Disrupted Nighttime Sleep (DNS) in Pediatric Narcolepsy

小儿发作性睡病的夜间睡眠 (DNS) 中断

• 批准号: 10401835
• 负责人: Kiran Prasad Maski
• 金额: $ 17.68万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10401835
• 关键词: Adolescence; Affect; Age; Behavior; Behavioral; Behavioral Sciences; Boston; Cataplexy; Child; Childhood; Chronic Disease; Clinical Trials; Cognition; Cognitive; Complement; Cross-Sectional Studies; Data; Development; Disease; Drowsiness; Emotional; Emotions; Environment; Evolution; Foundations; Frequencies; Goals; Guidelines; Hyperactivity; Impairment; Incidence; Intuition; Knowledge; Light; Link; Measures; Medicine; Memory; Mentors; Mentorship; Methods; Mood Disorders; Moods; Narcolepsy; Nerve Degeneration; Neurology; Neurons; Neurosciences; Outcome; Pathologic; Pathology; Patients; Pediatric Hospitals; Pediatric Neurology; Pediatric cohort; Pharmaceutical Preparations; Physicians; Physiology; Play; Problem Solving; Process; Prospective Studies; Protocols documentation; Public Health; Public Health Schools; REM Sleep; Rare Diseases; Research; Research Design; Research Methodology; Research Support; Role; Scientist; Sleep; Sleep Architecture; Sleep Disorders; Sleep Fragmentations; Sleep Stages; Sleep disturbances; Sodium Oxybate; Stage III Sleep; Symptoms; Techniques; Technology; Testing; Time; Training; age group; aged; analytical method; base; burden of illness; cognitive neuroscience; cohort; comorbidity; diagnostic biomarker; disorder control; emotion regulation; emotional functioning; experimental study; hypocretin; improved; indexing; innovation; mathematical model; medical schools; memory consolidation; memory process; multidisciplinary; negative affect; nervous system disorder; neurophysiology; non rapid eye movement; novel; pediatric patients; predictive marker; psychologic; skills; statistics; treatment strategy

ABSTRACT The proposal will support the research and further Dr. Kiran Maski's training as a physician-scientist in sleep neurology. Dr. Maski's long-term objectives are to examine the neurophysiology of nocturnal sleep in pediatric narcolepsy and its relationship to cognitive and psychological co-morbidities common to this disease, to identify potential sleep neurophysiological diagnostic and predictive biomarkers, and develop and test sleep- specific treatments to reduce disease burden of pediatric narcolepsy patients. To achieve these goals, a training plan focused on (1) analytic skills to study sleep dynamics, (2) fundamental knowledge in cognitive and behavioral neuroscience and sleep-wake physiology, (3) longitudinal and clinical trial research design to facilitate rare disease research is proposed to complement Dr. Maski's background in child neurology and sleep medicine. This training will be accomplished through formal coursework, hands on training, and multi- disciplinary mentorship with world-renown experts in sleep-wake neurophysiology (Dr. Thomas Scammell) and cognitive neuroscience (Dr. Robert Stickgold). Additional consultants and collaborators with expertise in mathematical modeling, statistics, behavioral science, and research methodology utilizing remote audiovisual technology will enrich Dr. Maski's training and proposed research. This training will occur in the context of the rich scholarly environment of Harvard Medical School, Harvard T.H. Chan School of Public Health and Boston Children's Hospital. The research plan is devised to test the central hypothesis that disrupted nighttime sleep (DNS) in pediatric narcolepsy type 1 (NT1) is a specific and dynamic form of sleep pathology that impairs normal emotional and memory processes that occur during sleep. To test this hypothesis, we propose three complimentary but independent aims. In Aim 1, we conduct a cross-sectional study to define DNS with measures unique to pediatric NT1 compared to other sleep disorders and controls. In Aim 2, we study changes in DNS using translational analytic methods within a pediatric NT1 cohort. Lastly, in Aim 3, we investigate predicted changes to sleep architecture between drug-free pediatric NT1 patients, pediatric NT1 patients on established sodium oxybate therapy (a sedating drug that treats DNS) and healthy, aged-matched controls to determine direct effects of sleep fragmentation on memory consolidation and post-sleep emotional processes. Public Health: Substantial evidence links sleep with cognitive and emotional processes. Yet , little is known of the specific pathologic sleep changes that occur in pediatric neurologic diseases and the role this pathology plays in the development of burdensome cognitive and psychological co-morbidities. This proposal serves to provide new analytic methods to characterize sleep pathology in neurological diseases like narcolepsy, test novel methods that show direct cognitive and psychological effects of sleep disruption, and forms the foundation for sleep-specific treatment strategies to reduce disease burden in neurological diseases.

