Jan 29, 2015Making Headway
From the cellular level on up, researchers are learning more about the ways concussions affect the brain, offering hope for better ways to prevent, diagnose, and treat this dangerous injury.
By David Hill
David Hill is a former Assistant Editor at Training & Conditioning.
For most athletic injuries, the management and rehabilitation are hands-on. A sprain, for example, gets iced, braced, and strengthened. Not so when the injury is a concussion. There is no icing, bracing, or strengthening for this type of injury. The best medicine is simply making sure the athlete recovers fully so that no more harm is done.
Researchers, however, are digging below the surface and looking deep inside the brain to better understand mild traumatic brain injuries. They are trying to fill gaps in understanding what happens to a brain that’s been concussed. Their work is helping to explain why concussions can go undetected at least temporarily, and why athletes who’ve suffered a mild traumatic brain injury are more susceptible to a second and potentially more serious episode. This, in turn, offers hope for improved detection and treatment while driving home the importance of properly managing concussions.
To understand recent developments in concussion management, we must follow researchers into the brain—deep inside, to the cells. Building on earlier work with animals and now armed with sophisticated imaging equipment, researchers have reached a general agreement on what happens during and after a concussion.
As described by David Hovda, PhD, Program Director at the UCLA Brain Injury Research Center, a concussion happens when the brain is jarred severely enough that most of its neurons fire at once, flooding the space between cells with chemical neurotransmitters. The neurons begin reuptake of the chemicals, but this leads to an imbalance, primarily from the excessive calcium and potassium ions in the cascade of neurotransmitters. Cells seek to restore balance, but this requires a tremendous amount of energy, which the brain obtains by diverting it from normal functions such as short-term memory.
The neurochemical cascade happens in the first few seconds after the injury, often resulting in retrograde and anterograde amnesia, a sign of vulnerability to further injury as cell-level energy is diverted into restoring the chemical balance. How long the increased risk lasts, however, isn’t clear. “In concussed animals, we know their brains are still vulnerable to a second concussion after seven days,” Hovda says. “But we don’t know if they are any more vulnerable at day one than they are at day seven.”
As scientists develop the chemistry-based model of concussion, there is hope that chemical tests and even drug treatment for concussion may emerge. “There are a couple of blood tests being researched that may indicate whether there is injury in the brain,” says Jeff Bazarian, MD, Associate Professor of Emergency Medicine at the University of Rochester.
Such blood tests work by detecting chemical evidence of brain trauma, such as damage to the axonal fibers connecting neurons to one another. “This axonal injury releases some cell products—proteins—into the blood where they can be detected by a test,” Bazarian says. “I can even envision using this on the sideline of an athletic event to help decide whether someone needs to go to the hospital or can return to the field.”
Designing therapy based on these chemical reactions, however, is a more distant goal. Most therapy trials focus on severe brain injury, says Hovda, where the objective is preventing cell death, which seems to be rare in concussions. However, one avenue being tested does hold the possibility of speeding recovery from mild traumatic brain injuries.
The hypothesis focuses on brain-derived neurotrophic factor (BDNF), a protein that helps facilitate learning. Its synthesis in the brain can be stimulated by diet and exercise, but in brain-injured animals, exercise too soon after an injury diverts energy away from damage repair—a downside that negates the benefits of increased BDNF production. “We’re exploring the possibility of taking people or animals with mild traumatic brain injury and giving them an alternative fuel to burn during exercise,” Hovda says. “Then that exercise could increase BDNF and improve their recovery.”
NOT ALL CONCUSSIONS ARE EQUAL
In addition to deepening their understanding of the cellular mechanisms of concussion, researchers are examining how different parts of the brain are affected by the injury. The emerging picture is complex.
Mark Lovell, PhD, Director of the Sports Concussion Program at the University of Pittsburgh Medical Center (UPMC), and colleagues have begun testing concussed high school athletes with functional MRI scanners. The images can show which parts of the brain are working normally and which have depressed metabolism, an indication that they’ve slowed or shut down.
One part of Lovell’s research correlates these functional images with the results of neurocognitive testing. Researchers are beginning to see how depressed activity in one area of the brain may result in impairment on a certain type of test, while injuries in another area show up through other tests.
“There is a suggestion that the type of hit you take can affect the type of concussion you experience,” Lovell explains. “If you have impact to the area of the brain that influences consciousness, then the characteristic pattern we see is people with slower reaction times. Meanwhile, a blow to the temporal lobes on the side of the head can often lead to difficulties with memory.”
