Motor Function after Stroke

描述（由申请人提供）：中风后的自然恢复通常是不完全的，使中风后残疾成为一个非常普遍的问题。新的治疗方法正在开发中，以减少中风慢性期患者的残疾。这种疗法的目的不是通过急性抢救组织，而是通过改变存活到慢性阶段的大脑元素的功能来改善行为状态。这种恢复性方法有可能达到高比例的中风受试者。有限的指导可用于此类治疗的最佳处方。在慢性平台期的患者中，哪些特征表明治疗有可能减少残疾，哪些特征表明缺陷是固定的？为了解决这一问题，将在多个领域对108名在过去20周内发生过卒中且运动状态已达到平台期的患者进行评估，包括人口统计学、临床、放射学、脑映射、神经生理学和遗传学测量。随后将进行为期3周的标准化手臂运动治疗，之后将重新检查与手臂运动功能相关的临床评估。本研究假设，使用行为检查（在这种情况下选择患者的常用方法）预测治疗反应的能力随着几项措施的增加而大大提高，特别是脑损伤和功能。分析还将定义一个损伤阈值，表明哪些患者可能或不可能通过治疗改善。其他分析将集中在一个拟议的学习废用模型：识别那些在中风后幸存下来的大脑区域使用不足的患者的能力将有助于慢性中风治疗。一个特别感兴趣的指标是BDNF基因型。BDNF val 66 met多态性存在于大约1/4的人群中，与某些皮质可塑性指标的降低相关，并且可能对预测自发性和治疗诱导的卒中恢复特别重要。这将在108例患者治疗研究以及9个研究中心150例患者自发恢复研究中进行评价。残疾影响中风患者多年。一些专注于CNS修复的新疗法可能会改善这种情况。然而，应用这些疗法的最佳方法尚不清楚，特别是选择那些最有可能对治疗有反应的患者的问题。拟议研究的总体假设是，表征中枢神经系统损伤和功能将提供神经生物学的见解有用的最佳应用恢复性治疗人类中风患者。这些知识应有助于减少适当目标中风患者的残疾。 公共卫生相关性： 中风是导致残疾的主要原因。一种相对较新的治疗方法可能有助于通过帮助大脑修复来减少这个问题的规模，即使是在中风的晚期。这里描述的研究旨在提出重要的问题，当这些问题得到回答时，将使这些新疗法更接近广泛使用。

DESCRIPTION (provided by applicant): Spontaneous recovery after stroke is generally incomplete, making post-stroke disability a highly prevalent problem. New therapies are in development to reduce disability in patients in the chronic phase of stroke. Such therapies aim to improve behavioral status not by acutely salvaging tissue but by changing function in brain elements that survive to the chronic phase. This restorative approach has the potential to reach a high fraction of subjects with stroke. Limited guidance is available for optimal prescription of such therapies. Among patients in the chronic plateau phase, which characteristics suggest potential for reducing disability with therapy, and which suggest that deficits are instead fixed? To address this issue, 108 patients who have had a stroke in the last 20 weeks and whose motor status has reached a plateau will be evaluated, in multiple domains, including demographic, clinical, radiological, brain mapping, neurophysiological, and genetic measures. A 3-week course of standardized arm motor therapy will follow, after which clinical assessments related to arm motor function will be rechecked. This study hypothesizes that the ability to predict treatment response using behavioral exam (the usual means of selecting patients in this context) is substantially improved with addition of several measures, particularly of brain injury and function. Analyses will also define an injury threshold that indicates which patients are, or are not, likely to improve with therapy. Other analyses will focus on a proposed model of learned disuse: the ability to identify those patients who are underusing brain regions that survived the stroke would aid chronic stroke therapies. One measure of particular interest is BDNF genotype. The BDNF val66met polymorphism is present in approximately 1/4th of people, has been associated with reduction in certain measures of cortical plasticity, and might be of particular importance to predicting both spontaneous and therapy-induced stroke recovery. This will be evaluated in the 108 patient therapy study, as well as a study of spontaneous recovery in 150 patients across 9 sites. Disability affects stroke patients for many years. A number of new therapies focused on CNS repair might improve this situation. However, optimal approach to applying these therapies is unclear, particularly the issue of selecting those patients most likely to respond to therapy. The overall hypothesis of the proposed study is that characterizing CNS injury and function will provide neurobiological insights useful for optimally applying restorative therapies to human patients with stroke. Such knowledge should facilitate reducing disability in appropriately targeted patients with stroke. PUBLIC HEALTH RELEVANCE: Stroke is a major cause of disability. A relatively new class of therapies might help reduce the size of this problem by aiding brain repair, even in the late stages of stroke. The studies described here aim to ask important questions that, when answered, will bring these new therapies a major step closer to widespread use.