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Metabolomics profiling of concussion in adolescent male hockey players: a novel diagnostic method

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Abstract

Introduction

Concussions are a major health concern as they cause significant acute symptoms and in some athletes, long-term neurologic dysfunction. Diagnosis of concussion can be difficult, as are the decisions to stop play.

Objective

To determine if concussions in adolescent male hockey players could be diagnosed using plasma metabolomics profiling.

Methods

Plasma was obtained from 12 concussed and 17 non-concussed athletes, and assayed for 174 metabolites with proton nuclear magnetic resonance and direct injection liquid chromatography tandem mass spectrometry. Data were analysed with multivariate statistical analysis and machine learning.

Results

The estimated time from concussion occurrence to blood draw at the first clinic visit was 2.3 ± 0.7 days. Using principal component analysis, the leading 10 components, each containing 9 metabolites, were shown to account for 82 % of the variance between cohorts, and relied heavily on changes in glycerophospholipids. Cross-validation of the classifier using a leave-one out approach demonstrated a 92 % accuracy rate in diagnosing a concussion (P < 0.0001). The number of metabolites required to achieve the 92 % diagnostic accuracy was minimized from 174 to as few as 17 metabolites. Receiver operating characteristic analyses generated an area under the curve of 0.91, indicating excellent concussion diagnostic potential.

Conclusion

Metabolomics profiling, together with multivariate statistical analysis and machine learning, identified concussed athletes with >90 % certainty. Metabolomics profiling represents a novel diagnostic method for concussion, and may be amenable to point-of-care testing.

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Acknowledgments

We thank Ms. Christy Barreira and Ms. Sandra Shaw for excellent technical support, and Ms. Kathryn Manning and Mr. Kevin Blackney for assistance with data. We graciously acknowledge analytic support from The Metabolomics Innovation Centre at the University of Alberta, Edmonton, AB (Ms. Rupasri Mandal, Ms. Jennifer D. Reid and Dr. David Wishart). This study was supported by the Children’s Health Foundation (http://childhealth.ca/) grant to DDF.

Author information

Authors and Affiliations

  1. Department of Computer Science, Western University, London, ON, Canada

    Mark Daley

  2. Molecular Medicine, Robarts Research Institute, Western University, London, ON, Canada

    Greg Dekaban

  3. Department of Medical Biophysics, Western University, London, ON, Canada

    Robert Bartha & Ravi S. Menon

  4. Department of Physiology and Pharmacology, Western University, London, ON, Canada

    Arthur Brown & Douglas D. Fraser

  5. Department of Surgery, Western University, London, ON, Canada

    Tanya Charyk Stewart

  6. Department of Physical Medicine and Rehabilitation, Western University, London, ON, Canada

    Timothy Doherty

  7. Department of Family Medicine, Western University, London, ON, Canada

    Lisa Fischer

  8. Department of Occupational Therapy, Western University, London, ON, Canada

    Jeff Holmes

  9. Departments of Biochemistry and Pathology and Laboratory Medicine, Western University, London, ON, Canada

    C. Anthony Rupar

  10. School of Kinesiology, Western University, London, ON, Canada

    J. Kevin Shoemaker

  11. Departments of Pediatrics and Clinical Neurological Sciences, Western University, London, ON, Canada

    Douglas D. Fraser

  12. Paediatric Critical Care Medicine, Children’s Hospital, London Health Sciences Centre, Western University, Room #C2-846, 800 Commissioners Road East, London, ON, N6A 5W9, Canada

    Douglas D. Fraser

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  1. Mark Daley
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  7. Lisa Fischer
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  12. Douglas D. Fraser
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Corresponding author

Correspondence to Douglas D. Fraser.

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Conflict of interest

The authors have filed a patent application for metabolomics profiling of central nervous system injury (US Trade and Patent Office No. 62/135886).

Ethical approval

This study was approved by the Human Research Ethics Board at Western University (#103365).

Informed consent

Written informed consent was obtained from the legal guardians and assent was obtained from adolescent subjects.

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Daley, M., Dekaban, G., Bartha, R. et al. Metabolomics profiling of concussion in adolescent male hockey players: a novel diagnostic method. Metabolomics 12, 185 (2016). https://doi.org/10.1007/s11306-016-1131-5

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