The Pharmacoresistant Epilepsy: An Overview on Existent and New Emerging Therapies

Picot, 2008, The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population-based study in a Western European country, Epilepsia, 49, 1230, 10.1111/j.1528-1167.2008.01579.x

Kwan, 2010, Definition of drug resistant epilepsy: consensus proposal by the ad hoc task force of the ILAE commission on therapeutic strategies, Epilepsia, 51, 1069, 10.1111/j.1528-1167.2009.02397.x

Brodie, 2012, Patterns of treatment response in newly diagnosed epilepsy, Neurology., 78, 1548, 10.1212/WNL.0b013e3182563b19

Berg, 2004, Understanding the delay before epilepsy surgery: who develops intractable focal epilepsy and when?, CNS Spectr, 9, 136, 10.1017/S109285290000849X

Kwan, 2002, Refractory epilepsy: a progressive, intractable but preventable condition?, Seizure, 11, 77, 10.1053/seiz.2002.0593

Kwan, 2011, Drug-resistant epilepsy, N Engl J Med, 365, 919, 10.1056/NEJMra1004418

Dalic, 2016, Managing drug-resistant epilepsy: challenges and solutions, Neuropsychiatr Dis Treat, 12, 2605, 10.2147/NDT.S84852

Kalilani, 2018, The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis, Epilepsia, 59, 2179, 10.1111/epi.14596

Inizio Pati, 2010, Pharmacoresistant epilepsy: from pathogenesis to current and emerging therapies, Cleve Clin J Med, 77, 457, 10.3949/ccjm.77a.09061

Callaghan, 2011, Remission and relapse in a drug-resistant epilepsy population followed prospectively, Epilepsia, 52, 619, 10.1111/j.1528-1167.2010.02929.x

Löscher, 2020, Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options, Pharmacol Rev, 72, 606, 10.1124/pr.120.019539

Nei, 2007, Seizure-related injury and death, Curr Neurol Neurosci Rep, 7, 335, 10.1007/s11910-007-0051-1

Verrotti, 2017, Childhood absence epilepsy and benign epilepsy with centro-temporal spikes: a narrative review analysis, World J Pediatr, 13, 106, 10.1007/s12519-017-0006-9

Matricardi, 2020, What are the challenges with the pharmacological management of epilepsy in patients with Attention Deficit Hyperactivity Disorder (ADHD)?, Exp Opin Pharmacother, 21, 737, 10.1080/14656566.2020.1732351

Coppola, 2019, Monitoring and managing depression in adolescents with epilepsy: current perspectives, Neuropsychiatr Dis Treat, 15, 2773, 10.2147/NDT.S192714

Nickels, 2016, Cognitive and neurodevelopmental comorbidities in paediatric epilepsy, Nat Rev Neurol, 12, 465, 10.1038/nrneurol.2016.98

Keezer, 2016, Comorbidities of epilepsy: current concepts and future perspectives, Lancet Neurol, 15, 106, 10.1016/S1474-4422(15)00225-2

Chen, 2018, Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study, JAMA Neurol, 75, 279, 10.1001/jamaneurol.2017.3949

Kwan, 2000, Early identification of refractory epilepsy, N Engl J Med, 342, 314, 10.1056/NEJM200002033420503

Schmidt, 2007, How reliable is early treatment response in predicting long-term seizure outcome?, Epilepsy Behav, 10, 588, 10.1016/j.yebeh.2007.02.011

Löscher, 2005, Drug resistance in brain diseases and the role of drug efflux transporters, Nat Rev Neurosci, 6, 591, 10.1038/nrn1728

Tang, 2017, Drug-resistant epilepsy: multiple hypotheses, few answers, Front Neurol, 8, 301, 10.3389/fneur.2017.00301

König, 2013, Transporters and drug-drug interactions: important determinants of drug disposition and effects, Pharmacol Rev, 65, 944, 10.1124/pr.113.007518

