Sensory-driven motor recovery in poorly recovered subacute stroke patients

描述（由申请人提供）：项目摘要中风是美国长期残疾的主要原因。大约70-88%的中风患者有一定程度的运动障碍。中风康复研究的一个主要目标是在神经损伤发生后利用大脑的重组能力，从而最终导致功能的成功恢复。来自动物和人类模型的数据表明，感觉输入在运动输出中起着重要作用，可能是通过影响皮质可塑性。然而，尽管到目前为止的进展，很少有人知道在何种程度上的感觉输入的形式周围神经刺激（PNS）可以成功地结合到运动训练，特别是在恢复不良的亚急性中风患者。本研究将评估持续PNS结合运动训练对改善亚急性脑卒中患者手部运动功能的有效性。我们在慢性中风患者中的初步数据表明，当PNS与运动训练配对时，运动功能可以得到显著增强。此外，一项针对仅接受运动训练的轻度运动缺陷患者的单独研究表明，提供运动训练的最佳治疗时间窗是在卒中后第一年内。行为运动功能的改善与皮质运动重组有关。因此，我们现在建议评估持续PNS配合运动训练的有效性，以促进亚急性脑卒中患者严重运动障碍的功能恢复。中心假设是，与接受假PNS和任务导向治疗的患者相比，以及与仅接受PNS的患者相比，接受PNS和强化任务导向治疗的严重运动缺陷的亚急性卒中患者的运动功能将得到改善。此外，这种行为测量的效果的程度将与经颅磁刺激测量的神经生理学效果相关。我们计划通过完成两个特定目的来接受或拒绝中心假设：1）测试PNS在任务导向治疗之前对手部运动功能的影响，以及2）测试PNS在任务导向治疗之前对经颅磁刺激测量的运动地图的影响。长期目标是：a）最大限度地恢复中风后的手部运动功能，B）确定这种干预对日常生活活动的影响。公共卫生相关性这个研究项目解决了一个无法通过其他方式回答的重要科学问题。使用周围神经刺激有可能促进功能恢复较差的亚急性卒中患者的恢复。本提案的主要目的是证明，与单独的强化训练或单独的神经刺激相比，外周神经刺激结合强化运动训练能够进一步改善手部运动功能。这项研究的结果有可能开发新的神经康复策略。本研究中受试者的风险非常低。

DESCRIPTION (provided by applicant): Project Summary Stroke is the leading cause of long-term disability in the United States. Approximately 70-88% of persons with stroke have some degree of motor impairment. A major goal of research in stroke rehabilitation is to harness the ability of the brain to reorganize after neurologic damage has occurred and thus ultimately lead to successful recovery of function. Data from animal and human models have suggested that sensory input plays an important role in motor output, possibly by influencing cortical plasticity. However, in spite of the advances to date, little is known about the extent to which sensory input in the form of peripheral nerve stimulation (PNS) can be successfully combined to motor training, especially in poorly recovered subacute stroke patients. The proposed study will evaluate the effectiveness of sustained PNS coupled with motor training, to improve hand motor function in subacute stroke patients with severe motor deficit. Our preliminary data in chronic stroke patients with severe motor deficit demonstrate that motor function can be substantially enhanced when PNS is paired with motor training. In addition, a separate study in patients with mild motor deficit receiving motor training alone suggests that the optimal therapeutic time window to deliver motor training is within the first year after stroke. The improvement of behavioral motor function was associated with corticomotor reorganization. Therefore, we now propose to evaluate the effectiveness of sustained PNS paired with motor training, to promote functional motor recovery in subacute stroke patients with severe motor deficit. The central hypothesis is that subacute stroke patients with severe motor deficit receiving PNS and intensive task-oriented therapy will have improved motor function compared to patients receiving sham-PNS and task-oriented therapy and also when compared to patients receiving PNS-only. Further, the degree of this behaviorally-measured effect will correlate with the neurophysiological effect measured by transcranial magnetic stimulation. We plan to accept or reject the central hypothesis by accomplishing two Specific Aims: 1) test the effect of PNS preceding task-oriented therapy on hand motor function, and 2) test the effect of PNS preceding task-oriented therapy on motor map measured by transcranial magnetic stimulation. The long-range goals are: a) to maximize the restoration of hand motor function after stroke, b) to determine the impact of this intervention in activities of daily living. PUBLIC HEALTH RELEVANCE This research project addresses a scientifically important question that cannot be answered by other means. The use of peripheral nerve stimulation has the potential to enhance recovery in subacute stroke patients with poor functional recovery. The primary objective of this proposal is to demonstrate that peripheral nerve stimulation combined with intensive motor training has the ability to further improve hand motor function when compared to intensive training alone or nerve stimulation alone. The results from this study have the potential to develop new strategies in neurorehabilitation. The risk involved to subjects in this study is very low.