Quantitative multimodal analyses in pediatric epilepsy surgery

描述（由申请人提供）：本研究的长期目标包括在颅内EEG和神经影像学数据定量分析的帮助下，建立儿童新皮质癫痫手术的更通用标准，以及使用体内定量多模态分析了解儿童新皮质癫痫EEG上观察到的发作性癫痫放电机制。这项建议的培训方面侧重于作为一名研究人员逐步走向独立。教育计划包括颅内EEG和神经成像定量分析的监督研究，以及应用生物统计学，数据管理和研究道德行为的正式培训和经验。五分之一的儿童癫痫是医学上难以治愈的。一个子集的儿童顽固性新皮质癫痫受益于各自的手术的假定致痫区。然而，据报道，在患有颞叶外癫痫的儿童中，通过相应的脑部手术获得长期无复发结局的机会低至50%。在我们研究所，正电子发射断层扫描（PET）成像上对异常的客观描绘最近取得了更好的手术结果（约80%无瘤），但即使这样也不是最佳的。申请人假设癫痫脑具有致癫痫性的空间梯度，并且一些失败的手术可能是由于致癫痫皮质切除不完全，这被成像研究和最佳EEG分析遗漏。致痫性梯度的概念得到以下观察结果的支持：1）一些患者在切除假定的致痫区后数年出现癫痫复发，包括神经影像学异常; 2）在明显成功的癫痫手术后停用抗癫痫药物会导致三分之一的患者癫痫复发。由于EEG参数在颅内电极之间保持连续值，我们将确定手术结果是否与手术未考虑的皮质神经生理异常程度相关，并建立导致新皮质癫痫（包括癫痫痉挛）儿童最佳手术结果的截止阈值。癫痫发作在脑电图上表现为持续的节律性发作放电，其潜在机制尚不清楚。由于发作性放电通常显示同步和传播到其他脑区，在体外分析的孤立的人脑组织可能不能代表整个癫痫电路。与此相反，在体内定量分析发作性脑电图变化的儿童与新皮质部分性癫痫发作，使用颅内脑电图和功能性神经影像学数据将提供一个不同的角度来看，发作性放电的机制和临床意义的脑电图。最终，这些知识可能会导致更好的外科手术和药物治疗癫痫病。如果获得资助，申请人将在良好的环境中获得必要的培训，以发展成为独立的调查员。

DESCRIPTION (provided by applicant): The long-range objectives of this research include establishment of more universal criteria for neocortical epilepsy surgery in children, with the assistance of quantitative analysis of intracranial EEG and neuroimaging data, as well as understanding of the mechanisms of ictal epileptic discharges seen on EEG in pediatric neocortical epilepsy using in vivo quantitative multimodality analyses. The training aspects of this proposal focus on progression to independence as a researcher. The educational plan include supervised research in quantitative analyses of intracranial EEG and neuroimaging as well as formal training and experience in applied biostatistics, data management, and the ethical conduct of research. One-fifth of epilepsy in children is medically intractable. A subset of children with intractable neocortical epilepsy have benefited from respective surgery of the presumed epileptogenic zone. Yet, the chance of long-term seizure-free outcome by respective brain surgery is reported as low as 50% in children with extra temporal lobe epilepsy. Objective delineation of abnormalities on positron emission tomography (PET) imaging has recently yielded better surgical outcomes (-80% seizure-free) in our institute, but even this is not optimum. The applicant hypothesizes that an epileptic brain has a spatial gradient of epileptogenicity and that some of the failed surgery may have been due to the incomplete resection of epileptogenic cortex, which is missed by imaging studies and optimal EEG analysis. The concept of a gradient of epileptogenicity is supported by observations that 1) some patients experience seizure recurrence several years after resection of the presumed epileptogenic zone, including neuroimaging abnormalities and 2) discontinuation of antiepileptic drugs after apparently successful epilepsy surgery induce seizure recurrence in one-third of patients. Since EEG parameters retain continuous values among intracranial electrodes, we will determine whether surgical outcome is correlated with the degree of neurophysiological abnormalities in the cortex not respected by surgery, and establish the cutoff threshold resulting in the best surgical outcome in children with neocortical epilepsy (including epileptic spasms). Epileptic seizures are represented as sustained rhythmic ictal discharges on EEG, of which underlying mechanisms are unknown. Since ictal discharges typically show synchronization and propagation to other brain regions, in vitro analysis of isolated human brain tissues may not be representative of the entire epileptic circuitry. In contrast, in vivo quantitative analyses of ictal electrographic changes in children with neocortical partial seizures, using intracranial EEG and functional neuroimaging data will provide a different perspective regarding the mechanism and clinical significance of ictal discharges on the EEG. Ultimately, such knowledge may lead to better surgical and pharmaco-therapies for seizure disorders. If funded, the applicant will achieve the necessary training in an excellent environment to develop into an independent investigator.