<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Child Neurology</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Child Neurology</journal-title><trans-title-group xml:lang="ru"><trans-title>Русский журнал детской неврологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2073-8803</issn><issn publication-format="electronic">2412-9178</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">268</article-id><article-id pub-id-type="doi">10.17650/2073-8803-2018-13-2-20-33</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>REVIEWS AND LECTURES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОБЗОРЫ И ЛЕКЦИИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Rufinamide (inovelon) in the treatment of Lennox–gastaut syndrome (a review of literature)</article-title><trans-title-group xml:lang="ru"><trans-title>Руфинамид (иновелон) в лечении синдрома Леннокса–Гасто (обзор литературы)</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Мukhin</surname><given-names>К. Yu.</given-names></name><name xml:lang="ru"><surname>Мухин</surname><given-names>К. Ю.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>5 Nagornaya St., Troitsk, Moscow 108840</italic></p></bio><bio xml:lang="ru"><p><bold>Константин Юрьевич Мухин </bold></p><p><italic>108840 Москва, Троицк, ул. Нагорная, 5</italic></p></bio><email>center@epileptologist.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Pylaeva</surname><given-names>О. A.</given-names></name><name xml:lang="ru"><surname>Пылаева</surname><given-names>О. Н.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>5 Nagornaya St., Troitsk, Moscow 108840</italic></p></bio><bio xml:lang="ru"><p><italic>108840 Москва, Троицк, ул. Нагорная, 5</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Svt. Luka’s Institute of Child Neurology and Epilepsy</institution></aff><aff><institution xml:lang="ru">ООО «Институт детской неврологии и эпилепсии им. Святителя Луки»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2018-04-15" publication-format="electronic"><day>15</day><month>04</month><year>2018</year></pub-date><volume>13</volume><issue>2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>20</fpage><lpage>33</lpage><history><date date-type="received" iso-8601-date="2018-11-30"><day>30</day><month>11</month><year>2018</year></date><date date-type="accepted" iso-8601-date="2018-11-30"><day>30</day><month>11</month><year>2018</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2018, Мukhin К.Y., Pylaeva О.A.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2018, Мухин К.Ю., Пылаева О.Н.</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="en">Мukhin К.Y., Pylaeva О.A.</copyright-holder><copyright-holder xml:lang="ru">Мухин К.Ю., Пылаева О.Н.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://rjdn.abvpress.ru/jour/article/view/268">https://rjdn.abvpress.ru/jour/article/view/268</self-uri><abstract xml:lang="en"><p><italic>Lennox–Gastaut syndrome (LGS) is a childhood epileptic encephalopathy characterized by frequent polymorphic seizures (including tonic axial seizures), pronounced cognitive impairment, typical changes in the electroencephalogram and drug resistance. Since the disease is quite common (accounts for 4–10 % of all childhood epilepsy) and is characterized by various seizures that are frequently resistant to multiple antiepileptic drugs, great hopes are currently centered on the development of novel antiepileptic drugs with principally different mechanisms of action aimed to treat this severe form of epilepsy. Rufinamide (inovelon) is a promising antiepileptic drug for LGS therapy. In 2008, it was approved by the FDA as an adjunctive treatment of seizures associated with LGS in adults and children over 4 years of age. Rufinamide demonstrated its efficacy against both drop seizures (tonic/atonic) and generalized seizures (tonic, atonic and tonic-clonic) in LGS. In January 2015, the drug was approved for use in the Russian Federation for seizures associated with LGS in patients over 4 years of age. Multiple studies have demonstrated high efficacy and good tolerability of rufinamide in children and adults with epilepsy. In this article, we provide a systematic review of the currently available data on the use of rufinamide in the treatment of seizures associated with LGS.