EEG-fMRI in Patients with JME

描述(由申请者提供)：NIH指导的以患者为导向的研究职业发展奖(K23)的申请是为了支持Jerzy Szaflarski博士改善对药物抵抗型癫痫患者的管理的长期职业目标。在美国约300万癫痫患者中，7%-10%的患者被诊断为青少年肌阵挛癫痫(JME)。JME是一种癫痫综合征，以遗传易感性为特征，发病年龄在11岁至19岁之间，失神和全身性癫痫发作，以及大量肌阵挛发作。虽然在约70-80%的JME患者中，癫痫发作通常是用丙戊酸(VPA)或其他抗癫痫药物(AED)控制的，但许多患者需要频繁的多次AED试验才能获得发作自由；20%-30%的患者有持续性癫痫发作。抗VPA的JME被定义为尽管进行了足够的生活方式调整和治疗试验，包括足够剂量的VPA，但仍有持续性癫痫发作。虽然对VPA的抵抗在JME患者中是常见的，但对VPA抵抗和VPA反应的JME患者之间的脑电差异知之甚少。这项研究的中心焦点是检验广泛性棘波放电的局部性和对称性与JME患者的药物反应之间存在相关性的假设。我们的目标是使用高场EEC触发的功能磁共振成像(EEG-fMRI)来定位两组患者中产生SWD的原因，并回答以下问题：VPA抵抗型JME患者是否有局灶性(如皮质)癫痫发作？如果预期的相关性得到证实，我们将能够设计进一步的研究，评估对VPA耐药的JME患者使用AEDs以外的治疗方法。本研究的目标是：(1)优化4T同步EEG和fMRI用于JME患者；(2)记录两组JME患者的同步EEG和fMRI数据；(3)将JME患者的EEG定位与根据VPA敏感和VPS抵抗患者的fMRI数据构建的激活图所指示的SWD定位相关联。Szaflarski博士的平行培训目标是培养必要的技能，以便在培训结束前获得独立研究资金，成为癫痫神经成像领域的独立临床调查员。

DESCRIPTION (provided by applicant): This NIH Mentored Patient-Oriented Research Career Development Award (K23) application is to support Dr. Jerzy Szaflarski's long-term career objective of improving the management of patients with medication resistant epilepsies. Among approximately 3 million patients with epilepsy in the U.S., 7-10% carry the diagnosis of juvenile myoclonic epilepsy (JME). JME is an epilepsy syndrome characterized by genetic predisposition, onset between the ages of 11 and 19, absence and generalized seizures, and massive myoclonic jerks. Although seizures are typically controlled with valproic acid (VPA) or other antiepileptic drugs (AED) in about 70-80% of patients with JME, many require frequent multiple AED trials to attain seizure freedom; 20-30% have persistent seizures. VPA-resistant JME is defined as persistent seizures despite adequate lifestyle adjustments and treatment trials including sufficient doses of VPA. Although resistance to VPA in patients with JME is a common occurrence, very little is known about the electroencephalographic differences between patients with VPA-resistant and VPA-responsive JME. The central focus of this study is to test the hypothesis that there is a correlation between localization and symmetry of the generalized spike and wave discharges and drug response in patients with JME. We aim to employ high-field EEC-triggered fMRI (EEG-fMRI) to localize the generators of SWD in both groups of patients and to answer the following question: Do patients with VPA-resistant JME have focal (e.g., cortical) seizure onset? If the expected correlations are confirmed, we will be able to design further studies evaluating treatments other than AEDs in patients with VPA-resistant JME. The objectives of this study are to: (Aim 1) Optimize simultaneous EEG and fMRI at 4T for use in patients with JME; (Aim 2) Record simultaneous EEG and fMRI data in two groups of JME patients; (Aim 3) Correlate SWD localization by EEG with that indicated by the activation maps constructed from the fMRI data in VPA-responsive and VPS-resistant patients with JME. The parallel training objective for Dr. Szaflarski is to develop skills necessary to become an independent clinical investigator in the area of neuroimaging in epilepsy, with independent research funding by the time the training is completed.