Non-convulsive seizures in critically ill children:physiology and outcome

危重儿童的非惊厥性癫痫发作：生理学和结果

• 批准号: 8325005
• 负责人: Nicholas Scott Abend
• 金额: $ 17.84万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325005
• 关键词: Accounting; Acute; Address; Adult; Agreement; Appearance; Behavioral; Biometry; Brain; Brain Injuries; Caring; Case Series; Cerebrovascular Circulation; Cerebrum; Characteristics; Child; Clinical; Clinical Investigator; Clinical Management; Clinical Research; Critical Illness; Critically ill children; Data; Detection; Development; Development Plans; Electrodes; Electroencephalography; Encephalopathies; Environment; Epidemiology; Etiology; Evaluable Disease; Event; Evolution; Financial compensation; Foundations; Funding; Future; Goals; Heart Arrest; Hour; Imaging Techniques; Impact Seizures; Injury; Institutes; International; Investigation; Label; Link; Measurement; Measures; Medical; Mentors; Mentorship; Metabolic; Methods; Metric; Modality; Monitor; Motor Seizures; Neurologic; Neurosciences; Nomenclature; Observational Study; Outcome; Outcomes Research; Oxygen; Oxygen Consumption; Patients; Pattern; Pediatric Hospitals; Pediatric Neurology; Pennsylvania; Philadelphia; Physiologic Monitoring; Physiological; Physiology; Prospective Studies; Reader; Research; Research Ethics; Research Infrastructure; Research Personnel; Research Training; Resuscitation; Seizures; System; Testing; Time; Training; Treatment outcome; United States National Institutes of Health; Universities; Work; base; career development; experience; improved; neonatal hypoxic-ischemic brain injury; neonate; neuroprotection; novel; optical imaging; patient oriented research; professor; prospective; response; symposium

DESCRIPTION (provided by applicant): Dr. Nicholas Abend is an Assistant Professor of Neurology and Pediatrics at the University of Pennsylvania (U Penn) and the Children's Hospital of Philadelphia (CHOP). Dr. Abend has completed initial studies demonstrating that non-convulsive seizures (NCS) are common in critically ill children with acute encephalopathy. However, their impact on physiology and outcome is unknown. As a natural extension of this work, his short-term goal is to conduct mentored research on critically ill children focused on the impact of NCS on cerebral physiology and neuro-developmental outcome, and to gain research training related to outcomes research and non-invasive optical imaging of cerebral physiology. His long-term goal is to become an independent investigator leading multi-disciplinary investigations of multi-modality physiologic monitoring and management to improve the neuro-developmental outcome of critically ill children. Research: Dr. Abend proposes three linked aims: (1) Develop a valid seizure burden metric that accounts for NCS anatomical extent and duration. This metric can be used by future studies evaluating the neurodevelopmental impact and optimal management of NCS. (2) Perform a prospective study to determine whether NCS and non-ictal rhythmic discharges (RD) have a detrimental impact on cerebral physiology, as measured by non-invasive optical imaging of cerebral blood flow and oxygenation. Discovery of a causal mechanism by which some NCS and RD could worsen outcome would suggest that NCS and RD detection and management could improve outcome. Additionally, rather than relying on standardized nomenclature to categorize RD based on electrographic appearance, RD could be categorized more physiologically. (3) Perform a prospective study evaluating the impact of NCS on neuro-developmental outcome. An association between NCS and worse neuro-developmental outcome would suggest that NCS identification and management could improve outcome. Dr. Abend will investigate children resuscitated from cardiac arrest, providing a singular etiology suitable for study. However, since NCS occur in a large number of critically ill children and adults with a wide variety of acute encephalopathies, extensions of this work may improve the outcome of many critically ill patients. Environment and Career Development: The scientific and career development plans build upon a mentorship and research infrastructure at CHOP and U Penn that has already made Dr. Abend very productive. This training network will be enhanced by additional mentors and collaborators, extensive one-on-one training in optical imaging acquisition and analysis, courses within the Center for Epidemiology and Biostatistics and The Neuroscience Institute (focused on clinical research, outcomes research, biostatistics, neuroprotection, and research ethics), and participation in a wide array of research conferences. Dr. Abend's mentorship team has extensive experience in NIH funded clinical research, a track record of training successful independent investigators, and a commitment to Dr. Abend's development into an independent researcher and international leader. The combination of expert mentorship, a well-developed clinical research infrastructure, and extensive didactic training will assure Dr. Abend's developing into an effective neuroscientist working to improve the outcome of treatment of critically ill children. Summary: The scientific and career development plans will provide an excellent patient-oriented research experience with world-class mentorship in an outstanding environment. Completion of these plans will provide Dr. Abend with the scientific and methodological foundation to conduct independent research focused on real-time multi-modal neuro-monitoring, which has the potential to reduce neurologic injury in critically ill patients.

