Tuesday, March 27, 2018

BY LAURA HEDLI

The science of concussion remains somewhat foggy. Concussions are notoriously hard to diagnose and the majority go unreported. Clearance to resume activity following a concussion is often a judgment call made by a health care provider who has scant data on the injury and very little expertise in brain trauma. These are all sizable problems when an estimated 1.1-1.9 million sports- and recreation-related concussions occur each year in children in the U.S.

Enter David Camarillo, PhD, and Gerald Grant, MD, who are among the nation’s foremost concussion experts. Their partnership is a synergistic one. Dr. Camarillo, bioengineer, explores the biomechanics of concussion, while Dr. Grant, neurosurgeon and military veteran, uses the data to make the best decisions for his patients. In the last two months, the researchers received a windfall in funding from the National Institutes of Health, Pac-12, and Tad and Dianne Taube of Taube Philanthropies, who have pledged $5 million to launch the Taube Stanford Concussion Collaborative.

Funding from Stanford Child Health Research Institute (CHRI) supported earlier efforts, serving as a building block to their current grants. In total, CHRI has given $1,550,000 to Drs. Camarillo and Grant and $835,000 towards concussion-specific research efforts. Beginning in 2013, CHRI awarded Dr. Camarillo with a two-year Transdisciplinary Initiative Program (TIP) grant for his research on improving the accuracy of diagnosing concussions by using biomechanical and plasma biomarkers.

Support from CHRI “allows you to just be so much more nimble,” says Dr. Camarillo, who played football in college, his experience as a linebacker adding to his intellectual curiosity. “You come up with an idea. You can test it out quickly.”

What’s the damage?

Members of the Camarillo Lab have developed mouthguard technology to help figure out what happens to the brain during a concussion; they began by supplying the Stanford’s football team with the devices. Because teeth are hard and connected to the skull, they are good surfaces for measuring how the skull moves. What the mouthguard data showed is how concussion produces strain deep within the brain. This runs counter to what was originally thought happen—namely that the outer edges of the brain sustained the most damage, the result of impact.

Dr. Camarillo explains in his 2016 TEDxStanford talk. He highlights a video available online as part of the CDC’s HEADS UP program for schools, parents, and kids. It shows a rendering of the brain sloshing around within the skull after a hit. But the head hitting something—that’s only part of the story. It may not even be a plot point at all in certain cases. Concussions can also occur from a blow to the body or fall. Researchers are determining that injury has less to do with impact and more to do with head rotation, which may stretch or twist the brain. Images from Dr. Camarillo’s lab show that brain tissue may be stretched up to 50 percent around the corpus callosum, which connects the right and left side of the brain.

“You don't even have to hit your head to have a concussion. That's provocative, but that's what we find,” Dr. Grant says. “It's the whiplash alone, without hitting your head, that can cause the same symptoms.” Helmets do little to help. In fact, helmets are designed and tested to prevent skull fracture, not concussion.

“CHRI has been that catalyst to help keep us going. It keeps me engaged in the project and encourages us all to brainstorm together about advancing the science about concussion.

In 2015, CHRI named Dr. Camarillo the Tashia and John Morgridge Faculty Scholar (FS) in Pediatric Translational Medicine. Coming at the tail end of his two-year TIP award, the FS award has extended his CHRI funding stream for seven years, allowing him to continue this work using the mouthguard technology to study the strain rate in the brain as a result of concussion. Equipped with an accelerometer and gyroscope (the same tech that’s in your smartphone but at a higher rate), the mouthguard measures g-forces that a cornerback, for instance, may experience when he’s tackled to the ground. Combined with video footage, this data can be translated to the clinic and the field. Health care providers can partner with trainers to examine a child’s risk for concussion and modify a player’s behavior, providing a personalized medicine approach to treatment.

“When you get down to the injury of a player and can help them, I think that's the really fun part because you're no longer then on a population level. It’s not just research,” says Dr. Grant, who was introduced to Dr. Camarillo in the context of working with Stanford athletes and trainers. “I really latched onto him because I believe his data was what was missing from the equation.

“CHRI has been that catalyst to help keep us going. It keeps me engaged in the project and encourages us all to brainstorm together about advancing the science about concussion.” Dr. Grant has mentored several postdoctoral fellows in the Camarillo lab who have received CHRI grants, including Mehmet Kurt, PhD, and Kaveh Laksara, PhD, both bioengineers and awardees for their research on concussion and brain trauma. Dr. Grant regularly meets with these trainees; he attends Dr. Camarillo’s lab meetings and has sat on thesis committees. “As a neurosurgeon that’s unusual, but it is crucial that these scientists understand the importance of their work and knowledge gaps we face in the clinic and on the field.” Both Drs. Kurt and Laksara have benefited from such mentorship and have gone on to successful engineering careers following their time at Stanford. Dr. Kurt is now a professor of mechanical engineering at the Stevens Institute of Technology in Hoboken, New Jersey, and Dr. Laksara is a professor of bioengineering at the University of Arizona in Tuczon, Arizona.

Where are the gaps in care?

