Symonds JD, Elliott KS, Shetty J, et al. Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants. Brain. 2021;144(9):2879–2891.

Hauser WA, Beghi E. First seizure definitions and worldwide incidence and mortality. Epilepsia. 2008;49(Suppl 1):8–12.

Camfield CS, Camfield PR, Gordon K, Wirrell E, Dooley JM. Incidence of epilepsy in childhood and adolescence: a population-based study in Nova Scotia from 1977 to 1985. Epilepsia. 1996;37(1):19–23.

Aaberg KM, Gunnes N, Bakken IJ, et al. Incidence and prevalence of childhood epilepsy: a nationwide cohort study. Pediatrics. 2017;139(5):e20163908.

Wirrell E, Wong-Kisiel L, Mandrekar J, Nickels K. Predictors and course of medically intractable epilepsy in young children presenting before 36 months of age: a retrospective, population-based study. Epilepsia. 2012;53(9):1563–1569.

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. Epilepsia. 2010;51(6):1069–1077.

Vignoli A, Peron A, Turner K, et al. Long-term outcome of epilepsy with onset in the first three years of life: findings from a large cohort of patients. Eur J Paediatr Neurol. 2016;20(4):566–572.

Berg AT, Wusthoff C, Shellhaas RA, et al. Immediate outcomes in early life epilepsy: a contemporary account. Epilepsy Behav. 2019;97:44–50.

Berg AT, Langfitt JT, Testa FM, et al. Global cognitive function in children with epilepsy: a community-based study. Epilepsia. 2008;49(4):608–614.

10.

Jennum P, Pickering L, Christensen J, Ibsen R, Kjellberg J. Morbidity and mortality of childhood- and adolescent-onset epilepsy: a controlled national study. Epilepsy Behav. 2017;66:80–85.

11.

Perry MS, Shandley S, Perelman M, et al. Surgical evaluation in children <3 years of age with drug-resistant epilepsy: patient characteristics, diagnostic utilization, and potential for treatment delays. Epilepsia. 2022;63(1):96–107.

12.

Grinspan ZM, Knupp KG, Patel AD, et al. Comparative effectiveness of initial treatment for infantile spasms in a contemporary US cohort. Neurology. 2021;97(12):e1217–e1228.

13.

Wilmshurst JM, Gaillard WD, Vinayan KP, et al. Summary of recommendations for the management of infantile seizures: task force report for the ILAE commission of pediatrics. Epilepsia. 2015;56(8):1185–1197.

14.

Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: an evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. 2023;32(2):266–280.

15.

Wirrell EC, Hood V, Knupp KG, et al. International consensus on diagnosis and management of Dravet syndrome. Epilepsia. 2022;63(7):1761–1777.

16.

Duis J, Nespeca M, Summers J, et al. A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome. Mol Genet Genomic Med. 2022;10(3):e1843.

17.

Reeves MJ, Fonarow GC, Smith EE, Sheth KN, Messe SR, Schwamm LH. Twenty years of get with the guidelines-stroke: celebrating past successes, lessons learned, and future challenges. Stroke. 2024;55(6):1689–1698.

18.

Hirsch M, Beck J, Brandt A, et al. Trends in referral patterns to presurgical evaluation at a European reference center. Seizure. 2023;111:78–86.

19.

Treadwell JR, Wu M, Tsou AY. Management of infantile epilepsies. comparative effectiveness review No. 252. (Prepared by the ECRI–Penn Medicine Evidence-based Practice Center under Contract No. 75Q80120D00002.) AHRQ Publication No. 22(23)-EHC004. PCORI Publication No. 2021-SR-01. Agency for Healthcare Research and Quality (AHRQ). Updated October 25, 2022.

View source

20.

FDA. DEPAKENE (valproic acid) label. PDF. FDA. Updated 11, 2016.

View source

21.

Star K, Edwards IR, Choonara I. Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. PLoS One. 2014;9(10):e108970.

22.

Gloss D. AES Clinical Practice Guideline Development Manual. Chicago, IL: American Epilepsy Society; 2020.

23.

Andrews J, Guyatt G, Oxman AD, et al. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol. 2013;66(7):719–725.

24.

Alonso-Coello P, Schünemann HJ, Moberg J, et al. GRADE evidence to decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. Br Med J. 2016;353:i2016.

25.

Balshem H, Helfand M, Schünemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–406.

26.

(PCORI) P-CORI. Management strategies for infantile epilepsy (a systematic review). Updated December 10, 2024.

View source

27.

(AHRQ) AfHRaQ. Management of infantile epilepsy. Research protocol. AHRQ. Updated July 2021.

View source

28.

