Bulbar Motor Deterioration in ALS

描述(申请人提供)：本申请的目的是提高对肌萎缩侧索硬化症(ALS)的球(头)恶化的了解，ALS，也被称为“Lou Gehrig病”，是一种致命的神经系统疾病，由运动皮质、脑干和脊髓中的运动神经元退化引起。尽管延髓退化对ALS患者的生存和生活质量造成了毁灭性的后果，包括言语障碍和吞咽障碍，但与ALS脊柱受累的研究相比，针对ALS延髓症状的研究寥寥无几。这一应用程序通过使用记录、测量和分析言语行为的既定和创新方法，纵向和全面地研究球部下降，回应了临床和科学知识的这一差距。100名肌萎缩侧索硬化症患者将在两年内每三个月接受一次研究。将使用多个球性能测量纵向跟踪每个参与者的语音恶化过程，其中每个测量大致被归类为在全局(即，语音系统)级别或子系统级别的代表性语音性能。语音子系统测量将代表已知的支持语音产生的多个球区域的功能完整性，包括呼吸、发音、共鸣和发音子系统。每个语音系统和子系统的下降模式将被用来解决四个具体目标：(1)确定疾病早期的语音子系统性能是否准确地预测长期的衰减率，(2)确定语音子系统的测量是否准确地预测言语衰退的开始和随后的口头交流的丧失，(3)确定球退化的开始和速度的敏感的量化指标，以及(4)确定几种可能的球ALS亚型。在短期内，确定球部受累的敏感指标将提高早期发现和预后准确性，并解决在未来的实验药物试验中对客观结果指标的迫切需求。这些发现还将提供关于语音子系统恶化对语音清晰度的影响的迫切需要的信息。从长远来看，本研究获得的更精细的延髓受累内表型(即遗传特征)可能会加强未来识别ALS遗传位点的努力，并提高该病的诊断和治疗特异性。与公共卫生相关：ALS，或Lou Gehrig病，是全球最常见和最具破坏性的神经肌肉疾病之一，影响所有种族和民族背景的女性和男性。大多数ALS患者最终都会出现言语丧失，无论这种疾病是从头/颈部还是脊柱开始的，并且是这种疾病最令人虚弱的后果之一。这项针对肌萎缩侧索硬化症患者的研究满足了这一人群中被广泛认可的三个需求：早期发现、提高预测准确性以及改善对疾病进展过程中个体差异的理解。

DESCRIPTION (provided by applicant): The goal of this application is to improve the understanding of bulbar (head) deterioration in Amyotrophic lateral sclerosis (ALS, also known as "Lou Gehrig's disease"), which is a fatal neurologic disease caused by degeneration of the motor neurons in the motor cortex, brainstem, and spinal cord. Despite the devastating consequences of bulbar deterioration, including impaired speech and swallowing, on the survival and quality of life of individuals with ALS, only a few studies have been conducted on ALS bulbar symptoms compared to research on ALS spinal involvement. This application responds to this gap in clinical and scientific knowledge by studying bulbar decline longitudinally and comprehensively using established and innovative methods for recording, measuring, and analyzing speech behaviors. One hundred persons with ALS will be studied every three months for a period of two years. The course of deterioration in each participant's speech will be tracked longitudinally using multiple measures of bulbar performance, with each measure broadly classified as either a representing speech performance at the global (i.e., speech system) level or subsystem level. The speech subsystem measures will represent the functional integrity of multiple bulbar regions known to support speech production, including the respiratory, phonatory, resonatory, and articulatory subsystems. Patterns of decline at each speech system and subsystem level will be used to address four specific aims: (1) determine if the rate of speech subsystem performance in the early stage of the disease accurately predicts the long-term rate of decline, (2) determine if speech subsystem measures accurately predict the onset of speech decline and the subsequent loss of oral communication, (3) identify sensitive quantitative indicators of the onset and rate of bulbar deterioration, and (4) identify several putative subtypes of bulbar ALS. In the short term, the identification of sensitive measures of bulbar involvement will improve early detection and prognostic accuracy and address the critical need for objective outcome measures in future experimental drug trials. The findings will also provide much needed information regarding the implications of speech subsystem deterioration on speech intelligibility. In the long term, the more refined endophenotype (i.e., hereditary characteristic) of bulbar involvement obtained from this research may strengthen future efforts at identifying the genetic loci of ALS and improving diagnostic and treatment specificity of the disease. PUBLIC HEALTH RELEVANCE: ALS, or Lou Gehrig's disease, is one of the most common and devastating neuromuscular diseases worldwide, affecting both women and men of all races and ethnic backgrounds. Loss of speech will eventually occur in most individuals with ALS whether the disease starts in the head/neck region or in the spine and is among the most debilitating outcomes of the disease. This research with ALS patients addresses three widely recognized needs in this population: early detection, improved prediction accuracy, and improved understanding of individual variation in the progression of the disease.