Innovative Biomarkers of Orofacial Dysfunction in Amyotrophic Lateral Sclerosis

肌萎缩侧索硬化症口面部功能障碍的创新生物标志物

• 批准号: 8908535
• 负责人: Courtney McIlduff
• 金额: $ 6.21万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-02 至 2017-03-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8908535
• 关键词: Acoustics; Age; Amyotrophic Lateral Sclerosis; Anterior Horn Cells; Architecture; Atrophic; Biological Markers; Breathing; Cerebrospinal Fluid Proteins; Clinical Trials; Cognitive; Communities; Connective Tissue; Control Groups; Data; Deglutition; Development; Diagnosis; Disease; Evaluation; Evolution; Face; Fatty acid glycerol esters; Fiber; Foundations; Frequencies; Functional disorder; Gender; Goals; Gray unit of radiation dose; Health; Health Status; Image; Individual; Inflammation; Iowa; Lead; Limb structure; Lip structure; Measurement; Measures; Methods; Movement; Muscle; Myography; Myopathy; Natural History; Neuromuscular Diseases; Onset of illness; Outcome; Painless; Patients; Performance; Peripheral Nervous System Diseases; Procedures; Questionnaires; Reproducibility; Serum; Speech; Speed; Symptoms; System; Technology; Testing; Therapeutic Agents; Therapeutic Clinical Trial; Therapeutic Trials; Time; Tongue; Training; Translating; Ultrasonography; Visit; Work; aged; base; career; design; effective intervention; electric impedance; global health; healthy volunteer; innovation; innovative technologies; instrument; interest; meetings; member; nervous system disorder; novel therapeutics; orofacial; public health relevance; response; tool; user-friendly; voltage

 DESCRIPTION (provided by applicant): Bulbar dysfunction inevitably develops in the course of amyotrophic lateral sclerosis (ALS), and approximately 25% of patients have predominantly bulbar symptoms at the time of disease onset. In addition to characterizing the evolution in muscle architecture that could underlie associated orofacial weakness, identifying new biomarkers is critical to the development and testing of novel therapeutic agents. As painless, non-invasive, portable technologies, quantitative ultrasonography (QUS) and electrical impedance myography (EIM) could meet the need for objective measures of bulbar dysfunction. In QUS, acoustic energy is applied to a muscle of interest; the resultant raw gray-scale or backscatter pictorial data are translated into a single value that reflects the health of the image muscle. Similarly, in EIM, a high-frequency, low-intensity alternating electrical current is applie to individual muscles, and the resulting voltages measured. Impedance values reflect changes in muscle architecture, including fiber atrophy, inflammation, and the replacement of muscle with fat or connective tissue. Both of these user-friendly methods can provide sensitive indicators of neuromuscular disease status when applied to the limbs. Although they have also been used to evaluate orofacial muscles in healthy volunteers and patients with primary muscle disorders, they have not yet been systematically studied in the ALS community. We hypothesize that quantitative ultrasonography (QUS) and electrical impedance myography (EIM) measurements can provide consistent, clinically meaningful information about orofacial muscle health in ALS. In a longitudinal natural history study of 32 individuals with ALS and 32 healthy subjects, we will test this hypothesis via three aims: 1.) To assess the reliability of orofacial QS and EIM in individuals with and without ALS; 2) To determine how the measurements of selected orofacial muscles in individuals with ALS evolve over an 18-month period; 3) To evaluate preliminarily whether orofacial QUS and EIM measurements in ALS patients correlate with results of functional tests. If QUS and EIM do provide reliable, meaningful surrogate information about ALS status as expected, they could be used to make proof-of- concept therapeutic trials more efficient. Furthermore, the innovative technologies could have broader application to the diagnosis and surveillance of other central and peripheral nervous system disorders with bulbar involvement.

 描述（由适用提供）：在肌萎缩性侧索硬化症（ALS）过程中不可避免地会出现鳞茎功能障碍，在疾病发作时，大约25％的患者主要患有鳞茎症状。除了表征肌肉结构的演变外，识别新生物标志物对于新型治疗剂的发展和测试至关重要。由于无痛，无创，便携式技术，定量超声检查（QU）和电阻止myagraphy（EIM）可以满足囊泡功能障碍的客观测量的需求。在QUS中，声能应用于感兴趣的肌肉。所得的原始灰度或反向散射图形数据被转化为一个反映图像肌肉健康的单个值。同样，在EIM中，将高频，低强度的替代电流应用于单个肌肉，并测量所得的电压。阻抗值反映了肌肉结构的变化，包括纤维萎缩，感染以及用脂肪或结缔组织代替肌肉。当将两种用户友好的方法应用于四肢时，都可以提供神经肌肉疾病状态的敏感指标。尽管它们也被用来评估健康志愿者和原发性肌肉疾病患者的口面肌肉，但尚未在ALS社区进行系统的研究。我们假设定量超声检查（QUS）和电阻抗密闭（EIM）测量可以为ALS提供有关临床上有意义的临床有意义的信息。在对32名ALS和32名健康受试者的纵向自然史研究中，我们将通过三个目的检验这一假设：1。）评估有或没有ALS的个体的口面QS和EIM的可靠性； 2）确定在18个月内ALS进化的个体中选定的口面肌肉的测量； 3）初步评估ALS患者的口面QUS和EIM测量是否与功能测试结果相关。如果QUS和EIM确实如预期提供了有关ALS状态的可靠，有意义的代孕信息，则可以用来使概念验证的治疗试验更有效。此外，创新技术可以更广泛地应用于其他中央和周围神经系统疾病的诊断和监视，并具有鳞茎的参与。