Treadwell JR, Kessler SK, Wu M, Abend NS, Massey SL, Tsou AY. Pharmacologic and dietary treatments for epilepsies in children aged 1–36 months: a systematic review. Neurology. 2023;100(1):e16–e27.

29.

Tsou AY, Kessler SK, Wu M, Abend NS, Massey SL, Treadwell JR. Surgical treatments for epilepsies in children aged 1–36 months: a systematic review. Neurology. 2023;100(1):e1–e15.

30.

Hultcrantz M, Rind D, Akl EA, et al. The GRADE working group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017;87:4–13.

31.

Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Br Med J. 2008;336(7650):924–926.

32.

Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360–3392.

33.

Arican P, Gencpinar P, Cavusoglu D, Olgac Dundar N. Levetiracetam monotherapy for the treatment of infants with epilepsy. Seizure. 2018;56:73–77.

34.

Arzimanoglou A, Lösch C, Garate P, Bentz J. Safety of levetiracetam among infants younger than 12 months–results from a European multicenter observational study. Eur J Paediatr Neurol. 2016;20(3):368–375.

35.

FDA. KEPPRA (levetiracetam) label. FDA. 2025.

View source

36.

Muthaffar OY, Almahmudi SM, Alrabghi MO, Bin Mahfouz MM, Alfawaz NS. Valproic acid for children below 2 years of age with epilepsy. Neurosciences. 2021;26(4):357–365.

37.

Zhao B, Liao S, Zhong X, et al. Effectiveness and safety of oxcarbazepine vs. levetiracetam as monotherapy for infantile focal epilepsy: a longitudinal cohort study. Front Neurol. 2022;13:909191.

38.

Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci USA. 2002;99(23):15089–15094.

39.

Sulzbacher S, Farwell JR, Temkin N, Lu AS, Hirtz DG. Late cognitive effects of early treatment with phenobarbital. Clin Pediatr. 1999;38(7):387–394.

40.

Grinspan ZM, Shellhaas RA, Coryell J, et al. Comparative effectiveness of levetiracetam vs phenobarbital for infantile epilepsy. JAMA Pediatr. 2018;172(4):352–360.

41.

Pressler RM, Abend NS, Auvin S, et al. Treatment of seizures in the neonate: guidelines and consensus-based recommendations-special report from the ILAE task force on neonatal seizures. Epilepsia. 2023;64(10):2550–2570.

42.

Kim JM, Kwon S, Seo HE, Choe BH, Cho MH, Park SP. Long-term effectiveness and tolerability of topiramate in children with epilepsy under the age of 2 years: 4-year follow-up. J Korean Med Sci. 2009;24(6):1078–1082.

43.

Xiong L, He H, Wang D, Liu T, Xiao N. Effectiveness and safety of lacosamide in pediatric patients with epilepsy under four years: results from a prospective cohort study in China. Seizure. 2024;118:71–79.

44.

Yang L, Liu Y, Deng Y, et al. Efficacy, safety, and tolerability of adjunctive lacosamide therapy for focal seizures in young children aged ≥1 month to ≤4 years: a real-world study. CNS Neurosci Ther. 2024;30(8):e14917.

45.

FDA. VIMPAT (lacosamide) label. PDF. FDA. Updated 10, 2023.

View source

46.

Grosso S, Galimberti D, Farnetani MA, et al. Efficacy and safety of topiramate in infants according to epilepsy syndromes. Seizure. 2005;14(3):183–189.

47.

Kholin A, Zavadenko N, Il'ina E, et al. Relationship between the efficacy and safety of topiramate and patients’ ages and types of epilepsy. Neurosci Behav Physiol. 2014;44(7):765–771.

48.

Manitpisitkul P, Shalayda K, Todd M, Wang SS, Ness S, Ford L. Pharmacokinetics and safety of adjunctive topiramate in infants (1–24 months) with refractory partial-onset seizures: a randomized, multicenter, open-label phase 1 study. Epilepsia. 2013;54(1):156–164.

49.

Novotny E, Renfroe B, Yardi N, et al. Randomized trial of adjunctive topiramate therapy in infants with refractory partial seizures. Neurology. 2010;74(9):714–720.

50.

Piña-Garza JE, Elterman RD, Ayala R, et al. Long-term tolerability and efficacy of lamotrigine in infants 1 to 24 months old. J Child Neurol. 2008;23(8):853–861.

51.

Piña-Garza JE, Levisohn P, Gucuyener K, et al. Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months. Neurology. 2008;70(22 Pt 2):2099–2108.

52.

Tanritanir A, Wang X, Loddenkemper T. Efficacy and tolerability of rufinamide in epileptic children younger than 4 years. J Child Neurol. 2021;36(4):281–287.

53.

