Spasticity and spinal mechanisms of human motor control

人体运动控制的痉挛和脊柱机制

• 批准号: 8342221
• 负责人: Mary Kay Floeter
• 金额: $ 67.6万
• 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/8342221
• 关键词: Affect; Age; Amyotrophic Lateral Sclerosis; Anisotropy; Axon; Brain; Chronic; Clinical; Collaborations; Corpus Callosum; Corticospinal Tracts; Cross-Sectional Studies; Data Analyses; Data Collection; Diffusion; Disease; Disease Progression; Epidemiology; Etiology; Fiber; Goals; Human; Image; Imaging Techniques; Interneurons; Magnetic Resonance Imaging; Measurement; Measures; Methodology; Motor; Motor Neuron Disease; Motor Neurons; Movement; Multicenter Studies; Neurons; Oxidative Stress; Patients; Pattern; Physiological; Physiology; Population; Primary Lateral Sclerosis; Property; Research; Research Personnel; Role; Spinal; Spinal Cord; Surveys; System; Time; United States National Institutes of Health; Universities; Vision; motor control; nervous system disorder; white matter

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 corresponds to the restriction of disease to the corticospinal, or upper motor neurons, of the brain. Understanding whether PLS and ALS represent different manifestations of the same disease, and factors that reduce disease progression are questions being examined in our group. In FY11 we completed the analysis of a multi-year cross-sectional study to examine structural differences between PLS and ALS patients with quantitative imaging techniques. We had previously shown that measurements of the fractional anisotropy and mean diffusivity of the white matter of corticospinal tract and corpus callosum could be made reliably in diffusion tensor MRI images (DTI) and were stable over a years time in healthy controls. Using the same methodology, we found that the pattern of corticospinal white matter alteration differed between ALS and PLS patients and from healthy age-matched controls. A consistent finding was that fractional anisotropy in the motor fibers of the corpus callosum in both PLS and ALS patients. This finding indicates that at least two populations of cortical projection neurons undergo degeneration in motor neuron disorders. We also completed data collection for a longitudinal imaging component from approximately half of the PLS and ALS patients in the cross-sectional study, and the analysis of these data is underway. A collaboration was begun with investigators at Columbia University as part of a multicenter study examining the role of oxidative stress in progression of motor neuron diseases. In FY11 we reached 80% of the accrual target for PLS patients, whose progression will be followed annually with clinical measures at NIH, and with epidemiological surveys and markers of oxidative stress in biofluids at Columbia over a 3-year period.

虽然原发性侧索硬化症通常被认为是一种运动神经元疾病，但它与肌萎缩侧索硬化症(ALS)和其他运动神经元疾病的关系尚不确定。PLS与ALS的病程不同，其中位生存期超过10年，而ALS的中位生存期为3-5年。长期存活与疾病对大脑皮质脊髓或上运动神经元的限制相对应。我们小组正在研究的问题是，了解偏头痛和肌萎缩侧索硬化症是否代表同一疾病的不同表现，以及减缓疾病进展的因素。在2011财年，我们完成了一项为期多年的横断面研究的分析，用定量成像技术检查了PLS和ALS患者之间的结构差异。我们先前已经证明，在弥散张量磁共振成像(DTI)中，可以可靠地测量皮质脊髓束和穹隆体白质的各向异性分数和平均弥散率，并在健康对照组中保持多年的稳定。使用相同的方法，我们发现ALS和PLS患者以及年龄匹配的健康对照组之间皮质脊髓白质改变的模式不同。一个一致的发现是，在偏头痛和肌萎缩侧索硬化症患者的胼胝体运动神经纤维中都存在分数各向异性。这一发现表明，在运动神经元疾病中，至少有两组皮质投射神经元经历了退化。在这项横断面研究中，我们还完成了来自大约一半的偏头痛和肌萎缩侧索硬化症患者的纵向成像成分的数据收集，这些数据的分析正在进行中。 作为一项多中心研究的一部分，哥伦比亚大学的研究人员开始了一项合作，研究氧化应激在运动神经元疾病进展中的作用。在2011财年，我们达到了PLS患者应计目标的80%，NIH将每年通过临床措施跟踪他们的进展，哥伦比亚大学将在3年内进行流行病学调查和生物液氧化应激标志物的跟踪。