Drgawki
Patofizjologia i mechanizm

Drgawki są klinicznym przejawem nadmiernych, hipersynchronicznych wyładowań neuronów korowych, wynikających z nagłej nierównowagi między pobudzeniem a hamowaniem w sieci neuronalnej, z przewagą pobudzenia. Na poziomie komórkowym inicjacja drgawek wiąże się z napływem zewnątrzkomórkowego Ca²⁺, otwarciem napięciowo-zależnych kanałów Na⁺ i generowaniem powtarzających się potencjałów czynnościowych, co prowadzi do paroksyzmalnych przesunięć depolaryzacyjnych (PDS). Epileptogeneza obejmuje zmiany w neurotransmisji glutaminianergicznej i GABA-ergicznej, modyfikacje kanałów jonowych oraz procesy zapalne i stres oksydacyjny, które zwiększają pobudliwość neuronalną i sprzyjają rozwojowi padaczki. Metabolit glikolityczny – kwas mlekowy – odgrywa rolę w inicjacji i zakończeniu napadów poprzez modulację receptorów NMDA, aktywację kanałów jonowych wrażliwych na kwasy oraz wzmocnienie hamującego działania GABA. Drgawki dzieli się na częściowe (ogniskowe) i uogólnione, z odmiennymi mechanizmami patofizjologicznymi, m.in. zaburzeniami rytmów wzgórzowo-korowych w napadach nieświadomości.

  1. Mechanizm drgawek (Seizures pathogenesis mechanism)
    1. Etapy powstawania drgawek
    2. Zaburzenia równowagi jonowej
    3. Mechanizmy komórkowe i molekularne
  2. Mechanizmy molekularne epileptogenezy
    1. Zaburzenia neurotransmiterów
    2. Rola stanu zapalnego
    3. Stres oksydacyjny
  3. Rodzaje drgawek i ich mechanizmy
    1. Mechanizmy napadów ogniskowych
    2. Mechanizmy napadów uogólnionych
  4. Czynniki wpływające na powstawanie drgawek
    1. Czynniki genetyczne
    2. Czynniki metaboliczne
    3. Rola cytokin w drgawkach gorączkowych
  5. Mechanizmy drgawek w szczególnych stanach klinicznych
    1. Mechanizm drgawek w udarze mózgu
    2. Mechanizm drgawek w chorobie Alzheimera
    3. Mechanizm drgawek w guzach mózgu
  6. Mechanizmy zakończenia drgawek
    1. Hipoteza wyczerpania energii
    2. Kwasica metaboliczna
    3. Rola czynników modulujących
  7. Implikacje terapeutyczne
    1. Leki przeciwdrgawkowe
    2. Nowe podejścia terapeutyczne
  8. Podsumowanie mechanizmu drgawek
    1. Kolejne rozdziały

Mechanizm drgawek (Seizures pathogenesis mechanism)

Drgawki (seizures) to kliniczne manifestacje nieprawidłowych, nadmiernych, hipersynchronicznych wyładowań populacji neuronów korowych. Są one wynikiem nagłej nierównowagi między pobudzeniem a hamowaniem w sieci neuronów korowych, z przewagą nagłego pobudzenia. 12 Stanowią przejściowe zjawisko, charakteryzujące się objawami lub oznakami wynikającymi z nieprawidłowej, nadmiernej lub synchronicznej aktywności neuronalnej w mózgu. 3

Etapy powstawania drgawek

Inicjacja drgawek charakteryzuje się dwoma równoczesnymi zjawiskami: 1) wyładowaniami o wysokiej częstotliwości oraz 2) hipersynchronizacją populacji neuronów. 4 Na poziomie komórkowym, drgawki rozpoczynają się od pobudzenia podatnych neuronów mózgowych, co prowadzi do synchronicznych wyładowań w coraz większych grupach połączonych neuronów. 5

Aktywność drgawkowa, wynikająca ze stosunkowo długotrwałej depolaryzacji błony neuronalnej, jest spowodowana napływem zewnątrzkomórkowego Ca2+, co prowadzi do otwarcia zależnych od napięcia kanałów Na+, napływu Na+ i generowania powtarzających się potencjałów czynnościowych. 6 Elektrofizjologicznym korelatem drgawek ogniskowych są paroksyzmalne przesunięcia depolaryzacyjne (PDS), które stanowią nadmierne pobudzenie neuronów. 7

Propagacja drgawek, czyli proces rozprzestrzeniania się napadów częściowych w mózgu, zachodzi, gdy występuje wystarczająca aktywacja do rekrutacji otaczających neuronów. 8 Napad musi rekrutować więcej tkanki nerwowej, aby stać się drgawką. 9

Zaburzenia równowagi jonowej

Zaburzenia równowagi jonowej w sieciach neuronalnych przyczyniają się do złożoności napadów padaczkowych, obejmując zmiany w napięciowo-zależnych kanałach sodowych i potasowych oraz tworzenie różnorodnych podtypów kanałów jonowych. 10

Koncept progu drgawkowego oznacza, że każda osoba znajduje się na kontinuum podatności na drgawki, na którą wpływa wiele czynników. 11 Napady padaczkowe i padaczka powstają z wielu przyczyn i są podtrzymywane poprzez proces pozytywnego wzmacniania, gdzie początkowa nierównowaga między hamowaniem a pobudzeniem neuronalnym wywołuje dalsze nierównowagi. 12

Mechanizmy komórkowe i molekularne

Na poziomie komórkowym i molekularnym, drgawki są wynikiem zaburzenia normalnej równowagi między pobudzeniem a hamowaniem. W zdrowych warunkach, pobudzająca neurotransmisja (głównie za pośrednictwem glutaminianu) i hamująca neurotransmisja (głównie poprzez GABA) utrzymują stabilność korową. Nadmiar pobudzenia lub brak hamowania może zaburzyć tę równowagę, sprzyjając hipersynchronicznemu wyładowaniu neuronalnemu charakterystycznemu dla napadów. 13

Badania wykazały, że glikoliza zwiększa się podczas napadów, a metabolit glikolityczny – kwas mlekowy, może być wykorzystany jako źródło energii. Mechanizm kwasu mlekowego obejmuje kilka aspektów, w tym hamowanie enzymu glikolitycznego 6-fosfofruktokinazy-1, hamowanie receptora NMDA, aktywację kanału jonowego wrażliwego na kwasy 1A, wzmocnienie mechanizmu receptorowego hamującego neuroprzekaźnika GABA i zmiany w wewnątrz- i zewnątrzkomórkowym środowisku. 14

Mechanizmy molekularne epileptogenezy

Epileptogeneza to proces, w którym normalnie funkcjonujący mózg ulega zmianom prowadzącym do rozwoju padaczki, angażując różne czynniki. 15 Jest to sekwencja zdarzeń, które przekształcają normalną sieć neuronalną w sieć nadpobudliwą. 16

Zaburzenia neurotransmiterów

Na poziomie komórkowym, główne mechanizmy obejmują:

  • Zwiększoną pobudzającą neurotransmisję glutaminianergiczną 17
  • Zmniejszoną hamującą neurotransmisję GABAergiczną 18
  • Zmiany w napięciowo-zależnych kanałach jonowych 19
  • Zmiany w wewnątrz- lub zewnątrzkomórkowych stężeniach jonów 20

Epileptogeneza wywołuje zmiany molekularne w hipokampie, w tym zmienioną neurogenezę i zwiększoną ekspresję czynników neurotroficznych i białek. 21 Zwiększona aktywacja szlaków mTOR (mammalian target of rapamycin) wpływa na epileptogenezę, oddziałując na pobudliwość neuronalną i tworzenie synaps, przy czym mutacje genetyczne przyczyniają się do zespołów padaczkowych, a modulacja autofagii odgrywa rolę w pojawianiu się napadów. 22

Rola stanu zapalnego

Stan zapalny odgrywa istotną rolę w progresji epileptogenezy. 23 Cytokiny prozapalne pochodzące z aktywowanych mikrogleju i astrocytów w tkance epileptycznej inicjują kaskadę zapalną, zwiększając pobudliwość neuronalną i wywołując aktywność podobną do padaczki. 24

Układ odpornościowy, zarówno wrodzony jak i nabyty, jest aktywowany u pacjentów z padaczką. Mikroglej i astrocyty jako komórki glejowe i nieneuronalne części ośrodkowego układu nerwowego są źródłem prozapalnych cytokin w tkance epileptycznej. Cytokiny zapalne odgrywają rolę w zmianie pobudliwości neuronalnej, produkcji mediatorów toksycznych i zwiększaniu przepuszczalności bariery krew-mózg. 25

Stres oksydacyjny

Stres oksydacyjny prowadzi do uszkodzenia komórek, zaburzenia systemów antyoksydacyjnych i dysfunkcji mitochondriów, stając się kluczowym elementem epileptogenezy i potencjalnych interwencji neuroprotekcyjnych. 26 Zmiana szlaków katabolicznych glukozy jest jednym z czynników wpływających na epileptogenezę. 27

Rodzaje drgawek i ich mechanizmy

Drgawki można klasyfikować jako częściowe (ogniskowe) lub uogólnione. W napadzie częściowym, najczęstszym typie napadu u dorosłych, najpierw aktywuje się jeden obszar kory mózgowej i może manifestować się poprzez proste objawy, takie jak zjawiska ruchowe lub czuciowe. Napady uogólnione wynikają z rozlanej aktywacji korowej na początku napadu lub uogólnienia aktywności napadu częściowego. 28

Mechanizmy napadów ogniskowych

Patofizjologia napadów ogniskowych różni się od mechanizmów leżących u podstaw napadów uogólnionych. 29 Następujące mechanizmy mogą współistnieć w różnych kombinacjach, powodując napady o początku ogniskowym:

  • Zmniejszone hamowanie
  • Wadliwa aktywacja neuronów GABA
  • Zwiększona aktywacja 30

Jeśli mechanizmy prowadzące do zwiększonej pobudliwości netto staną się trwałymi zmianami, u pacjentów może rozwinąć się padaczka ogniskowa oporna na farmakoterapię. 31