抽象的 该提案将支持这项研究，并进一步进一步的基兰·马斯基（Kiran Maski）博士作为医师科学家的培训 睡眠神经病学。 Maski博士的长期目标是检查夜间睡眠的神经生理学 小儿发肠病及其与这种疾病常见的认知和心理合并症的关系， 确定潜在的睡眠神经生理诊断和预测生物标志物，并发展和测试睡眠 特定治疗方法，以减轻小儿发病患者的疾病负担。为了实现这些目标， 培训计划的重点是（1）研究睡眠动态的分析技能，（2）认知和 行为神经科学和睡眠效果生理学，（3）纵向和临床试验研究设计 提出促进罕见疾病研究以补充马斯基博士在儿童神经病学和 睡眠医学。该培训将通过正式的课程，培训和多种多样来完成 与世界著名专家的纪律指导在睡眠效果神经生理学（Thomas Scammell博士）和 认知神经科学（Robert Stickgold博士）。具有专业知识的其他顾问和合作者 利用远程视听的数学建模，统计，行为科学和研究方法论 技术将丰富Maski博士的培训和拟议的研究。该培训将在 哈佛大学T.H.哈佛医学院丰富的学术环境陈公共卫生学院和波士顿 儿童医院。研究计划的设计是为了测试破坏夜间睡眠的中心假设 （DNS）在小儿发肠pypy术1（NT1）是一种特定而动态的睡眠病理学形式，会损害 睡眠期间发生的正常情绪和记忆过程。为了检验这一假设，我们提出了三个 免费但独立的目标。在AIM 1中，我们进行了一项横断面研究，以定义DNS 与其他睡眠障碍和对照相比，小儿NT1独有的措施。在AIM 2中，我们研究更改 在DNS中，使用小儿NT1队列中的翻译分析方法。最后，在AIM 3中，我们调查 预测无毒的小儿NT1患者，小儿NT1患者之间的睡眠结构变化 已建立的氧化钠疗法（一种治疗DNS的镇静药）和健康的，老年匹配的对照 确定睡眠碎片化对记忆巩固和睡眠后情绪过程的直接影响。 公共卫生：大量证据将睡眠与认知和情感过程联系起来。然而，知之甚少 小儿神经系统疾病中发生的特定病理睡眠变化以及这种病理的作用 发挥了繁重的认知和心理合并症的发展。该提议用于 提供新的分析方法，以表征性睡眠，例如测试的神经系统疾病中的睡眠病理 显示出睡眠中断的直接认知和心理影响并形成的新方法 针对特定睡眠治疗的基础，以减轻神经系统疾病的疾病负担。

项目成果

How should disrupted nocturnal sleep be characterized in narcolepsy type 1?

1 型发作性睡病的夜间睡眠中断应如何表征？

• DOI: 10.1093/sleep/zsac096
• 发表时间: 2022
• 期刊: Sleep
• 影响因子: 5.6
• 作者: Maski,Kiran;Trotti,LynnMarie
• 通讯作者: Trotti,LynnMarie

Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline.

• DOI: 10.5664/jcsm.9328
• 发表时间: 2021-09-01
• 期刊: Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
• 作者: Maski, Kiran;Trotti, Lynn Marie;Watson, Nathaniel F
• 通讯作者: Watson, Nathaniel F

Remote Assessment of Pediatric Patients with Daytime Sleepiness and Healthy Controls: A Pilot Study of Feasibility and Reliability.

• DOI: 10.1177/2329048x211048064
• 发表时间: 2021-01
• 期刊: Child neurology open
• 作者: Worhach J;Boduch M;Zhang B;Maski K
• 通讯作者: Maski K

Development and Validation of the Pediatric Hypersomnolence Survey.

儿科嗜睡症调查的开发和验证。

• DOI: 10.1212/wnl.0000000000200187
• 发表时间: 2022
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Maski,Kiran;Worhach,Jennifer;Steinhart,Erin;Boduch,Madeline;Morse,AnneMarie;Strunc,Michael;Scammell,Thomas;Owens,Judith;Jesteadt,Lindsay;Crisp,Claire;Williams,David;Sideridis,Georgios
• 通讯作者: Sideridis,Georgios