Epileptogenezis ve Epilepsinin Patofizyolojisi
Özet
Epilepsi en az bir epilepsi nöbeti varlığına ek olarak tekrarlayan nöbetleri oluşturmaya yatkın bir durum olarak ele alinir. Epileptogenez ise normal bir beynin epileptik nöbete duyarlı, spontan tekrarlayan nöbetler oluşturabilecek bir beyne dönüşmesi sürecine denir. Nöronal uyarılabilirliği aşamalı olarak değiştiren, önemli bağlantılar kuran ve belki de ilk spontan nöbet ortaya çıkmadan önce karmaşık yapısal değişiklikler gerektiren dinamik bir süreci ifade eder. Epilepsinin patofizyolojisi ve nedenleri henuz tam olarak aydinlatilamamistir. Epilepsinin değişik tiplerinin altında yatan ortak mekanizma eksitatör ve inhibitör nörotransmisyon dengesinin disregülasyonu ve bir grup nöronun nöronal uyarılabilirliğinin sürekli olarak artmasıdır. Epileptogenez ile ilgili çalışmalar ve bu konunun daha çok aydınlatılması özellikle dirençli epilepsilerde tedavi olasılığı açısından çok önemlidir. Ayrıca, nöbetler başlamadan önleyici tedavi seçeneklerinin geliştirilmesini de gündeme getirebilir. Bu bolumde epileptogenez mekanizmalari tartisilacaktir.
Epilepsy is a condition characterized by the presence of at least one epileptic seizure and a predisposition to recurrent seizures. Epileptogenesis is the process by which a normal brain is transformed into a brain susceptible to epileptic seizures and capable of producing spontaneous recurrent seizures. It refers to a dynamic process that progressively alters neuronal excitability, establishes important connections and requires complex structural changes, perhaps before the first spontaneous seizure occurs. The pathophysiology and causes of epilepsy have not yet been fully elucidated. The common mechanism underlying the different types of epilepsy is the dysregulation of the balance of excitatory and inhibitory neurotransmission and the continuous increase in neuronal excitability of a group of neurons. Studies on epileptogenesis and further elucidation of this issue are very important, especially in terms of the possibility of treatment in refractory epilepsies. It may also bring up the development of preventive treatment options before the onset of seizures. In this section, the mechanisms of epileptogenesis will be discussed.
Referanslar
Magiorkinis E, Sidiropoulou K, Diamantis A. Hallmarks in the history of epilepsy: epilepsy in antiquitiy. Epilepsy Behav.2010 Jan;17 (1):103-8.
Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014; 55:475–82.
Asla Pitkänen, Katarzyna Lukasiuk. Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol 2011; 10: 173–86.
Shellhaas RA, Glass HC, Chang T. Neonatal Seizures. In; Swaiman KF, Ashwal S, Ferriero DM, Schor NF, Finkel RS, Gropman AL, eds. Swaiman's Pediatric Neurology principles and practice (6th ed) Elsevier, Printed in China. 2017.p.129-37.
Pitkänen A, Engel J Jr. Past and present definitions of epileptogenesis and its biomarkers. Neurotherapeutics. (2014) 11:231–41.
Asla Pitkänen, Katarzyna Lukasiuk. Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol 2011; 10: 173–86.
Zara F, Bianchi A. The impact of genetics on the classifi cation of epilepsy syndromes. Epilepsia 2009; 50 (suppl 5): 11–14.
Engel J Jr, Pedley TA. What is epilepsy? In: Epilepsy: A comprehensive textbook. Philadelphia: Lippincott-Raven, 2005: 1–11.
Cayo Almeida , Renan Paschoalino Pongilio , Marília Inês Móvio et al. Distinct Cell-specific Roles of NOX2 and MyD88 in Epileptogenesis. Volume 10 – 2022 04 July 2022.
Sanjay N. Rakhade and Frances E. Jensen. Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol. 2009 July ; 5(7): 380.
Blair RE, Sombati S, Lawrence DC, Mc Cay BD, De Lorenzo RJ. Epileptogenesis causes acute and chronic increases in GABAA receptor endocytosis that contributes to the induction and maintenance of seizures in the hippocampal culture model of acquired epilepsy. J. Pharmacol, Exp. Ther. 2004;310: 871-80.
Dube C, Vezzani A, Behrens M, Bartfai T, Baram Tz. Interleukin-1β contributes to the generation of experimental febrile seizures. Ann. Neurol. 2005;57:152-5.
