Abstract
Epilepsy is a complex disease mainly defined by the susceptibility to spontaneous recurrent seizures but is also often associated with complex comorbid conditions. Despite the introduction of dozens of new antiseizure medications (ASMs), pharmacoresistance, which affects up to 30% of patients with epilepsy (PWE), remains a significant challenge for PWE and epileptologists. To better discuss the numerous proposed hypotheses of pharmacoresistance and the association of their underlying mechanisms, we have categorized them into bottom-up, drug-level, and top-down hypotheses. These categories aim to reflect the brain’s hierarchical “network within networks” organization, a concept that guided our discussion on how a complex systems approach, based on systems biology and systems pharmacology, may help solve the complex problem posed by pharmacoresistant epilepsy. Finally, we strongly propose the need for multi-institutional, transnational collaborative efforts that imply urgent paradigm shifts, the sharing of scientific and technological advances, and the construction and use of open algorithms and data repositories/platforms.
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Acknowledgments
This study was supported by the São Paulo Research Foundation (FAPESP-Brazil) grant: 19/05957-8 (NGC); Agencia Nacional de Promoción Científica y Tecnológica (PICT-Argentina) 2019-1075 [AT]). Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brazil – Finance Code 001 (GSM, NGC); National Council for Scientific and Technological Development (CNPq-Brazil), grant: 305883/2014-3; National Institutes for Science and Technology (INCT-Brazil) – “Translational Medicine,” grant: 14/50891-1 (FAPESP-Brazil) and 465458/2014-9 (CNPq-Brazil); NGC holds a CNPq 1A Research Fellowship (#309397/2018-9).
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Servilha-Menezes, G., Talevi, A., Garcia-Cairasco, N. (2023). On Complexity and Emergence: Linking the Hypotheses of Pharmacoresistance in Epilepsy. In: Rocha, L.L., Lazarowski, A., Cavalheiro, E.A. (eds) Pharmacoresistance in Epilepsy. Springer, Cham. https://doi.org/10.1007/978-3-031-36526-3_4
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