Ready Assessment of Prognostic Indicators and Diagnostics (RAPID) for Concussion

Abstract

Mild traumatic brain injury (mTBI) more commonly known as concussion impacts millions of individuals every year. Annually in Canada alone, approximately 400,000 individuals sustain a concussion. Fortunately, most individuals recover from this type of brain injury and have resolution of concussion symptoms within 2-4 weeks of injury. However, a substantial proportion, up to 30% of individuals, have prolonged recovery, known as persisting symptoms after concussion (PSaC). Prolonged recovery can have negative impacts on individuals’ quality of life and ability to participate in activities of daily living. Providing accurate prognosis for these individuals acutely post-concussion may aid in their ability to access acute concussion care and ultimately could reduce symptom burden. This thesis begins by characterizing our current knowledge on concussion prognosis by evaluating the literature using a systematic review and meta-analysis to identify clinical risk factors associated with PSaC in adults with concussion. The next chapter describes the protocol for a prospective observational case-controlled study, the Ready Assessment of Prognostic Indicators and Diagnostics (RAPID) for Concussion Study. In the following chapter, the 1 month outcomes of the RAPID Concussion Study are presented and risk factors of PSaC at 1 month as well as predictors of time to recovery are examined. The thesis then goes on to discuss clinical outcomes at 3 and 6 months post-concussion, and the potential utility of fluid biomarkers for concussion prognosis. This work aims to characterize our current knowledge on acute concussion prognosis for adults and build on the literature by evaluating risk factors of PSaC in an adult cohort that is representative of a diverse population of adults who sustain a concussion. The risk factors identified during the systematic review and meta-analysis were formative in guiding a priori risk factors that may be relevant for the RAPID Concussion Study. In this study, we identified age, sex, loss of consciousness (LOC), post-traumatic amnesia (PTA), and acute physical and emotional symptoms as important clinical factors associated with PSaC at 1 month and time to recovery in adults with concussion. Chapter 5 will present preliminary results evaluating risk factors of PSaC at 3 and 6 months post-concussion. Chapter 6 will present preliminary results examining the utility of fluid biomarkers as a potential objective marker of concussion recovery in adults. Together, this thesis provides data to suggest that there are acute variables including age, sex, clinical signs (LOC and PTA) and acute symptoms that are associated with PSaC. We also show that clinical predictors vary with time post-concussion and highlight the need for more objective risk factors of PSaC, potentially blood biomarkers, that may increase prognostic accuracy. Finally, larger prospective multicentre trials are necessary to validate the results presented here and develop a multivariable prognostic tool for clinical utility.