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Pediatric Epilepsy Mechanisms: Expanding the Paradigm of Excitation/Inhibition Imbalance

Division of Pediatric Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Children 2019, 6(2), 23; https://doi.org/10.3390/children6020023
Received: 10 January 2019 / Revised: 31 January 2019 / Accepted: 31 January 2019 / Published: 5 February 2019
(This article belongs to the Special Issue Advances in Pediatric Epilepsy)
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Abstract

Mechanisms underlying seizures and epilepsy have traditionally been considered to involve abnormalities of ion channels or synaptic function. Those considerations gave rise to the excitation/inhibition (E/I) imbalance theory, whereby increased excitation, decreased inhibition, or both favor a hyperexcitable state and an increased propensity for seizure generation and epileptogenesis. Several recent findings warrant reconsideration and expansion of the E/I hypothesis: novel genetic mutations have been identified that do not overtly affect E/I balance; neurotransmitters may exert paradoxical effects, especially during development; anti-seizure medications do not necessarily work by decreasing excitation or increasing inhibition; and metabolic factors participate in the regulation of neuronal and network excitability. These novel conceptual and experimental advances mandate expansion of the E/I paradigm, with the expectation that new and exciting therapies will emerge from this broadened understanding of how seizures and epilepsy arise and progress. View Full-Text
Keywords: seizures; epilepsy; excitation; inhibition; synaptic function; genetic mutations; STXBP1; antiseizure drugs; levetiracetam; metabolism; ketogenic diet seizures; epilepsy; excitation; inhibition; synaptic function; genetic mutations; STXBP1; antiseizure drugs; levetiracetam; metabolism; ketogenic diet
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Shao, L.-R.; Habela, C.W.; Stafstrom, C.E. Pediatric Epilepsy Mechanisms: Expanding the Paradigm of Excitation/Inhibition Imbalance. Children 2019, 6, 23.

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