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，有几种神经和发育并发症。虽然在神经系统筛查和治疗方面取得了进展并发症，特别是在明显的缺血性中风和沉默的脑梗塞方面，患有SCD的儿童仍然在没有明显的脑损伤的情况下，随着时间的流逝，认知恶化。有SCD和注意力的孩子赤字多动障碍（ADHD），没有中风或无声脑梗塞的先前史，被定义为隐源性多动症，代表了该脆弱人群的经过深入研究但重要的子集。我们假设隐源性多动症与白质损伤和血浆生物标志物相关脑损伤。我们将通过以下特定目标探讨这一假设。 AIM 1：确定SCD中隐性多动症的临床危险因素。通过回顾性图表回顾小儿SCD神经发育和血液学的患者诊所，我们将比较患有SCD和隐性ADHD儿童的临床特征 SCD，没有中风的历史，无声的脑梗塞或多动症和其他神经发育障碍。 AIM 2：建立隐源性多动症与白质脑损伤之间的关联。我们将使用SCD和Cryptogenic ADHD招募20名8至12岁的儿童和20名SCD儿童没有先前的中风病史，无声的脑梗塞，多动症和其他神经发育障碍参加案例控制研究。受试者将接受神经发育和神经心理学评估，包括DTI，动脉自旋标记，氧气提取分数和神经成像方案体积成像和抽血样品。 AIM 3：建立隐源性多动症与血浆生物标志物之间的关联。使用AIM 2中研究对象的血液样本，我们将测量各种水平神经元和神经胶质蛋白标记物，以鉴定神经系统损伤的潜在血浆生物标志物蛋白。我们将将蛋白质水平与DTI发现以及神经心理学措施进行比较。拟议的工作将定义患有SCD和隐性儿童的临床和神经影像型 ADHD，将该人群确立为小儿SCD中脑损伤的一部分。校长研究人员将需要对SCD和神经影像学的血液学管理进行额外的培训采集和分析技术以完成拟议的项目。未来的研究将涉及使用DTI 作为疾病严重程度的量度，预测认知结果并监测临床治疗的反应 AIM 2建立的研究小组的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。