Bench to Bedside | September 2017

Teaming Up to Quantify Youth Concussions

From the clinic to the lab to the playing field, tag-team science is the key to a new research initiative that will tackle the accuracy of youth concussion diagnoses head-on. With a $4.5 million grant from the National Institute of Neurological Disorders and Stroke, researchers from Children’s Hospital of Philadelphia and the University of Pennsylvania will lead a five-year venture to design evidence-based, diagnostic assessment tools for the clinic and the sidelines, as well as create the foundation for better headgear and other protective equipment.

The goal: Enhance the accuracy of sports-related concussion diagnoses that can provide prognoses of the time-to-recovery and safe return-to-play for youth athletes.

The game plan: Combine bioengineering and sports medicine expertise under the leadership of three passionate scientists: Kristy Arbogast, PhD, co-scientific director of the Center for Injury Research and Prevention; Christina Master, MD, primary care sports medicine specialist and co-director of the Concussion Care for Kids: Minds Matter Program; and Susan Margulies, PhD, Robert D. Bent Professor of Bioengineering at the University of Pennsylvania’s School of Engineering.

“I’m a parent of two athletes, and concussions are something that’s talked about on the sidelines,” Dr. Arbogast said. “Parents are concerned. What we’re hoping to do is provide some evidence-base that is specific to kids and contribute to the scientific foundation of what clinicians do in the clinic. We have to get past the current diagnostic approach of relying on subjective symptoms to be able to begin to understand the burden of these injuries long-term.”

While the heft of previous concussion research looks at college-aged and professional athletes, the CHOP and Penn team will widen their scope to study a high school population, for whom there is little available data on injury criteria and thresholds.

Moving Away From Subjective Symptoms

Clinicians currently rely on subjective symptomatology to diagnose youth concussions. From physical symptoms like headaches and fatigue to cognitive ones like mental fog, self-reported indicators don’t always provide the clearest of metrics.

“The child has to recognize the symptoms in themselves, report them to someone, and then many of the symptoms are either subjective or non-specific,” Dr. Arbogast said. “Symptoms like headaches and fatigue are common in adolescence and could be attributed to other causes besides concussion.”

To complicate the matter, Dr. Arbogast said that adolescents might conceal their symptoms or the severity of what they feel. Previous research has found that fewer than 50 percent of high school football players reported their concussions, perhaps because they don’t believe or don’t know that their symptoms might indicate a concussion, or because they would like to keep playing on a sports team.

“The motivation for an athlete might be that he or she wants to be cleared to go back to the big game so they don’t lose their starting spot,” Dr. Arbogast said. “That can lead to challenges for clinicians.”

If the research team can identify a suite of objective metrics that clinicians will use when diagnosing or treating a concussion, then they can begin to improve the accuracy and precision by which they identify concussed youth and monitor their recovery.

Quantifying Concussions in the Clinic

Because concussions are an injury of function rather than one of structure (meaning that they are measured by impaired function rather than a clearly broken body part), the team will use objective metrics that measure a child’s brain function, in order to build a suite of quantitative assessment tools.

Currently, outpatient clinicians assess children with qualitative assessments of balance (such as walking straight, backwards, or with their eyes closed). While these are useful, Dr. Master believes that it is time to develop more precise criteria for those kinds of assessments.

“We’re hoping to get away from qualitative,” Dr. Master said. “With objective metrics of diagnosis, we can sort out the injured from not injured cohort, and monitor their path through recovery.”

Enrolling participants from CHOP’s Concussion Care for Kids: Minds Matter program, the researchers will measure and track the objective metrics of balance, neurosensory processing (such as eye tracking), and cerebral blood flow in adolescents ages 14 to 18 with a diagnosed concussion, then compare those metrics to healthy controls.

All of these metrics measure brain function in different ways: If a child’s brain isn’t functioning well, they won’t have stable balance or controlled eye movements. Preliminary evidence also suggests that cerebral blood flow can decrease during concussion. The resulting data will facilitate the development of guidelines that can help clinicians determine how long a child will take to recover, or when a young athlete can return to play.

“What we’re hoping to do is use technology to better understand concussions and translate that into less expensive and more accessible techniques that could eventually be implemented in the clinic,” Dr. Master said. “Not everyone is fortunate enough to be right next to a children’s hospital with options for advanced imaging, so we’re really trying to develop objective but less expensive, portable, and user-friendly tools.”

From the Lab to the Field

Not content to stop there, Drs. Arbogast, Master, and Margulies will lead two other study components that run parallel to their collection of objective metrics.

With a head-impact sensor study, the researchers plan to track the magnitude and direction of head impacts of youth on the sports field. Equipped with head-impact sensors, the high school athletes will go about their play while the researchers take pre-and post-season objective clinical metrics data and analyze head impacts from the sensors. The head impact sensor component of the study will enroll research participants from suburban Philadelphia’s The Shipley School.

The data gleaned from those metrics will then help to inform a study using a porcine animal model of traumatic brain injury (TBI). Animal studies have long been used to study traumatic brain injury (with the University of Pennsylvania being one of the pioneers of such methods); for this study, they have adapted their porcine model of moderate and severe TBI to focus on concussion.

By studying both humans and animals rather than simply one or the other, the researchers can replicate the head rotations observed of adolescents on the playing field in the animal model. This translation gives them the control, range, and scope to study the very specific mechanisms of a concussion. For example, previous research has shown that tolerance to an injury can depend on the way the head moves, but with athletes in real time on the playing field, the researchers can’t control how their head might be hit. With animals in the lab, however, the researchers can carefully control direction and magnitude to truly understand concussion tolerance.

Another benefit of using pigs, Dr. Arbogast said, is the fact that their brains are initially in an uninjured state. Unlike adolescents, who naturally bring some injury history including the potential for previous concussions and TBI, the animals used in this study have an uninjured brain.

“While you always have to think how animal research translates to humans, it might not be perfect, but it does give us control over some of the parameters we think are important,” Dr. Arbogast said.

The Dream Team

The biggest strength of the study lies in its collaborative nature: It was essential to combine a bioengineering perspective with that of a sports medicine clinician, in order to best address the complicated research questions at hand, according to Dr. Arbogast. While Dr. Arbogast is a bioengineer focused on injury prevention and Dr. Margulies works as a lab-based bioengineer, Dr. Master brings the perspective of a sports medicine clinician as well as a primary care pediatrician. Together, the team can take a holistic and thorough view of concussion treatment.

“We had all been meeting broadly about concussions to brainstorm, and we realized that we were of like-mind,” said Dr. Arbogast of the team’s dynamic energy. “The research questions being addressed by this project can only be answered by interconnected study across the clinic, the lab, and on the field.  Each component informs the other’s research in important ways.”

Besides that, there is another exciting component to the team’s energy, according to Dr. Arbogast. “We think it’s exciting that this study is being led by three accomplished female scientists,” Dr. Arbogast said. “We’re really proud of this and hope that our working together to lead this aspect of concussion research can provide a model for other young women in the field.”


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Produced by The Children’s Hospital of Philadelphia Research Institute.

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