</italic></p></abstract><trans-abstract xml:lang="ru"><p/></trans-abstract><kwd-group xml:lang="en"><kwd>epilepsy</kwd><kwd>drug-resistant epilepsy</kwd><kwd>Lennox–Gastaut syndrome</kwd><kwd>epileptic seizure</kwd><kwd>tonic epileptic seizure</kwd><kwd>antiepileptic drug</kwd><kwd>rufinamide</kwd><kwd>mechanism of action</kwd><kwd>pharmacokinetics</kwd><kwd>efficacy</kwd><kwd>tolerability</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>эпилепсия</kwd><kwd>резистентные формы эпилепсии</kwd><kwd>синдром Леннокса–Гасто</kwd><kwd>эпилептический приступ</kwd><kwd>тонический эпилептический приступ</kwd><kwd>антиэпилептический препарат</kwd><kwd>руфинамид</kwd><kwd>механизм действия</kwd><kwd>фармакокинетика</kwd><kwd>эффективность</kwd><kwd>переносимость</kwd></kwd-group><funding-group><funding-statement xml:lang="en">Eisai Co., Ltd.</funding-statement><funding-statement xml:lang="ru">Компания Eisai</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Inovelon: medication package insert. (In Russ.).</mixed-citation><mixed-citation xml:lang="ru">Инструкция по применению лекарственного препарата для медицинского применения Иновелон.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">Mukhin K.Yu., Mironov M.B. Clinical, electroencephalographic and neuroimaging characteristics of epileptic syndromes with tonic seizures. Russkiy zhurnal detskoy nevrologii = Russian Journal of Child Neurology 2014;9(3):13–22. (In Russ.).</mixed-citation><mixed-citation xml:lang="ru">Мухин К.Ю., Миронов М.Б. Клинические, электроэнцефалографические и нейровизуализационные характеристики эпилептических синдромов, ассоциированных с тоническими приступами. Русский журнал детской неврологии 2014;9(3):13–22.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">Mukhin K.Yu., Pylaeva O.A. Rufinamide (Inovelon) in the treatment of Lennox– Gastaut syndrome (literature review and case report). Russkiy zhurnal detskoy nevrologii = Russian Journal of Child Neurology 2015;10(4):47–54. (In Russ.).</mixed-citation><mixed-citation xml:lang="ru">Мухин К.Ю., Пылаева О.А. Руфинамид (Иновелон) в лечении синдрома Леннокса–Гасто (обзор литературы и описание случая). Русский журнал детской неврологии 2015;10(4):47–54.</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">Pylaeva O.A., Mukhin K.Yu., Petrukhin A.S. Side effects of antiepileptic medication. Moscow: Granat, 2016. 236 p. (In Russ.).</mixed-citation><mixed-citation xml:lang="ru">Пылаева О.А., Мухин К.Ю., Петрухин А.С. Побочные эффекты антиэпилептической терапии. М.: Гранат, 2016. 236 с.</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><mixed-citation>Al-Banji M.H., Zahr D.K., Jan M.M. Lennox–Gastaut syndrome. Management update. Neurosciences (Riyadh) 2015;20(3):207–12. PMID: 26166587. DOI: 10.17712/nsj.2015.3.20140677.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Albini M., Morano A., Fanella M. et al. Effectiveness of rufinamide in the treatment of idiopathic generalized epilepsy with atypical evolution: case report and review of the literature. Clin EEG Neurosci 2016;47(2):162–6. DOI: 10.1177/1550059414559940.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Aldenkamp A., Besag F., Gobbi G. et al. Psychiatric and behavioural disorders in children with epilepsy (ILAE Task Force report): adverse cognitive and behavioral effects of antiepileptic drugs in children. Epileptic Disord 2016. PMID: 27184878. DOI: 10.1684/epd.2016.0817.</mixed-citation></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">Alsaad A.M., Koren G. Exposure to rufinamide and risks of CNS adverse events in drug-resistant epilepsy: a meta-analysis of randomized, placebo-controlled trials. Br J Clin Pharmacol 2014;78(6):1264–71. PMID: 25132372. DOI: 10.1111/ bcp.12479.