156
Views
0
CrossRef citations to date
0
Altmetric
Perspective

What are the considerations when initiating treatment for epilepsy in children?

& ORCID Icon
Pages 1081-1096 | Received 10 Aug 2023, Accepted 22 Nov 2023, Published online: 30 Nov 2023

References

  • Epilepsy Fact Sheet. World Health Organization. [cited 2023 Nov 22]. Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy
  • Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005;46(4):470–472. doi: 10.1111/j.0013-9580.2005.66104.x
  • Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475–482. doi: 10.1111/epi.12550
  • Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the international league against epilepsy: position paper of the ILAE commission for classification and terminology. Epilepsia. 2017;58(4):522–530. doi: 10.1111/epi.13670
  • Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology. Epilepsia. 2017;58(4):512–521. doi: 10.1111/epi.13709
  • 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
  • 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. 2010;51(6):1069–1077. doi: 10.1111/j.1528-1167.2009.02397.x
  • Sultana B, Panzini MA, Veilleux Carpentier A, et al. Incidence and prevalence of Drug-Resistant Epilepsy: a systematic review and meta-analysis. Neurology. 2021;96(17):805–817. doi: 10.1212/WNL.0000000000011839
  • Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314–319. doi: 10.1056/NEJM200002033420503
  • Geerts A, Arts WF, Stroink H, et al. Course and outcome of childhood epilepsy: a 15-year follow-up of the Dutch study of epilepsy in childhood. Epilepsia. 2010;51(7):1189–1197. doi: 10.1111/j.1528-1167.2010.02546.x
  • Medel-Matus JS, Orozco-Suárez S, Escalante RG. Factors not considered in the study of drug-resistant epilepsy: psychiatric comorbidities, age and gender. Epilepsia Open. 2022;7(Suppl 1):S81–S93. doi: 10.1002/epi4.12576
  • Rho JM, White HS. Brief history of anti-seizure drug development. Epilepsia Open. 2018;3(Suppl 2):114–119. doi: 10.1002/epi4.12268
  • Ismail FY, Fatemi A, Johnston MV. Cerebral plasticity: windows of opportunity in the developing brain. Eur J Paediatr Neurol. 2017;21(1):23–48. doi: 10.1016/j.ejpn.2016.07.007
  • Singhi S, Gupta A. A review of the selected and newer antiseizure medications used in childhood epilepsies. Indian J Pediatr. 2021;88(10):993–999. doi: 10.1007/s12098-021-03857-8
  • Tenney JR. Epilepsy-work-up and management in children. Semin Neurol. 2020;40(6):638–646. doi: 10.1055/s-0040-1718720
  • Reynolds EH, Shorvon SD. Monotherapy or polytherapy for epilepsy? Epilepsia. 1981;22(1):1–10. doi: 10.1111/j.1528-1157.1981.tb04327.x
  • Sankar R. Initial treatment of epilepsy with antiepileptic drugs: pediatric issues. Neurology. 2004;63(10, Suppl 4):S30–S39. doi: 10.1212/WNL.63.10_suppl_4.S30
  • Brodie MJ, Yuen AW. Lamotrigine substitution study: evidence for synergism with sodium valproate? 105 study group. Epilepsy Res. 1997;26(3):423–432. doi: 10.1016/S0920-1211(96)01007-8
  • Chiron C, Duchowny M. Treatment strategies. Handb Clin Neurol. 2013;111:727–739.
  • Leone MA, Giussani G, Nolan SJ, et al. Immediate antiepileptic drug treatment, versus placebo, deferred, or no treatment for first unprovoked seizure. Cochrane Database Syst Rev. 2016 5. CD007144. doi: 10.1002/14651858.CD007144.pub2
  • Jiménez-Villegas MJ, Lozano-García L, Carrizosa-Moog J. Update on first unprovoked seizure in children and adults: A narrative review. Seizure. 2021;90:28–33. doi: 10.1016/j.seizure.2021.03.027
  • Sveinsson O, Andersson T, Mattsson P, et al. Clinical risk factors in SUDEP: a nationwide population-based case-control study. Neurology. 2020;94(4):e419–e429. doi: 10.1212/WNL.0000000000008741
  • Kang JY, Mintzer S. Driving and Epilepsy: a review of important issues. Curr Neurol Neurosci Rep. 2016;16(9):80. doi: 10.1007/s11910-016-0677-y
  • Löscher W, Klein P. The pharmacology and clinical efficacy of antiseizure medications: from bromide salts to cenobamate and beyond. CNS Drugs. 2021;35(9):935–963. doi: 10.1007/s40263-021-00827-8
  • 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
  • Epilepsies in children, young people and adults – NICE Guidelines. National Institute For Health And Care Excellence. [cited 2023 Nov 22]. Available from: https://www.nice.org.uk/guidance/ng217.
