PATHOPHYSIOLOGY OF CHOREA

舞蹈病是一种运动障碍，是由于基底神经节损伤，由于各种原因在儿童。舞蹈病的特征是突然的、短暂的、不自主的肌肉收缩，引起似乎以不可预测的方式从身体部位流向身体部位的运动。与舞蹈病相关的疾病包括CNS感染、感染后和其他自身免疫性疾病、心肺转流期间的缺血、“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缺陷。在许多情况下，原因不明。在明确的神经病理学疾病中，舞蹈病与纹状体（尾状核和壳核）和丘脑底核（丘脑底核）的异常有关。然而，舞蹈病的基本病理生理学尚不清楚。这部分是由于缺乏非灵长类动物模型，部分是由于难以测量确实存在的灵长类动物模型中的不自主运动。目前舞蹈病的医学治疗选择很少，可能有显着的副作用，往往是无效的。拟议的实验将开发量化的三维运动学措施的舞蹈病，并用它们来衡量空间和时间特性的舞蹈病在成人和儿童不同的障碍。将在猴中使用基底神经节核的局灶性药理学操作以产生舞蹈病。将在猴中测量所得舞蹈病，并与人类舞蹈病进行比较，以验证猴模型，特别是儿童舞蹈病。然后，通过记录单个苍白球内段神经元在舞蹈病之前和期间的活动，将猴模型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，舞蹈病病理生理学的流行假设可以得到严格的检验。 有很大的潜力，以确定舞蹈病的基本机制。开发一种非侵入性的方法来量化儿童和猴子的舞蹈病，将是一个重要的进步，更好地表征不自主运动的病理生理学和更有效的药物治疗的发展。

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.