</mixed-citation><mixed-citation xml:lang="ru">Alsaad A.M., Koren G. Exposure to rufinamide and risks of CNS adverse events in drug-resistant epilepsy: a meta-analysis of randomized, placebo-controlled trials. Br J Clin Pharmacol 2014;78(6):1264–71. PMID: 25132372. DOI: 10.1111/bcp.12479.</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><mixed-citation>Beaumanoir A., Dravet Ch. The Lennox– Gastaut syndrome. In: Epileptic syndromes in infancy, childhood and adolescence. 2nd edn. Eds.: J. Roger, M. Bureau, Ch. Dravet et al. London: John Libbey, 1992. Pр. 307–312.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Brodie M.J., Rosenfeld W.E., Vazquez B. et al. Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial. Epilepsia 2009;50(8):1899–909. PMID: 19490053. DOI: 10.1111/j.1528-1167.2009.02160.x.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Cheng-Hakimian A., Anderson G.D., Miller J.W. Rufinamide: pharmacology, clinical trials, and role in clinical practice. Int J Clin Pract 2006;60(11):1497–501. PMID: 17073844. DOI: 10.1111/j.1742-1241.2006.01173.x.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Conry J.A., Ng Y.T., Paolicchi J.M. et al. Clobazam in the treatment of Lennox– Gastaut syndrome. Epilepsia 2009;50(5):1158–66. PMID: 19170737. DOI: 10.1111/j.1528-1167.2008.01935.x.</mixed-citation></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">Coppola G., Besag F., Cusmai R. et al. Current role of rufinamide in the treatment of childhood epilepsy: literature review and treatment guidelines. Eur J Paediatr Neurol 2014;18(6):685–90. DOI: 10.1016/j. ejpn.2014.05.008.</mixed-citation><mixed-citation xml:lang="ru">Coppola G., Besag F., Cusmai R. et al. Current role of rufinamide in the treatment of childhood epilepsy: literature review and treatment guidelines. Eur J Paediatr Neurol 2014;18(6):685–90. DOI: 10.1016/j.ejpn.2014.05.008.</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><mixed-citation>Coppola G., Grosso S., Franzoni E. et al. Rufinamide in children and adults with Lennox–Gastaut syndrome: first Italian multicenter experience. Seizure 2010;19(9):587–91. DOI: 10.1016/j.seizure.2010.09.008.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Coppola G. Update on rufinamide in childhood epilepsy. Neuropsychiatr Dis Treat 2011;7:399–407. PMID: 21792306. DOI: 10.2147/NDT.S13910.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Cross J.H., Auvin S., Falip M. et al. Expert opinion on the management of Lennox– Gastaut syndrome: treatment algorithms and practical considerations. Front Neurol 2017;8:505. PMID: 29085326. DOI: 10.3389/fneur.2017.00505.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Dodson W.E. Felbamate in the treatment of Lennox–Gastaut syndrome: results of a 12-month open-label study following a randomized clinical trial. Epilepsia 1993;34(Suppl 7):S18–24. DOI: 10.1111/j.1528-1157.1993.tb04590.x.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Epilepsies: diagnosis and management (2012, updated in 2016). NICE guideline CG137. Available at: http://www.nice.org.uk/guidance/CG137.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Gastaut H., Roger J., Soulayrol R. et al. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as “petit mal variant”) or Lennox syndrome. Epilepsia 1966;7(2):139–79. PMID: 4959714.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Genton P., Dravet Ch. The Lennox– Gastaut syndrome. In: Comprehensive еpileptology. 2nd edn. Eds.: J. Engel, T.A. Pedley. Philadelphia: Lippincott-Raven, 2007. Pр. 2417–2427.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Glauser T., Kluger G., Sachdeo R. et al. Rufinamide for generalized seizures associated with Lennox–Gastaut syndrome. Neurology 2008;70(21):1950–8. DOI: 10.1212/01.wnl.0000303813.95800.0d.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Glauser T.A., Levisohn P.M., Ritter F., Sachdeo R.C. Topiramate in Lennox– Gastaut syndrome: open-label treatment of patients completing a randomized controlled trial. Topiramate YL Study Group. Epilepsia 2000;41(Suppl 1):S86–90. DOI: 10.1111/j.1528-1157.2000.tb01563.x.