Yamada M, Suzuki K, Matsui D, Inoue Y, Ohtsuka Y. Long-term safety and effectiveness of stiripentol in patients with Dravet syndrome: interim report of a post-marketing surveillance study in Japan. Epilepsy Res. 2021;170:106535.

54.

Lagae L, Klotz KA, Fogarasi A, et al. Long-term safety and efficacy of adjunctive brivaracetam in pediatric patients with epilepsy: an open-label, follow-up trial. Epilepsia. 2023;64(11):2934–2946.

55.

FDA. BRIVIACT (brivaracetam) label. PDF. FDA. 8, 2025.

View source

56.

Sicca F, Contaldo A, Rey E, Dulac O. Phenytoin administration in the newborn and infant. Brain Dev. 2000;22(1):35–40.

57.

Jackson MC, Jafarpour S, Klehm J, et al. Effect of vigabatrin on seizure control and safety profile in different subgroups of children with epilepsy. Epilepsia. 2017;58(9):1575–1585.

58.

Liu Y, Wan J, Gao Z, Xu L, Kong L. Ketogenic diet and growth in Chinese infants with refractory epilepsy. Asia Pac J Clin Nutr. 2021;30(1):113–121.

59.

Kossoff EH, Zupec-Kania BA, Auvin S, et al. 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.

60.

Armeno M, Verini A, Caballero E, Cresta A, Valenzuela GR, Caraballo R. Long-term effectiveness and adverse effects of ketogenic diet therapy in infants with drug-resistant epilepsy treated at a single center in Argentina. Epilepsy Res. 2021;178:106793.

61.

Dressler A, Trimmel-Schwahofer P, Reithofer E, et al. The ketogenic diet in infants–advantages of early use. Epilepsy Res. 2015;116:53–58.

62.

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.

63.

El-Rashidy OF, Nassar MF, Abdel-Hamid IA, et al. Modified Atkins diet vs classic ketogenic formula in intractable epilepsy. Acta Neurol Scand. 2013;128(6):402–408.

64.

Kim JA, Yoon JR, Lee EJ, et al. Efficacy of the classic ketogenic and the modified Atkins diets in refractory childhood epilepsy. Epilepsia. 2016;57(1):51–58.

65.

Gupta S, Dabla S, Kaushik JS. Modified Atkins diet vs low glycemic index treatment for drug-resistant epilepsy in children: an open label, randomized controlled trial. Indian Pediatr. 2021;58(9):815–819.

66.

Roth J, Constantini S, Ekstein M, et al. Epilepsy surgery in infants up to 3 months of age: safety, feasibility, and outcomes: a multicenter, multinational study. Epilepsia. 2021;62(8):1897–1906.

67.

Makridis KL, Klotz KA, Ramantani G, et al. Epilepsy surgery in early infancy: a retrospective, multicenter study. Epilepsia Open. 2023;8(3):1182–1189.

68.

Gaillard WD, Jette N, Arnold ST, et al. Establishing criteria for pediatric epilepsy surgery center levels of care: report from the ILAE pediatric epilepsy surgery task force. Epilepsia. 2020;61(12):2629–2642.

69.

Cook SW, Nguyen ST, Hu B, et al. Cerebral hemispherectomy in pediatric patients with epilepsy: comparison of three techniques by pathological substrate in 115 patients. J Neurosurg. 2004;100(2 Suppl Pediatrics):125–141.

70.

Iwasaki M, Uematsu M, Osawa S, et al. Interhemispheric vertical hemispherotomy: a single center experience. Pediatr Neurosurg. 2015;50(5):295–300.

71.

Jonas R, Nguyen S, Hu B, et al. Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes. Neurology. 2004;62(10):1712–1721.

72.

Kadish NE, Bast T, Reuner G, et al. Epilepsy surgery in the first 3 years of life: predictors of seizure freedom and cognitive development. Neurosurgery. 2019;84(6):E368–E377.

73.

Kumar RM, Koh S, Knupp K, Handler MH, O'Neill BR. Surgery for infants with catastrophic epilepsy: An analysis of complications and efficacy. Childs Nerv Syst. 2015;31(9):1479–1491.

74.

Lettori D, Battaglia D, Sacco A, et al. Early hemispherectomy in catastrophic epilepsy: a neuro-cognitive and epileptic long-term follow-up. Seizure. 2008;17(1):49–63.

75.

Loddenkemper T, Holland KD, Stanford LD, Kotagal P, Bingaman W, Wyllie E. Developmental outcome after epilepsy surgery in infancy. Pediatrics. 2007;119(5):930–935.

76.

Otsuki T, Honda R, Takahashi A, et al. Surgical management of cortical dysplasia in infancy and early childhood. Brain Dev. 2013;35(8):802–809.

