As the Super Bowl Looms, Local Researchers Look to Improve Concussion Diagnoses

TGen fitted ASU football players' helmets with sensors to gather head-impact data.
TGen fitted ASU football players' helmets with sensors to gather head-impact data.
Evie Carpenter

Anyone can tell by looking at Kyle Middlebrooks' battered practice helmet that the guy has taken some hard knocks.

The Arizona State University senior running back sustained several serious injuries during his four-year college football career. Just months after recovering from surgery to repair a dislocated shoulder, Middlebrooks tore his anterior cruciate ligament in the final game of his sophomore season. And on top of that injury and its lengthy recovery time, he tore his right meniscus and chipped cartilage in his knee. It was a painful, months-long recovery process, he admits, and it kept him off the field for the entire 2013 season.

As a ball carrier, he's taken tackles that have dented his helmet and left him dizzy, confused, and even seeing colors that change right before his eyes.

But he's never been diagnosed with a concussion.

"It's crazy," Middlebrooks says. "But I don't think I've ever had [a concussion] because I've never had symptoms after the game."

That doesn't mean he hasn't had one.

From Pop Warner to pro ball, concussions are the biggest topic in football right now.

During his four years with the team, Kyle Middlebrooks played running back and wide receiver, in addition to serving as the team's primary kick returner in 2014.
During his four years with the team, Kyle Middlebrooks played running back and wide receiver, in addition to serving as the team's primary kick returner in 2014.
Sun Devil Athletics

Hundreds of lawsuits have been filed by thousands of former professional players, all of whom allege that they were not made aware of the damage the sport could do to their brains.

The legal action is the culmination of a 20-year saga during which some allege the National Football League covered up and ignored scientific evidence that playing football can lead to permanent brain damage. The issue has now trickled down to all levels of the sport, as a former Illinois high school football player filed the first football concussion-related class-action lawsuit against the Illinois High School Association in late November.

For all the talk, there's no definitive way to diagnose a concussion.

Instead, doctors like Phoenix neurologist Javier Cardenas use balance, vision, hearing, memory, and concentration tests to judge whether an athlete has injured his or her brain.

Because these tests measure the symptoms of a concussion rather than the biological cause, it's not a perfect system for identifying injury. But it's standard practice even for Cardenas, who's one of the nation's leading experts on concussion diagnosis and treatment.

In fact, Cardenas will be on the sidelines at this year's Super Bowl in Glendale, as part of the NFL's Unaffiliated Neurotrauma Consultant program, designed to better spot and treat athletes' brain injuries.

He is also a member of a team of researchers in Phoenix trying to find a definitive method to diagnose concussions.

Cardenas has partnered with researchers at the nonprofit Translational Genomics Research Institute (TGen), for a study of ASU football players. For two seasons, a team at TGen has gathered helmet impact data from about 40 players. Sensors in each player's helmet give the scientists real-time data on how hard a player's head has been hit, for how long, and where.

By comparing the helmet data to players' genetic data (taken both before and after a hit), Kendall Jensen and Matt Huentelman hope to identify the genetic change that takes place when players take hard hits and sustain a concussion. But first, they have to determine whether such a change happens at all and, if so, whether it indicates damage -- or just a normal response.

Two years into the study, they still don't know.

 

Kyle Middlebrooks' gold practice helmet shows signs of the many hits he took during the 2014 season.
Kyle Middlebrooks' gold practice helmet shows signs of the many hits he took during the 2014 season.
Lauren Saria

Early during a game against the Pittsburgh Steelers in 1992, New Orleans Saints guard Derek Kennard tried to tackle defensive back Rod Woodson. Woodson, now a Hall of Fame cornerback and safety, was coming out of the end zone on an interception return, but Kennard had him cornered.

"Then somebody came and hit me on my blind side," Kennard says. "I never saw it coming. They went ahead and got the touchdown. I was the last guy."

That was the last thing he remembered for the next three days.

Kennard, now 52 and living in Phoenix, says he played the rest of the game, went to practice the following Monday, and even took his wife out on Tuesday before waking on Wednesday with no memory of anything after the hit. It was terrifying, he acknowledges, but the mantra back then was, "If you don't practice, you don't play." So he did.

