Clinical Management of Drug Resistant Epilepsy: A Review on Current Strategies

References

• Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE commission on therapeutic strategies: definition of drug resistant epilepsy. Epilepsia. 2009;51(6):1069–1077. doi:10.1111/j.1528-1167.2009.02397.x19889013
   PubMed Web of Science ®Google Scholar
• Brodie MJ, Barry SJE, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548–1554. doi:10.1212/WNL.0b013e3182563b1922573629
   PubMed Web of Science ®Google Scholar
• Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314–319. doi:10.1056/NEJM20000203342050310660394
   PubMed Web of Science ®Google Scholar
• Schiller Y, Najjar Y. Quantifying the response to antiepileptic drugs: effect of past treatment history. Neurology. 2008;70(1):54–65. doi:10.1212/01.wnl.0000286959.22040.6e18166707
   PubMed Web of Science ®Google Scholar
• Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75(3):279. doi:10.1001/jamaneurol.2017.394929279892
   PubMed Web of Science ®Google Scholar
• Callaghan BC, Anand K, Hesdorffer D, Hauser WA, French JA. Likelihood of seizure remission in an adult population with refractory epilepsy. Ann Neurol. 2007;62(4):382–389. doi:10.1002/ana.2116617880009
   PubMed Web of Science ®Google Scholar
• Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007;62(4):375–381. doi:10.1002/ana.2106417253624
   PubMed Web of Science ®Google Scholar
• Callaghan B, Schlesinger M, Rodemer W, et al. Remission and relapse in a drug-resistant epilepsy population followed prospectively: drug-resistant epilepsy population. Epilepsia. 2011;52(3):619–626. doi:10.1111/j.1528-1167.2010.02929.x21269287
   PubMed Web of Science ®Google Scholar
• Ryvlin P, Cucherat M, Rheims S. Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials. Lancet Neurol. 2011;10(11):961–968. doi:10.1016/S1474-4422(11)70193-421937278
   PubMed Web of Science ®Google Scholar
• Choi H, Hayat MJ, Zhang R, et al. Drug-resistant epilepsy in adults: outcome trajectories after failure of two medications. Epilepsia. 2016;57(7):1152–1160. doi:10.1111/epi.1340627265407
   PubMed Web of Science ®Google Scholar
• Zaccara G, Mula M, Ferrò B, et al. Do neurologists agree in diagnosing drug resistance in adults with focal epilepsy? Epilepsia. 2019;60(1):175–183. doi:10.1111/epi.1462230585315
   PubMed Web of Science ®Google Scholar
• O’ Rourke G, O’ Brien JJ. Identifying the barriers to antiepileptic drug adherence among adults with epilepsy. Seizure. 2017;45:160–168. doi:10.1016/j.seizure.2016.12.00628063375
   PubMed Web of Science ®Google Scholar
• Anzellotti F, Dono F, Evangelista G, et al. Psychogenic non-epileptic seizures and pseudo-refractory epilepsy, a management challenge. Front Neurol. 2020;11:461. doi:10.3389/fneur.2020.0046132582005
   PubMed Web of Science ®Google Scholar
• Thomas P, Valton L, Genton P. Absence and myoclonic status epilepticus precipitated by antiepileptic drugs in idiopathic generalized epilepsy. Brain. 2006;129(5):1281–1292. doi:10.1093/brain/awl04716513683
   PubMed Web of Science ®Google Scholar
• Boylan LS, Labovitz DL, Jackson SC, Starner K, Devinsky O. Auras are frequent in idiopathic generalized epilepsy. Neurology. 2006;67(2):343–345. doi:10.1212/01.wnl.0000225185.37081.9716864837
   PubMed Web of Science ®Google Scholar
• Lombroso CT. Consistent EEG focalities detected in subjects with primary generalized epilepsies monitored for two decades. Epilepsia. 1997;38(7):797–812. doi:10.1111/j.1528-1157.1997.tb01467.x9579907
   PubMed Web of Science ®Google Scholar
• Kellinghaus C, Lüders HO. Frontal lobe epilepsy. Epileptic Disord. 2004;6(4):223–239.15634619
   PubMed Web of Science ®Google Scholar
• Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia. 2018;59(12):2179–2193. doi:10.1111/epi.1459630426482
   PubMed Web of Science ®Google Scholar
• Marson A, Jacoby A, Johnson A, et al. Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial. Lancet. 2005;365(9476):2007–2013. doi:10.1016/S0140-6736(05)66694-915950714
   PubMed Web of Science ®Google Scholar
• An S, Malhotra K, Dilley C, et al. Predicting drug-resistant epilepsy — a machine learning approach based on administrative claims data. Epilepsy Behavior. 2018;89:118–125. doi:10.1016/j.yebeh.2018.10.01330412924
   PubMed Web of Science ®Google Scholar