Kwan, 2005, Potential role of drug transporters in the pathogenesis of medically intractable epilepsy, Epilepsia, 46, 224, 10.1111/j.0013-9580.2005.31904.x

Sisodiya, 2002, Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy, Brain, 125, 22, 10.1093/brain/awf002

Remy, 2006, Molecular and cellular mechanisms of pharmacoresistance in epilepsy, Brain, 129, 18, 10.1093/brain/awh682

Remy, 2003, Anticonvulsant pharmacology of voltage-gated Na+ channels in hippocampal neurons of control and chronically epileptic rats, Eur J Neurosci, 17, 2648, 10.1046/j.1460-9568.2003.02710.x

Bethmann, 2008, Antiepileptic drug resistant rats differ from drug responsive rats in GABA a receptor subunit expression in a model of temporal lobe epilepsy, Neurobiol Dis, 31, 169, 10.1016/j.nbd.2008.01.005

Fang, 2011, A new hypothesis of drug refractory epilepsy: neural network hypothesis, Med Hypotheses, 76, 871, 10.1016/j.mehy.2011.02.039

Schmidt, 2005, Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms, Epilepsia, 46, 858, 10.1111/j.1528-1167.2005.54904.x

Rogawski, 2013, The intrinsic severity hypothesis of pharmacoresistance to antiepileptic drugs, Epilepsia, 2, 33, 10.1111/epi.12182

Balestrini, 2018, Pharmacogenomics in epilepsy, Neurosci Lett, 667, 27, 10.1016/j.neulet.2017.01.014

Löscher, 2009, The clinical impact of pharmacogenetics on the treatment of epilepsy, Epilepsia, 50, 1, 10.1111/j.1528-1167.2008.01716.x

Granata, 2021, Inflammation in pediatric epilepsies: update on clinical features and treatment options, Epilepsy Behav, 107959, 10.1016/j.yebeh.2021.107959

Marchi, 2014, Inflammatory pathways of seizure disorders, Trends Neurosci, 37, 55, 10.1016/j.tins.2013.11.002

Matricardi, 2019, Understanding childhood neuroimmune diseases of the central nervous system, Front Pediatr, 7, 511, 10.3389/fped.2019.00511

Terrone, 2017, Inflammation and epilepsy: preclinical findings and potential clinical translation, Curr Pharm Des, 23, 5569, 10.2174/1381612823666170926113754

Aronica, 2017, Neuroinflammatory targets and treatments for epilepsy validated in experimental models, Epilepsia, 58, 27, 10.1111/epi.13783

Iorio, 2015, The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy, Eur J Neurol, 22, 70, 10.1111/ene.12529

Deckers, 2001, Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study, Epilepsia, 42, 1387, 10.1046/j.1528-1157.2001.30800.x

Park, 2019, Antiepileptic drug therapy in patients with drug-resistant epilepsy, J Epilepsy Res, 9, 14, 10.14581/jer.19002

Wilmshurst, 2015, Summary of recommendations for the management of infantile seizures: task force report for the ILAE commission of pediatrics, Epilepsia, 56, 1185, 10.1111/epi.13057

Glauser, 2013, ILAE subcommission on AED guidelines: updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes, Epilepsia, 54, 551, 10.1111/epi.12074

Verrotti, 2020, The role of polytherapy in the management of epilepsy: suggestions for rational antiepileptic drug selection, Expert Rev Neurother, 20, 167, 10.1080/14737175.2020.1707668

Czuczwar, 2002, Polytherapy in epilepsy: the experimental evidence, Epilepsy Res, 52, 15, 10.1016/S0920-1211(02)00181-X

Lasoń, 2011, Basic mechanisms of antiepileptic drugs and their pharmacokinetic/pharmacodynamic interactions: an update, Pharmacol Rep, 63, 271, 10.1016/S1734-1140(11)70497-2

Besag, 1998, Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic interaction?, Epilepsia, 39, 183, 10.1111/j.1528-1157.1998.tb01356.x

