In a ‘before-and-after’ study design, the patient showed significant gains in walking speed and distance. Gait speed increased from 0.29 meters per second (m/s) before surgery, to 0.35 m/s after training but without muscle stimulation—a nonsignificant improvement.

But when muscle stimulation was turned on, gait speed increased dramatically: to 0.72 m/s. Detailed analysis of the patient’s walking ability also showed evidence of a “more symmetrical and dynamic gait.”

In addition, the patient was able to walk much farther. When first evaluated, he could walk only 76 meters before becoming fatigued. After training but without stimulation, he could walk about 300 meters (in 16 minutes). With stimulation, the patient’s maximum walking distance increased to more than 1,400 meters (in 41 minutes) with stimulation. “Thus his walking distances increased by 370 percent with stimulation while walking nearly twice as fast,” Dr. Makowski and colleagues write.

Even though the patient wasn’t walking with stimulation outside the laboratory, his walking ability in daily life improved significantly. He went from “household-only” ambulation to increased walking outside in the neighborhood.

“The therapeutic effect is likely a result of muscle conditioning during stimulated exercise and gait training,” according to the authors. “Persistent use of the device during walking may provide ongoing training that maintains both muscle conditioning and cardiovascular health.”

While the results of this initial experience in a single patient are encouraging, the researchers emphasize that large-scale studies will be needed to demonstrate the wider applicability of a neuroprosthesis for multi-joint control. If the benefits are confirmed, Dr. Makowski and colleagues conclude, “Daily use of an implanted system could have significant clinical relevance to a portion of the stroke population.”