卒中后癫痫研究进展:病理生理、诊断、治疗与预后
Research Progress of Post-Stroke Epilepsy: Pathophysiology, Diagnosis, Treatment and Prognosis
摘要: 卒中后癫痫(PSE)是卒中患者常见的严重并发症,显著影响其预后与生活质量。本文系统综述PSE的病理生理机制、诊断技术、治疗策略及预后因素的研究进展。病理生理方面,重点探讨脑损伤后神经递质失衡、离子通道异常、血脑屏障破坏及炎症反应的交互作用;诊断部分,结合脑电图、影像学与血液生物标志物的临床价值与局限性展开分析;治疗策略涵盖抗癫痫药物的选择、神经调控技术的应用及手术干预的适应证;预后部分则从卒中类型、发作特征及治疗依从性等多维度解析影响因素。本文旨在整合现有研究成果,为优化PSE的临床管理及未来的研究方向提供参考。
Abstract: Post-stroke epilepsy (PSE) is a common serious complication of stroke patients, which significantly affects their prognosis and quality of life. This article systematically reviews the research progress of the pathophysiological mechanism, diagnostic techniques, treatment strategies and prognostic factors of PSE. In terms of pathophysiology, it focuses on the interaction of neurotransmitter imbalance, ion channel abnormalities, blood-brain barrier disruption and inflammatory response after brain injury; in the diagnostic part, the clinical value and limitations of electroencephalography, imaging and blood biomarkers are analyzed; in the treatment strategy, the selection of anti-epileptic drugs, the application of neuroregulatory techniques and the indications of surgical intervention are covered; in the prognosis part, the influencing factors are analyzed from multiple dimensions such as stroke type, seizure characteristics and treatment compliance. The purpose of this paper is to integrate existing research results and provide a reference for optimizing the clinical management of PSE and future research directions.
文章引用:田丹丹, 毕建忠, 谢兆宏. 卒中后癫痫研究进展:病理生理、诊断、治疗与预后[J]. 临床医学进展, 2025, 15(3): 174-183. https://doi.org/10.12677/acm.2025.153602

参考文献

[1] Mohamed, A.A., Tan, J.K., Tan, M.M., Khoo, C.S., Wan Yahya, W.N.N., Abd Rahman, M.S.H., et al. (2024) Risk Factors for Post-Stroke Seizures in a Tertiary Care Center: A Case-Control Study. Neuropsychiatric Disease and Treatment, 20, 1615-1628. [Google Scholar] [CrossRef] [PubMed]
[2] Lühdorf, K., Jensen, L.K. and Plesner, A.M. (1986) Etiology of Seizures in the Elderly. Epilepsia, 27, 458-463. [Google Scholar] [CrossRef] [PubMed]
[3] Feyissa, A.M., Hasan, T.F. and Meschia, J.F. (2018) Stroke‐Related epilepsy. European Journal of Neurology, 26, 18-e3. [Google Scholar] [CrossRef] [PubMed]
[4] Misra, S., Kasner, S.E., Dawson, J., Tanaka, T., Zhao, Y., Zaveri, H.P., et al. (2023) Outcomes in Patients with Poststroke Seizures: A Systematic Review and Meta-Analysis. JAMA Neurology, 80, 1155-1165. [Google Scholar] [CrossRef] [PubMed]
[5] Wafa, H.A., Wolfe, C.D.A., Emmett, E., Roth, G.A., Johnson, C.O. and Wang, Y. (2020) Burden of Stroke in Europe: Thirty-Year Projections of Incidence, Prevalence, Deaths, and Disability-Adjusted Life Years. Stroke, 51, 2418-2427. [Google Scholar] [CrossRef] [PubMed]
[6] Beghi, E., Carpio, A., Forsgren, L., Hesdorffer, D.C., Malmgren, K., Sander, J.W., et al. (2010) Recommendation for a Definition of Acute Symptomatic Seizure. Epilepsia, 51, 671-675. [Google Scholar] [CrossRef] [PubMed]