Barcs, 2000, Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy, Epilepsia, 41, 1597, 10.1111/j.1499-1654.2000.001597.x

Sake, 2010, A pooled analysis of lacosamide clinical trial data grouped by mechanism of action of concomitant antiepileptic drugs, CNS Drugs, 24, 1055, 10.2165/11587550-000000000-00000

Margolis, 2014, Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action, JAMA Neurol, 71, 985, 10.1001/jamaneurol.2014.808

Brodie, 1997, Lamotrigine substitution study: evidence for synergism with sodium valproate?, Epilepsy Res, 26, 423, 10.1016/S0920-1211(96)01007-8

Rowan, 1983, Valproate-ethosuximide combination therapy for absence seizures, Arch Neurol, 40, 797, 10.1001/archneur.1983.04050120047006

Kinirons, 2006, Predicting drug-resistant patients who respond to add-on therapy with levetiracetam, Seizure, 15, 387, 10.1016/j.seizure.2006.05.001

Brigo, 2013, When one plus one makes three: the quest for rational antiepileptic polytherapy with supraadditive anticonvulsant efficacy, Epilepsy Behav, 27, 439, 10.1016/j.yebeh.2013.03.010

Chung, 2010, Examining the clinical utility of lacosamide: pooled analyses of three phase II/III clinical trials, CNS Drugs, 24, 1041, 10.2165/11586830-000000000-00000

Stephen, 1998, Lamotrigine and topiramate may be useful combination, Lancet, 351, 958, 10.1016/S0140-6736(05)60613-7

Brodie, 2016, Pharmacological treatment of drug-resistant epilepsy in adults: a practical guide, Curr Neurol Neurosci Rep, 16, 82, 10.1007/s11910-016-0678-x

Cross, 2019, Dravet syndrome: treatment options and management of prolonged seizures, Epilepsia, 60, 39, 10.1111/epi.16334

Chiron, 2000, Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group, Lancet, 356, 1638, 10.1016/S0140-6736(00)03157-3

Guerrini, 2002, Stiripentol in severe myoclonic epilepsy in infancy (SMEI): a placebo-controlled Italian trial, Epilepsia, 43, 155, 10.1111/j.1528-1167.2002.tb06320.x

Lee, 2014, Old versus new: why do we need new antiepileptic drugs?, J Epilepsy Res, 4, 39, 10.14581/jer.14010

Zaccara, 2007, Idiosyncratic adverse reactions to antiepileptic drugs, Epilepsia, 48, 1223, 10.1111/j.1528-1167.2007.01041.x

Aliyu, 2016, Heamatobiochemical alterations induced by carbamazepine and phenytoin: mini review, Biochem Pharmacol, 5, 219, 10.4172/2167-0501.1000219

Kwan, 2006, Combination therapy in epilepsy: when and what to use, Drugs, 66, 1817, 10.2165/00003495-200666140-00004

Canevini, 2010, Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsy, Epilepsia, 51, 797, 10.1111/j.1528-1167.2010.02520.x

Lammers, 1995, Monotherapy or polytherapy for epilepsy revisited: a quantitative assessment, Epilepsia, 36, 440, 10.1111/j.1528-1157.1995.tb00484.x

Kessler, 2019, A practical guide to treatment of childhood absence epilepsy, Paediatr Drugs, 21, 15, 10.1007/s40272-019-00325-x

Franzoni, 2015, Refractory absence seizures: an Italian multicenter retrospective study, Eur J Paediatr Neurol, 19, 660, 10.1016/j.ejpn.2015.07.008

Brigo, 2018, Emerging drugs for the treatment of Dravet syndrome, Exp Opin Emerg Drugs, 23, 261, 10.1080/14728214.2018.1552937

Wirrell, 2017, Optimizing the diagnosis and management of Dravet syndrome: recommendations from a North American consensus panel, Pediatr Neurol, 68, 18, 10.1016/j.pediatrneurol.2017.01.025

