Longitudinal Neuroimaging in Sturge-Weber Syndrome

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、神经症状和生命最初几年的进行性认知能力下降。虽然这种疾病通常是进行性的，但目前还没有客观的标记物来识别具有毁灭性后果的最高风险的患者。本建议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学数据，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/波谱（MRI/MRS），我们希望（基于我们的初步数据）找到客观的标记，以识别具有进行性认知能力下降和严重癫痫发作主要风险的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，因此该研究结果将通过为精心挑选的患者的早期手术干预奠定基础，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，脑糖代谢异常与临床进展密切相关。具体来说，伴有轻度低代谢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相矛盾，可能是通过促进未受影响的大脑区域的重组过程。MRS检测到受病皮层谷氨酸浓度升高和NAA降低分别与致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：目的1 .确定患有单侧SWS的幼儿（首次扫描时为3个月至5岁）受影响半球代谢和结构异常的变化（在每一年进行3次测量中）。目标2。识别与认知障碍发展相关的代谢和结构脑异常模式。目标3。识别与高癫痫发作频率相关的代谢和结构脑异常模式。目标4。目的：确定脑皮层切除术是否能逆转SWS患者的认知能力下降。

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.