The Electrophysiology of Motor Neuron Diseases

运动神经元疾病的电生理学

• 批准号: 6529714
• 负责人: Mark B. Bromberg
• 金额: $ 13.85万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6529714
• 关键词: amyotrophic lateral sclerosis; child (0-11); clinical research; computer program /software; computer system design /evaluation; data collection methodology /evaluation; degenerative motor system disease; electromyography; electrophysiology; genotype; human subject; infant human (0-1 year); innervation; longitudinal human study; method development; motor neurons; muscle strength; neurogenetics; phenotype; polymerase chain reaction; progressive spinal muscular atrophy; technology /technique development

DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders of unknown etiology. They have in common death of lower motor neurons (LMN) causing muscle weakness, and both disorders are fatal. Mechanisms of LMN death differ for SMA and ALS. In SMA, LMN death may occur over a limited period of time. Unanswered is whether there is late or continued LMN loss. Recent genetic studies in SMA indicate a relationship between survival motor neuron gene (SMN2) copy number and SMA type. Unanswered is the relationship between copy number and LMN number. In ALS, no single mechanism of LMN death explains known features, and a cascade of events ultimately leading to LMN death is likely. Unanswered in ALS is the natural pattern of progression of LMN loss from muscle to muscle. Although muscle weakness is the clinical manifestation of LMN loss for both disorders, the rate of loss of strength does not accurately reflect the rate of loss of LMNs. The discrepancy is due to the compensatory effects of reinnervation of denervated fibers by collateral sprouting from surviving motor nerve terminals. Similarly, routine electrophysiologic tests do not accurately measure LMN loss. Unanswered for both disorders is the dynamics of the compensatory process that determines the clinical state and level of function. Motor unit number estimation (MUNE) is a special electrophysiologic test that can directly assess the number of LMNs innervating a muscle. There are no data on the natural course of LMN loss for SMA, and little data for ALS. We propose to develop and refine MUNE and other electrophysiologic techniques to study, and follow the course of LMN loss and associated compensatory changes. For SMA, we will adapt MUNE techniques to study infants and children. For older SMA and ALS, we will refine MUNE techniques to optimize data collection. For SMA, we will correlate LMN loss with clinical type and SMN2 copy number. We will begin, in the two years of the grant-performing serial studies, to assess whether there is continued LMN loss. For ALS, we will determine and compare the rate and pattern of LMN loss in distal and proximal muscles. In older SMA and ALS, we will assess relationships between LMN loss and measures of collateral reinnervation and strength. We anticipate that MUNE and other electrophysiologic techniques will have direct applicability to the design of clinical trials for SMA and ALS, because these techniques can be used as informative end-point measures. To facilitate the use of MUNE in clinical trials, we will develop and refine the techniques in a form that can be used in any clinical center participating in trials. Currently, most MUNE techniques rely on proprietary software. We will develop software for use on PC-based computer systems, making them available to all laboratories.

描述（由申请人提供）： 脊柱肌肉萎缩（SMA）和肌萎缩性侧性硬化症（ALS）是 未知病因的神经退行性疾病。他们有共同的死亡 较低运动神经元（LMN）引起肌肉无力，两种疾病均为 致命的。 LMN死亡的机制在SMA和ALS方面有所不同。在SMA，LMN死亡可能 发生在有限的时间内。未解决的是迟到还是 继续LMN损失。 SMA中最近的遗传研究表明一种关系 在生存运动神经元基因（SMN2）拷贝数和SMA类型之间。未得到答复 是复制号和LMN号码之间的关系。在ALS中，没有一个 LMN死亡的机制解释了已知特征和一系列事件 最终可能导致LMN死亡。在ALS中未得到答复是自然的 LMN从肌肉到肌肉的损失的模式。虽然肌肉 弱点是两种疾病的LMN损失的临床表现，率 强度损失不能准确反映出LMN的损失率。这 差异是由于重新支配开发的补偿性影响 纤维通过持续的运动神经末端发芽的纤维。相似地， 常规电生理测试不能准确测量LMN损失。未得到答复 对于这两种疾病，都是决定补偿过程的动态 临床状态和功能水平。 电机单位编号估计（MUNE）是一种特殊的电生理测试 可以直接评估肌肉支配的LMN数量。没有数据 关于SMA的LMN损失的自然过程，ALS的数据很少。我们建议 开发和完善宗教和其他电生理技术来研究， 并遵循LMN损失和相关的补偿性变化的过程。对于SMA， 我们将适应宗教技术来研究婴儿和儿童。对于年长的SMA和 ALS，我们将完善Mune技术以优化数据收集。对于SMA，我们 将将LMN损失与临床类型和SMN2拷贝数相关。我们将开始， 在授予授予的序列研究的两年中，以评估是否 LMN持续损失。对于ALS，我们将确定并比较速率 远端和近端肌肉中LMN丧失的模式。在较老的SMA和ALS中， 我们将评估LMN损失与抵押措施之间的关系 加重和力量。我们预计这是穆恩和其他 电生理技术将直接适用于设计 SMA和ALS的临床试验，因为这些技术可以用作 信息终点措施。促进在临床中使用穆恩 试验，我们将以可以使用的形式开发和完善技术 任何参加试验的临床中心。目前，大多数穆恩技术 依靠专有软件。我们将开发用于基于PC的软件 计算机系统，使其可用于所有实验室。

项目成果

Comparison of conventional and decomposition-enhanced spike triggered averaging techniques.

传统和分解增强尖峰触发平均技术的比较。

• DOI: 10.1016/j.clinph.2003.11.006
• 发表时间: 2004
• 期刊: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
• 作者: Lawson,VictoriaH;Bromberg,MarkB;Stashuk,Daniel
• 通讯作者: Stashuk,Daniel