[7] Fisher, R.S., Acevedo, C., Arzimanoglou, A., Bogacz, A., Cross, J.H., Elger, C.E., et al. (2014) ILAE Official Report: A Practical Clinical Definition of Epilepsy. Epilepsia, 55, 475-482. [Google Scholar] [CrossRef] [PubMed]
[8] Galovic, M., Ferreira-Atuesta, C., Abraira, L., Döhler, N., Sinka, L., Brigo, F., et al. (2021) Seizures and Epilepsy after Stroke: Epidemiology, Biomarkers and Management. Drugs & Aging, 38, 285-299. [Google Scholar] [CrossRef] [PubMed]
[9] Bentes, C., Franco, A.C., Peralta, A.R., Viana, P., Martins, H., Morgado, C., et al. (2017) Epilepsia partialis Continua after an Anterior Circulation Ischaemic Stroke. European Journal of Neurology, 24, 929-934. [Google Scholar] [CrossRef] [PubMed]
[10] Boyko, M., Gruenbaum, S.E., Gruenbaum, B.F., Shapira, Y. and Zlotnik, A. (2014) Brain to Blood Glutamate Scavenging as a Novel Therapeutic Modality: A Review. Journal of Neural Transmission, 121, 971-979. [Google Scholar] [CrossRef] [PubMed]
[11] Campos, F., Sobrino, T., Ramos-Cabrer, P., Castellanos, M., Blanco, M., Rodríguez-Yáñez, M., et al. (2011) High Blood Glutamate Oxaloacetate Transaminase Levels Are Associated with Good Functional Outcome in Acute Ischemic Stroke. Journal of Cerebral Blood Flow & Metabolism, 31, 1387-1393. [Google Scholar] [CrossRef] [PubMed]
[12] Sandoval, K.E. and Witt, K.A. (2008) Blood-brain Barrier Tight Junction Permeability and Ischemic Stroke. Neurobiology of Disease, 32, 200-219. [Google Scholar] [CrossRef] [PubMed]
[13] Campos, F., Sobrino, T., Pérez-Mato, M., Rodríguez-Osorio, X., Leira, R., Blanco, M., et al. (2013) Glutamate Oxaloacetate Transaminase: A New Key in the Dysregulation of Glutamate in Migraine Patients. Cephalalgia, 33, 1148-1154. [Google Scholar] [CrossRef] [PubMed]
[14] Campos, F., Pérez-Mato, M., Agulla, J., Blanco, M., Barral, D., Almeida, Á., et al. (2012) Glutamate Excitoxicity Is the Key Molecular Mechanism Which Is Influenced by Body Temperature during the Acute Phase of Brain Stroke. PLOS ONE, 7, e44191. [Google Scholar] [CrossRef] [PubMed]
[15] Gruenbaum, B.F., Schonwald, A., Boyko, M. and Zlotnik, A. (2024) The Role of Glutamate and Blood-Brain Barrier Disruption as a Mechanistic Link between Epilepsy and Depression. Cells, 13, Article 1228. [Google Scholar] [CrossRef] [PubMed]
[16] Clarkson, A.N., Overman, J.J., Zhong, S., Mueller, R., Lynch, G. and Carmichael, S.T. (2011) AMPA Receptor-Induced Local Brain-Derived Neurotrophic Factor Signaling Mediates Motor Recovery after Stroke. The Journal of Neuroscience, 31, 3766-3775. [Google Scholar] [CrossRef] [PubMed]
[17] Frank, D., Gruenbaum, B.F., Zlotnik, A., Semyonov, M., Frenkel, A. and Boyko, M. (2022) Pathophysiology and Current Drug Treatments for Post-Stroke Depression: A Review. International Journal of Molecular Sciences, 23, Article 15114. [Google Scholar] [CrossRef] [PubMed]
[18] Nicolo, J., O’Brien, T.J. and Kwan, P. (2019) Role of Cerebral Glutamate in Post-Stroke Epileptogenesis. NeuroImage: Clinical, 24, Article ID: 102069. [Google Scholar] [CrossRef] [PubMed]
