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Review

The latest advances in the pharmacological management of focal epilepsies in children: a narrative review

, , , , , , & show all
Pages 371-381 | Received 22 Jan 2024, Accepted 29 Feb 2024, Published online: 05 Mar 2024

References

  • Nascimento FA, Friedman D, Peters JM, et al. Focal epilepsies: Update on diagnosis and classification. Epileptic Disord. 2023;25(1):1–17. doi: 10.1002/epd2.20045
  • Specchio N, Wirrell EC, Scheffer IE, et al. International league against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ilae task force on nosology and definitions. Epilepsia. 2022;63(6):1398–1442. doi: 10.1111/epi.17241
  • Hirsch E, French J, Scheffer IE, et al. ILAE definition of the idiopathic generalized epilepsy syndromes: position statement by the ILAE task force on nosology and definitions. Epilepsia. 2022;63(6):1475–1499. doi: 10.1111/epi.17236
  • Riney K, Bogacz A, Somerville E, et al. International league against epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE task force on nosology and definitions. Epilepsia. 2022;63(6):1443–1474. doi: 10.1111/epi.17240
  • Zuberi SM, Wirrell E, Yozawitz E, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE task force on nosology and definitions. Epilepsia. 2022;63(6):1349–1397. doi: 10.1111/epi.17239
  • Hakami T, Mcintosh A, Todaro M, et al. MRI-identified pathology in adults with new-onset seizures. Neurology. 2013;81(10):920–927. doi: 10.1212/WNL.0b013e3182a35193
  • Fattorusso A, Matricardi S, Mencaroni E, et al. The pharmacoresistant epilepsy: an overview on existant and new emerging therapies. Front Neurol. 2021;12:674483. doi: 10.3389/fneur.2021.674483
  • The epilepsies: evidence update February 2014: a summary of selected new evidence relevant to NICE clinical guideline 137 ‘the epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care’.London: National Institute for Health and Care Excellence (NICE); 2012. p. 2014.
  • Arya R, Glauser TA. Pharmacotherapy of focal epilepsy in children: a systematic review of approved agents. CNS Drugs. 2013;27(4):273–286. doi: 10.1007/s40263-013-0048-z
  • Sun S, Li X, Liu X. Efficacy, tolerability and safety of perampanel in children and adolescents with epilepsy: systematic review and meta-analysis. Brain Dev. 2023;45(5):260–269. doi: 10.1016/j.braindev.2023.02.007
  • Pascarella A, Iannone LF, Di Gennaro G, et al. The efficacy of perampanel as adjunctive therapy in drug-resistant focal epilepsy in a “real world” context: focus on temporal lobe epilepsy. J Neurolog Sci. 2020;415:116903. doi: 10.1016/j.jns.2020.116903
  • Piña-Garza JE, Lagae L, Villanueva V, et al. Long-term effects of adjunctive perampanel on cognition in adolescents with partial seizures. Epilepsy Behav. 2018;83:50–58. doi: 10.1016/j.yebeh.2018.03.029
  • Nissenkorn A, Kluger G, Schubert‐Bast S, et al. Perampanel as precision therapy in rare genetic epilepsies. Epilepsia. 2023;64(4):866–874. doi: 10.1111/epi.17530
  • Moraes JS, Hepworth G, Ignatiadis S, et al. Improved irritability, mood, and quality of life following introduction of perampanel as late adjunctive treatment for epilepsy. Epilepsy Behav. 2020;104:106883. doi: 10.1016/j.yebeh.2019.106883
  • Trinka E, Steinhoff BJ, Nikanorova M, et al. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurol Scand. 2016;133(3):160–172. doi: 10.1111/ane.12529
  • Operto FF, Vivenzio V, Scuoppo C, et al. Perampanel and visuospatial skills in children with epilepsy. Front Neurol. 2021;12:696946. doi: 10.3389/fneur.2021.696946
  • Operto FF, Pastorino GMG, Mazza R, et al. Perampanel tolerability in children and adolescents with focal epilepsy: effects on behavior and executive functions. Epilepsy Behav. 2020;103:106879. doi: 10.1016/j.yebeh.2019.106879
