High-frequency oscillations during hypersynchronous-onset and low-voltage fast-onset temporal lobe seizures: Pathophysiological links and clinical implications

超同步发作和低电压快速发作颞叶癫痫发作期间的高频振荡：病理生理学联系和临床意义

• 批准号: 361763863
• 负责人: Dr. Jan Schönberger
• 金额: --
• 依托单位: Klinik für Neuropädiatrie und Muskelerkrankungen
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/361763863?language=en
• 关键词: frequency; oscillations; during; hypersynchronous; onset

Temporal lobe epilepsy (TLE) is the most frequent partial epilepsy and often drug-resistant. If patients have generalized tonic-clonic seizures (GTCSs), their safety and quality of life is severely impaired. It is largely unclear why some seizures generalize secondarily, while others do not. Recent rodent model studies suggest that mesial temporal lobe seizures arise based on different cellular mechanisms, which are reflected by specific electroencephalography (EEG) seizure-onset and propagation patterns. New approaches to intracranial EEG analysis might be helpful in revealing these mechanisms in TLE patients, and possibly allow to estimate the likelihood of secondary generalization shortly after seizure onset. This hypothesis is based on two animal model findings: GTCSs were often observed after low-voltage fast (LVF) activity, whereas hypersynchronous-onset (HYP) seizures often remained focal. Besides, these two seizure-onset patterns were accompanied by different sub-bands of high-frequency oscillations (HFOs): LVF activity was associated with an increase in ripple activity (80-200 Hz), while HYP seizures co-occurred with fast ripples (250-500 Hz). In human beings these correlations have not yet been demonstrated, although both LVF and HYP pattern have been reported in TLE patients. HFOs are a promising biomarker of pathogenic networks in epilepsy patients, and converging lines of evidence indicate an involvement in ictogenesis as well. The first goal of this project is to demonstrate in TLE patients that fast ripples reflect a distinct pattern of neuronal activity that plays a key role in the initiation of HYP-onset seizures. Ripples, on the other hand, are to be characterized as a correlate of the cellular interactions that generate LVF-onset seizures. The second goal is to show that the risk of GTCSs is low if fast ripples occur in the seizure-onset zone and high if ripple-band activity is increased in onset and propagation areas. If this was true, HFO analysis might also be helpful for therapeutic decision making in TLE patients.

颞叶癫痫(TLE)是最常见的部分性癫痫，且常耐药。如果患者有全身性强直阵挛发作(GTCS)，他们的安全和生活质量会受到严重损害。目前很大程度上还不清楚为什么有些癫痫发作是继发性的，而另一些则不是。最近的啮齿动物模型研究表明，内侧颞叶癫痫的发生基于不同的细胞机制，这反映在特定的脑电(EEG)癫痫发作的开始和传播模式上。颅内脑电分析的新方法可能有助于揭示TLE患者的这些机制，并可能允许估计癫痫发作后不久继发泛化的可能性。这一假说基于两个动物模型的发现：GTCS通常在低电压快速(LVF)活动后观察到，而超同步发作(HYP)发作通常仍是局灶性发作。此外，这两种发作模式伴随着不同的高频振荡(HFO)亚带：LVF活动与波纹活动增加(80-200赫兹)相关，而HYP发作与快速波纹活动(250-500赫兹)共存。在人类中，这些相关性尚未被证实，尽管在TLE患者中已经报道了LVF和HYP模式。HFO是癫痫患者致病网络的一个很有前途的生物标志物，越来越多的证据表明它也参与了细胞分裂的发生。该项目的第一个目标是在TLE患者中证明快速涟漪反映了一种独特的神经元活动模式，这种模式在HYP发作的启动中起着关键作用。另一方面，涟漪将被描述为产生LVF发作的细胞相互作用的相互关系。第二个目标是表明，如果发作起始区出现快速波纹，则GTCSs的风险较低，如果起始区和传播区的波纹带活动增加，则GTCSs的风险较高。如果这是真的，HFO分析也可能有助于TLE患者的治疗决策。

项目成果

Fast ripple analysis in human mesial temporal lobe epilepsy suggests two different seizure-generating mechanisms

• DOI: 10.1016/j.nbd.2019.03.030
• 发表时间: 2019-07-01
• 期刊: NEUROBIOLOGY OF DISEASE
• 影响因子: 6.1
• 作者: Schoenberger, Jan;Frauscher, Birgit;Gotman, Jean
• 通讯作者: Gotman, Jean