Mechanizmy napadów uogólnionych

Najlepiej zrozumiałym przykładem mechanizmów patofizjologicznych napadów uogólnionych jest interakcja wzgórzowo-korowa, która może leżeć u podstaw typowych napadów nieświadomości. Obwód wzgórzowo-korowy ma normalne rytmy oscylacyjne, z okresami stosunkowo zwiększonego pobudzenia i okresami stosunkowo zwiększonego hamowania. 32

Zakłócenie obwodów łączących wzgórze i korę mózgową stanowi mechanizm napędowy padaczki nieświadomości. 33 Zmienione rytmy wzgórzowo-korowe mogą prowadzić do pierwotnych napadów o początku uogólnionym. 34

Napady nieświadomości powstają z hipersynchronicznych patologicznych oscylacji w sieci wzgórzowo-korowej. Zmiany we współdziałaniu między neuronami pobudzającymi a hamującymi w mikrobwodach korowych i wzgórzowych mogą generować patologiczną rytmiczną aktywność obserwowaną w wyładowaniach iglica-fala. 35

Czynniki wpływające na powstawanie drgawek

Napady mogą być wywołane (provoked) lub niewywołane (unprovoked). Napady wywołane, znane również jako ostre objawowe napady, mogą wynikać z zaburzeń elektrolitowych, toksyn, urazów głowy, procesów zakaźnych, anomalii naczyniowych, guzów lub innych zmian masowych, i wielu innych przyczyn. 36

Czynniki genetyczne

Epileptogeneza jest determinowana przez wiele czynników, w tym stres oksydacyjny, zmiany neurochemiczne w mózgu spowodowane przez neuroprzekaźniki i kanały jonowe, wahania stężenia jonów, różnice w receptorach powierzchni komórek oraz obecność stanu zapalnego. 37

Mechanizmy epigenetyczne, które nie są związane ze zmianami w sekwencji DNA, ale raczej z regulacją transkrypcji lub potranskrypcyjną, mogą odgrywać rolę w epileptogenezie. 38

Czynniki metaboliczne

Pobudliwość mózgu i równowaga metaboliczna są ściśle powiązane. Dostarczanie energii do neuronów zależy krytycznie od glukozy, której wahania mogą sprzyjać natychmiastowej nadpobudliwości, prowadząc do ostrych objawowych napadów. 39

Hiperglikemia może bezpośrednio zwiększyć pobudliwość neuronalną działając na kanały potasowe wrażliwe na ATP w neuronach hipokampa i kory mózgowej; hipoglikemia obniża poziom GABA, zwiększając przekaźnictwo pobudzające. 40

Glikoliza, ważny szlak obejściowy dla dostarczania energii, może złagodzić niedobór energii spowodowany uszkodzeniem energetycznym metabolizmu tlenowego. Metabolit glikolityczny – kwas mlekowy – jest zaangażowany w początek napadów i dostarcza energii we wczesnych okresach napadu. 41

Rola cytokin w drgawkach gorączkowych

Drgawki gorączkowe (FS), które występują u gorączkujących dzieci bez podstawowych problemów zdrowotnych, są najczęstszym typem zaburzeń drgawkowych u dzieci. Sugerowana patogeneza FS, wywnioskowana z kilku badań na zwierzętach i ludziach, jest wieloczynnikowa i dyskusyjna. Nadpobudliwość neuronalna, która rozwija się podczas odpowiedzi zapalnych towarzyszących gorączce, prowokuje drgawki. 42

W podatnym niedojrzałym OUN zwiększona pobudliwość neuronalna sprzyja drgawkom, a cytokiny produkowane i uwalniane podczas ostrych odpowiedzi zapalnych towarzyszących gorączce odgrywają rolę w zwiększaniu pobudliwości neuronalnej. Odpowiedzi zapalne poza OUN zwiększają stężenie cytokin w OUN (sieć neuro-immunologiczna), a uwolnione cytokiny wywołują nadpobudliwość neuronalną w OUN, generując FS. 43

Mechanizmy drgawek w szczególnych stanach klinicznych

Mechanizm drgawek w udarze mózgu

Udar jest najczęstszą przyczyną wtórnej padaczki u osób starszych. Występowanie padaczki jest ściśle związane z typem i lokalizacją udaru. 44

Badania wykazały, że odkładanie się hemosyderyny jest ściśle związane z występowaniem wczesnych napadów padaczkowych po krwotoku podpajęczynówkowym. Zwiększenie stężenia glutaminianu i zmniejszenie stężenia GABA prowadzą do zwiększonej pobudliwości neuronów i obniżenia progu drgawek, co powoduje zwiększoną podatność na napady. 45

Ważnym powodem napadów padaczkowych po udarze niedokrwiennym jest zaburzenie gradientu stężenia jonów. Następnie istnieją trzy czynniki, które wpływają na rozprzestrzenianie się napadów padaczkowych po udarze niedokrwiennym: masowe uwalnianie glutaminianu, nadmierna aktywacja receptorów i wysokie zewnątrzkomórkowe stężenie potasu. 46

Mechanizm drgawek w chorobie Alzheimera

Osoby z chorobą Alzheimera (AD) są 6-10 razy bardziej narażone na rozwój drgawek niż zdrowa populacja osób starszych. 47

Wiodącą hipotezą nadpobudliwości w AD jest to, że odkładanie się amyloidu beta prowadzi do neurodegeneracji i nieprawidłowej nadaktywności, w tym drgawek, co z kolei skutkuje zwiększonym obciążeniem amyloidem, prowadząc do samowzmacniającej się kaskady neurodegeneracyjnej. 4849

Kluczowym wynikiem badań jest to, że wcześniej zgłaszane zmiany w połączeniach funkcjonalnych w AD skutkują sieciami mózgowymi, które łatwiej generują drgawki w odpowiedzi na zwiększoną pobudliwość korową niż u zdrowych osób. 5051

Mechanizm drgawek w guzach mózgu

Guzy mózgu i przerzuty mogą powodować drgawki poprzez różne mechanizmy; zmiany w pobudzającym przekaźnictwie nerwowym i zewnątrzkomórkowych prądach jonowych są uważane za najbardziej prawdopodobne. Inne potencjalne mechanizmy obejmują hipoksję, kwasicę, stan zapalny, efekty mechaniczne i zakłócenie lokalnej homeostazy ze zmianami elektrolitów, perfuzji i metabolizmu. 52

Padaczka związana z guzami mózgu (BTRE) jest trudnym zagadnieniem, ponieważ mechanizmy patofizjologiczne nie są jeszcze w pełni zrozumiałe. Niemniej jednak, uważa się, że neurozapalenie odgrywa kluczową rolę. Oprócz neurozapalenia, odkrycia dotyczące patogenezy BTRE ustaliły, że zaangażowane są pewne mutacje genetyczne, z których najbardziej znane są mutacje IDH w glejakach. 53

Mechanizmy zakończenia drgawek

Główne mechanizmy zakończenia napadów obejmują zużycie energii i kwasicę metaboliczną. Kwas mlekowy wywołuje kwasicę poprzez kilka możliwych szlaków: hamuje aktywność kinazy-1 6-fosfofruktozy i receptorów NMDA, aktywuje kanał jonowy wrażliwy na kwasy 1A i wzmacnia mechanizm receptorowy hamującego neuroprzekaźnika GABA. 54

Hipoteza wyczerpania energii

Hipoteza wyczerpania energii opiera się na fakcie, że neurony nieprawidłowo wyładowują się podczas napadów, co prowadzi do wyczerpania energii, które może prowadzić do zakończenia napadów. 55

Kwasica metaboliczna

Kwasica metaboliczna może być kolejnym mechanizmem zakańczającym drgawki. Podczas procesu wyładowania epileptycznego, nagromadzenie różnych metabolitów generowanych przez nieprawidłowe wyładowania neuronów podczas napadów prowadzi do kwasicy, co może być zaangażowane w proces zakończenia napadu. 56

Glikoliza produkuje duże ilości kwasu mlekowego, powodując obniżenie pH, co skutkuje kwasicą zewnątrzkomórkową. Obniżenie pH do 6,7 zwiększa interwał między zdarzeniami podobnymi do napadów, a zakwaszenie spowalnia szybkość propagacji napadów. 57

Rola czynników modulujących

Leki działające na receptor GABA w celu wzmocnienia lokalnego hamowania bez zwiększania sedacji lub tachyfilaksji stanowiłyby poprawę w stosunku do benzodiazepin, które są wartościowe głównie w ostrej kontroli napadów. 58

Leki ukierunkowane na transportery chlorku i gradienty mogą kontrolować zespoły napadów zależne od wieku. Leki ukierunkowane na kinazę adenozyny, receptory endokannabinoidu i NPY oraz zmieniające środowisko hormonalne mogą poprawić kontrolę napadów i ich zakończenie. 59

Stymulacja nerwu błędnego (Blount JP i wsp. 2006), inicjowana przez pacjenta, zatrzyma aktywność napadową i może być rozszerzona na modyfikujące napady obwody, takie jak przednie wzgórze, część siatkowata istoty czarnej i jądro podwzgórzowe. 60

Implikacje terapeutyczne

Wiedza o mechanizmach drgawek ma kluczowe znaczenie dla rozwoju nowych terapii przeciwpadaczkowych. Leki przeciwdrgawkowe mogą wpływać na drgawki poprzez dwa mechanizmy: (i) tłumienie określonych wzorców aktywności napadowej (stanów) w sposób wszystko albo nic oraz (ii) skrócenie czasu trwania innych wzorców napadowych. 61

Leki przeciwdrgawkowe

Leki przeciwpadaczkowe są zaprojektowane do modyfikacji procesów neuronalnych w taki sposób, aby sprzyjać hamowaniu nad pobudzeniem, a tym samym zatrzymać lub zapobiec aktywności napadowej. 62

Leki przeciwpadaczkowe można pogrupować według ich głównego mechanizmu działania, chociaż wiele z nich ma kilka działań, a inne mają nieznane mechanizmy działania:

