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Researchers Hope New Biomarkers Will Lead to Potentially Life-Saving Sports Pitch-Side Test for Brain Injury
Researchers at the University of Birmingham have identified inflammatory biomarkers which indicate whether the brain has suffered injury.
The team, led by Professor Antonio Belli, at the University’s College of Medical and Dental Sciences, now hopes to use these new biomarkers to develop a test which can be used on the side of a sports pitch or by paramedics to detect brain injury at the scene of an incident.
Dr Lisa Hill, of the Institute of Inflammation and Ageing at the University of Birmingham, said: “Traumatic brain injury (TBI) is the leading cause of death and disability among young adults and, according to the World Health Organization, by 2020 TBI will become the world’s leading cause of neurological disability across all age groups.
“Early and correct diagnosis of traumatic brain injury is one of the most challenging aspects facing clinicians.
“Being able to detect compounds in the blood which help to determine how severe a brain injury is would be of great benefit to patients and aid in their treatment.
“Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries that impair function, damage other brain structures and promote further cell death.
“Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions.”
Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins.
In this novel study published today in Scientific Reports, blood samples were taken from 30 injured patients within the first hour of injury prior to the patient arriving at hospital.
Subsequent blood samples were taken at intervals of four hours, 12 hours and 72 hours after injury. These blood samples were then screened for inflammatory biomarkers which correlated with the severity of the injury using protein detection methods.
In the laboratory, the team used a panel of 92 inflammation-associated human proteins when analysing the blood samples, which were screened simultaneously.
The serum biomarkers were analysed from patients with mild TBI with extracranial injury, severe TBI with extracranial injury and extracranial injury only and all groups were compared to a control group of healthy volunteer patients.
The results identified three inflammatory biomarkers, known as CST5, AXIN1 and TRAIL, as novel early biomarkers of TBI.
CST5 identified patients with severe TBI from all other cohorts and, importantly, was able to do so within the first hour of injury.
AXIN1 and TRAIL were able to discriminate between TBI and uninjured patient controls in under an hour.
Dr Valentina Di Pietro, also of the Institute of Inflammation and Ageing at the University of Birmingham, said: “Early and objective pre-hospital detection of TBI would support clinical decision making and the correct triage of major trauma.
“Moreover, the correct diagnosis of TBI, which is one of hardest diagnosis to make in medicine, would allow clinicians to implement strategies to reduce secondary brain injury at early stage, for example, by optimising blood and oxygen delivery to the brain and avoiding manoeuvres that could potentially increase intracranial pressure.
“In addition, this has potential implications for drug development, as novel compounds could be given immediately after injury and potentially commenced at the roadside, if there was sufficient confidence in the diagnosis of TBI.
“We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.”
A newly released hockey helmet has earned four out of five stars from the Virginia Tech Helmet Ratings, scoring higher than any other helmet since the first hockey ratings were released two years ago.
The new helmet, the Bauer RE-AKT 200, is the first to earn more than three stars. The star rating system, developed by researchers in the Virginia Tech Helmet Lab, rates a helmet’s ability to reduce the risk of concussion in the event of a head impact. All sports helmets, including those for hockey, must meet an impact-protection standard that evaluates the ability of helmets to minimize catastrophic head injury on a pass-fail basis.
“We supplement the standard by providing additional data so consumers can see the relative differences between helmets,” said Steve Rowson, an assistant professor of biomedical engineering and mechanics in the College of Engineering and director of the Helmet Lab. “We make that data available and release our testing methodology, which then becomes an additional design tool for the manufacturers.”
Using a headform instrumented with sensors, the Helmet Lab team simulates a range of impacts that a player might experience during a game, and measures how much the helmet reduces the head’s linear and rotational acceleration.
Rowson and Stefan Duma, the Harry Wyatt Professor of Engineering and interim director of the Institute for Critical Technology and Applied Science, began evaluating football helmets in 2011, designing the test methods based on millions of impacts they recorded from Virginia Tech football players.
The Helmet Lab team started testing hockey helmets a few years later, and has since rated more than 40 models.
Hockey players hit their heads on the ice, the glass around the rink, or each other; these surfaces can be rigid and players are typically traveling at high speeds, so impacts may be more severe than in other contact sports.
And hockey helmets tend to be light and thin, which limits their ability to reduce the force of a hit. In order to effectively absorb energy during an impact, thinner foam must be stiff. Thicker, softer foam that has more time to compress can cushion a broader range of impacts. The new Bauer helmet has slightly thicker padding than other models.
“I think this is the first example of the hockey helmet manufacturers using this test methodology and ratings protocol to influence the design,” Rowson said. “What we wanted to do was set a framework for improvement in protective design.”
The team’s methods have already contributed to improvements in football helmet design. When the first batch of ratings was released, only one helmet earned five stars. Today, 16 do, and virtually all new helmets get high marks.
“With the helmet ratings, we provide unbiased data and a transparent process that manufacturers can use to inform their design process and consumers can use to guide their choices,” Duma said. “We’ve been glad to have the opportunity to work with helmet companies to drive innovation, because we all have the same goal: to keep athletes as safe as possible.”
The team is also developing five-star ratings for bicycle and lacrosse helmets and soccer headgear.
