Recurrent laryngeal nerve connective tissues as a factor in vocal fold paralysis

描述（由申请人提供）：本研究的目标是开发迷走神经喉返支（RLN）结缔组织的“包装”或结缔组织的生物力学特性的计算模型，以确定其在单侧声带麻痹（UVP）发病中的作用。声带对吞咽时气道的保护、呼吸的调节和发声都很重要。UVP患者在进食时经常出现窒息、呼吸困难和说话困难。大多数被诊断为UVP的个体年龄在45岁以上。UVP最常见的发病与手术有关，第二常见的发病（12-42%）没有已知原因（即特发性）。UVP的外科病因与手术期间或术后遭受的神经或神经组织损伤有关。先前对马特发性UVP发病的研究表明，慢性压迫RLN发生在主动脉弓或下气管附近。事实上，最近的研究表明，患有特发性UVP的个体可能在主动脉弓水平有与胸动脉瘤相关的RLN损伤。动脉瘤，或者说是主动脉顺应性的增加，会对靠近主动脉的RLN施加更多的拉伸和压迫，从而损害神经功能。我们最近的研究发现，双侧颈部的RLN结缔组织组成与左侧胸腔内的RLN部分（包括主动脉弓区域）存在差异。这些发现支持了桑德兰的理论，即周围神经内的结缔组织模式可能是对神经所暴露的环境力量作出反应而形成的。此外，仔猪和年轻成年猪以及中年人和老年人之间RLN的数量和组成存在差异，这表明结缔组织的变化会随着年龄的增长而持续。鉴于UVP在老年人中比在年轻人和动物中更常见，这表明有必要考虑与年龄相关的结缔组织变化是一个潜在的促成因素。拟议研究的目的是开发RLN结缔组织的计算模型，该模型将用于测试在有和没有UVP的受试者中施加在RLN上的力的差异。该模型还将用于进行模拟，以预测引起RLN结缔组织损伤所需的拉伸或压缩程度，从而导致可能与手术病因相关的神经损伤。使用猪和人类RLN组织开发的该模型可以比较这两个物种之间的异同，以便将来使用猪模型对引起UVP发作所需的RLN组织变形预测水平的研究结果可以推广到人类。

DESCRIPTION (provided by applicant): The goal of this research is to develop a computational model of the biomechanical properties of the "packaging," or connective tissues of the recurrent laryngeal branch (RLN) of the vagus nerve to formulate their role in the onset of unilateral vocal fold paralysis (UVP). The vocal folds are important for protection of the airway during swallowing, the regulation of breathing, and for voice production. Individuals with UVP frequently experience choking while eating, difficulty breathing, and difficulty speaking. The majority of individuals diagnosed with UVP are older than 45 years of age. The most common onset of UVP occurs related to surgery with the second most common onset (12-42%) having no known cause (i.e. idiopathic). Surgical etiology of UVP is associated with nerve or nerve tissue damage suffered during or possibly after surgery. Previous work studying idiopathic onset of UVP in horses suggested that chronic compression to the RLN occurred near the aortic arch or inferior trachea. In fact, recent research has shown that individuals with idiopathic UVP may have damage to the RLN at the level of the aortic arch related to a thoracic aneurysm. An aneurysm, or alternatively, increased aortic compliance, would impose increased stretch and compression to the RLN where it is adjacent to the aorta that can impair nerve function. Our recent studies have found differences in the composition of the RLN connective tissues between its location within the neck bilaterally and the portion of the left RLN within the thorax, including the aortic arch region. These findings support Sunderland's theory that connective tissue patterns within peripheral nerves may develop in response to environmental forces to which the nerve is exposed. In addition, differences in the quantity and composition of the RLN were demonstrated between piglets and young adult pigs and between middle age adults and elderly humans indicating that connective tissue changes continue with aging. Given that UVP occurs more often in older than younger humans and animals suggests the need to consider age-related connective tissue changes as a potential contributing factor. The purpose of the proposed research is to develop a computational model of RLN connective tissues that will be used to test for differences in forces imposed on the RLN in subjects with and without UVP. This model will also be used to conduct simulations to predict the degree of stretch or compression necessary to cause damage to RLN connective tissues leading to nerve impairment such as might occur related to the surgical etiology. Development of this model using both pig and human RLN tissues allows for comparison of the similarities and differences between these species so that outcomes from future investigation of predicted levels of RLN tissue deformation necessary to cause onset of UVP using a pig model can be generalized to people.