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Hakimian S., Cheng-Hakimian A., Anderson G.D., Miller J.W. Rufinamide: a new antiepileptic medication. Expert Opin Pharmacother 2007;8(12):1931–40. PMID: 17696794. DOI: 10.1517/14656566.8.12.1931.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Hancock E.C., Cross J.H. Treatment of Lennox–Gastaut syndrome. Cochrane Database Syst Rev 2013;2:CD003277. DOI: 10.1002/14651858.CD003277.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Inovelon® (rufinamide) Summary of Product Characteristics. Eisai Ltd. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000660/WC500032937.pdf.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Jaraba S., Santamarina E., Miró J. et al. Rufinamide in children and adults in routine clinical practice. Acta Neurol Scand 2017;135(1):122–8. DOI: 10.1111/ane.12572.</mixed-citation></ref><ref id="B27"><label>27.</label><citation-alternatives><mixed-citation xml:lang="en">Kerr M., Kluger G., Philip S. Evolution and management of Lennox–Gastaut syndrome through adolescence and into adulthood: are seizures always the primary issue? Epileptic Disord 2011;13(Suppl 1):S15– S26. PMID: 21669559. DOI: 10.1684/ epd.2011.0409.</mixed-citation><mixed-citation xml:lang="ru">Kerr M., Kluger G., Philip S. Evolution and management of Lennox–Gastaut syndrome through adolescence and into adulthood: are seizures always the primary issue? Epileptic Disord 2011;13(Suppl 1):S15– S26. PMID: 21669559. DOI: 10.1684/epd.2011.0409.</mixed-citation></citation-alternatives></ref><ref id="B28"><label>28.</label><mixed-citation>Kessler S.K., McCarthy A., Cnaan A., Dlugos D.J. Retention rates of rufinamide in pediatric epilepsy patients with and without Lennox–Gastaut Syndrome. Epilepsy Res 2015;112:18–26. PMID: 25847334. DOI: 10.1016/j.eplepsyres.2015.02.003.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Kim J.Y., Lee C.G., Yu H.J. et al. The efficacy and tolerability of rufinamide in intractable pediatric epilepsy. J Epilepsy Res 2012;2(2):33–7. PMID: 24649460. DOI: 10.14581/jer.12009.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Kim S.H., Lee J.H., Ryu H.W. et al. Shortterm efficacy and tolerability of rufinamide adjunctive therapy in children with refractory generalised epilepsy. Epileptic Disord 2013;15(1):49–54. PMID: 23531645. DOI: 10.1684/epd.2013.0557.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Kluger G., Haberlandt E., Kurlemann G. et al. First European long-term experience with the orphan drug rufinamide in childhood-onset refractory epilepsy. Epilepsy Behav 2010;17(4):546–8. PMID: 20185372. DOI: 10.1016/j.yebeh.2010.01.005.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Kluger G., Glauser T., Krauss G. et al. Adjunctive rufinamide in Lennox–Gastaut syndrome: a long-term, open-label extension study. Acta Neurol Scand 2010 Sep;122(3):202–8. PMID: 20199521. DOI: 10.1111/j.1600-0404.2010.01334.x.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Kluger G., Bauer B. Role of rufinamide in the management of Lennox–Gastaut syndrome (childhood epileptic encephalopathy). Neuropsychiatr Dis Treat 2007;3(1):3–11. PMID: 19300535.</mixed-citation></ref><ref id="B34"><label>34.</label><citation-alternatives><mixed-citation xml:lang="en">Lee E.H., Yum M.S., Ko T.S. Effectiveness and tolerability of rufinamide in children and young adults with Lennox–Gastaut syndrome: a single center study in Korea. Clin Neurol Neurosurg 2013;115(7): 926–9. PMID: 23083943. DOI: 10.1016/j. clineuro.2012.09.021.</mixed-citation><mixed-citation xml:lang="ru">Lee E.H., Yum M.S., Ko T.S. Effectiveness and tolerability of rufinamide in children and young adults with Lennox–Gastaut syndrome: a single center study in Korea. Clin Neurol Neurosurg 2013;115(7): 926–9. PMID: 23083943. DOI: 10.1016/j.clineuro.2012.09.021.</mixed-citation></citation-alternatives></ref><ref id="B35"><label>35.</label><mixed-citation>Liao W.P., Shi Y.W., Long Y.S. et al. Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs: associated with loss of function of Na(v) 1.1. Epilepsia 2010;51(9):1669–78. PMID: 20550552. DOI: 10.1111/j.1528-1167.2010.02645.x.