High frequency activity in infants with epilepsy

描述(申请人提供)：这个探索性的项目将测试一个假设，即我们最近观察到的癫痫婴儿发作间歇期的高频信号(HFS)是癫痫发生的生物标记物。在人类和动物研究的基础上，加州大学洛杉矶分校的Engel和其他人提出，在250-500赫兹范围内的HFS，即所谓的快速涟漪(FR)，叠加在发作间期棘波上，是成人内侧颞叶癫痫发生的生物标志物。找到癫痫发生的生物标志物很重要，因为这将使临床医生能够识别最终能够产生癫痫发作的区域。不幸的是，根据Gotman和他的同事来自癫痫患者的颅内数据，通过脑磁图(MEG)或脑电(EEG)似乎无法在头皮上检测到来自内侧颞叶的这种FR。目前尚不清楚FR是否是成人新皮质癫痫发生的生物标志物。在这里，我们将重点放在婴儿癫痫上，因为这是可以从这种生物标记物中受益最大的人群。由于许多类型的婴儿癫痫起源于新皮质，类似的FR应该更容易被检测到。我们最近开发了一种名为BabySQUID的新型脑磁图仪器，该仪器最适合测量婴儿的皮质活动。由于其磁场感应线圈比传统脑磁图系统的线圈更接近头皮(6vs20 Mm)，而且婴儿的头皮和头盖骨很薄，所以可以测量到更弱的新皮质信号。因此，在我们的初步研究中，我们使用BabySQUID在婴儿中寻找了FR的类似物，并发现在70-120 Hz的范围内存在HFS，仅在一些癫痫患者中发现的一些发作间期棘波中存在，在类似年龄范围的正常对照组的连续记录中没有观察到。这张HFS显示了一串感应线圈上的极性反转，表明它起源于大脑皮层。我们的具体目的是测试这种HFS是否与癫痫的电信号迹象有关，因为这是将HFS确定为可能的生物标记物的第一步。由于婴儿的脑电活动并不总是伴随着行为发作，因此可以使用没有运动伪影的脑磁图来测量它。我们将研究&lt；3岁婴儿是否存在HFS，如果发现，我们将测试其生成器和癫痫生成器的位置是否一致。我们还预测，癫痫发作的部位与发作间期棘波的位置不一致。将对年龄匹配的正常对照组进行研究，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，防止癫痫在广泛的大脑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：识别与婴儿发作间期棘波相关的癫痫发生的生物标志物有可能为确定年轻婴儿癫痫发作的位置提供一种非侵入性方法。这可以显著降低与侵入性诊断相关的风险，同时提供信息，在大脑最能够完全恢复的时候更好地指导治疗过程，并可能导致儿童的正常结果。

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.