Hovda points out how this knowledge could eventually affect concussion management. “Let’s say a region of the brain that is responsible for appreciation of art was affected,” he says. “If that athlete doesn’t use that part of the brain very often or you don’t ask about it, you won’t recognize any symptoms associated with that.”
The location of the injury could also affect the nature of any subsequent injuries. “If you bang the front part of your head, then the temporal lobes on the side of the brain may not be vulnerable,” says Hovda. “So fi you bang your head again before you’ve fully recovered, the frontal lobes could be devastated while the sides remain uninjured.”
Researchers are finding complexities in how concussion affects different populations of athletes. These, too, have implications for assessment and management of the injury.
“Children between the ages of 5 and probably 14 have a much different response to mild traumatic brain injury than do older people,” Hovda says. “And males respond differently to mild traumatic brain injury than females, whose responses differ depending on where they are in their menstrual cycle, since estrogen can help protect the brain.”
Lovell has seen drastic differences in recovery times between high school and professional football players. His observations were confirmed in a study led by Elliott Pellman, MD, chairman of the NFL Mild Traumatic Brain Injury committee, and published in the February issue of Neurosurgery. Concussed NFL and high school players were given neurocognitive exams and those scores were compared to their baseline records. The majority of the pro players returned to their pre-injury levels within two days post-concussion, while high school players typically took a week, with some showing effects four weeks post-injury.
“I’ve been running the NFL and National Hockey League concussion research programs for more than 10 years, and it always amazes me how fast the professional players bounce back compared to high school kids,” says Lovell. “We see about 100 kids a week in our clinic, and there’s no question in my mind that high school kids take longer to recover.”
One possible reason that young athletes’ brains are more susceptible to injury and take longer to recover is that their neural networks aren’t completely formed and are still fragile. “We know that the brain matures up until about age 25,” says Mickey Collins, PhD, Assistant Director of the UPMC Sports Concussion Program. “There’s myelization occurring in the frontal lobes, and the brain is still maturing through the teenage years and into the young-adult years. Another hypothesis is that kids are more sensitive to changes in the neurotransmitter glutamate.”
For any age, the danger of multiple concussions is real. However, younger athletes again appear to be the most vulnerable. “Among high school athletes, we’ve found a threshold effect where if they have three or more concussions, they tend to show detriments in memory, concentration, and attention span,” Lovell says. “We did a similar study of NFL players and didn’t find that. We also know that second-impact syndrome has only happened in younger brains, 18 years old and under.”
However, a study published in the October issue of Neurology found retired NFL players more likely to suffer dementia than other men their age. Retired players having experienced three or more concussions were five times more likely to be diagnosed with mild cognitive impairment, and three times more likely to report significant memory problems compared to players without a history of concussion, according to co-lead researcher Kevin Guskiewicz, PhD, ATC, Director of the Sports Medicine Research Laboratory at the University of North Carolina.
A BIGGER TOOLBOX
While researchers grapple with the hows and whys of concussion, athletic trainers are left to deal with the day-to-day evaluation and management of concussed athletes. Although observation of symptoms still plays a central role, technology is broadening the arsenal of weapons athletic trainers have at their disposal.
For example, Virginia Tech has been testing a system that uses motion sensors in football helmets to detect and measure heavy impacts. More of a research tool than a clinical one at this point, the HIT system (High Impact Telemetry) may eventually be able to validate the number and severity of strong blows well enough to signal that an athlete is concussed.
For two football seasons, Mike Goforth, MS, ATC, Head Athletic Trainer at Virginia Tech, has distributed specially outfitted helmets among the Virginia Tech football team at practices and games. Goforth says it is not only the size of the force that determines a concussion’s severity, but also the location of the blow. Each helmet contains small motion sensors that detect and measure impacts and each has telemetry devices that instantly relay the information to a sideline computer. The goal is to define the amount of force required to cause a concussion, and determine which areas of the brain are more susceptible to cognitive impairment.
At Virginia Tech, not every player gets a high-tech helmet, but over a two-year period a lot of information has been gleaned about how many hits players at each position take and where on their head the impact comes. Linebackers and running backs get hit in the face mask and front of the helmet, while wide receivers get more hits to the side of the helmet. Defensive linemen get the most hits, typically in a Mohawk-like pattern on top of the head, Goforth, says.
And players get hit hard—up to 150 times the force of gravity. “To hear that the human body can take a 50-G blow and not have any clinical signs or even a headache—to me that was pretty amazing, and it shows us the sport is a lot safer than we thought,” Goforth says. “It shows the usefulness of our helmets and the toughness of the human body.”