[19] Kharlamov, E.A., Downey, K.L., Jukkola, P.I., Grayson, D.R. and Kelly, K.M. (2008) Expression of GABAA Receptor Α1 Subunit Mrna and Protein in Rat Neocortex Following Photothrombotic Infarction. Brain Research, 1210, 29-38. [Google Scholar] [CrossRef] [PubMed]
[20] Yang, H., Rajah, G., Guo, A., Wang, Y. and Wang, Q. (2018) Pathogenesis of Epileptic Seizures and Epilepsy after Stroke. Neurological Research, 40, 426-432. [Google Scholar] [CrossRef] [PubMed]
[21] Tanaka, T. and Ihara, M. (2017) Post-Stroke Epilepsy. Neurochemistry International, 107, 219-228. [Google Scholar] [CrossRef] [PubMed]
[22] Köhling, R. and Wolfart, J. (2016) Potassium Channels in Epilepsy. Cold Spring Harbor Perspectives in Medicine, 6, a022871. [Google Scholar] [CrossRef] [PubMed]
[23] Wei, F., Yan, L., Su, T., He, N., Lin, Z., Wang, J., et al. (2017) Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy. Neuroscience Bulletin, 33, 455-477. [Google Scholar] [CrossRef] [PubMed]
[24] Gruenbaum, B.F., Zlotnik, A., Frenkel, A., Fleidervish, I. and Boyko, M. (2022) Glutamate Efflux across the Blood-Brain Barrier: New Perspectives on the Relationship between Depression and the Glutamatergic System. Metabolites, 12, Article 459. [Google Scholar] [CrossRef] [PubMed]
[25] Meijer, W.C. and Gorter, J.A. (2024) Role of Blood-Brain Barrier Dysfunction in the Development of Poststroke Epilepsy. Epilepsia, 65, 2519-2536. [Google Scholar] [CrossRef] [PubMed]
[26] Marchi, N., Granata, T. and Janigro, D. (2014) Inflammatory Pathways of Seizure Disorders. Trends in Neurosciences, 37, 55-65. [Google Scholar] [CrossRef] [PubMed]
[27] da Fonseca, A.C.C., Matias, D., Garcia, C., Amaral, R., Geraldo, L.H., Freitas, C., et al. (2014) The Impact of Microglial Activation on Blood-Brain Barrier in Brain Diseases. Frontiers in Cellular Neuroscience, 8, Article 362. [Google Scholar] [CrossRef] [PubMed]
[28] Vezzani, A., Balosso, S. and Ravizza, T. (2019) Neuroinflammatory Pathways as Treatment Targets and Biomarkers in Epilepsy. Nature Reviews Neurology, 15, 459-472. [Google Scholar] [CrossRef] [PubMed]
[29] Heinemann, U., Kaufer, D. and Friedman, A. (2012) Blood‐brain Barrier Dysfunction, Tgfβ Signaling, and Astrocyte Dysfunction in Epilepsy. Glia, 60, 1251-1257. [Google Scholar] [CrossRef] [PubMed]
[30] Vezzani, A., French, J., Bartfai, T. and Baram, T.Z. (2010) The Role of Inflammation in Epilepsy. Nature Reviews Neurology, 7, 31-40. [Google Scholar] [CrossRef] [PubMed]
[31] Maroso, M., Balosso, S., Ravizza, T., Iori, V., Wright, C.I., French, J., et al. (2011) Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice. Neurotherapeutics, 8, 304-315. [Google Scholar] [CrossRef] [PubMed]
[32] Tröscher, A.R., Gruber, J., Wagner, J.N., Böhm, V., Wahl, A. and von Oertzen, T.J. (2021) Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-Stroke Epilepsy. Frontiers in Aging Neuroscience, 13, Article 781174. [Google Scholar] [CrossRef] [PubMed]
