Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9534910.26442/20751753.2020.9.200273ArticlesСтатьиReview ArticlePost-stroke seizures and epilepsy after strokeЭпилептические приступы и эпилепсия у больных с инсультомMaksimovaMarina Yu.МаксимоваМарина Юрьевна

д-р мед. наук, проф., рук. 2-го неврологического отд-ния

ncnmaximova@mail.ruShalimanovaElena V.ШалимановаЕлена Витальевна

аспирант 2-го неврологического отд-ния

BrutyanAmayak G.БрутянАмаяк Грачевич

канд. мед. наук, зав. лаб. клинической нейрофизиологии

Research Center of NeurologyФГБНУ «Научный центр неврологии»15092020229VOL 9, NO22 (2020)ТОМ 22, №9 (2020)384528122021Copyright ©; 2020, Consilium MedicumCopyright ©; 2020, ООО "Консилиум Медикум"2020Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/95349

The occurrence of epileptic seizures and epilepsy after stroke is an example of their close relationship with cerebrovascular pathology. According to various researchers, incidence of epileptic seizures in all stroke patients lies between 3-6 and 12%. Post-stroke seizures can occur in the acute period of a stroke or later. Post-stroke epilepsy is associated with significant decrease of the quality of life, and slowing of the household, social and professional adaptation. Terminological, epidemiological, pathophysiological aspects, risk factors and predictors of post-stroke epileptic seizures and epilepsy are discussed in this article.

Возникновение эпилептических приступов и эпилепсии после инсульта является примером их тесной связи с цереброваскулярной патологией. По данным разных исследователей, эпилептические приступы у пациентов, перенесших инсульт, встречаются с частотой от 3-6 до 12%. Постинсультные приступы могут возникать в остром периоде инсульта или в более поздние сроки. Эпилепсия у больных с инсультом значительно ухудшает качество их жизни, замедляет бытовую, социальную и профессиональную адаптацию. В статье рассматриваются терминологические, эпидемиологические, патофизиологические аспекты, факторы риска и предикторы эпилептических приступов и эпилепсии у больных с инсультом.

strokepost-stroke seizurespost-stroke epilepsyинсультэпилептические приступы и постинсультная эпилепсияDumanis SB, French JA, Bernard C et al. Seizure Forecasting from Idea to Reality. Outcomes of the My Seizure Gauge Epilepsy Innovation Institute Workshop. eNeuro 2017 Dec 27; 4 (6). DOI: 10.1523/ENEURO.0349-17.2017Dalic L, Cook MJ. Managing drug-resistant epilepsy: challenges and solutions. Neuropsychiatr Dis Treat 2016 Oct 12; 12: 2605-16. DOI: 10.2147/NDT.S84852Гехт А.Б., Лебедева А.В., Рулева З.С. и др. Эпилепсия у больных инсультом. РМЖ. 2000; 2: 14-7. [Gekht A.B., Lebedeva A.V., Ruleva Z.S. et al. Epilepsiya u bol'nykh insul'tom. RMZh. 2000; 2: 14-7 (in Russian).]Silverman IE, Restrepo L, Mathews GC. Poststroke seizures. Arch Neurol 2002; 59 (2): 195-201. DOI: 10.1001/archneur.59.2.195Myint PK, Staufenberg EF, Sabanathan K. Post-stroke seizure and post-stroke epilepsy. Postgrad Med J 2006; 82 (971): 568-72. DOI: 10.1136/pgmj.2005.041426Holtkamp M, Beghi E, Benninger F et al. European Stroke Organisation guidelines for the management of post-stroke seizures and epilepsy. Eur Stroke J 2017; 2 (2): 103-15. DOI: 10.1177/2396987317705536Pitkanen A, Nehlig A, Brooks-Kayal AR et al. Issues related to development of antiepileptogenic therapies. Epilepsia 2013; 54 (Suppl. 4): 35^3. DOI: 10.1111/epi.12297Pitkanen A, Sutula TP. