Effects of Strength Training on Bulbar Function in Amyotrophic Lateral Sclerosis

描述(申请人提供)：肌萎缩侧索硬化症(ALS)中以进行性言语、吞咽和呼吸障碍为形式的延髓功能障碍非常普遍，加起来占疾病死亡率的95%。虽然进行性肌肉无力是肌萎缩侧索硬化症的主要症状，但运动和力量训练对这一患者群体的影响存在争议。虽然历史上一直不鼓励ALS患者进行运动，因为担心肌肉负担过重可能会导致身体衰退，但最近的动物和人类数据表明，在疾病的早期进行中等强度的运动可能对ALS起到神经保护作用。事实上，来自我们实验室的令人兴奋的初步数据表明，对轻、中度ALS患者进行呼气肌力训练(EMST)方案对呼气力生成能力、吞咽时的呼吸道保护和咳嗽、吞咽运动学、自我报告的吞咽严重程度和与吞咽相关的生活质量有积极效果。这项建议的中心目标是通过一项盲法、假对照、随机临床试验来研究为期8周的Emst方案对轻度至中度ALS患者球功能的影响。这一建议的中心假设是，每天8周的中等强度耐力运动将积极参与ALS患者的呼气和精神下肌肉，阻止废用萎缩，并延长ALS患者的呼吸道保护、吞咽和功能性口服功能。这项拟议的研究旨在具体确定Emst对以下方面的影响：1)呼气力产生能力(最大呼气压力)；2)吞咽过程中的吞咽生理和呼吸道安全；3)咳嗽功能；4)口服功能、吞咽相关的生活质量和自我报告的吞咽严重程度；5)轻至中度ALS患者的疾病进展。这一结果将为肌力训练在改善ALS患者球功能方面的潜在作用提供有价值的见解，并将有助于指导这种毁灭性疾病的未来研究和治疗方向。

DESCRIPTION (provided by applicant): Bulbar dysfunction in the form of progressive speech, swallow and respiratory impairment are highly prevalent in Amyotrophic Lateral Sclerosis (ALS) and together account for 95% of disease mortality. Although progressive muscle weakness is the primary sign of ALS, the effects of exercise and strength training in this patient population i controversial. While exercise in persons with ALS has historically been discouraged due to fear that muscle overburden may execrate physical decline, recent animal and human data suggest that moderate intensity exercise applied early in the disease may serve a neuroprotective role in ALS. Indeed, exciting preliminary data from our laboratory indicate that a regimen of expiratory muscle strength training (EMST) in persons with mild-moderate ALS has a positive effect on expiratory force generating abilities, airway protection and cough during swallowing, swallow kinematics, self-reported swallow severity and swallow- related quality of life. The central goal o this proposal is to investigate the effects of an eight-week regimen of EMST on bulbar function in persons with mild to moderate ALS using a blinded, sham-controlled, randomized clinical trial. The central hypothesis of this proposal is that eight-weeks of daily moderate intensity resistance EMST exercise will actively engage the expiratory and submental musculature, deter disuse atrophy and prolong function of airway protection, swallowing and functional oral intake in persons with ALS. The proposed study is designed to specifically determine the effect of EMST on: 1) expiratory force generating ability (maximum expiratory pressure); 2) swallow physiology and airway safety during swallow; 3) cough function; 4) functional oral intake, swallow-related quality of life and self-reported swallow severity; 5) and subsequent disease progression in persons with mild to moderate ALS. The results will provide valuable insight into the potential role of muscle strength training for improving bulbar function in persons with ALS and will help guide the future direction of research and treatment for this devastating disorder.