  • The treatment of epilepy in pediatrics guidelines. The Italian society of child and adolescent neuropsychiatry. [cited 2023 Nov 22]. Available from: https://sinpia.eu/wp-content/uploads/2019/02/2017_1.pdf.
  • Glauser T, Ben-Menachem E, Bourgeois B, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013;54(3):551–563. doi: 10.1111/epi.12074
  • Mostacci B, Ranzato F, Giuliano L, et al. Alternatives to valproate in girls and women of childbearing potential with idiopathic generalized epilepsies: state of the art and guidance for the clinician proposed by the epilepsy and gender Commission of the Italian League Against Epilepsy (LICE). Seizure. 2021;85:26–38. doi: 10.1016/j.seizure.2020.12.005
  • Balagura G, Iapadre G, Verrotti A, et al. Moving beyond sodium valproate: choosing the right anti-epileptic drug in children. Expert Opin Pharmacother. 2019;20(12):1449–1456. doi: 10.1080/14656566.2019.1617850
  • Höfler J, Unterberger I, Dobesberger J, et al. Seizure outcome in 175 patients with juvenile myoclonic epilepsy–a long-term observational study. Epilepsy Res. 2014;108(10):1817–1824. doi: 10.1016/j.eplepsyres.2014.09.008
  • Talwar D, Arora MS, Sher PK. EEG changes and seizure exacerbation in young children treated with carbamazepine. Epilepsia. 1994;35(6):1154–1159. doi: 10.1111/j.1528-1157.1994.tb01782.x
  • Guerrini R, Dravet C, Genton P, et al. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia. 1998;39(5):508–512. doi: 10.1111/j.1528-1157.1998.tb01413.x
  • Lux AL, Edwards SW, Hancock E, et al. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial. Lancet Neurol. 2005;4(11):712–717. doi: 10.1016/S1474-4422(05)70199-X
  • Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev. 2013;6:CD001770. doi: 10.1002/14651858.CD001770.pub3
  • O’Callaghan FJK, Edwards SW, Alber FD, et al. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. Lancet Neurol. 2017;16(1):33–42. doi: 10.1016/S1474-4422(16)30294-0
  • O’Callaghan FJK, Edwards SW, Alber FD, et al. Vigabatrin with hormonal treatment versus hormonal treatment alone (ICISS) for infantile spasms: 18-month outcomes of an open-label, randomised controlled trial. Lancet Child Adolesc Health. 2018;2(10):715–725. doi: 10.1016/S2352-4642(18)30244-X
  • Perucca E, Gram L, Avanzini G, et al. Antiepileptic drugs as a cause of worsening seizures. Epilepsia. 1998 Jan;39(1):5–17. doi: 10.1111/j.1528-1157.1998.tb01268.x
  • Rubboli G, Gardella E, Cantalupo G, et al. Encephalopathy related to status epilepticus during slow sleep (ESES). Pathophysiological insights and nosological considerations. Epilepsy Behav. 2023;140:109105. doi: 10.1016/j.yebeh.2023.109105
  • Van Bogaert P. Epileptic encephalopathy with continuous spike-waves during slow-wave sleep including Landau-kleffner syndrome. Handb Clin Neurol. 2013;111:635–640.