Shapiro LA, Wang L, Ribak CE. Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia. 2008;49(2):33-41.
Anna-Maria Katsarou, Aristea S. Galanopoulou, and Solomon L. Moshé. Epileptogenesis in neonatal brain. Semin Fetal Neonatal Med. 2018 June ; 23(3): 159–167.
Simeone TA, Sanchez RM, Rho JM. Molecular biology and ontogeny of glutamate receptors in the mammalian center nervous system. J Child Neurol. 2004 May;19(5):343-60.
Lukasiuk K, Pitkänen A. Seizure-induced gene expression. In: Encyclopedia of basic epilepsy research. Oxford: Academic Press, 2009: 1302–09.
Gaetano Terrone, Alberto Pauletti , Rosaria Pascente et al. Preventing epileptogenesis: A realistic goal? Pharmacological research. 110(2016) 96-100.
Erkan Aksöz. Nöroinflamasyonun Epileptogenezdeki Rolü ve Antiepileptojenik Tedavide Nöroinflamasyona Yönelik Hedefler. Sdü Sağlık Bilimleri Enstitüsü Dergisİ. Cilt 9 Sayı 2 / 2018.
Ekici A. Epilepsinin patofizyolojisi. Kumandaş S, Canpolat M, editörler. Çocukluk Çağı Epilepsileri. 1. Baskı. Ankara: Türkiye Klinikleri; 2020. p.8-14
Aronica E, Bauer S, Bozzi Y, Caleo M, Dingledine R, Gorter JA, et al. Neuroinflammatory targets and treatments for epilepsy validated in experimental models. Epilepsia. 2017; 58: 27-38.
Ostendorf AP, Wong M. mTOR inhibition in epilepsy: rationale and clinical perspectives. CNS Drugs. 2015;29(2):91-9.
Aroniadou-Anderjaska v, Fritsch B, Qashu F, Braga MF. Pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy. Epilepsy Res. 2008;78(2-3):102-16.
Henshall DC, Engel T. Contribution of apoptosis-associated signaling pathways to epileptogenesis: lessons from Bcl-2 family knockouts. Front Cell Neurosci. 2013;7: 110.
Parent JM. The role of seizure-induced neurogenesis in epileptogenesis and brain repair. Epilepsy Res. 2002;50(1-2):179-89.
Lukasiuk K, Dabrowski M, Adach A, et al. Epileptogenesis-related genes revisited.Prog Brain Res 2006;158:223-41.
Robel S Susan C Buckingham, Jessica L Boni et al. Reactive astrogliosis causes the development of spontaneous seizures. J. Neurosci 35, 3330–3345 (2015).
Uhlmann EJ et al. Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann. Neurol 52, 285–296 (2002).
Thomas Sutula. Seizure-Induced Axonal Sprouting: Assessing Connections Between Injury, Local Circuits, and Epileptogenesis. Epilepsy Curr. 2002;2(3):86-91.
Baker AJ, Phan N, Moulton RJ, et al. Attenuation of the electrophysiological function of the corpus callosum after fluid percussion injury in the rat. J Neurotrauma. 2002;19:587-99.
Gall CM, Lynch G. Integrins, synaptic plasticity and epileptogenesis. Adv Exp Med Biol. 2004;548:12-33.
Van vliet EA, da Costa Araújo S, Redeker S, van Schaik R, Aronica E, Gorter JA. Blood–brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain. 2007;130: 521-34.
Dityatev A. Remodeling of extracellular matrix and epileptogenesis. Epilepsia. 2010;51:61-5.
Lapo Bonosi, Umberto Emanuele Benigno, Sofia Musso et al. The Role of Aquaporins in Epileptogenesis—A Systematic Review. Int J Mol Sci. 2023 Jul 25;24(15):11923.
Iori v, Iyer AM, Ravizza T, Beltrame L, Paracchini L, Marchini S, et al. Blockade of the IL1R1/TLR4 pathway mediates disease modification therapeutic effects in a model of acquired epilepsy. Neurobiol Dis. 2017;99:12- 23.
Schutte SS, Schutte RJ, Barragan Ev, O'- Dowd DK. Model systems for studying cellular mechanisms of SCN1A-related epilepsy. J Neurophysiol. 2016;115(4):1755-66.
Gary Jean , Joseph Carton , Kaleem Haq et al. Front. Cell. Neurosci., 02 August 2023.