  • Majid O, Laurenza A, Ferry J, et al. Impact of perampanel on pharmacokinetics of concomitant antiepileptics in patients with partial‐onset seizures: pooled analysis of clinical trials. Br J Clin Pharmacol. 2016;82(2):422–430. doi: 10.1111/bcp.12951
  • Rohracher A, Zimmermann G, Villanueva V, et al. Perampanel in routine clinical use across Europe: pooled, multicenter, observational data. Epilepsia. 2018;59(9):1727–1739. doi: 10.1111/epi.14520
  • Meador KJ, Yang H, Piña‐Garza JE, et al. Cognitive effects of adjunctive perampanel for partial‐onset seizures: a randomized trial. Epilepsia. 2016;57(2):243–251. doi: 10.1111/epi.13279
  • Villanueva V, Montoya J, Castillo A, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12‐month GENERAL study. Epilepsia. 2018;59(9):1740–1752. doi: 10.1111/epi.14522
  • Gasparini S, Ferlazzo E, Neri S, et al. Effectiveness of perampanel as the only add‐on: retrospective, multicenter, observational real‐life study on epilepsy patients. Epilepsia Open. 2022;7(4):687–696. doi: 10.1002/epi4.12649
  • Pascarella A, Gasparini S, Manzo L, et al. Perampanel as only add-on epilepsy treatment in elderly: a subgroup analysis of real-world data from retrospective, multicenter, observational study. J Neurolog Sci. 2023;455:122797. doi: 10.1016/j.jns.2023.122797
  • Matricardi S, Cesaroni E, Bonanni P, et al. Long‐term effectiveness of add‐on perampanel in patients with Lennox–gastaut syndrome: a multicenter retrospective study. Epilepsia. 2023;64(6). doi: 10.1111/epi.17601
  • Fernandes M, Dainese F, Operto F, et al. Perampanel effectiveness and tolerability in patients with epilepsy at long-term follow-up. Epilepsy Behav. 2021;121:108069. doi: 10.1016/j.yebeh.2021.108069
  • De Liso P, Moavero R, Coppola G, et al. Current role of perampanel in pediatric epilepsy. Ital J Pediatr. 2017;43(1):51. doi: 10.1186/s13052-017-0368-6
  • Scorrano G, Lattanzi S, Salpietro V, et al. The cognitive and behavioural effects of perampanel in children with neurodevelopmental disorders: a systematic review. JCM. 2024;13(2):372.
  • Biró A, Stephani U, Tarallo T, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies: first experiences. Neuropediatrics. 2015;46(02):110–115. doi: 10.1055/s-0035-1546276
  • De Liso P, Vigevano F, Specchio N, et al. Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies—an Italian observational multicenter study. Epilepsy Res. 2016;127:93–100. doi: 10.1016/j.eplepsyres.2016.08.021
  • Bresnahan R, Panebianco M, Marson AG. Brivaracetam add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev. 2022;2022(3). doi: 10.1002/14651858.CD011501.pub3
  • Nissenkorn A, Tzadok M, Bar-Yosef O, et al. Treatment with brivaracetam in children – the experience of a pediatric epilepsy center. Epilepsy Behav. 2019;101:106541. doi: 10.1016/j.yebeh.2019.106541
  • Tulli E, Di Cara G, Iapadre G, et al. An update on brivaracetam for the treatment of pediatric partial epilepsy. Expert Opin Pharmacother. 2021;22(11):1387–1395. doi: 10.1080/14656566.2021.1921151
  • Moseley BD, Chanteux H, Nicolas J-M, et al. A review of the drug−drug interactions of the antiepileptic drug brivaracetam. Epilepsy Res. 2020;163:106327. doi: 10.1016/j.eplepsyres.2020.106327
  • Steinhoff BJ, Bacher M, Blickhan M, et al. Is brivaracetam-induced elevation of carbamazepine-epoxide levels common and clinically relevant? — A case series. Epilepsy Res. 2020;159:106236. doi: 10.1016/j.eplepsyres.2019.106236
  • Brodie MJ, Ben-Menachem E. Cannabinoids for epilepsy: what do we know and where do we go? Epilepsia. 2018;59(2):291–296.
