Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review

OBJECTIVE: Determine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC). DESIGN: Systematic review. DATA SOURCES: Searches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants. RESULTS: A total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research. CONCLUSIONS: Advanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice. PROSPERO REGISTRATION NUMBER: CRD42020164558

Salivary MicroRNA as a Concussion Biomarker and the Implications for Athletic Trainers\u27 Practices

Many concussions are sustained globally each year; however, research suggests that a large number may go undiagnosed due to a reliance on subjective information from patients and limitations of current objective measures. Recently, efforts have been focused on identifying clinical biomarkers of concussions, including salivary microRNA (miRNA), to improve healthcare professionals’ concussion management practices. Even if salivary miRNA were shown to be a valid and reliable measure for managing concussions, healthcare professionals, such as athletic trainers (ATs), must be familiar with the tool and have positive attitudes toward the implementation into clinical practice. Therefore, the purpose of this dissertation was to better understand salivary miRNA as a concussion biomarker through three studies. In our first study, we performed a scoping review to identify specific salivary miRNA that have demonstrate potential in acting as a diagnostic or prognostic indicator of concussions. Overall, we found forty-nine salivary miRNA across nine studies throughout the literature. Of those forty-nine, thirty-four show potential for being a concussion diagnostic marker and twenty-one correlated to multiple concussions or symptom trends. Of those identified, five were identified in multiple studies. As previously stated, even if identified as a valid and reliable tool for concussion management, healthcare professionals such as ATs should demonstrate familiarity with these tools and show positive attitudes toward the implementation into clinical practice. Therefore, the second study of this dissertation aimed to evaluate ATs familiarity with biomarkers of concussion and their attitudes toward the future implementation into clinical practice. Overall, the results of this study indicated that ATs self-reported a lack of familiarity with current literature surrounding the use of biomarkers for concussion management but a large majority self-reported positive attitudes towards the future implementation of such a tool into clinical practice. Lastly, to address a limitation for the application of salivary miRNA as a concussion biomarker, we aimed to evaluate the effects of one NCAA Division I football season. In this study, we found that although simple inferential statistics revealed no significant differences between pre- and post-season expression of salivary miRNA, further analysis through intraclass correlation coefficient statistics revealed a lack of reliability in each of the six target salivary miRNA. Although these target miRNA did not demonstrate reliability from pre- to post-season, sub-analyses revealed a ratio of two miRNA that showed high sensitivity when identifying concussed individuals. Overall, research should continue to evaluate the potential for salivary miRNA to act as a concussion biomarker by evaluating other target miRNA

Expert consensus document: Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

Sports-related concussions and repetitive subconcussive exposure are increasingly recognized as potential dangers to paediatric populations, but much remains unknown about the short-term and long-term consequences of these events, including potential cognitive impairment and risk of later-life dementia. This Expert Consensus Document is the result of a 1-day meeting convened by Safe Kids Worldwide, the Alzheimer\u27s Drug Discovery Foundation, and the Andrews Institute for Orthopaedics and Sports Medicine. The goal is to highlight knowledge gaps and areas of critically needed research in the areas of concussion science, dementia, genetics, diagnostic and prognostic biomarkers, neuroimaging, sports injury surveillance, and information sharing. For each of these areas, we propose clear and achievable paths to improve the understanding, treatment and prevention of youth sports-related concussions

J Neurotrauma

The Center for Disease Control and Prevention (CDC)'s 2018 Guideline for current practices in pediatric mild traumatic brain injury (mTBI; also referred to as concussion herein) systematically identified the best up-to-date practices based on current evidence and, specifically, identified recommended practices regarding computed tomography (CT), magnetic resonance imaging (MRI), and skull radiograph imaging. In this article, we discuss types of neuroimaging not discussed in the guideline in terms of their safety for pediatric populations, their potential application, and the research investigating the future use of certain modalities to aid in the diagnosis and treatment of mTBI in children. The role of neuroimaging in pediatric mTBI cases should be considered for the potential contribution to children's neural and social development, in addition to the immediate clinical value (as in the case of acute structural findings). Selective use of specific neuroimaging modalities in research has already been shown to detect aspects of diffuse brain injury, disrupted cerebral blood flow, and correlate physiological factors with persistent symptoms, such as fatigue, cognitive decline, headache, and mood changes, following mTBI. However, these advanced neuroimaging modalities are currently limited to the research arena, and any future clinical application of advanced imaging modalities in pediatric mTBI will require robust evidence for each modality's ability to provide measurement of the subtle conditions of brain development, disease, damage, or degeneration, while accounting for variables at both non-injury and time-post-injury epochs. Continued collaboration and communication between researchers and healthcare providers is essential to investigate, develop, and validate the potential of advanced imaging modalities in pediatric mTBI diagnostics and management.CC999999/ImCDC/Intramural CDC HHS/United States2022-01-01T00:00:00Z32640874PMC7757527890

