Spasticity and Upper Motor Neuron Disorders

痉挛和上运动神经元疾病

• 批准号: 9157502
• 负责人: Mary Kay Floeter
• 金额: $ 103.46万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9157502
• 关键词: Affect; Amyotrophic Lateral Sclerosis; Blood; Brain Stem; Characteristics; Clinical; Clinical Markers; Clinical Research; Clinical assessments; Collection; Cross-Sectional Studies; DNA; Data Collection; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Etiology; Genes; Genome; Genomics; Goals; Image; Intramural Research Program; Life; Longitudinal Studies; Motor Cortex; Motor Neuron Disease; Motor Neurons; Movement; National Institute of Neurological Disorders and Stroke; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Oxidative Stress; Parents; Patients; Pattern; Physiological; Physiology; Primary Lateral Sclerosis; Recruitment Activity; Research; Role; Site; Spinal; Spinal Cord; Symptoms; Universities; Variant; Work; clinical phenotype; cohort; exome sequencing; follow-up; interest; nervous system disorder; progression marker; white matter

Primary lateral sclerosis (PLS) is a rare upper motor neuron disorder that may be related to amyotrophic lateral sclerosis (ALS). PLS differs from ALS in that patients have a long survival, and motor neurons of the spinal cord and brainstem are spared. In PLS neurodegeneration fails to spread beyond the motor cortex to any significant extent. There is considerable interest in whether PLS patients may provide clues to potential mechanisms that halt progression of neurodegeneration. Previous work from our group showed different patterns of change in white matter tracts in patients with ALS and patients with long-standing, established PLS using diffusion tensor imaging. During FY15, we continued longitudinal clinical assessments and imaging of the current cohort of patients with PLS, and recruited new patients within 5 years of symptom onset to focus on early periods of degeneration. Progress was also made on a cross-sectional analysis of diffusion tensor imaging in cohorts of patients with either PLS, ALS, and FTD to determine if clinical phenotypes could be distinguished by patterns of diffusion changes in white matter tracts. In FY15 we completed data collection as a site in a collaborative study to examine the role of oxidative stress in progression of motor neuron diseases coordinated by Columbia University. In that study (PLS-COSMOS), as part of the analysis of the baseline characteristics of 41 PLS patients, exome sequencing was carried out which identified sequence variants of different genes causing varied neurological disorders in several patients. As a new project, our group began collecting blood for genomic analysis of PLS patients with living parents (trios). This strategy, by comparing patient genomes with their unaffected parentss genomes, will help to focus on disease-causing variants that can be selected for further follow-up studies. Collection of DNA for the PLS-trio project will continue through FY16 until a sufficient number have been collected for batch sequencing.

原发性侧索硬化症（PLS）是一种罕见的上运动神经元疾病，可能与肌萎缩侧索硬化症（ALS）有关。 PLS 与 ALS 的不同之处在于，患者的生存期较长，并且脊髓和脑干的运动神经元不会受到影响。在 PLS 中，神经变性无法在任何显着程度上扩散到运动皮层之外。人们对 PLS 患者是否可以提供阻止神经变性进展的潜在机制的线索非常感兴趣。我们小组之前的研究表明，ALS 患者和长期存在的 PLS 患者的白质束变化模式不同，使用弥散张量成像。 2015 财年，我们继续对当前 PLS 患者队列进行纵向临床评估和影像学检查，并招募症状出现 5 年内的新患者，重点关注退化的早期阶段。对 PLS、ALS 和 FTD 患者队列的弥散张量成像横断面分析也取得了进展，以确定是否可以通过白质束弥散变化模式来区分临床表型。 2015 财年，我们完成了一项合作研究的数据收集工作，以研究氧化应激在哥伦比亚大学协调的运动神经元疾病进展中的作用。在该研究 (PLS-COSMOS) 中，作为 41 名 PLS 患者基线特征分析的一部分，进行了外显子组测序，确定了导致几名患者出现不同神经系统疾病的不同基因的序列变异。作为一个新项目，我们小组开始收集血液，对父母健在的 PLS 患者（三人组）进行基因组分析。该策略通过将患者基因组与其未受影响的父母的基因组进行比较，将有助于重点关注可以选择用于进一步后续研究的致病变异。 PLS-trio 项目的 DNA 收集工作将持续到 2016 财年，直到收集到足够数量用于批量测序。