Department of Physiology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Developmental Epileptology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic; Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic.
Department of Developmental Epileptology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic; Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic.
Neurobiol Dis. 2021 Jul;154:105347. doi: 10.1016/j.nbd.2021.105347. Epub 2021 Mar 24.
The seemingly random and unpredictable nature of seizures is a major debilitating factor for people with epilepsy. An increasing body of evidence demonstrates that the epileptic brain exhibits long-term fluctuations in seizure susceptibility, and seizure emergence seems to be a consequence of processes operating over multiple temporal scales. A deeper insight into the mechanisms responsible for long-term seizure fluctuations may provide important information for understanding the complex nature of seizure genesis. In this study, we explored the long-term dynamics of seizures in the tetanus toxin model of temporal lobe epilepsy. The results demonstrate the existence of long-term fluctuations in seizure probability, where seizures form clusters in time and are then followed by seizure-free periods. Within each cluster, seizure distribution is non-Poissonian, as demonstrated by the progressively increasing inter-seizure interval (ISI), which marks the approaching cluster termination. The lengthening of ISIs is paralleled by: increasing behavioral seizure severity, the occurrence of convulsive seizures, recruitment of extra-hippocampal structures and the spread of electrographic epileptiform activity outside of the limbic system. The results suggest that repeated non-convulsive seizures obey the 'seizures-beget-seizures' principle, leading to the occurrence of convulsive seizures, which decrease the probability of a subsequent seizure and, thus, increase the following ISI. The cumulative effect of repeated convulsive seizures leads to cluster termination, followed by a long inter-cluster period. We propose that seizures themselves are an endogenous factor that contributes to long-term fluctuations in seizure susceptibility and their mutual interaction determines the future evolution of disease activity.
癫痫患者大脑长期存在发作易感性的波动，而发作的出现似乎是多个时间尺度上运行的过程的结果，这一证据越来越多。深入了解导致长期发作波动的机制可能为理解发作起源的复杂性质提供重要信息。在这项研究中，我们在颞叶癫痫的破伤风毒素模型中探索了发作的长期动力学。结果表明，发作的概率存在长期波动，发作在时间上形成簇，然后是无发作期。在每个簇内，发作分布是非泊松分布，这表现为逐渐增加的发作间隔（ISI），这标志着簇的接近结束。ISI 的延长与以下情况平行：行为性发作严重程度增加、出现全身强直-阵挛性发作、海马外结构的募集以及电描记癫痫样活动在边缘系统外的扩散。结果表明，反复非惊厥性发作遵循“发作引起发作”的原则，导致全身强直-阵挛性发作的发生，从而降低了随后发作的概率，从而增加了随后的 ISI。反复全身强直-阵挛性发作的累积效应导致簇的终止，随后是长的簇间间期。我们提出，发作本身是一个内源性因素，导致发作易感性的长期波动，它们的相互作用决定了疾病活动未来的演变。
