Longitudinal Neuroimaging in Sturge-Weber Syndrome

斯特奇-韦伯综合征的纵向神经影像学

• 批准号: 6911477
• 负责人: CSABA JUHASZ
• 金额: $ 31.36万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6911477
• 关键词: bioimaging /biomedical imaging; brain; brain disorder diagnosis; brain imaging /visualization /scanning; brain metabolism; brain morphology; clinical research; cognition; congenital nervous system disorder; epilepsy; glucose metabolism; hemangioma; human subject; human therapy evaluation; infant human (0-1 year); longitudinal human study; magnetic resonance imaging; neural plasticity; neuroimaging; neuropsychological tests; neurosurgery; nuclear magnetic resonance spectroscopy; pathologic process; patient oriented research; positron emission tomography; preschool child (1-5); prognosis; syndrome

DESCRIPTION (provided by applicant): Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome that typically manifests as seizures, neurological signs, and progressive cognitive decline in the first few years of life. Although the disease is often progressive, there are, at present, no objective markers to identify patients at highest risk for a devastating outcome. The overall aim of this proposal is to collect quantitative structural and functional neuroimaging data in a prospective, longitudinal way in children with unilateral SWS, and to correlate these with clinical variables. Using positron emission tomography (PET) and magnetic resonance imaging/spectroscopy (MRI/MRS), we expect to find (based on our preliminary data) objective markers that identify children with SWS who are at major risk for progressive cognitive decline and severe seizures. Since surgical resection of affected brain regions may be an effective way of preventing clinical progression, and facilitating brain plasticity in young children, the findings will have a major impact on clinical management in SWS by establishing a ground for early surgical intervention in carefully selected patients. This expectation is based on our preliminary studies showing that brain glucose metabolic abnormalities are closely related to the clinical progression. Specifically, large cortical regions with mild hypometabolism are associated with severe seizures, while rapid unilateral structural brain damage may be paradoxically associated with good cognitive outcome, supposedly by facilitating reorganizational processes in unaffected brain regions. Increased glutamate concentration and decreased NAA detected by MRS in the affected cortex appear to be related to epileptogenicity and progressive neuronal dysfunction, respectively. In this study we propose four aims: Aim l. To determine the changes (among 3 measurements made at one year intervals) in abnormalities of metabolism and structure in the affected hemisphere in young children (3 months - 5 years of age at time of first scans) with unilateral SWS. Aim 2. To identify patterns of metabolic and structural brain abnormalities that are related to development of cognitive impairment. Aim 3. To identify patterns of metabolic and structural brain abnormalities that are associated with high seizure frequency. Aim 4. To determine whether cortical resection in SWS can reverse cognitive decline. The study will identify neuroimaging markers, which may be used as diagnostic predictors of clinical progression in SWS. This may aid in the selection of patients who could benefit from early resective surgery. The MRS studies can also provide novel data on the role of glutamatergic neurotransmitter toxicity in the pathophysiology of SWS; this may open new therapeutic approaches. Further, the findings will help to better understand the effect of early brain lesion on reorganizational processes in the developing brain.

描述（由申请人提供）：斯特奇-韦伯综合征 (SWS) 是一种神经皮肤综合征，通常表现为癫痫发作、神经系统体征和生命最初几年进行性认知能力下降。尽管这种疾病通常是进展性的，但目前还没有客观的标志物来识别出现毁灭性后果的最高风险的患者。该提案的总体目标是以前瞻性、纵向的方式收集单侧 SWS 儿童的定量结构和功能神经影像数据，并将这些数据与临床变量相关联。使用正电子发射断层扫描 (PET) 和磁共振成像/光谱学 (MRI/MRS)，我们期望找到（基于我们的初步数据）客观标记，以识别患有进行性认知衰退和严重癫痫发作的主要风险的 SWS 儿童。由于手术切除受影响的大脑区域可能是预防临床进展和促进幼儿大脑可塑性的有效方法，因此这些发现将为精心挑选的患者的早期手术干预奠定基础，从而对 SWS 的临床管理产生重大影响。这一预期是基于我们的初步研究表明，脑葡萄糖代谢异常与临床进展密切相关。具体来说，具有轻度代谢低下的大皮质区域与严重癫痫发作有关，而快速的单侧结构性脑损伤可能与良好的认知结果矛盾地相关，据称是通过促进未受影响的大脑区域的重组过程。 MRS 在受影响的皮质中检测到的谷氨酸浓度增加和 NAA 减少似乎分别与致癫痫性和进行性神经元功能障碍有关。在这项研究中，我们提出了四个目标： 目标l。通过单侧 SWS 确定幼儿（首次扫描时 3 个月至 5 岁）受影响半球代谢和结构异常的变化（每隔一年进行 3 次测量）。目标 2. 确定与认知障碍发展相关的代谢和结构性大脑异常模式。目标 3. 确定与高癫痫发作频率相关的代谢和结构性大脑异常模式。目标 4. 确定 SWS 中的皮质切除是否可以逆转认知能力下降。 该研究将鉴定神经影像标记物，这些标记物可用作 SWS 临床进展的诊断预测因子。这可能有助于选择可以从早期切除手术中受益的患者。 MRS 研究还可以提供关于谷氨酸能神经递质毒性在 SWS 病理生理学中的作用的新数据；这可能会开辟新的治疗方法。此外，这些发现将有助于更好地了解早期脑损伤对发育中大脑重组过程的影响。