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Role of advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion: a systematic review
  1. Michael McCrea1,
  2. Timothy Meier1,2,
  3. Daniel Huber1,
  4. Alain Ptito3,4,
  5. Erin Bigler5,
  6. Chantel T Debert6,
  7. Geoff Manley7,
  8. David Menon8,
  9. Jen-Kai Chen9,
  10. Rachel Wall10,
  11. Kathryn J Schneider11,
  12. Thomas McAllister10
  1. 1 Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
  2. 2 Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
  3. 3 Departments of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
  4. 4 Research Institute and Department of Psychology, McGill University Health Centre, Montreal, Quebec, Canada
  5. 5 Department of Psychology and Neuroscience Center, Brigham Young University, Provo, Utah, USA
  6. 6 Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
  7. 7 Department of Neurosurgery, University of California San Francisco, San Francisco, California, USA
  8. 8 Division of Anaesthesia, University of Cambridge, Cambridge, UK
  9. 9 Cognitive Neuroscience Unit, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada
  10. 10 Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA
  11. 11 Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
  1. Correspondence to Dr Michael McCrea, Department of Neurosurgery, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee 53226, Wisconsin, USA; mmccrea{at}


Objective To conduct a systematic review of published literature on advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion (SRC).

Data sources Computerised searches of Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Scopus and Cochrane Library from 1 January 2000 to 31 December 2016 were done. There were 3222 articles identified.

Study selection In addition to medical subject heading terms, a study was included if (1) published in English, (2) represented original research, (3) involved human research, (4) pertained to SRC and (5) involved data from neuroimaging, fluid biomarkers or genetic testing collected within 6 months of injury. Ninety-eight studies qualified for review (76 neuroimaging, 16 biomarkers and 6 genetic testing).

Data extraction Separate reviews were conducted for neuroimaging, biomarkers and genetic testing. A standardised data extraction tool was used to document study design, population, tests employed and key findings. Reviewers used a modified quality assessment of studies of diagnostic accuracy studies (QUADAS-2) tool to rate the risk of bias, and a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to rate the overall level of evidence for each search.

Data synthesis Results from the three respective reviews are compiled in separate tables and an interpretive summary of the findings is provided.

Conclusions Advanced neuroimaging, fluid biomarkers and genetic testing are important research tools, but require further validation to determine their ultimate clinical utility in the evaluation of SRC. Future research efforts should address current gaps that limit clinical translation. Ultimately, research on neurobiological and genetic aspects of SRC is predicted to have major translational significance to evidence-based approaches to clinical management of SRC, much like applied clinical research has had over the past 20 years.

  • concussion
  • sports injuries
  • mild traumatic brain injury
  • neuroimaging
  • biomarkers
  • genetics

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  • Contributors All authors contributed to article review and interpretation of data, drafting and revision of the manuscript, and final approval of the manuscript, and agreed to be accountable for all aspects of the work.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.