Heart-Brain Retraining: Forced Aerobic exercise for Stroke Rehabilitation

描述（由申请人提供）：本研究的目的是收集关于强迫有氧运动促进卒中患者功能恢复的潜力的初步数据。中风是心血管疾病的终点，是美国残疾的主要原因，估计有580万美国人患有中风所致的残余神经功能缺损。目前的中风康复方法涉及密集的，治疗师指导的任务实践，这是昂贵的，在某些情况下，在促进功能性神经运动恢复无效。确定一种安全、具有成本效益的方法，如强迫有氧运动，以促进卒中后功能的恢复，将降低与强化康复相关的成本，同时降低卒中幸存者中普遍存在的心血管危险因素。动物和人类的文献表明，高速率有氧运动的急性发作导致神经营养因子，包括脑源性神经营养因子（BDNF）和胶质源性神经营养因子（GDNF）的浓度增加。这些神经营养因子被认为是促进神经保护、神经恢复和神经可塑性的机制。据报道，运动和认知功能的临床改善是由于密集的有氧运动训练，假设是由于这种内源性神经营养素的释放。这些神经功能的整体变化尚未在卒中患者中报道。PI假设中风的病理生理学限制了持续的高速率和高强度运动，阻止了这些神经营养因子的内源性释放。PI在帕金森病（PD）患者中开发了一种安全的下肢强制运动干预，使他们能够达到高于自愿运动率的运动率。经过8周的强迫运动干预，PD患者在整体运动功能、精细运动上肢功能、认知和嗅觉方面表现出显著改善。基于fMRI数据，PD患者的急性强迫运动表明强迫运动和抗帕金森病药物之间的皮质和皮质下激活模式相似，这表明强迫运动确实改变了脑功能。为探讨有氧运动对脑卒中患者功能恢复的影响，拟进行为期两年的单中心、平行组、评分者盲法初步研究。将总共30例慢性（术后6-12个月）脑卒中伴残余轻偏瘫患者随机分配至三组之一：强迫运动和重复性任务练习联合组（FE+RTP）、自主运动和重复性任务练习联合组（VE+RTP）或剂量匹配的仅RTP组（仅RTP）。所有三组将在8周的疗程中接受相同剂量的康复时间（每周3次）;然而，组合组将在50%的疗程中进行强迫或自愿运动，并在剩余的50%疗程中进行RTP。只有RTP组将专门从事RTP。将在基线、治疗中期和治疗结束（EOT）时收集结局。假设强迫运动干预将有助于预充中枢神经系统，从而改善FE+RTP组的临床结局。预计两个运动组的有氧能力都有相当的改善。如果强迫运动被证明是有效的，它可能成为目前神经康复方法的一个可行的辅助手段，在促进神经恢复的同时改善心血管健康。

DESCRIPTION (provided by applicant): The goal of this study is to gather initial data regarding the potential of forced aerobic exercise to augment recovery of function in patients with stroke. Stroke, an endpoint of cardiovascular disease, is the leading cause of disability in the United States, and an estimated 5.8 million Americans are living with residual neurologic deficit due to stroke. Current approaches to stroke rehabilitation involve intensive, therapist-directed task practice that is both expensive and, in some cases, ineffective in fostering functional neuromotor recovery. The identification of a safe, cost-effective approach, such as forced aerobic exercise, to augment the recovery of function post-stroke would reduce the cost associated with intensive rehabilitation while simultaneously decreasing the cardiovascular risk factors prevalent in stroke survivors. Animal and human literature reveal that acute bouts of high-rate aerobic exercise results in increased concentrations of neurotrophic factors including brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF). These neurotrophic factors have been implicated as the mechanism that promotes neuroprotection, neurorecovery, and neuroplasticity. Clinical improvements in motor and cognitive function have been reported as a result of intensive aerobic exercise training, hypothesized to be due to this endogenous release of neurotrophins. These global changes in neurologic function have not been reported in patients with stroke. The PIs hypothesize that the pathophysiology of stroke, which limits sustained high rate and high intensity exercise, prevents the endogenous release of these neurotrophic factors. The PIs developed a safe lower extremity forced exercise intervention in Parkinson's disease (PD) patients that allows them to achieve an exercise rate greater than their voluntary rate. Following an eight week forced exercise intervention, PD patients exhibit significant improvements in global motor functioning, fine motor upper extremity function, cognition and olfaction. Based on fMRI data, acute forced exercise in PD patients indicates a similar pattern of cortical and subcortical activation between forced exercise and antiparkinsonian medication, suggesting forced-exercise does alter brain function. To investigate the effects of aerobic exercise on the recovery of function in stroke patients, a two year, single-center, parallel-group, rater-blind preliminary study is proposed. A total of 30 chronic (6-12 months post) stroke patients with residual hemiparesis will be randomized to one of three groups: combined forced-exercise and repetitive task practice (FE+RTP), combined voluntary exercise and repetitive task practice (VE+RTP) or a dose-matched RTP only (RTP only) group. All three groups will receive an identical dose of rehabilitation time over a course o 8 weeks (3X per week); however, the combination groups will perform forced or voluntary exercise for 50% of the session and RTP for the remaining 50% of the session. The RTP only group will engage in RTP exclusively. Outcomes will be gathered at baseline, mid-treatment and end of treatment (EOT). It is hypothesized that the forced-exercise intervention will serve to prime the central nervous system resulting in improved clinical outcomes for the FE+RTP group. Comparable improvements in aerobic capacity are expected for both exercise groups. If forced exercise is shown effective, it could become a viable adjunct to current neurorehabilitation approaches in driving neural recovery while simultaneously improving cardiovascular health.