  • Leki blokujące kanały sodowe zapobiegają powrotowi tych kanałów do stanu aktywnego, stabilizując je w stanie nieaktywnym. 63
  • Kanały wapniowe funkcjonują jako „rozruszniki” normalnej rytmicznej aktywności mózgu. Jest to szczególnie prawdziwe w przypadku wzgórza. 64
  • System GABA może być wzmocniony przez bezpośrednie wiązanie się z receptorami GABA-A, przez blokowanie presynaptycznego wychwytu GABA, przez hamowanie metabolizmu GABA przez transaminazę GABA i przez zwiększenie syntezy GABA. 65
  • Leki, które modyfikują receptory glutaminianowe, są antagonistyczne wobec glutaminianu. 66

Nowe podejścia terapeutyczne

Cenobamate, niedawno zatwierdzony lek przeciwdrgawkowy o podwójnym mechanizmie działania – pozytywnej modulacji GABA-A i hamowaniu kanałów sodowych – został oceniony jako leczenie uzupełniające u dorosłych z niekontrolowanymi napadami o początku ogniskowym (FOS). 67

Badania wykazały, że leki aktywujące sygnalizację adenozynową mogą być możliwą drogą leczenia dysplazji korowej ogniskowej, związanej z najczęstszą przyczyną napadów, których nie można kontrolować lekami u dzieci. 6869

Badanie ujawnia wcześniej nieznany sposób, w jaki kannabidiol (CBD), substancja zawarta w konopiach, zmniejsza napady w wielu lekoopornych formach padaczki dziecięcej. CBD blokuje pozytywną pętlę sprzężenia zwrotnego, w której napady zwiększają sygnalizację LPI-GPR55, co prawdopodobnie sprzyja kolejnym napadom, co z kolei zwiększa poziom zarówno LPI, jak i GPR55. 70

Podsumowanie mechanizmu drgawek

Drgawki są wynikiem złożonych interakcji między czynnikami genetycznymi, molekularnymi i środowiskowymi, które prowadzą do zaburzenia równowagi między pobudzeniem a hamowaniem w mózgu. Mechanizmy obejmują:

  • Zaburzenia kanałów jonowych i neurotransmiterów
  • Nieprawidłową synchronizację neuronów
  • Procesy zapalne i neuroimmunologiczne
  • Zmiany w metabolizmie energetycznym mózgu
  • Modyfikacje strukturalne sieci neuronalnych

Zrozumienie tych mechanizmów jest kluczowe dla opracowania skutecznych strategii terapeutycznych dla różnych rodzajów drgawek i padaczki. 7172

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  1. 10.04.2026
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Materiały źródłowe

