CLINICAL NEUROPHYSIOLOGY OF RETT SYNDROME

本项目的目的是研究其病理生理学。 RETT患者的呼吸障碍，以确定其特征 癫痫发作的临床和脑电参数 RETT患者体验到的，利用神经生理学 参数，以评估这种综合征的演变，并 评估这些患者对药物的反应 治疗方式。本研究将分为四个部分 阶段：第一阶段，治疗前的基线阶段；第二阶段， 使用短效阿片类拮抗剂的急性治疗期， 纳洛酮；第三阶段，对阿片类药物纳曲酮的评价 在一项双盲/交叉研究中，拮抗剂与安慰剂； 第四阶段，长期随访。在这四个阶段中，50- 60名自闭症患者和12名自闭症对照组患者参加了 项目I将通过使用神经生理学技术进行评估 这将包括(1)通宵睡眠研究；(2)延长 脑电/视频监测，包括基于计算机的背景脑电 分析；(3)呼吸机化疗药物敏感性评估 缺氧和高碳水化合物的挑战；以及(4)评估 部分呼气流量容量曲线和部分呼气流量曲线的气道功能 清醒和睡眠时呼吸努力的多道描记记录。 这些数据将被用来检验以下假设：(1) 这些患者有异常的清醒/行为控制 呼吸。(2)上呼吸道功能障碍 呼吸紊乱发作时的肌肉组织。(3) 雷特综合征的表现，包括呼吸道 干扰，在一定程度上是潜在干扰的结果 或β-内啡肽和/或阿片受体异常 敏感度。(4)一些被报告为癫痫发作的事件可能是 呼吸紊乱或手部刻板印象 动静。这些数据还将用于与 从其他项目获得的数据，以提供进一步的 Rett综合征的特征，对其更好的定义 临床分期，以及其变异体的鉴定。

The purpose of this project is to investigate the pathophysiology of the respiratory disturbance in Rett patients, to characterize the clinical and electroencephalographic parameters of seizures experienced by Rett patients, to utilize neurophysiological parameters to evaluate the evolution of this syndrome, and to evaluate the response of these patients to pharmacological treatment modalities. The research will be divided into four phases: Phase I, a baseline phase prior to treatment; Phase II, an acute treatment phase with a short-acting opiate antagonist, naloxone; Phase III, evaluation of naltrexone, an opiate antagonist, vs placebo, during a double-blind/crossover study; and, Phase IV, long-term follow-up. During these four phases, the 50- 60 Rett patients and 12 autistic control patients enrolled in Project I will be evaluated by use of neurophysiological techniques that will include (1) overnight sleep studies; (2) prolonged EEG/video monitoring, including computer-based background EEG analysis; (3) assessment of ventilatory chemosensitivity during hepoxic and hypercarbic challenges; and (4) evaluation of upper airway function by partial expiratory flow volume curves and polygraphic recordings of respiratory effort, awake and asleep. The data will be utilized to test the following hypothesis: (1) These patients have abnormal awake/behavioral control of breathing. (2) There is a dysfunction of the upper airway musculature during episodes of disorganized breathing. (3) The manifestations of the Rett syndrome, including the respiratory disturbance, are, in part, the result of an underlying disturbance or abnormality in beta-endorphins and/or opiate-receptor sensitivity. (4) Some events reported to be seizures may be episodes of disorganized breathing or stereotyped hand movements. These data will also be utilized in correlation with data obtained from other projects to provide a further characterization of the Rett syndrome, a better definition of its clinical stages, and an identification of its variants.