CLINICAL NEUROPHYSIOLOGY OF RETT SYNDROME

RETT 综合征的临床神经生理学

• 批准号: 3842914
• 负责人: DANIEL G GLAZE
• 金额: --
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 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/3842914
• 关键词: Rett syndrome; autism; chemoreceptors; child (0-11); degenerative motor system disease; electroencephalography; endorphins; generalized seizures; human subject; naloxone; naltrexone; neuromuscular disorder chemotherapy; neuropharmacologic agent; neurophysiology; pulmonary respiration; respiratory airflow disorder; respiratory airflow measurement; respiratory muscles; sleep

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.

该项目的目的是研究病理生理学 Rett 患者呼吸障碍的研究，以表征 癫痫发作的临床和脑电图参数 Rett 患者所经历的，利用神经生理学 参数来评估该综合征的演变，并 评估这些患者对药物的反应 治疗方式。 研究将分为四部分 阶段：第一阶段，治疗前的基线阶段；第二阶段， 使用短效阿片拮抗剂的急性治疗阶段， 纳洛酮； III 期，阿片类药物纳曲酮的评估 在双盲/交叉研究期间，拮抗剂与安慰剂对比；和， 第四阶段，长期随访。 在这四个阶段中，50- 60 名 Rett 患者和 12 名自闭症对照患者入组 项目 I 将使用神经生理学技术进行评估 其中包括 (1) 夜间睡眠研究； (2) 延长 脑电图/视频监测，包括基于计算机的背景脑电图 分析; (3) 通气化疗敏感性评估 缺氧和高碳酸挑战； (4)上层评估 气道功能通过部分呼气流量曲线和 清醒和睡眠状态下的呼吸努力的多描记记录。 该数据将用于检验以下假设：（1） 这些患者的清醒/行为控制能力异常 呼吸。 (2)上呼吸道功能障碍 呼吸紊乱期间的肌肉组织。 (3) 的 雷特综合征的表现，包括呼吸道疾病 干扰，部分是潜在干扰的结果 或β-内啡肽和/或阿片受体异常 敏感性。 (4) 一些报告为癫痫发作的事件可能是 呼吸紊乱或手部定型的发作 动作。 这些数据还将用于相关 从其他项目获得的数据可提供进一步的 Rett 综合征的特征，更好的定义 临床阶段及其变异的鉴定。