The Juvenile Myoclonic Epilepsy Connectome Project

青少年肌阵挛癫痫连接组项目

• 批准号: 10550233
• 负责人: Aaron F Struck
• 金额: $ 54.83万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10550233
• 关键词: Academic achievement; Accounting; Adolescence; Adolescent; Age; Age of Onset; Anticonvulsants; Attention deficit hyperactivity disorder; Behavioral; Behavioral Symptoms; Biological Markers; Brain; Brain region; Child; Chronic; Clinical; Clinical Markers; Cognitive; Cohort Studies; Data; Databases; Development; Diagnosis; Disease; Disease Marker; Disease Progression; Drug resistance; Electroencephalography; Epilepsy; Failure; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Generalized Epilepsy; Generalized seizures; Genetic; Human; Image; Imaging Device; Individual; Intractable Epilepsy; Juvenile Myoclonic Epilepsy; Lead; Link; Longevity; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mediating; Medical; Mental disorders; Methodology; Methods; Myoclonus; Nature; Neurocognitive; Neurodegenerative Disorders; Neurologic; Neuropsychology; Outcome; Participant; Pathogenicity; Patients; Pattern; Persons; Pharmaceutical Preparations; Recurrence; Refractory; Resolution; Resources; Rest; Risk; Scientist; Seizures; Selection for Treatments; Severities; Severity of illness; Standardization; Structure; Testing; Tonic - clonic seizures; Unemployment; United States; Variant; autism spectrum disorder; behavior measurement; clinical predictors; comorbidity; connectome; cost; epileptiform; experience; health care service utilization; imaging modality; interest; neurobehavioral; neurodevelopment; novel; novel marker; novel strategies; optimal treatments; outcome prediction; personalized management; predictive marker; predictive modeling; prognostication; prospective; psychiatric comorbidity; psychosocial; quantitative imaging; response; risk prediction; socioeconomics; structural imaging; tool; treatment response

Abstract: Of an estimated 2.5 million people with epilepsy in the United States, close to 250,000 (~10%) have Juvenile Myoclonic Epilepsy (JME). The majority of patients with JME experience seizure onset during a neuro- developmentally vulnerable period and are at risk for long term cognitive and psychiatric comorbidities which carry significant associated socioeconomic and health-care utilization costs. Medications can yield lasting seizure control in some JME patients and mitigate the progressive neurodevelopmental consequences of chronically uncontrolled seizures, but for many JME patients medications do not adequately control seizures. Accurate early prediction of which patients will respond favorably to medications is crucial for optimizing selection of treatment options, but current methods for predicting the clinical course and response to treatment of JME remain inadequate. There exist no reliable biomarkers that predict the likelihood of drug resistance, disease progression, or the presence, nature and severity of cognitive or psychiatric consequences of JME, all of which vary widely between patients. Powerful imaging tools are now available for quantitatively characterizing structural and functional connections between brain regions that make up epileptic networks, providing a promising new approach for understanding, predicting, and treating refractory epilepsy. The Juvenile Myoclonic Epilepsy Connectome Project (JMECP) will collect detailed structural and connectivity measurements in 160 children and adolescents of age range 12-20 yrs (80 JME, 80 healthy controls) including DTI to evaluate structural connections and fMRI to evaluate dynamic network interactions and structural MRI to evaluate patterns of cortical and subcortical volume loss. The methods will closely mirror those currently used by the Human Connectome Project (HCP) to study network connectivity in healthy participants. These comparisons, based on large cohorts studied with sensitive, state-of-the-art methods, will investigate the full extent of abnormal network structure and function in JME. The data will be used to test several important hypotheses: 1) that recurring seizures lead to progressive connectivity abnormalities in JME, 2) that these connectivity abnormalities are linked to the cognitive and psychosocial dysfunction, 3) that severity of connectivity abnormalities predicts the risk of prospective decline in cognitive, psychosocial function, and in developing medically refractory seizures, 4) that connectivity abnormalities unique to participants with JME are associated with disease-related variables such as epilepsy duration, seizure type providing important novel biomarkers. Evidence supporting these hypotheses will lead directly to novel clinical tools for diagnosis & personalized management of JME patients based on quantitative imaging of connectome.

抽象的： 在美国估计有250万人患有癫痫病的人中，近25万（约10％）有少年 Myoclonic癫痫（JME）。大多数JME患者在神经期间经历癫痫发作 发育脆弱的时期，有长期认知和精神病合并症的风险 承担大量相关的社会经济和医疗保健利用成本。药物可以持久 一些JME患者的癫痫发作控制，并减轻进行性神经发育后果 长期无法控制的癫痫发作，但对于许多JME患者而言，药物不能充分控制癫痫发作。 准确的早期预测患者对药物的反应良好对于优化至关重要 选择治疗方案，但是当前用于预测临床过程和对治疗反应的方法 JME的遗物仍然不足。没有可靠的生物标志物可以预测耐药性的可能性， 疾病的进展，或JME认知或精神病后果的存在，性质和严重性 其中的患者之间的差异很大。功能强大的成像工具现在可用于定量 表征组成癫痫网络的大脑区域之间的结构和功能连接， 提供了一种有希望的新方法，用于理解，预测和治疗难治性癫痫。这 青少年肌阵挛性癫痫连接素蛋白项目（JMECP）将收集详细的结构和连接性 年龄范围12-20年的160名儿童和青少年的测量（80 JME，80个健康对照）包括 DTI评估结构连接和fMRI，以评估动态网络相互作用和结构MRI 评估皮质和皮质下体积损失的模式。这些方法将密切反映当前使用的方法 由人类Connectome项目（HCP）研究健康参与者的网络连通性。这些 比较基于使用敏感的，最先进的方法研究的大型队列，将研究完整 JME中的网络结构和功能异常的程度。数据将用于测试一些重要的 假设：1）反复出现的癫痫发作导致JME的进行性连通性异常，2） 连通性异常与认知和社会心理功能障碍有关，3） 连通性异常可以预测认知能力，社会心理功能的预期下降的风险 开发医学难治性癫痫发作，4）JME参与者独有的连通性异常是 与疾病相关的变量（例如癫痫持续时间）相关，癫痫发作类型可提供重要的新颖性 生物标志物。支持这些假设的证据将直接导致诊断的新型临床工具 基于Connectome的定量成像对JME患者的个性化管理。