Playing the Long Game: Current and Future Paths in TBI and Concussion

Concussion is a relatively new player on the crowded field of public health issues. Unlike many other diseases that occupy the public consciousness, concussion arrived at this place as a result of its inevitable relationship to the contact sports that command widespread attention from the American public. As continued research has revealed more about the health implications of traumatic brain injury, the National Football League (NFL) and several other sports organizations took bigger steps to implement safety protocols. Community and educational sports organizations have been slow to catch up, but public interest in concussion prevention and management may soon result in changes at institutional and regulatory levels.

While much work remains to bring concussion into clearer focus, the broader shift toward greater awareness and action underlines the most important finding from the collective inquiry thus far, according to Kristine H. O’Phelan, MD, Associate Professor of Clinical Neurology at the University of Miami Health System: That brain injuries of all types have long-term consequences. “Most of us recognize that people who crash their car and are in the hospital for several months will likely have problems for the rest of their lives, but only recently have we understood that mild injuries may also have long-term effects,” says Dr. O’Phelan. These include cognitive and emotional problems, high incidence of depression, and psychological sequela.

As the relevance of concussion in the public sphere has grown, scientific inquiries to better understand and manage its effects have deepened. As Dr. O’Phelan explains in the following Q&A, research in various medical disciplines is digging deeper into the nuances of traumatic brain injury (TBI), such as how it impacts brain health over the long term and how multiple concussions affect developing brains.

Can you discuss how new advances in concussion research have changed the overall spectrum of TBI research and also guidelines for play?

According to Dr. O’Phelan, the similarities and contrasts between mild TBI and severe trauma are both intriguing and potentially revealing. “If you look at metabolism and blood flow of brains after they get concussed, many of them are very abnormal and look similar to people who may be in a coma. The clinical manifestations are very different but the metabolic changes at the tissue level are similar,” says Dr. O’Phelan. These metabolic changes may partially explain why sufferers of concussion are so vulnerable to second impact syndrome. “When the brain is depleted of the necessary reserves, brain cells have no way of getting the energy they need to recover from a second injury, and that’s where you see secondary injury and overwhelming brain swelling,” says Dr. O’Phelan. “It is essential to allow the brain enough time to recover metabolically and blood flow-wise.”

Given the brain’s vulnerability immediately after a concussion, many pediatric organizations have released return to play guidelines. However, some athletes resist following protocols and may try to play through injuries or return to the field if they are assessed for an injury. “Our culture places so much emphasis on sports and notoriety from being a successful athlete, and kids feel a lot of pressure,” says Dr. O’Phelan. Sometimes, parents even pressure physicians to allow their children to return to play, which reflects the extent to which athletic achievement is ingrained in our culture. “Some suggest that sports involving physical contact are necessary from a psychological perspective and help divert aggression,” which possibly contributes to indifference or strategic ignorance about the dangers of concussion. “No one thinks a concussion will happen to them,” says Dr. O’Phelan, but this emphasis should shift to focus on how to recognize and deal with concussions when they happen, she adds.

Can you talk about recent advances regarding the use of technological tools to assess and/or diagnose concussion?

One of the problems with assessing for concussion is how it is defined clinically, observes Dr. O’Phelan. “You have to ask the right questions to get a good diagnosis,” she explains. “If someone is involved in a car accident, we can often see something abnormal on a CAT scan. With concussion, the imaging is often normal and we learn that something is wrong when the patient alerts us to symptoms.” Despite these difficulties, widespread interest in concussion has helped spark the development of sideline tools and technology to measure cognitive function. According to Dr. O’Phelan, these tools may provide certain advantages over the more traditional oral and written assessments. “Certain devices can be used to perform baseline studies on team members, which may provide a measure of when to allow players to return to play.” She observes further that tech-driven devices can help overcome the learning effect of question-and-answer methods, which could be helpful for athletes or parents who insist on return to play.

Another area of interest and development is imaging studies. “Metabolic imaging, functional imaging, and structural imaging have really taken off in last 10 to 15 years.” Among the functional imaging techniques are PET-based technologies for CTE, such as specific tracers that can be used to look at abnormal protein deposition in individuals who are alive. “It’s not an absolute diagnosis because ultimately you need pathology to diagnose CTE, but certainly we may get to the point where we can be pretty sure in the correct clinical scenario.” In addition, she notes that diffusion tensor imaging (DTI) MRI studies are showing injury to the long tracks of axons that go from the deeper part of the brain, particularly to the frontal lobes. “There is very good research showing that these are absolutely correlated with the degree of injury and types of deficits people have after they get injured, and that’s true for severe as well as mild TBI.”

While different types of DTI measures can be used to assess the full scope of the injury, Dr. O’Phelan points out that gaining 100 percent certainty can be challenging, given the dynamic nature of the brain. “Some of those injured axons will repair themselves, so if you image someone at three days, then again at three months, and then once again at one year, it’s probably going to look different,” she says. Moreover, predicting when and how recovery takes place remains unknown.

Nevertheless, despite current limitations, imaging technologies potentially offer a way to stratify risk, which, as Dr. O’Phelan explains, could play a significant role in shaping the field moving forward. “These tools may allow us to say that a given person appears to have an injury that puts them at risk for specific types of problems—cognitive, emotional, psychological—and then follow that person or provide that person with resources to then avoid some of the long-term consequences.”

