Management of Developmental and Epileptic Encephalopathies

Abstract

Developmental and epileptic encephalopathies (DEEs) are a group of rare, severe, early-onset epilepsies characterized by pharmacoresistance, marked electroencephalographic abnormalities, and delayed or regressive psychomotor development. DEEs are associated with poor long-term outcomes and increased mortality; however, early recognition and targeted treatment can impact neurodevelopmental outcomes and overall quality of life. Treatment with antiseizure medication is often challenging given drug resistance, chronic polypharmacy, and medication interactions. With advances in genetic testing and increased understanding of the neurobiological mechanisms of DEEs, the treatment approach is evolving and includes repurposed antiseizure medications and targeted therapies, as well as early surgical intervention in select patients. In addition to high seizure burden and neurodevelopmental delay, DEEs are associated with comorbidities affecting a range of body systems; these can include intellectual disability, psychiatric disorders, motor dysfunction, and respiratory and gastrointestinal problems. Over time, these comorbidities increase the complexity of management and have important implications on the disease burden and quality of life for both patients and their caregivers. Multidisciplinary care in DEEs is paramount. We summarize the current evidence on the management of specific DEEs, focusing on targeted therapies and optimizing outcomes.

Keywords

developmental and epileptic encephalopathy - intractable epilepsy - management - comorbidities - therapies

Publikationsverlauf

Artikel online veröffentlicht:
24. Februar 2025

• References

• 1 Berg AT, Berkovic SF, Brodie MJ. et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010; 51 (04) 676-685
• 2 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 (04) 512-521
• 3 Radaelli G, de Souza Santos F, Borelli WV. et al. Causes of mortality in early infantile epileptic encephalopathy: a systematic review. Epilepsy Behav 2018; 85: 32-36
• 4 Berg AT, Nickels K, Wirrell EC. et al. Mortality risks in new-onset childhood epilepsy. Pediatrics 2013; 132 (01) 124-131
• 5 Brunklaus A, Feng T, Brünger T. et al. Gene variant effects across sodium channelopathies predict function and guide precision therapy. Brain 2022; 145 (12) 4275-4286
• 6 Symonds JD, Elliott KS, Shetty J. et al. Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants. Brain 2021; 144 (09) 2879-2891
• 7 Agarwala P, Narang B, Geetha TS. et al. Early-infantile developmental and epileptic encephalopathy: the aetiologies, phenotypic differences and outcomes—a prospective observational study. Brain Commun 2023; 5 (05) fcad243
• 8 Vatta M, Tennison MB, Aylsworth AS. et al. A novel STXBP1 mutation causes focal seizures with neonatal onset. J Child Neurol 2012; 27 (06) 811-814
• 9 Dong M, Zhang T, Hu R, Li M, Wang G, Liu X. Genotype and phenotype spectrum of 10 children with STXBP1 gene-related encephalopathy and epilepsy. Front Pediatr 2022; 10: 1010886
• 10 Pisano T, Numis AL, Heavin SB. et al. Early and effective treatment of KCNQ2 encephalopathy. Epilepsia 2015; 56 (05) 685-691
• 11 Allen NM, Mannion M, Conroy J. et al. The variable phenotypes of KCNQ-related epilepsy. Epilepsia 2014; 55 (09) e99-e105
• 12 Kato M, Yamagata T, Kubota M. et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia 2013; 54 (07) 1282-1287
• 13 Numis AL, Angriman M, Sullivan JE. et al. KCNQ2 encephalopathy: delineation of the electroclinical phenotype and treatment response. Neurology 2014; 82 (04) 368-370
• 14 McTague A, Nair U, Malhotra S. et al. Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy. Neurology 2018; 90 (01) e55-e66
• 15 El Kosseifi C, Cornet MC, Cilio MR. Neonatal developmental and epileptic encephalopathies. Semin Pediatr Neurol 2019; 32: 100770
