Association of Hemodynamic and Cerebrovascular Responses to Exercise With Symptom Severity in Adolescents and Young Adults With Concussion

Background and Objectives:Aerobic exercise has become a useful method to assist with post-concussion management. Exercise can exacerbate concussion symptoms even when symptoms are not apparent at rest. Few studies have examined the reasons for symptom exacerbation during exercise following a concussion. We had two primary objectives. 1) To delineate cardiopulmonary and cerebrovascular responses to exercise in adolescents and young adults with a concussion and healthy controls. 2) To determine the association between cerebrovascular responses and symptom burden.Methods:We recruited participants with a recent concussion from a sport concussion clinic between 9/1/2018-2/22/2020. They were included if their concussion occurred <3 weeks before initial testing and if they were symptomatic at rest. Participants were excluded if they sustained a concussion in the past year (excluding index injury), reported history of neurological disorders, or were using medications/devices that may alter neurological function. Participants completed a progressive, symptom-limited, sub-maximal exercise protocol on a stationary bike. We assessed heart rate, blood pressure, fraction of end tidal CO2 (FETCO2) and middle cerebral artery blood flow velocity (CBF) and cerebrovascular function (vasoreactivity and autoregulation) at seated rest and during exercise.Results:We conducted 107 exercise tests (40 concussed, 37 healthy participants initially; 30 concussed at follow-up). Concussed participants were tested initially (mean=17.6±2.2 [SD] years old; 55% female; mean=12.5±4.7 days post-concussion) and again 8 weeks later (mean=73.3±9.5 days post-concussion). Control participants (mean=18.3±2.4 years; 62% female) were tested once. FETCO2 increased throughout the exercise protocol as heart rate increased, reached a plateau, and declined at higher exercise intensities. CO2 explained >25% of the variation in resting CBF (R2>0.25; p<0.01) in most (73% individuals). Within the concussion group, resting symptom severity and the heart rate at which FETCO2 reached a plateau explained ∼two-thirds of variation in exercise-induced symptom exacerbation (R2=0.65; FETCO2 β=-1.210±0.517[S.E.], p<0.05). There was a moderate, statistically significant relationship between cerebrovascular responses to CO2 at rest (cerebral vasoreactivity) and cerebrovascular responses to exercise-induced changes in FETCO2 (R2=0.13, p=0.01).Discussion:The arterial CO2 response and symptom exacerbation relationship during post-concussion aerobic exercise may be mediated by increased sensitivity of cerebral vasculature to exercise-related increase in CO2.