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol 2002; 1 (3): 173-81. DOI: 10.1016/s1474-4422 (02)00073-xScharfman HE. The neurobiology of epilepsy. Curr Neurol Neurosci Rep 2007; 7 (4): 348-54. DOI: 10.1007/s11910-007-0053-zBen-Ari Y. Epilepsies and neuronal plasticity: for better or for worse? Dialogues Clin Neurosci 2008; 10 (1): 17-27. PMCID: PMC3181861.Hauser WA, Rich SS, Lee JR et al. Risk of recurrent seizures after two unprovoked seizures. N Engl J Med 1998; 338 (7): 429-34. DOI: 10.1056/NEJM199802123380704Fisher RS, Acevedo C, Arzimanoglou A et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014; 55 (4): 475-82. DOI: 10.1111/epi.12550Beghi E, Carpio A, Forsgren L et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia 2010; 51 (4): 671-5. DOI: 10.1111/j.1528-1167.2009.02285.xHesdorffer DC, Benn EK, Cascino GD, Hauser WA. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia 2009; 50 (5): 1102-8. DOI: 10.1111/j.1528-1167.2008.01945.xBladin CF, Alexandrov AV, Bellavance A et al. Seizures after stroke: a prospective multicenter study. Arch Neurol 2000; 57 (11): 1617-22. DOI: 10.1001/archneur.57.11.1617Burn J, Dennis M, Bamford J et al. Epileptic seizures after a first stroke: the Oxfordshire Community Stroke Project. BMJ 1997; 315 (7122): 1582-7. DOI: 10.1136/bmj.315.7122.1582Arboix A, Garcia-Eroles L, Massons JB et al. Predictive factors of early seizures after acute cerebrovascular disease. Stroke 1997; 28 (8): 1590^. DOI: 10.1161/01.str.28.8.1590So EL, Annegers JF, Hauser WA et al. Population-based study of seizure disorders after cerebral infarction. Neurology 1996; 46 (2): 350-5. DOI: 10.1212/wnl.46.2.350Labovitz DL, Hauser WA, Sacco RL. Prevalence and predictors of early seizure and status epilepticus after first stroke. Neurology 2001; 57 (2): 200-6. DOI: 10.1212/wnl.57.2.200Lamy C, Domigo V, Semah F et al. Early and late seizures after cryptogenic ischemic stroke in young adults. Neurology 2003; 60 (3): 400-4. DOI: 10.1212/wnl.60.3.400Berges S, Moulin T, Berger E et al. Seizures and epilepsy following strokes: recurrence factors. Eur Neurol 2000; 43 (1): 3-8. DOI: 10.1159/000008120Kilpatrick CJ, Davis SM, Tress BM et al. Epileptic seizures in acute stroke. Arch Neurol 1990; 47 (2): 157-60. PMID: 2302087.Lancman ME, Golimstok A, Norscini J, Granillo R. Risk factors for developing seizures after a stroke. Epilepsia 1993; 34 (1): 141-3. DOI: 10.1111/j.1528-1157.1993.tb02386.xGupta SR, Naheedy MH, Elias D, Rubino FA. Postinfarction seizures. A clinical study. Stroke 1988; 19 (12): 1477-81. DOI: 10.1161/01.str.19.12.1477Lossius MI, Ronning OM, Slapo GD et al. Poststroke epilepsy: occurrence and predictors--a long-term prospective controlled study (Akershus Stroke Study). Epilepsia 2005; 46 (8): 1246-51. DOI: 10.1111/j.1528-1167.2005.57904.xRoivainen R, Haapaniemi E, Putaala J et al. Young adult ischaemic stroke related acute symptomatic and late seizures: risk factors. Eur J Neurol 2013; 20 (9): 1247-55. DOI: 10.1111/ene.12157Lee JC, Lin KL, Wang HS et al. Seizures in childhood ischemic stroke in Taiwan. Brain Dev 2009; 31 (4): 294-9. DOI: 10.1016/j.braindev.2008.05.006Hsu CJ, Weng WC, Peng SS, Lee WT. Early-onset seizures are correlated with late-onset seizures in children with arterial ischemic stroke. Stroke 2014 Apr; 45 (4): 1161-3. DOI: 10.1161/STRO-KEAHA.113.004015Giroud M, Gras P, Fayolle H et al. Early seizures after acute stroke: a study of 1.640 cases. Epilepsia 1994; 35 (5): 959-64. DOI: 10.1111/j.1528-1157.1994.tb02540.x.Zhao Y, Li X, Zhang K et al. The Progress of Epilepsy after Stroke. Curr Neuropharmacol 2018; 16 (1): 71-8. DOI: 10.2174/1570159X15666170613083253Габашвили В.