MRI Connectivity Biomarkers of Treatment Response in Focal Epilepsy

项目摘要 癫痫由于癫痫发作负担以及相关的抑郁和焦虑而对生活质量产生负面影响， 此外，发病率和死亡率也有所增加。颞叶癫痫（TLE）是最常见的形式之一， 局灶性癫痫抗癫痫药物成功治疗了约60-70%的此类患者。在 剩余的病人，通常经过长期的，不成功的药物试验，手术干预的假定癫痫发作 集中导致50-80%的患者无癫痫发作。因此，更准确的早期预测 需要药物和手术治疗结果来改善这些疾病的临床管理 患者这项工作的科学前提是，虽然癫痫发作病灶的识别起着重要作用， 在指导局灶性癫痫患者的管理中发挥重要作用，治疗结果（药理学 和外科手术）受到跨大型广泛网络的连接性的显著影响。 本项目的目标是利用MRI开发药物反应性和手术结果的早期生物标志物 功能和结构连接性量化。在药物难治性近中TLE的同质组中， 根据目前的临床评估，癫痫发作病灶被假定为海马的患者， 癫痫发作传播中静息态功能与结构网络完整性关系 使用MRI非侵入性地量化网络。这些网络改变与疾病有关， 手术前后的认知特征。这使得初步的核磁共振成像技术得以发展 近中颞叶癫痫患者术后癫痫发作结局的连接性生物标志物在此基础上， 该提案的具体目标将导致功能和结构连接性生物标志物的改进 近中TLE的手术结局（目标1），以及开发用于其他TLE的类似生物标志物 癫痫发作起源于内侧颞叶结构外的颞叶的患者（目的2）。的 目标3的成功将提供一种方法，以便及早识别那些对抗- 癫痫药物，以减少长期的药物试验。这项工作的总体成果将直接涉及 2014年NINDS癫痫研究基准第三部分B：确定用于评估或 预测治疗反应，包括可以识别可能患有 好的结果或产生不良反应。因此，这项研究有可能导致显着 改善了对常见衰弱性疾病的临床管理。

PROJECT SUMMARY Epilepsy negatively impacts quality of life due to the seizure burden and associated depression and anxiety, in addition to increased morbidity and mortality. Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Anti-epileptic medication is successful in treating about 60-70% of these patients. In the remaining patients, usually after long, unsuccessful drug trials, surgical intervention of the presumed seizure focus leads to seizure freedom in 50-80% of patients. Therefore, more accurate early predictors of pharmacological and surgical treatment outcome are needed to improve clinical management of these patients. The scientific premise of this work is that while the identification of the seizure focus plays an important role in directing management of focal epilepsy patients, the outcome of treatment (pharmacological and surgical) is significantly influenced by the connectivity across large widespread network(s).Therefore, the goal of this project is to develop early biomarkers of drug responsiveness and surgical outcome using MRI functional and structural connectivity quantification. In a homogeneous group of drug refractory mesial TLE patients whose seizure focus was presumed to be the hippocampus based on current clinical assessments, the relationship between resting-state functional and structural network integrity in seizure propagation networks were quantified non-invasively using MRI. These network alterations were related to disease and cognitive characteristics before and after surgery. This allowed the development of a preliminary MRI connectivity biomarker for post-surgical seizure outcome in mesial TLE. Building on this foundation, the specific aims of this proposal will result in the improvement of functional and structural connectivity biomarkers of surgical outcome in mesial TLE (Aim 1), and the development of similar biomarkers for use in other TLE patients with seizures originating in the temporal lobe outside the mesial temporal structures (Aim 2). The success of Aim 3 will provide a method for early identification of those who will and will not respond to anti- epileptic medication to reduce prolonged drug trials. The overall outcome of this work will directly address the 2014 NINDS Benchmarks for Epilepsy Research section III part B: to identify biomarkers for assessing or predicting treatment response, including markers that may identify specific populations that are likely to have good outcomes or develop adverse responses. As such, this study has the potential to result in significantly improved clinical management of a common debilitating disorder.