Advances in the Treatment of Drug-Resistant Pediatric Epilepsy

Ernesto Gonzalez-Giraldo; Joseph E. Sullivan

doi:10.1055/s-0040-1702941

Seminars in Neurology, Table of Contents

Semin Neurol 2020; 40(02): 257-262
DOI: 10.1055/s-0040-1702941

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Advances in the Treatment of Drug-Resistant Pediatric Epilepsy

Ernesto Gonzalez-Giraldo

¹Department of Neurology and Pediatrics, Pediatric Epilepsy Center of Excellence, Benioff Children's Hospital, University of California San Francisco, San Francisco, California

,

Joseph E. Sullivan

¹Department of Neurology and Pediatrics, Pediatric Epilepsy Center of Excellence, Benioff Children's Hospital, University of California San Francisco, San Francisco, California

› Author Affiliations

Abstract

Epilepsy is a common disorder in children and adults that causes significant morbidity and affects many aspects of a patient's lives. Two-thirds of patients with epilepsy are controlled with established antiseizure medications, leaving a significant number of patients searching for other options. The purpose of this review is to provide an overview of recent advancements in the management of treatment-resistant epilepsy in pediatric patients. Recent publications have shown the efficacy of new pharmaceutical options such as fenfluramine and cannabidiol, some of which have been tested specifically in patients with childhood-onset epilepsy syndromes such as Dravet's syndrome and Lennox–Gastaut's syndrome. Furthermore, recent approval by the U.S. Food and Drug Administration of stiripentol has made available a previously difficult-to-obtain option for patients with Dravet's syndrome. Finally, implanted responsive neurostimulation devices for direct cortical stimulation and deep brain stimulation have shown efficacy in adult patients and may represent a thrilling new horizon for pediatric patients.