• Mohanraj R, Brodie MJ. Outcomes of newly diagnosed idiopathic generalized epilepsy syndromes in a non-pediatric setting. Acta Neurol Scand. 2007;115(3):204–208. doi:10.1111/j.1600-0404.2006.00791.x17295717
   PubMed Web of Science ®Google Scholar
• Szaflarski JP, Lindsell CJ, Zakaria T, Banks C, Privitera MD. Seizure control in patients with idiopathic generalized epilepsies: EEG determinants of medication response. Epilepsy Behavior. 2010;17(4):525–530. doi:10.1016/j.yebeh.2010.02.00520227351
   PubMed Web of Science ®Google Scholar
• Holtkamp M, Kowski AB, Merkle H, Janz D. Long-term outcome in epilepsy with grand mal on awakening: forty years of follow-up. Ann Neurol. 2014;75(2):298–302. doi:10.1002/ana.2410324395517
   PubMed Web of Science ®Google Scholar
• Senf P, Schmitz B, Holtkamp M, Janz D. Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors. Neurology. 2013;81(24):2128–2133. doi:10.1212/01.wnl.0000437303.36064.f824212391
   PubMed Web of Science ®Google Scholar
• Gomez-Ibañez A, McLachlan RS, Mirsattari SM, Diosy DC, Burneo JG. Prognostic factors in patients with refractory idiopathic generalized epilepsy. Epilepsy Res. 2017;130:69–73. doi:10.1016/j.eplepsyres.2017.01.01128157601
   PubMed Web of Science ®Google Scholar
• Gesche J, Khanevski M, Solberg C, Beier CP. Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies. Epilepsia. 2017;58(4):e64–e69. doi:10.1111/epi.1370228230254
   PubMed Web of Science ®Google Scholar
• Catarino CB, Liu JYW, Liagkouras I, et al. Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology. Brain. 2011;134(10):2982–3010. doi:10.1093/brain/awr12921719429
   PubMed Web of Science ®Google Scholar
• Genton P, Velizarova R, Dravet C. Dravet syndrome: the long-term outcome: long-term outcome. Epilepsia. 2011;52:44–49. doi:10.1111/j.1528-1167.2011.03001.x21463279
   PubMed Web of Science ®Google Scholar
• Singh R, Scheffer IE, Crossland K, Berkovic SF. Generalized epilepsy with febrile seizures plus: a common childhood-onset genetic epilepsy syndrome. Ann Neurol. 1999;45(1):75–81. doi:10.1002/1531-8249(199901)45:1<75::aid-art13>3.0.co;2-w9894880
   PubMed Web of Science ®Google Scholar
• Margari L, Legrottaglie AR, Vincenti A, et al. Association between SCN1A gene polymorphisms and drug resistant epilepsy in pediatric patients. Seizure. 2018;55:30–35. doi:10.1016/j.seizure.2018.01.00229353705
   PubMed Web of Science ®Google Scholar
• Roy PL, Ronquillo LH, Ladino LD, Tellez-Zenteno JF. Risk factors associated with drug resistant focal epilepsy in adults: a case control study. Seizure. 2019;73:46–50. doi:10.1016/j.seizure.2019.10.02031734466
   PubMed Web of Science ®Google Scholar
• Semah F, Picot M-C, Adam C, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology. 1998;51(5):1256–1262. doi:10.1212/WNL.51.5.12569818842
   PubMed Web of Science ®Google Scholar
• Perucca E, French J, Bialer M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol. 2007;6(9):793–804. doi:10.1016/S1474-4422(07)70215-617706563
   PubMed Web of Science ®Google Scholar
• Beghi E, Gatti G, Tonini C, et al. Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial. Epilepsy Res. 2003;57(1):1–13. doi:10.1016/j.eplepsyres.2003.09.00714706729
   PubMed Web of Science ®Google Scholar
• Millul A, Iudice A, Adami M, et al. Alternative monotherapy or add-on therapy in patients with epilepsy whose seizures do not respond to the first monotherapy: an Italian multicenter prospective observational study. Epilepsy Behav. 2013;28(3):494–500. doi:10.1016/j.yebeh.2013.05.03823892580
   PubMed Web of Science ®Google Scholar
• Brodie MJ, Yuen AWC. Lamotrigine substitution study: evidence for synergism with sodium valproate? Epilepsy Res. 1997;26(3):423–432. doi:10.1016/S0920-1211(96)01007-89127723
   PubMed Web of Science ®Google Scholar
• Chiron C, Marchand M, Tran A, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. Lancet. 2000;356(9242):1638–1642. doi:10.1016/S0140-6736(00)03157-311089822
   PubMed Web of Science ®Google Scholar
• Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376(21):2011–2020. doi:10.1056/NEJMoa161161828538134
   PubMed Web of Science ®Google Scholar
• Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. Lancet Neurol. 2012;11(9):792–802. doi:10.1016/S1474-4422(12)70153-922832500