[33] Eid, T., Williamson, A., Lee, T.W., Petroff, O.A. and De Lanerolle, N.C. (2008) Glutamate and Astrocytes—Key Players in Human Mesial Temporal Lobe Epilepsy? Epilepsia, 49, 42-52. [Google Scholar] [CrossRef] [PubMed]
[34] Patabendige, A., Singh, A., Jenkins, S., Sen, J. and Chen, R. (2021) Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke. International Journal of Molecular Sciences, 22, Article 4280. [Google Scholar] [CrossRef] [PubMed]
[35] Robel, S. (2016) Astroglial Scarring and Seizures: A Cell Biological Perspective on Epilepsy. The Neuroscientist, 23, 152-168. [Google Scholar] [CrossRef] [PubMed]
[36] Xiang, J., Tang, Y., Li, C., Su, E.J., Lawrence, D.A. and Keep, R.F. (2016) Mechanisms Underlying Astrocyte Endfeet Swelling in Stroke. In: Applegate, R., Chen, G., Feng, H. and Zhang, J., Eds., Brain Edema XVI, Springer, 19-22. [Google Scholar] [CrossRef] [PubMed]
[37] Yang, H., Song, Z., Yang, G., Zhang, B., Chen, M., Wu, T., et al. (2014) The ALDH2 Rs671 Polymorphism Affects Post-Stroke Epilepsy Susceptibility and Plasma 4-HNE Levels. PLOS ONE, 9, e109634. [Google Scholar] [CrossRef] [PubMed]
[38] Misra, S., Khan, E.I., Lam, T.T., Mazumder, R., Gururangan, K., Hickman, L.B., et al. (2023) Common Pathways of Epileptogenesis in Patients with Epilepsy Post-Brain Injury: Findings from a Systematic Review and Meta-Analysis. Neurology, 101, e2243-e2256. [Google Scholar] [CrossRef] [PubMed]
[39] Pitkänen, A., Roivainen, R. and Lukasiuk, K. (2016) Development of Epilepsy after Ischaemic Stroke. The Lancet Neurology, 15, 185-197. [Google Scholar] [CrossRef] [PubMed]
[40] Bentes, C., Martins, H., Peralta, A.R., Casimiro, C., Morgado, C., Franco, A.C., et al. (2017) Post-Stroke Seizures Are Clinically Underestimated. Journal of Neurology, 264, 1978-1985. [Google Scholar] [CrossRef] [PubMed]
[41] Wen, L., Li, R., Wang, Y., Kong, Q. and Xia, M. (2024) Electroencephalogram Findings in 10 Patients with Post-Stroke Epilepsy: A Retrospective Study. World Journal of Clinical Cases, 12, 249-255. [Google Scholar] [CrossRef] [PubMed]
[42] Bentes, C., Martins, H., Peralta, A.R., Morgado, C., Casimiro, C., Franco, A.C., et al. (2018) Early EEG Predicts Poststroke Epilepsy. Epilepsia Open, 3, 203-212. [Google Scholar] [CrossRef] [PubMed]
[43] Zelano, J., Holtkamp, M., Agarwal, N., Lattanzi, S., Trinka, E. and Brigo, F. (2020) How to Diagnose and Treat Post‐stroke Seizures and Epilepsy. Epileptic Disorders, 22, 252-263. [Google Scholar] [CrossRef] [PubMed]
[44] Garbelli, R., Milesi, G., Medici, V., Villani, F., Didato, G., Deleo, F., et al. (2012) Blurring in Patients with Temporal Lobe Epilepsy: Clinical, High-Field Imaging and Ultrastructural Study. Brain, 135, 2337-2349. [Google Scholar] [CrossRef] [PubMed]
[45] Ferlazzo, E., Gasparini, S., Beghi, E., Sueri, C., Russo, E., Leo, A., et al. (2016) Epilepsy in Cerebrovascular Diseases: Review of Experimental and Clinical Data with Meta‐Analysis of Risk Factors. Epilepsia, 57, 1205-1214. [Google Scholar] [CrossRef] [PubMed]