Keywords

treatment-resistant epilepsy - Dravet's syndrome - Lennox–Gastaut's syndrome

Full Text

References

References
1 Thurman DJ, Beghi E, Begley CE. , et al; ILAE Commission on Epidemiology. Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia 2011; 52 (07) 2-26
2 Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia 2010; 51 (05) 883-890
3 Aaberg KM, Gunnes N, Bakken IJ. , et al. Incidence and prevalence of childhood epilepsy: a nationwide cohort study. Pediatrics 2017; 139 (05) e20163908
4 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342 (05) 314-319
5 Engel Jr J, Wiebe S, French J. , et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy. Epilepsia 2003; 44 (06) 741-751
6 Wiebe S, Bellhouse DR, Fallahay C, Eliasziw M. Burden of epilepsy: the Ontario Health Survey. Can J Neurol Sci 1999; 26 (04) 263-270
7 Camfield CS, Camfield PR. Long-term social outcomes for children with epilepsy. Epilepsia 2007; 48 (09) 3-5
8 Ficker DM, So EL, Shen WK. , et al. Population-based study of the incidence of sudden unexplained death in epilepsy. Neurology 1998; 51 (05) 1270-1274
9 Muramatsu K, Sawaura N, Ogata T. , et al. Efficacy and tolerability of levetiracetam for pediatric refractory epilepsy. Brain Dev 2017; 39 (03) 231-235
10 Dwivedi R, Ramanujam B, Chandra PS. , et al. Surgery for drug-resistant epilepsy in children. N Engl J Med 2017; 377 (17) 1639-1647
11 Yan H, Toyota E, Anderson M. , et al. A systematic review of deep brain stimulation for the treatment of drug-resistant epilepsy in childhood. J Neurosurg Pediatr 2018; 23 (03) 274-284
12 Wheless JW, Gienapp AJ, Ryvlin P. Vagus nerve stimulation (VNS) therapy update. Epilepsy Behav 2018; 88S: 2-10
13 Singhal NS, Numis AL, Lee MB. , et al. Responsive neurostimulation for treatment of pediatric drug-resistant epilepsy. Epilepsy Behav Case Rep 2018; 10: 21-24
14 Kossoff EH, Zupec-Kania BA, Auvin S. , et al; Charlie Foundation; Matthew's Friends; Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open 2018; 3 (02) 175-192
15 Dravet C. The core Dravet syndrome phenotype. Epilepsia 2011; 52 (02) 3-9
16 Wirrell EC, Laux L, Franz DN. , et al. Stiripentol in Dravet syndrome: results of a retrospective U.S. study. Epilepsia 2013; 54 (09) 1595-1604
17 Fisher JL. The anti-convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator. Neuropharmacology 2009; 56 (01) 190-197
18 Chiron C, Marchand MC, Tran A. , et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group. Lancet 2000; 356 (9242): 1638-1642
19 Thanh TN, Chiron C, Dellatolas G. , et al. Efficacité et tolérance à long terme du stiripentol dans le traitement de l'épilepsie myoclonique sévère du nourrisson (syndrome de Dravet). Arch Pediatr 2002; 9 (11) 1120-1127
20 Inoue Y, Ohtsuka Y. ; STP-1 Study Group. Long-term safety and efficacy of stiripentol for the treatment of Dravet syndrome: a multicenter, open-label study in Japan. Epilepsy Res 2015; 113: 90-97
21 Myers KA, Lightfoot P, Patil SG, Cross JH, Scheffer IE. Stiripentol efficacy and safety in Dravet syndrome: a 12-year observational study. Dev Med Child Neurol 2018; 60 (06) 574-578
22 Gowers WR. Epilepsy and Other Chronic Convulsive Diseases. London: Churchill; 1881: 224
23 Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia 2014; 55 (06) 783-786
24 Porcari GS, Fu C, Doll ED, Carter EG, Carson RP. Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: practical experiences in a tertiary medical center. Epilepsy Behav 2018; 80: 240-246
25 Brodie MJ, Ben-Menachem E. Cannabinoids for epilepsy: what do we know and where do we go?. Epilepsia 2018; 59 (02) 291-296
26 Devinsky O, Cross JH, Laux L. , et al; Cannabidiol in Dravet Syndrome Study Group. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017; 376 (21) 2011-2020
27 Abenhaim L, Moride Y, Brenot F. , et al; International Primary Pulmonary Hypertension Study Group. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 1996; 335 (09) 609-616
28 Fuller RW, Snoddy HD, Robertson DW. Mechanisms of effects of d-fenfluramine on brain serotonin metabolism in rats: uptake inhibition versus release. Pharmacol Biochem Behav 1988; 30 (03) 715-721
29 Schoonjans A-S, Lagae L, Ceulemans B. Low-dose fenfluramine in the treatment of neurologic disorders: experience in Dravet syndrome. Ther Adv Neurol Disorder 2015; 8 (06) 328-338
30 Ceulemans B, Boel M, Leyssens K. , et al. Successful use of fenfluramine as an add-on treatment for Dravet syndrome. Epilepsia 2012; 53 (07) 1131-1139
31 Ceulemans B, Schoonjans A-S, Marchau F, Paelinck BP, Lagae L. Five-year extended follow-up status of 10 patients with Dravet syndrome treated with fenfluramine. Epilepsia 2016; 57 (07) e129-e134
32 Schoonjans A, Paelinck BP, Marchau F. , et al. Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients. Eur J Neurol 2017; 24 (02) 309-314
33 Lagae L, Sullivan J, Knupp K. , et al. A randomised, placebo-controlled trial of fenfluramine for the treatment of seizures in Dravet syndrome. Lancet 2019
34 Dressler A, Trimmel-Schwahofer P, Reithofer E. , et al. Efficacy and tolerability of the ketogenic diet in Dravet syndrome - comparison with various standard antiepileptic drug regimen. Epilepsy Res 2015; 109: 81-89
35 Yan N, Xin-Hua W, Lin-Mei Z. , et al. Prospective study of the efficacy of a ketogenic diet in 20 patients with Dravet syndrome. Seizure 2018; 60: 144-148
36 van Rijckevorsel K. Treatment of Lennox-Gastaut syndrome: overview and recent findings. Neuropsychiatr Dis Treat 2008; 4 (06) 1001-1019
37 Heiskala H. Community-based study of Lennox-Gastaut syndrome. Epilepsia 1997; 38 (05) 526-531
38 Trevathan E, Murphy CC, Yeargin-Allsopp M. Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children. Epilepsia 1997; 38 (12) 1283-1288
39 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 (01) 82-93
40 Thiele EA, Marsh ED, French JA. , et al; GWPCARE4 Study Group. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018; 391 (10125): 1085-1096
41 Devinsky O, Patel AD, Cross JH. , et al; GWPCARE3 Study Group. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med 2018; 378 (20) 1888-1897
42 Lagae L, Schoonjans A-S, Gammaitoni AR, Galer BS, Ceulemans B. A pilot, open-label study of the effectiveness and tolerability of low-dose ZX008 (fenfluramine HCl) in Lennox-Gastaut syndrome. Epilepsia 2018; 59 (10) 1881-1888
43 Devinsky O, Marsh E, Friedman D. , et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol 2016; 15 (03) 270-278
44 Szaflarski JP, Bebin EM, Comi AM. , et al; CBD EAP study group. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: expanded access program results. Epilepsia 2018; 59 (08) 1540-1548
45 Heck CN, King-Stephens D, Massey AD. , et al. 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 2014; 55 (03) 432-441
46 Kokoszka MA, Panov F, La Vega-Talbott M, McGoldrick PE, Wolf SM, Ghatan S. Treatment of medically refractory seizures with responsive neurostimulation: 2 pediatric cases. J Neurosurg Pediatr 2018; 21 (04) 421-427
47 Fisher R, Salanova V, Witt T. , et al; SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010; 51 (05) 899-908