Clinical and Neuroimaging Phenotypes of Neurodevelopmental Disorders inPediatric Sickle Cell Disease

摘要_ 镰状细胞病是一种遗传性血液疾病，具有多种神经系统和发育性疾病。 并发症。虽然在神经性疾病的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无症状脑梗塞方面，患有SCD的儿童仍然 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。SCD儿童与注意力 缺陷多动障碍(ADHD)，无中风或无症状性脑梗塞病史，定义为 隐匿性ADHD代表了这一弱势群体中一个未被充分研究但却很重要的子集。我们 假设隐源性ADHD与脑白质损伤和血浆生物标记物相关 脑部受伤。我们将通过以下具体目标来探索这一假说。 目的1：明确SCD隐源性ADHD的临床危险因素。 通过对儿童SCD神经发育和血液学患者的回顾图表回顾 临床，我们将比较SCD和隐源性ADHD儿童与 无中风、无症状性脑梗塞或ADHD等神经发育障碍病史。 目的2：建立隐源性ADHD与脑白质损伤之间的联系。 我们将招募20名患有SCD和隐源性ADHD的8至12岁儿童和20名SCD儿童 既往无中风、无症状性脑梗塞或ADHD等神经发育障碍病史 参加病例对照研究。受试者将接受神经发育和神经心理学检查。 评估，神经成像方案，包括DTI，动脉自旋标记，氧提取分数，和 体积成像和血样抽取。 目的3：建立隐源性ADHD与血浆生物标记物之间的联系。 利用目标2中研究对象组的血液样本，我们将测量不同类型的 神经和神经胶质蛋白标记物用于确定神经损伤的潜在血浆生物标记物蛋白。我们 将把蛋白质水平与DTI结果以及神经心理测量结果进行比较。 拟议的工作将确定SCD和隐源性儿童的临床和神经影像表型。 ADHD，将这一人群确立为儿童SCD所见的脑损伤谱的一部分。《校长》 调查员将需要在SCD的血液学管理和神经成像方面的额外培训 获取和分析技术，以完成提议的项目。未来的研究将涉及到DTI的使用 作为疾病严重程度的衡量标准，预测认知结果，并监测临床治疗反应 对目标2中设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。

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.