Verrotti, 2018, The pharmacological management of Lennox-Gastaut syndrome and critical literature review, Seizure, 63, 17, 10.1016/j.seizure.2018.10.016

Verrotti, 2021, Novel therapeutic options for Dravet and Lennox-Gastaut syndrome, Expert Rev Neurother, 11, 1, 10.1080/14737175.2020.1862651

Brigo, 2021, Anti-seizure medications for Lennox-Gastaut syndrome, Cochrane Database Syst Rev, 4, CD003277, 10.1002/14651858.CD003277.pub4

Kwan, 2000, Epilepsy after the first drug fails: substitution or add-on?, Seizure, 9, 464, 10.1053/seiz.2000.0442

Louis, 2009, Truly “Rational” polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects, Curr Neuro Pharmacol, 7, 96, 10.2174/157015909788848929

Brodie, 2005, Medical therapy of epilepsy: when to initiate treatment and when to combine?, J Neurol, 252, 125, 10.1007/s00415-005-0735-x

Shi, 2017, Epilepsy treatment in adults and adolescents: expert opinion, 2016, Epilepsy Behav, 69, 186, 10.1016/j.yebeh.2016.11.018

Lee, 2019, Clinical opinion: earlier employment of polytherapy in sequential pharmacotherapy of epilepsy, Epilepsy Res, 156, 106, 10.1016/j.eplepsyres.2019.106165

López, 2015, Drug-resistant epilepsy: definition and treatment alternatives, Neurologia, 30, 439, 10.1016/j.nrleng.2014.04.002

French, 2012, Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304, Neurology, 79, 589, 10.1212/WNL.0b013e3182635735

French, 2013, Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305, Epilepsia, 54, 117, 10.1111/j.1528-1167.2012.03638.x

Krauss, 2012, Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures, Neurology, 78, 1408, 10.1212/WNL.0b013e318254473a

Krauss, 2014, Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: results from phase III extension study 307, Epilepsia, 55, 1058, 10.1111/epi.12643

Krauss, 2018, Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open-label extension of phase III randomized trials: Study 307, Epilepsia, 59, 866, 10.1111/epi.14044

French, 2015, Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy a randomized trial, Neurology, 85, 950, 10.1212/WNL.0000000000001930

Operto, 2020, Perampanel tolerability in children and adolescents with focal epilepsy: effects on behavior and executive functions, Epilepsy Behav, 103, 106879, 10.1016/j.yebeh.2019.106879

Lattanzi, 2016, Brivaracetam add-on for refractory focal epilepsy: a systematic review and meta-analysis, Neurology, 86, 1344, 10.1212/WNL.0000000000002545

Verrotti, 2021, Potential role of brivaracetam in pediatric epilepsy, Acta Neurol Scand, 143, 19, 10.1111/ane.13347

Contin, 2021, Cannabidiol in Pharmacoresistant Epilepsy: clinical pharmacokinetic data from an expanded access program, Front Pharmacol, 12, 637801, 10.3389/fphar.2021.637801

Devinsky, 2017, Cannabidiol in Dravet syndrome study group. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome, N Engl J Med, 376, 2011, 10.1056/NEJMoa1611618

Devinsky, 2018, GWPCARE1 part a study group: randomized, dose ranging safety trial of cannabidiol in Dravet syndrome, Neurology, 90, 1204, 10.1212/WNL.0000000000005254

Devinsky, 2018, GWPCARE3 study group: effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome, N Engl J Med, 378, 1888, 10.1056/NEJMoa1714631

Thiele, 2018, Cannabidiol in patients with seizures associated with Lennox-Gastautsyndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial, Lancet, 391, 1085, 10.1016/S0140-6736(18)30136-3

Devinsky, 2019, Long-term cannabidiol treatment in patients with Dravet syndrome: an open-label extension trial, Epilepsia, 60, 294, 10.1111/epi.14628

Lattanzi, 2019, Cannabidiol as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, Drugs Today, 55, 177, 10.1358/dot.2019.55.3.2909248

