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

颞叶癫痫（TLE）是最常见的部分性癫痫，通常具有耐药性。如果患者有全身性强直-阵挛性发作（gtcs），他们的安全和生活质量将受到严重损害。目前还不清楚为什么有些癫痫发作会继发，而另一些则不会。最近的啮齿动物模型研究表明，中颞叶癫痫的发生基于不同的细胞机制，这可以通过特定的脑电图（EEG）癫痫发作和传播模式来反映。颅内脑电图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。这一假设基于两个动物模型的发现：gtcs通常在低压快速（LVF）活动后观察到，而超同步发作（HYP）发作通常保持局灶性。此外，这两种发作模式均伴有不同的高频振荡（HFOs）子带：LVF活动与纹波活动增加（80-200 Hz）相关，而HYP发作与快速纹波（250-500 Hz）同时发生。在人类中，这些相关性尚未得到证实，尽管在TLE患者中有LVF和HYP模式的报道。hfo是一种很有希望的癫痫患者致病网络的生物标志物，越来越多的证据表明hfo也参与了癫痫的形成。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，这种模式在高血压发作癫痫发作的开始中起着关键作用。另一方面，波纹的特征是细胞相互作用产生左心室起搏癫痫发作的相关性。第二个目标是表明，如果在发作区发生快速波纹，则gtcs的风险较低，如果在发作区和传播区增加波纹带活动，则风险较高。如果这是真的，HFO分析也可能有助于TLE患者的治疗决策。

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.