77.

Pepper J, Lo WB, Agrawal S, et al. Functional hemispherotomy for epilepsy in the very young. J Neurosurg Pediatr. 2022;30(4):400–409.

78.

Pinto AL, Lohani S, Bergin AM, et al. Surgery for intractable epilepsy due to unilateral brain disease: A retrospective study comparing hemispherectomy techniques. Pediatr Neurol. 2014;51(3):336–343.

79.

Reinholdson J, Olsson I, Edelvik A, et al. Long-term follow-up after epilepsy surgery in infancy and early childhood–a prospective population based observational study. Seizure. 2015;30:83–89.

80.

Schramm J, Kuczaty S, Sassen R, Elger CE, von Lehe M. Pediatric functional hemispherectomy: outcome in 92 patients. Acta Neurochir (Wien). 2012;154(11):2017–2028.

81.

Steinbok P, Gan PY, Connolly MB, et al. Epilepsy surgery in the first 3 years of life: a Canadian survey. Epilepsia. 2009;50(6):1442–1449.

82.

Dou X, Wang Z, Li X, et al. Efficacy and tolerability of ketogenic diet therapy in 55 Chinese children with drug-resistant epilepsy in northwest China. Acta Epileptologica. 2022;4:10.

83.

Jayalakshmi S, Panigrahi M, Nanda SK, Vadapalli R. Surgery for childhood epilepsy. Ann Indian Acad Neurol. 2014;17(Suppl 1):69–79.

84.

Liu YD, Zhu FJ, Chen Y, et al. Preliminary observation on clinical outcome and safety of surgery in early infants (<12 months) with drug-resistant epilepsy. Seizure. 2024;122:165–171.

85.

Puka K, Jones M, Mathern GW. Functional cognitive and language outcomes after cerebral hemispherectomy for hemimegalencephaly. Epilepsia. 2021;62(12):2932–2940.

86.

Ramantani G, Kadish NE, Strobl K, et al. Seizure and cognitive outcomes of epilepsy surgery in infancy and early childhood. Eur J Paediatr Neurol. 2013;17(5):498–506.

87.

Roth J, Nagar S, Constantini S, Fried I. Hemispherotomy for treatment of refractory epilepsy in children. Harefuah. 2017;156(8):482–485.

88.

Sood S, Ilyas M, Marupudi NI, et al. Anatomical hemispherectomy revisited-outcome, blood loss, hydrocephalus, and absence of chronic hemosiderosis. Childs Nerv Syst. 2019;35(8):1341–1349.

89.

Ngan Kee N, Foster E, Marquina C, et al. Systematic review of cost-effectiveness analysis for surgical and neurostimulation treatments for drug-resistant epilepsy in adults. Neurology. 2023;100(18):e1866–e1877.

90.

Widjaja E, Li B, Schinkel CD, et al. Cost-effectiveness of pediatric epilepsy surgery compared to medical treatment in children with intractable epilepsy. Epilepsy Res. 2011;94(1-2):61–68.

91.

Lhatoo S, Noebels J, Whittemore V. The NINDS Center for SUDEP Research. Sudden unexpected death in epilepsy: Identifying risk and preventing mortality. Epilepsia. 2015;56(11):1700–1706.

92.

Kalbhenn T, Cloppenborg T, Wörmann FG, et al. Operative posterior disconnection in epilepsy surgery: Experience with 29 patients. Epilepsia. 2019;60(9):1973–1983.

93.

Maton B, Jayakar P, Resnick T, Morrison G, Ragheb J, Duchowny M. Surgery for medically intractable temporal lobe epilepsy during early life. Epilepsia. 2008;49(1):80–87.

94.

Gong P, Fang T, Yang Z, et al. Surgical outcomes of infants with focal cortical dysplasia. Seizure. 2017;52:160–166.

95.

Puka K, Jones M, Mathern GW. Long-term functional, cognitive, and language outcomes after cerebral hemispherectomy for hemimegalencephaly. Epilepsia. 2021;62(12):2932–2940.

96.

Dwivedi R, Ramanujam B, Chandra PS, et al. Surgery for drug-resistant epilepsy in children. N Engl J Med. 2017;377(17):1639–1647.

97.

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.

98.

Engel J Jr, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy. Neurology. 2003;60(4):538–547.

99.

Zhang J, Yang Z, Fang T, et al. Surgical outcomes for supratentorial brain tumors in infants with epilepsy. Pediatr Neurosurg. 2020;55(1):21–28.

100.

Elliott RE, Morsi A, Geller EB, et al. Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response. Epilepsy Behav. 2011;20(1):57–63.

Related Clinical Tools