STROKE RISK IN CHILDREN WITH SICKLE CELL ANEMIA

中风是镰状细胞性贫血患儿的主要并发症 (SCA)，几项主要研究表明，25%的儿童 SCA在脑MRI研究时有梗死证据。 大约8-10%的SCA儿童患有症状性卒中， 高达18%或更多的人患有无症状中风。症状性中风的高峰年龄是 2-5年，SCA患者的卒中并发症包括上学 失败，运动障碍和癫痫症。 大多数儿童中风是由于渐进性闭塞的结果， 主要的颅内血管，但中风的病理生理学在很大程度上是 未知血管受累的组织学解释表明 内皮损伤和纤维化。因此，有趣的是， 越来越多的人认识到免疫系统参与疾病 其特征在于内皮损伤，例如莫亚莫亚病。自从莫亚 在SCA患者中观察到的烟雾样改变在病理学上与那些 在莫亚莫亚病的初步研究中， 54例SCA患儿的HLA分型是否与脑卒中有关。这些数据 研究表明HLA表型与中风之间存在显著相关性。的 研究人员首次发现SCA患者中风风险存在多基因影响。 其他初步数据显示，初步筛选 在69名SCA儿童中寻找可能与卒中相关的标志物。这些 数据表明特定的等位基因可能与中风风险相关， 但是小样本量排除了统计学意义， 在小样本量中不能评估多个基因。 值得注意的是，SCD中的中风可能是遗传和 环境因素和轶事证据表明， 在SCA的兄弟姐妹中。最后，经颅多普勒超声是唯一 诊断模式已被证明是有用的，在确定病人 有症状性中风的风险;不幸的是， 有无症状性梗死风险的儿童。 本研究的目的是评估多基因的可能性， 通过同时评估多个遗传位点来评估SCA中卒中的参与。 具体目标包括：（1）候选基因的鉴定 使用一种新的、基于PCR的多重方法影响SCA儿童的卒中风险 测定; 2.）特异性临床和 SCA儿童中风风险的遗传因素; 3.）发展 一种新的基于PCR的多重检测条，专门用于评估 SCA儿童中风风险。

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.