STROKE RISK IN CHILDREN WITH SICKLE CELL ANEMIA

中风是镰状细胞性贫血儿童的主要并发症 (SCA)，几项主要研究表明，25%的儿童患有 在脑MRI检查时，SCA有脑梗塞的证据。 大约8%-10%的SCA儿童患有症状性中风，而 高达18%或更多的人有无症状中风。出现症状性中风的高峰期是 2-5年，SCA患者卒中并发症包括学校 衰竭、运动障碍和癫痫。 儿童中的大多数中风是由于渐进性咬合导致的 主要的颅内血管，但中风的病理生理学很大程度上 未知。血管受累的组织病理学解释显示 内皮损伤和纤维化。因此，有趣的是，有 越来越多的人认识到免疫系统参与了疾病 以内皮损伤为特征的，如烟雾病。从莫亚人开始 SCA患者出现的烟雾样改变在病理上类似于 在Moya Moya病中，调查人员在初步研究中调查了 54例SCA患儿中是否存在HLA型与卒中的相关性。这些数据 研究表明，人类白细胞抗原表型与中风之间存在显著的相关性。这个 研究者首先发现了SCA对中风风险的多基因影响。 提供了其他初步数据，这些数据演示了初步筛选 寻找可能与69名SCA儿童中风相关的标志物。这些 数据表明，特定的等位基因可能与中风风险有关， 但由于样本量较小，不可能有统计学意义，也不会产生影响 在样本量较小的情况下，无法评估多个基因。 值得注意的是，SCD的中风很可能是遗传和 环境因素，而且坊间证据表明中风经常发生 在SCA的兄弟姐妹中。最后，经颅多普勒超声是唯一 已被证明对识别患者有用的诊断模式 有中风症状的风险；不幸的是，到目前为止还没有测试 有无症状脑梗塞风险的儿童。 这项研究的目的是评估多基因突变的可能性 通过同时评估多个遗传位点参与卒中的SCA。 具体目标包括：1.候选基因的鉴定 用一种新的、基于聚合酶链式反应的多重方法影响SCA儿童的卒中风险 检测；2.)特异性临床诊断与临床诊断之间相互作用的相关性 遗传因素对SCA儿童卒中风险的影响；发展 一种新的基于聚合酶链式反应的多重检测条带的建立 SCA儿童的卒中风险。

Stroke is a major complication of children with sickle cell anemia (SCA), and several major studies have demonstrated that 25% of children with SCA have evidence of infarction at the time of cerebral MRI studies. Approximately 8-10% of children with SCA suffer from symptomatic stroke, while up to 18% or more have silent stroke. The peak age for symptomatic stroke is 2-5 years, and complications of stroke in patients with SCA include school failure, motor handicaps and seizure disorders. The majority of strokes in children are the result of progressive occlusion of the major intracranial vessels, but the pathophysiology of stroke is largely unknown. Histopathologic interpretation of vessel involvement demonstrates endothelial damage and fibrosis. It is of interest therefore, that there is increasing recognition of the involvement of the immune system in diseases characterized by endothelial injury such as Moya Moya disease. Since the Moya Moya-like changes seen in patients with SCA are pathologically similar to those in Moya Moya disease, in a preliminary study the investigators investigated whether HLA type was associated with stroke in 54 children with SCA. These data demonstrated a significant association between HLA phenotype and stroke. The investigator was first to find a multigenic influence on stroke risk in SCA. Other preliminary data were presented which demonstrated a preliminary screen for markers potentially associated with stroke in 69 children with SCA. These data demonstrated that particular alleles may be associated with stroke risk, but the small sample size precluded statistical significance and the effects of multiple genes could not be assessed in the small sample size. Of note, stroke in SCD is likely to be the result of both genetic and environmental factors, and anecdotal evidence suggests that stroke occurs often in siblings with SCA. Finally, transcranial Doppler ultrasound is the only diagnostic modality which has been shown to be useful in identifying patients at risk for symptomatic stroke; unfortunately there is as yet no test for children at risk for silent infarct. The objectives of this study are to evaluate the possibility of a multigenic involvement in stroke in SCA by simultaneously assessing multiple genetic loci. The specific aims include the following: 1.) Identification of candidate genes influencing stroke risk in children with SCA using a novel, PCR-based multiplex assay; 2.) Correlation of the interactions between specific clinical and genetic factors on the risk of stroke in children with SCA; and 3.) Development of a new PCR-based multiplex assay strip specifically for use in assessing stroke risk in children with SCA.