  • Veggiotti P, Pera MC, Teutonico F, et al. Therapy of encephalopathy with status epilepticus during sleep (ESES/CSWS syndrome): an update. Epileptic Disord. 2012;14(1):1–11. doi: 10.1684/epd.2012.0482
  • Pisani F, Seri S, Pelliccia A. Landau-kleffner syndrome and atypical benign partial epilepsy of childhood: the effectiveness of acetazolamide. Neuropediatrics. 1999;30(3):164. doi: 10.1055/s-2007-973485
  • Fine AL, Wirrell EC, Wong-Kisiel LC, et al. Acetazolamide for electrical status epilepticus in slow-wave sleep. Epilepsia. 2015;56(9):e134–8. doi: 10.1111/epi.13101
  • Morrell F, Whisler WW, Smith MC, et al. Landau-kleffner syndrome. Treatment with subpial intracortical transection. Brain. 1995;118(Pt 6):1529–1546. doi: 10.1093/brain/118.6.1529
  • Valproate and related substances. European medicines Agency (EMA). Available from: https://www.ema.europa.eu/en/medicines/human/referrals/valproate-related-substances
  • Eriksson K, Viinikainen K, Mönkkönen A, et al. Children exposed to valproate in utero: population-based evaluation of risks and confounding factors for long-term neurocognitive development. Epilepsy Res. 2005;65(3):189–200. doi: 10.1016/j.eplepsyres.2005.06.001
  • Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 2011;10(7):609–617. doi: 10.1016/S1474-4422(11)70107-7
  • Veroniki AA, Rios P, Cogo E, et al. Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis. BMJ Open. 2017;7(7):e017248. doi: 10.1136/bmjopen-2017-017248
  • Chateauvieux S, Morceau F, Dicato M, et al. Molecular and therapeutic potential and toxicity of valproic acid. J Biomed Biotechnol. 2010;2010:1–18. doi: 10.1155/2010/479364
  • Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1016–1026. doi: 10.1016/S0140-6736(07)60461-9
  • Mermi Dibek D, Öztura İ, Baklan B. Our reasons for converting to valproic acid treatment in female patients with genetic generalized epilepsy: a retrospective, single-centre study. Neurol Sci. 2022;43:517–523. doi: 10.1007/s10072-021-05261-8
  • Giuliano L, Vecchio C, Mastrangelo V, et al. Sex differences in side effects of antiseizure medications in pediatric patients with epilepsy: a systematic review. Seizure. 2022;102:6–13. doi: 10.1016/j.seizure.2022.09.013
  • Reiter E, Feucht M, Hauser E, et al. Changes in body mass index during long-term topiramate therapy in paediatric epilepsy patients–a retrospective analysis. Seizure. 2004;13:491–493. doi: 10.1016/j.seizure.2003.12.001
  • Grosso S, Franzoni E, Iannetti P, et al. Efficacy and safety of topiramate in refractory epilepsy of childhood: long-term follow-up study. J Child Neurol. 2005;20(11):893–897. doi: 10.1177/08830738050200110601
  • Sicca F, Contaldo A, Rey E, et al. Phenytoin administration in the newborn and infant. Brain Dev. 2000;22(1):35–40. doi: 10.1016/S0387-7604(99)00110-2
  • Guidelines on Clinical Investigation of Medicinal Products in the Treatment of Epileptic Disorders. European Medicines Agency[internet]. 2018. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-clinical-investigation-medicinal-products-treatment-epileptic-disorders-revision-3_en.pdf.
  • Drugs for treatment of partial onset seizures: full extrapolation of efficacy from adults to pediatric patients 2 years of age and older guidance for industry. The FDA. 2019. Available from: www.fda.gov/media/130449/download
  • Pellock JM, Carman WJ, Thyagarajan V, et al. Efficacy of antiepileptic drugs in adults predicts efficacy in children: a systematic review. Neurology. 2012;79(14):1482–1489. doi: 10.1212/WNL.0b013e31826d5ec0
  • French JA, Cleary E, Dlugos D, et al. Considerations for determining the efficacy of new antiseizure medications in children age 1 month to younger than 2 years. Epilepsia. 2022;63(10):2664–2670. doi: 10.1111/epi.17366
  • Håkansson S, Wickström R, Zelano J. Selection and continuation of antiseizure medication in children with epilepsy in Sweden from 2007 to 2020. Pediatr Neurol. 2023;144:19–25. doi: 10.1016/j.pediatrneurol.2023.03.016
  • Sourbron J, Auvin S, Arzimanoglou A, et al. Medical treatment in infants and young children with epilepsy: off-label use of antiseizure medications. Survey report of ILAE task force medical therapies in children. Epilepsia Open. 2023;8(1):77–89. doi: 10.1002/epi4.12666
  • Bellis JR, Kirkham JJ, Nunn AJ, et al. Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to a paediatric hospital. Br J Clin Pharmacol. 2014;77(3):545–553. doi: 10.1111/bcp.12222
  • Schrier L, Hadjipanayis A, Stiris T, et al. Off-label use of medicines in neonates, infants, children, and adolescents: a joint policy statement by the European Academy of paediatrics and the European society for developmental perinatal and pediatric pharmacology. Eur J Pediatr. 2020;179(5):839–847. doi: 10.1007/s00431-019-03556-9
  • Laville F, Montana M, Roux N, et al. Factors limiting adherence to antiepileptic treatment: a French online patient survey. J Clin Pharm Ther. 2018;43(1):73–79. doi: 10.1111/jcpt.12615
  • Pironi V, Ciccone O, Beghi E, et al. ILAE task force on access to treatment. Survey on the worldwide availability and affordability of antiseizure medications: report of the ILAE task force on access to treatment. Epilepsia. 2022;63(2):335–351. doi: 10.1111/epi.17155.
