Spasticity and Upper Motor Neuron Disorders

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，患者存活时间长，脊髓和脑干的运动神经元得以保留。在PLS中，神经退行性变未能以任何显著程度扩散到运动皮层之外。有相当大的兴趣，PLS患者是否可以提供线索的潜在机制，停止神经变性的进展。我们小组以前的工作显示ALS患者和长期存在的PLS患者的白色物质束的不同变化模式，使用扩散张量成像。在2015财年，我们继续对当前PLS患者队列进行纵向临床评估和成像，并招募了症状发作5年内的新患者，以关注早期退行性变。在PLS、ALS和FTD患者队列中进行的扩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色物质束的扩散变化模式区分临床表型。 在2015财年，我们作为一个研究中心完成了一项合作研究的数据收集，该研究旨在检查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患者的基线特征分析的一部分，进行了外显子组测序，其鉴定了在几名患者中引起各种神经障碍的不同基因的序列变体。作为一个新的项目，我们的小组开始收集血液用于父母在世的PLS患者（三人组）的基因组分析。通过比较患者基因组与其未受影响的父母基因组，这一策略将有助于关注可选择用于进一步随访研究的致病变异。PLS-trio项目的DNA收集将持续到2016财年，直到收集到足够数量的DNA用于批次测序。

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.