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An update on the seizures beget seizures theory

Lookup NU author(s): Dr Yujiang WangORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.Seizures beget seizures is a longstanding theory that proposed that seizure activity can impact the structural and functional properties of the brain circuits in ways that contribute to epilepsy progression and the future occurrence of seizures. Originally proposed by Gowers, this theory continues to be quoted in the pathophysiology of epilepsy. We critically review the existing data and observations on the consequences of recurrent seizures on brain networks and highlight a range of factors that speak for and against the theory. The existing literature demonstrates clearly that ictal activity, especially if recurrent, induces molecular, structural, and functional changes including cell loss, connectivity reorganization, changes in neuronal behavior, and metabolic alterations. These changes have the potential to modify the seizure threshold, contribute to disease progression, and recruit wider areas of the epileptic network into epileptic activity. Repeated seizure activity may, thus, act as a pathological positive-feedback mechanism that increases seizure likelihood. On the other hand, the time course of self-limited epilepsies and the presence of seizure remission in two thirds of epilepsy cases and various chronic epilepsy models oppose the theory. Experimental work showed that seizures could induce neural changes that increase the seizure threshold and decrease the risk of a subsequent seizure. Due to the complex nature of epilepsies, it is wrong to consider only seizures as the key factor responsible for disease progression. Epilepsy worsening can be attributed to the various forms of interictal epileptiform activity or underlying disease mechanisms. Although seizure activity can negatively impact brain structure and function, the “seizures beget seizures” theory should not be used dogmatically but with extreme caution.

Publication metadata

Author(s): Jiruska P, Freestone D, Gnatkovsky V, Wang Y

Publication type: Article

Publication status: Published

Journal: Epilepsia

Year: 2023

Volume: 64

Issue: S3

Pages: S13-S14

Print publication date: 01/12/2023

Online publication date: 19/07/2023

Acceptance date: 17/07/2023

Date deposited: 13/09/2023

ISSN (print): 0013-9580

ISSN (electronic): 1528-1167

Publisher: John Wiley and Sons Inc


DOI: 10.1111/epi.17721

PubMed id: 37466948


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Funder referenceFunder name
Agentura Pro Zdravotnický Výzkum České Republiky
EU - Next Generation EU: LX22NPO5107
Grantová Agentura České Republiky
Ministry of Education, Youth and Sports of the Czech Republic