PREDICTING SEIZURE RECURRENCE USING BASELINE FUNCTIONAL NETWORK CHANGES IN EARLY

描述（由申请人提供）：癫痫发作复发和顽固性导致癫痫患者显著的发病率和死亡率，以及显著的个人和社会成本。抗癫痫药物（AED）治疗往往遵循缓解和复发的过程，许多患者并没有实现癫痫发作的自由。除了特定的危险因素外，什么增加了患者癫痫复发的风险仍然不完全清楚。至关重要的是，最终导致癫痫的病理过程可能在疾病临床发作之前就开始了，这使得早期干预具有吸引力。晚期癫痫患者的大脑功能组织发生根本性改变。这项研究的长期目标是使用功能性神经成像技术来识别早期癫痫（理想情况下是临床前癫痫）的脑功能重组模式，预测未来疾病的严重程度，并可供医生用于指导早期干预和更积极的治疗。中心假设是癫痫发作时癫痫脑的功能重组， 疾病反映了潜在的癫痫发生过程，包括个体癫痫复发的倾向，而在疾病后期发生的变化反映了疾病进展/癫痫负担。因此，该项目有两个目标。第一个目标是候选人使用前瞻性，纵向研究的成年人，以评估早期癫痫的功能网络的变化，并确定他们是否可以预测癫痫复发或顽固性。第二个目标是利用华盛顿大学的支持性环境，为候选人提供以下方面的培训：1）纵向研究设计和实施方法，2）应用于多维系统的多元统计方法，例如功能连接性研究。我们的目标是支持R 01应用程序的开发，并通过使用先进的神经成像技术从疾病的早期阶段开始前瞻性地研究癫痫的研究计划逐步独立。该项目的研究结果对临床实践具有很大的适用性。具体而言，使用异常功能网络特性在早期阶段预测疾病严重程度的能力可以通过引导临床医生在病程早期寻求更积极的AED治疗，以及通过允许跟踪疾病进展和早期考虑其他治疗选择（包括癫痫手术）来显著降低发病率和死亡率。此外，该提案获得的数据将成为早期癫痫功能网络变化的更大前瞻性纵向研究的基础，目的是将这些知识转化为针对疾病的个性化干预措施， 它会造成不可逆转的伤害。

DESCRIPTION (provided by applicant): Seizure recurrence and intractability cause significant morbidity and mortality in patients with epilepsy, as well as significant individual and societal costs. Antiepileptic drug (AED) therapy often follows a course of remission and relapse, and many patients do not achieve seizure freedom. What increases patient's risk for seizure recurrence remains incompletely understood, except for specific risk factors. Critically, the pathologic process that ultimately leads to epilepsy likely begins well before the clinical onset o the disease, making early intervention attractive. The functional organization of the brain of patients with late stage epilepsy is fundamentally altered. The long-term goal of this research is to use functional neuroimaging techniques to identify patterns of brain function reorganization in early epilepsy (and ideally preclinical epilepsy) that predict future disease severity and can be used by physicians to guide early intervention and more aggressive therapy. The central hypothesis is that the functional reorganization of epileptic brains near the clinical onset of the disease reflects the underlying epileptogenic process, including an individual's propensity for seizure recurrence, while changes that occur in later stages of the disease reflect disease progression/seizure burden. This project has thus two objectives. The first objective is for the candidate to use a prospective, longitudinal study of adults to assess functional network changes in early epilepsy and determine whether they can predict seizure recurrence or intractability. The second objective is to leverage the extremely supportive environment at Washington University to provide the candidate with training in 1) methods of longitudinal study design and conduction and 2) methods of multivariate statistics applied to multidimensional systems, such as those studied with functional connectivity. The goal is to support the development of an R01 application and a progression to independence with a research program that uses advanced neuroimaging techniques to study epilepsy prospectively, beginning in the early stages of the disease. Findings from this project would have great applicability to clinical practice. Specifically the ability to predict disease severity at an early stage using abnormal functional network properties could significantly reduce morbidity and mortality by leading clinicians to pursue more aggressive AED therapy earlier in the course, and by allowing tracking of disease progression and early consideration of other therapeutic options, including epilepsy surgery. Furthermore the data obtained with this proposal will be the basis of a larger prospective longitudinal study in the functional network changes of early epilepsy, with the goal of translating this knowledge into individually tailored interventions targeting the disease before it produces irreversible damage.