М., Прохорова Э.С., Шакаришвили Р.С. Эпилептические припадки при сосудистых заболеваниях головного мозга. Тбилиси: Мецниереба, 1986.Сорокина Н.Д., Селицкий Г.В., Косицын Н.С., Свинов М.М. Нейробиологические аспекты ишемии мозга и постинсультной эпилепсии. Журн. высш. нервной деятельности им. И.П. Павлова. 2002; 52 (6): 656-65.Lo YK, Yiu CH, Hu HH et al. Frequency and characteristics of eariy seizures in Chinese acute stroke. Acta Neurol Scand 1994; 90 (2): 83-5. DOI: 10.1111/j.1600-0404.1994.tb02684.xГехт А.Б., Лебедева А.В., Полетаев А.Б. и др. Постинсультная эпилепсия. Журн. неврологии и психиатрии им. С.С. Корсакова. Инсульт. 2003 (9): 195-7.Olafsson E, Ludvigsson P, Gudmundsson G et al. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study. Lancet Neurol 2005; 4 (10): 627-34.Graham NS, Crichton S, Koutroumanidis M et al. Incidence and associations of poststroke epilepsy: the prospective South London Stroke Register. Stroke 2013; 44 (3): 605-11. DOI: 10.1161/STRO-KEAHA.111.000220Adelow C, Andersson T, Ahlbom A, Tomson T. Prior hospitalization for stroke, diabetes, myocardial infarction, and subsequent risk of unprovoked seizures. Epilepsia 2011; 52 (2): 301-7. DOI: 10.1111/j.1528-1167.2010.02757.xHeiss WD, Huber M, Fink GR et al. Progressive derangement of periinfarct viable tissue in ischemic stroke. J Cereb Blood Flow Metab 1992; 12 (2): 193-203. DOI: 10.1038/jcbfm.1992.29Luhmann HJ. Ischemia and lesion induced imbalances in cortical function. Prog Neurobiol 1996; 48 (2): 131-66. DOI: 10.1016/0301-0082(95)00042-9Marchi N, Granata T, Ghosh C, Janigro D. Blood-brain barrier dysfunction and epilepsy: pathophysiologic role and therapeutic approaches. Epilepsia 2012; 53 (11): 1877-86. DOI: 10.1111/j.1528-1167.2012.03637.xVan Vliet EA, Aronica E, Gorter JA. Blood-brain barrier dysfunction, seizures and epilepsy. Semin. Cell Dev Biol 2015; 38: 26-34. DOI: 10.1016/j.semcdb.2014.10.003Mizielinska SM, Greenwood SM, Tummala H, Connolly CN. Rapid dendritic and axonal responses to neuronal insults. Biochem Soc Trans 2009; 37 (6): 1389-93. DOI: 10.1042/BST0371389Sahu S, Nag DS, Swain A, Samaddar DP. Biochemical changes in the injured brain. World J Biol Chem 2017; 8 (1): 21-31. DOI: 10.4331/wjbc.v8.i1.21Tanaka T, Ihara M. Post-stroke epilepsy. Neurochem Int 2017; 107: 219-28. DOI: 10.1016/j.neuint.2017.02.002Sun DA, Sombati S, DeLorenzo RJ. Glutamate injury-induced epileptogenesis in hippocampal neurons: an in vitro model of stroke-induced “epilepsy”. Stroke 2001; 32 (10): 2344-50. DOI: 10.1161/hs1001.097242Ferlazzo E, Gasparini S, Beghi E et al. Epilepsy in cerebrovascular diseases: Review of experimental and clinical data with meta-analysis of risk factors. Epilepsia 2016; 57 (8): 1205-14. DOI: 10.1111/epi.13448Pitkanen A, Loscher W, Vezzani A et al. Advances in the development of biomarkers for epilepsy. Lancet Neurol 2016; 15 (8): 843-56. DOI: 10.1016/S1474-4422 (16)00112-5Iijima T, Mies G, Hossmann KA. Repeated negative DC deflections in rat cortex following middle cerebral artery occlusion are abolished by MK-801: effect on volume of ischemic injury. J Cereb Blood Flow Metab 1992; 12 (5): 727-33. DOI: 10.1038/jcbfm.1992.103Kamp MA, Dibue M, Schneider T et al. Calcium and potassium channels in experimental subarachnoid hemorrhage and