  • Farkas MK, Kang H, Fogarasi A, et al. Pharmacokinetics, safety, and tolerability of intravenous brivaracetam in pediatric patients with epilepsy: an open‐label trial. Epilepsia. 2022;63(4):855–864. doi: 10.1111/epi.17187
  • Patel AD, Badalamenti V, Gasalla T, et al. Safety and tolerability of adjunctive brivaracetam in children with focal seizures: interim analysis of pooled data from two open-label trials. Eur J Paediatr Neurol. 2020;25:68–76. doi: 10.1016/j.ejpn.2019.11.007
  • Russo A, Pruccoli J, Cesaroni CA, et al. Brivaracetam add-on treatment in pediatric patients with severe drug-resistant epilepsy: Italian real-world evidence. Seizure. 2022;102:120–124. doi: 10.1016/j.seizure.2022.10.001
  • McGuire S, Silva G, Lal D, et al. Safety and efficacy of brivaracetam in pediatric refractory epilepsy: a single-center clinical experience. J Child Neurol. 2020;35(2):102–105. doi: 10.1177/0883073819879276
  • Schubert-Bast S, Willems LM, Kurlemann G, et al. Postmarketing experience with brivaracetam in the treatment of focal epilepsy in children and adolescents. Epilepsy Behav. 2018;89:89–93. doi: 10.1016/j.yebeh.2018.10.018
  • Liu E, Dilley D, McDonough B, et al. Safety and tolerability of adjunctive brivaracetam in pediatric patients < 16 years with epilepsy: an open-label trial. Pediatr Drugs. 2019;21:291–301. doi: 10.1007/s40272-019-00332-y
  • Visa-Reñé N, Raspall-Chaure M, Paredes-Carmona F, et al. Clinical experience with brivaracetam in a series of 46 children. Epilepsy Behav. 2020;107:107067. doi: 10.1016/j.yebeh.2020.107067
  • Kwan P, Trinka E, Van Paesschen W, et al. Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial. Epilepsia. 2014;55(1):38–46. doi: 10.1111/epi.12391
  • Van Paesschen W, Hirsch E, Johnson M, et al. Efficacy and tolerability of adjunctive brivaracetam in adults with uncontrolled partial-onset seizures: A phase IIb, randomized, controlled trial: Brivaracetam in Partial-Onset Seizures. Epilepsia. 2013;54(1):89–97. doi: 10.1111/j.1528-1167.2012.03598.x
  • Biton V, Berkovic SF, Abou‐Khalil B, et al. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: A phase III randomized, double‐blind, placebo‐controlled trial. Epilepsia. 2014;55(1):57–66. doi: 10.1111/epi.12433
  • Verrotti A, Grasso EA, Cacciatore M, et al. Potential role of brivaracetam in pediatric epilepsy. Acta Neurol Scand. 2021;143(1):19–26. doi: 10.1111/ane.13347
  • Nakamura M, Cho J-H, Shin H, et al. Effects of cenobamate (YKP3089), a newly developed anti-epileptic drug, on voltage-gated sodium channels in rat hippocampal CA3 neurons. Eur J Pharmacol. 2019;855:175–182. doi: 10.1016/j.ejphar.2019.05.007
  • Buckley CT, Waters OR, DeMaagd G. Cenobamate: a new adjunctive agent for drug-resistant focal onset epilepsy. Ann Pharmacother. 2021;55(3):318–329. doi: 10.1177/1060028020941113
  • Makridis KL, Bast T, Prager C, et al. Real-world experience treating pediatric epilepsy patients with cenobamate. Front Neurol. 2022;13:950171. doi: 10.3389/fneur.2022.950171
  • Varughese RT, Shah YD, Karkare S, et al. Adjunctive use of cenobamate for pediatric refractory focal-onset epilepsy: a single-center retrospective study. Epilepsy Behav. 2022;130:108679. doi: 10.1016/j.yebeh.2022.108679
  • Sperling MR, Klein P, Aboumatar S, et al. Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open‐label safety study. Epilepsia. 2020;61(6):1099–1108. doi: 10.1111/epi.16525
