Motor Function after Stroke

描述(申请人提供)：中风后的自然恢复通常是不完整的，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切地挽救组织，而是通过改变存活到慢性期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中风患者的很高比例。对于此类疗法的最佳处方，可提供的指导有限。在处于慢性高原阶段的患者中，哪些特征表明有可能通过治疗减少残疾，哪些特征表明缺陷是固定的？为了解决这个问题，108名在过去20周内中风且运动状态达到平台期的患者将接受多个领域的评估，包括人口统计学、临床、放射学、脑成像、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有关的临床评估。这项研究假设，通过行为检查(在这种情况下选择患者的常用手段)预测治疗反应的能力在增加几项指标后得到显著改善，特别是脑损伤和功能。分析还将定义一个伤害阈值，表明哪些患者可能会通过治疗改善，或者不会。其他分析将集中在一个拟议的习得性停用模型上：识别那些中风后幸存下来的大脑区域未得到充分利用的患者的能力，将有助于慢性中风治疗。其中一个特别令人感兴趣的指标是BDNF基因。BDNF Val66Met多态存在于大约四分之一的人中，与某些皮质可塑性指标的降低有关，可能对预测自发性和治疗诱导的卒中康复具有特别重要的意义。这将在108名患者的治疗研究中进行评估，以及对9个地点的150名患者的自然恢复进行研究。残疾多年来一直影响着中风患者。一些专注于中枢神经系统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。这项拟议研究的总体假设是，表征中枢神经系统的损伤和功能将提供有助于对人类中风患者进行最佳恢复性治疗的神经生物学见解。这些知识应该有助于减少适当针对性的中风患者的残疾。公共卫生相关性：中风是致残的主要原因。一种相对较新的疗法可能会帮助大脑修复，甚至在中风的晚期，从而帮助减少这个问题的规模。这里描述的研究旨在提出一些重要的问题，这些问题一旦得到回答，将使这些新疗法离广泛应用更近一大步。

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.