transient global ischemia. Stroke Res Treat 2012; 2012: 382146. DOI: 10.1155/2012/382146Back T, Ginsberg MD, Dietrich WD, Watson BD. Induction of spreading depression in the ischemic hemisphere following experimental middle cerebral artery occlusion: effect on infarct morphology. J Cereb Blood Flow Metab 1996; 16 (2): 202-13. DOI: 10.1097/00004647-199603000-00004Maggio N, Shavit E, Chapman J, Segal M. Thrombin induces long-term potentiation of reactivity to afferent stimulation and facilitates epileptic seizures in rat hippocampal slices: toward understanding the functional consequences of cerebrovascular insults. J Neurosci 2008; 28 (3): 732-6. DOI: 10.1523/JNEUROSCI.3665-07.2008Martinc B, Grabnar I, Vovk T. The role of reactive species in epileptogenesis and influence of antiepileptic drug therapy on oxidative stress. Curr Neuropharmacol 2012; 10 (4): 328-43. DOI: 10.2174/157015912804143504IK. Extracellular hemoglobin: the case of a friend turned foe.Front Physiol 2015; 6: 96. DOI: 10.3389/fphys.2015.00096Uchino H, Smith ML, Bengzon J et al. Characteristics of postischemic seizures in hyperglycemic rats. J Neurol Sci 1996; 139 (1): 21-7. PMID: 8836968.Carmichael ST. Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol 2006; 59 (5): 735-42. DOI: 10.1002/ana.20845Feyissa AM, Hasan TF, Meschia JF. Stroke-related epilepsy. Eur J Neurol 2019; 26 (1): 18-e3. DOI: 10.1111/ene.13813Степанова Т.С., Грачев К.В. Электрофизиология патогенетического стереотаксиса при эпилепсии: материалы конференции по проблемам эпилепсии. Ереван, 1976: 87-91.Карлов В.А. Эпилепсия как клиническая и нейрофизиологическая проблема. Журн. неврологии и психиатрии им. С.С. Корсакова. 2000; 100 (9): 7-15.Карлов В.А. Эпилепсия у детей и взрослых женщин и мужчин. Руководство для врачей. Бином.Spencer SS. Neural networits in human epilepsy: evidence of and implications for treatment. Epilepsia 2002 Mar; 43 (3): 219-27. DOI: 10.1046/j.1528-1157.2002.26901.xEngel J. Can we replace the therms “focal” and “generalized”. In: Generalized seizures: from clinical phenomenology to understanding system and networks (Hirsch E, Andermann F, Chauvel P, Engel J, Lopes da Silva F, Luders H, eds), 2006, pp. 305-25. Montrouge: John Libbey Eurotext.Perez Velazquez JL, Carien PL. Gap junctions, synchrony and seizures. Trends Neurosci 2000; 23 (2): 6874. DOI: 10.1016/s0166-2236(99)01497-6Avoli M, Louvel J, Pumain R, Kohling R. Cellular and molecular mechanisms of epilepsy in the human brain. Prog Neurobiol 2005; 77 (3): 166-200. DOI: 10.1016/j.pneurobio.2005.09.006He Y, Chen ZJ, Evans AC. Small-world anatomical networks in the human brain revealed by cortical thickness from MRI. Cereb Cortex 2007; 17 (10): 2407-19. DOI: 10.1093/cercor/bhl149.Wang L, Yu C, Chen H et al. Dynamic functional reorganization of the motor execution network after stroke. Brain 2010; 133 (4): 1224-38. DOI: 10.1093/brain/awq043Waites AB, Briellmann RS, Saling MM et al. Functional connectivity networks are disrupted in left temporal lobe epilepsy. Ann Neurol 2006; 59 (2): 335-43. DOI: 10.1002/ana.20733Silasi G, Murphy TH. Stroke and the connectome: how connectivity guides therapeutic intervention. Neuron 2014; 83 (6): 1354-68. DOI: 10.1016/j.neuron.2014.08.052Batten SR, Whiteheart SW, Gerhardt GA, Slevin JT. Neurotransmitter Function Presynaptic Neurotransmission: Alterations in Exocytotic/Secretory Machinery and Glutamate Signaling in Kindling. In: Reference Module in Neuroscience and Biobehavioral Psychology, 2017: 1-9.Goddard GV, McIntyre DC, Leech CK. A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 1969; 25 (3): 295-330. DOI:10.1016/0014-4886(69)90128-9Morimoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus models of epilepsy: rewiring the brain. Prog Neurobiol 2004; 73 (1): 1-60. DOI: 10.1016/.pneurobio.2004.03.009Глебов Р.