The Juvenile Myoclonic Epilepsy Connectome Project

摘要： 在美国估计的250万癫痫患者中，近25万（约10%）患有青少年癫痫。 肌阵挛性癫痫（JME）。大多数患有JME的患者在神经系统疾病发作期间经历癫痫发作， 发育脆弱期，并有长期认知和精神共病的风险， 带来重大的相关社会经济和保健利用成本。药物可以产生持久的 在一些JME患者中控制癫痫发作，并减轻 慢性不受控制的癫痫发作，但对许多JME患者来说，药物不能充分控制癫痫发作。 准确的早期预测哪些患者将对药物产生有利的反应对于优化治疗方案至关重要。 治疗方案的选择，但目前用于预测临床过程和治疗反应的方法 但JME仍然不够。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认知或精神后果的存在、性质和严重程度，所有 不同的患者之间差异很大。强大的成像工具现在可以定量地 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。的 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 160名年龄范围为12-20岁的儿童和青少年（80名JME，80名健康对照），包括 DTI评估结构连接，fMRI评估动态网络相互作用，结构MRI评估 评估皮质和皮质下容量损失的模式。这些方法将密切反映目前使用的方法 人类连接组计划（HCP）研究健康参与者的网络连接。这些 比较，基于敏感的，最先进的方法研究的大队列，将调查整个 JME网络结构和功能异常的程度。这些数据将用于测试几个重要的 假设：1）反复发作导致JME中进行性连接异常，2）这些 连接异常与认知和心理社会功能障碍有关，3） 连接异常可预测认知、心理社会功能和认知功能的预期下降风险。 发生医学难治性癫痫发作，4）JME参与者特有的连接异常， 与疾病相关的变量，如癫痫持续时间，癫痫发作类型，提供了重要的新的 生物标志物。支持这些假设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患者的个性化管理。

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.