Miller, 2020, Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in Dravet Syndrome: a randomized clinical trial, JAMA Neurol, 77, 613, 10.1001/jamaneurol.2020.0073

Geffrey, 2015, Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy, Epilepsia, 56, 1246, 10.1111/epi.13060

Devinsky, 2020, Cannabidiol efficacy independent of clobazam: meta-analysis of four randomized controlled trials, Acta Neurol Scand, 142, 531, 10.1111/ane.13305

Anderson, 2019, Coadministered cannabidiol and clobazam: preclinical evidence for both pharmacodynamic and pharmacokinetic interactions, Epilepsia, 60, 2224, 10.1111/epi.16355

Lattanzi, 2020, Cannabidiol efficacy and clobazam status: a systematic review and meta-analysis, Epilepsia, 61, 1090, 10.1111/epi.16546

Schoonjans, 2015, Low-dose fenfluramine in the treatment of neurologic disorders: experience in Dravet syndrome, Ther Adv Neurol Disord, 8, 328, 10.1177/1756285615607726

Balagura, 2020, Fenfluramine for the treatment of Dravet syndrome and lennox-gastaut syndrome, CNS Drugs, 34, 1001, 10.1007/s40263-020-00755-z

Ceulemans, 2012, Successful use of fenfluramine as an add-on treatment for Dravet syndrome, Epilepsia, 53, 1131, 10.1111/j.1528-1167.2012.03495.x

Schoonjans, 2017, Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients, Eur J Neurol, 24, 309, 10.1111/ene.13195

Lagae, 2020, Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial, Lancet, 394, 2243, 10.1016/S0140-6736(19)32500-0

Nabbout, 2019, Fenfluramine for treatment-resistant seizures in patients with Dravet syndrome receiving stiripentol-inclusive regimens: a randomized clinical trial, JAMA Neurol, 77, 300, 10.1001/jamaneurol.2019.4113

Lagae, 2018, A pilot, open-label study of the effectiveness and tolerability of low-dose ZX008 (fenfluramine HCl) in Lennox-Gastaut syndrome, Epilepsia, 59, 1881, 10.1111/epi.14540

Lai, 2020, Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: analysis of an ongoing long-term open-label safety extension study, Epilepsia, 61, 2386, 10.1111/epi.16638

Bialer, 2018, Progress report on new antiepileptic drugs: a summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). I. drugs in preclinical and early clinical development, Epilepsia, 59, 1811, 10.1111/epi.14557

Krauss, 2020, 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, 19, 38, 10.1016/S1474-4422(19)30399-0

Ragona, 2014, Refractory absence epilepsy and glut1 deficiency syndrome: a new case report and literature review, Neuropediatrics, 45, 328, 10.1055/s-0034-1378130

Perucca, 2019, Identifying mutations in epilepsy genes: Impact on treatment selection, Epilepsy Res, 152, 18, 10.1016/j.eplepsyres.2019.03.001

Wang, 2017, Epilepsy-associated genes, Seizure, 44, 11, 10.1016/j.seizure.2016.11.030

Simasathien, 2013, Improved outcomes with earlier surgery for intractable frontal lobe epilepsy, Ann Neurol, 73, 646, 10.1002/ana.23862

Barba, 2020, Trends in pediatric epilepsy surgery in Europe between 2008 and 2015: country-, center-, and age-specific variation, Epilepsia, 61, 216, 10.1111/epi.16414

Lattanzi, 2018, Palliative non-resective surgery for drug-resistant epilepsy, Brain Dev, 40, 512, 10.1016/j.braindev.2017.12.012

Boon, 2018, Neurostimulation for drug-resistant epilepsy: a systematic review of clinical evidence for efficacy, safety, contraindications and predictors for response, Curr Opin Neurol, 31, 198, 10.1097/WCO.0000000000000534

Starnes, 2019, A review of neurostimulation for epilepsy in pediatrics, Brain Sci, 9, 283, 10.3390/brainsci9100283