• 16 Wolff M, Johannesen KM, Hedrich UBS. et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain 2017; 140 (05) 1316-1336
• 17 Gardella E, Marini C, Trivisano M. et al. The phenotype of SCN8A developmental and epileptic encephalopathy. Neurology 2018; 91 (12) e1112-e1124
• 18 Johannesen KM, Liu Y, Koko M. et al. Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications. Brain 2022; 145 (09) 2991-3009
• 19 Darra F, Monchelato M, Loos M. et al. CDKL5-associated developmental and epileptic encephalopathy: a long-term, longitudinal electroclinical study of 22 cases. Epilepsy Res 2023; 190: 107098
• 20 Bahi-Buisson N, Bienvenu T. CDKL5-related disorders: from clinical description to molecular genetics. Mol Syndromol 2012; 2 (3-5): 137-152
• 21 Beal JC, Cherian K, Moshe SL. Early-onset epileptic encephalopathies: Ohtahara syndrome and early myoclonic encephalopathy. Pediatr Neurol 2012; 47 (05) 317-323
• 22 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
• 23 Biervert C, Steinlein OK. Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions. Hum Genet 1999; 104 (03) 234-240
• 24 Weckhuysen S, Mandelstam S, Suls A. et al. KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 2012; 71 (01) 15-25
• 25 Nguyen HM, Miyazaki H, Hoshi N. et al. Modulation of voltage-gated K+ channels by the sodium channel β1 subunit. Proc Natl Acad Sci U S A 2012; 109 (45) 18577-18582
• 26 Knight D, Mahida S, Kelly M, Poduri A, Olson HE. Ezogabine impacts seizures and development in patients with KCNQ2 developmental and epileptic encephalopathy. Epilepsia 2023; 64 (07) e143-e147
• 27 Millichap JJ, Park KL, Tsuchida T. et al. KCNQ2 encephalopathy: features, mutational hot spots, and ezogabine treatment of 11 patients. Neurol Genet 2016; 2 (05) e96
• 28 Nissenkorn A, Kornilov P, Peretz A. et al. Personalized treatment with retigabine for pharmacoresistant epilepsy arising from a pathogenic variant in the KCNQ2 selectivity filter. Epileptic Disord 2021; 23 (05) 695-705
• 29 Coppola G, Plouin P, Chiron C, Robain O, Dulac O. Migrating partial seizures in infancy: a malignant disorder with developmental arrest. Epilepsia 1995; 36 (10) 1017-1024
• 30 Coppola G. Malignant migrating partial seizures in infancy: an epilepsy syndrome of unknown etiology. Epilepsia 2009; 50 (Suppl. 05) 49-51
• 31 McTague A, Appleton R, Avula S. et al. Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum. Brain 2013; 136 (Pt 5): 1578-1591
• 32 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 (06) 1349-1397
• 33 Caraballo RH, Fontana E, Darra F. et al. Migrating focal seizures in infancy: analysis of the electroclinical patterns in 17 patients. J Child Neurol 2008; 23 (05) 497-506
• 34 Burgess R, Wang S, McTague A. et al; EIMFS Consortium. The genetic landscape of epilepsy of infancy with migrating focal seizures. Ann Neurol 2019; 86 (06) 821-831
• 35 Barba C, Darra F, Cusmai R. et al; CDG Group. Congenital disorders of glycosylation presenting as epileptic encephalopathy with migrating partial seizures in infancy. Dev Med Child Neurol 2016; 58 (10) 1085-1091
• 36 Fitzgerald MP, Fiannacca M, Smith DM. et al. Treatment responsiveness in KCNT1-related epilepsy. Neurotherapeutics 2019; 16 (03) 848-857
• 37 Borlot F, Abushama A, Morrison-Levy N. et al. KCNT1-related epilepsy: an international multicenter cohort of 27 pediatric cases. Epilepsia 2020; 61 (04) 679-692
• 38 Numis AL, Nair U, Datta AN. et al. Lack of response to quinidine in KCNT1-related neonatal epilepsy. Epilepsia 2018; 59 (10) 1889-1898
• 39 Dilena R, DiFrancesco JC, Soldovieri MV. et al. Early treatment with quinidine in 2 patients with epilepsy of infancy with migrating focal seizures (EIMFS) due to gain-of-function KCNT1 mutations: functional studies, clinical responses, and critical issues for personalized therapy. Neurotherapeutics 2018; 15 (04) 1112-1126