Dr. Grant first began treating concussions when he was caring for soldiers suffering from blast trauma while serving in Operation Iraqi Freedom. Now he sees children in his comprehensive concussion clinic, where he puts them through a three-hour battery of tests to determine the level of injury and if they’re ready to resume activity. This includes vestibular physical therapy, speech therapy, eye tracking, a questionnaire about their medical history and prior concussions; parents are sometimes even consulted separately from the child to make sure stories line up to determine if their son or daughter can go back to play.

Many kids are cleared by health care providers who many not have any knowledge about concussion or future risk in an athlete with a history of several prior concussions or prolonged recovery. Dr. Grant explains providers might say, “‘Oh, you look pretty good to me today. You're cleared.’ In addition, most kids don't come to the emergency room, so clearance decisions are often made on the field by trainers.”  

As of 2014, all fifty states passed laws related to youth concussion, including the stipulation that a player be removed from the field if a concussion is suspected. Laws were based off of Washington State’s Zachary Lystedt Law, passed in 2009 and named for a high school football player who continued playing after sustaining a concussion and suffered brain damage as a result. The Associated Press released a report showing the majority of state laws contain language saying before returning to practice or a game, any child suspected of sustaining a concussion must be cleared by a health care provider trained in the evaluation and management of concussion. A few do not include this element, however, and several others require a provider’s signature, though the provider need not have any experience treating concussion. Without more data and a better understanding of what defines a concussion, Dr. Grant worries general providers are equipped with few tools to make this call while the pressures to return the athlete to play are immense.

Taube Stanford Concussion Collaborative aims to change this, at least in the Bay Area where doctors will have access to more data than ever before. The $5 million gift from the Taubes will help spread Dr. Camarillo’s mouthguard technology and Stanford’s research infrastructure to community high schools.

How to disrupt the concussion field

The Concussion Collaborative will be the first of its kind. It’s a local initiative with a longitudinal approach, where football players will be tracked over their four-year high school career. Treatment and behavior modification is the goal. Because the Concussion Collaborative is only collecting data on male athletes, its scope it still limited. In the future, Drs. Camarillo and Grant plan to test female athletes and players of other sports. Other considerations include studying concussions from bike accidents or even falls, the latter of which account for 50 percent of brain injuries in children.

Part of the initial work will be to establish an infrastructure to support scientific clinical trials for pediatric concussion research. These trials could test drug therapies and protective equipment, or aim to improve concussion diagnosis through blood biomarkers.

“It's been difficult to do a simple blood test and prove that someone had a concussion,” said Dr. Grant, whose expertise is in studying the blood-brain barrier. He is currently the CHRI Arline and Pete Harman Faculty Scholar, investigating the blood brain barrier as it relates to pediatric brain tumors. He is also interested in exploring the barrier as it relates to trauma. “The thought is that if the blood-brain barrier is open for a short time after the concussion, biomarkers can leak out of the brain and we can try to pick them up in the blood.” According to Dr. Grant, there are some promising blood biomarkers for investigation but they still are not ready for primetime.

Given that the funds are flexible and unrestricted, it could really supercharge our helmet technology project. If we could re-channel some of those resources into some of the helmet stuff, we could actually not just study concussions after they occur but start preventing them.

Both Drs. Camarillo and Grant are very excited about the Concussion Collaborative’s potential to aggregate data and disseminate information. “I feel like my role is to help people become aware of the limitations and benefits of the technologies that are out there,” says Dr. Camarillo, noting that there are many products marketed to consumers for concussion diagnosis or treatment that try to subvert regulations and don’t work.

Part of the Taube’s funding will go toward supporting interactive educational resources called CrashCourse to address misconceptions about concussions, support brain health and safety, and increase the reporting of concussions. This effort called TeachAids is being headed up by Stanford Graduate School of Education lecturer Piya Sorcar, PhD. The hope is to eventually reach 10,000 schools nationwide.

“We can get the hard data, then we can spin it into education,” Dr. Camarillo says. “Then we can actually disseminate the education in this clinical center and test the effectiveness of the education.”

Ultimate goal: prevention

While it sounds like an unachievable aim, Dr. Camarillo believes we can devise helmets that can prevent concussions from happening altogether. “I used to think that it was not realistic or possible, at least within the confines of football,” Dr. Camarillo says. “But I've changed my opinion over time; I think there's a real opportunity there.”

His lab is studying neck biomechanics and has tested prototypes of a new kind of bike helmet. Instead of a thick foam layer that covers the skull, the helmet is a soft neck pillow that can deploy like an airbag when it senses a collision. In 2016, Drs. Camarillo and Grant published results in the Annals of Biomedical Engineering, showing that airbag helmets reduce the risk of concussion by nearly eight times compared to traditional foam helmets. Work is underway to continue to refine the helmet’s thickness, air pressure, and deployment in a variety of accident scenarios.

With so much funding now going into the mouthguard technology, Dr. Camarillo believes CHRI may be able to support his new concussion research in exciting ways. “Given that the funds are flexible and unrestricted, it could really supercharge our helmet technology project,” he says. “If we could re-channel some of those resources into some of the helmet stuff, we could actually not just study concussions after they occur but start preventing them.”

Laura Hedli is a writer for the Division of Neonatal and Developmental Medicine in the Department of Pediatrics and contributes stories to the Stanford Child Health Research Institute.