Spasticity and spinal mechanisms of human motor control

虽然原发性侧索硬化症（PLS）通常被认为是一种运动神经元疾病，但其与肌萎缩性侧索硬化症（ALS）和其他运动神经元疾病的关系尚不确定。PLS与ALS的持续时间不同，中位生存期超过十年，而ALS的中位生存期为3-5年。长期存活与疾病限制在大脑的皮质脊髓或上运动神经元密切相关。了解运动神经元疾病的进展很重要，因为大多数患者只有在疾病开始后才能被发现，治疗可能会集中在阻止疾病进展上。目前尚不清楚PLS患者的临床症状是否会在其一生中持续进展，以及进展是否以稳定的速度发生。在2009财年，我们对2000年至2008年期间参加纵向自然病史方案的50例PLS患者的运动速度和功能进行了前瞻性临床测量，并进行了汇编和分析。这项研究发现，主要在一种亚型的患者中，症状从一个肢体稳定地传播到另一个肢体，其症状从腿部开始并上升。然而，在PLS患者的所有亚型的新受影响的肢体内，运动的临床测量在头几年以更快的速度恶化，随后稳定而没有继续进展。这一发现对在未来的临床试验中使用运动速度的临床测量作为结果测量具有意义。 一种假设是，不同的运动神经元疾病表型进行性肌萎缩症，ALS，额颞叶痴呆症（FTD）和PLS是相同的神经退行性过程的变体，具有病理分布的区域差异。为了验证这一假设，我们进行了一项为期3年的方案，包括神经心理学测试，精神评估和定量MRI成像。本研究的目的是确定PLS患者的非运动、额叶皮质功能障碍的程度，并将其与ALS患者和年龄匹配的健康对照受试者进行比较。影像学研究将阐明皮质灰质和白色物质解剖学受累的区域差异。本方案的入组和基线测试已于2009财年完成，数据分析正在进行中。在准备分析患者图像时，在2009财年进行了一项方法学研究，以检查定量成像方法的评价者内和评价者间可靠性以及重测可靠性。

Although primary lateral sclerosis (PLS) is generally considered to be a motor neuron disorder, its relationship to amyotrophic lateral sclerosis (ALS) and other motor neuron disorders is uncertain. PLS differs from ALS in its duration, with a median survival of more than a decade, in contrast to the median survival of 3-5 years in ALS. The long survival is closely linked to the restriction of disease to the corticospinal, or upper motor neurons, of the brain. Understanding progression in motor neuron diseases is important because most patients will only be identified after disease begins, and treatments will likely focus on arresting disease progression. It is not really known whether clinical symptoms continue to progress throughout the lifetime of a patient with PLS and whether progression occurs at a steady pace. In FY09, we compiled and analyzed prospectively obtained clinical measures of motor speed and function in 50 patients with PLS who were enrolled in a longitudinal natural history protocol between 2000 and 2008. This study found steady spread of symptoms from one limb to another primarily in one subtype of patients, whose symptoms began in their legs and ascended. However, within newly affected limbs of all subtypes of PLS patients, clinical measures of movement worsened at a more rapid pace in the first years, and subsequently stabilized without continued progression. This finding has implications for using clinical measures of motor speed as an outcome measure in future clinical trials. One hypothesis is that the different motor neuron disorder phenotypes progressive muscular atrophy, ALS, frontotemporal dementia (FTD) and PLS are variants of the same neurodegenerative process with regional differences in the distribution of pathology. To test this hypothesis we have been carrying out a 3-year protocol that includes neuropsychological tests, psychiatric assessment, and quantitative MRI imaging. The goals of this study is determine the extent of non-motor, frontal cortical dysfunction in PLS patients, and to compare these to patients with ALS and age-matched healthy control subjects. The imaging studies will elucidate regional differences in anatomical involvement of cortical grey and white matter. The enrollment and baseline testing for this protocol was completed in FY09, and data analysis is underway. In preparation for analyzing patient images, a methodological study to examine the intra- and inter-rater reliability and test-retest reliability of the quantitative imaging methods was carried out in FY09.