• 40 Takase C, Shirai K, Matsumura Y. et al. KCNT1-positive epilepsy of infancy with migrating focal seizures successfully treated with nonnarcotic antitussive drugs after treatment failure with quinidine: a case report. Brain Dev 2020; 42 (08) 607-611
• 41 Bearden D, Strong A, Ehnot J, DiGiovine M, Dlugos D, Goldberg EM. Targeted treatment of migrating partial seizures of infancy with quinidine. Ann Neurol 2014; 76 (03) 457-461
• 42 Merdariu D, Delanoë C, Mahfoufi N, Bellavoine V, Auvin S. Malignant migrating partial seizures of infancy controlled by stiripentol and clonazepam. Brain Dev 2013; 35 (02) 177-180
• 43 Coppola G. Malignant migrating partial seizures in infancy. Handb Clin Neurol 2013; 111: 605-609
• 44 Vendrame M, Poduri A, Loddenkemper T, Kluger G, Coppola G, Kothare SV. Treatment of malignant migrating partial epilepsy of infancy with rufinamide: report of five cases. Epileptic Disord 2011; 13 (01) 18-21
• 45 Poisson K, Wong M, Lee C, Cilio MR. Response to cannabidiol in epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations: an open-label, prospective, interventional study. Eur J Paediatr Neurol 2020; 25: 77-81
• 46 Saade D, Joshi C. Pure cannabidiol in the treatment of malignant migrating partial seizures in infancy: a case report. Pediatr Neurol 2015; 52 (05) 544-547
• 47 Caraballo R, Noli D, Cachia P. Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet. Epileptic Disord 2015; 17 (02) 194-197
• 48 Mori T, Imai K, Oboshi T. et al. Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy. Brain Dev 2016; 38 (06) 601-604
• 49 Glauser TA. Following catastrophic epilepsy patients from childhood to adulthood. Epilepsia 2004; 45 (Suppl. 05) 23-26
• 50 Riikonen R. Infantile spasms: outcome in clinical studies. Pediatr Neurol 2020; 108: 54-64
• 51 Yuskaitis CJ, Ruzhnikov MRZ, Howell KB. et al. Infantile spasms of unknown cause: predictors of outcome and genotype-phenotype correlation. Pediatr Neurol 2018; 87: 48-56
• 52 Goldberg-Stern H, Strawsburg RH, Patterson B. et al. Seizure frequency and characteristics in children with Down syndrome. Brain Dev 2001; 23 (06) 375-378
• 53 Zhongshu Z, Weiming Y, Yukio F, Cheng-LNing Z, Zhixing W. Clinical analysis of West syndrome associated with phenylketonuria. Brain Dev 2001; 23 (07) 552-557
• 54 Michaud JL, Lachance M, Hamdan FF. et al. The genetic landscape of infantile spasms. Hum Mol Genet 2014; 23 (18) 4846-4858
• 55 Strømme P, Mangelsdorf ME, Scheffer IE, Gécz J. Infantile spasms, dystonia, and other X-linked phenotypes caused by mutations in Aristaless related homeobox gene, ARX. Brain Dev 2002; 24 (05) 266-268
• 56 Archer HL, Evans J, Edwards S. et al. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet 2006; 43 (09) 729-734
• 57 Otsuka M, Oguni H, Liang JS. et al. STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome—result of Japanese cohort study. Epilepsia 2010; 51 (12) 2449-2452
• 58 Paciorkowski AR, Thio LL, Dobyns WB. Genetic and biologic classification of infantile spasms. Pediatr Neurol 2011; 45 (06) 355-367
• 59 Blume WT, Lüders HO, Mizrahi E, Tassinari C, van Emde Boas W, Engel Jr J. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia 2001; 42 (09) 1212-1218
• 60 Gibbs EL, Fleming MM, Gibbs FA. Diagnosis and prognosis of hypsarhythmia and infantile spasms. Pediatrics 1954; 13 (01) 66-73
• 61 Gaily E, Liukkonen E, Paetau R, Rekola R, Granström ML. Infantile spasms: diagnosis and assessment of treatment response by video-EEG. Dev Med Child Neurol 2001; 43 (10) 658-667
• 62 Chiron C, Dumas C, Jambaqué I, Mumford J, Dulac O. Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res 1997; 26 (02) 389-395
• 63 Elterman RD, Shields WD, Bittman RM, Torri SA, Sagar SM, Collins SD. Vigabatrin for the treatment of infantile spasms: final report of a randomized trial. J Child Neurol 2010; 25 (11) 1340-1347
