Brain MRI to pre-symptomatically predict seizure onset for Sturge-Weber Syndrome

脑部 MRI 可在症状前预测斯特奇-韦伯综合征的癫痫发作

• 批准号: 10680386
• 负责人: ANNE M COMI
• 金额: $ 20.8万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10680386
• 关键词: 2 year old; 3-Dimensional; Absence Epilepsy; Address; Affect; Age; Algorithms; Area; Artificial Intelligence; Aspirin; Biological Markers; Boston; Brain; Brain Diseases; Brain Injuries; Brain region; Cannabidiol; Caring; Clinical; Clinical Data; Clinical Trials; Conduct Clinical Trials; Consensus; Data; Databases; Diffusion; Dose; Effectiveness; Electroencephalography; Epidiolex; Epilepsy; FDA approved; Goals; Handedness; Heterogeneity; Investigation; Leadership; Lesion; Levetiracetam; Life; Location; Magnetic Resonance Imaging; Modeling; Neurocognition; Neurocognitive; Neurocognitive Deficit; Newborn Infant; Oral; Outcome; Patient Selection; Patients; Pattern; Pediatric Hospitals; Pharmaceutical Preparations; Phase; Port-Wine Stain; Prognosis; Property; Publishing; Rare Diseases; Reaction Time; Reporting; Research Personnel; Risk; Role; Sample Size; School-Age Population; Seizures; Signal Transduction; Sirolimus; Site; Specificity; Stroke; Sturge-Weber Syndrome; Symptoms; Syndrome; Testing; Texture; Thick; Transfer Agreement; Validation; Work; analysis pipeline; artificial intelligence algorithm; base; biomarker development; brain based; brain magnetic resonance imaging; candidate marker; clinical biomarkers; clinical database; data exchange; editorial; experience; feature selection; high risk; improved; injured; large datasets; magnetic resonance imaging biomarker; multi-site trial; multidisciplinary; multimodality; nervous system disorder; neuroimaging marker; outcome prediction; prognostic; sex; symptom treatment; therapeutic candidate; therapy design; treatment arm; treatment effect; treatment strategy; trial planning; tumor; unnecessary treatment

Abstract Sturge-Weber syndrome (SWS) is a rare neurological disease, and its biggest concern is neurocognitive impairments by school age (6-10 years). To improve neurocognitive outcomes, Kenndy Krieger Institute (Dr. Comi, co-PI of this R21) and Boston Children’s Hospital (Dr. Pinto, co-PI of this R21) have been the leading or key sites in various clinical trials, to test new treatment (NCT02332655 (2014-19); NCT0304980 (2017-19); NCT04447846 (2019-21)), or to develop neuroimaging biomarkers that can select at-risk patients (NCT01345305 (2010-2012); NCT01425944 (2010-2020); NCT04717427 (2021-2024)). However, all these trials focus on the post-symptomatic phase – after seizure symptoms have occurred. Our recent evidence suggested that pre-symptomatic treatment – treating patients before seizure symptoms occur, ideally before 2 years of age – may delay or avoid seizure symptoms. This is important, because those without seizure symptoms by 2 years of age (10-25% of SWS patients) often enjoy good neurocognitive outcomes by school age. Motivated by this, multidisciplinary experts gathered and reached a consensus in 2018, 2019, and 2021, calling for immediate investigations of pre-symptomatic treatments. In a timely response to this call, KKI and BCH, the two largest national centers that treat SWS pre-symptomatically, are planning for a trial to comprehensively evaluate the effect of anti-epilepsy drugs Levetiracetam, in two treatment arms (Levetiracetam with versus without low-dose aspirin) for pre-symptomatic treatment. The bottleneck issue for this planned trial, though, is the lack of a biomarker to accurately and pre-symptomatically identify SWS patients who are at risk to develop seizure symptoms by 2 years of age. Those at-risk patients should be ideal candidates to be included in our planned trial. This R21 aims to address this bottleneck biomarker problem. We plan to retrospectively build the largest multi-site presymptomatic database from clinical data in KKI and BCH (Aim 1). We will thoroughly evaluate two clinical and brain MRI biomarkers to identify at-risk patients pre-symptomatically (Aim 2). The central hypothesis is that sophisticated features that artificial intelligence (AI) algorithms extract from clinical and brain MRI could serve as a biomarker to pre-symptomatically identify SWS patients at risk of developing seizure symptoms by 2 years of age. This is the first AI-powered, large-dataset-driven rigorous study for presymptomatic clinical and MRI biomarkers for this rare disease. Such a biomarker will be immediately used in our planned clinical trials to evaluate Levetiracetam with or without low-dose aspirin for pre-symptomatic treatment.

抽象的 Sturge-Weber综合征（SWS）是一种罕见的神经系统疾病，其最大关注的是神经认知 划分为学龄（6-10岁）。为了改善肯尼·克里格研究所（Kenndy Krieger Institute）的神经认知结果（博士 R21的COPI和波士顿儿童医院（Pinto博士，该R21的Co-Pi）一直是领导者或 各种临床试验中的关键站点，用于测试新治疗（NCT02332655（2014-19）； NCT0304980（2017-19）； NCT04447846（2019-21），或开发可以选择高危患者的神经影像标志物 （NCT01345305（2010-2012）; NCT01425944（2010-2020）; NCT04717427（2021-2024））。但是，所有这些试验 关注癫痫发作症状后的症状后阶段。我们最近的证据表明 症状前治疗 - 在癫痫发作症状发生之前治疗患者，理想情况下，在2年之前 年龄 - 可能延迟或避免癫痫发作症状。这很重要，因为那些没有癫痫发作症状的人2 年龄（10-25％的SWS患者）经常在学龄前享有良好的神经认知结果。动机 这位多学科专家在2018年，2019年和2021年达成共识，呼吁立即 对症状前治疗的研究。在对这个电话的及时回应中，KKI和BCH，两个最大的 对对称进行对抗的国家中心正在计划进行试验，以全面评估 在两个治疗臂中抗癫痫药物的左旋药物的作用 阿司匹林）进行症状前治疗。但是，该计划中的瓶颈问题是缺乏 生物标志物可准确和对称地识别有癫痫发作风险的SWS患者 症状在2岁时。那些处于危险的患者应该是我们计划中的理想候选人 审判。此R21旨在解决此瓶颈生物标志物问题。我们计划回顾性建造最大的 来自KKI和BCH中的临床数据的多站点预胞菌数据库（AIM 1）。我们将彻底评估两个 临床和脑MRI生物标志物以对称鉴定高危患者（AIM 2）。中央 假设是人工智能（AI）算法提取的临床和大脑提取的复杂特征 MRI可以用作生物标志物，以对称性地识别有癫痫发作风险的SWS患者 症状在2岁时。这是第一个由AI驱动的大型大型驱动的严格研究 这种罕见疾病的临床和MRI生物标志物。这样的生物标志物将立即在我们的计划中使用 临床试验评估有或没有低剂量阿司匹林的左维氏菌素以进行止痛药的治疗。