High frequency activity in infants with epilepsy

描述（由申请人提供）：这个探索性项目将测试一个假设，即我们最近在癫痫婴儿间歇尖峰期间观察到的高频信号（HFS）是癫痫发生的生物标志物。基于他们对人类和动物的研究，加州大学洛杉矶分校的恩格尔和其他人提出，250-500赫兹范围内的高频振荡，即所谓的快速纹波（FR），叠加在间隔尖峰上，是中颞叶癫痫成人癫痫发生的生物标志物。发现癫痫发生的生物标志物是很重要的，因为这将使临床医生能够确定最终能够产生癫痫发作的区域。不幸的是，根据Gotman和他的同事对癫痫患者的颅内数据，这种来自内侧颞叶的FR在头皮上似乎无法用脑磁图（MEG）或脑电图（EEG）检测到。目前尚不清楚FR是否是成人新皮层癫痫发生的生物标志物。在这里，我们重点关注婴儿癫痫，因为这是可以从这种生物标志物中获益最多的人群。由于许多类型的婴儿癫痫起源于新皮层，FR的类似物应该更容易检测到。我们最近开发了一种名为babySQUID的新型脑磁脑图仪器，它被优化用于测量婴儿的皮层活动。因为它的磁场感应线圈比传统MEG系统的线圈更接近头皮（6毫米对20毫米），而且婴儿的头皮和头骨很薄，所以可以测量到更弱的新皮层信号。因此，我们在初步研究中使用babySQUID寻找婴儿FR的类似物，发现在70-120 Hz范围内存在HFS，仅在一些癫痫患者中发现的一些间歇峰中存在，而在类似年龄范围的正常对照的连续记录中未观察到。HFS显示一组感应线圈的极性反转，表明它起源于皮层。我们的具体目的是测试HFS是否与癫痫发作的电图迹象有关，因为这是确定HFS作为可能的生物标志物的第一步。由于电图活动并不总是伴随着婴儿的行为癫痫发作，因此可以使用MEG来测量，而不需要运动伪影。我们将研究小于3岁的婴儿是否存在HFS，如果发现HFS，我们将测试其产生器和癫痫发作器的位置是否一致。我们还预测癫痫发作部位不会与没有HFS的间歇尖峰位置重合。将对年龄匹配的正常对照进行研究，以确定HFS是癫痫的特征。如果成功，这项研究将为预防和治疗婴儿癫痫开辟新的可能性，防止癫痫对大脑的广泛区域造成不可修复的损害，导致普遍的认知能力下降。相关性：鉴定与婴儿间期尖峰相关的癫痫发生生物标志物有可能为确定幼儿癫痫发作部位提供一种无创方法。这可以显著降低与侵入性诊断相关的风险，同时提供信息，以便在大脑最有可能完全恢复的时候更好地指导治疗过程，并可能为孩子带来正常的结果。

DESCRIPTION (provided by applicant): This exploratory project will test a hypothesis that the high-frequency signal (HFS) we have recently observed during interictal spikes in infants with epilepsy is a biomarker of epileptogenesis. Based on their human and animal studies, Engel and others at UCLA have proposed that an HFS in the range of 250-500 Hz, the so- called fast ripple (FR), superimposed on interictal spikes is a biomarker of epileptogenesis in adults with mesial temporal lobe epilepsy. Finding a biomarker of epileptogenesis is important since this would enable a clinician to identify areas eventually capable of producing seizures. Unfortunately, this FR from the mesial temporal lobe does not appear to be detectable over the scalp with magnetoencephalography (MEG) or electroencephalography (EEG) according to the intracranial data of Gotman and his coworkers from epilepsy patients. It is still unknown whether the FR is a biomarker of epileptogenesis in neocortical epilepsy in adults. Here we focus on epilepsy in infants since this is the population that can benefit most from such a biomarker. Since many types of infantile epilepsy is neocortical in origin, an analog of FR should be more easily detectable. We have recently developed a new MEG instrument called babySQUID that is optimized for measuring cortical activity in infants. Because its magnetic field sensing coils are much closer to the scalp than the coils of conventional MEG systems (6 vs 20 mm) and the scalp and skull of infants are thin, much weaker neocortical signals are measurable. Therefore, we have looked for an analog of FR in infants using the babySQUID in our preliminary study and found that there is an HFS in the range of 70-120 Hz, which is present only in some interictal spikes identified in some patients with epilepsy and not observed in continuous recordings from normal controls in a similar age range. This HFS shows polarity reversal over a cluster of sensing coils, indicating that it was cortical in origin. Our specific aim is to test whether this HFS is associated with electrographic signs of seizure since that is the first step in establishing the HFS as a possible biomarker. Since the electrographic activity is not always accompanied by behavioral seizures in infants, it can be measured using MEG without movement artifacts. We will study <3 year old infants for the presence of the HFS and, if found, we will test if the locations of its generator and the seizure generator coincide. We also predict that the seizure site will not coincide with locations of interictal spikes without HFS. Age matched normal controls will be studied to ascertain that the HFS is characteristic of epilepsy. If successful, this research will open new possibilities for the prevention and treatment of epilepsy in infants before epilepsy causes irreparable damage in a wide region of the brain, leading to general cognitive decline.Relevance: Identification of a biomarker for epileptogenesis associated with interictal spikes in infants has the potential to provide a noninvasive method for determining the site of seizure onset in young infants. This could significantly decrease the risk associated with invasive diagnosis, while at the same time providing information to better direct the course of treatment at a time when the brain is most able to fully recover and possibly lead to a normal outcome for the child.