  • Jost J, Preux PM, Druet-Cabanac M, et al. How to reduce the treatment gap for people with epilepsy in resource-limited settings by innovative galenic formulations: a review of the current situation, overview of potential techniques, interests and limits. Epilepsy Res. 2016;119:49–61. doi: 10.1016/j.eplepsyres.2015.10.004
  • Messahel S, Bracken L, Appleton R. Optimal management of status epilepticus in children in the emergency setting: a review of recent advances. Open Access Emerg Med. 2022;14:491–506. doi: 10.2147/OAEM.S293258
  • Seiden LG, Connor GS. The importance of drug titration in the management of patients with epilepsy. Epilepsy Behav. 2022;128:108517. doi: 10.1016/j.yebeh.2021.108517
  • Cameron A, Bansal A, Dua T, et al. Mapping the availability, price, and affordability of antiepileptic drugs in 46 countries. Epilepsia. 2012;53(6):962–969. doi: 10.1111/j.1528-1167.2012.03446.x.
  • Niyongere J, Welty TE, Bell MW, et al. Barriers to generic antiseizure medication use: results of a global survey by the international league against epilepsy generic substitution task force. Epilepsia Open. 2022;7(2):260–270. doi: 10.1002/epi4.12583
  • Perucca E. Extended-release formulations of antiepileptic drugs: rationale and comparative value. Epilepsy Curr. 2009;9(6):153–157. doi: 10.1111/j.1535-7511.2009.01326.x
  • Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med. 1985;313:145–151. doi: 10.1056/NEJM198507183130303
  • Hakami T. Neuropharmacology of Antiseizure Drugs. Neuropsychopharmacol Rep. 2021;41(3):336–351. doi: 10.1002/npr2.12196
  • Operto FF, Pastorino GMG, Mazza R, et al. Effects on executive functions of antiepileptic monotherapy in pediatric age. Epilepsy Behav. 2020;102:106648. doi: 10.1016/j.yebeh.2019.106648
  • Auvin S. Paediatric epilepsy and cognition. Dev Med Child Neurol. 2022;64(12):1444–1452. doi: 10.1111/dmcn.15337
  • Williams J, Phillips T, Griebel ML, et al. Factors associated with academic achievement in children with controlled epilepsy. Epilepsy Behav. 2001;2(3):217–223. doi: 10.1006/ebeh.2001.0166
  • Löring DW, Marino S, Meador KJ. Neuropsychological and behavioral effects of antiepilepsy drugs. Neuropsychol rev. 2007;17(4):413–425. doi: 10.1007/s11065-007-9043-9
  • Hermann B, Meador KJ, Gaillard WD, et al. Cognition across the lifespan: antiepileptic drugs, epilepsy, or both? Epilepsy Behav. 2010;17(1):1–5. doi: 10.1016/j.yebeh.2009.10.019
  • Hamed SA. The aspects and mechanisms of cognitive alterations in epilepsy: the role of antiepileptic medications. CNS Neurosci Ther. 2009;15(2):134–156. doi: 10.1111/j.1755-5949.2008.00062.x
  • Ortinski P, Meador KJ. Cognitive side effects of antiepileptic drugs. Epilepsy Behav. 2004;5:60–65. doi: 10.1016/j.yebeh.2003.11.008
  • Eddy CM, Rickards HE, Cavanna AE. The cognitive impact of antiepileptic drugs. Ther Adv Neurol Disord. 2011;4(6):385–407. doi: 10.1177/1756285611417920
  • Lagae L. Cognitive side effects of anti-epileptic drugs: the relevance in childhood epilepsy. Seizure. 2006;15(4):235–241. doi: 10.1016/j.seizure.2006.02.013
  • Farwell JR, Lee YJ, Hirtz DG, et al. Phenobarbital for febrile seizures–effects on intelligence and on seizure recurrence. N Engl J Med. 1990;322(6):364–369. doi: 10.1056/NEJM199002083220604
