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）：Sturge-weber综合征（SWS）是一种神经疾病综合征，通常表现为生命最初几年的癫痫发作，神经系统迹象和渐进认知的下降。尽管该疾病通常是渐进的，但目前尚无客观标记来识别患有灾难性结果风险最高的患者。该提案的总体目的是在单侧SWS的儿童中以前瞻性的纵向方式收集定量结构和功能性神经影像学数据，并将其与临床变量相关联。使用正电子发射断层扫描（PET）和磁共振成像/光谱法（MRI/MRS），我们希望（基于我们的初步数据）目标标记，这些标记识别出患有SWS的儿童，而SWS的儿童具有渐进性下降和严重癫痫发作的主要风险。由于对受影响的大脑区域的手术切除可能是预防临床进展并促进幼儿脑可塑性的有效方法，因此，通过在精心挑选的患者中为早期的手术干预建立基础，这些发现将对SWS的临床管理产生重大影响。这种期望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。具体而言，具有轻度低代谢的大型皮质区域与严重的癫痫发作有关，而快速的单方面结构性脑损伤可能与良好的认知结果相关，据说是通过促进不受影响的大脑区域的重组过程。谷氨酸浓度升高并在受影响的皮层中MRS检测到的NAA降低似乎分别与癫痫发作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。为了确定因单侧SWS的幼儿（在初次扫描时3个月-5岁的3个月 - 5岁）中的半球的代谢和结构异常的变化（在一年间隔一年间进行的3个测量中）。目的2。确定与认知障碍发展有关的代谢和结构脑异常的模式。目标3。确定与高癫痫发作频率相关的代谢和结构脑异常的模式。目标4。确定SWS中的皮质切除是否可以逆转认知能力下降。 该研究将确定神经影像学标记物，可以用作SWS临床进展的诊断预测指标。这可能有助于选择可以从早期切除手术中受益的患者。 MRS研究还可以提供有关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。这可能打开新的治疗方法。此外，这些发现将有助于更好地理解早期脑部病变对发育中大脑中重组过程的影响。