Spasticity and Upper Motor Neuron Disorders

原发性脊髓侧索硬化症（PLS）是一种罕见的散发性上运动神经元疾病，被认为与肌萎缩性脊髓侧索硬化症（ALS）有关。PLS与ALS的不同之处在于，神经退行性变不能扩散到运动皮层以外的任何显著程度。与ALS不同，PLS患者存活时间长，脊髓和脑干的运动神经元在临床上幸免于难。有相当大的兴趣在PLS的原因和PLS患者是否可能提供线索的潜在机制，限制神经退行性疾病的进展。本研究组先前的工作显示，使用扩散张量成像，ALS患者和长期存在的PLS患者的白色物质束有不同的改变。在2016财年，我们继续对一组临床确诊的PLS患者和症状发作5年内入组的新PLS患者进行纵向临床评估和成像，以寻找早期神经影像学变化。成像组合包括扩散张量成像、高分辨率T1图像和静息状态fMRI。神经成像数据的采集已完成，分析将于2017财年开始。 PLS患者队列将继续接受临床随访，尽管额外患者的入组已经结束。 两个项目正在进行中，以探索PLS的潜在原因。与大卫王博士合作，iPS神经元已从PLS患者淋巴细胞中产生，以研究候选疾病机制。此外，我们还收集了父母健在的PLS患者（三人组）和单个PLS患者（单例）的血液用于全基因组测序。在与国家老龄化研究所Bryan Traynor博士的实验室合作下，已经收集了50个基因组，并准备从2016财年末开始批量测序。计划在2017财年进行基因组数据分析。

Primary lateral sclerosis (PLS) is a rare, sporadic upper motor neuron disorder thought to be related to amyotrophic lateral sclerosis (ALS). PLS differs from ALS in that neurodegeneration fails to spread to any significant extent beyond the motor cortex. Unlike ALS, PLS patients have a long survival, and motor neurons of the spinal cord and brainstem are clinically spared. There is considerable interest in the causes of PLS and whether PLS patients may provide clues to potential mechanisms that limit progression of neurodegeneration. Previous work from our group showed different alterations of white matter tracts in patients with ALS and patients with long-standing, established PLS using diffusion tensor imaging. During FY16, we continued longitudinal clinical assessments and imaging of a cohort of patients with clinically definite PLS and new PLS patients enrolled within 5 years of symptom onset to look for early neuroimaging changes. The imaging battery included diffusion tensor imaging, high resolution T1 images, and resting state fMRI. The acquisition of neuroimaging data was completed, and analysis will begin in FY17. The cohort of PLS patients will continue to be followed clinically, although enrollment of additional patients has ended. Two projects are underway to explore potential causes of PLS. In collaboration with Dr. David Wang, iPS neurons have been generated from PLS patient lymphocytes to study candidate disease mechanisms. Additionally, we have collected blood for whole genome sequencing of PLS patients with living parents (trios), and from individual PLS patients (singletons). In collaboration with the laboratory of Dr. Bryan Traynor, National Institute of Aging, fifty genomes have been collected and the DNA is ready for sequencing as a batch, beginning at end FY16. Analysis of genomic data is planned for FY17.