[46] Wu, C., Ferreira, F., Fox, M., Harel, N., Hattangadi-Gluth, J., Horn, A., et al. (2021) Clinical Applications of Magnetic Resonance Imaging Based Functional and Structural Connectivity. NeuroImage, 244, Article ID: 118649. [Google Scholar] [CrossRef] [PubMed]
[47] Chakraborty, A.R., Almeida, N.C., Prather, K.Y., O’Neal, C.M., Wells, A.A., Chen, S., et al. (2020) Resting‐State Functional Magnetic Resonance Imaging with Independent Component Analysis for Presurgical Seizure Onset Zone Localization: A Systematic Review and Meta‐Analysis. Epilepsia, 61, 1958-1968. [Google Scholar] [CrossRef] [PubMed]
[48] Eriksson, H., Löwhagen Hendén, P., Rentzos, A., Pujol-Calderón, F., Karlsson, J., Höglund, K., et al. (2020) Acute Symptomatic Seizures and Epilepsy after Mechanical Thrombectomy. Epilepsy & Behavior, 104, Article ID: 106520. [Google Scholar] [CrossRef] [PubMed]
[49] Abraira, L., López-Maza, S., Quintana, M., Fonseca, E., Toledo, M., Campos-Fernández, D., et al. (2024) Exploratory Study of Blood Biomarkers in Patients with Post-Stroke Epilepsy. European Stroke Journal, 9, 763-771. [Google Scholar] [CrossRef] [PubMed]
[50] Consoli, D., Bosco, D., Postorino, P., Galati, F., Plastino, M., Perticoni, G.F., et al. (2012) Levetiracetam versus Carbamazepine in Patients with Late Poststroke Seizures: A Multicenter Prospective Randomized Open-Label Study (Epic Project). Cerebrovascular Diseases, 34, 282-289. [Google Scholar] [CrossRef] [PubMed]
[51] Marson, A., Burnside, G., Appleton, R., Smith, D., Leach, J.P., Sills, G., et al. (2021) The SANAD II Study of the Effectiveness and Cost-Effectiveness of Levetiracetam, Zonisamide, or Lamotrigine for Newly Diagnosed Focal Epilepsy: An Open-Label, Non-Inferiority, Multicentre, Phase 4, Randomised Controlled Trial. The Lancet, 397, 1363-1374. [Google Scholar] [CrossRef] [PubMed]
[52] Goldstein, R., Rabkin, N., Buchman, N., Jacobs, A.R., Sandouka, K., Raccah, B., et al. (2024) The Effect of Levetiracetam Compared with Enzyme-Inducing Antiseizure Medications on Apixaban and Rivaroxaban Peak Plasma Concentrations. CNS Drugs, 38, 399-408. [Google Scholar] [CrossRef] [PubMed]
[53] Josephson, C.B., Engbers, J.D.T., Jette, N., Patten, S.B., Singh, S., Sajobi, T.T., et al. (2019) Prediction Tools for Psychiatric Adverse Effects after Levetiracetam Prescription. JAMA Neurology, 76, 440-446. [Google Scholar] [CrossRef] [PubMed]
[54] Rosenow, F., Brandt, C., Bozorg, A., Dimova, S., Steiniger‐Brach, B., Zhang, Y., et al. (2020) Lacosamide in Patients with Epilepsy of Cerebrovascular Etiology. Acta Neurologica Scandinavica, 141, 473-482. [Google Scholar] [CrossRef] [PubMed]
[55] Mangiardi, M., Pezzella, F.R., Cruciani, A., et al. (2024) Long-Term Safety and Efficacy of Lacosamide Combined with NOACs in Post-Stroke Epilepsy and Atrial Fibrillation: A Prospective Longitudinal Study. Journal of Personalized Medicine, 14, Article 1125.
