Saliva Test a Game Changer for Identifying Concussion?


March 26, 2021

March 26, 2021 — Researchers in the United Kingdom have created a a test using saliva to successfully diagnose concussion in professional rugby players — a potential game-changer, given that it would be a noninvasive test for mild traumatic brain injury.

The study identified 96% of players with concussion in the study, which enrolled 1,028 male professional rugby athletes from the two top-tier leagues in England over two seasons.

“The results of our exciting and ground-breaking research shows that for the first time we have successfully identified that these specific salivary biomarkers can be used to indicate if a player has been concussed,” study investigator Antonio Belli, MD, senior author and professor of trauma neurosurgery, University of Birmingham, said England, at a press briefing.

Belli noted that the study showed that the signs of concussion were released within minutes of brain injury.

“Although the biomarkers evolve over time, it is possible to make a diagnosis even at a really early timepoint,” he said, characterizing this as “one of the most exciting aspects of the study.”

The study was published online March 23 in the British Journal of Sports Medicine.

A True Signature of Concussion?

The researchers began the trial soon after they identified a concentration of specific molecules in the saliva that change rapidly after brain injury. The molecules play a role in mild and severe traumatic brain injury.

Researchers collected saliva samples from all athletes during the preseason. This baseline sampling helped eliminate any influence of pre-existing factors.

Samples were taken in-game during the first season, but not season two, as they were deemed not necessary. Samples were taken immediately after each game and 36 to 48 hours postgame from players with head injuries, uninjured players, and players with other injuries. The samples were analyzed on equipment available to most labs.

All players with suspected head injury also went through the head injury assessment (protocol developed by World Rugby that English rugby teams follow.

Over two seasons, 106 of 393 players were found to have head injuries.

‘A Substantial Advance’

A rapid concussion test would give be useful in sports, at the bedside, and for first responder and military needs, said Belli.

The test, being developed by Marker Diagnostics “provides an invaluable tool to help clinicians diagnose concussion more consistently and more accurately,” he said.

“This is a very substantial and very novel finding,” said study co-author Simon Kemp, MD, the medical director of the Rugby Football Union, the national governing body for rugby in England.

“We’ve validated the biomarkers in our elite professional setting,” he said, adding that now players and medical staff will work together “to refine the value-adds and operationalize it to move from a laboratory-based test to a test that could deliver results in real time.”

However, neither scientists nor Marker Diagnostics have a rapid test yet.

The first stage was to confirm the concussion biomarkers exist in saliva, said Belli. “The next stage will be to then to make it faster and portable,” he said.

Belli said more studies will be conducted to further validate the test in rugby players, as well as to determine its usefulness in women, young athletes, and amateur players.

The researchers want to get the two English rugby leagues to widen testing so they can validate whether it can be used as a real-time diagnostic. Then, “if the results from next 300 cases match the results we’ve had, and there’s no reason to believe they won’t, it’s a very substantial advance,” said Kemp.

Results in men can’t be directly extrapolated to women, said Patrick O’Halloran, MD, at the briefing. O’Halloran is a research scientist with Marker Diagnostics and a study investigator.

“There are a number of sources out there that suggest female response to concussion is different,” said O’Halloran. For women, “We think of ourselves as a step behind,” he said, but added that the company is trying to get more saliva samples from women to advance studies.

Need for More Research

Commenting on the findings, Christina Master, MD, a sports medicine pediatrician at Children’s Hospital of Philadelphia, said the biomarkers “do appear to be associated with concussion in this specific population.”

“It will be interesting to see how these biomarkers perform in a larger, more diverse cohort,” she said.

Master said given how little is known about these specific biomarkers, “it is hard to predict whether they would be similar or different, expressed at greater or lesser levels, in younger individuals or women.”

She added that a rapid test “would have tremendous utility on the sidelines and in the athletic training rooms for sports medicine physicians and certified athletic trainers.” However, she said, she believes the data in this study only support its usefulness 36 to 48 hours postgame.

Studies should be extended across the age spectrum and to young athletes, nonathletes, females, and multiple races and ethnicities to understand how the biomarkers might perform in diagnosing concussion in these various groups, she added.

Also commenting on the findings for Medscape, Julian Bailes, MD, chair of neurosurgery at the NorthShore Neurological Institute in Chicago, described the study as “really intriguing.”

“However, more work needs to be done, not only to clarify the science but also on the logistics of the application of the science to the field of play,” said Bailes, who has been a sideline doctor for the NFL and NCAA for 30 years, and is also medical director of the Center for Study of Retired Athletes at the University of North Carolina, Chapel Hill.

In U.S. professional sports, trainers and doctors make immediate on-field or on-court diagnoses based on multiple factors, with an eye toward taking the player out or keeping them in a game, said Bailes. “There’s no time to wait for a test” that has to be sent to a lab, he said.

However, a saliva-based lab test would still be valuable if it could give an objective postgame result and if, eventually, it “quantified as to how bad a concussion or how significant a concussion was,” Bailes added.

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