  • #1 Basic Mechanisms Underlying Seizures and Epilepsy – An Introduction to Epilepsy – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK2510/
    A seizure (from the Latin sacire to take possession of) is the clinical manifestation of an abnormal, excessive, hypersynchronous discharge of a population of cortical neurons. […] Epileptogenesis is the sequence of events that turns a normal neuronal network into a hyperexcitable network. […] The hypersynchronous discharges that occur during a seizure may begin in a very discrete region of cortex and then spread to neighboring regions. Seizure initiation is characterized by two concurrent events: 1) high-frequency bursts of action potentials, and 2) hypersynchronization of a neuronal population. […] The bursting activity resulting from the relatively prolonged depolarization of the neuronal membrane is due to influx of extracellular Ca++, which leads to the opening of voltage-dependent Na+ channels, influx of Na+, and generation of repetitive action potentials.
  • #2 Seizure – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK430765/
    A seizure represents the uncontrolled, abnormal electrical activity of the brain that may cause changes in the level of consciousness, behavior, memory, or feelings. […] Seizures can classify as partial or generalized. In a partial seizure, the most common seizure type in adults, one area of the cortex activates first and may manifest through simple symptoms such as a motor or sensory phenomena. Generalized seizures result from diffuse cortical activation at seizure onset or generalization of partial seizure activity. […] An epileptic seizure is a transient occurrence with signs or symptoms due to abnormal excessive and synchronous neuronal activity in the brain. […] Current classification designates two large categories – partial or generalized. […] Partial seizures may rapidly secondarily generalize and spread to involve all cortical areas. Generalized seizures result from diffuse cortical activation at seizure onset.
  • #3 Seizure – Wikipedia
    https://en.wikipedia.org/wiki/Seizure
    A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. […] Seizures are classified as provoked, when triggered by a known cause such as fever, head trauma, or metabolic imbalance, or unprovoked, when no immediate trigger is identified. Recurrent unprovoked seizures define the neurological condition epilepsy. […] Seizures are the result of abnormal, excessive, and hypersynchronous neuronal activity in the brain. At a cellular level, they reflect a disruption of the normal balance between excitatory and inhibitory neurotransmission. Under healthy conditions, excitatory neurotransmission (mainly mediated by glutamate) and inhibitory neurotransmission (primarily via GABA) maintain cortical stability. An excess of excitation or a failure of inhibition can tip this balance, promoting hypersynchronous neuronal firing characteristic of seizures.
  • #4 Basic Mechanisms Underlying Seizures and Epilepsy – An Introduction to Epilepsy – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK2510/
    A seizure (from the Latin sacire to take possession of) is the clinical manifestation of an abnormal, excessive, hypersynchronous discharge of a population of cortical neurons. […] Epileptogenesis is the sequence of events that turns a normal neuronal network into a hyperexcitable network. […] The hypersynchronous discharges that occur during a seizure may begin in a very discrete region of cortex and then spread to neighboring regions. Seizure initiation is characterized by two concurrent events: 1) high-frequency bursts of action potentials, and 2) hypersynchronization of a neuronal population. […] The bursting activity resulting from the relatively prolonged depolarization of the neuronal membrane is due to influx of extracellular Ca++, which leads to the opening of voltage-dependent Na+ channels, influx of Na+, and generation of repetitive action potentials.
  • #5 Seizure – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK430765/
    The concept of a seizure threshold means that each individual exists on a seizure susceptibility continuum with many factors influencing that susceptibility. […] On a cellular level, seizures start with the excitation of susceptible cerebral neurons, which leads to synchronous discharges of progressively larger groups of connected neurons. […] An imbalance of excess excitation and decreased inhibition initiates the abnormal electrical activity. […] These electrical paroxysmal depolarization shifts (PDS) seem to trigger epileptiform activity. Increased activation or decreased inhibition of such discharges could result in seizures. […] Generalized convulsive status epilepticus is accompanied by systemic changes of lactic acidosis, increased catecholamine levels, hyperthermia, respiratory compromise, and other systemic alterations.
  • #6 Basic Mechanisms Underlying Seizures and Epilepsy – An Introduction to Epilepsy – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK2510/
    A seizure (from the Latin sacire to take possession of) is the clinical manifestation of an abnormal, excessive, hypersynchronous discharge of a population of cortical neurons. […] Epileptogenesis is the sequence of events that turns a normal neuronal network into a hyperexcitable network. […] The hypersynchronous discharges that occur during a seizure may begin in a very discrete region of cortex and then spread to neighboring regions. Seizure initiation is characterized by two concurrent events: 1) high-frequency bursts of action potentials, and 2) hypersynchronization of a neuronal population. […] The bursting activity resulting from the relatively prolonged depolarization of the neuronal membrane is due to influx of extracellular Ca++, which leads to the opening of voltage-dependent Na+ channels, influx of Na+, and generation of repetitive action potentials.
  • #7 Epilepsy and Seizures: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1184846-overview
    Seizures are paroxysmal manifestations of the electrical properties of the cerebral cortex. A seizure results when a sudden imbalance occurs between the excitatory and inhibitory forces within the network of cortical neurons in favor of a sudden-onset net excitation. […] The pathophysiology of focal-onset seizures differs from the mechanisms underlying generalized-onset seizures. Overall, cellular excitability is increased, but the mechanisms of synchronization appear to substantially differ between these 2 types of seizure and are therefore discussed separately. […] The electroencephalographic (EEG) hallmark of focal-onset seizures is the focal interictal epileptiform spike or sharp wave. The cellular neurophysiologic correlate of an interictal focal epileptiform discharge in single cortical neurons is the paroxysmal depolarization shift (PDS).
  • #8 Basic Mechanisms Underlying Seizures and Epilepsy – An Introduction to Epilepsy – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK2510/
    Seizure propagation, the process by which a partial seizure spreads within the brain, occurs when there is sufficient activation to recruit surrounding neurons. […] Our understanding of the CNS abnormalities causing patients to have recurrent seizures remains limited. It is important to understand that seizures and epilepsy can result from many different pathologic processes that upset the balance between excitation and inhibition. […] Epileptogenesis: The Transformation of a Normal Network Into a Hyperexcitable Network […] Changes occurring during this period could include delayed necrosis of inhibitory interneurons (or the excitatory interneurons driving them), or sprouting of axonal collaterals leading to reverberating, or self-reinforcing, circuits.
  • #9 Epilepsy and Seizures: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1184846-overview
    Several factors may be associated with the transition from an interictal spike to an epileptic seizure. The spike has to recruit more neural tissue to become a seizure. When any of the mechanisms that underlie an acute seizure becomes a permanent alteration, the person presumably develops a propensity for recurrent seizures (ie, epilepsy). […] The following mechanisms (discussed below) may coexist in different combinations to cause focal-onset seizures: Decreased inhibition, Defective activation of gamma-aminobutyric acid (GABA) neurons, Increased activation. […] If the mechanisms leading to a net increased excitability become permanent alterations, patients may develop pharmacologically intractable focal-onset epilepsy. […] The best-understood example of the pathophysiologic mechanisms of generalized seizures is the thalamocortical interaction that may underlie typical absence seizures. The thalamocortical circuit has normal oscillatory rhythms, with periods of relatively increased excitation and periods of relatively increased inhibition. It generates the oscillations observed in sleep spindles. […] Altered thalamocortical rhythms may result in primary generalized-onset seizures.
  • #10 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. […] Epileptogenesis triggers molecular changes in hippocampus, including altered neurogenesis and enhanced expression of neurotrophic factors and proteins. […] Oxidative stress leads to cellular damage, disrupted antioxidant systems, and mitochondrial dysfunction, making it a key player in epileptogenesis and potential neuroprotective interventions. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells.
  • #11 Seizure – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK430765/
    The concept of a seizure threshold means that each individual exists on a seizure susceptibility continuum with many factors influencing that susceptibility. […] On a cellular level, seizures start with the excitation of susceptible cerebral neurons, which leads to synchronous discharges of progressively larger groups of connected neurons. […] An imbalance of excess excitation and decreased inhibition initiates the abnormal electrical activity. […] These electrical paroxysmal depolarization shifts (PDS) seem to trigger epileptiform activity. Increased activation or decreased inhibition of such discharges could result in seizures. […] Generalized convulsive status epilepticus is accompanied by systemic changes of lactic acidosis, increased catecholamine levels, hyperthermia, respiratory compromise, and other systemic alterations.
  • #12 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Epileptic seizures and epilepsy arise from a multitude of causes and sustained through a process of positive reinforcement, where an initial imbalance between neural inhibition and excitation triggers further imbalances. […] Epileptogenesis is influenced by factors including oxidative stress, neurochemical alterations in the brain due to neurotransmitters and ion channels, fluctuations in ion concentration, variations in cell surface receptors, and the presence of inflammation. […] The role of inflammation in epileptic seizure and epilepsy. […] Inflammation indeed plays a significant role in the progression of epileptogenesis. […] The release of cytokines, chemokines, lipid mediators, and protectins into the neuronal environment indicates that brain trauma has caused an organized cascade of biological processes.
  • #13 Seizure – Wikipedia
    https://en.wikipedia.org/wiki/Seizure
    A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. […] Seizures are classified as provoked, when triggered by a known cause such as fever, head trauma, or metabolic imbalance, or unprovoked, when no immediate trigger is identified. Recurrent unprovoked seizures define the neurological condition epilepsy. […] Seizures are the result of abnormal, excessive, and hypersynchronous neuronal activity in the brain. At a cellular level, they reflect a disruption of the normal balance between excitatory and inhibitory neurotransmission. Under healthy conditions, excitatory neurotransmission (mainly mediated by glutamate) and inhibitory neurotransmission (primarily via GABA) maintain cortical stability. An excess of excitation or a failure of inhibition can tip this balance, promoting hypersynchronous neuronal firing characteristic of seizures.
  • #14
    https://journals.lww.com/nrronline/fulltext/2013/08140/glycolysis_in_energy_metabolism_during_seizures_.8.aspx
    Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. […] The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter -aminobutyric acid, and changes in the intra- and extracellular environment. […] Glycolysis, an important in vivo bypass for energy supply, can relieve the energy shortage caused by the energy damage of aerobic metabolism. The glycolytic metabolite lactic acid is involved in seizure onset and provides energy in the early periods of the seizure. As seizures progress, lactic acid can terminate the seizures.
  • #15 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Epileptogenesis is the process by which a normally functioning brain undergoes alterations leading to the development of epilepsy, involving various factors. […] Pro-inflammatory cytokines from activated microglia and astrocytes in epileptic tissue initiate an inflammatory cascade, heightening neuronal excitability and triggering epileptiform activity. […] The mammalian target of rapamycin (mTOR) pathways excessive activation influences epileptogenesis, impacting neuronal excitability, and synapse formation, with genetic mutations contributing to epilepsy syndromes and the modulation of autophagy playing a role in seizure onset. […] The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis.
  • #16 Basic Mechanisms Underlying Seizures and Epilepsy – An Introduction to Epilepsy – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK2510/
