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 斯特奇-韦伯综合征（SWS）是一种罕见的神经系统疾病，其最大的问题是神经认知 为了改善神经认知结果，肯迪·克里格研究所（Kendy Krieger Institute）（Dr. Comi，本 R21 的联合 PI）和波士顿儿童医院（Dr. Pinto，本 R21 的联合 PI）一直是领先或 在各种临床试验的关键地点，测试新的治疗方法（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生物标志物 （NCT01345305（2010-2012）；NCT01425944（2010-2020）；NCT04717427（2021-2024））然而，所有这些试验。 重点关注症状后阶段——我们最近的证据表明出现癫痫症状后。 症状前治疗——在癫痫症状出现之前对患者进行治疗，最好是在癫痫发作 2 年前 年龄 – 可能会延迟或避免癫痫症状 这很重要，因为那些没有癫痫症状的人 2 岁。 10-25% 的 SWS 患者通常在学龄期就享有良好的神经认知结果。 对此，多学科专家在2018年、2019年和2021年聚集并达成共识，呼吁立即采取行动 为了及时响应这一号召，两家最大的公司 KKI 和 BCH 开始了对症状前治疗的调查。 治疗症状前 SWS 的国家中心正在计划进行一项试验，以全面评估 抗癫痫药物左乙拉西坦在两个治疗组中的效果（左乙拉西坦联合与不联合低剂量 然而，这项计划试验的瓶颈问题是缺乏一种治疗方法。 生物标志物可在症状发生前准确识别有癫痫发作风险的 SWS 患者 那些在 2 岁时出现症状的高危患者应该是纳入我们计划的理想人选。 这个 R21 旨在解决这个瓶颈生物标志物问题，我们计划回顾性地建立最大的。 来自 KKI 和 BCH 临床数据的多站点症状前数据库（目标 1）。 临床和脑 MRI 生物标志物可在出现症状前识别高危患者（目标 2）。 假设是人工智能（AI）算法从临床和大脑中提取的复杂特征 MRI 可作为生物标志物，在出现症状前识别有癫痫发作风险的 SWS 患者 这是第一个由人工智能驱动、大数据集驱动的症状前严格研究。 这种罕见疾病的临床和 MRI 生物标志物将立即用于我们的计划中。 评估左乙拉西坦联合或不联合小剂量阿司匹林进行症状前治疗的临床试验。