The Role of Network Connectivity in Post-Surgical Seizure Recurrence in Temporal Lobe Epilepsy

网络连接在颞叶癫痫术后癫痫复发中的作用

• 批准号: 10409633
• 负责人: Victoria L Morgan
• 金额: $ 49.15万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409633
• 关键词: Address; Animal Model; Antiepileptic Agents; Benchmarking; Biological Markers; Brain; Characteristics; Clinical Management; Clinical assessments; Deoxyglucose; Development; Disease; Disease Progression; Epilepsy; Epileptogenesis; Evaluation; Evolution; Excision; Freedom; Functional Magnetic Resonance Imaging; Goals; Gold; Hippocampus (Brain); Human; Individual; Ipsilateral; Knowledge; Lead; Length; Magnetic Resonance Imaging; Measures; Methods; Modeling; Monitor; Morbidity - disease rate; National Institute of Neurological Disorders and Stroke; Neurocognitive; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Population; Positron-Emission Tomography; Prediction of Response to Therapy; Process; Property; Quality of life; Recurrence; Refractory; Reporting; Research; Role; Seizures; Sensitivity and Specificity; Structural Models; Techniques; Temporal Lobe; Temporal Lobe Epilepsy; Time; Treatment outcome; Variant; Work; base; biomarker development; cohort; health related quality of life; human model; imaging biomarker; interest; mortality; network models; outcome prediction; response; success; surgery outcome

PROJECT SUMMARY Epileptic seizure burden decreases health related quality of life, and is associated with increased morbidity and mortality. Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy. For about 60-70% of these patients, anti-epileptic medication is a successful treatment. In a subset of TLE patients gold standard clinical assessments identify the hippocampus as the seizure focus (mesial TLE or mTLE), and surgical resection of this region is a potential treatment for those that are drug refractory. However, even in these seemingly homogeneous patients with a well-defined seizure focus, seizure freedom rates from surgery range from approximately 58% to 80% of patients. Our recent work suggests that while the seizure focus may be the same across this group of patients, the network of seizure propagation may be variable. Using Magnetic Resonance Imaging (MRI) a presurgical functional and structural model network was characterized in those patients that were seizure free one year post surgery. Subsequent patients with networks that differed from this model had unsuccessful outcomes with no improvement or worsening of seizures within the first year after surgery. In patients with improvement from surgery whose presurgical propagation network was consistent with the model, variations in a few specific connections were associated with length of time until seizure recurrence (up to 3 years). This suggests a similar network is responsible for late seizure recurrence in these patients. Furthermore, by identifying this unique cohort of mTLE patients with similar network properties in whom late seizures may recur, we hypothesize that it is possible to quantify networks longitudinally as recurrence develops after surgery. Therefore, the overall goal of this project is to quantify presurgical and post-surgical MRI network connectivity and their relationship to seizure recurrence after mesial temporal lobe surgery. In Aim 1 the previously defined presurgical MRI functional and structural connectivity model of mTLE will be further developed and validated as a biomarker of long term seizure outcome. While the biomarker will include only presurgical connectivity measures, the development will be informed by the knowledge of how networks evolve after surgery as determined in Aims 2 and 3. In Aim 2 longitudinal post-surgical MRIs will be used to quantify functional and structural network evolution for three years after surgery and localize networks responsible for post-surgical seizures. Finally, Positron Emission Tomography (PET) will be used to localize the seizure focus via hypometabolism after seizure recurrence to compare with and to inform the networks identified in Aim 2. This work will ultimately result in the quantification of network evolution in seizure recurrence, and biomarkers of long term seizure outcome in mTLE.

项目总结 癫痫发作负担降低了与健康相关的生活质量，并与发病率和 死亡率。颞叶癫痫(TLE)是最常见的癫痫类型之一。约60%-70%的 对这些患者来说，抗癫痫药物是一种成功的治疗方法。在TLE患者的一个子集中，黄金标准 临床评估确定海马体为癫痫灶(内侧TLE或MTLE)和外科手术 对于那些药物耐药的患者，切除这一区域是一种潜在的治疗方法。然而，即使是在这些 看起来相似的患者有明确的癫痫灶，手术范围内的癫痫自由率 从大约58%到80%的患者。我们最近的研究表明，虽然癫痫发作的焦点可能是 在这组患者中，癫痫的传播网络可能是不同的。使用磁力 磁共振成像(MRI)是一个术前功能和结构模型网络的特征 术后一年无癫痫发作的患者。后续患者的网络与此不同 模型结果不成功，癫痫发作在第一年内没有改善或恶化 做手术。在手术改善的患者中，术前传播网络与 在模型中，少数特定连接的变化与癫痫复发前的时间长短有关 (最多3年)。这表明类似的网络是这些患者迟发性癫痫复发的原因。 此外，通过识别这一独特的MTLE患者队列，这些患者具有相似的网络属性， 癫痫可能会复发，我们假设有可能将网络纵向量化为复发 在手术后发展。因此，这个项目的总体目标是量化手术前和手术后 MRI网络连通性与内侧颞叶手术后癫痫复发的关系。在……里面 目的1先前定义的MTLE的术前MRI功能和结构连接模型将是 进一步开发和验证为长期癫痫发作结果的生物标志物。而生物标记物将包括 只有术前采取连通性措施，才能了解网络的发展情况 根据AIMS 2和AIMS 3中确定的手术后发展。在AIMS 2中，将使用手术后纵向磁共振成像来 量化手术后三年的功能和结构网络演变，并定位网络 对手术后的癫痫负责。最后，正电子发射断层扫描(PET)将被用于定位 癫痫复发后低代谢的癫痫灶与网络的比较和通报 在目标2中确定。这项工作最终将导致癫痫发作中网络进化的量化 MTLE的复发和长期癫痫预后的生物标记物。