    A seizure (from the Latin sacire to take possession of) is the clinical manifestation of an abnormal, excessive, hypersynchronous discharge of a population of cortical neurons. […] Epileptogenesis is the sequence of events that turns a normal neuronal network into a hyperexcitable network. […] The hypersynchronous discharges that occur during a seizure may begin in a very discrete region of cortex and then spread to neighboring regions. Seizure initiation is characterized by two concurrent events: 1) high-frequency bursts of action potentials, and 2) hypersynchronization of a neuronal population. […] The bursting activity resulting from the relatively prolonged depolarization of the neuronal membrane is due to influx of extracellular Ca++, which leads to the opening of voltage-dependent Na+ channels, influx of Na+, and generation of repetitive action potentials.
  • #17 Basic mechanism of epilepsy | PPT
    https://www.slideshare.net/slideshow/basic-mechanism-of-epilepsy/238668886
    Seizures are caused by abnormal excessive neuronal excitation and synchronization in the brain. […] Epilepsy is a tendency toward recurrent seizures. […] Epileptogenesis is the process by which a brain network that was previously normal is functionally altered toward increased seizure susceptibility, thus having an enhanced probability to generate spontaneous recurrent seizures (SRSs). […] The mechanism of epilepsy is not just about excitation-inhibition imbalance. It should also explain the episodic nature of seizures and the varied etiology. […] In epilepsy there is predisposition to recurrent seizures. […] A hyperexcitable state can also result when several synchronous subthreshold excitatory stimuli occur, allowing their temporal summation in the post synaptic neurons. […] Increased excitatory neurotransmission
  • #18 Basic mechanism of epilepsy | PPT
    https://www.slideshare.net/slideshow/basic-mechanism-of-epilepsy/238668886
    Decreased inhibitory neurotransmission […] Alteration in voltage gated ion channels […] Alteration in intra or extra cellular ion concentrations. […] Neuroinflammation plays a role in epileptogenesis. […] The final common pathway is disturbance of excitation-inhibition balance (neuronal homeostasis) resulting in self-reinforcing episodic shifts in neuronal and network excitability. […] This involves multiple neurotransmitters (primarily GABA and Glutamate), ion conductance (primarily Na, K, Ca, Cl) and genetic factors. […] Major role for interneurons and glial cells in epileptogenesis.
  • #19 Basic mechanism of epilepsy | PPT
    https://www.slideshare.net/slideshow/basic-mechanism-of-epilepsy/238668886
    Decreased inhibitory neurotransmission […] Alteration in voltage gated ion channels […] Alteration in intra or extra cellular ion concentrations. […] Neuroinflammation plays a role in epileptogenesis. […] The final common pathway is disturbance of excitation-inhibition balance (neuronal homeostasis) resulting in self-reinforcing episodic shifts in neuronal and network excitability. […] This involves multiple neurotransmitters (primarily GABA and Glutamate), ion conductance (primarily Na, K, Ca, Cl) and genetic factors. […] Major role for interneurons and glial cells in epileptogenesis.
  • #20 Basic mechanism of epilepsy | PPT
    https://www.slideshare.net/slideshow/basic-mechanism-of-epilepsy/238668886
    Decreased inhibitory neurotransmission […] Alteration in voltage gated ion channels […] Alteration in intra or extra cellular ion concentrations. […] Neuroinflammation plays a role in epileptogenesis. […] The final common pathway is disturbance of excitation-inhibition balance (neuronal homeostasis) resulting in self-reinforcing episodic shifts in neuronal and network excitability. […] This involves multiple neurotransmitters (primarily GABA and Glutamate), ion conductance (primarily Na, K, Ca, Cl) and genetic factors. […] Major role for interneurons and glial cells in epileptogenesis.
  • #21 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. […] Epileptogenesis triggers molecular changes in hippocampus, including altered neurogenesis and enhanced expression of neurotrophic factors and proteins. […] Oxidative stress leads to cellular damage, disrupted antioxidant systems, and mitochondrial dysfunction, making it a key player in epileptogenesis and potential neuroprotective interventions. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells.
  • #22 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Epileptogenesis is the process by which a normally functioning brain undergoes alterations leading to the development of epilepsy, involving various factors. […] Pro-inflammatory cytokines from activated microglia and astrocytes in epileptic tissue initiate an inflammatory cascade, heightening neuronal excitability and triggering epileptiform activity. […] The mammalian target of rapamycin (mTOR) pathways excessive activation influences epileptogenesis, impacting neuronal excitability, and synapse formation, with genetic mutations contributing to epilepsy syndromes and the modulation of autophagy playing a role in seizure onset. […] The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis.
  • #23 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Epileptic seizures and epilepsy arise from a multitude of causes and sustained through a process of positive reinforcement, where an initial imbalance between neural inhibition and excitation triggers further imbalances. […] Epileptogenesis is influenced by factors including oxidative stress, neurochemical alterations in the brain due to neurotransmitters and ion channels, fluctuations in ion concentration, variations in cell surface receptors, and the presence of inflammation. […] The role of inflammation in epileptic seizure and epilepsy. […] Inflammation indeed plays a significant role in the progression of epileptogenesis. […] The release of cytokines, chemokines, lipid mediators, and protectins into the neuronal environment indicates that brain trauma has caused an organized cascade of biological processes.
  • #24 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Epileptogenesis is the process by which a normally functioning brain undergoes alterations leading to the development of epilepsy, involving various factors. […] Pro-inflammatory cytokines from activated microglia and astrocytes in epileptic tissue initiate an inflammatory cascade, heightening neuronal excitability and triggering epileptiform activity. […] The mammalian target of rapamycin (mTOR) pathways excessive activation influences epileptogenesis, impacting neuronal excitability, and synapse formation, with genetic mutations contributing to epilepsy syndromes and the modulation of autophagy playing a role in seizure onset. […] The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis.
  • #25 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    The innate and acquired immune systems are activated in patients with epilepsy. […] Microglia and astrocytes as glial cells and non-neuronal parts of the central nervous system are the source of pro-inflammatory cytokines in epileptic tissue. […] Inflammatory cytokines play a role in changing neuronal excitability, producing toxic mediators, and making the BBB more impermeable. […] The excessive activation of the mTOR signaling pathway directly influences the progression of epileptogenesis and neuronal excitability. […] Glutamate receptor-mediated excitotoxicity is also recognized as a major mechanism contributing to cell death in various disorders of the central nervous system (CNS). […] The complexity of neuronal cell death associated with neurodegeneration is not mitigated by neuronal cell death triggered by epileptic seizures.
  • #26 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. […] Epileptogenesis triggers molecular changes in hippocampus, including altered neurogenesis and enhanced expression of neurotrophic factors and proteins. […] Oxidative stress leads to cellular damage, disrupted antioxidant systems, and mitochondrial dysfunction, making it a key player in epileptogenesis and potential neuroprotective interventions. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells.
  • #27 Glycaemic Imbalances in Seizures and Epilepsy of Paediatric Age: A Literature Review
    https://www.mdpi.com/2077-0383/12/7/2580
    Cerebral excitability and systemic metabolic balance are closely interconnected. Energy supply to neurons depends critically on glucose, whose fluctuations can promote immediate hyperexcitability resulting in acute symptomatic seizures. […] In epilepsy, there is a derailment of glucose catabolic pathways. Seizures greatly enhance the cerebral metabolic rate, increasing oxygen consumption, cerebral blood flow, and glucose uptake by neurons. Glucose metabolism is acutely shifted towards glycolysis and lactate production (ictal hypermetabolism), followed by a postictal decrease below baseline (postictal hypometabolism). […] On the other side, the disruption of mitochondrial oxphos could be involved in epileptogenesis. Experimental oxphos inhibition results in the destabilization of hippocampal membrane potentials and provokes epileptiform activity in initially healthy male rats.
  • #28 Seizure – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK430765/
    A seizure represents the uncontrolled, abnormal electrical activity of the brain that may cause changes in the level of consciousness, behavior, memory, or feelings. […] Seizures can classify as partial or generalized. In a partial seizure, the most common seizure type in adults, one area of the cortex activates first and may manifest through simple symptoms such as a motor or sensory phenomena. Generalized seizures result from diffuse cortical activation at seizure onset or generalization of partial seizure activity. […] An epileptic seizure is a transient occurrence with signs or symptoms due to abnormal excessive and synchronous neuronal activity in the brain. […] Current classification designates two large categories – partial or generalized. […] Partial seizures may rapidly secondarily generalize and spread to involve all cortical areas. Generalized seizures result from diffuse cortical activation at seizure onset.
  • #29 Epilepsy and Seizures: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1184846-overview
    Seizures are paroxysmal manifestations of the electrical properties of the cerebral cortex. A seizure results when a sudden imbalance occurs between the excitatory and inhibitory forces within the network of cortical neurons in favor of a sudden-onset net excitation. […] The pathophysiology of focal-onset seizures differs from the mechanisms underlying generalized-onset seizures. Overall, cellular excitability is increased, but the mechanisms of synchronization appear to substantially differ between these 2 types of seizure and are therefore discussed separately. […] The electroencephalographic (EEG) hallmark of focal-onset seizures is the focal interictal epileptiform spike or sharp wave. The cellular neurophysiologic correlate of an interictal focal epileptiform discharge in single cortical neurons is the paroxysmal depolarization shift (PDS).
  • #30 Epilepsy and Seizures: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1184846-overview
    Several factors may be associated with the transition from an interictal spike to an epileptic seizure. The spike has to recruit more neural tissue to become a seizure. When any of the mechanisms that underlie an acute seizure becomes a permanent alteration, the person presumably develops a propensity for recurrent seizures (ie, epilepsy). […] The following mechanisms (discussed below) may coexist in different combinations to cause focal-onset seizures: Decreased inhibition, Defective activation of gamma-aminobutyric acid (GABA) neurons, Increased activation. […] If the mechanisms leading to a net increased excitability become permanent alterations, patients may develop pharmacologically intractable focal-onset epilepsy. […] The best-understood example of the pathophysiologic mechanisms of generalized seizures is the thalamocortical interaction that may underlie typical absence seizures. The thalamocortical circuit has normal oscillatory rhythms, with periods of relatively increased excitation and periods of relatively increased inhibition. It generates the oscillations observed in sleep spindles. […] Altered thalamocortical rhythms may result in primary generalized-onset seizures.
  • #31 Epilepsy and Seizures: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1184846-overview
    Several factors may be associated with the transition from an interictal spike to an epileptic seizure. The spike has to recruit more neural tissue to become a seizure. When any of the mechanisms that underlie an acute seizure becomes a permanent alteration, the person presumably develops a propensity for recurrent seizures (ie, epilepsy). […] The following mechanisms (discussed below) may coexist in different combinations to cause focal-onset seizures: Decreased inhibition, Defective activation of gamma-aminobutyric acid (GABA) neurons, Increased activation. […] If the mechanisms leading to a net increased excitability become permanent alterations, patients may develop pharmacologically intractable focal-onset epilepsy. […] The best-understood example of the pathophysiologic mechanisms of generalized seizures is the thalamocortical interaction that may underlie typical absence seizures. The thalamocortical circuit has normal oscillatory rhythms, with periods of relatively increased excitation and periods of relatively increased inhibition. It generates the oscillations observed in sleep spindles. […] Altered thalamocortical rhythms may result in primary generalized-onset seizures.
  • #32 Epilepsy and Seizures: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1184846-overview
    Several factors may be associated with the transition from an interictal spike to an epileptic seizure. The spike has to recruit more neural tissue to become a seizure. When any of the mechanisms that underlie an acute seizure becomes a permanent alteration, the person presumably develops a propensity for recurrent seizures (ie, epilepsy). […] The following mechanisms (discussed below) may coexist in different combinations to cause focal-onset seizures: Decreased inhibition, Defective activation of gamma-aminobutyric acid (GABA) neurons, Increased activation. […] If the mechanisms leading to a net increased excitability become permanent alterations, patients may develop pharmacologically intractable focal-onset epilepsy. […] The best-understood example of the pathophysiologic mechanisms of generalized seizures is the thalamocortical interaction that may underlie typical absence seizures. The thalamocortical circuit has normal oscillatory rhythms, with periods of relatively increased excitation and periods of relatively increased inhibition. It generates the oscillations observed in sleep spindles. […] Altered thalamocortical rhythms may result in primary generalized-onset seizures.
