Advancing Concussion Assessment in Pediatrics (A-CAP): a prospective, concurrent cohort, longitudinal study of mild traumatic brain injury in children: study protocol

Abstract

IntroductionPaediatric mild traumatic brain injury (mTBI) is a public health burden. Clinicians urgently need evidence-based guidance to manage mTBI, but gold standards for diagnosing and predicting the outcomes of mTBI are lacking. The objective of the Advancing Concussion Assessment in Pediatrics (A-CAP) study is to assess a broad pool of neurobiological and psychosocial markers to examine associations with postinjury outcomes in a large sample of children with either mTBI or orthopaedic injury (OI), with the goal of improving the diagnosis and prognostication of outcomes of paediatric mTBI.Methods and analysisA-CAP is a prospective, longitudinal cohort study of children aged 8.00–16.99 years with either mTBI or OI, recruited during acute emergency department (ED) visits at five sites from the Pediatric Emergency Research Canada network. Injury information is collected in the ED; follow-up assessments at 10 days and 3 and 6 months postinjury measure a variety of neurobiological and psychosocial markers, covariates/confounders and outcomes. Weekly postconcussive symptom ratings are obtained electronically. Recruitment began in September 2016 and will occur for approximately 24 months. Analyses will test the major hypotheses that neurobiological and psychosocial markers can: (1) differentiate mTBI from OI and (2) predict outcomes of mTBI. Models initially will focus within domains (eg, genes, imaging biomarkers, psychosocial markers), followed by multivariable modelling across domains. The planned sample size (700 mTBI, 300 OI) provides adequate statistical power and allows for internal cross-validation of some analyses.Ethics and disseminationThe ethics boards at all participating institutions have approved the study and all participants and their parents will provide informed consent or assent. Dissemination will follow an integrated knowledge translation plan, with study findings presented at scientific conferences and in multiple manuscripts in peer-reviewed journals.

Imaging in Pediatric Concussion: A Systematic Review

“…AD, axial diffusivity; BA, Brodmann area; CP, cerebral peduncles; CR, corona radiate; RD, radial diffusivity. 26 The data presented here suggest that they may not provide useful information with which to predict recovery from mTBI in children and/or adolescents.…”

“…The identification of the brain biomarkers of pediatric mTBI will enable the quantification of the impact of an injury and trajectory of recovery. 13,26 This will directly inform future research and the impact of persistent post-mTBI symptoms, which may help refine return-toactivity decision-making and assist in the development of effective interventions.…”

Protocol for a prospective, longitudinal, cohort study of recovery pathways, acute biomarkers and cost for children with persistent postconcussion symptoms: the Take CARe Biomarkers study

“…The present study is being conducted at a single site, the RCH (a paediatric tertiary hospital). While the presentation of concussion is significant at RCH (~1000 per year), it is possible that this will limit the recruitment options relative to other studies (eg, A-CAP)44 and reduce statistical power.…”

The Clinical Utility of Magnetic Resonance Spectroscopy in Traumatic Brain Injury: Recommendations from the ENIGMA MRS Working Group

“…Similarly, consequences of injury such as not being able to participate in normal daily activities can impact outcomes. Therefore, some studies have opted to use an orthopedic injury (OI) cohort as the control group, as it shares traumatic event exposure and the associated recovery, can be recruited using a similar recruitment pathway (i.e., presentation in emergency rooms), as well as other factors that are non-specific to brain injury but mediate recovery (Yeates et al, 2017(Yeates et al, , 2009. However, this practice has been called into question as some studies have shown no clear advantage over community controls (Beauchamp, Landry-Roy, Gravel, Beaudoin, & Bernier, 2017;Mathias, Dennington, Bowden, & Bigler, 2013).…”

“…When developing multisite studies, one option is to use human phantoms and scan the same individuals at all sites to at least be able to quantify and understand the differences in metabolite quantification. This approach was recently used in a 5-site child and adolescent concussion study (Yeates et al, 2017). Nonetheless, at the present time, MRS findings from multisite studies have been limited (Vagnozzi et al, 2010) e. Selected volume size and location: minimum of 6 cm 3 placed in the frontal white matter ( Figure 6).…”