Delineating Physiologic Mechanisms of Swallowing impairment and Decline in ALS

肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病， 虚弱和吞咽障碍（吞咽困难）。吞咽困难导致营养不良、脱水、气管 吸入和肺炎导致ALS死亡率的26%。目前的提案动机很强 基础知识差距导致ALS患者的临床护理欠佳 以及缺乏管理ALS患者进行性吞咽障碍的正式实践指南。 这项工作的总体目标是通过1）增加我们对以下方面的理解来改善临床实践： ALS中吞咽困难的控制机制和进展，以及2）鉴定 吞咽功能障碍，以建立一个临床吞咽困难的风险指数工具。我们将表演一系列的器乐 100例ALS患者（50例延髓发作，50例脊髓发作）的吞咽评估 并提供关键的纵向数据，以帮助建立第一个时间过程模型 吞咽能力下降的几率需要这样一个模型来指导最佳做法建议， 干预措施，用于规划和设计未来的临床试验，以及解释实验性治疗 方面的影响.我们还将测试一组有前途的临床标志物的判别能力和临床效用， 吞咽下降，实用地设计为易于传播到ALS临床环境中。我们长久以来- 长期目标是改善ALS吞咽障碍的临床护理。这项研究将提供新的 深入了解ALS患者不安全和无效吞咽的病理生理机制， 制定未来的干预战略，并导致更早和更准确地识别 吞咽障碍ALS吞咽功能障碍的早期识别和更好的治疗策略 将导致口服摄入量，营养，肺部健康和生活质量的改善，并最终减少 吸入性肺炎相关的死亡率。

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing progressive muscle weakness and impairments in swallowing (dysphagia). Dysphagia leads to malnutrition, dehydration, tracheal aspiration and pneumonia that contribute to 26% of ALS mortality. The current proposal is strongly motivated by fundamental knowledge gaps that have contributed to sub-optimal clinical care of individuals with ALS and a lack of formal practice guidelines in the management of progressive swallowing impairment in ALS. The overarching goal of this work is to improve clinical practice by 1) increasing our understanding of governing mechanisms and progression of dysphagia in ALS and 2) identification of sensitive biomarkers of swallowing dysfunction to build a clinical dysphagia risk index tool. We will perform serial instrumental swallowing evaluations in 100 individuals with ALS (50 bulbar-onset, 50 spinal-onset) from disease diagnosis to feeding-tube dependence and provide critical longitudinal data to help establish the first time-course model of ALS swallowing decline. Such a model is needed to guide best practice recommendations, optimal timing of interventions, for planning and design of future clinical trials, and for interpretation of experimental treatment effects. We will also test the discriminant ability and clinical utility of a set of promising clinical markers of swallowing decline that are pragmatically designed for easy dissemination into ALS clinical settings. Our long- term goal is to improve clinical care of swallowing disorders in ALS. The proposed study will deliver new insights into the pathophysiologic mechanisms of unsafe and inefficient swallowing in ALS to drive the development of future intervention strategies and lead to earlier and more accurate identification of swallowing impairment. Earlier identification and better treatment strategies for swallowing dysfunction in ALS will lead to improvements in oral intake, nutrition, pulmonary health and quality of life and ultimately reduce aspiration pneumonia associated mortality in this challenging population.