  • #33 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    The disruption of the circuitry connecting the thalamus and the cerebral cortex constitutes the driving mechanism behind absence epilepsy. […] The hippocampus that works in memory and spatial navigation also has complicated connections with the cortex that contribute to brain activity regulation. […] Epigenetic mechanisms that are not linked to changes in DNA sequence but rather to transcription or post-transcriptional regulation can play a role in epileptogenesis.
  • #34 Epilepsy and Seizures: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1184846-overview
    Several factors may be associated with the transition from an interictal spike to an epileptic seizure. The spike has to recruit more neural tissue to become a seizure. When any of the mechanisms that underlie an acute seizure becomes a permanent alteration, the person presumably develops a propensity for recurrent seizures (ie, epilepsy). […] The following mechanisms (discussed below) may coexist in different combinations to cause focal-onset seizures: Decreased inhibition, Defective activation of gamma-aminobutyric acid (GABA) neurons, Increased activation. […] If the mechanisms leading to a net increased excitability become permanent alterations, patients may develop pharmacologically intractable focal-onset epilepsy. […] The best-understood example of the pathophysiologic mechanisms of generalized seizures is the thalamocortical interaction that may underlie typical absence seizures. The thalamocortical circuit has normal oscillatory rhythms, with periods of relatively increased excitation and periods of relatively increased inhibition. It generates the oscillations observed in sleep spindles. […] Altered thalamocortical rhythms may result in primary generalized-onset seizures.
  • #35 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention
    https://www.mdpi.com/1422-0067/25/18/9821
    The main aim is to critically review the literature that has contributed to unravelling causative molecular mechanisms underpinning absence seizures genesis and thereby identify potential targets for future therapeutic intervention. […] Absence seizures arise from hypersynchronous pathological oscillations within the CTC network. […] Alterations in the interplay between excitatory and inhibitory neurons in cortical and thalamic microcircuits can generate the pathological rhythmic activity seen in SWDs. […] This hypersynchronous, oscillatory activity is crucial for the propagation of absence seizures. […] However, the precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial.
  • #36 Seizure – StatPearls – NCBI Bookshelf
    https://www.ncbi.nlm.nih.gov/books/NBK430765/
    However, the ongoing excessive electrical activity that occurs with status epilepticus is damaging to the brain. […] The electrical activity reflected by EEG evolves as well. […] Seizures may be either provoked or unprovoked. […] Provoked seizures, also known as acute symptomatic seizures, may result from electrolyte disorders, toxins, head injury, infectious processes, vascular anomalies, tumors or other mass lesions, and many other causes. […] Epilepsy occurs because of a predisposition to seizures from genetic susceptibility or a chronic pathologic process. […] Recurrent unprovoked seizures define epilepsy. […] The prognosis of patients with seizures depends mostly on any underlying cause. […] Convulsive status epilepticus leads to brain damage on the cellular level and may itself be epileptogenic.
  • #37 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Epileptic seizures and epilepsy arise from a multitude of causes and sustained through a process of positive reinforcement, where an initial imbalance between neural inhibition and excitation triggers further imbalances. […] Epileptogenesis is influenced by factors including oxidative stress, neurochemical alterations in the brain due to neurotransmitters and ion channels, fluctuations in ion concentration, variations in cell surface receptors, and the presence of inflammation. […] The role of inflammation in epileptic seizure and epilepsy. […] Inflammation indeed plays a significant role in the progression of epileptogenesis. […] The release of cytokines, chemokines, lipid mediators, and protectins into the neuronal environment indicates that brain trauma has caused an organized cascade of biological processes.
  • #38 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    The disruption of the circuitry connecting the thalamus and the cerebral cortex constitutes the driving mechanism behind absence epilepsy. […] The hippocampus that works in memory and spatial navigation also has complicated connections with the cortex that contribute to brain activity regulation. […] Epigenetic mechanisms that are not linked to changes in DNA sequence but rather to transcription or post-transcriptional regulation can play a role in epileptogenesis.
  • #39 Glycaemic Imbalances in Seizures and Epilepsy of Paediatric Age: A Literature Review
    https://www.mdpi.com/2077-0383/12/7/2580
    Cerebral excitability and systemic metabolic balance are closely interconnected. Energy supply to neurons depends critically on glucose, whose fluctuations can promote immediate hyperexcitability resulting in acute symptomatic seizures. […] In epilepsy, there is a derailment of glucose catabolic pathways. Seizures greatly enhance the cerebral metabolic rate, increasing oxygen consumption, cerebral blood flow, and glucose uptake by neurons. Glucose metabolism is acutely shifted towards glycolysis and lactate production (ictal hypermetabolism), followed by a postictal decrease below baseline (postictal hypometabolism). […] On the other side, the disruption of mitochondrial oxphos could be involved in epileptogenesis. Experimental oxphos inhibition results in the destabilization of hippocampal membrane potentials and provokes epileptiform activity in initially healthy male rats.
  • #40 Glycaemic Imbalances in Seizures and Epilepsy of Paediatric Age: A Literature Review
    https://www.mdpi.com/2077-0383/12/7/2580
    Hyperglycaemia can directly increase neuronal excitability acting on the ATP-sensitive potassium channels of hippocampal and neocortical neurons; hypoglycaemia depresses GABA levels enhancing excitatory transmission. […] Seizures usually improve with the control of glycaemic status in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), whereas fluctuations in blood glucose have been associated with drug-resistant epilepsy. […] The interplay between blood sugar levels and susceptibility to seizures is especially complex. […] The characteristics of hypoglycaemia-provoked epilepsy have been especially described in low-income countries, wherein hypoglycaemia is not rare due to the limited availability of routine blood glucose monitoring at birth. […] The role of DKA in seizure development is conflicting and not completely clear.
  • #41
    https://journals.lww.com/nrronline/fulltext/2013/08140/glycolysis_in_energy_metabolism_during_seizures_.8.aspx
    Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. […] The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter -aminobutyric acid, and changes in the intra- and extracellular environment. […] Glycolysis, an important in vivo bypass for energy supply, can relieve the energy shortage caused by the energy damage of aerobic metabolism. The glycolytic metabolite lactic acid is involved in seizure onset and provides energy in the early periods of the seizure. As seizures progress, lactic acid can terminate the seizures.
  • #42 Pathogenetic and etiologic considerations of febrile seizures
    https://e-cep.org/journal/view.php?number=20125555595
    Febrile seizure (FS), which occurs in febrile children without underlying health problems, is the most common type of seizure disorder in children. The suggested pathogenesis of FS derived from several animal and human studies is multifactorial and debatable. Neuronal hyperexcitability, which develops during inflammatory responses that accompany fever, provokes seizures. However, the exact role of each inflammatory mediator (e.g., cytokines) is undefined in terms of the connection between systemic or local inflammation and the central nervous system, and the mechanisms by which cytokines increase neuronal excitability remain unclear. […] In the vulnerable immature CNS, increased neuronal excitability promotes seizures, and cytokines produced and released during acute inflammatory responses accompanying fever play a role in increasing neuronal excitability. Inflammatory responses outside the CNS increase cytokine concentrations in the CNS (neuro-immune network), and the released cytokines trigger neuronal hyperexcitability in the CNS (cytokine roles in the brain parenchyma) to generate FS. This concept can be applied to the generation of afebrile seizures or epilepsy accompanied by various types of inflammation with non-infectious causes, including trauma, toxic injury, hypoxic injury, and autoimmune reactions. […] The pathogenesis of FS is multifactorial and heterogeneous. There are no consistent and definite results regarding the connection between systemic or local inflammation and the CNS or on the mechanisms for increasing neuronal excitability in the CNS during fever.
  • #43 Pathogenetic and etiologic considerations of febrile seizures
    https://e-cep.org/journal/view.php?number=20125555595
    Febrile seizure (FS), which occurs in febrile children without underlying health problems, is the most common type of seizure disorder in children. The suggested pathogenesis of FS derived from several animal and human studies is multifactorial and debatable. Neuronal hyperexcitability, which develops during inflammatory responses that accompany fever, provokes seizures. However, the exact role of each inflammatory mediator (e.g., cytokines) is undefined in terms of the connection between systemic or local inflammation and the central nervous system, and the mechanisms by which cytokines increase neuronal excitability remain unclear. […] In the vulnerable immature CNS, increased neuronal excitability promotes seizures, and cytokines produced and released during acute inflammatory responses accompanying fever play a role in increasing neuronal excitability. Inflammatory responses outside the CNS increase cytokine concentrations in the CNS (neuro-immune network), and the released cytokines trigger neuronal hyperexcitability in the CNS (cytokine roles in the brain parenchyma) to generate FS. This concept can be applied to the generation of afebrile seizures or epilepsy accompanied by various types of inflammation with non-infectious causes, including trauma, toxic injury, hypoxic injury, and autoimmune reactions. […] The pathogenesis of FS is multifactorial and heterogeneous. There are no consistent and definite results regarding the connection between systemic or local inflammation and the CNS or on the mechanisms for increasing neuronal excitability in the CNS during fever.
  • #44 Pathogenesis of seizures and epilepsy after stroke | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-021-00068-8
    Stroke is the most frequent cause of secondary epilepsy in the elderly. […] The occurrence of epilepsy is closely related to the type and location of stroke. […] The exact pathophysiologic mechanism has not yet formed a unified conclusion. It has been found that ion channels, neurotransmitters, proliferation of glial cells, genetics and other factors are involved in the occurrence and development of PSE. […] The early-onset epileptic seizures can also be caused by the disruption of the dynamic balance of neurotransmitters. […] The increased NO can increase the excitability of the CNS by blocking the M-type K+ channels, causing epileptic seizures. […] In conclusion, in the early stage of acute stroke, the high serum level of cortisol is an important contributor to the onset of convulsion.
  • #45 Pathogenesis of seizures and epilepsy after stroke | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-021-00068-8
    Studies have shown that hemosiderin deposition is closely related to the occurrence of early epileptic seizures after subarachnoid hemorrhage. […] The increase of glutamate and the decrease of GABA result in increased excitability of neurons and decreased threshold of seizures, leading to increased susceptibility to seizures. […] BBB injury causes a flow of a large amount of blood-derived fluid to the extravascular space. […] The increased expression of NMDAR can promote the formation of axons and the formation of new synapses. […] The pathogenesis of epilepsy after stroke has been studied in depth, with some mechanisms confirmed while others being new hypotheses that awaits confirmation. […] It is important to investigate the new brain network structure in patients with epilepsy after stroke to determine whether there is a new fixed epileptogenic network.
  • #46
    https://link.springer.com/article/10.1007/s11071-022-07577-2
