CLINICAL NEUROPHYSIOLOGY OF RETT SYNDROME

本项目的目的是研究 Rett患者的呼吸障碍，以表征 癫痫发作的临床和脑电图参数 Rett患者的经验，利用神经生理学 参数来评估这种综合征的演变，并 评价这些患者对药物治疗的反应， 治疗方式。 研究将分为四个部分 阶段：I期，治疗前的基线阶段; II期， 用短效阿片拮抗剂的急性治疗期， 纳洛酮; III期，阿片类药物纳洛酮的评价 双盲/交叉研究期间，拮抗剂vs安慰剂;以及， 第四阶段，长期随访。 在这四个阶段，50- 60名Rett患者和12名自闭症对照患者入组研究， 项目I将通过使用神经生理学技术进行评估 这将包括（1）夜间睡眠研究;（2）长期 EEG/视频监测，包括基于计算机的背景EEG 分析;（3）评估化疗期间的药物敏感性 肝功能和高碳水化合物的挑战;和（4）评估上 通过部分呼气流量容积曲线测定气道功能， 记录清醒和睡眠时的呼吸努力。 这些数据将用于检验以下假设：（1） 这些患者的清醒/行为控制异常， 呼吸了 (2)上呼吸道功能障碍 在呼吸紊乱的情况下，肌肉组织。 (3)的 Rett综合征的临床表现，包括呼吸道 干扰，是，部分，潜在的干扰的结果， 或β-内啡肽和/或阿片受体异常 灵敏度 (4)一些报告为癫痫发作的事件可能 呼吸紊乱或刻板的手 动作 这些数据还将用于与 从其他项目中获得的数据， Rett综合征的特征，更好地定义其 临床分期，以及其变体的鉴定。

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.