• 64 Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics 1996; 97 (03) 375-379
• 65 Hrachovy RA, Frost Jr JD, Kellaway P, Zion TE. Double-blind study of ACTH vs prednisone therapy in infantile spasms. J Pediatr 1983; 103 (04) 641-645
• 66 Lux AL, Edwards SW, Hancock E. et al. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet 2004; 364 (9447) 1773-1778
• 67 Knupp KG, Coryell J, Nickels KC. et al; Pediatric Epilepsy Research Consortium. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol 2016; 79 (03) 475-484
• 68 Wanigasinghe J, Arambepola C, Sri Ranganathan S, Sumanasena S, Attanapola G. Randomized, single-blind, parallel clinical trial on efficacy of oral prednisolone versus intramuscular corticotropin on immediate and continued spasm control in West syndrome. Pediatr Neurol 2015; 53 (03) 193-199
• 69 Chang YH, Chen C, Chen SH, Shen YC, Kuo YT. Effectiveness of corticosteroids versus adrenocorticotropic hormone for infantile spasms: a systematic review and meta-analysis. Ann Clin Transl Neurol 2019; 6 (11) 2270-2281
• 70 Li S, Zhong X, Hong S, Li T, Jiang L. Prednisolone/prednisone as adrenocorticotropic hormone alternative for infantile spasms: a meta-analysis of randomized controlled trials. Dev Med Child Neurol 2020; 62 (05) 575-580
• 71 Brunson KL, Avishai-Eliner S, Baram TZ. ACTH treatment of infantile spasms: mechanisms of its effects in modulation of neuronal excitability. Int Rev Neurobiol 2002; 49: 185-197
• 72 Baram TZ. What are the reasons for the strikingly different approaches to the use of ACTH in infants with West syndrome?. Brain Dev 2001; 23 (07) 647-648
• 73 Hodgeman RM, Kapur K, Paris A. et al. Effectiveness of once-daily high-dose ACTH for infantile spasms. Epilepsy Behav 2016; 59: 4-8
• 74 Hrachovy RA, Frost Jr JD, Glaze DG. High-dose, long-duration versus low-dose, short-duration corticotropin therapy for infantile spasms. J Pediatr 1994; 124 (5 Pt 1): 803-806
• 75 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 (08) 1185-1197
• 76 Sánchez Fernández I, Amengual-Gual M, Gaínza-Lein M. et al. Cost-effectiveness of adrenocorticotropic hormone versus oral steroids for infantile spasms. Epilepsia 2021; 62 (02) 347-357
• 77 French JA. Vigabatrin. Epilepsia 1999; 40 (Suppl. 05) S11-S16
• 78 Vigevano F, Cilio MR. Vigabatrin versus ACTH as first-line treatment for infantile spasms: a randomized, prospective study. Epilepsia 1997; 38 (12) 1270-1274
• 79 Elterman RD, Shields WD, Mansfield KA, Nakagawa J, Group USISVS. US Infantile Spasms Vigabatrin Study Group. Randomized trial of vigabatrin in patients with infantile spasms. Neurology 2001; 57 (08) 1416-1421
• 80 Chiron C, Dulac O, Beaumont D, Palacios L, Pajot N, Mumford J. Therapeutic trial of vigabatrin in refractory infantile spasms. J Child Neurol 1991; (Suppl. 02) S52-S59
• 81 Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev 2008; (04) CD001770
• 82 Curatolo P, Nabbout R, Lagae L. et al. Management of epilepsy associated with tuberous sclerosis complex: updated clinical recommendations. Eur J Paediatr Neurol 2018; 22 (05) 738-748
• 83 Willmore LJ, Abelson MB, Ben-Menachem E, Pellock JM, Shields WD. Vigabatrin: 2008 update. Epilepsia 2009; 50 (02) 163-173
• 84 van der Poest Clement EA, Sahin M, Peters JM. Vigabatrin for epileptic spasms and tonic seizures in tuberous sclerosis complex. J Child Neurol 2018; 33 (08) 519-524
• 85 Mackay MT, Weiss SK, Adams-Webber T. et al; American Academy of Neurology, Child Neurology Society. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology 2004; 62 (10) 1668-1681
• 86 Pesaturo KA, Spooner LM, Belliveau P. Vigabatrin for infantile spasms. Pharmacotherapy 2011; 31 (03) 298-311
• 87 Krueger DA. Management of CNS-related disease manifestations in patients with tuberous sclerosis complex. Curr Treat Options Neurol 2013; 15 (05) 618-633
