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The decision to return a player to competition after suffering a concussion is based on a careful evaluation of an athlete’s symptoms, successfully passing established protocols to measure progress after a graded exercise program is underway, as well as understanding that each player is unique when it comes to recovery.
Neurologists, trainers and team physicians use a systematic approach to decide when it is appropriate for an athlete to return to play.
With the Super Bowl just about to kick off, all eyes will be focused on the field. But during the regular season and playoffs, there have been some questionable return-to-play decisions making the public feel less confident that players are being treated appropriately after suffering a concussion.
After a concussion, what is often referred to as “brain slosh,” or jarring of the brain in the skull, releases compounds which cross from fluid surrounding the brain into the blood stream. This passage of proteins in the fluid represents an ideal opportunity to sample the degree of injury .
A blood sample of one compound-- tau protein--represents an opportunity to assess whether a player is truly making a recovery , as tau protein appears in the serum in elevated concentrations after head trauma, and may thus serve as a marker to determine whether a player is demonstrating clinical improvement.
Contrasted with the potential utility of tau protein to evaluate players who might not have classic symptoms such as dizziness, nausea or balance abnormalities, is the harsh reality is that existing methods to determine whether a player can safely resume play are quite subjective, and may even be manipulated by athletes who complete preseason baseline tests knowing that they may “game” the system by purposely underperforming to give the false impression of improvement.
Athletes who manipulate return-to-play protocols may place themselves at risk for not only a longer recovery, but also a second impact system that can be fatal. Add to this the increased risk for chronic neurodegenerative diseases such as ALS, Parkinson's or chronic traumatic encephalopathy (CTE), and the benefits of measuring such a biomarker as tau protein become quite evident.
Now a new study published in Neurology by Gill and colleagues demonstrates the potential of such a blood test to be able to predict recovery time after a concussion, helping to craft a safer and more accurate approach for making decisions regarding return to play.
Taking advantage of ultrasensitive Simoa technology developed at Quanternix, researchers found that athletes who had a prolonged recovery after suffering a concussion had significantly higher levels of tau protein in their bloodstream at the sixth hour post-injury compared with those players who were cleared to return to play in a shorter time frame.
Researchers have attempted to measure tau protein in the blood stream in the past, but encountered difficulty because it is present in very small quantities in the bloodstream (picograms/ml). Simoa technology, however, enabled Gill’s team to measure minute amounts of the compound that were previously technically difficult to detect and monitor.
The Simoa approach is unique and measures both normal and phosphorylated tau protein using a combination of monoclonal antibodies that react with both types of tau protein, thus increasing its sensitivity of detection. Previous reports using an older approach to detect tau, known as digital immunoassay, demonstrated elevations in peripheral tau, but only at much higher concentrations.
“Generally speaking, objective measures for concussion are highly desirable,” said Dr. Uzma Samadani, associate professor of Neurosurgery at University of Minnesota and director of brain injury at Hennepin County Medical Center. “While a blood test that needs to be performed within a specific time window after injury may not always be practical, it can potentially contribute to our understanding of injury.”
Samadani, however, cautioned that tau protein is also present in non-brain cell types, and because the study did not include non-concussion body collision subjects, “we don’t know how specific the results are for brain injury or concussion versus bodily injury which could confound the data.”
“Given the size of the investigational group, it should have been possible to compare the concussed athletes to athletes with orthopedic or other injuries,” she explained, offering that “inclusion of such a group would strengthen the investigators’ conclusions.”
Another expert, Dr. Thomas Terrell, associate professor at the University of Tennessee and a sports medicine physician who has investigated the genetics associated with post concussive risk, explains that overall there is a paucity of medical literature evaluating tau protein as a marker for head injury, referring to a collection of small studies, one of which evaluated hockey players in the recent past.
That said, Terrell explains that “the problem with using one genetic marker to determine an association with concussion risk is that concussion is likely determined by a large number of genetic polymorphisms that work together to influence the outcome of concussion.” Genetic and brain injury experts, he explains, “feel that the influence of genes on concussion outcome, if there is one, is polygenic.”
Terrell adds that “the literature is replete with studies that show that APOE4 is associated with a poorer TBI outcome,” with these studies having a greater number of patients with moderate and severe TBI.
According to Terrell, researchers have a keen eye on tau protein as a biomarker for return to play, not only for the ability to measure its concentration in the blood stream, but with “great interest in finding an imaging agent that will allow clinicians to image brains with PET CT scans or other imaging modalities to detect tau protein deposition.
Overall, Terrell explains that he is “not impressed with the ability of an isolated serum tau level to predict appropriate return to play." Instead, he believes that it will likely need to be a “combination of biomarkers and also consideration of secondary modifying factors—entities that increase risk of a more severe concussion such as a prior history of ADD, prior multiple concussions, or migraine headaches.”
While it may be attractive to envision a return to play decision based solely on a blood test, the bottom line is that the decision is complex, and must take into individual as well as subjective factors. Objective measures such as blood tests--if they eventually become part of a standard multimodal evaluation--are just one aspect of potentially clearing a player for return to competition.
