The Juvenile Myoclonic Epilepsy Connectome Project

青少年肌阵挛癫痫连接组项目

• 批准号: 10228401
• 负责人: Aaron F Struck
• 金额: $ 10.85万
• 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: 2020-07-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10228401
• 关键词: Academic achievement; Accounting; Adolescence; Adolescent; Age; Age of Onset; 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; Methodology; Methods; Myoclonus; Nature; Nerve Degeneration; Neurocognitive; Neurologic; Neuropsychology; Outcome; Participant; Pathogenicity; Patients; Pattern; Pharmaceutical Preparations; Refractory; Resolution; Resources; Rest; Risk; Scientist; Seizures; Selection for Treatments; Severities; Severity of illness; Standardization; Structure; Testing; Thalamic structure; Tonic - clonic seizures; Unemployment; United States; Variant; base; behavior measurement; clinical predictors; comorbidity; connectome; cost; experience; health care service utilization; imaging modality; interest; neurobehavioral; neurodevelopment; novel; novel marker; novel strategies; optimal treatments; outcome prediction; personalized diagnostics; personalized management; predictive marker; predictive modeling; prospective; psychosocial; quantitative imaging; response; socioeconomics; 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.

摘要： 据估计，美国有250万癫痫患者，其中近25万人(约10%)患有青少年 肌阵挛癫痫(JME)。大多数JME患者在神经性癫痫发作时发作。 处于发育脆弱期，有患长期认知和精神合并症的风险 承担大量相关的社会经济和卫生保健利用成本。药物可以产生持久的效果 部分JME患者的癫痫控制和减轻JME进行性神经发育的后果 慢性失控的癫痫发作，但对许多JME患者来说，药物不足以控制癫痫发作。 准确的早期预测哪些患者会对药物有良好的反应是优化的关键 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的产量仍然不足。目前还没有可靠的生物标志物来预测耐药性的可能性， 疾病进展，或JME认知或精神后果的存在、性质和严重程度，均 不同患者之间的差异很大。现在有强大的成像工具可用于定量 表征组成癫痫网络的大脑区域之间的结构和功能联系， 为了解、预测和治疗难治性癫痫提供了一个有希望的新途径。这个 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性 对160名12-20岁儿童和青少年(80名JME，80名健康对照)进行了测量，包括 DTI用于评估结构连接，fMRI用于评估动态网络相互作用，结构MRI用于 评估皮质和皮质下体积丢失的类型。这些方法将密切反映当前使用的方法 由人类连接组项目(HCP)研究健康参与者的网络连接。这些 比较，基于用敏感的、最先进的方法研究的大量队列，将调查完整的 JME中网络结构和功能异常的程度。这些数据将被用来测试几个重要的 假设：1)反复发作导致JME连通性进行性异常，2)这些 连接异常与认知和心理社会功能障碍有关，3)严重的 连通性异常预测认知、心理社会功能和 出现医学上难治性癫痫，4)JME参与者特有的连接异常是 与疾病相关的变量，如癫痫持续时间、发作类型提供了重要的新 生物标志物。支持这些假说的证据将直接导致新的临床诊断工具& 基于连接体定量成像的JME患者个性化管理。