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： 据估计，美国有 250 万癫痫患者，其中近 25 万（约 10%）患有青少年癫痫症 肌阵挛性癫痫（JME）。大多数 JME 患者在神经系统疾病期间都会经历癫痫发作。 发育脆弱期，有长期认知和精神合并症的风险 承担巨大的相关社会经济和医疗保健利用成本。药物可以产生持久的效果 控制一些 JME 患者的癫痫发作并减轻进行性神经发育后果 慢性癫痫发作不受控制，但对于许多 JME 患者来说，药物并不能充分控制癫痫发作。 准确的早期预测哪些患者会对药物产生良好反应对于优化至关重要 治疗方案的选择，但目前预测临床病程和治疗反应的方法 JME 仍然不足。不存在可靠的生物标志物来预测耐药性的可能性， 疾病进展，或 JME 的认知或精神后果的存在、性质和严重程度，所有 其中患者之间差异很大。强大的成像工具现在可用于定量 表征构成癫痫网络的大脑区域之间的结构和功能连接， 为理解、预测和治疗难治性癫痫提供了一种有前途的新方法。这 青少年肌阵挛癫痫连接组项目 (JMECP) 将收集详细的结构和连接 对 160 名 12-20 岁儿童和青少年（80 名 JME，80 名健康对照）进行测量，包括 DTI 评估结构连接，fMRI 评估动态网络交互，结构 MRI 评估 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 由人类连接组计划 (HCP) 负责研究健康参与者的网络连接。这些 基于使用敏感的、最先进的方法研究的大型队列的比较，将调查全面的 JME 中网络结构和功能异常的程度。该数据将用于测试几个重要的 假设：1）反复发作导致 JME 进行性连接异常，2）这些 连接异常与认知和心理社会功能障碍有关，3） 连接异常预示着认知、心理社会功能和精神障碍的预期下降的风险 发展为医学难治性癫痫发作，4) JME 参与者特有的连接异常是 与疾病相关变量（例如癫痫持续时间、癫痫发作类型）相关，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用于诊断和治疗的新型临床工具的出现。 基于连接组定量成像的 JME 患者个性化管理