Abstract

The identification of clinical phenotypes may help parse the substantial heterogeneity that characterizes children with concussion. This study used latent class analysis (LCA) to identify discernible phenotypes among children with acute concussion and examine the association between phenotypes and persistent post-concussive symptoms (PPCS) at 4 and 12 weeks post-injury. We conducted LCA of variables representing pre-injury history, clinical presentation, and parent symptom ratings, derived from a prospective cohort, observational study that recruited participants from August 2013 until June 2015 at nine pediatric emergency departments within the Pediatric Emergency Research Canada network. This substudy included 2323 children from the original cohort ages 8.00–17.99 years who had data for at least 80% of all variables included in each LCA. Concussion was defined according to Zurich consensus statement diagnostic criteria. The primary outcome was PPCS at 4 and 12 weeks after enrollment. Participants were 39.5% female and had a mean age of 12.8 years (standard deviation = 2.6). Follow-up was completed by 1980 (85%) at 4 weeks and 1744 (75%) at 12 weeks. LCA identified four groups with discrete pre-injury histories, four groups with discrete clinical presentations, and seven groups with discrete profiles of acute symptoms. Clinical phenotypes based on the profile of group membership across the three LCAs varied significantly in their predicted probability of PPCS at 4 and 12 weeks. The results indicate that children with concussion can be grouped into distinct clinical phenotypes, based on pre-injury history, clinical presentation, and acute symptoms, with markedly different risks of PPCS. With further validation, clinical phenotypes may provide a useful heuristic for clinical assessment and management.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 36Issue Number 11June 2019
Pages: 1758 - 1767
PubMed: 30618356

History

Published in print: June 2019
Published online: 22 May 2019
Published ahead of print: 6 March 2019
Published ahead of production: 8 January 2019

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Keith Owen Yeates [email protected]
Department of Psychology, Alberta Children's Hospital Research Institute, and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Kenneth Tang
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Nick Barrowman
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Stephen B. Freedman
Department of Pediatrics, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Jocelyn Gravel
Department of Pediatrics, Hospital Sainte Justine, University of Montreal, Montreal, Quebec, Canada.
Isabelle Gagnon
Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
Gurinder Sangha
Department of Pediatrics, Children's Hospital of Western Ontario, Western University, London, Ontario, Canada.
Kathy Boutis
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Darcy Beer
Department of Pediatrics, Manitoba Children's Hospital, Winnipeg, Manitoba, Canada.
William Craig
Department of Pediatrics, Stollery Children's Hospital, Edmonton, Alberta, Canada.
Emma Burns
Department of Emergency Medicine, IWK Health Centre, Halifax, Nova Scotia, Canada.
Ken J. Farion
Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
Angelo Mikrogianakis
Department of Pediatrics, Alberta Children's Hospital, Calgary, Alberta, Alberta.
Karen Barlow
Department of Pediatrics, Alberta Children's Hospital, Calgary, Alberta, Alberta.
Alexander S. Dubrovsky
Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.
Willem Meeuwisse
Sport Injury Prevention Research Centre, Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.
Gerard Gioia
Department of Neuropsychology, Children's National Health System, George Washington University School of Medicine, Rockville, Maryland.
William P. Meehan, III
Sports Concussion Clinic, Boston Children's Hospital, Boston, Massachusetts.
Miriam H. Beauchamp
Ste. Justine Research Center, University of Montreal, Montreal, Quebec, Canada.
Yael Kamil
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Anne M. Grool
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Blaine Hoshizaki
Department of Kinesiology, University of Ottawa, Ottawa, Ontario, Canada.
Peter Anderson
Department of Psychology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Brian L. Brooks
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Michael Vassilyadi
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Division of Neurosurgery, Department of Surgery, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Terry Klassen
Department of Pediatrics, Manitoba Children's Hospital, Winnipeg, Manitoba, Canada.
Michelle Keightley
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
Lawrence Richer
Department of Neurology, Stollery Children's Hospital, Edmonton, Alberta, Canada.
Carol DeMatteo
School of Rehabilitation Science, McMaster University, Hamilton, Ontario, Canada.
Martin H. Osmond
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
Roger Zemek
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.

Notes

*
Information on the Pediatric Emergency Research Canada (PERC) Predicting Persistent Postconcussive Problems in Pediatrics (5P) Concussion Team is listed in the Acknowledgments section at the end of text.
Address correspondence to: Keith Owen Yeates, PhD, Department of Psychology (AD 254), University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N1N4, Canada [email protected]

Author Disclosure Statement

Dr. Stephen Freedman is supported by the Alberta Children's Hospital Foundation Professorship in Child Health and Wellness. Dr. Gioia is the author of the PCSI, a tool used in this manuscript; the PCSI is freely available, and he receives no financial benefit for its use. Dr. Meehan receives royalties from ABC-Clio publishing for the sale of the book: Kids, Sports, and Concussion: A Guide for Coaches and Parents and royalties from Wolters-Kluwer as an author for UpToDate®. Dr. Meehan is under contract with ABC-Clio publishing for a future book entitled: Concussions, and with Springer International publishing for a future book entitled: Head and Neck Injuries in Young Athletes. Dr. Meehan's research is also funded, in part, by a grant from the National Football League Players Association and by philanthropic support from the National Hockey League Alumni Association through the Corey C. Griffin Pro-Am Tournament. Dr. Brooks is funded by the CIHR Embedded Clinician Research program and receives royalties for the sales of the Pediatric Forensic Neuropsychology textbook (Oxford University Press, 2012) and three pediatric neuropsychological tests (Child and Adolescent Memory Profile [ChAMP; Sherman and Brooks, 2015, PAR Inc.], Memory Validity Profile [MVP; Sherman and Brooks, 2015, PAR Inc.], and Multidimensional Everyday Memory Ratings for Youth [MEMRY; Sherman and Brooks, 2017, PAR Inc.]). He has received in-kind support (free test credits) from the publisher of a computerized cognitive test (CNS Vital Signs, Chapel Hill, NC). Dr. Yeates is supported by the University of Calgary Robert and Irene Ward Chair in Pediatric Brain Injury, funded by the Alberta Children's Hospital Foundation. Dr. Zemek is supported by the University of Ottawa Brain and Mind Research Institute Clinical Research Chair in Pediatric Concussion. The other authors report no competing financial interests.

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