[56] Yan, C., Yang, T., Sun, Y., Hu, J., Yi, X., Li, C., et al. (2024) Efficacy and Safety of Perampanel in the Treatment of Post Stroke Epilepsy: A Multicenter, Real-World Study. Heliyon, 10, e26376. [Google Scholar] [CrossRef] [PubMed]
[57] Pascarella, A., Manzo, L., Gasparini, S., Marsico, O., Abelardo, D., Torino, C., et al. (2024) Perampanel in Post-Stroke Epilepsy: Clinical Practice Data from the Perampanel as Only Concomitant Antiseizure Medication (PEROC) Study. Journal of the Neurological Sciences, 462, Article ID: 123106. [Google Scholar] [CrossRef] [PubMed]
[58] Mintzer, S., Skidmore, C.T., Abidin, C.J., Morales, M.C., Chervoneva, I., Capuzzi, D.M., et al. (2009) Effects of Antiepileptic Drugs on Lipids, Homocysteine, and C‐Reactive Protein. Annals of Neurology, 65, 448-456. [Google Scholar] [CrossRef] [PubMed]
[59] Holtkamp, M., Beghi, E., Benninger, F., Kälviäinen, R., Rocamora, R. and Christensen, H. (2017) European Stroke Organisation Guidelines for the Management of Post-Stroke Seizures and Epilepsy. European Stroke Journal, 2, 103-115. [Google Scholar] [CrossRef] [PubMed]
[60] Klomjai, W., Katz, R. and Lackmy-Vallée, A. (2015) Basic Principles of Transcranial Magnetic Stimulation (TMS) and Repetitive TMS (rTMS). Annals of Physical and Rehabilitation Medicine, 58, 208-213. [Google Scholar] [CrossRef] [PubMed]
[61] Rossi, S., Hallett, M., Rossini, P.M. and Pascual-Leone, A. (2009) Safety, Ethical Considerations, and Application Guidelines for the Use of Transcranial Magnetic Stimulation in Clinical Practice and Research. Clinical Neurophysiology, 120, 2008-2039. [Google Scholar] [CrossRef] [PubMed]
[62] Yang, Y., Han, Y., Wang, J., Zhou, Y., Chen, D., Wang, M., et al. (2023) Effects of Altered Excitation-Inhibition Imbalance by Repetitive Transcranial Magnetic Stimulation for Self-Limited Epilepsy with Centrotemporal Spikes. Frontiers in Neurology, 14, Article 1164082. [Google Scholar] [CrossRef] [PubMed]
[63] Jiang, Y., Guo, Z., McClure, M.A., He, L. and Mu, Q. (2020) Effect of RTMs on Parkinson’s Cognitive Function: A Systematic Review and Meta-Analysis. BMC Neurology, 20, Article No. 377. [Google Scholar] [CrossRef] [PubMed]
[64] Dawson, J., Abdul-Rahim, A.H. and Kimberley, T.J. (2024) Neurostimulation for Treatment of Post-Stroke Impairments. Nature Reviews Neurology, 20, 259-268. [Google Scholar] [CrossRef] [PubMed]
[65] Lefaucheur, J., Antal, A., Ayache, S.S., Benninger, D.H., Brunelin, J., Cogiamanian, F., et al. (2017) Evidence-Based Guidelines on the Therapeutic Use of Transcranial Direct Current Stimulation (TDCS). Clinical Neurophysiology, 128, 56-92. [Google Scholar] [CrossRef] [PubMed]
[66] Simula, S., Daoud, M., Ruffini, G., Biagi, M.C., Bénar, C., Benquet, P., et al. (2022) Transcranial Current Stimulation in Epilepsy: A Systematic Review of the Fundamental and Clinical Aspects. Frontiers in Neuroscience, 16, Article 909421. [Google Scholar] [CrossRef] [PubMed]
[67] van der Meij, A., van Walderveen, M.A.A., Kruyt, N.D., van Zwet, E.W., Liebler, E.J., Ferrari, M.D., et al. (2020) Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke (NOVIS): A Study Protocol for a Randomized Clinical Trial. Trials, 21, Article No. 878. [Google Scholar] [CrossRef] [PubMed]
