Modulating Exercise Dosage to Improve Concussion Rehabilitation: A Randomized Clinical Trial

项目摘要 脑震荡被定义为一种轻微的创伤性脑损伤，导致急性神经功能障碍。 最近的研究表明，脑震荡后的有氧运动强度低于症状恶化 安然无恙。然而，现有随机对照试验的临床益处表明有很大的改进空间。 此外，我们目前对潜在的神经生理学变化的反应还不完全了解。 运动疗法。确定获得治疗所需的精确运动剂量(体积/强度) 脑震荡后的反应将导致加强和更精确的脑震荡后康复策略。 我们公布的和试点的数据表明，轻微的脑震荡后锻炼与更快的症状有关 解决时间和不那么严重的症状，但我们依赖于自我报告的数据和观察设计。 此外，我们已经确定了区分脑震荡和非脑震荡的最佳运动量 一个月后的症状为每周160分钟，高于标准运动量处方 (&gt；每周100分钟)，并与现有的心血管健康建议(&gt；每周150分钟)一致。 除此之外，考虑到经常进行适度运动以减少炎症的积极效果(例如，白介素6) 而恢复脑血管调节，这些生理功能代表着可行和可行的康复 目标。因此，采用前瞻性随机临床试验设计，我们的目标是确定大剂量运动是否 每周个性化强度水平)，相对于标准护理，导致：症状更快/更慢 分辨率降低、生理功能改变或继发性后遗症减少。我们的多学科调查 团队拥有研究脑震荡、运动生理学、体液生物标记物、脑血管生理学、 以及心理社会结果。因此，我们将对13-18岁的青少年进行登记、初步测试和随机分组 ≤在脑震荡后10天进行大剂量有氧运动或标准护理(症状受限，自我指导 体力活动)，并在症状缓解和症状缓解后8周重新评估。我们将获得 每次就诊时的脑血管功能和血清生物标记物数据，并量化运动、症状和 继发性后遗症不断。首先，我们的目标是检查剂量(强度、持续时间和频率)如何 脑震荡后10天内开始的有氧运动计划会影响症状缓解的时间 到青少年中的标准护理。第二，我们的目标是评估 有氧运动、神经炎症的生物标志物和脑血管功能。第三，我们的目标是澄清 脑震荡后高剂量运动对持续性继发性后遗症的影响(焦虑， 抑郁、运动恐惧症、同伴关系、学业问题)。通过挑战目前被接受的， 运动相关脑震荡的锻炼建议，我们将朝着改善的方向开辟新的天地 康复策略。

Project Summary Concussions are defined as a mild form of traumatic brain injury that result in acute neurological dysfunction. Recent work suggests post-concussion aerobic exercise at an intensity level below symptom exacerbation is safe. Yet, clinical benefits from existing randomized controlled trials indicate substantial room for improvement. Also, we currently have an incomplete understanding of the neurophysiology underlying changes in response to exercise treatment. Identifying the precise exercise dose (volume/intensity) required to elicit a therapeutic response following concussion will lead to enhanced and more precise post-concussion rehabilitation strategies. Our published and pilot data indicate light post-concussion exercise was associated with faster symptom resolution time and less severe symptoms, yet we relied on self-reported data and observational designs. Furthermore, we have identified that the optimal exercise volume to differentiate those with/without concussion symptoms after one month was >160 minutes/week, which is higher than standard exercise volumes prescribed (>100 minutes/week), and in line with existing recommendations for cardiovascular health (>150 minutes/week). Beyond this, given the positive effects of regular moderate exercise to reduce inflammation (e.g., interleukin 6) and restore cerebrovascular regulation, these physiological functions represent viable and feasible rehabilitation targets. Thus, using a prospective randomized clinical trial design, we aim to identify if high dose exercise >(150 minutes/week at an individualized intensity level), relative to standard-of-care, results in: faster/slower symptom resolution, altered physiological function, or reduced secondary sequalae. Our multidisciplinary investigative team has expertise investigating concussion, exercise physiology, fluid biomarkers, cerebrovascular physiology, and psychosocial outcomes. Thus, we will enroll, initially test, and randomize adolescents ages 13-18 years old ≤10 days post-concussion to high dose aerobic exercise or standard-of-care (symptom limited, self-guided physical activity), and reassess upon symptom resolution and 8-weeks post symptom resolution. We will obtain cerebrovascular function and serum biomarker data at each visit, and quantify exercise, symptoms, and secondary sequalae continuously. First, we aim to examine how the dose (intensity, duration, and frequency) of an aerobic exercise program initiated within 10 days of concussion affects time to symptom resolution, relative to standard-of-care, among adolescents. Second, we aim to assess the mechanistic relationship between aerobic exercise, biomarkers of neuroinflammation, and cerebrovascular function. Third, we aim to elucidate how high dose exercise after concussion affects persistent secondary sequalae development (anxiety, depression, kinesiophobia, peer relationships, academic concerns). By challenging the currently accepted, exercise recommendations for sport-related concussion, we will break new ground toward improving rehabilitation strategies.