• 88 Pearl PL, Vezina LG, Saneto RP. et al. Cerebral MRI abnormalities associated with vigabatrin therapy. Epilepsia 2009; 50 (02) 184-194
• 89 Wang CJ, Jonas R, Fu CM, Ng CY, Douglass L. Quality-of-care indicators for infantile spasms. J Child Neurol 2013; 28 (01) 13-20
• 90 Pellock JM, Hrachovy R, Shinnar S. et al. Infantile spasms: a U.S. consensus report. Epilepsia 2010; 51 (10) 2175-2189
• 91 Prezioso G, Carlone G, Zaccara G, Verrotti A. Efficacy of ketogenic diet for infantile spasms: a systematic review. Acta Neurol Scand 2018; 137 (01) 4-11
• 92 Song JM, Hahn J, Kim SH, Chang MJ. Efficacy of treatments for infantile spasms: a systematic review. Clin Neuropharmacol 2017; 40 (02) 63-84
• 93 Chugani HT, Ilyas M, Kumar A. et al. Surgical treatment for refractory epileptic spasms: the Detroit series. Epilepsia 2015; 56 (12) 1941-1949
• 94 Moseley BD, Nickels K, Wirrell EC. Surgical outcomes for intractable epilepsy in children with epileptic spasms. J Child Neurol 2012; 27 (06) 713-720
• 95 Symonds JD, Zuberi SM, Stewart K. et al. Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort. Brain 2019; 142 (08) 2303-2318
• 96 Li W, Schneider AL, Scheffer IE. Defining Dravet syndrome: an essential pre-requisite for precision medicine trials. Epilepsia 2021; 62 (09) 2205-2217
• 97 Dravet C. The core Dravet syndrome phenotype. Epilepsia 2011; 52 (Suppl. 02) 3-9
• 98 Battaglia D, Chieffo D, Lucibello S. et al. Multicenter prospective longitudinal study in 34 patients with Dravet syndrome: neuropsychological development in the first six years of life. Brain Dev 2021; 43 (03) 419-430
• 99 Wyers L, Van de Walle P, Hoornweg A. et al. Gait deviations in patients with Dravet syndrome: a systematic review. Eur J Paediatr Neurol 2019; 23 (03) 357-367
• 100 Skluzacek JV, Watts KP, Parsy O, Wical B, Camfield P. Dravet syndrome and parent associations: the IDEA League experience with comorbid conditions, mortality, management, adaptation, and grief. Epilepsia 2011; 52 (Suppl. 02) 95-101
• 101 Dravet C, Oguni H. Dravet syndrome (severe myoclonic epilepsy in infancy). Handb Clin Neurol 2013; 111: 627-633
• 102 Brunklaus A, Dorris L, Ellis R. et al. The clinical utility of an SCN1A genetic diagnosis in infantile-onset epilepsy. Dev Med Child Neurol 2013; 55 (02) 154-161
• 103 Wu YW, Sullivan J, McDaniel SS. et al. Incidence of Dravet syndrome in a US population. Pediatrics 2015; 136 (05) e1310-e1315
• 104 Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001; 68 (06) 1327-1332
• 105 Marini C, Scheffer IE, Nabbout R. et al. The genetics of Dravet syndrome. Epilepsia 2011; 52 (Suppl. 02) 24-29
• 106 Nabbout R, Kozlovski A, Gennaro E. et al. Absence of mutations in major GEFS+ genes in myoclonic astatic epilepsy. Epilepsy Res 2003; 56 (2-3): 127-133
• 107 Wallace RH, Hodgson BL, Grinton BE. et al. Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms. Neurology 2003; 61 (06) 765-769
• 108 Depienne C, Bouteiller D, Keren B. et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet 2009; 5 (02) e1000381
• 109 Mei D, Cetica V, Marini C, Guerrini R. Dravet syndrome as part of the clinical and genetic spectrum of sodium channel epilepsies and encephalopathies. Epilepsia 2019; 60 (Suppl. 03) S2-S7
• 110 Carvill GL, Weckhuysen S, McMahon JM. et al. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology 2014; 82 (14) 1245-1253
• 111 Wirrell EC, Hood V, Knupp KG. et al. International consensus on diagnosis and management of Dravet syndrome. Epilepsia 2022; 63 (07) 1761-1777
• 112 Martin P, de Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B. Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav 2020; 105: 106989
• 113 Sourbron J, Smolders I, de Witte P, Lagae L. Pharmacological analysis of the anti-epileptic mechanisms of fenfluramine in scn1a mutant zebrafish. Front Pharmacol 2017; 8: 191