What has the growing spectrum of inquiry into concussion and TBI taught us about these conditions?

One trend that has gained more visibility of late is the overlap between TBI with other neurological disease states. “Increasingly, we are understanding that if you have a brain injury early in your life, you are more at risk for dementia and potentially other neurodegenerative problems,” says Dr. O’Phelan. This is particularly concerning given the common nature of TBI, with roughly nine million cases diagnosed worldwide annually. Moreover, individuals with repetitive injuries seem to be at greater risk for these conditions.

More research is needed to better understand the links between TBI and various other neurological diseases, but Dr. O’Phelan is hopeful that new strategies can be developed to improve outcomes in a global sense. This, she points out, will be a multi-faceted process. “Now that more people are aware of it, we’re hoping we can stratify risk and prevent people from having worsening outcomes, either by preventing second impact syndrome or catching people who are going to have post-concussion syndrome and giving them resources early,” she explains. “Not everyone develops second impact syndrome or post-concussion syndrome, so the idea of homing in on people at risk and focusing resources on these individuals will improve outcomes ultimately, and then you can hope that fewer people are going to suffer these long-term consequences.”

One challenge to improving outcomes, however, is that the symptoms of many post-concussion conditions are fairly broad, such as headache, cognitive problems, and depression. “There’s a broad range, and we haven’t really defined the best way to measure outcomes and say ‘we’re winning’.” Another challenge from a science perspective, according to Dr. O’Phelan, is the need for longer study periods. “We really need to measure outcomes out to a year or maybe even beyond that, and we need funding to do that.”

Are there any particularly compelling research threads worth following as the future unfolds?

One study currently underway may play a pivotal role in the future of TBI, says Dr. O’Phelan. “The TRACK TBI study is a comprehensive trial spanning multiple centers across the US and including patients with various levels of severity,” she explains. “In addition to looking at demographics, talking to families, assessing background characteristics, the study is also doing acute evaluations, including imaging, EEG, MRI, as well as lab and blood values over several years.” The goal is to develop a comprehensive and granular database, which may lead to the development of better outcome measures.

According to Dr. O’Phelan, the TRACK TBI study may play an important role in helping physicians determine expected outcomes, what they should be concerned about, and which interventions will help. “Right now, we have a bucket full of things that may help and a very rough way of looking at outcomes,” she observes. “Ultimately, what we’d like to do is refine these data to determine specific interventions and measure outcomes.”

The TRACK TBI study is currently two years into data collection. Though the study’s prospects are exciting, Dr. O’Phelan notes that big changes often take time, particularly in an emerging field such as this one. For example, in the realm of severe trauma, Dr. O’Phelan points out that guidelines have been refined subtly over several decades. Nevertheless, she is hopeful that overall awareness for concussion may assist in expediting the process for mild TBI and concussion. “People are now recognizing that you have to assess return to play and the vulnerabilities, which has actually changed practice more quickly,” she says. “It may be that we do see some of the changes based on awareness happen more quickly, if only because the media can get the message out more quickly than the science.”

Given the advancements we’ve already seen, how do you expect the field to evolve over the next several years?

The uniquely multidisciplinary nature of concussion and TBI research and care will yield continued gains in the field, according to Dr. O’Phelan: “Disciplines include neurology, sports medicine, physical medicine and rehabilitation, and neuropsychology, all of them very interested, engaged, and helping to promote the field.” Dr. O’Phelan notes that experimental and translational research in all of these fields is producing new insights and directions into concussion and will continue to increase in exposure and raise awareness for brain injury. “Translational research is essential, because people in general are difficult to study in this arena, due to the variability in injuries,” she says. On the other hand, “experimental models are often very different from human data, but they allow us to home in on fundamental mechanisms that are going to be important, so that you at least know where to look when studying humans.”

Efforts are also underway to create translational science that can expand further into technology and biomedical engineering, according to Dr. O’Phelan. One area of particular interest here is in building an interface for rehabilitation. “For the very severely injured, we’re seeing the development of interfaces with EEG, so that someone who doesn’t have use of a limb can do something by thinking about it.” Research is also underway looking at the potential of restorative medicine, though this is decidedly more experimental at this time. Additionally, some studies have explored stem cells for the mitigation of damage and restoration of function. While these threads are intriguing, Dr. O’Phelan notes that they remain speculative. “We can put stem cells in a lot of places, but trying to get them to do what we want them to do is a different story.”

With a variety of compelling research threads actively under investigation and public interest continuing to rise, Dr. O’Phelan is confident that the horizon of concussion management and prevention holds great promise. “The next decade will likely see significant advances in evaluation, risk stratification, and treatment of all severities of TBI,” she notes. Regarding what clinicians can extrapolate from the collective evidence available, Dr. O’Phelan stresses the importance of early recognition in the long-term outlook of concussion management. “Early recognition of concussion is essential to provide resources and prevent worsening injury due to a second brain injury.”

Kristine H. O’Phelan, MD is an Associate Professor of Clinical Neurology at the University of Miami Health System, where she is also Chief of the Neurocritical Care Section and Co-Director of the Neurosciences Critical Care Unit.