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>McMurray R., Striano P. Treatment of adults with Lennox–Gastaut syndrome: further analysis of efficacy and safety/ tolerability of rufinamide. Neurol Ther 2016;5(1):35–43. PMID: 26861566. DOI: 10.1007/s40120-016-0041-9.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Moavero R., Santarone M.E., Galasso C., Curatolo P. Cognitive and behavioral effects of new antiepileptic drugs in pediatric epilepsy. Brain Dev 2017;39(6):464–9. PMID: 28202262. DOI: 10.1016/j.braindev.2017.01.006.</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Montouris G.D., Wheless J.W., Glauser T.A. The efficacy and tolerability of pharmacologic treatment options for Lennox– Gastaut syndrome. Epilepsia 2014; 55(Suppl 4):10–20. PMID: 25284033. DOI: 10.1111/epi.12732.</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Motte J., Trevathan E., Arvidsson J.F. et al. Lamotrigine for generalized seizures associated with the Lennox–Gastaut syndrome. N Engl J Med 1997;337(25):1807–12. DOI: 10.1056/NEJM199712183372504.</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Mourand I., Crespel A., Gelisse P. Dramatic weight loss with rufinamide. Epilepsia 2013;54(1):e5–8. PMID: 22780580. DOI: 10.1111/j.1528-1167.2012.03579.x.</mixed-citation></ref><ref id="B41"><label>41.</label><citation-alternatives><mixed-citation xml:lang="en">Ng Y.T., Conry J.A., Drummond R. et al. Randomized, phase III study results of clobazam in Lennox–Gastaut syndrome. Neurology 2011;77(15):1473–81. PMID: 21956725. DOI: 10.1212/ WNL.0b013e318232de76.</mixed-citation><mixed-citation xml:lang="ru">Ng Y.T., Conry J.A., Drummond R. et al. Randomized, phase III study results of clobazam in Lennox–Gastaut syndrome. Neurology 2011;77(15):1473–81. PMID: 21956725. DOI: 10.1212/WNL.0b013e318232de76.</mixed-citation></citation-alternatives></ref><ref id="B42"><label>42.</label><mixed-citation>Nikanorova M., Brandt C., Auvin S., McMurray R. Real-world data on rufinamide treatment in patients with Lennox– Gastaut syndrome: results from a European noninterventional registry study. Epilepsy Behav 2017;76:63–70. PMID: 28927712. DOI: 10.1016/j.yebeh.2017.08.026.</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Ohtsuka Y., Yoshinaga H., Shirasaka Y. et al. Long-term safety and seizure outcome in Japanese patients with Lennox–Gastaut syndrome receiving adjunctive rufinamide therapy: an open-label study following a randomized clinical trial. Epilepsy Res 2016;121:1–7. PMID: 26827266. DOI: 10.1016/j. eplepsyres.2016.01.002.</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Ohtsuka Y., Yoshinaga H., Shirasaka Y. et al. Rufinamide as an adjunctive therapy for Lennox–Gastaut syndrome: a randomized double-blind placebo-controlled trial in Japan. Epilepsy Res 2014;108(9): 1627–36. PMID: 25219353. DOI: 10.1016/j.eplepsyres.2014.08.019.</mixed-citation></ref><ref id="B45"><label>45.</label><citation-alternatives><mixed-citation xml:lang="en">Ostendorf A.P., Ng Y.T. Treatment-resistant Lennox–Gastaut syndrome: therapeutic trends, challenges and future directions. Neuropsychiatr Dis Treat 2017;13:1131– 40. PMID: 28461749. DOI: 10.2147/NDT. S115996.</mixed-citation><mixed-citation xml:lang="ru">Ostendorf A.P., Ng Y.T. Treatment-resistant Lennox–Gastaut syndrome: therapeutic trends, challenges and future directions. Neuropsychiatr Dis Treat 2017;13:1131– 40. PMID: 28461749. DOI: 10.2147/NDT.S115996.</mixed-citation></citation-alternatives></ref><ref id="B46"><label>46.</label><mixed-citation>Palhagen S., Canger R., Henriksen O. et al. Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy. Epilepsy Res 2001;43(2):115–24. PMID: 11164700.</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Panayotopoulos С.P. Principles of therapy in the epilepsies. In: A clinical guide to epileptic syndromes and their treatment. London: Springer, 2007. Pp. 155–184.</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Panayiotopoulos C.P. A clinical guide to epileptic syndromes and their treatment: Based on the ILAE classifications and practice parameter guidelines. 