Н. Особенности дизрегуляции нейрональной и синаптической активности при эпилептогенезе. В кн.: Дизрегуляторная патология: Руководство для врачей и биологов. Под ред. Г.Н. Крыжановского. М.: Медицина, 2002: 587-632.Morrell F. Secondary epileptogenic lesions. Epilepsia 1960; 1: 538-60. DOI: 10.1111/j.1528-1157.1959.tb04288.xХалилов И.А., Ситдикова Г.Ф., Хазипов Р.Н., Зефиров А.Л. Вторичный эпилептогенез в незрелом мозге: роль ГАМК. Журн. неврологии и психиатрии им. С.С. Корсакова. Спецвыпуски. 2014; 114 (4): 41-51.Richardson EP Jr, Dodge PR. Epilepsy in cerebral vascular disease; a study of the incidence and nature of seizures in 104 consecutive autopsy-proven cases of cerebral infarction and hemorrhage. Epilepsia 1954; 3: 49-74. DOI: 10.1111/j.1528-1157.1954.tb03153.xMeyer JS, Charney JZ, Rivera VM, Mathew NT. Cerebral embolization: prospective clinical analysis of 42 cases. Stroke 1971; 2 (6): 541-54. DOI: 10.1161/01.str.2.6.541Lesser RP, Luders H, Dinner DS, Morris HH. Epileptic seizures due to thrombotic and embolic cerebrovascular disease in older patients. Epilepsia 1985; 26 (6): 622-30. DOI: 10.1111/j.1528-1157.1985.tb05702.xBogousslavsky J, Van Melle G, Regli F. The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke 1988; 19 (9): 1083-92. DOI: 10.1161/01.str.19.9.1083Kittner SJ, Sharkness CM, Price TR et al. Infarcts with a cardiac source of embolism in the NINCDS Stroke Data Bank: historical features. Neurology 1990; 40 (2): 281-4. DOI: 10.1212/wnl.40.2.281Reith J, Jorgensen HS, Nakayama H et al. Seizures in acute stroke: predictors and prognostic significance. The Copenhagen Stroke Study. Stroke 1997; 28 (8): 1585-9. DOI: 10.1161/01.str.28.8.1585Bentes C, Pimentel J, Ferro JM. Epileptic seizures following subcortical infarcts. Cerebrovasc Dis 2001; 12 (4): 331-4. DOI: 10.1159/000047730Zhang C, Wang X, Wang Y et al. Risk factors for post-stroke seizures: a systematic review and meta-ana-lysis. Epilepsy Res 2014; 108 (10): 1806-16. DOI: 10.1016/j.eplepsyres.2014.09.030Arntz R, Rutten-Jacobs L, Maaijwee N et al. Post-stroke epilepsy in young adults: a long-term follow-up study. PLoS One 2013; 8 (2): e55498. DOI: 10.1371/joumal.pone.0055498Jungehulsing GJ, Heuschmann PU, Holtkamp M et al. Incidence and predictors of post-stroke epilepsy. Acta Neurol Scand 2013; 127 (6): 427-30. DOI: 10.1111/ane.12070Heuts-van Raak L, Lodder J, Kessels F. Late seizures following a first symptomatic brain infarct are related to large infarcts involving the posterior area around the lateral sulcus. Seizure 1996; 5 (3): 185-94. DOI: 10.1016/s1059-1311 (96)80034-3Leone MA, Tonini MC, Bogliun G et al. Risk factors for a first epileptic seizure after stroke: a case control study. J Neurol Sci 2009; 277 (1-2): 138^2. DOI: 10.1016/j.jns.2008.11.004Miyaji Y, Kawabata Y, Joki H et al. Late Seizures after Stroke in Clinical Practice: The Prevalence of Non-convulsive Seizures. Intern Med 2017; 56 (6): 627-30. DOI: 10.2169/internalmedicine.56.7162Benbir G, Ince B, Bozluolcay M. The epidemiology of post-stroke epilepsy according to stroke subtypes. Acta Neurol Scand 2006; 114 (1): 