   PubMed Web of Science ®Google Scholar
• Gilliam FG, Fessler AJ, Baker G, Vahle V, Carter J, Attarian H. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology. 2004;62(1):23–27. doi:10.1212/WNL.62.1.2314718691
   PubMed Web of Science ®Google Scholar
• Perucca P, Carter J, Vahle V, Gilliam FG. Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy. Neurology. 2009;72(14):1223–1229. doi:10.1212/01.wnl.0000345667.45642.6119349601
   PubMed Web of Science ®Google Scholar
• Perucca E, Gram L, Avanzini G, Dulac O. Antiepileptic drugs as a cause of worsening seizures. Epilepsia. 1998;39(1):5–17. doi:10.1111/j.1528-1157.1998.tb01268.x9578007
   PubMed Web of Science ®Google Scholar
• Rheims S, Ryvlin P. Pharmacotherapy for tonic–clonic seizures. Expert Opin Pharmacother. 2014;15(10):1417–1426. doi:10.1517/14656566.2014.91502924798217
   PubMed Web of Science ®Google Scholar
• Rheims S, Perucca E, Cucherat M, Ryvlin P. Factors determining response to antiepileptic drugs in randomized controlled trials. A systematic review and meta-analysis: response to AEDs in Randomized Trials. Epilepsia. 2011. doi:10.1111/j.1528-1167.2010.02915.x
   Web of Science ®Google Scholar
• Thieffry S, Klein P, Baulac M, et al. Understanding the challenge of comparative effectiveness research in focal epilepsy: a review of network meta‐analyses and real‐world evidence on antiepileptic drugs. Epilepsia. 2020;61(4):595–609. doi:10.1111/epi.1647632201951
   PubMed Web of Science ®Google Scholar
• Rheims S, Cucherat M, Arzimanoglou A, Ryvlin P. Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy. PLoS Med. 2008;5(8):e166. doi:10.1371/journal.pmed.005016618700812
   PubMed Web of Science ®Google Scholar
• Gazzola DM, Balcer LJ, French JA. Seizure-free outcome in randomized add-on trials of the new antiepileptic drugs. Epilepsia. 2007;48(7):1303–1307. doi:10.1111/j.1528-1167.2007.01136.x17521343
   PubMed Web of Science ®Google Scholar
• Krauss GL, Klein P, Brandt C, et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020;19(1):38–48. doi:10.1016/S1474-4422(19)30399-031734103
   PubMed Web of Science ®Google Scholar
• Hemery C, Ryvlin P, Rheims S. Prevention of generalized tonic-clonic seizures in refractory focal epilepsy: a meta-analysis. Epilepsia. 2014;55(11):1789–1799. doi:10.1111/epi.1276525182978
   PubMed Web of Science ®Google Scholar
• Arzimanoglou A, French J, Blume WT, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009;8(1):82–93. doi:10.1016/S1474-4422(08)70292-819081517
   PubMed Web of Science ®Google Scholar
• Guery D, Rheims S. Is the mechanism of action of antiseizure drugs a key element in the choice of treatment? Fundam Clin Pharmacol. 2020;fcp.12614. doi:10.1111/fcp.12614
   Web of Science ®Google Scholar
• Trinka E, Brigo F. Antiepileptogenesis in humans: disappointing clinical evidence and ways to move forward. Curr Opin Neurol. 2014;27(2):227–235. doi:10.1097/WCO.000000000000006724556736
   PubMed Web of Science ®Google Scholar
• Perucca P, Perucca E. Identifying mutations in epilepsy genes: impact on treatment selection. Epilepsy Res. 2019;152:18–30. doi:10.1016/j.eplepsyres.2019.03.00130870728
   PubMed Web of Science ®Google Scholar
• French JA, Lawson JA, Yapici Z, et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a Phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016;388(10056):2153–2163. doi:10.1016/S0140-6736(16)31419-227613521
   PubMed Web of Science ®Google Scholar
• Mirzaa GM, Campbell CD, Solovieff N, et al. Association of MTOR mutations with developmental brain disorders, including megalencephaly, focal cortical dysplasia, and pigmentary mosaicism. JAMA Neurol. 2016;73(7):836. doi:10.1001/jamaneurol.2016.036327159400
   PubMed Web of Science ®Google Scholar
• Baldassari S, Ribierre T, Marsan E, et al. Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta Neuropathol. 2019;138(6):885–900. doi:10.1007/s00401-019-02061-531444548
   PubMed Web of Science ®Google Scholar
• Griffith JL, Wong M. The mTOR pathway in treatment of epilepsy: a clinical update. Future Neurol. 2018;13(2):49–58. doi:10.2217/fnl-2018-000130505235
   PubMed Web of Science ®Google Scholar
• Guerrini R, Duchowny M, Jayakar P, et al. Diagnostic methods and treatment options for focal cortical dysplasia. Epilepsia. 2015;56(11):1669–1686. doi:10.1111/epi.1320026434565