  • Glauser TA, Cnaa A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010;362(9):790–799. doi: 10.1056/NEJMoa0902014
  • Besag FMC, Vasey MJ. Neurocognitive effects of antiseizure medications in children and adolescents with epilepsy. Paediatr Drugs. 2021;23(3):253–286. doi: 10.1007/s40272-021-00448-0
  • Glauser TA. Behavioral and psychiatric adverse events associated with antiepileptic drugs commonly used in pediatric patients. J Child Neurol. 2004;19(Suppl 1):S25–S38. doi: 10.1177/088307380401900104
  • Halma E, de Louw AJ, Klinkenberg S, et al. Behavioral side effects of levetiracetam in children with epilepsy: a systematic review. Seizure. 2014;23(9):685–691. doi: 10.1016/j.seizure.2014.06.004
  • Faircloth VC, Hunt SL, Yuncker LA, et al. Levetiracetam adjunctive therapy for refractory pediatric focal-onset epilepsy. Epilepsia. 2001;42(S7):54.
  • Steinhoff BJ, Klein P, Klitgaard H, et al. Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: a systematic review. Epilepsy Behav. 2021;118:107939. doi: 10.1016/j.yebeh.2021.107939
  • Romoli M, Perucca E, Sen A. Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review. Epilepsy Behav. 2020;103(Pt A):106861. doi: 10.1016/j.yebeh.2019.106861
  • Marino S, Vitaliti G, Marino SD, et al. Pyridoxine add-on treatment for the control of behavioral adverse effects induced by levetiracetam in children: a case-control prospective study. Ann Pharmacother. 2018;52(7):645–649. doi: 10.1177/1060028018759637
  • Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by Pyridoxine. A randomized Double blind controlled study. Pediatr Neurol. 2021;119:15–21. doi: 10.1016/j.pediatrneurol.2021.02.010
  • Glauser TA, Pellock JM. Tropical review: zonisamide in pediatric epilepsy: review of the Japanese experience. J Child Neurol. 2002;17(2):87–96. doi: 10.1177/088307380201700201
  • Besag F, Aldenkamp A, Caplan R, et al. Psychiatric and behavioural disorders in children with epilepsy: an ILAE task force report. Epileptic Disord. 2016;18(Suppl 1):1–86. doi: 10.1684/epd.2016.0815
  • Moavero R, Santarone ME, Galasso C, et al. Cognitive and behavioral effects of new antiepileptic drugs in pediatric epilepsy. Brain Dev. 2017;39(6):464–469. doi: 10.1016/j.braindev.2017.01.006
  • Ijff DM, Aldenkamp AP. Cognitive side-effects of antiepileptic drugs in children. Handb Clin Neurol. 2013;111:707–718.
  • Strzelczyk A, Schubert-Bast S. Psychobehavioural and cognitive adverse events of anti-seizure medications for the treatment of developmental and epileptic encephalopathies. CNS Drugs. 2022;36(10):1079–1111. doi: 10.1007/s40263-022-00955-9
  • Helmstaedter C, Witt JA. Anticonvulsant drugs and cognition. In: Riederer P, Laux G, Mulsant B, Le W Nagatsu T, editors. NeuroPsychopharmacotherapy. Cham: Springer; 2020. doi: 10.1007/978-3-319-56015-1_375-1
  • Vidaurre J, Gedela S, Yarosz S. Antiepileptic drugs and liver disease. Pediatr Neurol. 2017;77:23–36. doi: 10.1016/j.pediatrneurol.2017.09.013
  • Kellogg M, Meador KJ. Neurodevelopmental effects of antiepileptic drugs. Neurochem Res. 2017;42(7):2065–2070. doi: 10.1007/s11064-017-2262-4
  • Wyllie E. Wyllie’s treatment of epilepsy. Wyllie E, editor. Philadelphia: Wolters Kluwer; 2021.
