Concussion result from forces caused by a direct or indirect blow to an individual's head, ultimately resulting in a rapid acceleration or deceleration of the individual's brain within the skull.
Field-side assessment of sports-related concussion relies on the participants honest reporting of symptoms. Further management also heavily relies on subjective input, with signs and symptoms varying between individuals, and between each concussion event. MRI and CT scans cannot identify concussions, and instead are occasionally used to rule out a more significant injury. As a result, there has been much interest in developing a biological test (biomarker) for concussion. Biomarkers have been defined by the World Health Organisation as "a substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease". A biomarker would add objectivity to the diagnosis and management of sports-related concussion, thereby reducing the external pressures on athletes to report symptoms.
Over the past decade, the majority of research has focused on neuronal imaging, proteins, and metabolites as potential biomarkers. Although proteins initially showed some potential, they are subject to degradation, making identification of their presence complex and time-sensitive.
Researchers then started to investigate potential biomarkers that could be used by clinicians in a variety of non-clinic settings. Di Petro et al. (2018) initially discovered that microRNA in saliva, was significantly upregulated, as indicated by higher concentrations being present, in six concussed patients when compared to six non-concussed patients. In that same year, six salivary microRNA were identified in paediatric concussions, in a study of sixty. Hicks et al (2020) later identified four microRNA which accurately distinguished concussed individuals from non-concussed individuals. A recent study by Di Petro et al. (2021) looked to identify salivary microRNA which accurately distinguishes concussed from non-concussed elite professional rugby players. From this study of over 1000 players, the researchers identified a panel of 7 microRNA which may be predictive. Nine studies to date have investigated microRNA as a potential biomarker of concussion. microRNA are involved in neuronal injury and repair, and with over 2000 types present, researchers have their work cut out for them as they look to identify the key panels indicative of concussion.
To make things harder, individual characteristics, such as previous concussion history may impact baseline microRNA levels. Additionally microRNA may reflect physiological changes, such as fatigue, musculoskeletal injury and /or enhanced conditioning.
This is a promising and exciting area of research, that we are excited to be a part of at Foundation Clinic. As part of a World Rugby led initiative, baseline saliva samples are being collected by all Farah Palmer Cup Players. If an athlete then happens to sustain a concussion, we collect further saliva samples throughout their rehabilitation. It may be a few years before we see an objective measure of concussion being used pitch-side, but we are excited to be part of the journey.
Di Pietro V, Porto E, Ragusa M, Barbagallo C, Davies D, Forcione M, Logan A, Di Pietro C, Purrello M, Grey M, et al. Salivary microRNAs: diagnostic markers of mild traumatic brain injury in contact-sport. Front Mol Neurosci. 2018;11:290.
Di Pietro V, O’Halloran P, Watson CN, Begum G, Acharjee A, Yakoub KM, Bentley C, Davies DJ, Iliceto P, Candilera G, et al. Unique diagnostic signatures of concussion in the saliva of male athletes: the study of concussion in rugby union through microRNAs (SCRUM). Br J Sports Med. 2021;55(24):1395–404. Published online March 23. doi:10.1136/bjsports-2020-103274.
Hicks SD, Onks C, Kim RY, Zhen KJ, Loeffert J, Loeffert AC, Olympia RP, Fedorchak G, DeVita S, Rangnekar A, et al. Diagnosing mild traumatic brain injury using saliva RNA compared to cognitive and balance testing. Clin Transl Med. 2020;10 (6). doi:10.1002/ctm2.197.
Hicks SD, Johnson J, Carney MC, Bramley H, Olympia RP, Loeffert AC, Thomas NJ. Overlapping microRNA expression in saliva and cerebrospinal fluid accurately identifies pediatric traumatic brain injury. J Neurotrauma. 2018;35(1):64–72. doi:10.1089/ neu.2017.5111.
Di Pietro V, Ragusa M, Davies D, Su Z, Hazeldine J, Lazzarino G, Hill LJ, Crombie N, Foster M, Purrello M, et al. MicroRNAs as novel biomarkers for the diagnosis and prognosis of mild and severe traumatic brain injury. J Neurotrauma. 2017;34 (11):1948–56. doi:10.1089/neu.2016.4857.