   PubMed Web of Science ®Google Scholar
• Klepper J, Akman C, Armeno M, et al. Glut1 Deficiency Syndrome (Glut1DS): state of the art in 2020 and recommendations of the international Glut1DS study group. Epilepsia Open. 2020;5(3):354–365. doi:10.1002/epi4.1241432913944
   PubMedGoogle Scholar
• Lagae L, Sullivan J, Knupp K, et al. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10216):2243–2254. doi:10.1016/S0140-6736(19)32500-031862249
   PubMed Web of Science ®Google Scholar
• Hatini PG, Commons KG. Serotonin abnormalities in Dravet syndrome mice before and after the age of seizure onset. Brain Res. 2019;1724:146399. doi:10.1016/j.brainres.2019.14639931445030
   PubMed Web of Science ®Google Scholar
• Griffin AL, Jaishankar P, Grandjean J-M, Olson SH, Renslo AR, Baraban SC. Zebrafish studies identify serotonin receptors mediating antiepileptic activity in Dravet syndrome. Brain Commun. 2019;1(1):fcz008. doi:10.1093/braincomms/fcz00831667472
   PubMedGoogle Scholar
• Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC. Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain. 2017;aww342. doi:10.1093/brain/aww342
   Web of Science ®Google Scholar
• Pierson TM, Yuan H, Marsh ED, et al. GRIN2A mutation and early‐onset epileptic encephalopathy: personalized therapy with memantine. Ann Clin Transl Neurol. 2014;1(3):190–198. doi:10.1002/acn3.3924839611
   PubMed Web of Science ®Google Scholar
• Ihara Y, Tomonoh Y, Deshimaru M, et al. Retigabine, a Kv7.2/Kv7.3-channel opener, attenuates drug-induced seizures in knock-in mice harboring Kcnq2 Mutations. PLoS One. 2016;11(2):e0150095. doi:10.1371/journal.pone.015009526910900
   PubMed Web of Science ®Google Scholar
• Löscher W, Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci. 2005;6(8):591–602. doi:10.1038/nrn172816025095
   PubMed Web of Science ®Google Scholar
• Leandro K, Bicker J, Alves G, Falcão A, Fortuna A. ABC transporters in drug-resistant epilepsy: mechanisms of upregulation and therapeutic approaches. Pharmacol Res. 2019;144:357–376. doi:10.1016/j.phrs.2019.04.03131051235
   PubMed Web of Science ®Google Scholar
• Asadi-Pooya AA, Razavizadegan SMA, Abdi-Ardekani A, Sperling MR. Adjunctive use of verapamil in patients with refractory temporal lobe epilepsy: a pilot study. Epilepsy Behavior. 2013;29(1):150–154. doi:10.1016/j.yebeh.2013.07.00623973639
   PubMed Web of Science ®Google Scholar
• Hesdorffer DC, Stables JP, Hauser WA, Annegers JF, Cascino G. Are certain diuretics also anticonvulsants? Ann Neurol. 2001;50(4):458–462. doi:10.1002/ana.113611601497
   PubMed Web of Science ®Google Scholar
• Ben-Ari Y, Gaiarsa J-L, Tyzio R, Khazipov R. GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev. 2007;87(4):1215–1284. doi:10.1152/physrev.00017.200617928584
   PubMed Web of Science ®Google Scholar
• Khalilov I, Holmes GL, Ben-Ari Y. In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures. Nat Neurosci. 2003;6(10):1079–1085. doi:10.1038/nn112514502289
   PubMed Web of Science ®Google Scholar
• Cohen I. On the origin of interictal activity in human temporal lobe epilepsy in vitro. Science. 2002;298(5597):1418–1421. doi:10.1126/science.107651012434059
   PubMed Web of Science ®Google Scholar
• Dzhala VI, Talos DM, Sdrulla DA, et al. NKCC1 transporter facilitates seizures in the developing brain. Nat Med. 2005;11(11):1205–1213. doi:10.1038/nm130116227993
   PubMed Web of Science ®Google Scholar
• Pressler RM, Boylan GB, Marlow N, et al. Bumetanide for neonatal seizures-back from the cotside. Nat Rev Neurol. 2015;11(12):724. doi:10.1038/nrneurol.2015.11626526530
   PubMed Web of Science ®Google Scholar
• Hampel P, Römermann K, Gramer M, Löscher W. The search for brain-permeant NKCC1 inhibitors for the treatment of seizures: pharmacokinetic-pharmacodynamic modelling of NKCC1 inhibition by azosemide, torasemide, and bumetanide in mouse brain. Epilepsy Behav. 2021;114(PtA):107616. doi:10.1016/j.yebeh.2020.10761633279441
   PubMed Web of Science ®Google Scholar
• Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol. 2011;7(1):31–40. doi:10.1038/nrneurol.2010.17821135885
   PubMed Web of Science ®Google Scholar
• Ravizza T, Lucas S-M, Balosso S, et al. Inactivation of caspase-1 in rodent brain: a novel anticonvulsive strategy. Epilepsia. 2006;47(7):1160–1168. doi:10.1111/j.1528-1167.2006.00590.x16886979
