Intermuscular coherence: A novel biomarker for upper motor neuron dysfunction in ALS

项目摘要/摘要 肌萎缩侧索硬化症(ALS)是一种由神经元死亡引起的致死性神经退行性疾病。 在运动系统中，在大脑和脊髓中。它会导致全身逐渐虚弱， 通常在症状出现后3年内死于呼吸衰竭。治疗启动与药物 缺乏这种疾病的定量生物标志物在一定程度上阻碍了这种疾病的发展。在建议的 项目将进行多中心研究，以验证和进一步表征潜在的生物标记物 肌萎缩侧索硬化症，称为肌肉间连贯性(IMC)。IMC测量两个肌肉之间的活动相关性 它代表了大脑和脊髓运动神经元对肌肉的共同输入。体内研究 在非人类灵长类动物和人类中，IMC都表明在15-40赫兹(β-to-γ频率)的范围内 代表从上运动神经元到肌肉对的输入。当大脑中的运动神经元受损时，如 发生在肌萎缩侧索硬化症时，在βγ频率范围内IMC降低。在一份初步报告中，我们显示患者 与年龄和性别匹配的对照组相比，ALS患者在βγ范围内的IMC较低。因为 IMC的测量是快速、非侵入性、无痛苦的，并且只需要标准临床中的设备 神经生理学实验室，如果得到验证，该方法将成为ALS的重要生物标记物。 建议在临床环境中进行IMC的多中心验证研究。首先，准确度，敏感度， 生物标志物的特异性将在到神经科诊所进行初步诊断的患者中确定。 当怀疑为ALS时进行评估。为了提供最具特异性，IMC值的分布将 在几个人口统计亚组的神经典型受试者中表现出特征。最后，IMC将成为 对肌萎缩侧索硬化症患者进行随时间的监测，以确定IMC随着肌萎缩侧索硬化症疾病进展的变化。 初步数据表明，IMC可能是诊断ALS的有用生物标记物，允许区分 肌萎缩侧索硬化症类似肌萎缩侧索硬化症的疾病，它可以用于客观监测肌萎缩侧索硬化症的进展 时间到了。在这种方法可以使用之前，测试这些初步发现的有效性的多中心研究是重要的 将被实施，以加快诊断，并为患者提供更快的ALS治疗途径。

Project Summary/Abstract Amyotrophic lateral sclerosis (ALS) is a uniformly fatal neurodegenerative disease caused by neuronal death in the motor system, both in the brain and spinal cord. It results in progressive weakness throughout the body, with death typically from respiratory failure within 3 years of symptom onset. Therapy initiation and drug development are hindered, in part, by the lack of quantitative biomarkers for the disease. In the proposed project a multi-center study will be carried out to validate and further characterize a potential biomarker for ALS, known as intermuscular coherence (IMC). IMC measures the correlation of activity between two muscles and represents the shared input to the muscles from motor neurons in the brain and spinal cord. In vivo studies in both non-human primates and humans suggest that IMC in the range of 15-40 Hz (β-to-γ frequencies) represents input to muscle pairs from upper motor neurons. When motor neurons in the brain are damaged, as happens in ALS, IMC decreases in the βγ frequency range. In a preliminary report we showed that patients with ALS have lower IMC in the βγ range than do age- and sex-matched control subjects. Because the measurement of IMC is quick, non-invasive, painless, and requires only equipment found in standard clinical neurophysiology labs, the method, if validated, would be an important biomarker for ALS. Proposed is a multi-center validation study of IMC in the clinical environment. First, the accuracy, sensitivity, and specificity of the biomarker will be determined in patients who present to neurology clinic for an initial evaluation when ALS is suspected. In order to provide the most specificity, the distribution of IMC values will be characterized in neurotypical subjects across several demographic subgroups. Finally, IMC will be monitored over time in patients with ALS to determine how IMC changes with ALS disease progression. Preliminary data suggest that IMC could be a useful biomarker for diagnosing ALS, allowing differentiation of ALS from ALS-mimic disorders, and that it can be used to objectively monitor the progression of ALS over time. A multi-center study to test the validity of these preliminary findings is important before this method can be implemented to speed diagnosis and provide faster access to treatments of ALS for patients.