He knows things have changed a lot since then, but concussions still affect thousands of athletes every year.

It's estimated that as many as 300,000 concussions occur in athletics every year. Not surprisingly, football carries the highest risk of any male sport. About 55,000 high school football players get concussions annually and during the 2014 season, NFL teams reported 123 player concussions. That number represents a 20 percent decrease from last season, but concussions remain a serious problem for the league.

Still, the statistics could represent only a portion of the actual number of concussions athletes suffer every year. Kennard, for one, says he probably sustained countless numbers of concussions during his 11 years in the league. The Super Bowl XXX winner and former St. Louis and Phoenix Cardinal says he probably had so many go undiagnosed that he just laughs when doctors ask him to estimate a total number.

Unlike a broken leg, which can be confirmed with a simple X-ray and then treated, concussions elude visual detection. Doctors can identify the symptoms of the injury, such as confusion, dizziness, or loss of consciousness. They can even witness the cause, usually a direct blow to the head. But with current technology, they can't see or measure the physical damage that happens to the brain.

This makes concussion identification and treatment complicated. Even when a doctor diagnoses a concussion, there's no definitive way to know when the injury has healed or whether it has caused long-term changes to brain function. Researchers in Phoenix want to change that by creating a genetically based test to determine when a concussion occurs. Such a test might change forever the way we address the injury.

In addition to gathering helmet-impact data, lead researchers Kendall Jensen and Matt Huentelman have taken blood, urine, and saliva samples from ASU football players throughout the past two seasons. They plan to analyze the genetic makeup of these samples in hopes of identifying a small change that occurs in the players' RNA when they take a hard hit or suffer a concussion. This change, referred to as a genetic marker, could be the silver bullet for concussion diagnoses. Its presence in a person's DNA would definitely confirm a brain injury or concussion.

The discovery also could provide a clue about the toll football takes on the brain over an extended period of time. Scientists at Boston University have found chronic traumatic encephalopathy (CTE), a progressive degenerative brain disease, in the brains of 59 dead former pro football players. They believe the disease occurs as a result of repetitive brain trauma and concussions, but a genetic marker tied to such injuries could provide solid evidence of the connection. And if the genetic marker persists over time, it could prove that football can cause long-term brain damage.

As we wait for science to answer these questions and more, football teams at all levels are increasing efforts to educate and provide support for athletes.

Since 2007, the NFL has instituted increasingly stringent rules governing concussion protocol, most recently introducing standardized sideline concussion tests in 2011.

In October, the Arizona Super Bowl Host Committee and the NFL Foundation provided a $150,000 grant to put one athletic trainer at every Arizona Interscholastic Association postseason game last fall, the first state to do so. Experts say having an an athletic trainer or other medical personnel at sporting events is key in identifying and managing concussions.

At the collegiate and high school levels, Arizona athletes benefit from the Barrow Concussion Network. The statewide network includes two concussion educational programs, preseason baseline testing for athletes, and concussion consultation for high school athletic trainers, among other initiatives, making this the most comprehensive concussion program anywhere.

As medical director of the Barrow Concussion and Brain Injury Center, Javier Cardenas has been instrumental in the network's creation.

"When it comes to concussion, in the state of Arizona -- and especially as you compare to what's being done around the country -- we can stand very tall with what we've done," Cardenas says.

His work also targets what he believes will be the next community to draw attention for high rates of brain trauma: victims of domestic violence. Partnering with local shelters, Cardenas treats women and men who have suffered concussions at the hands of a partner.

Still, without a way to consistently identify and monitor recovery, these doctors can do only so much.

 

Researchers Kendall Jensen and Matt Huentelman will use genetic sequencing machines to try to learn more about concussions.
Researchers Kendall Jensen and Matt Huentelman will use genetic sequencing machines to try to learn more about concussions.
Evie Carpenter

The first record of concussion appears in the Hippocratic Corpus, a collection of more than 60 medical works written mostly between 430 and 330 B.C. The work describes commotio cerebri, or cerebral concussion, described as "when commotion of the brain is caused by a blow, the victim loses his speech and cannot see or hear."

In 1705, Baron Guillaume Dupuytren became the first to differentiate between loss of consciousness with a physical injury and without, or a concussion. And by 1941, neurologists proved that concussions could cause sudden interferences to brain function without also causing physical damage. This discovery serves as the foundation for the medical definition of concussions even today.