The blows are recorded and can be correlated with game film footage. Each player’s case history, so to speak, is also matched to his performance as judged by coaches. Researchers are looking to see if any trends emerge linking repeated blows or possibly concussive blows with a change in performance—missing a blocking assignment or botching a pass route, for instance.
The research has reinforced the knowledge that no two concussions are alike, and each one needs individualized management. “Take our defensive linemen,” Goforth says. “They’ll have 25 75-G blows a game and not show any critical signs. And then you might have a kid take one 4-G blow and have a concussion. It depends on their susceptibility and the location of the hit.”
When a very hard blow is detected, a red flag is raised, and Goforth gives that player a close look on the sidelines. Someday, he says, it might be possible to validate the number or severity of blows, or both, well enough for the HIT system to signal a concussion on its own. But the science isn’t there yet.
Neurocognitive testing, meanwhile, is gaining mainstream acceptance in the treatment and management of concussions, including return-to-play decisions. It’s already looked at as a way to detect concussions on the sideline.
Engineers and neuroscientists at Georgia Tech and Emory University are working on a neurocognitive device that might help athletic trainers and other medical professionals better detect concussions without removing players from the stadium. During the 2005 season, Georgia Tech’s football team provided test subjects for DETECT (Display Enhanced Testing for Concussion and mTBI system). The device administers a seven-minute battery of cognitive tests through a headset designed to filter out noise and visual distractions. Like computer-based neurocognitive systems—ImPACT and Concussion Sentinel are two widely used products—DETECT requires a pre-injury baseline from each athlete to compare against.
“We’re trying to pick up subtle changes in cognitive function that aren’t detectable through conventional means,” says Michelle La Placa, PhD, Assistant Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. “And it’s intended to pick up signs of a concussion earlier than the other platforms, which typically are used two to three days post-injury. It’s not diagnostic—if it indicates a problem, we recommend more testing on a larger and more comprehensive system.”
La Placa notes that DETECT is designed for picking up mild concussions—the kind that might otherwise go unnoticed during a game but would nonetheless leave an athlete vulnerable to long-lasting problems if he or she were reinjured. “If a player can’t walk straight or they don’t know what day it is, they’re already going to be kept out of the game and sent for further evaluation,” she says. “We’re trying to pick up subtle concussions in players who show few outward symptoms.”
For now, though, the basic assessment and management message for people on the sports-medicine front lines remains the same: Be cautious when dealing with concussions. The most recent international consensus statement on sports concussion came out of a November 2004 meeting in Prague, and the takeaway message was the same as at the 2001 meeting in Vienna: Concussed athletes need to sit out, should not compete again until symptoms have resolved, and older systems of grading concussion that rely on severity of immediate symptoms are outdated.
Regardless of the presence of high-tech systems, the decision to let someone play or hold them out will still be made by people. And nothing in current research has led experts to deviate from the cautious approach. “I agree with the overall principles that came out of both the Vienna and Prague meetings,” Lovell says. “Don’t let somebody play who has symptoms—when in doubt, sit them out. If you believe the athlete is lying to you or downplaying their symptoms, hold them out. And we definitely believe in gradually returning athletes to play as they go through a systematic increase in their activity level.
“The brain is not a muscle, and it’s not a joint,” Lovell concludes. “It’s the most complex organ in the human body, and I think we need to have a great deal of respect for protecting it.”
Sidebar: EQUIPMENT TRENDS
Recently developed football helmets are being marketed as potentially able to reduce the risk of concussions. A study published in February shows they help to do just that, but that they do not necessarily reduce the severity of injuries that do occur.
Researchers at the University of Pittsburgh Medical Center Sports Concussion Program had 1,000 high school players wear traditional helmets and 1,000 wear the new model, the Riddell Revolution. (Other similar helmets were not included in the study.) Among all the players, 6.2 percent suffered a concussion: those wearing the traditional helmet, 7.6 percent, and 5.4 percent of those wearing the newer design. That translates to a 31-percent reduction in risk.
But when the concussed players’ cognitive function was assessed against their baseline results, there was no difference in severity of impairment or time of recovery. And that, says Mickey Collins, PhD, Assistant Director of the Concussion Program, has significant implications for what happens after the injury.
“Up to 20 percent of the sample hadn’t recovered by three weeks,” says Collins. “We’re talking about a significant proportion of these kids who were taking a long time to recover from the injury. A very important lesson here is that if an athlete has a concussion and has not recovered and goes back to play, the risk levels are very high—and it doesn’t matter what helmet he’s wearing.”