PATHOPHYSIOLOGY OF CHOREA

舞蹈病是一种由多种原因引起的儿童基底神经节损伤引起的运动障碍。舞蹈病的特点是突然的、短暂的、不自主的肌肉收缩，导致运动似乎以不可预测的方式从身体的一个部位流向另一个身体部位。与舞蹈病相关的疾病包括中枢神经系统感染、感染后和其他自身免疫性疾病、体外循环缺血、锥体外系脑瘫、各种毒性和急性代谢过程、退行性疾病和先天性代谢错误。在许多情况下，病因不明。在具有明确神经病理学的疾病中，舞蹈病与纹状体（尾状核和壳核）和丘脑底核（STN）的异常有关。然而，舞蹈病的基本病理生理机制尚不清楚。这部分是由于缺乏非灵长类动物模型，部分是由于测量存在的灵长类动物模型中不自主运动的困难。目前治疗舞蹈病的药物选择很少，可能有明显的副作用，而且往往无效。提出的实验将开发定量的舞蹈病三维运动学测量，并使用它们来测量患有不同疾病的成人和儿童舞蹈病的空间和时间特性。对基底节区核的局灶性药理学操作将用于猴子产生舞蹈病。由此产生的舞蹈病将在猴子中进行测量，并与人类舞蹈病进行比较，以验证猴子模型，特别是在儿童舞蹈病方面。然后，通过记录单个苍白球内段神经元在舞蹈病发生之前和期间的活动，这些猴子模型将被用于研究舞蹈病的基本病理生理学。通过结合神经生理学和运动学技术来研究实验产生的舞蹈病，可以严格地检验流行的舞蹈病病理生理学假设。有很强的潜力来确定舞蹈病的基本机制。开发一种非侵入性方法来量化儿童和猴子的舞蹈病，将是更好地表征不自主运动的病理生理学和开发更有效的医学治疗的重要进展。

Chorea is a movement disorder that results from basal ganglia injury due to a variety of causes in children. Chorea is characterized by sudden, brief, involuntary muscle contractions causing movements that appear to flow from body part to body part in an unpredictable manner. Disorders associated with chorea include CNS infections, post-infectious and other autoimmune diseases, ischemia during cardiopulmonary bypass, 'extrapyramidal' cerebral palsy, a variety of toxic and acute metabolic processes, degenerative conditions, and inborn errors of metabolism. In many cases the cause is unknown. In diseases with well defined neuropathology, chorea has been associated with abnormalities in the striatum (caudate and putamen) and the subthalamic nucleus (STN). However, the fundamental pathophysiology of chorea is not known. This is due in part to the lack of non-primate models and in part to the difficulty of measuring involuntary movements in the primate models that do exist. Current medical treatment options for chorea are few, may have significant side effects, and are often ineffective. The proposed experiments will develop quantitative 3-dimensional kinematic measures of chorea and use them measure spatial and temporal properties of chorea in adults and children with different disorders. Focal pharmacologic manipulation of basal ganglia nuclei will be used in monkeys to produce chorea. The resulting chorea will be measured in the monkeys and compared to human chorea in order to validate the monkey models, especially with respect to childhood chorea. The monkey models will then be used to investigate the fundamental pathophysiology of chorea by recording the activity of individual globus pallidus internal segment neurons before and during chorea. Through a combination of neurophysiologic and kinematic techniques to study experimentally produced chorea, the prevailing hypotheses of chorea pathophysiology can be tested rigorously. There is strong potential to identify the fundamental mechanisms of chorea. Development of a non-invasive method to quantify chorea in children and in monkeys will be an important advance toward better characterization of the pathophysiology of involuntary movements and development of more effective medical therapies.