Clinical and Neuroimaging Phenotypes of Neurodevelopmental Disorders inPediatric Sickle Cell Disease

小儿镰状细胞病神经发育障碍的临床和神经影像表型

基本信息

批准号：
9385561
负责人：
EBONI I LANCE
金额：
$ 18.14万
依托单位：
HUGO W. MOSER RES INST KENNEDY KRIEGER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-15 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9385561
关键词：
12 year old Address Age Anisotropy Area Attention Attention deficit hyperactivity disorder Biological Markers Blood Blood Pressure Blood specimen Brain Brain Injuries Brain region Brain-Derived Neurotrophic Factor Case-Control Studies Cerebral Infarction Characteristics Child Childhood Clinic Clinical Clinical Investigator Clinical Research Clinical Trials Cognition Cognitive Coupled Data Databases Development Diagnosis Diffuse Diffusion Magnetic Resonance Imaging Disease Doctor of Philosophy Doppler Ultrasound Early Diagnosis Enrollment Etiology Evaluation Functional disorder Future Gender General Population Glial Fibrillary Acidic Protein Goals Hematological Disease Hematology Hemoglobin Image Immunoassay Impaired cognition Infarction Inflammatory Inherited Injury Instruction Intercellular Adhesion Molecules Ischemia Ischemic Stroke Knowledge Lead Logistic Regressions Longitudinal cohort Measures Medical Mentors Monitor Monocyte Chemoattractant Protein-1 Nervous System Trauma Neurodevelopmental Disorder Neurologic Neurons Neuropsychology Outcome Outcomes Research Oxygen Pathogenesis Pathway interactions Phenotype Plasma Plasma Proteins Population Principal Investigator Protein Analysis Proteins Protocols documentation Recording of previous events Recruitment Activity Research Research Subjects Risk Risk Factors Role Sampling Schools Services Severity of illness Sickle Cell Anemia Spin Labels Stroke Techniques Testing Therapeutic Intervention Time Training Vulnerable Populations Work case control clinical phenotype clinical risk disorder control executive function frontal lobe imaging study modifiable risk neurodevelopment neurogranin neuroimaging neuroimaging marker pediatric patients potential biomarker prognostic prospective protein biomarkers response sample collection screening standard of care stroke treatment success targeted treatment tau Proteins treatment response ubiquitin C-terminal hydrolase visinin white matter white matter injury

项目摘要

ABSTRACT _____ ________________________ ______________ _____ _ Sickle cell disease (SCD) is an inherited blood disorder with several neurological and developmental complications. While there has been progress in terms of screening and treatment of neurological complications, particularly in terms of overt ischemic stroke and silent cerebral infarct, children with SCD still have worsening cognition over time in the absence of obvious brain injury. Children with SCD and attention deficit hyperactivity disorder (ADHD) and no prior history of stroke or silent cerebral infarct, defined as cryptogenic ADHD, represent an understudied yet important subset of this vulnerable population. We hypothesize that cryptogenic ADHD is associated with white matter injury and plasma biomarkers associated with brain injury. We will explore this hypothesis through the following Specific Aims. Aim 1: Identify clinical risk factors of cryptogenic ADHD in SCD. Through a retrospective chart review of patients from pediatric SCD neurodevelopmental and hematology clinics, we will compare the clinical characteristics of children with SCD and cryptogenic ADHD to children with SCD and no prior history of stroke, silent cerebral infarct, or ADHD and other neurodevelopmental disorders. Aim 2: Establish associations between cryptogenic ADHD and white matter brain injury. We will recruit 20 children 8 to 12 years of age with SCD and cryptogenic ADHD and 20 children with SCD without a prior history of stroke, silent cerebral infarct, or ADHD and other neurodevelopmental disorders to participate in a case control study. Subjects will undergo neurodevelopmental and neuropsychological evaluations, neuroimaging protocols including DTI, arterial spin labeling, oxygen extraction fraction, and volumetric imaging, and blood sample draw. Aim 3: Establish associations between cryptogenic ADHD and plasma biomarkers. Using the blood samples from the group of research subjects in Aim 2, we will measure the levels of various neuronal and glial protein markers to identify potential plasma biomarker proteins of neurological injury. We will compare the protein levels to DTI findings as well as neuropsychological measures. The proposed work will define a clinical and neuroimaging phenotype of children with SCD and cryptogenic ADHD, establishing this population as part of the spectrum of brain injury seen in pediatric SCD. The Principal Investigator will require additional training in the hematological management of SCD and neuroimaging acquisition and analysis techniques to complete the proposed projects. Future research will involve use of DTI as a measure of disease severity, predict cognitive outcomes, and monitor response to treatment in clinical trials research and longitudinal assessment of the research group established in Aim 2 to establish their risk of future neurological complications.

抽象的 _____ ________________________ ______________ _____ _ 镰状细胞病 (SCD) 是一种遗传性血液疾病，伴有多种神经和发育障碍并发症。尽管在神经系统疾病的筛查和治疗方面取得了进展并发症，特别是明显的缺血性中风和无症状脑梗塞，患有 SCD 的儿童仍然存在并发症在没有明显脑损伤的情况下，随着时间的推移，认知能力会恶化。患有 SCD 的儿童和注意力缺陷性多动障碍 (ADHD) 并且既往无中风或无症状脑梗塞病史，定义为隐源性注意力缺陷多动症（ADHD）代表了这一弱势群体中未被充分研究但很重要的一个子集。我们假设隐源性 ADHD 与白质损伤和血浆生物标志物相关患有脑损伤。我们将通过以下具体目标来探讨这一假设。目标 1：确定 SCD 中隐源性 ADHD 的临床危险因素。通过对小儿 SCD 神经发育和血液学患者的回顾性图表审查在诊所中，我们将比较 SCD 和隐源性 ADHD 儿童与患有 SCD 和隐源性 ADHD 的儿童的临床特征。 SCD 且既往无中风、无症状脑梗死、或多动症和其他神经发育障碍病史。目标 2：建立隐源性 ADHD 与白质脑损伤之间的关联。我们将招募 20 名 8 至 12 岁患有 SCD 和隐源性 ADHD 的儿童和 20 名患有 SCD 的儿童既往无中风、无症状性脑梗塞、多动症或其他神经发育障碍病史参加病例对照研究。受试者将接受神经发育和神经心理学测试评估、神经影像方案，包括 DTI、动脉自旋标记、氧提取分数和体积成像和血液样本抽取。目标 3：建立隐源性 ADHD 和血浆生物标志物之间的关联。使用目标 2 中研究对象组的血液样本，我们将测量各种神经元和神经胶质蛋白标记物，用于识别神经损伤的潜在血浆生物标记物蛋白。我们将蛋白质水平与 DTI 结果以及神经心理学测量结果进行比较。拟议的工作将定义 SCD 和隐源性儿童的临床和神经影像表型 ADHD 将该人群确定为儿科 SCD 脑损伤范围的一部分。校长研究者将需要接受 SCD 血液学管理和神经影像学方面的额外培训采集和分析技术来完成拟议的项目。未来的研究将涉及 DTI 的使用作为疾病严重程度的衡量标准、预测认知结果并监测临床治疗的反应对目标 2 中建立的研究小组进行试验研究和纵向评估，以确定其风险未来的神经系统并发症。