Editing Epilepsy (section)

== Mechanism ==
Understanding the mechanism of epilepsy involves two related but distinct questions: how the brain develops a long-term tendency to generate seizures ([[epileptogenesis]]), and how individual seizures begin and spread ([[ictogenesis]]). While these processes are not yet fully understood, research has identified a number of cellular, molecular, and network-level changes that contribute to each.<ref name="Pitkänen2014">{{Cite journal |last=Pitkänen |first=Asla |last2=Engel |first2=Jerome |date=2014 |title=Past and present definitions of epileptogenesis and its biomarkers |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC3996117/ |journal=Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics |volume=11 |issue=2 |pages=231–241 |doi=10.1007/s13311-014-0257-2 |issn=1878-7479 |pmc=3996117 |pmid=24492975}}</ref>

=== Seizures ===
In a healthy brain, neurons communicate through electrical signals that are generally desynchronized. This activity is tightly regulated by a balance between excitatory and inhibitory influences. Intracellular factors that influence neuronal excitability include the type, number, and distribution of [[Ion channel|ion channels]], as well as alterations in [[Receptor (biochemistry)|receptor]] function and [[gene expression]]. Extracellular factors include ionic concentrations in the surrounding environment, [[synaptic plasticity]], and the regulation of neurotransmitter breakdown by [[Neuroglia|glial cells]].<ref>{{cite journal |vauthors=Blumenfeld H |year=2005 |title=Cellular and network mechanisms of spike-wave seizures |journal=Epilepsia |volume=46 |issue=Suppl.9 |pages=21–33 |doi=10.1111/j.1528-1167.2005.00311.x |pmid=16302873 |doi-access=free}}</ref><ref name="Intro2006">{{cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK2510/ |title=An Introduction to Epilepsy |vauthors=Bromfield EB |publisher=American Epilepsy Society |year=2006 |chapter=Basic Mechanisms Underlying Seizures and Epilepsy}}</ref>

During a seizure, this balance breaks down, leading to a sudden and excessive synchronization of neuronal firing. A localized group of neurons may begin firing together in an abnormal and repetitive pattern, overwhelming normal inhibitory controls. This abnormal activity can remain confined to a specific region of the brain or propagate to other areas. The process by which this transition occurs is known as [[ictogenesis]]. It involves a shift in network dynamics, typically beginning with excessive excitatory activity in a susceptible area of cortex — known as a seizure focus — and failure of inhibitory mechanisms to contain it. At the cellular level, ictogenesis is often marked by a [[paroxysmal depolarizing shift]], a characteristic pattern of sustained neuronal depolarization followed by rapid repetitive firing.<ref>{{cite book |url=https://books.google.com/books?id=WjSoQVt-taYC&pg=PA167 |title=Ions in the Brain Normal Function, Seizures, and Stroke. |vauthors=Somjen GG |publisher=Oxford University Press |year=2004 |isbn=978-0-19-803459-9 |location=New York |page=167}}</ref> As excitatory feedback loops engage and inhibition further declines, the seizure may become self-sustaining and spread to other regions of the brain.<ref name="Epi2008p483">{{cite book |url=https://books.google.com/books?id=TwlXrOBkAS8C&pg=PA483 |title=Epilepsy: a comprehensive textbook |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |year=2008 |isbn=978-0-7817-5777-5 |veditors=Engel J, Pedley TA |edition=2nd |location=Philadelphia |page=483}}</ref>

There is evidence that epileptic seizures are usually not a random event. Seizures are often brought on by factors (also known as triggers) such as stress, [[Alcohol use disorder|excessive alcohol use]], flickering light, or a lack of sleep, among others. The term [[seizure threshold]] is used to indicate the amount of [[Stimulus (physiology)|stimulus]] necessary to bring about a seizure; this threshold is lowered in epilepsy.<ref name="quyen2003">{{cite journal |vauthors=Le Van Quyen M, Navarro V, Martinerie J, Baulac M, Varela FJ |year=2003 |title=Toward a neurodynamical understanding of ictogenesis |journal=Epilepsia |volume=44 |issue=Suppl.12 |pages=30–43 |doi=10.1111/j.0013-9580.2003.12007.x |pmid=14641559 |doi-access=free}}</ref> The seizures can be described on different scales, from the cellular level<ref name="pmid35031915">{{cite journal |vauthors=Depannemaecker D, Ivanov A, Lillo D, Spek L, Bernard C, Jirsa V |date=February 2022 |title=A unified physiological framework of transitions between seizures, sustained ictal activity and depolarization block at the single neuron level |journal=Journal of Computational Neuroscience |volume=50 |issue=1 |pages=33–49 |doi=10.1007/s10827-022-00811-1 |pmc=8818009 |pmid=35031915}}</ref> to the whole brain.<ref>{{cite journal |vauthors=Depannemaecker D, Destexhe A, Jirsa V, Bernard C |date=August 2021 |title=Modeling seizures: From single neurons to networks |journal=Seizure |volume=90 |pages=4–8 |doi=10.1016/j.seizure.2021.06.015 |pmid=34219016 |doi-access=free}}</ref>

=== Epilepsy ===
While ictogenesis explains how individual seizures arise, it does not account for why the brain develops a persistent tendency to generate them. This longer-term process is known as [[epileptogenesis]] — the sequence of biological events that transforms a previously non-epileptic brain into one capable of producing spontaneous seizures. It can occur after a wide range of brain insults, including traumatic brain injury, stroke, central nervous system infections, brain tumors, or prolonged seizures (such as [[status epilepticus]]). In most cases, no clear cause is identified. Although not fully understood, it involves a range of biological changes, including neuronal loss, synaptic reorganization, gliosis, neuroinflammation, and disruption of the blood–brain barrier.<ref name="Pitkänen2014" /><ref name="Noebels2014">{{cite book |url=https://books.google.com/books?id=T2_LVTB7ftgC&pg=466 |title=Jasper's Basic Mechanisms of the Epilepsies |vauthors=Noebels JL, Avoli M |date=29 June 2012 |publisher=Oxford University Press |isbn=978-0-19-974654-5 |pages=466, 470 |access-date=16 October 2014}}</ref>

Together, these changes contribute to the formation of hyperexcitable neural networks, often anchored around a seizure focus. Once established, this pathological network increases the brain's susceptibility to seizures, even in the absence of ongoing injury. Although many of the processes underlying ictogenesis and epileptogenesis have been identified, the exact mechanisms by which the brain transitions into a seizure or becomes epileptic remain unknown.<ref name="Noebels2014" /> Research continues to explore how genetic, molecular, and network-level factors interact to produce the diverse manifestations of epilepsy.