A University of Birmingham-led study of top-flight UK rugby players has identified a method of accurately diagnosing concussion using saliva, paving the way for the first non-invasive clinical test for concussion for use in sport and other settings.

The results of SCRUM (Study of Concussion in Rugby Union through MicroRNAs) — carried out in collaboration with the Rugby Football Union (RFU), Premiership Rugby, and Marker Diagnostics — was published recently in British Journal of Sports Medicine.

Salivary Biomarkers Tested

Following the team’s previous research, which identified that the concentration of specific molecules in saliva changes rapidly after a traumatic brain injury, the researchers embarked on a three-year study in elite rugby to establish if these “biomarkers” could be used as a diagnostic test for sport-related concussion.

Using DNA sequencing technology in the laboratory at the University of Birmingham, the research team tested these biomarkers in saliva samples from 1,028 professional men’s rugby players competing in English rugby’s top two leagues — the Premiership and Championship.

Results from the study suggest that specific salivary biomarkers can be used to indicate if a player has been concussed. Additionally, the research has found these biomarkers provide further insights into the body’s response to injury as it evolves from immediately after trauma, to several hours and even days later.

The scientific breakthrough provides a new laboratory-based non-invasive salivary biological concussion test, which could have wide-reaching use and potential to reduce the risk of missing concussions not only in sport — from grassroots to professional levels — but also in wider settings such as military and healthcare, a media release from University of Birmingham explains.

May Provide Comparable Diagnostic Test

In community sport, these biomarkers may provide a diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting. While, at an elite level of rugby, the concussion test may be used in addition to the existing World Rugby Head Injury Assessment (HIA) protocol.

Marker Diagnostics, a subsidiary of Swiss biotechnology company Marker AG, is in the process of commercialising the patented salivary concussion test as an over-the-counter test for elite male athletes. It has also obtained a CE Mark for test, which has been named MDx.100.

The team now aims to collect further samples from players in two elite men’s rugby competitions in order to provide additional data to expand the test and develop its use to guide the prognosis and safe return to play after concussion and to further establish how it will work alongside the HIA process.

The team will present their findings and planned next research steps at the upcoming World Rugby Laws and Welfare Symposium, per the release.

Additional Studies

Meanwhile, Marker Diagnostics and the University of Birmingham are also currently carrying out several additional studies to further validate and expand the test for use in different groups that were not included in the SCRUM study, including women, young athletes and community sports players.

The research is part of the REpetitive COncussion in Sport (ReCoS) research programme being led by the University of Birmingham through the National Institute for Health Research’s Surgical Reconstruction and Microbiology Research Centre (NIHR SRMRC) based at University Hospitals Birmingham NHS Foundation Trust (UHB).

“Concussion can be difficult to diagnose, particularly in settings such as grass roots sports where evaluation by a specialist clinician is not possible. Consequently, some concussions may go undiagnosed. There are also concerns regarding the long-term brain health of those exposed to repeated concussions.

“A non-invasive and accurate diagnostic test using saliva is a real game changer and may provide an invaluable tool to help clinicians diagnose concussions more consistently and accurately. In professional sports, this diagnostic tool may be used in addition to current head injury assessment protocols and return to play evaluation to ensure the safety of individuals.”

— First author Dr Valentina Di Pietro, of the University of Birmingham and NIHR SRMRC

“Conducting a study in a professional contact sports setting has meant we have been able to collect invaluable data enabling us to make significant advances in our biological knowledge and understanding of concussion and its diagnosis.

“Crucially, the differences in the salivary concentration of these biomarkers are measurable within minutes of injury, which means we can make rapid diagnoses. The ability to rapidly diagnose concussion using biomarkers in addition to existing tools solves a major unmet need in the sporting world as well as in military and healthcare settings, particularly in injuries without significant visible symptoms.”

— Senior author Antonio Belli, Professor of Trauma Neurosurgery at the University of Birmingham, Consultant Neurosurgeon at UHB, and Director of NIHR SRMRC

“This study is an important part of the portfolio of collaborative research initiatives the RFU undertakes into concussion. While still a way from having something that can be used in community rugby, it is extremely encouraging to now be able to start to develop a rapid and non-invasive test which could add real value particularly at a grassroots level of the game.”

— Author Dr Simon Kemp, RFU’s Medical Services Director

“The findings from the study are clearly promising and highlight the potential for salivary biomarkers to further support clinical decision making and the accurate identification and diagnosis of concussion in a range of different sporting and non-sporting settings.

— Author Dr Matt Cross, Head of Science and Medical Operations at Premiership Rugby

“Elite Rugby’s Head Injury Assessment process has proven an invaluable tool in the identification of concussion with an accuracy of over 90 percent, but we are continually evaluating the latest developments in science and technology to identify potential enhancements. This study, its rigour and outcomes demonstrates the value in a targeted, scientific approach and reflects rugby’s progressive commitment to player welfare.”

— Dr Éanna Falvey, World Rugby Chief Medical Officer

“This ground-breaking validation of the biomarker panel shows that we can use the simple swab collection of saliva to accurately and specifically diagnose concussion. It is a biological measure of mild traumatic brain injury and will contribute to a new global standard of care for the injury and a meaningful reduction of the cost and health burden associated with concussion.”

— Tinus Maree, CEO of Marker AG

Study Details

The study, supported by The Rugby Players’ Association, saw the team obtaining saliva samples from male professional players in the top two tiers of England’s elite rugby union competition during the 2017-18 and 2018-19 rugby seasons.

Saliva samples were collected pre-season from 1,028 players. They were also collected from 156 of these players during standardised World Rugby head injury assessments (HIAs) at three time points — in-game, post-game, and 36-48 hours post-game. The HIA protocol, used by rugby medical staff, includes a neurological examination, a series of cognitive tests and evaluation of gait and balance to determine if a player has been concussed.

“Control” samples were also collected from 102 uninjured players and 66 players who were removed from the game due to musculoskeletal injuries.

Using samples collected during the 2017-18 season, the team identified a panel of a combination of 14 salivary biomarkers — known as small non-coding RNAs or sncRNAs — that was highly accurate (96%) at identifying concussed players from all other groups.

This included players with suspicion of mild traumatic brain injury who had a concussion ruled out after a structured HIA; uninjured controls from the same game; and players who had suffered musculoskeletal injuries.

The panel was prospectively tested during the 2018-19 season, and the research showed it could successfully predict whether players would be positive or negative for concussion via the HIA protocol in 94% of cases, the release further explains.

[Source(s): University of Birmingham, Science Daily]

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