8-12. DOI: 10.1111/j.1600-0404.2006.00642.xCleary P, Shorvon S, Tallis R. Late-onset seizures as a predictor of subsequent stroke. Lancet 2004; 363 (9416): 1184-6. DOI: 10.1016/S0140-6736(04)15946-1Brigo F, Tezzon F, Nardone R. Late-onset seizures and risk of subsequent stroke: a systematic review. Epilepsy Behav 2014; 31: 9-12. DOI: 10.1016/j.yebeh.2013.11.003Yang H, Song Z, Yang GP et al. The ALDH2 rs671 polymorphism affects post-stroke epilepsy susceptibility and plasma 4-HNE levels. PLoS One 2014; 9 (10): e109634. DOI: 10.1371/journal.pone.0109634Zhang B, Chen M, Yang H et al. Evidence for involvement of the CD40/CD40L system in post-stroke epilepsy. Neurosci Lett 2014; 567: 6-10. DOI: 10.1016/j.neulet.2014.03.003Goldstein LB, Adams R, Alberts MJ et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline. Stroke 2006; 37 (6): 1583-633. DOI: 10.1161/01.STR.0000223048.70103.F1Szaflarski JP, Rackley AY, Kleindorfer DO et al. Incidence of seizures in the acute phase of stroke: a population-based study. Epilepsia 2008; 49 (6): 974-81. DOI: 10.1111/j.1528-1167.2007.01513.xTemkin NR. Preventing and treating posttraumatic seizures: the human experience. Epilepsia 2009; 50 (Suppl. 2): 10-3. DOI: 10.1111/j.1528-1167.2008.02005.xTrinka E, Brigo F. Antiepileptogenesis in humans: disappointing clinical evidence and ways to move forward. Curr Opin Neurol 2014; 27 (2): 227-35. DOI: 10.1097/WCO.0000000000000067Rumbach L, Sablot D, Berger E et al. Status epilepticus in stroke: report on a hospital-based stroke cohort. Neurology 2000; 54 (2): 350-4. DOI: 10.1212/wnl.54.2.350Bateman BT, Claassen J, Willey JZ et al. Convulsive status epilepticus after ischemic stroke and intracerebral hemorrhage: frequency, predictors, and impact on outcome in a large administrative dataset. Neurocrit Care 2007; 7 (3): 187-93. DOI: 10.1007/s12028-007-0056-2Belcastro V, Vidale S, Gorgone G et al. Non-convulsive status epilepticus after ischemic stroke: a hospitalbased stroke cohort study. J Neurol 2014; 261 (11): 2136^2. DOI: 10.1007/s00415-014-7471-zConrad J, Pawlowski M, Dogan M et al. Seizures after cerebrovascular events: risk factors and clinical features. Seizur 2013; 22 (4): 275-82. DOI: 10.1016/j.seizure.2013.01.014Nadeau SE, Lu X, Dobkin B et al. A prospective test of the late effects of potentially antineuroplastic drugs in a stroke rehabilitation study. Int J Stroke 2014; 9 (4): 449-56. DOI: 10.1111/j.1747-4949.2012.00920.xDe Reuck J, Van Maele G. Acute ischemic stroke treatment and the occurrence of seizures. Clin Neurol Neurosurg 2010; 112 (4): 328-31. DOI: 10.1016/j.clineuro.2010.01.004Alvarez V, Rossetti AO, Papavasileiou V, Michel P. Acute seizures in acute ischemic stroke: does thrombolysis have a role to play? J Neurol 2013; 260 (1): 55-61. DOI: 10.1007/s00415-012-6583-6Schmitz ML, Simonsen CZ, Hundborg H et al. Acute ischemic stroke and long-term outcome after thrombolysis: nationwide propensity score-matched follow-up study. Stroke 2014; 45 (10): 3070-2. DOI: 10.1161/STROKEAHA.114.006570Machado C, Pinho J, Alves JN et al. Five-Year Outcome in Stroke Patients Submitted to Thrombolysis. Stroke 2015; 46 (8): 23124 DOI: 10.1161/STROKEAHA.115.009842Couillard P, Almekhlafi MA, Irvine A et al. Neurocrit Care 2012; 16 (2): 241-5. DOI: 10.1007/s12028-011-9657-xGensicke H, Seiffge DJ, Polasek AE et al. Long-term outcome in stroke patients treated with IV thrombolysis. Neurology 2013; 80 (10): 919-25. DOI: 10.1212/WNL.0b013e3182840c35