PREDICTING SEIZURE RECURRENCE USING BASELINE FUNCTIONAL NETWORK CHANGES IN EARLY

利用早期基线功能网络变化预测癫痫发作复发

• 批准号: 8767519
• 负责人: Luigi Maccotta
• 金额: $ 18.13万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8767519
• 关键词: Adult; Affect; Age; Antiepileptic Agents; Attention; Biological Neural Networks; Blood; Brain; Brain imaging; Brain region; Clinical; Data; Development; Disease; Disease Progression; Disease remission; Early Intervention; Environment; Epilepsy; Freedom; Future; Goals; Imaging Techniques; Individual; Intervention; Knowledge; Life; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Medical; Methods; Morbidity - disease rate; Motor; Onset of illness; Operative Surgical Procedures; Pathologic Processes; Patients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Process; Property; Recurrence; Relapse; Research; Research Design; Research Project Grants; Resistance; Rest; Risk; Risk Factors; Seizures; Series; Severity of illness; Source; Staging; System; Techniques; Therapeutic; Time; Training; Translating; Universities; Washington; aggressive therapy; base; clinical practice; cohort; cost; indexing; mortality; neuroimaging; pre-clinical; programs; prospective; public health relevance; response; somatosensory; statistics

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.

描述（由申请人提供）：癫痫复发和难治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）治疗通常有一个缓解和复发的过程，许多患者不能实现癫痫发作的自由。除了特定的危险因素外，是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早在疾病临床发作之前就开始了，这使得早期干预很有吸引力。晚期癫痫患者的大脑功能组织发生了根本性的改变。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（理想的是临床前癫痫）的脑功能重组模式，预测未来疾病的严重程度，并可用于指导医生早期干预和更积极的治疗。中心假设是癫痫大脑的功能重组接近临床发病