[68] Du, L., He, X., Xiong, X., Zhang, X., Jian, Z. and Yang, Z. (2023) Vagus Nerve Stimulation in Cerebral Stroke: Biological Mechanisms, Therapeutic Modalities, Clinical Applications, and Future Directions. Neural Regeneration Research, 19, 1707-1717. [Google Scholar] [CrossRef] [PubMed]
[69] Ekmekçi, H. and Kaptan, H. (2017) Vagal Nerve Stimulation. Open Access Macedonian Journal of Medical Sciences, 5, 391-394. [Google Scholar] [CrossRef] [PubMed]
[70] Dorfmüller, G. and Delalande, O. (2013) Pediatric Epilepsy Surgery. Handbook of Clinical Neurology, 111, 785-795. [Google Scholar] [CrossRef] [PubMed]
[71] Marchi, A., Pennaroli, D., Lagarde, S., McGonigal, A., Bonini, F., Carron, R., et al. (2019) Epileptogenicity and Surgical Outcome in Post Stroke Drug Resistant Epilepsy in Children and Adults. Epilepsy Research, 155, Article ID: 106155. [Google Scholar] [CrossRef] [PubMed]
[72] Arntz, R., Rutten-Jacobs, L., Maaijwee, N., Schoonderwaldt, H., Dorresteijn, L., van Dijk, E., et al. (2013) Post-Stroke Epilepsy in Young Adults: A Long-Term Follow-Up Study. PLOS ONE, 8, e55498. [Google Scholar] [CrossRef] [PubMed]
[73] Arntz, R.M., Maaijwee, N.A.M., Rutten-Jacobs, L.C.A., Schoonderwaldt, H.C., Dorresteijn, L.D., van Dijk, E.J., et al. (2013) Epilepsy after TIA or Stroke in Young Patients Impairs Long-Term Functional Outcome: The FUTURE Study. Neurology, 81, 1907-1913. [Google Scholar] [CrossRef] [PubMed]
[74] Bentes, C., Peralta, A.R., Martins, H., Casimiro, C., Morgado, C., Franco, A.C., et al. (2017) Seizures, Electroencephalographic Abnormalities, and Outcome of Ischemic Stroke Patients. Epilepsia Open, 2, 441-452. [Google Scholar] [CrossRef] [PubMed]
[75] Zelano, J., Redfors, P., Åsberg, S. and Kumlien, E. (2016) Association between Poststroke Epilepsy and Death: A Nationwide Cohort Study. European Stroke Journal, 1, 272-278. [Google Scholar] [CrossRef] [PubMed]
[76] Conrad, J., Pawlowski, M., Dogan, M., Kovac, S., Ritter, M.A. and Evers, S. (2013) Seizures after Cerebrovascular Events: Risk Factors and Clinical Features. Seizure, 22, 275-282. [Google Scholar] [CrossRef] [PubMed]
[77] Zou, S., Wu, X., Zhu, B., Yu, J., Yang, B. and Shi, J. (2015) The Pooled Incidence of Post-Stroke Seizure in 102008 Patients. Topics in Stroke Rehabilitation, 22, 460-467. [Google Scholar] [CrossRef] [PubMed]
[78] Mohamed, C. and Kissani, N. (2015) Early Seizures in Acute Stroke. Pan African Medical Journal, 20, Article 136. [Google Scholar] [CrossRef] [PubMed]
[79] Kang, B.S., Kim, D.W., Kim, K.K., Moon, H.J., Kim, Y., Kim, H.K., et al. (2016) Prediction of Mortality and Functional Outcome from Status Epilepticus and Independent External Validation of STESS and EMSE Scores. Critical Care, 20, Article No. 25. [Google Scholar] [CrossRef] [PubMed]
[80] Perucca, E. and Meador, K.J. (2005) Adverse Effects of Antiepileptic Drugs. Acta Neurologica Scandinavica, 112, 30-35. [Google Scholar] [CrossRef] [PubMed]
[81] Molugulu, N., Gubbiyappa, K., Vasudeva Murthy, C., Lumae, L. and Mruthyunjaya, A. (2016) Evaluation of Self-Reported Medication Adherence and Its Associated Factors among Epilepsy Patients in Hospital Kuala Lumpur. Journal of Basic and Clinical Pharmacy, 7, 105-109. [Google Scholar] [CrossRef] [PubMed]