Galanopoulou AS. Mutations affecting GABAergic signaling in seizures and epilepsy. Pflügers Archiv. 2010; 460:505–23.
Ure J, Baudry M, Perassolo M. Metabotropic glutamate receptors and epilepsy. J Neurol Sci. 2006 Aug 15;247 (1):1-9.
Lancaster E. The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol (Seoul, Korea). 2016;12(1):1–13. 10.
Geis C, Planagumà J, Carreño M, Graus F, Dalmau J. Autoimmune seizures and epilepsy. J Clin Invest. 2019;129(3):926–40. 11.
Julia Flammer Tradite Neziraj Stephan Rüegg et al. Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes. Drugs (2023) 83:135–158.
Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010;30(17):5866–75.].
Petit-Pedrol M, Sell J, Planagumà J, Mannara F, Radosevic M, Haselmann H, et al. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain. 2018;141(11):3144–59.
Spatola M, Petit-Pedrol M, Simabukuro MM, Armangue T, Castro FJ, Barcelo Artigues MI, et al. Investigations in GABA(A) receptor antibody-associated encephalitis. Neurology. 2017;88(11):1012–20.
Referanslar
Magiorkinis E, Sidiropoulou K, Diamantis A. Hallmarks in the history of epilepsy: epilepsy in antiquitiy. Epilepsy Behav.2010 Jan;17 (1):103-8.
Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014; 55:475–82.
Asla Pitkänen, Katarzyna Lukasiuk. Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol 2011; 10: 173–86.
Shellhaas RA, Glass HC, Chang T. Neonatal Seizures. In; Swaiman KF, Ashwal S, Ferriero DM, Schor NF, Finkel RS, Gropman AL, eds. Swaiman's Pediatric Neurology principles and practice (6th ed) Elsevier, Printed in China. 2017.p.129-37.
Pitkänen A, Engel J Jr. Past and present definitions of epileptogenesis and its biomarkers. Neurotherapeutics. (2014) 11:231–41.
Asla Pitkänen, Katarzyna Lukasiuk. Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol 2011; 10: 173–86.
Zara F, Bianchi A. The impact of genetics on the classifi cation of epilepsy syndromes. Epilepsia 2009; 50 (suppl 5): 11–14.
Engel J Jr, Pedley TA. What is epilepsy? In: Epilepsy: A comprehensive textbook. Philadelphia: Lippincott-Raven, 2005: 1–11.
Cayo Almeida , Renan Paschoalino Pongilio , Marília Inês Móvio et al. Distinct Cell-specific Roles of NOX2 and MyD88 in Epileptogenesis. Volume 10 – 2022 04 July 2022.
Sanjay N. Rakhade and Frances E. Jensen. Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol. 2009 July ; 5(7): 380.
Blair RE, Sombati S, Lawrence DC, Mc Cay BD, De Lorenzo RJ. Epileptogenesis causes acute and chronic increases in GABAA receptor endocytosis that contributes to the induction and maintenance of seizures in the hippocampal culture model of acquired epilepsy. J. Pharmacol, Exp. Ther. 2004;310: 871-80.
Dube C, Vezzani A, Behrens M, Bartfai T, Baram Tz. Interleukin-1β contributes to the generation of experimental febrile seizures. Ann. Neurol. 2005;57:152-5.
Shapiro LA, Wang L, Ribak CE. Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia. 2008;49(2):33-41.
Anna-Maria Katsarou, Aristea S. Galanopoulou, and Solomon L. Moshé. Epileptogenesis in neonatal brain. Semin Fetal Neonatal Med. 2018 June ; 23(3): 159–167.
Simeone TA, Sanchez RM, Rho JM. Molecular biology and ontogeny of glutamate receptors in the mammalian center nervous system. J Child Neurol. 2004 May;19(5):343-60.
Lukasiuk K, Pitkänen A. Seizure-induced gene expression. In: Encyclopedia of basic epilepsy research. Oxford: Academic Press, 2009: 1302–09.
Gaetano Terrone, Alberto Pauletti , Rosaria Pascente et al. Preventing epileptogenesis: A realistic goal? Pharmacological research. 110(2016) 96-100.
Erkan Aksöz. Nöroinflamasyonun Epileptogenezdeki Rolü ve Antiepileptojenik Tedavide Nöroinflamasyona Yönelik Hedefler. Sdü Sağlık Bilimleri Enstitüsü Dergisİ. Cilt 9 Sayı 2 / 2018.
