Invisible Injuries: Diagnosing concussions in young male athletes
Image from: Kenny Webster (Unsplash)
In soccer, heading the ball is a staple technique - used to control a ball that is too high to kick. This can happen tens of times every game, which can happen on a weekly basis, totaling to hundreds of times every year. Normally, heading to ball can be relatively safe if you use the proper technique. However, we don’t all start off as masters. Depending on where the ball lands on your head (i.e., forehead, top of the head, back of the head), this can dramatically impact the consequences of repeated headers. I remember preparing to head the ball after a goalie’s drop kick. The ball must have been going at 100km per hour at the time. I was watching the ball fall from the sky, planning the line up for a header, and then cutting to a ringing headache, feeling spaced out and dizzy, pain shooting down the back of my head into my spine. I must have looked out of it because my coach immediately pulled me off. I never went to the doctor, but I suspect I experienced a concussion.
A concussion is a type of traumatic brain injury caused when the head rapidly accelerates or decelerates. The brain experiences damage either from colliding with the skull or shear stress. Normally, the brain is surrounded by a fluid (cerebrospinal fluid) protecting it from excess movement. However, when your skull is hit sufficiently hard with an external force, the brain continues to move in the direction it was moving until it physically cannot– slamming against your skull.
We often hear about professional athletes, frequently in the National Football League (NFL), suffering from the consequences of repeated concussions years to decades after they have retired. They often experience severe cognitive impairment, depression, and anxiety. This problem is not unique to professional athletes. The National Ambulatory Care Reporting System, which collects information from Canadian hospitals, reported in 2016 to 2017 that 46,000 children between the ages of 5 to 19 have experienced a concussion. Brain injuries made up 80% of emergency department visits, out of all head injuries related to sports and recreation. This large prevalence of concussions is concerning. Concussions affect children differently than adults – impacting critical neural and social developmental periods. If these critical periods are disturbed, learning specific skills, such as language acquisition, may be very difficult in the future. What is even more concerning is that diagnosis of concussions can be unreliable, especially since timely rehabilitation and treatment is critical for successful outcomes and preventing future injuries.
Concussion diagnoses are often imperfect, typically requires self-reported descriptions of injury and symptoms, such as headaches, head pressure, fatigue, and sensory sensitivity and are often imperfect. Tests to assess brain condition from molecules in our blood do exist but are not recommended due to insufficient evidence in research. Researchers at Western University took advantage of a new technique to pinpoint reliable objective proteins that are released into the blood during the early stages of a concussion to overcome the previously mentioned challenges.
Image from: Matthieu Petiard (Unsplash)
The researchers utilized a new technique that rapidly tracks the abundance of proteins in a blood sample that may be released from tissue after an injury. This technique is called Proximity Extension Assay (PEA). The researchers enrolled male ice hockey athletes between the ages of 12-14 years old that were suspected of receiving a concussion just within 72 hours prior to the study. Non-injured athletes were also used as controls to compare against the injured athletes. Just under 1.5 tablespoons of blood was drawn from all athletes on their first visit to the clinic visit along with a full history and examination. All injured athletes then underwent full standardized concussion care. Using PEA, the researchers measured 1,472 proteins in the blood to see if there were any that were consistently different between injured and non-injured athletes.
A total of 11 injured athletes were confirmed to exhibit concussion status by self-reported symptom evaluation in addition to brain imaging. Over half of the patients had their blood drawn 2 days after the concussion occurrence. After measuring the 1,472 blood proteins from each athlete, only six proteins were identified as being potentially important biomarkers that tracked the presence of a concussion. When the researchers performed statistical tests, they found a combination of three proteins (ATOX1, SPARC, and NT5C3A) had the greatest predictive power. This combination of three proteins could correctly identify patients with a disease (sensitivity), in addition to correctly identifying people without the disease (specificity) – the hallmark of a useful biomarker. Interestingly, all three of these biomarkers have roles in modulating tissue inflammation and regulating brain blood vessel formation, which are elevated after a brain injury.
While this study appears to provide potentially excellent candidates for concussion diagnostic biomarkers, there were a number of limitations. The study had a small number of participants and lacked female representation. Despite this, this research adds to the growing body of literature that may eventually form clearer and more reliable diagnostic guidelines.
When it comes to brain injuries that are often more invisible to us than broken arms, accurate and rapid diagnosis is important. Research into developing a wide panel of robust biomarkers for successful diagnosis of concussions will provide athletes with the ability to safely treat their invisible injuries so they can continue to play the game they love.
Original article: Miller MR, Robinson M, Fischer L, et al. Putative concussion biomarkers identified in adolescent male athletes using targeted plasma proteomics. Front Neurol. 2021;12:787480.
https://pubmed.ncbi.nlm.nih.gov/34987469/