   PubMed Web of Science ®Google Scholar
• Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 2013;103(1):2–30. doi:10.1016/j.eplepsyres.2012.10.00123219031
   PubMed Web of Science ®Google Scholar
• Vogrig A, Joubert B, André-Obadia N, Gigli GL, Rheims S, Honnorat J. Seizure specificities in patients with antibody-mediated autoimmune encephalitis. Epilepsia. 2019;60(8):1508–1525. doi:10.1111/epi.1628231283859
   PubMed Web of Science ®Google Scholar
• Hirsch LJ, Gaspard N, van Baalen A, et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia. 2018;59(4):739–744. doi:10.1111/epi.1401629399791
   PubMed Web of Science ®Google Scholar
• Rheims S, Auvin S. Attention deficit/hyperactivity disorder and epilepsy. Curr Opin Neurol. 2021;34(2):219–225. doi:10.1097/WCO.000000000000090333464761
   PubMed Web of Science ®Google Scholar
• Sherman EMS, Slick DJ, Connolly MB, Eyrl KL. ADHD, Neurological correlates and health-related quality of life in severe pediatric epilepsy. Epilepsia. 2007;48(6):1083–1091. doi:10.1111/j.1528-1167.2007.01028.x17381442
   PubMed Web of Science ®Google Scholar
• Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age. Clin Pharmacokinet. 2006;45(4):351–363. doi:10.2165/00003088-200645040-0000216584283
   PubMed Web of Science ®Google Scholar
• Sirven JI, Fife TD, Wingerchuk DM, Drazkowski JF. Second-generation antiepileptic drugs’ impact on balance: a meta-analysis. Mayo Clin Proc. 2007;82(1):40–47. doi:10.4065/82.1.4017285784
   PubMed Web of Science ®Google Scholar
• Finkle WD, Der JS, Greenland S, et al. Risk of fractures requiring hospitalization after an initial prescription for zolpidem, alprazolam, lorazepam, or diazepam in older adults. J Am Geriatr Soc. 2011;59(10):1883–1890. doi:10.1111/j.1532-5415.2011.03591.x22091502
   PubMed Web of Science ®Google Scholar
• Tomson T, Battino D, Bromley R, et al. Management of epilepsy in pregnancy: a report from the International league against epilepsy task force on women and pregnancy. Epileptic Disord. 2019;21(6):497–517. doi:10.1684/epd.2019.110531782407
   PubMed Web of Science ®Google Scholar
• Keni RR, Jose M, Sarma PS, Thomas SV. For the Kerala Registry of Epilepsy and Pregnancy Study Group. Teratogenicity of antiepileptic dual therapy: dose-dependent, drug-specific, or both? Neurology. 2018;90(9):e790–e796. doi:10.1212/WNL.000000000000503129429975
   PubMed Web of Science ®Google Scholar
• Kanner AM. Management of psychiatric and neurological comorbidities in epilepsy. Nat Rev Neurol. 2016;12(2):106–116. doi:10.1038/nrneurol.2015.24326782334
   PubMed Web of Science ®Google Scholar
• Chen Z, Lusicic A, O’Brien TJ, Velakoulis D, Adams SJ, Kwan P. Psychotic disorders induced by antiepileptic drugs in people with epilepsy. Brain. 2016;139(10):2668–2678. doi:10.1093/brain/aww19627503872
   PubMed Web of Science ®Google Scholar
• Mula M. The pharmacological management of psychiatric comorbidities in patients with epilepsy. Pharmacol Res. 2016;107:147–153. doi:10.1016/j.phrs.2016.03.02227001226
   PubMed Web of Science ®Google Scholar
• Verrotti A, Tambucci R, Di Francesco L, et al. The role of polytherapy in the management of epilepsy: suggestions for rational antiepileptic drug selection. Expert Rev Neurother. 2020;20(2):167–173. doi:10.1080/14737175.2020.170766831855066
   PubMed Web of Science ®Google Scholar
• Stephen LJ, Forsyth M, Kelly K, Brodie MJ. Antiepileptic drug combinations—Have newer agents altered clinical outcomes? Epilepsy Res. 2012;98(2–3):194–198. doi:10.1016/j.eplepsyres.2011.09.00821982026
   PubMed Web of Science ®Google Scholar
• Jonker DM, Voskuyl RA, Danhof M. Synergistic Combinations of Anticonvulsant Agents: what Is the Evidence from Animal Experiments? Epilepsia. 2007;48(3):412–434. doi:10.1111/j.1528-1167.2006.00952.x17346245
   PubMed Web of Science ®Google Scholar
• Stafstrom CE. Mechanisms of action of antiepileptic drugs: the search for synergy. Curr Opin Neurol. 2010;23(2):157–163. doi:10.1097/WCO.0b013e32833735b520125013
   PubMed Web of Science ®Google Scholar
• Poolos NP, Warner LN, Humphreys SZ, Williams S. Comparative efficacy of combination drug therapy in refractory epilepsy. Neurology. 2012;78(1):62–68. doi:10.1212/WNL.0b013e31823ed0dd22170887