  • Chen Z, Brodie MJ, Liew D, et al. 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):279–286. doi: 10.1001/jamaneurol.2017.3949
  • Diemar SS, Sejling AS, Eiken P, et al. An explorative literature review of the multifactorial causes of osteoporosis in epilepsy. Epilepsy Behav. 2019;100:106511. doi: 10.1016/j.yebeh.2019.106511
  • Uvebrant P, Bauziene R. Intractable epilepsy in children. The efficacy of lamotrigine treatment, including non-seizure-related benefits. Neuropediatrics. 1994;25(6):284–289. doi: 10.1055/s-2008-1073041
  • Sherard ES Jr, Steiman GS, Couri D. Treatment of childhood epilepsy with valproic acid: results of the first 100 patients in a 6-month trial. Neurology. 1980;30:31–35. doi: 10.1212/WNL.30.1.31
  • Verity CM, Hosking G, Easter DJ, et al. A multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy. Dev Med Child Neurol. 1995;37(2):97–108. doi: 10.1111/j.1469-8749.1995.tb11978.x
  • Balestrini S, Chiarello D, Gogou M, et al. Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies. J Neurol Neurosurg Psychiatry. 2021;92(10):1044–1052. doi: 10.1136/jnnp-2020-325932
  • Myers KA, Scheffer IE. Precision medicine approaches for infantile-onset developmental and epileptic encephalopathies. Annu Rev Pharmacol Toxicol. 2022;62(1):641–662. doi: 10.1146/annurev-pharmtox-052120-084449
  • Marini C, Giardino M. Novel treatments in epilepsy guided by genetic diagnosis. Br J Clin Pharmacol. 2022;88(6):2539–2551. doi: 10.1111/bcp.15139
  • Wirrell EC, Nabbout R. Recent advances in the drug treatment of Dravet syndrome. CNS Drugs. 2019;33(9):867–881. doi: 10.1007/s40263-019-00666-8
  • Pisano T, Numis AL, Heavin SB, et al. Early and effective treatment of KCNQ2 encephalopathy. Epilepsia. 2015;56(5):685–691. doi: 10.1111/epi.12984
  • Elterman RD, Shields WD, Mansfield KA, et al. Randomized trial of vigabatrin in patients with infantile spasms. Neurology. 2001;57(8):1416–1421. doi: 10.1212/WNL.57.8.1416
  • Bombardieri R, Pinci M, Moavero R, et al. Early control of seizures improves long-term outcome in children with tuberous sclerosis complex. Eur J Paediatr Neurol. 2010;14(2):146–149. doi: 10.1016/j.ejpn.2009.03.003
  • De Ridder J, Verhelle B, Vervisch J, et al. Early epileptiform EEG activity in infants with tuberous sclerosis complex predicts epilepsy and neurodevelopmental outcomes. Epilepsia. 2021;62(5):1208–1219. doi: 10.1111/epi.16892
  • Sasongko TH, Kademane K, Chai Soon Hou S, et al. Rapamycin and rapalogs for tuberous sclerosis complex. Cochrane Database Syst Rev. 2023;7(7). CD011272. doi: 10.1002/14651858.CD011272.pub3
  • Wolff M, Johannesen KM, Hedrich UBS, et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain. 2017;140(5):1316–1336. doi: 10.1093/brain/awx054
  • Marini C, Porro A, Rastetter A, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141(11):3160–3178. doi: 10.1093/brain/awy263
  • Hedrich UBS, Lauxmann S, Wolff M, et al. 4-aminopyridine is a promising treatment option for patients with gain-of-function KCNA2-encephalopathy. Sci Transl Med. 2021;13(609):eaaz4957. doi: 10.1126/scitranslmed.aaz4957
  • Partemi S, Cestèle S, Pezzella M, et al. Loss-of-function KCNH2 mutation in a family with long QT syndrome, epilepsy, and sudden death. Epilepsia. 2013;54(8):e112–6. doi: 10.1111/epi.12259
  • Zhou Y, Hao N, Sander JW, et al. KCNH2 variants in a family with epilepsy and long QT syndrome: a case report and literature review. Epileptic Disord. 2023 Mar 22;25(4):492–499. Online ahead of print. doi: 10.1002/epd2.20046
  • Mandelenaki D, Juvené E, Lederer D, et al. Precision medicine: Vinpocetine as a potential treatment for GABRG2-related epilepsy. Epileptic Disord. 2023;25(3):383–389. doi: 10.1002/epd2.20015