On a physical level, a concussion occurs when the brain, which sits in cerebrospinal fluid within the skull cavity, collides with the walls of the skull. This can happen as a result of a direct hit to the head or when the head suddenly accelerates in one direction, causing whiplash. The movement of the brain disrupts neural signals, essentially suppressing the brain's normal function as a high-speed connection to that of a dial-up.

Football, the roots of which can be traced back to games played by Native Americans, has always carried some level of association with this type of injury. As far back as 1583, critics describe the sport as a bloody and dangerous practice. At that time, the term "football" applied to any number of games that involved kicking, catching, and carrying a ball, most of which were played in city streets.

Football as we know it today wouldn't emerge until the 19th century, when college students with extra time on their hands played games to occupy themselves between classes. Eventually, schools began to organize intramural and intercollegiate games, and therefore began to establish set rules for the sport. Through the late 1870s, football remained a modified form of rugby, but by the early 1880s, American football began to differentiate itself from its mother sport. With the establishment of regulations such as a line of scrimmage and the limit of 11 players per team, American football began to take shape.

In the first college football game ever, a match between Princeton and Rutgers in 1869, no players wore head gear. Even into the late 1890s, there was no consistent mention of head gear in the sport, and helmets weren't made mandatory at the college level until 1939. These early helmets were often made out of leather and offered little in the way of real protection. The first major advancement only arrived in the 1940s, when Riddell patented the first plastic football helmet.

The company's helmets have been the gold standard in the sport ever since, and Riddell served as the official helmet of the NFL until 2013. Today, players can wear helmets by any manufacturer they choose, though the company remains the most popular throughout the league.

Ironically, today's most popular helmets do little to protect against concussions, researchers at Florida State University discovered. A 2014 study found that wearing a helmet only reduced mild traumatic brain injuries by 20 percent.

To assess brain injury, clinicians and athletic trainers rely on tests that gauge the severity of the symptoms of concussion, as opposed to the direct cause. As recently as the 1990s, that meant asking athletes to recall the date or their name. Today, concussion tests are more advanced and even include smartphone applications that sense a player's balance and coordination, not unlike field-sobriety tests. Doctors also can assess a player's level of brain function with computerized cognitive tests that measure reasoning and thinking skill.

Tamara McLeod, director of the athletic training program at A.T. Still University, an osteopathic medical school in Mesa, has spent years researching and developing age-appropriate concussion assessments for athletes. Even with the technological advances in concussion testing, McLeod says diagnoses and treatment can be complicated.

"Unfortunately, while we've come a long way and we have much better tests, we don't have perfect tests," McLeod says.

In the NFL, progress in terms of concussion protocol has been slow, and the league has drawn intense criticism from fans and the media. Though the NFL established a committee to investigate the issue of concussions in 1994, it failed to make regulatory changes until more than a decade later. By that time, evidence that football could cause long-term problems, including depression, early onset Alzheimer's, and CTE, had become impossible to ignore.

In 2002, Pennsylvania medical examiner Bennet Omalu accidentally discovered signs of CTE in former Pittsburgh Steelers player Mike Webster, who died in September of that year. Though CTE previously had been associated with professional boxers, this was the first instance of the disease in a pro football player's brain. For the next seven years, the NFL rejected mounting scientific evidence, including studies commissioned by the league, of the connection between football and permanent cognitive impairment.

As a part of a 2011 collective-bargaining agreement between the players association and the league, the NFL created the Unaffiliated Neurotrauma Consultant Program to better handle concussions and other brain injuries. The program places an independent neurologist or neurosurgeon on each sideline at every NFL game. These medical professionals are charged with spotting potentially concussed athletes, pulling them off the field, and clearing them for play.

It's the most aggressive response the league has taken to date, but it was too little, too late to protect the NFL from a costly legal battle. In July 2014, a federal judge approved a settlement that gave former players millions of dollars for brain injury-related diseases.

The settlement should help thousands of athletes like Derek Kennard, who says he experiences difficulty with day-to-day tasks because both his long- and short-term memory are failing. He makes adjustments to help compensate, such as having friends text him dates and names after they discuss plans. Even still, he sometimes forgets.