Sports Concussion: A Clinical Overview

Concussion is an injury risk associated with participation in collision sports. It has been identified as a research priority for many contacts and collision sports governing bodies worldwide. However, concussion remains under-researched in terms of clinical translation from both experimental models to clinical understanding, and from clinical studies to sports policy. Currently, the clinical management of concussion is largely guided by the presence or absence of symptoms with recovery indicated once all post-injury symptoms have resolved. Management of concussion includes physical and cognitive rest until acute symptoms resolve, with a graded program of exertion implemented prior to medical clearance and return-to-play. Considering the potential sequelae, the heterogeneity of symptoms, and the lack of an intervention known to prevent concussion, it is not any wonder that concussion is one of the most complex and perplexing injuries faced by medical professionals, and why making the return-to-play decision can be quite challenging. This chapter will provide an overview of the current clinical management guidelines and research literature pertaining to identification and diagnosis of injury, acute and post-acute management, and return-to-play decision-making. The traditional standard assessment process (e.g., symptom reporting, cognitive assessment, balance testing), new methods and advanced technology (e.g., ocular-motor testing, neuroimaging techniques), and biomarkers (e.g., blood plasma and serum, fluid) have led to greater insights into sports concussion and will also be briefly explored in this chapter

Role of diffusion tensor imaging as an imaging biomarker and theranostic tool in structural imaging of traumatic brain injury

Neuroimaging technology is at a "newborn" stage in the evaluation of TBI. While additional literature are obviously required to decide whether these modalities and progress in knowledge with noninvasive monitors will allow early and consistent recognition of revocable secondary brain damages, the final query is whether these new modalities will help in treatment plans that will absolutely mark result. DTI is an influential instrument for assessing white matter anatomy and related anomalies. DTI was formerly an investigation tool, but is using clinical practice. Accepting the terms and basic ideas of this method can aid in the clinical implementation and interpretation of this blend of structural and physiologic white matter evaluation. In conclusion, although DTI is as a diagnostic tool for severity of TBI and as an outcome predictor, but severe preclinical and clinical validation of each imaging method should be a top importance

Study of Concussion in Rugby Union through MicroRNAs (SCRUM): a study protocol of a prospective, observational cohort study

The diagnosis of mild traumatic brain injury or sports-related concussion is a challenge for all clinicians, players, coaches and parents involved in contact sports. Currently, there is no validated objective biomarker available to assess the presence or severity of concussion in sport, and so it is necessary to rely on subjective measures like self-reporting of symptoms which depend on the cooperation of the athlete. There is a significant health risk associated with repetitive injury if the diagnosis is missed, and so there is great value in an objective biomarker to assist diagnostic and prognostic decisions. To establish a panel of non-invasive MicroRNA biomarkers in urine and saliva for the rapid diagnosis of sports-related concussion and investigate the kinetics and clinical utility of these biomarkers in assisting diagnostic, prognostic and return-to-play decisions. Observational, prospective, multicentre cohort study recruiting between the 2017-2018 and 2018-2019 Rugby Union seasons. Professional rugby players in the two highest tiers of senior professional domestic rugby competition in England will be recruited prospectively to the study. During the season, three groups will be identified: athletes entering the World Rugby Head Injury Assessment (HIA) protocol, uninjured control athletes and control athletes with musculoskeletal injuries. Saliva and urine will be collected from these athletes at multiple timepoints, coinciding with key times in the HIA protocol and return-to-play process. Ethics approval has been obtained. The compiled and analysed results will be presented at national and international conferences concerning the care of patients with traumatic brain injury. Results will also be submitted for peer review and publication in the subject journals/literature. [Abstract copyright: © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.

Post-concussion return to boxing protocol

Background: Concussion is a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces. Immediately following a concussion, an athlete is usually advised physical and cognitive rest until post-concussion symptoms abate. The athlete then enters a stepwise return-to-play protocol. Premature return to play risks a second concussion, second impact syndrome, exacerbation and persistence of post-concussive symptoms. Various sports governing organisations such as the National Football League have developed post-concussion return to play protocols.Discussion: Professional boxing is a popular contact sport in which concussions are common. Professional boxing currently lacks a standardised post-concussion return to boxing protocol. Professional boxers are arbitrarily suspended for periods ranging from 30 to 90 days after suffering a technical knockout (TKO) due to multiple head and body shots or after a knockout (KO). For some boxers a neurology clearance is requested prior to their return to boxing.Conclusion: Developing and implementing a post-concussion return to the boxing protocol will standardise a return to boxing decision-making process and help to protect a boxer’s health. This paper proposes a post-concussion return to boxing protocol with the recommendation that the proposed protocol be debated vigorously by the scientific community and evidence-based guidelines be developed by the medical community in conjunction with the professional boxing governing bodies