   PubMed Web of Science ®Google Scholar
• Sake J-K, Hebert D, Isojärvi J, et al. A pooled analysis of lacosamide clinical trial data grouped by mechanism of action of concomitant antiepileptic drugs. CNS Drugs. 2010;24(12):1055–1068. doi:10.2165/11587550-000000000-0000021090839
   PubMed Web of Science ®Google Scholar
• Besag FMC, Berry DJ, Pool F, Newbery -J-JE, Subel B. Carbamazepine Toxicity with Lamotrigine: pharmacokinetic or Pharmacodynamic Interaction? Epilepsia. 1998;39(2):183–187. doi:10.1111/j.1528-1157.1998.tb01356.x9577998
   PubMed Web of Science ®Google Scholar
• Engel J, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in Association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology. 2003;60(4):538–547. doi:10.1212/01.WNL.0000055086.35806.2D12601090
   PubMed Web of Science ®Google Scholar
• Haneef Z, Stern J, Dewar S, Engel J. Referral pattern for epilepsy surgery after evidence-based recommendations: a retrospective study. Neurology. 2010;75(8):699–704. doi:10.1212/WNL.0b013e3181eee45720733145
   PubMed Web of Science ®Google Scholar
• Ryvlin P, Cross JH, Rheims S. Epilepsy surgery in children and adults. Lancet Neurol. 2014;13(11):1114–1126. doi:10.1016/S1474-4422(14)70156-525316018
   PubMed Web of Science ®Google Scholar
• Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311–318. doi:10.1056/NEJM20010802345050111484687
   PubMed Web of Science ®Google Scholar
• Engel J. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012;307(9):922. doi:10.1001/jama.2012.22022396514
   PubMed Web of Science ®Google Scholar
• Dwivedi R, Ramanujam B, Chandra PS, et al. Surgery for drug-resistant epilepsy in children. N Engl J Med. 2017;377(17):1639–1647. doi:10.1056/NEJMoa161533529069568
   PubMed Web of Science ®Google Scholar
• Wyllie E, Lachhwani DK, Gupta A, et al. Successful surgery for epilepsy due to early brain lesions despite generalized EEG findings. Neurology. 2007;69(4):389–397. doi:10.1212/01.wnl.0000266386.55715.3f17646632
   PubMed Web of Science ®Google Scholar
• Janecek JK, Swanson SJ, Sabsevitz DS, et al. Language lateralization by fMRI and Wada testing in 229 patients with epilepsy: rates and predictors of discordance. Epilepsia. 2013;54(2):314–322. doi:10.1111/epi.1206823294162
   PubMed Web of Science ®Google Scholar
• Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019;393(10172):689–701. doi:10.1016/S0140-6736(18)32596-030686584
   PubMed Web of Science ®Google Scholar
• Gavvala J, Zafar M, Sinha SR, Kalamangalam G, Schuele S. Stereotactic EEG practices: a survey of United States tertiary referral epilepsy centers. J Clin Neurophysiol. 2020. doi:10.1097/WNP.0000000000000794
   Web of Science ®Google Scholar
• Ryvlin P, Rheims S. Predicting epilepsy surgery outcome. Curr Opin Neurol. 2016;29(2):182–188. doi:10.1097/WCO.000000000000030626886359
   PubMed Web of Science ®Google Scholar
• Jain P, Smith ML, Speechley K, et al. Seizure freedom improves health‐related quality of life after epilepsy surgery in children. Dev Med Child Neurol. 2020;62(5):600–608. doi:10.1111/dmcn.1439031709524
   PubMed Web of Science ®Google Scholar
• Ramos-Perdigués S, Baillés E, Mané A, et al. A prospective study contrasting the psychiatric outcome in drug-resistant epilepsy between patients who underwent surgery and a control group. Epilepsia. 2016;57(10):1680–1690. doi:10.1111/epi.1349727562413
   PubMed Web of Science ®Google Scholar
• Morrison-Levy N, Go C, Ochi A, et al. Children with autism spectrum disorders and drug-resistant epilepsy can benefit from epilepsy surgery. Epilepsy Behavior. 2018;85:200–204. doi:10.1016/j.yebeh.2018.06.02330032808
   PubMed Web of Science ®Google Scholar
• Lang JD, Grell L, Hagge M, et al. Long-term outcome after epilepsy surgery in older adults. Seizure. 2018;57:56–62. doi:10.1016/j.seizure.2018.02.01229604610
   PubMed Web of Science ®Google Scholar
• Lazow SP, Thadani VM, Gilbert KL, et al. Outcome of frontal lobe epilepsy surgery: outcome of Frontal Lobe Epilepsy Surgery. Epilepsia. 2012;53(10):1746–1755. doi:10.1111/j.1528-1167.2012.03582.x22780836
   PubMed Web of Science ®Google Scholar
• Chassoux F, Landré E, Mellerio C, et al. Type II focal cortical dysplasia: electroclinical phenotype and surgical outcome related to imaging: phenotype and Imaging in TTFCD. Epilepsia. 2012;53(2):349–358. doi:10.1111/j.1528-1167.2011.03363.x22221288