  • Lattanzi S, Trinka E, Striano P, et al. Highly purified cannabidiol for epilepsy treatment: a systematic review of epileptic conditions beyond dravet syndrome and Lennox–gastaut syndrome. CNS Drugs. 2021;35(3):265–281. doi: 10.1007/s40263-021-00807-y
  • Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55(6):791–802. doi: 10.1111/epi.12631
  • Ibeas Bih C, Chen T, Nunn AVW, et al. Molecular targets of Cannabidiol in neurological disorders. Neurotherapeutics. 2015;12(4):699–730. doi: 10.1007/s13311-015-0377-3
  • McPartland JM, Duncan M, Di Marzo V, et al. Are cannabidiol and Δ 9 -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review: mechanistic studies (in vivo and ex vivo) of CBD and THCV. Br J Pharmacol. 2015;172:737–753. doi: 10.1111/bph.12944
  • Patel AD, Mazurkiewicz‐Bełdzińska M, Chin RF, et al. Long‐term safety and efficacy of add‐on cannabidiol in patients with Lennox–gastaut syndrome: results of a long‐term open‐label extension trial. Epilepsia. 2021;62(9):2228–2239. doi: 10.1111/epi.17000
  • 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/NEJMoa1611618
  • Devinsky O, Patel AD, Cross JH, et al. Effect of Cannabidiol on drop seizures in the Lennox–Gastaut syndrome. N Engl J Med. 2018;378(20):1888–1897. doi: 10.1056/NEJMoa1714631
  • Thiele EA, Marsh ED, French JA, et al. 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. doi: 10.1016/S0140-6736(18)30136-3
  • Miller I, Scheffer IE, Gunning B, et al. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in dravet syndrome: a randomized clinical trial. JAMA Neurol. 2020;77(5):613. doi: 10.1001/jamaneurol.2020.0073
  • Amin MR, Ali DW. Pharmacology of medical cannabis. In: Bukiya A, editor. Recent advances in cannabinoid physiology and pathology. Vol. 1162. Cham: Springer International Publishing; 2019. p. 151–165. doi: 10.1007/978-3-030-21737-2_8
  • Kaplan JS, Stella N, Catterall WA, et al. Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. Proc Natl Acad Sci, USA. 2017;114(42):11229–11234. doi: 10.1073/pnas.1711351114
  • Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci, USA. 2006;103(20):7895–7900. doi: 10.1073/pnas.0511232103
  • Geffrey AL, Pollack SF, Bruno PL, et al. Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56(8):1246–1251. doi: 10.1111/epi.13060
  • Gaston TE, Allendorfer JB, Nair S, et al. Effects of highly purified cannabidiol (CBD) on fMRI of working memory in treatment-resistant epilepsy. Epilepsy Behav. 2020;112:107358. doi: 10.1016/j.yebeh.2020.107358
  • Brigo F, Jones K, Eltze C, et al. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021;4(9): CD003277. doi: 10.1002/14651858.CD003277.pub4
  • Riva A, Coppola A, Bonaventura CD, et al. An Italian consensus on the management of lennox-gastaut syndrome. Seizure. 2022;101:134–140. doi: 10.1016/j.seizure.2022.07.004
  • Contin M, Mohamed S, Santucci M, et al. Cannabidiol in pharmacoresistant epilepsy: clinical pharmacokinetic data from an expanded access program. Front Pharmacol. 2021;12:637801. doi: 10.3389/fphar.2021.637801
  • Nenert R, Allendorfer JB, Bebin EM, et al. Cannabidiol normalizes resting-state functional connectivity in treatment-resistant epilepsy. Epilepsy Behav. 2020;112:107297. doi: 10.1016/j.yebeh.2020.107297
  • Allendorfer JB, Nenert R, Bebin EM, et al. fMRI study of cannabidiol-induced changes in attention control in treatment-resistant epilepsy. Epilepsy Behav. 2019;96:114–121. doi: 10.1016/j.yebeh.2019.04.008