Pérez-Carbonell, 2020, Vagus nerve stimulation for drug-resistant epilepsy, Pract Neurol, 20, 189, 10.1136/practneurol-2019-002210

Morris, 2013, Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology, Neurology, 81, 1453, 10.1212/WNL.0b013e3182a393d1

Ben-Menachem, 1995, Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures, Epilepsy Res, 20, 221, 10.1016/0920-1211(94)00083-9

Fisher, 2021, Responsive vagus nerve stimulation for drug resistant epilepsy: a review of new features and practical guidance for advanced practice providers, Front Neurol, 11, 610379, 10.3389/fneur.2020.610379

Chambers, 2013, Electrical stimulation for drug-resistant epilepsy: an evidence-based analysis, Ont Health Technol Assess Ser., 13, 1

Panebianco, 2015, Vagus nerve stimulation for partial seizures, Cochrane Database Syst Rev, 2015, CD002896, 10.1002/14651858.CD002896.pub2

Klinkenberg, 2012, Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial, Dev Med Child Neurol, 54, 855, 10.1111/j.1469-8749.2012.04305.x

Fisher, 2010, Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy, Epilepsia, 51, 899, 10.1111/j.1528-1167.2010.02536.x

Salanova, 2015, Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy, Neurology, 84, 1017, 10.1212/WNL.0000000000001334

Li, 2018, Deep brain stimulation for drug-resistant epilepsy, Epilepsia, 59, 273, 10.1111/epi.13964

Lim, 2016, Low and high frequency hippocampal stimulation for drug-resistant mesial temporal lobe epi-lepsy, Neuromodulation, 19, 365, 10.1111/ner.12435

Valentin, 2013, Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies, Epilepsia, 54, 1823, 10.1111/epi.12352

Matias, 2019, Responsive neurostimulation for the treatment of epilepsy, Neurosurg Clin N Am, 30, 231, 10.1016/j.nec.2018.12.006

Bergey, 2015, Long-term treatment with responsive brain stimulation in adults with refractory partial seizures, Neurology, 84, 810, 10.1212/WNL.0000000000001280

Geller, 2017, Brain responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy, Epilepsia., 58, 994, 10.1111/epi.13740

Nair, 2020, Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy, Neurology, 95, e1244, 10.1212/WNL.0000000000010154

Heck, 2014, Two year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS system pivotal trial, Epilepsia, 55, 432, 10.1111/epi.12534

Lundstrom, 2017, Chronic subthreshold cortical stimulation: a therapeutic and potentially restorative therapy for focal epilepsy, Expert Rev Neurother, 17, 661, 10.1080/14737175.2017.1331129

Lefaucheur, 2014, Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS), Clin Neurophysiol, 125, 2150, 10.1016/j.clinph.2014.05.021

Lefaucheur, 2020, Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018), Clin Neurophysiol, 131, 474, 10.1016/j.clinph.2020.02.003

Fregni, 2020, Evidence-based guidelines and secondary meta-analysis for the use of transcranial direct current stimulation (tDCS) in neurological and psychiatric disorders, Int J Neuropsychopharmacol, 26, pyaa051, 10.1093/ijnp/pyaa051

Yang, 2020, Transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: a randomized, double-blind, sham-controlled, and three-arm parallel multicenter study, Brain Stimul, 13, 109, 10.1016/j.brs.2019.09.006

Verrotti, 2020, Diet in the treatment of epilepsy: what we know so far, Nutrients, 12, 2645, 10.3390/nu12092645

Operto, 2020, The ketogenic diet for the treatment of mood disorders in comorbidity with epilepsy in children and adolescents, Front Pharmacol, 11, 578396, 10.3389/fphar.2020.578396

Martin-McGill, 2020, Ketogenic diets for drug-resistant epilepsy, Cochrane Database Syst Rev, 6, CD001903, 10.1002/14651858.CD001903.pub5