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。我们在PLS患者中进行了一项纵向研究，结果显示，一旦每个身体部位出现症状，该部位的临床严重程度在最初几年下降得更快，随后稳定下来，没有继续进展。这一发现表明，皮质脊髓输入功能的丧失可能以间歇性的方式进展。它还表明进展不是线性的，反对在未来的临床试验中使用临床下降的斜率作为结果，并强调需要疾病活动的生物标志物。 我们已经完成了一项多年的横断面研究，以评估ALS和PLS是一种常见的神经退行性过程的变体的假设，由于病理学的区域差异，表型不同。我们首先在PLS和ALS患者中寻找与非运动皮层区域对应的临床功能障碍的重叠和差异，这些患者具有相似程度的上运动神经元功能障碍。神经心理学测试和精神病学评估表明，认知障碍在PLS中不太常见，PLS患者的抑郁程度略高于ALS患者。为了将临床测量与区域解剖测量相关联，在ALS和PLS患者以及健康年龄匹配的对照组中获得了扩散张量MRI成像和皮质厚度测量。我们以前表明，定量测量皮质脊髓束可以从DTI图像与良好的内部和内部的信度和重测信度的控制。我们目前正在完成对这些数据的分析，并在横断面研究中对PLS和ALS患者的子集进行纵向成像研究。

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. We carried out a longitudinal study in PLS patients that showed that once each body region exhibited symptoms, measures of clinical severity of that region declined more rapidly in the first years and subsequently stabilized without continued progression. This finding suggests that loss of corticospinal input may progress in an intermittent fashion. It also indicates that progression is not linear, arguing against using the slope of clinical decline as an outcome in future clinical trials and highlighting the need for biological markers of disease activity. We have completed a multi-year cross-sectional study to evaluate the hypothesis that ALS and PLS are variants of a common neurodegenerative process that differ phenotypically because of regional differences in pathology. We first looked for overlap and differences in clinical dysfunction corresponding to non-motor cortical regions in PLS and ALS patients with similar extents of upper motor neuron dysfunction. Neuropsychological tests and psychiatric assessments showed that cognitive impairment is less common in PLS, and that PLS patients have a modestly greater extent of depression compared to ALS patients. To correlate clinical measures to regional anatomical measures, diffusion tensor MRI imaging and measures of cortical thickness have been obtained in ALS and PLS patients and healthy age-matched controls. We previously showed that quantitative measures of the corticospinal tract can be made from DTI images with good intra- and inter-rater reliability and test-retest reliability in controls. We are currently completing analysis of these data and are obtaining longitudinal imaging studies on a subset of the PLS and ALS patients in the cross-sectional study.