• 114 Nabbout R, Mistry A, Zuberi S. et al; FAiRE, DS Study Group. Fenfluramine for treatment-resistant seizures in patients with Dravet syndrome receiving stiripentol-inclusive regimens: a randomized clinical trial. JAMA Neurol 2020; 77 (03) 300-308
• 115 Lagae L, Sullivan J, Knupp K. et al; FAiRE DS Study Group. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet 2019; 394 (10216): 2243-2254
• 116 Sullivan J, Wirrell EC. Dravet syndrome as an example of precision medicine in epilepsy. Epilepsy Curr 2022; 23 (01) 4-7
• 117 Sullivan J, Gunning B, Zafar M. et al. Phase 2, placebo-controlled clinical study of oral ganaxolone in PCDH19-clustering epilepsy. Epilepsy Res 2023; 191: 107112
• 118 Sullivan J, Scheffer IE, Lagae L. et al. Fenfluramine HCl (Fintepla^®) provides long-term clinically meaningful reduction in seizure frequency: analysis of an ongoing open-label extension study. Epilepsia 2020; 61 (11) 2396-2404
• 119 Connolly HM, Crary JL, McGoon MD. et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337 (09) 581-588
• 120 Fisher JL. The anti-convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator. Neuropharmacology 2009; 56 (01) 190-197
• 121 Vasquez A, Wirrell EC, Youssef PE. Stiripentol for the treatment of seizures associated with Dravet syndrome in patients 6 months and older and taking clobazam. Expert Rev Neurother 2023; 23 (04) 297-309
• 122 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
• 123 Chiron C. Stiripentol. Expert Opin Investig Drugs 2005; 14 (07) 905-911
• 124 Guerrini R, Chancharme L, Serraz B, Chiron C. Additional results from two randomized, placebo-controlled trials of stiripentol in Dravet syndrome highlight a rapid antiseizure efficacy with longer seizure-free periods. Neurol Ther 2024; 13 (03) 869-884
• 125 Klein P, Tolbert D, Gidal BE. Drug-drug interactions and pharmacodynamics of concomitant clobazam and cannabidiol or stiripentol in refractory seizures. Epilepsy Behav 2019; 99: 106459
• 126 Devinsky O, Verducci C, Thiele EA. et al. Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Epilepsy Behav 2018; 86: 131-137
• 127 Coppola G, Capovilla G, Montagnini A. et al. Topiramate as add-on drug in severe myoclonic epilepsy in infancy: an Italian multicenter open trial. Epilepsy Res 2002; 49 (01) 45-48
• 128 Nieto-Barrera M, Candau R, Nieto-Jimenez M, Correa A, del Portal LR. Topiramate in the treatment of severe myoclonic epilepsy in infancy. Seizure 2000; 9 (08) 590-594
• 129 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
• 130 Kröll-Seger J, Portilla P, Dulac O, Chiron C. Topiramate in the treatment of highly refractory patients with Dravet syndrome. Neuropediatrics 2006; 37 (06) 325-329
• 131 Wang YQ, Fang ZX, Zhang YW, Xie LL, Jiang L. Efficacy of the ketogenic diet in patients with Dravet syndrome: a meta-analysis. Seizure 2020; 81: 36-42
• 132 Chen S, Li M, Huang M. Vagus nerve stimulation for the therapy of Dravet syndrome: a systematic review and meta-analysis. Front Neurol 2024; 15: 1402989
• 133 Wirrell EC, Laux L, Donner E. et al. Optimizing the diagnosis and management of Dravet syndrome: recommendations from a North American Consensus Panel. Pediatr Neurol 2017; 68: 18-34.e3
• 134 Trivisano M, Specchio N, Cappelletti S. et al. Myoclonic astatic epilepsy: an age-dependent epileptic syndrome with favorable seizure outcome but variable cognitive evolution. Epilepsy Res 2011; 97 (1-2): 133-141
• 135 Kilaru S, Bergqvist AGC. Current treatment of myoclonic astatic epilepsy: clinical experience at the Children's Hospital of Philadelphia. Epilepsia 2007; 48 (09) 1703-1707
• 136 Nickels K, Kossoff EH, Eschbach K, Joshi C. Epilepsy with myoclonic-atonic seizures (Doose syndrome): clarification of diagnosis and treatment options through a large retrospective multicenter cohort. Epilepsia 2021; 62 (01) 120-127
• 137 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 (06) 1398-1442
