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: 8557022
• 负责人: Mary Kay Floeter
• 金额: $ 70.34万
• 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/8557022
• 关键词: Affect; Age; Amyotrophic Lateral Sclerosis; Anisotropy; Autopsy; Axon; Biological Markers; Brain; Brain Stem; Chronic; Clinical; Corpus Callosum; Corticospinal Tracts; Data; Diagnosis; Disease; Disease Progression; Early Diagnosis; Enrollment; Etiology; Evolution; Fiber; Functional disorder; Goals; Human; Image; Imaging Techniques; Interneurons; Iron; Magnetic Resonance Imaging; Measures; Microglia; Motor; Motor Cortex; Motor Neuron Disease; Motor Neurons; Movement; Neurons; Oxidative Stress; Patients; Pattern; Physiological; Physiology; Primary Lateral Sclerosis; Property; Reproducibility; Research; Research Personnel; Role; Signal Transduction; Site; Spinal; Spinal Cord; System; Testing; Universities; Visit; arm; base; follow-up; healthy volunteer; interest; longitudinal analysis; motor control; motor neuron degeneration; 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. Patients with PLS have a median survival of more than a decade, in contrast to the 3-5 year median survival of patients after diagnosis of ALS. In PLS, degeneration is restricted to the corticospinal, or upper motor neurons, in the brain, without significant degeneration of motor neurons in the spinal cord and brainstem. There is considerable interest in whether PLS and ALS are the same disorder and, if so, factors that limit disease progression in PLS. We have been studying imaging biomarkers that may distinguish PLS and ALS or correspond to clinical measures of progression. In FY12 we completed analysis of the longitudinal arm of a study of structural MRI changes in brains of PLS and ALS patients with quantitative imaging techniques. In the cross-sectional arm of this study, we found that the pattern of white matter disruption in the corticospinal tract 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 was reduced in both PLS and ALS patients. Approximately half of the patients were able to complete follow-up testing a mean of 1 year (ALS) or 2 years (PLS) later. Based on the longitudinal data, we hypothesize that there is an evolution of imaging changes as upper motor neurons degenerate, with early disruption of affected white matter tracts. Postmortem study of two ALS patients showed accumulation of iron within microglia in the motor cortex, corresponding to a particular signal seen on MRI studies, most evident with 7Tesla imaging. The next step in this project is to identify imaging markers that change earlier in the course of the disease. Toward that end, in FY12 we began a new study in healthy volunteers to assess the reproducibility of imaging markers and physiological measures that are candidates for earlier detection of upper motor neuron dysfunction. In FY12, we completed our sites accrual target for the multicenter collaborative study with investigators at Columbia University to examine the role of oxidative stress in progression of motor neuron diseases. We completed the annual visits on previously enrolled patients, and are on target for completing the last visit in this study in 3 years.

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患者的中位生存期超过十年，而ALS患者的中位生存期为3-5年。在PLS中，变性仅限于大脑中的皮质脊髓或上运动神经元，而脊髓和脑干中的运动神经元没有显著变性。有相当大的兴趣，PLS和ALS是否是相同的障碍，如果是这样，限制PLS疾病进展的因素。 我们一直在研究可能区分PLS和ALS或对应于进展的临床措施的成像生物标志物。在2012财年，我们利用定量成像技术完成了PLS和ALS患者大脑结构MRI变化研究的纵向臂分析。在本研究的横断面研究中，我们发现ALS和PLS患者皮质脊髓束的白色物质破坏模式与健康年龄匹配的对照组不同。一个一致的发现是，分数各向异性的胼胝体运动纤维减少PLS和ALS患者。大约一半的患者能够在平均1年（ALS）或2年（PLS）后完成随访测试。基于纵向数据，我们假设有一个演变的成像变化，上运动神经元退化，早期中断受影响的白色物质束。对两名ALS患者的尸检研究显示，运动皮层中的小胶质细胞内铁的积累，对应于MRI研究中观察到的特定信号，最明显的是7特斯拉成像。该项目的下一步是确定在疾病过程中早期变化的成像标记物。为此，在2012财年，我们在健康志愿者中开始了一项新的研究，以评估成像标志物和生理指标的可重复性，这些指标是早期检测上运动神经元功能障碍的候选指标。 在2012财年，我们与哥伦比亚大学的研究者完成了多中心合作研究的临床试验机构招募目标，以检查氧化应激在运动神经元疾病进展中的作用。我们完成了对既往入组患者的年度访视，并计划在3年内完成本研究的末次访视。