描述（由申请人提供）：Nicholas Abend 博士是宾夕法尼亚大学 (U Penn) 和费城儿童医院 (CHOP) 的神经病学和儿科助理教授。 Abend 博士完成的初步研究表明，非惊厥性癫痫发作 (NCS) 在患有急性脑病的危重儿童中很常见。然而，它们对生理和结果的影响尚不清楚。作为这项工作的自然延伸，他的短期目标是对危重儿童进行指导性研究，重点关注 NCS 对脑生理学和神经发育结果的影响，并获得与结果研究和非侵入性治疗相关的研究培训。脑生理学的光学成像。他的长期目标是成为一名独立研究者，领导多学科的多模式生理监测和管理研究，以改善危重儿童的神经发育结果。 研究：Abend 博士提出了三个相互关联的目标：(1) 制定有效的癫痫发作负担指标，以解释 NCS 的解剖范围和持续时间。未来的研究可以使用该指标来评估 NCS 的神经发育影响和最佳管理。 (2) 进行一项前瞻性研究，以确定 NCS 和非发作性节律性放电 (RD) 是否对脑生理学产生有害影响，通过脑血流和氧合的无创光学成像进行测量。发现某些 NCS 和 RD 可能使结果恶化的因果机制表明 NCS 和 RD 检测和管理可以改善结果。此外，与其依赖标准化命名法根据电图外观对 RD 进行分类，不如从生理学角度对 RD 进行分类。 (3) 进行前瞻性研究，评估 NCS 对神经发育结果的影响。 NCS 与较差的神经发育结果之间的关联表明 NCS 的识别和管理可以改善结果。阿本德博士将调查心脏骤停复苏的儿童，提供适合研究的单一病因。然而，由于 NCS 发生在大量患有各种急性脑病的危重儿童和成人中，因此这项工作的扩展可能会改善许多危重患者的预后。 环境和职业发展：科学和职业发展计划建立在 CHOP 和宾夕法尼亚大学的指导和研究基础设施的基础上，这已经使 Abend 博士非常富有成效。 该培训网络将通过额外的导师和合作者、光学成像采集和分析方面的广泛一对一培训、流行病学和生物统计学中心以及神经科学研究所内的课程（重点是临床研究、结果研究、生物统计学、神经保护）得到加强。和研究伦理），并参加各种研究会议。 Abend 博士的导师团队在 NIH 资助的临床研究方面拥有丰富的经验，在培训成功的独立研究者方面拥有丰富的经验，并致力于将 Abend 博士发展成为一名独立研究者和国际领导者。专家指导、完善的临床研究基础设施和广泛的教学培训相结合，将确保阿本德博士发展成为一名有效的神经科学家，致力于改善危重儿童的治疗结果。摘要：科学和职业发展计划将在良好的环境中提供卓越的以患者为中心的研究经验以及世界一流的指导。这些计划的完成将为 Abend 博士提供科学和方法基础，以开展专注于实时多模式神经监测的独立研究，这有可能减少危重患者的神经损伤。