STROKE AND NEUROLOGICAL ASPECTS OF SICKLE CELL DISEASES

该项目是正在进行的调查的继续， 关注镰状细胞病的两大神经系统并发症： 即中风和慢性脑病。 中风代表一个局灶性 脑损伤，而慢性脑病代表弥漫性脑损伤， 涉及认知和记忆的障碍。 中风的易感性 从我们的研究中， 和其他调查员的工作 这两个过程的个体发育 需要进一步研究，才能明确阐明机制; 需要对脑血管灌注进行协调评估， 解读局灶性灌注缺损与闭塞之间的关系 大脑的大小血管 这些调查需求代表了 后续研究设计和可检验假设的基础。 我们 我拟检验三个假设：（1）临床无症状的头颅MRI 异常代表神经血管的最小表达， 是临床上明显中风的先兆（研究A）; (2)镰状细胞病患者发生脑梗死， 导致这种神经系统疾病的诱发风险因素 并发症（研究B）;和（3）镰状细胞病患者发生 慢性脑病和痴呆症是独立的 神经血管素质（研究C）。 将入组150例受试者 这些研究。 该人群将包括100例SCD患者， 50个不带SCD的对照品。 100名受试者（50名患者和50名同胞或 最近的相对对照）将参与研究A、B和C;以及 50名受试者（25名SCD患者-卒中患者，25名SCD患者- 临床上无中风）将参与研究B。 患者 研究A、B和C中的对照组年龄范围为6 - 12岁。 研究B回顾性部分的患者将是年轻人 成年人了 研究A是对50名6岁的SCD儿童的前瞻性评价 至12年，试图确定一个亚组的患者的风险， 临床上明显的中风的发展。 这些患者将被 临床评估，并将接受MRI扫描，磁共振 血管造影（MRA）和单光子发射计算机断层扫描 （SPECT）。 研究B代表两项旨在分析风险因素的研究 治疗中风 第一项研究是回顾性病例对照分析， 25名年轻人遭受了一次或多次中风。 这些患者将 与临床上无SCD的SCD对照组年龄匹配 中风，并将进行MRI、MRA和SPECT研究。 第二项研究 代表了一个前瞻性的病例对照分析的儿童谁是 在研究A中。 研究C是一项50例SCD患者的前瞻性研究 儿童和50名年龄匹配的兄弟姐妹或最近的亲属。 每年的神经系统检查和神经心理学评估将 寻找慢性脑病的证据， 痴呆 纵向研究设计是必要的，以剖析出 导致认知缺陷的微妙变量。 改进 理解这两种毁灭性的 SCD的神经系统并发症应该得到预防， 有效治疗。

This project represents a continuation of ongoing investigations that focus on the two major neurological complications of sickle cell disease: namely, stroke and chronic encephalopathy. Stroke represents a focal brain insult whereas chronic encephalopathy represents a diffuse brain disturbance involving cognition and memory. The predisposition to stroke and the potential for dementia are increasingly apparent from our studies and the work of other investigators. The ontogeny of these two processes requires further study before the mechanisms can be clearly articulated; and a coordinate assessment of cerebrovascular perfusion is needed to decipher the relationship between focal perfusion deficits and occlusion of large and small cerebral vessels. These investigative needs represent the basis for the subsequent study design and testable hypotheses. We propose to test three hypotheses: (1) clinically-silent cranial MRI abnormalities represent the minimal expression of the neurovascular diathesis, and are the harbingers of clinically-overt strokes (study A); (2) sickle cell disease patients who develop cerebral infarctions have a predisposing risk factor(s) that contributes to this neurological complication (study B); and (3) sickle cell disease patients develop a chronic encephalopathy and dementia that is independent of the neurovascular diathesis (study C). 150 subjects will be enrolled in these studies. This population will include 100 patients with SCD and 50 controls without SCD. 100 subjects (50 patients and 50 siblings or nearest relative controls) will participate in studies A, B and C; and 50 subjects (25 SCD patients - stroke victims, and 25 SCD patients - clinically free of strokes) will participate in study B. The patients and controls in studies A, B, and C will range in age from 6 to 12 years. The patients in the retrospective portion of study B will be young adults. Study A is a prospective evaluation of 50 SCD children aged 6 to 12 years attempting to identify a subgroup of patients at risk for the development of a clinically-apparent stroke. These patients will be evaluated clinically, and will undergo MRI scan, magnetic resonance angiography (MRA), and single photon emission computerized tomography (SPECT). Study B represents two studies designed to analyze risk factors for stroke. The first study is a retrospective case-control analysis of 25 young adults who suffered one or more strokes. These patients will be age-matched to an SCD control group who have been clinically free of strokes and will have MRI, MRA, and SPECT studies. The second study represents a prospective case-control analysis of children who are being followed in study A. Study C represents a prospective study of 50 SCD children, and 50 age-matched siblings or closest available relatives. Annual neurological examinations and neuropsychological evaluations will be performed searching for evidence of chronic encephalopathy and dementia. The longitudinal study design is necessary to dissect out the subtle variables that contribute to the cognitive deficits. Improved understanding of the mechanisms underlying these two devastating neurological complications of SCD should result in prevention or effective treatment.