STROKE AND NEUROLOGICAL ASPECTS OF SICKLE CELL DISEASES

该项目代表了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。中风代表一个焦点 脑侮辱，而慢性脑病代表弥漫性脑 涉及认知和记忆的干扰。中风的易感性 从我们的研究来看，患痴呆症的可能性越来越明显 以及其他调查人员的工作。这两个过程的个体发育 需要进一步研究，才能清楚地阐明这些机制； 需要对脑血管灌注进行协调评估，以 破译局灶性血流灌注不足与闭塞的关系 大大小小的脑血管。这些调查需求代表了 为后续的研究设计和可检验的假设奠定基础。我们 建议检验三个假设：(1)临床上无症状的头颅MRI 异常表现为神经血管的最小表达。 素质，是临床显性卒中的先兆(研究A)； (2)发生脑梗塞的镰状细胞病患者有 导致这种神经病的易感危险因素(S) 并发症(研究B)；和(3)镰状细胞病患者发生 慢性脑病和痴呆症独立于 神经血管素质(研究C)。将有150个科目报名参加 这些研究。这一人群将包括100名SCD患者和 对照组50例，无SCD。100名受试者(50名患者和50名兄弟姐妹或 最近亲属对照)将参加研究A、B和C；以及 50名受试者(25名SCD患者-中风患者，25名SCD患者- 临床上没有中风)将参与研究B 而研究A、B和C中的对照组年龄从6岁到12岁不等。 研究B的回顾部分的患者将是年轻的 成年人。研究A是对50名6岁SCD儿童的前瞻性评估 到12年，试图确定一组有风险的患者 临床上明显的中风的发展。这些病人将会是 临床评估，并将接受MRI扫描，磁共振 血管造影术(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。第一项研究为回顾性病例对照分析。 25名患有一次或多次中风的年轻人。这些病人会 年龄与临床上无症状的SCD对照组相匹配 并将进行MRI、MRA和SPECT研究。第二项研究 代表了一项对儿童的前瞻性病例对照分析 接下来是研究A。研究C代表对50例SCD的前瞻性研究。 儿童，以及50名年龄匹配的兄弟姐妹或最接近的亲属。 每年一次的神经学检查和神经心理评估将 进行搜索慢性脑病的证据和 痴呆症。纵向研究设计是必要的，以解剖出 导致认知缺陷的微妙变量。改进 对这两起毁灭性事件背后的机制的理解 SCD的神经系统并发症应预防或 有效的治疗。

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.