  • Billakota S, Andresen JM, Gay BC, et al. Personalized medicine: vinpocetine to reverse effects of GABRB3 mutation. Epilepsia. 2019;60(12):2459–2465. doi: 10.1111/epi.16394
  • Samanta D. DEPDC5-related epilepsy: a comprehensive review. Epilepsy Behav. 2022;130:108678. doi: 10.1016/j.yebeh.2022.108678
  • De Giorgis V, Tagliabue A, Bisulli F, et al. Ketogenic dietary therapies in epilepsy: recommendations of the Italian League against epilepsy dietary therapy study group. Front Neurol. 2023;14:1215618. doi: 10.3389/fneur.2023.1215618
  • Tomson T, Battino D, Perucca E. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time honoured drug. Lancet Neurol. 2016;15:210–218. doi: 10.1016/S1474-4422(15)00314-2
  • Milligan CJ, Li M, Gazina EV, et al. KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine. Ann Neurol. 2014;75(4):581–590. doi: 10.1002/ana.24128
  • Fitzgerald MP, Fiannacca M, Smith DM, et al. Treatment responsiveness in KCNT1-related epilepsy. Neurotherapeutics. 2019;16(3):848–857. doi: 10.1007/s13311-019-00739-y
  • Borlot F, Abushama A, Morrison-Levy N, et al. KCNT1-related epilepsy: an international multicenter cohort of 27 pediatric cases. Epilepsia. 2020;61(4):679–692. doi: 10.1111/epi.16480
  • Jehi L, Jette N, Kwon CS, et al. Timing of referral to evaluate for epilepsy surgery: expert consensus recommendations from the surgical therapies commission of the international league against epilepsy. Epilepsia. 2022;63(10):2491–2506. doi: 10.1111/epi.17350
  • Kossoff EH, Zupec-Kania BA, Auvin S, et al.; 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(2):175–192. doi: 10.1002/epi4.12225
  • Winter Y, Sandner K, Glaser M, et al. Synergistic effects of vagus nerve stimulation and antiseizure medication. J Neurol. 2023;270(10):4978–4984. doi: 10.1007/s00415-023-11825-9
  • Schulze-Bonhage A, Hirsch M, Knake S, et al. Focal Cortex Stimulation With a Novel Implantable Device and Antiseizure Outcomes in 2 Prospective Multicenter Single-Arm Trials. JAMA Neurol. 2023;80(6):588–596. doi: 10.1001/jamaneurol.2023.0066
  • Müller P, Takacs DS, Hedrich UBS, et al. KCNA1 gain-of-function epileptic encephalopathy treated with 4-aminopyridine. Ann Clin Transl Neurol. 2023;10(4):656–663. doi: 10.1002/acn3.51742
  • Grover S, Kukreti R. HLA alleles and hypersensitivity to carbamazepine: an updated systematic review with meta-analysis. Pharmacogenet Genom. 2014;24(2):94–112. doi: 10.1097/FPC.0000000000000021
  • Balestrini S, Sisodiya SM. Pharmacogenomics in epilepsy. Neurosci Lett. 2018;667:27–39. doi: 10.1016/j.neulet.2017.01.014
  • Chouchi M, Kaabachi W, Klaa H, et al. Relationship between ABCB1 3435TT genotype and antiepileptic drugs resistance in epilepsy: updated systematic review and meta-analysis. BMC neurol. 2017;17(1):32. doi: 10.1186/s12883-017-0801-x
  • Ghosh C, Westcott R, Perucca E, et al. Cytochrome P450-mediated antiseizure medication interactions influence apoptosis, modulate the brain BAX/Bcl-XL ratio and aggravate mitochondrial stressors in human pharmacoresistant epilepsy. Front Pharmacol. 2022;13:983233. doi: 10.3389/fphar.2022.983233
  • André EA, Forcelli PA, Pak DT. What goes up must come down: homeostatic synaptic plasticity strategies in neurological disease. Future Neurol. 2018;13(1):13–21. doi: 10.2217/fnl-2017-0028
  • Maljevic S, Reid CA, Petrou S. Models for discovery of targeted therapy in genetic epileptic encephalopathies. J Neurochem. 2017;143(1):30–48. doi: 10.1111/jnc.14134
  • Qiu Y, O’Neill N, Maffei B, et al. On-demand cell-autonomous gene therapy for brain circuit disorders. Science. 2022;378(6619):523–532. doi: 10.1126/science.abq6656

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.