Rowson says that helmets are just one piece of the equation in eliminating concussions. Behavioral changes in sports — for example, banning body-checking in youth hockey — can make an even more significant difference in reducing the number of injuries.
“You want to eliminate as many head impacts as you can, and then have the very best head protection in the event that you do hit your head,” he said.
The team’s current ratings are available online, and updated on a rolling basis.
Using an advanced imaging technique, researchers at Albert Einstein College of Medicine and Montefiore Health System were able to predict which patients who’d recently suffered concussions were likely to fully recover. The study also sheds light on the brain’s mechanisms for repairing or compensating for concussion injuries—information that could speed the development of therapies. The study was published online today in the American Journal of Neuroradiology.
“Our study presents for the first time a precision approach to harness imaging at the time of concussion to forecast outcome a year later,” said study leader Michael L. Lipton, M.D., Ph.D., professor of radiology, of psychiatry and behavioral sciences, and of neuroscience, as well as associate director of the Gruss Magnetic Resonance Research Center (MRRC) at Einstein and director of MRI services at Montefiore. “While we still lack effective treatments, we now have a better understanding of the neurological mechanisms that underlie a favorable response to concussion, which opens a new window on how to look at therapies and to measure their effectiveness.”
Each year, 2.5 million people in the United States sustain traumatic brain injuries (TBI), according to the Centers for Disease Control and Prevention. Concussions account for at least 75 percent of these injuries. Diagnosing concussion is based on assessing symptoms.
“While most people think of concussions as a mild and short-lived injury, 15 to 30 percent of patients are left with symptoms that persist indefinitely,” said Sara Strauss, M.D., the study’s lead author and resident in the department of radiology at Montefiore. “Until now, we haven’t had a reliable way to differentiate in advance those who may be burdened long-term and those who would have a complete recovery.”
Conventional imaging techniques, such as CT scans and MRI, cannot detect the subtle damage to axons (the nerve fibers that constitute the brain’s white matter) that is associated with concussions. But in a previous study, Dr. Lipton and his colleagues demonstrated that an advanced form of MRI called diffusion tensor imaging (DTI) can detect concussion-related damage to axons. It does so by “seeing” the movement of water molecules along axons, which allows researchers to measure the uniformity of water movement (called fractional anisotropy, or FA) throughout the brain. Finding a low FA brain region, for example, indicates structural damage that has impeded water movement in that area.
In the current study, Dr. Lipton tested whether brain abnormalities identified on DTI of individual concussion patients could distinguish between those patients who will eventually recover and those who will not. DTI was performed on 39 patients diagnosed with mild TBI by an emergency room physician within 16 days of the initial injury and on 40 healthy controls. The DTI image of each patient was compared with images for the entire group of healthy controls to see where patients’ brains were abnormal. Patients were also assessed for three measures: cognitive function, post-concussion symptoms and health-related quality of life measures. A year later, 26 of the concussion patients returned for follow-up assessments.
DTI imaging comparing concussion patients and healthy controls revealed two types of white-matter abnormalities in patients: (1) areas of abnormally low FA (red, in associated image) that correlate with axon damage and the cognitive impairment that can affect concussion patients; and (2) other brain areas with abnormally high FA (blue) that may indicate where the brain has responded favorably to injury, perhaps by more efficiently connecting axons or by remyelinating injured tissue (i.e., forming fatty tissue around nerves, which allows nerve impulses to move more quickly).
The amount of high FA imaged in brains predicted patients’ outcomes following concussion. Having a greater volume of abnormally high FA white-matter areas (perhaps indicating good compensation for concussion damage) was associated with better outcomes on follow-up assessments. (This doesn’t mean that the low FA areas showing white-matter damage aren’t important—just that they’re not useful in predicting recovery from concussion a year later.)
“Being able to predict which patients have a good or bad prognosis has tremendous implications for discovering and evaluating treatments for concussion,” said Dr. Lipton. “Developing an effective intervention requires first identifying the people who need it. Seventy to 85 percent of concussion patients get better by themselves, which makes it difficult to learn whether any treatment is actually helping. Our imaging technique allows researchers to test potential therapies on those concussion patients who can truly benefit from them.”
Dr. Lipton noted that most therapies tried so far for TBI have focused on reducing damage from brain injury or preventing an injury from progressing, but none has proven effective. “Our findings,” he said, “suggest that it might be worthwhile to try a different strategy—namely, attempting to enhance the brain’s innate abilities to compensate functionally and structurally for whatever damage has been done.”
Dr. Lipton cautions that further studies are needed to validate this approach for predicting concussion outcomes. “While we were able to predict the outcomes for the patients in our study; more refined approaches—incorporating additional patient and injury characteristics, for example—may be needed when applying the test on widely differing individuals,” he said.
The study is titled, “Bidirectional Changes in Anisotropy are Associated with Outcomes in Mild Traumatic Brain Injury.” The other contributors are: S. B. Strauss, Namhee Kim, Ph.D., Craig Branch, Ph.D., M.E. Kahn, Mimi Kim, Sc.D., Richard Lipton, M.D., Jennifer Provataris, M.D., H.F. Scholl and Molly Zimmerman, Ph.D., all at Einstein.
The study was funded by grants from the National Institutes of Health (NS082432-03).