  • Bishop KI, Isquith PK, Gioia GA, et al. Fenfluramine treatment is associated with improvement in everyday executive function in preschool-aged children (<5 years) with dravet syndrome: a critical period for early neurodevelopment. Epilepsy Behav. 2023;138:108994. doi: 10.1016/j.yebeh.2022.108994
  • Bishop KI, Isquith PK, Gioia GA, et al. Improved everyday executive functioning following profound reduction in seizure frequency with fenfluramine: analysis from a phase 3 long-term extension study in children/young adults with dravet syndrome. Epilepsy Behav. 2021;121:108024. doi: 10.1016/j.yebeh.2021.108024
  • Nabbout R, Mistry A, Zuberi S, et al. Fenfluramine for Treatment-resistant seizures in patients with dravet syndrome receiving stiripentol-inclusive regimens: a randomized clinical trial. JAMA Neurol. 2020;77(3):300. doi: 10.1001/jamaneurol.2019.4113
  • Tabaee Damavandi P, Fabin N, Giossi R, et al. Efficacy and safety of fenfluramine in epilepsy: a systematic review and meta-analysis. Neurol Ther. 2023;12(2):669–686. doi: 10.1007/s40120-023-00452-1
  • Lattanzi S, Trinka E, Russo E, et al. Pharmacotherapy for dravet syndrome: a systematic review and network meta-analysis of randomized controlled trials. Drugs. 2023;83(15):1409–1424. doi: 10.1007/s40265-023-01936-y
  • Aeby A, Sculier C, Bouza AA, et al. SCN1B ‐linked early infantile developmental and epileptic encephalopathy. Ann Clin Transl Neurol. 2019;6(12):2354–2367. doi: 10.1002/acn3.50921
  • Gil-Nagel A, Sullivan J, Ceulemans B, et al. Treatment with fenfluramine in patients with dravet syndrome has no long-term effects on weight and growth. Epilepsy Behav. 2021;122:108212. doi: 10.1016/j.yebeh.2021.108212
  • Freri E, Matricardi S, Gozzo F, et al. Perisylvian, including insular, childhood epilepsy: presurgical workup and surgical outcome. Epilepsia. 2017;58(8):1360–1369.
  • Verrotti A, Iapadre G, Di Donato G, et al. Pharmacokinetic considerations for anti-epileptic drugs in children. Expert Opin Drug Metab Toxicol. 2019;15(3):199–211. doi: 10.1080/17425255.2019.1575361
  • Vecchi M, Barba C, De Carlo D, et al. Symptomatic and presumed symptomatic focal epilepsies in childhood: an observational, prospective multicentre study. Epilepsia. 2016;57(11):1808–1816. doi: 10.1111/epi.13574
  • 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 Neurotherapeutics. 2020;20(2):167–173. doi: 10.1080/14737175.2020.1707668
  • Shishmanova-Doseva M, Atanasova D, Uzunova Y, et al. Effects of lacosamide treatment on epileptogenesis, neuronal damage and behavioral comorbidities in a rat model of temporal lobe epilepsy. IJMS. 2021;22(9):4667. doi: 10.3390/ijms22094667
  • Palleria C, Coppola A, Citraro R, et al. Perspectives on treatment options for mesial temporal lobe epilepsy with hippocampal sclerosis. Expert Opin Pharmacother. 2015;16(15):2355–2371. doi: 10.1517/14656566.2015.1084504
  • Barba C, Cross JH, Braun K, et al. Trends in pediatric epilepsy surgery in Europe between 2008 and 2015: country‐, center‐, and age‐specific variation. Epilepsia. 2020;61(2):216–227. doi: 10.1111/epi.16414
  • Perucca E, Brodie MJ, Kwan P, et al. 30 years of second-generation antiseizure medications: impact and future perspectives. Lancet Neurol. 2020;19(6):544–556. doi: 10.1016/S1474-4422(20)30035-1

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