title: Dynamics of convulsive seizure termination and postictal generalized EEG suppression.
abstract: It is not fully understood how seizures terminate and why some seizures are followed by a period of complete brain activity suppression, postictal generalized EEG suppression. This is clinically relevant as there is a potential association between postictal generalized EEG suppression, cardiorespiratory arrest and sudden death following a seizure. We combined human encephalographic seizure data with data of a computational model of seizures to elucidate the neuronal network dynamics underlying seizure termination and the postictal generalized EEG suppression state. A multi-unit computational neural mass model of epileptic seizure termination and postictal recovery was developed. The model provided three predictions that were validated in EEG recordings of 48 convulsive seizures from 48 subjects with refractory focal epilepsy (20 females, age range 15-61 years). The duration of ictal and postictal generalized EEG suppression periods in human EEG followed a gamma probability distribution indicative of a deterministic process (shape parameter 2.6 and 1.5, respectively) as predicted by the model. In the model and in humans, the time between two clonic bursts increased exponentially from the start of the clonic phase of the seizure. The terminal interclonic interval, calculated using the projected terminal value of the log-linear fit of the clonic frequency decrease was correlated with the presence and duration of postictal suppression. The projected terminal interclonic interval explained 41% of the variation in postictal generalized EEG suppression duration (P < 0.02). Conversely, postictal generalized EEG suppression duration explained 34% of the variation in the last interclonic interval duration. Our findings suggest that postictal generalized EEG suppression is a separate brain state and that seizure termination is a plastic and autonomous process, reflected in increased duration of interclonic intervals that determine the duration of postictal generalized EEG suppression.
authors.affiliation: Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.|NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Prisca R
authors.initials: PR
authors.lastname: Bauer
authors.affiliation: Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.|NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.|Department of Neurology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Roland D
authors.initials: RD
authors.lastname: Thijs
authors.affiliation: Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lamberts
authors.affiliation: Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.
authors.forename: Demetrios N
authors.initials: DN
authors.lastname: Velis
authors.affiliation: Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Visser
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Else A
authors.initials: EA
authors.lastname: Tolner
authors.affiliation: Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.|NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.|Epilepsy Society, Chalfont St Peter SL9 0RJ, UK.
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.affiliation: Center of Neurosciences, Swammerdam Institute of Life Sciences, University of Amsterdam, P.O. Box 94215 1090 GE, The Netherlands.|Instituto Superior Técnico, University of Lisbon, 1049-001, Lisbon, Portugal.
authors.forename: Fernando H
authors.initials: FH
authors.lastname: Lopes da Silva
authors.affiliation: Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.|Image Sciences Institute, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Stiliyan N
authors.initials: SN
authors.lastname: Kalitzin
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D058256:Brain Waves / Q000502:physiology*; D003198:Computer Simulation; D003645:Death, Sudden; D004569:Electroencephalography; D005260:Female; D006323:Heart Arrest / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D017711:Nonlinear Dynamics; D012640:Seizures / Q000503:physiopathology*; D055815:Young Adult
keywords: SUDEP; clonic slowing; critical slowing down; epilepsy