    Epilepsy is the second largest neurological disease which seriously threatens human life and health. The one important reason of inducing epileptic seizures is ischemic stroke which causes insufficient oxygen supply from blood vessels to neurons. […] To explore the mechanism, this paper establishes a coupled network model consisting of neurons and astrocytes, and introduces a blood vessel to simulate the condition of ischemic stroke. First, we study the effect of the degree of vascular blockage on the generation of epileptic seizures. The results demonstrate that the important reason of epileptic seizures after ischemic stroke is the disruption of ion concentration gradient. […] Then, we study three factors that influence the epileptic seizures propagation after ischemic stroke: massive glutamate release, excessive receptor activation and high extracellular potassium concentration. The results demonstrate that massive glutamate acting on postsynaptic neurons and the excessive activation of glutamate receptors on postsynaptic neurons promote the epileptic seizures propagation in neuronal population, and massive glutamate acting on astrocytes and excessive activation of metabotropic glutamate receptors on presynaptic neurons inhibit the epileptic seizures propagation, and the potassium uptake by astrocytes suppresses the epileptic seizures propagation. […] Our results on the generation and propagation of epileptic seizures after ischemic stroke could offer theoretical guidelines for the treatment of epileptic seizures after ischemic stroke.
  • #47 A large-scale brain network mechanism for increased seizure propensity in Alzheimer’s disease | PLOS Computational Biology
    https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009252
    People with Alzheimers disease (AD) are 6-10 times more likely to develop seizures than the healthy aging population. […] However, in the general population of people with epilepsy, large-scale brain network organization additionally plays a role in determining seizure likelihood and phenotype. Here, we propose that alterations to large-scale brain network organization seen in AD may contribute to increased seizure likelihood. […] As cortical tissue excitability was increased in the simulations, AD simulations were more likely to transition into seizures than simulations from healthy controls, suggesting an increased group-level probability of developing seizures at a future time for AD participants. […] We found the most important regions for seizure generation were those typically burdened by amyloid-beta at the early stages of AD, as previously reported by in-vivo and post-mortem staging of amyloid plaques.
  • #48 A large-scale brain network mechanism for increased seizure propensity in Alzheimer’s disease | PLOS Computational Biology
    https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009252
    This research suggests avenues for future studies testing patients with seizures, e.g. co-morbid AD/epilepsy patients, and comparisons with PET and MRI scans to relate regional seizure propensity with AD pathologies. […] A leading hypothesis for hyperexcitability in AD is that A deposition leads to neurodegeneration and abnormal hyperactivity including seizures, which in turn result in increased amyloid burden, leading to a self-amplifying neurodegenerative cascade. […] Understanding seizures in AD is crucial for developing novel treatments and a fuller understanding of both disorders, since the rate of occurrence of seizures are believed to be positively correlated with the rate of cognitive decline in AD. […] While these hypotheses potentially explain increased excitability of local tissue in AD, evidence suggests the propensity of a brain to generate seizures is not only a result of local network excitability, but is also related to its large-scale functional network structure.
  • #49 A Large-Scale Brain Network Mechanism for Increased Seizure Propensity in Alzheimer’s Disease | bioRxiv
    https://www.biorxiv.org/content/10.1101/2021.01.19.427236v1
    People with Alzheimer’s disease (AD) are 6-10 times more likely to develop seizures than the healthy aging population. […] However, both local dynamics and large-scale brain network structure are believed to be crucial for determining seizure likelihood and phenotype. […] In this study, we combine computational modelling with electrophysiological data to demonstrate a potential large-scale brain network mechanism for increased seizure propensity in people with AD. […] As cortical tissue excitability was increased in the simulations, network models of AD simulations were more likely to transition into seizures than simulations from healthy controls. […] Our results suggest an increased group-level probability of developing seizures at a future time for AD participants. […] We found the most important regions for seizure generation were those typically burdened by amyloid-beta at the early stages of AD, as previously reported by in-vivo and post-mortem staging of amyloid plaques. […] Our results also provide a potential explanation for why people with AD are more likely to have generalized seizures (i.e. seizures involving the whole brain, as opposed to ‘focal’ seizures which only involve certain areas) than the general population with epilepsy.
  • #50 A large-scale brain network mechanism for increased seizure propensity in Alzheimer’s disease | PLOS Computational Biology
    https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009252
    A key result of our study is that previously reported alterations to functional connectivity in AD result in brain networks which more readily generate seizures in response to increased cortical excitability than cognitively healthy controls. […] This hyperactivity mediates an increase in A and tau burden, which in turn may amplify excitability. […] Our findings suggest that ictogenicity is more homogeneously distributed across the cortex in people with AD than controls, which in turn may imply that people with AD are more susceptible to generalized seizures than controls.
  • #51 A large-scale brain network mechanism for increased seizure propensity in Alzheimer’s disease | PLOS Computational Biology
    https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009252&rev=1
    While these hypotheses potentially explain increased excitability of local tissue in AD, evidence suggests the propensity of a brain to generate seizures is not only a result of local network excitability, but is also related to its large-scale functional network structure. […] It is therefore possible that altered long-range functional connectivity in AD may contribute to increased susceptibility to seizures and, under the hypothesis of cyclical amplification of AD pathology and local excitability, facilitate the spread of pathological cortical hyperexcitability. […] A key result of our study is that previously reported alterations to functional connectivity in AD result in brain networks which more readily generate seizures in response to increased cortical excitability than cognitively healthy controls.
  • #52 Seizures in patients with primary and metastatic brain tumors – UpToDate
    https://www.uptodate.com/contents/seizures-in-patients-with-primary-and-metastatic-brain-tumors
    Seizures are a common and potentially devastating complication of both primary and metastatic brain tumors. Such seizures are focal in origin and may either remain focal or secondarily generalize. The etiology, epidemiology, evaluation, and treatment of seizures and the limited role of prophylactic antiseizure therapy in patients with brain tumors will be reviewed here. […] Brain tumors and metastases can cause seizures by a variety of mechanisms; alterations in excitatory neurotransmission and extracellular ion currents are considered the most likely. Other potential mechanisms include hypoxia, acidosis, inflammation, mechanical effects, and disruption of local homeostasis with changes in electrolytes, perfusion, and metabolism. […] Seizures may also be caused by factors other than metastases in patients with tumors arising outside the central nervous system. Examples of potential seizure etiologies that are more common in patients with cancer compared with the general population include metabolic encephalopathies such as hyponatremia or hypoglycemia, opportunistic infections, or side effects of therapy. Paraneoplastic encephalitis is another potential cause of seizures and altered mental status in patients with systemic cancer.
  • #53 Seizures in brain tumors: pathogenesis, risk factors and management (Review)
    https://www.spandidos-publications.com/10.3892/ijmm.2025.5523/abstract
    Seizures in the context of brain tumors are a relatively common symptom, with higher occurrence rates observed in glioneuronal tumors and gliomas. […] Brain tumorrelated epilepsy (BTRE) is a challenging entity because the pathophysiological mechanisms are not fully understood yet. Nonetheless, neuroinflammation is considered to play a pivotal role. Next to neuroinflammation, findings on the pathogenesis of BTRE have established that certain genetic mutations are involved, of which the most known would be IDH mutations in gliomas. Others discussed more thoroughly in the present review include genes such as PTEN, TP53, IGSF3, and these findings all provide fresh and fascinating insights into the pathogenesis of BTRE. […] The present review summarizes and retrospectively analyzes the literature on the pathogenesis and management of BTRE to provide an updated comprehensive understanding.
  • #54
    https://journals.lww.com/nrronline/fulltext/2013/08140/glycolysis_in_energy_metabolism_during_seizures_.8.aspx
    The main mechanisms of seizure termination include energy consumption and metabolic acidosis. Lactic acid induces acidosis by several possible pathways: lactic acid inhibits the activity of 6 diphosphate kinase-1 and N-methyl-D-aspartate receptors, activates the acid-sensitive 1A ion channel, and strengthens the receptive mechanism of the inhibitory neurotransmitter -aminobutyric acid. […] The energy depletion hypothesis is based on the fact that neurons abnormally discharge during seizures, resulting in energy depletion, which may lead to termination of seizures. […] Metabolic acidosis may be another mechanism by which seizures are terminated. During the epileptic discharge process, the accumulation of various metabolites that are generated by neuron misfiring during seizures leads to acidosis, and this may be involved in the process of seizure termination. Anaerobic glycolysis is known to increase seizures, and its metabolite lactic acid terminates seizures.
  • #55
    https://journals.lww.com/nrronline/fulltext/2013/08140/glycolysis_in_energy_metabolism_during_seizures_.8.aspx
    The main mechanisms of seizure termination include energy consumption and metabolic acidosis. Lactic acid induces acidosis by several possible pathways: lactic acid inhibits the activity of 6 diphosphate kinase-1 and N-methyl-D-aspartate receptors, activates the acid-sensitive 1A ion channel, and strengthens the receptive mechanism of the inhibitory neurotransmitter -aminobutyric acid. […] The energy depletion hypothesis is based on the fact that neurons abnormally discharge during seizures, resulting in energy depletion, which may lead to termination of seizures. […] Metabolic acidosis may be another mechanism by which seizures are terminated. During the epileptic discharge process, the accumulation of various metabolites that are generated by neuron misfiring during seizures leads to acidosis, and this may be involved in the process of seizure termination. Anaerobic glycolysis is known to increase seizures, and its metabolite lactic acid terminates seizures.
  • #56
    https://journals.lww.com/nrronline/fulltext/2013/08140/glycolysis_in_energy_metabolism_during_seizures_.8.aspx
    The main mechanisms of seizure termination include energy consumption and metabolic acidosis. Lactic acid induces acidosis by several possible pathways: lactic acid inhibits the activity of 6 diphosphate kinase-1 and N-methyl-D-aspartate receptors, activates the acid-sensitive 1A ion channel, and strengthens the receptive mechanism of the inhibitory neurotransmitter -aminobutyric acid. […] The energy depletion hypothesis is based on the fact that neurons abnormally discharge during seizures, resulting in energy depletion, which may lead to termination of seizures. […] Metabolic acidosis may be another mechanism by which seizures are terminated. During the epileptic discharge process, the accumulation of various metabolites that are generated by neuron misfiring during seizures leads to acidosis, and this may be involved in the process of seizure termination. Anaerobic glycolysis is known to increase seizures, and its metabolite lactic acid terminates seizures.
  • #57
    https://journals.lww.com/nrronline/fulltext/2013/08140/glycolysis_in_energy_metabolism_during_seizures_.8.aspx
    Glycolysis produces large amounts of lactic acid, causing the pH to decrease, resulting in extracellular acidosis. […] Studies show that lowering the pH to 6.7 by either means increases the interval between seizure-like events, and acidification slows the rate of seizure propagation in [Mg2+ ]-induced epileptiform bursting in hippocampal slices and entorhinal cortex preparation, which is presumably by activation of N-methyl-D-aspartate receptors, which show blockade of N-methyl-D-aspartate currents by protons. […] Lactic acid brings about an increase in H+ ions in the extracellular environment and a reduction of pH, which leads to acidosis. Furthermore, the reduction in pH can also inhibit voltage-gated Na+ and Ca2+ channels, thereby suppressing seizures.
  • #58 Mechanism of Seizure Termination | Pediatric Neurology Briefs
    https://pediatricneurologybriefs.com/articles/10.15844/pedneurbriefs-22-10-4
    Physiological mechanisms contributing to seizure termination and organized according to membranes, synapses, networks, and circuits are reviewed by researchers from Albert Einstein College of Medicine, and Montefiore Medical Center, Bronx, New York. […] A better understanding of these mechanisms may lead to novel anticonvulsant therapies. Agents that enhance termination of paroxysmal depolarizing shifts might decrease excitatory amplification in epileptic neurons. […] Modification of extracellular environment or intracellular ion gradients across membranes may raise seizure threshold and speed seizure termination (Ochoa, 2006). […] Disrupting gap junction connections between neurons and intemeurons may reduce neuronal synchrony. […] Drugs targeting the GABA receptor to enhance local inhibition without increasing sedation or tachyphylaxis would provide an improvement over benzodiazepines that are of value mainly in acute seizure control.
  • #59 Mechanism of Seizure Termination | Pediatric Neurology Briefs