2nd edn. London: Springer, 2010. 654 p.</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Resnick T., Arzimanoglou A., Brown L.W. et al. Rufinamide from clinical trials to clinical practice in the United States and Europe. Epileptic Disord 2011;13(Suppl 1):S27–43. PMID: 21669560. DOI: 10.1684/epd.2011.0421.</mixed-citation></ref><ref id="B50"><label>50.</label><citation-alternatives><mixed-citation xml:lang="en">Sachdeo R.C., Glauser T.A., Ritter F. et al. A double-blind, randomized trial of topiramate in Lennox–Gastaut syndrome. Neurology 1999;52(9):1882–7. DOI: 10.1212/ WNL.52.9.1882.</mixed-citation><mixed-citation xml:lang="ru">Sachdeo R.C., Glauser T.A., Ritter F. et al. A double-blind, randomized trial of topiramate in Lennox–Gastaut syndrome. Neurology 1999;52(9):1882–7. DOI: 10.1212/WNL.52.9.1882.</mixed-citation></citation-alternatives></ref><ref id="B51"><label>51.</label><citation-alternatives><mixed-citation xml:lang="en">Schimpf R., Veltmann C., Papavassiliu T. et al. Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide. Heart Rhythm 2012;9(5):776–81. PMID: 22245794. DOI: 10.1016/j. hrthm.2012.01.006.</mixed-citation><mixed-citation xml:lang="ru">Schimpf R., Veltmann C., Papavassiliu T. et al. Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide. Heart Rhythm 2012;9(5):776–81. PMID: 22245794. DOI: 10.1016/j.hrthm.2012.01.006.</mixed-citation></citation-alternatives></ref><ref id="B52"><label>52.</label><mixed-citation>The Felbamate Study Group in Lennox– Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox–Gastaut syndrome). N Engl J Med 1993;328(1):29–33. DOI: 10.1056/NEJM199301073280105.</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Thome-Souza S., Kadish N.E., Ramgopal S. et al. Safety and retention rate of rufinamide in 300 patients: a single pediatric epilepsy center experience. Epilepsia 2014;55(8):1235–44. PMID: 25070475. DOI: 10.1111/epi.12689.</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Tomson T., Marson A., Boon P. et al. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia 2015;56(7):1006–19. DOI: 10.1111/epi.13021.</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Vendrame M., Loddenkemper T., Gooty V.D. et al. Experience with rufinamide in a pediatric population: a single center's experience. Pediatr Neurol 2010;43(3):155–8. PMID: 20691934. DOI: 10.1016/j.pediatrneurol.2010.04.003.</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Verrotti A., Loiacono G., Ballone E. et al. Efficacy of rufinamide in drug-resistant epilepsy: a meta-analysis. Pediatr Neurol 2011;44(5):347–9. PMID: 21481742. DOI: 10.1016/j.pediatrneurol.2010.12.005.</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Verrotti A., Loiacono G., Rossi A. et al. Successful treatment of refractory seizures with rufinamide in children with schizencephaly: report of 3 cases. J Child Neurol 2015;30(8):1079–83. DOI: 10.1177/0883073814542951.</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Wheless J.W., Clarke D.F., Arzimanoglou A., Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord 2007;9(4):353–412. PMID: 18077226. DOI: 10.1684/epd.2007.0144.</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Wheless J.W., Clarke D.F., Carpenter D. Treatment of pediatric epilepsy: expert opinion, 2005. J Child Neurol 2005;20(suppl 1):S1–56. PMID: 16615562. DOI: 10.1177/088307380502000101.</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Wheless J.W., Conry J., Krauss G. et al. Safety and tolerability of rufinamide in children with epilepsy: a pooled analysis of 7 clinical studies. J Child Neurol 2009;24(12):1520–5. PMID: 19955344. DOI: 10.1177/0883073809350508.</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Wier H.A., Cerna A., So T.Y. Rufinamide for pediatric patients with Lennox–Gastaut syndrome: a comprehensive overview. Paediatric Drugs 2011;13(2):97–106. PMID: 21351809. DOI: 10.2165/11586920-000000000-00000.</mixed-citation></ref></ref-list></back></article>