 

Researchers Kendall Jensen and Matt Huentelman will use genetic sequencing machines to try to learn more about concussions.
Researchers Kendall Jensen and Matt Huentelman will use genetic sequencing machines to try to learn more about concussions.
Evie Carpenter

On a crisp morning in early December, ASU's football team runs drills at the Kajikawa Practice Facility just south of the Tempe campus. With 10 days left until the Sun Bowl in San Antonio, the mood is relaxed, but the distinctive thwack of helmets meeting football pads rings loudly in the winter air.

About half of the more than 100 players wear gold jerseys and maroon football pants, while the rest sport the opposite color combination. You'd never be able to know by looking, but a few players also wear special helmets equipped with wireless sensors that transmit data about the location, magnitude, and duration of each hit they take to the head.

Among the players equipped with these special helmets is ASU redshirt junior linebacker Jason Franklin. During the 2014 season, Franklin sustained at least two concussions. He was cleared to play after the second injury, but Franklin says he knew something was wrong.

"You always want to play, especially being a linebacker," he says. "But when your friends come up to you and say, 'Jason, you haven't been the same in weeks,' [I figured it was time] I went to the doctor."

He ended up staying off the field for a month. At the end of the season, he got to see quantitative helmet data gathered from the hit that he believes caused the concussion.

"They said it was like as if I was going 40 miles an hour into a brick wall," Franklin says. "That's when I sat back and was like, 'Wow, that's a pretty rough thing to take in.'"

Jensen and Huentelman's research team at TGen has this data and more thanks to a system called the Riddell Sideline Response System, sponsored by the helmet company. It gives researchers not only a way to measure the force of each hit, but also information about the point of impact and duration. Though the system is available to the general public for purchase, no one until now has brought together a team and a research organization to compare players' genetic information with head impact data.

In the study, Jensen and Huentelman will examine the players' RNA. These small molecules serve as the messengers for DNA. When a cell decides it needs something done or repaired, the DNA inside it tells the RNA which proteins to build.

During this process, small strands of RNA escape into the outer portion of a cell as well as into the blood, urine, and saliva. By looking at which types of RNA are present in the football players' samples normally and then after taking a hit to the head, Jensen and Huentelman hope to find out which RNA correlate to concussion.

The presence of this specific RNA, or genetic marker, would then be used to diagnose concussions.

They may be looking for a single marker. Or there may be a half-dozen. A marker or markers may not exist at all, though the researchers are confident they'll find something. In any case, they face the daunting task of mapping the genetic makeup of the samples they've collected in an effort to find the correct bit of information.

The problem is that analyzing samples takes money, of which the researchers have a finite amount. And though they don't know whether their best bet of finding what they need lies in the genetic code of one player's samples or the next, they have to choose.

In selecting which to analyze, they literally will put their money on the line.

"It's totally a gamble," Jensen says.

Even if they do find a biological marker that appears after athletes sustain sub-concussive hits, Jensen and Huentelman still will have to determine whether the marker suggests an injury or inflammation associated with injury.

And that will require more data.

"The unfortunate matter about research is that a lot of times, what we care about -- we, the public, cares about -- is those longer-term questions and answers," Huentelman says. "And those are the hardest ones to fund and study."

 

Dr. Javier Cardenas, a leading expert on brain injury, has helped Arizona build comprehensive concussion education and treatment programs.
Dr. Javier Cardenas, a leading expert on brain injury, has helped Arizona build comprehensive concussion education and treatment programs.
Barrow Neurological Institute

Dr. Javier Cardenas says he never imagined he'd have a front-row seat to football's biggest event. Yet that's exactly where he'll be on February 1, standing on the 25 yard line at Super Bowl XLIX.

In fact, Cardenas has been at each NFL game played at University of Phoenix Stadium this season, carefully watching every play and looking for potential brain injuries.

As one of the nation's top concussion experts, Cardenas also helped establish Arizona's statewide concussion programs for students. In 2011, he created a concussion education program called Barrow Brainbook that's now required for all high school athletes. It's one of several initiatives that fall under the umbrella of the Barrow Concussion Network, other aspects of which include free baseline cognitive testing for athletes and free neurological consultation for all high school athletic trainers.

