Longitudinal Neuroimaging in Sturge-Weber Syndrome

描述（由申请人提供）：Sturge-Weber综合征（SWS）是一种神经皮肤综合征，通常在生命的最初几年表现为癫痫发作、神经系统体征和进行性认知下降。虽然这种疾病通常是进行性的，但目前还没有客观的标志物来识别具有毁灭性结局的最高风险的患者。这项建议的总体目标是收集定量的结构和功能的神经影像学数据，在一个前瞻性的，纵向的方式在儿童单侧SWS，并将这些与临床变量。使用正电子发射断层扫描（PET）和磁共振成像/波谱（MRI/MRS），我们希望找到（基于我们的初步数据）客观的标志物，以确定SWS儿童谁是进行性认知能力下降和严重癫痫发作的主要风险。由于手术切除受影响的大脑区域可能是预防临床进展的有效方法，并促进幼儿的大脑可塑性，这些发现将对SWS的临床管理产生重大影响，为精心挑选的患者建立早期手术干预的基础。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，大的皮质区域与轻度代谢低下与严重的癫痫发作，而快速的单侧结构性脑损伤可能与良好的认知结果相关联，据说是通过促进未受影响的大脑区域的重组过程。在受影响的皮质中，MRS检测到谷氨酸浓度增加和NAA降低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1。确定单侧SWS幼儿（首次扫描时3个月-5岁）受累半球代谢和结构异常的变化（每隔1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脑异常模式。目标4。确定SWS患者的皮质切除术是否可以逆转认知功能下降。 该研究将确定神经影像学标记物，可用作SWS临床进展的诊断预测因子。这可能有助于选择早期切除手术受益的患者。MRS研究还可以提供新的数据，在SWS的病理生理学中的作用，多巴胺能神经递质的毒性，这可能会打开新的治疗方法。此外，这些发现将有助于更好地理解早期脑损伤对发育中大脑重组过程的影响。

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.