Motor impairment related changes in muscles properties in chronic stroke

 描述(申请人提供)：手臂功能受损是中风幸存者慢性残疾的主要原因。已经开发了许多治疗方法来促进手臂功能的恢复，针对中风引起的运动损伤，如瘫痪、痉挛和导致不自主肘关节、手腕关节控制丧失的运动障碍。 以及抬臂时手指屈曲(即屈曲协同作用)。然而，我们对此的理解 目前还不清楚肌肉如何随着时间的推移适应这些损伤，也不清楚肌肉特性的变化如何影响瘫痪手臂的功能使用。因此，我们建议确定偏瘫手臂骨骼肌结构变化的程度，这是由于持续存在显著的屈曲协同作用、轻瘫和与瘫痪上肢相关的废用。随后，我们建议通过使用手臂和手的组合运动的新的模拟来展示这些继发性肌肉骨骼变化对产生功能性手臂运动的能力的影响。我们推测，中风导致的屈曲协同、轻瘫和瘫痪上肢的慢性废弃，导致被动和主动肌肉特性的实质性变化，从而限制了产生功能性手臂运动的能力，即使来自大脑的正常神经驱动将被恢复。在目标1中，我们建议调查异常的屈曲协同作用和被动僵硬增加之间的关系，这会导致中风患者更多的手臂屈曲姿势。在目标2中，我们建议描述中风后肌肉结构参数(即肌束和肌节长度以及肌肉体积)的变化，并通过计算肌肉生理横截面积来确定年龄匹配的健全个体的任何结构偏差对最大等长力产生能力的影响，肌肉生理横截面积是衡量单个肌肉产生力量的标准解剖学指标。最后，作为目标3的一部分，我们建议使用最先进的正向动力学模拟技术，使用集成手臂和手的上肢模型来确定肌肉属性改变(目标1和2)和异常肌肉协同激活模式(目标1)在多大程度上解释了慢性偏瘫中风患者上肢功能使用的严重限制。这项拟议的研究的基本原理是，确定肌肉特性改变对慢性偏瘫后偏瘫上肢功能使用的确切作用将有助于设计更有效的康复干预措施。这将通过强调各种肌肉骨骼变化的相对重要性来改变临床医生处理瘫痪上肢康复的方式，这些变化与拟议的测量工具相结合，提供了设计和测试治疗方法的手段，以减少或防止中风后肌肉的有害变化。

 DESCRIPTION (provided by applicant): Impaired arm function is a major cause of chronic disability among stroke survivors. A number of treatment approaches have been developed to facilitate the recovery of arm function, targeting stroke induced motor impairments such as paresis, spasticity and losses of independent joint control that result in involuntary elbow, wrist and finger flexion while lifting the arm (i.e., the flexion synergy). However, our understanding of how muscle adapts to these impairments over time is not clear at this juncture nor how changes in muscle properties impact the functional use of the paretic arm. Therefore, we propose to determine the extent of structural changes in the skeletal muscles of the paretic arm due to the persistence of a prominent flexion synergy, paresis, and the associated disuse of the paretic upper limb. Subsequently, we propose to demonstrate the effects of these secondary musculoskeletal changes on the ability to generate functional arm movements by using novel simulations of combined arm and hand motion. We postulate that the flexion synergy, paresis, and the chronic disuse of the paretic upper limb that results from the stroke, induce substantial changes in both passive and active muscle properties, thus limiting the ability to generate functional arm movements, even if normal neural drive from the brain would be restored. In Aim 1, we propose to investigate the relationship between the abnormal flexion synergy and increases in passive stiffness that result in more flexed arm postures in individuals with stroke. In Aim 2 we propose to characterize changes in muscle architectural parameters (i.e., fascicle and sarcomere length, and muscle volume) following stroke and determine the effect of any structural deviations from age-matched able-bodied individuals on maximum isometric force generation ability, as indicated by calculating muscle physiological cross-sectional area, a standard anatomical measure of an individual muscle's ability to generate force. Finally, as part of Aim 3 we propose to employ state-of-the-art forward dynamics simulation techniques using an upper limb model that integrates the arm and hand to determine the extent to which altered muscle properties (Aims 1 & 2) and abnormal muscle co-activation patterns (Aim 1) account for the severe limitations in functional use of the upper limb experienced by individuals with chronic hemiparetic stroke. The rationale that underlies the proposed research is that determining the exact role of altered muscle properties on functional use of the paretic upper limb following chronic hemiparetic stroke will allow for the design of more effective rehabilitation interventions This will change the way clinicians approach the rehabilitation of the paretic upper limb by highlighting the relative importance of the various musculoskeletal changes which combined with the proposed measurement tools provide the means to design and test therapies to reduce or prevent detrimental changes in muscle following stroke.