About 50 percent of Arizona high schools have a trainer, and those that do can consult with concussion specialists, including Cardenas, in real time when they suspect a student may have suffered a concussion.

Cardenas also helped create new football rules that have been adopted by the national organization that regulates most high school sports in the United States. As chair of the Sport Medical Advisory Committee for the Arizona Interscholastic Association, Cardenas wanted to find a way to encourage students to wear football helmets properly.

In response, the AIA instituted an experimental rule requiring that students sit out for a play or take a timeout every time a student's helmet came off during play. In one season, the rule led to an 80 percent decrease in helmets flying off during games and the rule has since been adopted for high schools nationwide. In 2012, the NCAA also adopted a similar policy.

"It is a very big deal, so we're quite happy that it came from here," Cardenas says.

His next goal for concussion awareness will also tie in to football, though it's not a connection he saw coming until recently.

Cardenas says general awareness of concussions initially increased as soldiers began to return home with brain injuries sustained at war, and the issue easily translated to professional sports. Next, Cardenas believes the issue will bring awareness to victims of domestic violence, up to 90 percent of whom suffer brain injuries.

"I call it the third chapter in the brain-injury story," Cardenas says.

Like professional athletes, victims of domestic violence also are at a high risk for sustaining concussions and other brain traumas.

And unlike well-paid football players, these women and men rarely have support, money, and other resources necessary to get help.

To address this need, the Barrow Concussion and Brain Injury Center has partnered with local domestic-violence shelters to give victims comprehensive neurological care. This includes access to everything from a neurorehabilitation specialist to a neuropsychologist and psychiatrist.

"What I think is probably one of the most special things is that we can have one person who is a domestic-violence victim who's homeless and then -- and this has happened on several occasions -- I walk across the hall into another room and there's a multimillion-dollar professional athlete," Cardenas says. "And we provide them the same exact care."

The idea for the program came from Phoenix social worker Ashley Bridwell, who became aware of the prevalence of brain injury in domestic-violence victims and in the homeless population when working on a survey of people living on the street.

"It got me to thinking: Is anyone talking about this?" Bridwell says. "And does the medical community know about this?"

She approached Cardenas with the idea, and though it took several years, the pair eventually obtained grant funding for the program. In the past two and a half years, the program has helped more than 200 victims of domestic violence get comprehensive neurological care.

Cardenas' two worlds collided last fall, when TMZ published video of Baltimore Ravens running back Ray Rice brutally punching his then-fiancée, Janay Palmer, in the face. The video and resulting scandal set off a media storm surrounding the NFL's rules regarding domestic violence, eventually leading to the establishment of a new domestic-violence policy.

"What's interesting about the whole Janay Rice and Ray Rice incident is that when Janay Rice was knocked out, people talked obviously about domestic violence," Cardenas says.

"But they didn't talk about the fact that she [obviously] suffered a brain injury at that moment when she was knocked out."

 

During his four years with the team, Kyle Middlebrooks played running back and wide receiver, in addition to serving as the team's primary kick returner in 2014.
During his four years with the team, Kyle Middlebrooks played running back and wide receiver, in addition to serving as the team's primary kick returner in 2014.
Sun Devil Athletics

After four years of playing college ball, Kyle Middlebrooks' football career probably has come to an end -- but he's far from done with sports. In fact, he's already transitioned into winter track, and he'll run short sprints for ASU's team in the coming season. Within the next year, he'll also finish a master's degree in sports law and business. After graduating, he says, he hopes to work in sports in some capacity.

Middlebrooks, who's been playing football since age 6, admits that he'd love to go to the NFL if given the chance. But even then, he says, he wouldn't want to play for long. The potential for injury is just too high.

He got a bold reminder of the damage football can do as recently as his final college football appearance. During the Sun Bowl, Middlebrooks says he went to make a block and had a hard collision with a Duke player. He lost the entire side of his white-and-maroon football helmet.

"It was like, 'Boom!'" Middlebrooks says. "It, like, exploded."

He still has never been diagnosed with a concussion, but he says he knows his brain probably has been affected by years of playing football. He's not sure how his brain function will differ from that of someone who didn't spend years getting knocked in the head, but Middlebrooks says he doesn't regret a single hit.

"It's just a part of the game," he says.


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