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: 10634545
• 负责人: Victoria L Morgan
• 金额: $ 46.9万
• 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/10634545
• 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; Hippocampus; Human; Individual; Ipsilateral; Knowledge; 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; biomarker development; biomarker identification; cohort; health related quality of life; human model; imaging biomarker; improved; 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.

项目摘要 癫痫发作负担降低了健康相关的生活质量，并与发病率和死亡率增加有关。 mortality.颞叶癫痫（TLE）是癫痫最常见的形式之一。大约60-70% 这些患者，抗癫痫药物是一个成功的治疗。在TLE患者的金标准亚组中， 临床评估确定海马为癫痫发作病灶（近中TLE或mTLE）， 切除该区域对于那些药物难治性的患者是一种潜在的治疗。然而，即使在这些 具有明确癫痫病灶的看似同质的患者，手术无癫痫发生率范围 约58%至80%的患者。我们最近的研究表明，虽然癫痫发作的重点可能是 在这组患者中，癫痫发作传播的网络可能是可变的。使用磁 核磁共振成像（MRI）是一种术前功能和结构模型网络，其特征在于， 手术后一年癫痫发作消失的患者。随后的患者网络与此不同 模型的结果不成功，在治疗后的第一年内癫痫发作没有改善或恶化。 手术在术前传播网络与手术后改善的患者中， 在该模型中，一些特定连接的变化与癫痫复发的时间长度相关 (up 3年）。这表明类似的网络是这些患者晚期癫痫复发的原因。 此外，通过识别具有相似网络特性的mTLE患者的独特队列， 癫痫发作可能复发，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，本项目的总体目标是量化术前和术后 MRI网络连接及其与内侧颞叶手术后癫痫复发的关系。在 目的1：将先前定义的mTLE术前MRI功能和结构连接模型 进一步开发和验证作为长期癫痫发作结果的生物标志物。虽然生物标志物将包括 只有手术前的连通性措施，发展将通过网络如何的知识， 如目标2和3所确定的，在手术后发生变化。在Aim 2中，纵向术后MRI将用于 量化手术后三年的功能和结构网络演变， 导致术后癫痫发作最后，正电子发射断层扫描（PET）将用于定位 通过癫痫发作复发后的低代谢来比较癫痫发作焦点，并告知网络 在目标2中确定。这项工作将最终导致量化的网络演变在扣押 复发和mTLE中长期癫痫发作结果的生物标志物。