Clustering of spontaneous recurrent seizures separated by long seizure-free periods: An extended video-EEG monitoring study of a pilocarpine mouse model

PLoS One. 2018 Mar 20;13(3):e0194552. doi: 10.1371/journal.pone.0194552. eCollection 2018.

Abstract

Seizure clustering is a common and significant phenomenon in patients with epilepsy. The clustering of spontaneous recurrent seizures (SRSs) in animal models of epilepsy, including mouse pilocarpine models, has been reported. However, most studies have analyzed seizures for a short duration after the induction of status epilepticus (SE). In this study, we investigated the detailed characteristics of seizure clustering in the chronic stage of a mouse pilocarpine-induced epilepsy model for an extended duration by continuous 24/7 video-EEG monitoring. A seizure cluster was defined as the occurrence of one or more seizures per day for at least three consecutive days and at least five seizures during the cluster period. We analyzed the cluster duration, seizure-free period, cluster interval, and numbers of seizures within and outside the seizure clusters. The video-EEG monitoring began 84.5±33.7 days after the induction of SE and continued for 53.7±20.4 days. Every mouse displayed seizure clusters, and 97.0% of the seizures occurred within a cluster period. The seizure clusters were followed by long seizure-free periods of 16.3±6.8 days, showing a cyclic pattern. The SRSs also occurred in a grouped pattern within a day. We demonstrate that almost all seizures occur in clusters with a cyclic pattern in the chronic stage of a mouse pilocarpine-induced epilepsy model. The seizure-free periods between clusters were long. These findings should be considered when performing in vivo studies using this animal model. Furthermore, this model might be appropriate for studying the unrevealed mechanism of ictogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Electroencephalography / methods*
  • Epilepsy / chemically induced
  • Epilepsy / diagnosis*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscarinic Agonists / toxicity
  • Neurophysiological Monitoring / methods*
  • Pilocarpine / toxicity
  • Status Epilepticus / chemically induced
  • Status Epilepticus / diagnosis
  • Time Factors
  • Video Recording / methods*

Substances

  • Muscarinic Agonists
  • Pilocarpine

Grants and funding

This study was by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C25020000 and HI13C1558). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The Advanced Neural Technologies provided support in the form of salaries for Daejong Jeon, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.