High frequency activity in infants with epilepsy

描述（由申请人提供）：该探索性项目将检验一个假设，即我们最近在癫痫婴儿发作间期观察到的高频信号（HFS）是癫痫发生的生物标志物。基于他们的人类和动物研究，UCLA的Engel和其他人提出，叠加在发作间期棘波上的250-500 Hz范围内的HFS（所谓的快速涟漪（FR））是内侧颞叶癫痫成年人癫痫发生的生物标志物。发现癫痫发生的生物标志物是重要的，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及其同事从癫痫患者获得的颅内数据，脑磁图（MEG）或脑电图（EEG）似乎无法在头皮上检测到来自内侧颞叶的FR。FR是否是成人新皮质癫痫发生的生物标志物仍不清楚。在这里，我们专注于婴儿癫痫，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是新皮质起源，FR的类似物应该更容易检测。我们最近开发了一种名为babySQUID的新型脑磁图仪器，该仪器针对测量婴儿大脑皮层活动进行了优化。由于其磁场感应线圈比传统MEG系统的线圈更接近头皮（6 mm vs 20 mm），并且婴儿的头皮和头骨很薄，因此可以测量到弱得多的新皮层信号。因此，我们在我们的初步研究中使用babySQUID在婴儿中寻找FR的类似物，并发现在70-120 Hz范围内存在HFS，其仅存在于一些癫痫患者中鉴定的一些发作间期尖峰中，并且在类似年龄范围的正常对照的连续记录中未观察到。该HFS显示了一组感应线圈的极性反转，表明其起源于皮质。我们的具体目标是测试这种HFS是否与癫痫发作的电图体征相关，因为这是将HFS确立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，它可以使用MEG测量没有运动伪影。我们将研究<3岁的婴儿是否存在HFS，如果发现，我们将测试其发生器和癫痫发生器的位置是否一致。我们还预测，癫痫发作的网站将不符合发作间期尖峰没有HFS的位置。将研究年龄匹配的正常对照，以确定HFS是癫痫的特征。如果成功的话，这项研究将开辟新的可能性，为预防和治疗癫痫的婴儿癫痫癫痫之前，癫痫造成不可挽回的损害，在广泛的区域的大脑，导致一般的认知declination.Relevance：识别的生物标志物与婴儿癫痫发作间期棘波有可能提供一个非侵入性的方法来确定在年幼的婴儿癫痫发作的网站。这可以显着降低与侵入性诊断相关的风险，同时提供信息，以便在大脑最能够完全恢复并可能导致儿童正常结果的时候更好地指导治疗过程。

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.