   PubMed Web of Science ®Google Scholar
• Kang JY, Sperling MR. Magnetic resonance imaging-guided laser interstitial thermal therapy for treatment of drug-resistant epilepsy. Neurotherapeutics. 2017;14(1):176–181. doi:10.1007/s13311-016-0498-327905093
   PubMed Web of Science ®Google Scholar
• Shimamoto S, Wu C, Sperling MR. Laser interstitial thermal therapy in drug-resistant epilepsy. Curr Opin Neurol. 2019;32(2):237–245. doi:10.1097/WCO.000000000000066230694919
   PubMed Web of Science ®Google Scholar
• Bourdillon P, Cucherat M, Isnard J, et al. Stereo-electroencephalography-guided radiofrequency thermocoagulation in patients with focal epilepsy: a systematic review and meta-analysis. Epilepsia. 2018;59(12):2296–2304. doi:10.1111/epi.1458430345535
   PubMed Web of Science ®Google Scholar
• Benbadis SR, Geller E, Ryvlin P, et al. Putting it all together: options for intractable epilepsy. Epilepsy Behavior. 2018;88:33–38. doi:10.1016/j.yebeh.2018.05.03030216929
   PubMed Web of Science ®Google Scholar
• Orosz I, McCormick D, Zamponi N, et al. Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children. Epilepsia. 2014;55(10):1576–1584. doi:10.1111/epi.1276225231724
   PubMed Web of Science ®Google Scholar
• Ryvlin P, Gilliam FG, Nguyen DK, et al. The long‐term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long‐term Effectiveness) trial. Epilepsia. 2014;55(6):893–900. doi:10.1111/epi.1261124754318
   PubMed Web of Science ®Google Scholar
• Bouwens van der Vlis TAM, Schijns OEMG, Schaper FLWVJ, et al. Deep brain stimulation of the anterior nucleus of the thalamus for drug-resistant epilepsy. Neurosurg Rev. 2019;42(2):287–296. doi:10.1007/s10143-017-0941-x29306976
   PubMed Web of Science ®Google Scholar
• Salanova V, Witt T, Worth R, et al. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015;84(10):1017–1025. doi:10.1212/WNL.000000000000133425663221
   PubMed Web of Science ®Google Scholar
• Velasco AL, Velasco F, Jimenez F, et al. Neuromodulation of the centromedian thalamic nuclei in the treatment of generalized seizures and the improvement of the quality of life in patients with lennox–gastaut syndrome. Epilepsia. 2006;47(7):1203–1212. doi:10.1111/j.1528-1167.2006.00593.x16886984
   PubMed Web of Science ®Google Scholar
• Skarpaas TL, Jarosiewicz B, Morrell MJ. Brain-responsive neurostimulation for epilepsy (RNS® System). Epilepsy Res. 2019;153:68–70. doi:10.1016/j.eplepsyres.2019.02.00330850259
   PubMed Web of Science ®Google Scholar
• Nune G, Arcot Desai S, Razavi B, et al. Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS® System: efficacy and description of chronic electrophysiological recordings. Clin Neurophysiol. 2019;130(8):1196–1207. doi:10.1016/j.clinph.2019.04.70631163364
   PubMed Web of Science ®Google Scholar
• Lambrechts DAJE, de Kinderen RJA, Vles JSH, de Louw AJA, Aldenkamp AP, Majoie HJM. A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy. Acta Neurol Scand. 2017;135(2):231–239. doi:10.1111/ane.1259227027847
   PubMed Web of Science ®Google Scholar
• Martin-McGill KJ, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Systematic Rev. 2020. doi:10.1002/14651858.CD001903.pub5
   Web of Science ®Google Scholar
• Kverneland M, Taubøll E, Molteberg E, et al. Pharmacokinetic interaction between modified Atkins diet and antiepileptic drugs in adults with drug‐resistant epilepsy. Epilepsia. 2019;60(11):2235–2244. doi:10.1111/epi.1636431602644
   PubMed Web of Science ®Google Scholar
• Gómez-Eguílaz M, Ramón-Trapero JL, Pérez-Martínez L, Blanco JR. The beneficial effect of probiotics as a supplementary treatment in drug-resistant epilepsy: a pilot study. Benef Microbes. 2018;9(6):875–881. doi:10.3920/BM2018.001830198325
   PubMed Web of Science ®Google Scholar
• Leidy NK, Elixhauser A, Vickrey B, Means E, Willian MK. Seizure frequency and the health-related quality of life of adults with epilepsy. Neurology. 1999;53(1):162. doi:10.1212/WNL.53.1.16210408553
   PubMed Web of Science ®Google Scholar
• Jacoby A, Baker GA, Steen N, Potts P, Chadwick DW. The clinical course of epilepsy and its psychosocial correlates: findings from a U.K. Community Study. Epilepsia. 1996;37(2):148–161. doi:10.1111/j.1528-1157.1996.tb00006.x8635425