Ekici A. Epilepsinin patofizyolojisi. Kumandaş S, Canpolat M, editörler. Çocukluk Çağı Epilepsileri. 1. Baskı. Ankara: Türkiye Klinikleri; 2020. p.8-14
Aronica E, Bauer S, Bozzi Y, Caleo M, Dingledine R, Gorter JA, et al. Neuroinflammatory targets and treatments for epilepsy validated in experimental models. Epilepsia. 2017; 58: 27-38.
Ostendorf AP, Wong M. mTOR inhibition in epilepsy: rationale and clinical perspectives. CNS Drugs. 2015;29(2):91-9.
Aroniadou-Anderjaska v, Fritsch B, Qashu F, Braga MF. Pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy. Epilepsy Res. 2008;78(2-3):102-16.
Henshall DC, Engel T. Contribution of apoptosis-associated signaling pathways to epileptogenesis: lessons from Bcl-2 family knockouts. Front Cell Neurosci. 2013;7: 110.
Parent JM. The role of seizure-induced neurogenesis in epileptogenesis and brain repair. Epilepsy Res. 2002;50(1-2):179-89.
Lukasiuk K, Dabrowski M, Adach A, et al. Epileptogenesis-related genes revisited.Prog Brain Res 2006;158:223-41.
Robel S Susan C Buckingham, Jessica L Boni et al. Reactive astrogliosis causes the development of spontaneous seizures. J. Neurosci 35, 3330–3345 (2015).
Uhlmann EJ et al. Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann. Neurol 52, 285–296 (2002).
Thomas Sutula. Seizure-Induced Axonal Sprouting: Assessing Connections Between Injury, Local Circuits, and Epileptogenesis. Epilepsy Curr. 2002;2(3):86-91.
Baker AJ, Phan N, Moulton RJ, et al. Attenuation of the electrophysiological function of the corpus callosum after fluid percussion injury in the rat. J Neurotrauma. 2002;19:587-99.
Gall CM, Lynch G. Integrins, synaptic plasticity and epileptogenesis. Adv Exp Med Biol. 2004;548:12-33.
Van vliet EA, da Costa Araújo S, Redeker S, van Schaik R, Aronica E, Gorter JA. Blood–brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain. 2007;130: 521-34.
Dityatev A. Remodeling of extracellular matrix and epileptogenesis. Epilepsia. 2010;51:61-5.
Lapo Bonosi, Umberto Emanuele Benigno, Sofia Musso et al. The Role of Aquaporins in Epileptogenesis—A Systematic Review. Int J Mol Sci. 2023 Jul 25;24(15):11923.
Iori v, Iyer AM, Ravizza T, Beltrame L, Paracchini L, Marchini S, et al. Blockade of the IL1R1/TLR4 pathway mediates disease modification therapeutic effects in a model of acquired epilepsy. Neurobiol Dis. 2017;99:12- 23.
Schutte SS, Schutte RJ, Barragan Ev, O'- Dowd DK. Model systems for studying cellular mechanisms of SCN1A-related epilepsy. J Neurophysiol. 2016;115(4):1755-66.
Gary Jean , Joseph Carton , Kaleem Haq et al. Front. Cell. Neurosci., 02 August 2023.
Galanopoulou AS. Mutations affecting GABAergic signaling in seizures and epilepsy. Pflügers Archiv. 2010; 460:505–23.
Ure J, Baudry M, Perassolo M. Metabotropic glutamate receptors and epilepsy. J Neurol Sci. 2006 Aug 15;247 (1):1-9.
Lancaster E. The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol (Seoul, Korea). 2016;12(1):1–13. 10.
Geis C, Planagumà J, Carreño M, Graus F, Dalmau J. Autoimmune seizures and epilepsy. J Clin Invest. 2019;129(3):926–40. 11.
Julia Flammer Tradite Neziraj Stephan Rüegg et al. Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes. Drugs (2023) 83:135–158.
Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci. 2010;30(17):5866–75.].
Petit-Pedrol M, Sell J, Planagumà J, Mannara F, Radosevic M, Haselmann H, et al. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain. 2018;141(11):3144–59.
Spatola M, Petit-Pedrol M, Simabukuro MM, Armangue T, Castro FJ, Barcelo Artigues MI, et al. Investigations in GABA(A) receptor antibody-associated encephalitis. Neurology. 2017;88(11):1012–20.