    https://pediatricneurologybriefs.com/articles/10.15844/pedneurbriefs-22-10-4
    Drugs that alter chloride transporters and gradients might control age-dependent seizure syndromes. (Dzhala et al, 2005). […] Drugs targeting adenosine kinase, and endocannibanoid and NPY receptors, and altering the hormonal milieu may enhance seizure control and termination. […] Vagal nerve stimulation (Blount JP et al. 2006), initiated by a patient, will halt seizure activity and may be extended to seizure modifying circuits such as the anterior thalamus, substantia nigra pars reticulata and subthalamic nucleus. […] COMMENT. Factors influencing seizure termination are less well understood than those responsible for seizure initiation, propagation and recurrence. […] Several factors may be responsible for seizure initiation and termination, and these mechanisms may be modified by age, sex, fever and infection, structural brain injury, and genetics.
  • #60 Mechanism of Seizure Termination | Pediatric Neurology Briefs
    https://pediatricneurologybriefs.com/articles/10.15844/pedneurbriefs-22-10-4
    Drugs that alter chloride transporters and gradients might control age-dependent seizure syndromes. (Dzhala et al, 2005). […] Drugs targeting adenosine kinase, and endocannibanoid and NPY receptors, and altering the hormonal milieu may enhance seizure control and termination. […] Vagal nerve stimulation (Blount JP et al. 2006), initiated by a patient, will halt seizure activity and may be extended to seizure modifying circuits such as the anterior thalamus, substantia nigra pars reticulata and subthalamic nucleus. […] COMMENT. Factors influencing seizure termination are less well understood than those responsible for seizure initiation, propagation and recurrence. […] Several factors may be responsible for seizure initiation and termination, and these mechanisms may be modified by age, sex, fever and infection, structural brain injury, and genetics.
  • #61 [2504.01887] Dual mechanism of Anti-Seizure Medications in controlling seizure activity
    http://arxiv.org/abs/2504.01887
    Prolongation of existing seizure patterns – Even in seizures without taper-emergent states, lower ASM levels still resulted in approx. 12-224% longer durations depending on the ASM dosage and tapering ($\beta$ = -0.049, p 0.001). […] ASMs influence seizures through two mechanisms: they (i) suppress specific seizure activity patterns (states) in an all-or-nothing fashion and (ii) curtail the duration of other seizure patterns. […] These findings highlight the complex role of ASMs in seizure modulation and could inform personalized dosing strategies for epilepsy management.
  • #62 Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers
    https://emedicine.medscape.com/article/1187334-overview
    Modern treatment of seizures started in 1850 with the introduction of bromides, which was based on the theory that epilepsy was caused by an excessive sex drive. […] In 1940, phenytoin (PHT) was found to be an effective drug for the treatment of epilepsy, and since then it has become a major first-line antiepileptic drug (AED) in the treatment of partial and secondarily generalized seizures. […] The AEDs are designed to modify these processes so as to favor inhibition over excitation and thereby stop or prevent seizure activity. […] The AEDs can be grouped according to their main mechanism of action, although many of them have several actions and others have unknown mechanisms of action. […] AEDs that target the sodium channels prevent the return of these channels to the active state by stabilizing them in the inactive state. In doing so, they prevent repetitive firing of the axons.
  • #63 Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers
    https://emedicine.medscape.com/article/1187334-overview
    Modern treatment of seizures started in 1850 with the introduction of bromides, which was based on the theory that epilepsy was caused by an excessive sex drive. […] In 1940, phenytoin (PHT) was found to be an effective drug for the treatment of epilepsy, and since then it has become a major first-line antiepileptic drug (AED) in the treatment of partial and secondarily generalized seizures. […] The AEDs are designed to modify these processes so as to favor inhibition over excitation and thereby stop or prevent seizure activity. […] The AEDs can be grouped according to their main mechanism of action, although many of them have several actions and others have unknown mechanisms of action. […] AEDs that target the sodium channels prevent the return of these channels to the active state by stabilizing them in the inactive state. In doing so, they prevent repetitive firing of the axons.
  • #64 Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers
    https://emedicine.medscape.com/article/1187334-overview
    Calcium channels function as the „pacemakers” of normal rhythmic brain activity. This is particularly true of the thalamus. T-calcium channels have been known to play a role in the 3 per second spike-and-wave discharges of absence seizures. AEDs that inhibit these T-calcium channels are particularly useful for controlling absence seizures. […] The GABA system can be enhanced by binding directly to GABA-A receptors, by blocking presynaptic GABA uptake, by inhibiting the metabolism of GABA by GABA transaminase, and by increasing the synthesis of GABA. […] AEDs that modify these receptors are antagonistic to glutamate. […] Inhibition of the enzyme carbonic anhydrase increases the concentration of hydrogen ions intracellularly and decreases the pH. […] The role of SV2A in epilepsy is confirmed by the finding that SV2A knockout mice develop a strong seizure phenotype a few weeks after birth.
  • #65 Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers
    https://emedicine.medscape.com/article/1187334-overview
    Calcium channels function as the „pacemakers” of normal rhythmic brain activity. This is particularly true of the thalamus. T-calcium channels have been known to play a role in the 3 per second spike-and-wave discharges of absence seizures. AEDs that inhibit these T-calcium channels are particularly useful for controlling absence seizures. […] The GABA system can be enhanced by binding directly to GABA-A receptors, by blocking presynaptic GABA uptake, by inhibiting the metabolism of GABA by GABA transaminase, and by increasing the synthesis of GABA. […] AEDs that modify these receptors are antagonistic to glutamate. […] Inhibition of the enzyme carbonic anhydrase increases the concentration of hydrogen ions intracellularly and decreases the pH. […] The role of SV2A in epilepsy is confirmed by the finding that SV2A knockout mice develop a strong seizure phenotype a few weeks after birth.
  • #66 Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers
    https://emedicine.medscape.com/article/1187334-overview
    Calcium channels function as the „pacemakers” of normal rhythmic brain activity. This is particularly true of the thalamus. T-calcium channels have been known to play a role in the 3 per second spike-and-wave discharges of absence seizures. AEDs that inhibit these T-calcium channels are particularly useful for controlling absence seizures. […] The GABA system can be enhanced by binding directly to GABA-A receptors, by blocking presynaptic GABA uptake, by inhibiting the metabolism of GABA by GABA transaminase, and by increasing the synthesis of GABA. […] AEDs that modify these receptors are antagonistic to glutamate. […] Inhibition of the enzyme carbonic anhydrase increases the concentration of hydrogen ions intracellularly and decreases the pH. […] The role of SV2A in epilepsy is confirmed by the finding that SV2A knockout mice develop a strong seizure phenotype a few weeks after birth.
  • #67 Cenobamate for Drug-Resistant Epilepsy May Reduce Seizures, Improve Retention – Neurology Advisor
    https://www.neurologyadvisor.com/news/cenobamate-drug-resistant-epilepsy-reduce-seizures-improve-retention/
    After 3 months on cenobamate maintenance therapy, 49.3% of patients achieved at least a 50% reduction in seizure frequency. […] Cenobamate, a recently approved ASM with dual mechanisms, positive GABA-A modulation and sodium channel inhibition, was evaluated as an adjunctive treatment in adults with uncontrolled focal-onset seizures (FOS). […] Our study evidenced that CNB can be considered generally well tolerated and effective in highly refractory focal or combined generalized and focal epilepsy. […] After 3 months on cenobamate maintenance therapy, 49.3% of patients achieved the primary endpoint of at least a 50% reduction in seizure frequency. […] Complete seizure freedom was achieved in 13.6% of patients at the 3-month mark, increasing to 24.2% at 6 months and 45% at 12 months. […] Our study evidenced that CNB [cenobamate] can be considered generally well tolerated and effective in highly refractory focal or combined generalized and focal epilepsy, the researchers concluded.
  • #68 A mechanism underlying most common cause of epileptic seizures revealed | EurekAlert!
    https://www.eurekalert.org/news-releases/926530
    An interdisciplinary study shows that neurons carrying somatic mutations in MTOR can lead to focal epileptogenesis via non-cell-autonomous hyperexcitability of nearby nonmutated neurons. […] This condition is the most common cause of seizures that cannot be controlled with medication in children and the second most common cause in adults. […] Only 1 to 2% of neurons carrying mutations in the mTOR signaling pathway that regulates cell signaling in the brain have been found to include seizures in animal models of focal cortical dysplasia, said Professor Jong-Woo Sohn from the Department of Biological Sciences. […] Seizures are a result of extreme activity, called hyperexcitability. […] The seizure-triggering hyperexcitability originated not in the mutation-carrying neurons, but instead in the nearby non-mutated neurons, he said. […] With less adenosine, the non-mutated neurons became hyperexcitable, leading to seizures. […] our results support the medical use of drugs to activate adenosine signaling as a possible treatment pathway for focal cortical dysplasia, Professor Lee said.
  • #69 A mechanism underlying most common cause of epileptic seizures revealed | ScienceDaily
    https://www.sciencedaily.com/releases/2021/08/210826111711.htm
    „The seizure-triggering hyperexcitability originated not in the mutation-carrying neurons, but instead in the nearby non-mutated neurons,” he said. […] The mutated neurons excreted more adenosine kinase, reducing the adenosine levels in the local environment of all the cells. With less adenosine, the non-mutated neurons became hyperexcitable, leading to seizures. […] „While we need further investigate into the relationship between the concentration of adenosine and the increased excitation of nearby neurons, our results support the medical use of drugs to activate adenosine signaling as a possible treatment pathway for focal cortical dysplasia,” Professor Lee said.
  • #70 Study Reveals How Cannabidiol Counters Epileptic Seizures | NYU Langone News
    https://nyulangone.org/news/study-reveals-how-cannabidiol-counters-epileptic-seizures
    A study reveals a previously unknown way in which cannabidiol (CBD), a substance found in cannabis, reduces seizures in many treatment-resistant forms of pediatric epilepsy. […] The current findings argue for the first time that LPI also weakens signals that counter seizures, further explaining the value of CBD treatment. […] Our results deepen the fields understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches, says corresponding author Richard W. Tsien, PhD, chair of the Department of Physiology and Neuroscience at NYU Langone Health. […] The authors propose that CBD blocks a positive feedback loop in which seizures increase LPIGPR55 signaling, which likely encourages more seizures, which in turn increases levels of both LPI and GPR55. The proposed vicious cycle provides one process that could explain repeated epileptic seizures, although future studies are needed to confirm this. […] LPI could also serve as a biomarker of seizures or predictor of clinical responsiveness to CBD, providing an area of future research.
  • #71 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text
    https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0
    Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. […] Epileptogenesis triggers molecular changes in hippocampus, including altered neurogenesis and enhanced expression of neurotrophic factors and proteins. […] Oxidative stress leads to cellular damage, disrupted antioxidant systems, and mitochondrial dysfunction, making it a key player in epileptogenesis and potential neuroprotective interventions. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells.
  • #72 Epilepsy and Seizures: Practice Essentials, Background, Pathophysiology
    https://emedicine.medscape.com/article/1184846-overview
    Several factors may be associated with the transition from an interictal spike to an epileptic seizure. The spike has to recruit more neural tissue to become a seizure. When any of the mechanisms that underlie an acute seizure becomes a permanent alteration, the person presumably develops a propensity for recurrent seizures (ie, epilepsy). […] The following mechanisms (discussed below) may coexist in different combinations to cause focal-onset seizures: Decreased inhibition, Defective activation of gamma-aminobutyric acid (GABA) neurons, Increased activation. […] If the mechanisms leading to a net increased excitability become permanent alterations, patients may develop pharmacologically intractable focal-onset epilepsy. […] The best-understood example of the pathophysiologic mechanisms of generalized seizures is the thalamocortical interaction that may underlie typical absence seizures. The thalamocortical circuit has normal oscillatory rhythms, with periods of relatively increased excitation and periods of relatively increased inhibition. It generates the oscillations observed in sleep spindles. […] Altered thalamocortical rhythms may result in primary generalized-onset seizures.

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