   PubMed Web of Science ®Google Scholar
• Guekht AB, Mitrokhina TV, Lebedeva AV, et al. Factors influencing on quality of life in people with epilepsy. Seizure. 2007;16(2):128–133. doi:10.1016/j.seizure.2006.10.01117157536
   PubMed Web of Science ®Google Scholar
• Johnson EK, Jones JE, Seidenberg M, Hermann BP. The relative impact of anxiety, depression, and clinical seizure features on health-related quality of life in epilepsy. Epilepsia. 2004;45(5):544–550. doi:10.1111/j.0013-9580.2004.47003.x15101836
   PubMed Web of Science ®Google Scholar
• Cramer J. A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or an anxiety disorder during clinical trials. Epilepsy Behavior. 2003;4(2):124–132. doi:10.1016/S1525-5050(03)00005-212697136
   PubMed Web of Science ®Google Scholar
• Sheikh SR, Thompson N, Frech F, Malhotra M, Jehi L. Quantifying the burden of generalized tonic‐clonic seizures in patients with drug‐resistant epilepsy. Epilepsia. 2020;61(8):1627–1637. doi:10.1111/epi.1660332658343
   PubMed Web of Science ®Google Scholar
• Sherman EMS, Slick DJ, Eyrl KL. Executive dysfunction is a significant predictor of poor quality of life in children with epilepsy. Epilepsia. 2006;47(11):1936–1942. doi:10.1111/j.1528-1167.2006.00816.x17116035
   PubMed Web of Science ®Google Scholar
• Giovagnoli AR, Parente A, Tarallo A, Casazza M, Franceschetti S, Avanzini G. Self-rated and assessed cognitive functions in epilepsy: impact on quality of life. Epilepsy Res. 2014;108(8):1461–1468. doi:10.1016/j.eplepsyres.2014.06.00225060995
   PubMed Web of Science ®Google Scholar
• Sarkis RA, McGinnis S, Rushia SN, Park S, Ansari EE, Willment KC. Growing older with drug-resistant epilepsy: cognitive and psychosocial outcomes. J Neurol. 2018;265(5):1059–1064. doi:10.1007/s00415-018-8805-z29478222
   PubMed Web of Science ®Google Scholar
• Camfield PR, Andrade D, Camfield CS, et al. How can transition to adult care be best orchestrated for adolescents with epilepsy? Epilepsy Behavior. 2019;93:138–147. doi:10.1016/j.yebeh.2018.12.01530642688
   PubMed Web of Science ®Google Scholar
• Tellez-Zenteno JF, Patten SB, Jetté N, Williams J, Wiebe S. Psychiatric comorbidity in epilepsy: a population-based analysis. Epilepsia. 2007. doi:10.1111/j.1528-1167.2007.01222.x
   Google Scholar
• Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case–control study. Lancet Neurol. 2007;6(8):693–698. doi:10.1016/S1474-4422(07)70175-817611160
   PubMed Web of Science ®Google Scholar
• Beyenburg S, Mitchell AJ, Schmidt D, Elger CE, Reuber M. Anxiety in patients with epilepsy: systematic review and suggestions for clinical management. Epilepsy Behavior. 2005;7(2):161–171. doi:10.1016/j.yebeh.2005.05.01416054870
   PubMed Web of Science ®Google Scholar
• Almanza-Sepulveda ML, Smith ML, Widjaja E. Influence of patient, caregiver, and family factors on unmet healthcare needs in children with drug-resistant epilepsy undergoing epilepsy surgery evaluation. Epilepsy Behavior. 2019;99:106502. doi:10.1016/j.yebeh.2019.10650231493734
   PubMed Web of Science ®Google Scholar
• Gilliam FG, Barry JJ, Hermann BP, Meador KJ, Vahle V, Kanner AM. Rapid detection of major depression in epilepsy: a multicentre study. Lancet Neurol. 2006;5(5):399–405. doi:10.1016/S1474-4422(06)70415-X16632310
   PubMed Web of Science ®Google Scholar
• Kanner AM. Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: a review of the evidence. Epilepsy Behavior. 2016;61:282–286. doi:10.1016/j.yebeh.2016.03.02227236241
   PubMed Web of Science ®Google Scholar
• Conway CR, Udaiyar A, Schachter SC. Neurostimulation for depression in epilepsy. Epilepsy Behavior. 2018;88:25–32. doi:10.1016/j.yebeh.2018.06.00730212725
   PubMed Web of Science ®Google Scholar
• Tang V, Poon WS, Kwan P. Mindfulness-based therapy for drug-resistant epilepsy: an assessor-blinded randomized trial. Neurology. 2015;85(13):1100–1107. doi:10.1212/WNL.000000000000196726333801
   PubMed Web of Science ®Google Scholar
• Wilson S. the Task Force members. In response: indications and expectations for neuropsychological assessment in routine epilepsy care: report of the ILAE Neuropsychology Task Force, Diagnostic Methods Commission, 2013–2017. Epilepsia. 2015;56(8):1316–1317. doi:10.1111/epi.1305526235735
   PubMed Web of Science ®Google Scholar