Treatment effects in epilepsy: a mathematical framework for understanding response over time

Front Netw Physiol. 2024 Jun 26:4:1308501. doi: 10.3389/fnetp.2024.1308501. eCollection 2024.

Abstract

Epilepsy is a neurological disorder characterized by recurrent seizures, affecting over 65 million people worldwide. Treatment typically commences with the use of anti-seizure medications, including both mono- and poly-therapy. Should these fail, more invasive therapies such as surgery, electrical stimulation and focal drug delivery are often considered in an attempt to render the person seizure free. Although a significant portion ultimately benefit from these treatment options, treatment responses often fluctuate over time. The physiological mechanisms underlying these temporal variations are poorly understood, making prognosis a significant challenge when treating epilepsy. Here we use a dynamic network model of seizure transition to understand how seizure propensity may vary over time as a consequence of changes in excitability. Through computer simulations, we explore the relationship between the impact of treatment on dynamic network properties and their vulnerability over time that permit a return to states of high seizure propensity. For small networks we show vulnerability can be fully characterised by the size of the first transitive component (FTC). For larger networks, we find measures of network efficiency, incoherence and heterogeneity (degree variance) correlate with robustness of networks to increasing excitability. These results provide a set of potential prognostic markers for therapeutic interventions in epilepsy. Such markers could be used to support the development of personalized treatment strategies, ultimately contributing to understanding of long-term seizure freedom.

Keywords: anti-seizure medication; brain network ictogenicity; brain network model; brain surgery; epilepsy; honeymoon effect; network physiology.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. JT acknowledges the support of the EPSRC via grants EP/T0277031/1, EP/W035030/1. WW acknowledges the support of Epilepsy Research United Kingdom via grant F2002. LJ acknowledges the support of the Waterloo Foundation via grant no. 1970/3346. All authors gratefully acknowledge the support of the University of Birmingham Dynamic Investment Fund.