Surgical and Rehabilitative Management of Facial Nerve Injury

描述(申请人提供)：运动神经损伤通常是毁灭性的；即使是最复杂的修复受伤的神经也很少能导致令人满意的功能恢复。面部神经的损伤尤其严重，因为眨眼、吃饭、说话和通过面部表情交流的能力都受到了极大的影响。与之相关的严重面部毁容也会产生深远的社会和心理后果。在过去的五年里，我们的实验室创建了一种高度定量的方法学，用于实时测量啮齿类动物面神经损伤后的恢复情况。通过这个系统，我们已经证明了几种药物可以加速恢复，几种不能，某些类型的机械刺激和电刺激分别对肌肉和神经都有促进和改善面神经损伤恢复的作用。康复领域的最新发现有力地表明，机器人或计算机辅助的康复方法可以改善神经损伤后的运动恢复，特别是在将动机和学习的元素引入治疗范式的情况下。通过纳入患者在任何给定恢复点的精确功能水平的数据，并通过激励策略确保患者参与，定制的感觉运动康复已被证明比简单的被动辅助疗法更有效，后者提供机械辅助，无论受试者的功能水平如何。在这项建议中，我们应用和比较了几种不同的康复方法来修复轴突切断(挤压)和神经切断(切割)损伤后再生的啮齿动物面神经。我们将通过逐次近似的方式提供口头奖励疗法，以介绍被证明是人类运动恢复的重要因素的激励因素。我们还将为失神经肌肉提供不同形式的被动辅助治疗(机械刺激)。我们将比较固定时间表的被动辅助疗法和定制的动态被动辅助疗法，这些疗法旨在对啮齿动物的正常和恢复行为(即，将老鼠的解剖向外移动以配合它们预期的运动输出)做出反应，并将研究这两种方式的组合。此外，我们还将通过感觉神经与失神经肌肉的粘连来研究保留面肌结构对面神经损伤和修复后整体恢复的影响。 与公共卫生相关：在美国，周围神经损伤是巨大残疾的一个来源；发现更有效的方法来加速和改善这些损伤的康复将是巨大的好处。利用啮齿动物模型，我们建议在面神经损伤和修复后采用计算机辅助的、针对患者的感觉和运动康复治疗，以衡量其益处并使其效果最大化。

DESCRIPTION (provided by applicant): Motor nerve injuries are often devastating; even the most sophisticated repair of an injured nerve rarely leads to satisfactory restoration of function. Damage to the facial nerve is particularly disabling because the ability to blink, eat, speak, and communicate through facial expressions are all dramatically affected. The associated severe facial disfigurement also has profound social and psychological consequences. Over the past five years, our laboratory has created a highly quantitative methodology for real-time measurement of recovery from facial nerve injury in the rodent. With this system we have demonstrated that several pharmacologic agents accelerate recovery, several do not, and that certain types of mechanical and electrical stimulation to the muscles and nerves, respectively, both accelerate and improve recovery from facial nerve injury. Recent findings in the field of rehabilitation strongly suggest that robot- or computer-assisted rehabilitation methods improve motor recovery after neurologic injury, particularly when the elements of motivation and learning are introduced into the therapeutic paradigm. By incorporating data from the precise level of patient function at any given point in recovery, and assuring patient participation via motivational strategies, customized sensorimotor rehabilitation has proven more effective than simple passive assistance therapies, which provide mechanical assistance irrespective of the subject's level of function. In this proposal, we apply and compare several different rehabilitative modalities to the regenerating rodent facial nerve after both axonotmesis (crush) and neurotmesis (cut) injuries. We will delivery oral reward therapy through successive approximations, in order to introduce the motivational element demonstrated to be an important factor in human motor recovery. We will also deliver different forms of passive assistance therapy (mechanical stimulation) to denervated muscles. We will compare fixed-schedule passive assistance therapy with customized, dynamic passive assistance therapy designed to respond to the rodent's normal and recovering behavior (i.e. externally moving the rat's anatomy in concert with their intended motor output), and will also examine combinations of both modalities together. In addition, we will examine the effect of preserving facial muscle architecture, via coaptation of a sensory nerve to the denervated muscle, on overall recovery following facial nerve injury and repair. PUBLIC HEALTH RELEVANCE: Peripheral nerve injuries are a source of enormous disability in the United States; the discovery of more effective ways of accelerating and improving recovery from these injuries would be of enormous benefit. Using a rodent model, we propose to employ computer-assisted, patient-specific sensory and motor rehabilitative therapy following facial nerve injury and repair, to measure its benefit and maximize its effect.