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)的“包装”或结缔组织的生物力学特性的计算模型，以阐明它们在单侧声带瘫痪(UVP)发病中的作用。声带在吞咽过程中对保护呼吸道、调节呼吸和发声都很重要。患有UVP的患者经常在进食时窒息，呼吸困难，说话困难。大多数被诊断为UVP的人年龄都在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%)没有已知的原因(即特发性)。UVP的外科病因与术中或术后所遭受的神经或神经组织损伤有关。先前在马身上研究特发性UVP的工作表明，RLN的慢性压迫发生在主动脉弓或下气管附近。事实上，最近的研究表明，特发性UVP患者可能与胸主动脉瘤相关的主动脉弓水平的RLN受损。动脉瘤，或者是主动脉顺应性增加，会对毗邻主动脉的RLN施加更大的拉伸和压缩，从而损害神经功能。我们最近的研究发现，位于两侧颈部的喉返神经结缔组织与位于胸腔内的左侧喉返神经部分(包括主动脉弓区)的结缔组织成分存在差异。这些发现支持桑德兰的理论，即周围神经内的结缔组织模式可能会随着神经暴露在环境中的力量而发展。此外，仔猪和青年猪之间以及中年和老年人之间RLN的数量和组成也存在差异，这表明结缔组织的变化随着年龄的增长而继续变化。考虑到UVP在年龄较大的人和动物中比年轻人更常见，这表明有必要考虑与年龄相关的结缔组织变化作为一个潜在的促成因素。这项拟议研究的目的是开发一个关于喉返神经结缔组织的计算模型，该模型将被用来测试在有无UVP的受试者中施加于喉返神经的力的差异。该模型还将用于进行模拟，以预测对喉返神经结缔组织造成损害所需的拉伸或压缩程度，从而导致神经损害，如可能发生的与手术病因有关的损害。利用猪和人的喉返神经组织开发这一模型，可以比较这些物种之间的异同，以便将来使用猪模型对引起UVP发病所需的喉返神经组织变形水平的预测研究的结果可以推广到人。

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.