EEG-fMRI in Patients with JME

描述（由申请人提供）：该NIH指导的以患者为导向的研究职业发展奖（K23）申请旨在支持Jerzy Szaflarski博士的长期职业目标，即改善耐药性癫痫患者的管理。在美国大约300万癫痫患者中，7-10%的患者被诊断为青少年肌阵挛性癫痫（JME）。JME是一种癫痫综合征，其特征在于遗传易感性，发病年龄在11至19岁之间，失神和全身性癫痫发作，以及大量肌阵挛性抽搐。虽然在约70-80%的JME患者中，通常使用丙戊酸（VPA）或其他抗癫痫药物（AED）控制癫痫发作，但许多患者需要频繁的多次AED试验才能获得癫痫发作自由; 20-30%的患者持续癫痫发作。VPA耐药JME被定义为持续性癫痫发作，尽管有足够的生活方式调整和治疗试验，包括足够剂量的VPA。虽然JME患者对VPA的耐药是常见的，但对VPA耐药和VPA反应性JME患者之间的脑电图差异知之甚少。本研究的中心焦点是检验假设，即在JME患者中，广义棘波和波放电的定位和对称性与药物反应之间存在相关性。我们的目标是采用高场EEC触发的fMRI（EEG-fMRI）来定位两组患者中SWD的发生器，并回答以下问题：VPA耐药JME患者是否有局灶性（例如，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VPA耐药JME患者中AED以外的治疗。本研究的目的是：（目的1）优化用于JME患者的4 T同步EEG和fMRI;（目的2）记录两组JME患者的同步EEG和fMRI数据;（目的3）将EEG的SWD定位与由VPA反应和VPS抵抗的JME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成为癫痫神经影像学领域独立临床研究者所需的技能，并在培训完成时获得独立的研究资金。

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.