• 138 Joshi C, Nickels K, Demarest S, Eltze C, Cross JH, Wirrell E. Results of an international Delphi consensus in epilepsy with myoclonic atonic seizures/Doose syndrome. Seizure 2021; 85: 12-18
• 139 Tang S, Pal DK. Dissecting the genetic basis of myoclonic-astatic epilepsy. Epilepsia 2012; 53 (08) 1303-1313
• 140 Caraballo RH, Chamorro N, Darra F, Fortini S, Arroyo H. Epilepsy with myoclonic atonic seizures: an electroclinical study of 69 patients. Pediatr Neurol 2013; 48 (05) 355-362
• 141 Camfield PR. Definition and natural history of Lennox-Gastaut syndrome. Epilepsia 2011; 52 (Suppl. 05) 3-9
• 142 Ferlazzo E, Nikanorova M, Italiano D. et al. Lennox-Gastaut syndrome in adulthood: clinical and EEG features. Epilepsy Res 2010; 89 (2-3): 271-277
• 143 Kerr M, Kluger G, Philip S. Evolution and management of Lennox-Gastaut syndrome through adolescence and into adulthood: are seizures always the primary issue?. Epileptic Disord 2011; 13 (Suppl. 01) S15-S26
• 144 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
• 145 Lee YJ, Kang HC, Lee JS. et al. Resective pediatric epilepsy surgery in Lennox-Gastaut syndrome. Pediatrics 2010; 125 (01) e58-e66
• 146 Conry JA, Ng YT, Paolicchi JM. et al. Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia 2009; 50 (05) 1158-1166
• 147 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
• 148 Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). N Engl J Med 1993; 328 (01) 29-33
• 149 Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology 2008; 70 (21) 1950-1958
• 150 Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G. Topiramate YL Study Group. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Neurology 1999; 52 (09) 1882-1887
• 151 Eriksson AS, Nergårdh A, Hoppu K. The efficacy of lamotrigine in children and adolescents with refractory generalized epilepsy: a randomized, double-blind, crossover study. Epilepsia 1998; 39 (05) 495-501
• 152 Cross JH, Auvin S, Falip M, Striano P, Arzimanoglou A. Expert opinion on the management of Lennox-Gastaut syndrome: treatment algorithms and practical considerations. Front Neurol 2017; 8: 505
• 153 Knupp KG, Scheffer IE, Ceulemans B. et al. Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: interim analysis of an open-label extension study. Epilepsia 2023; 64 (01) 139-151
• 154 Knupp KG, Scheffer IE, Ceulemans B. et al. Efficacy and safety of fenfluramine for the treatment of seizures associated with Lennox-Gastaut syndrome: a randomized clinical trial. JAMA Neurol 2022; 79 (06) 554-564
• 155 Lancman G, Virk M, Shao H. et al. Vagus nerve stimulation vs. corpus callosotomy in the treatment of Lennox-Gastaut syndrome: a meta-analysis. Seizure 2013; 22 (01) 3-8
• 156 Dalic LJ, Warren AEL, Bulluss KJ. et al. DBS of thalamic centromedian nucleus for Lennox-Gastaut syndrome (ESTEL Trial). Ann Neurol 2022; 91 (02) 253-267
• 157 Cross JH, Benítez A, Roth J. et al. A comprehensive systematic literature review of the burden of illness of Lennox-Gastaut syndrome on patients, caregivers, and society. Epilepsia 2024; 65 (05) 1224-1239
• 158 Harden C, Tomson T, Gloss D. et al. Practice guideline summary: sudden unexpected death in epilepsy incidence rates and risk factors: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsy Curr 2017; 17 (03) 180-187
• 159 Ogawa K, Kanemoto K, Ishii Y. et al. Long-term follow-up study of Lennox-Gastaut syndrome in patients with severe motor and intellectual disabilities: with special reference to the problem of dysphagia. Seizure 2001; 10 (03) 197-202
• 160 Nickels K, Wirrell E. Electrical status epilepticus in sleep. Semin Pediatr Neurol 2008; 15 (02) 50-60
• 161 Yan Liu X, Wong V. Spectrum of epileptic syndromes with electrical status epilepticus during sleep in children. Pediatr Neurol 2000; 22 (05) 371-379
• 162 Kramer U, Sagi L, Goldberg-Stern H, Zelnik N, Nissenkorn A, Ben-Zeev B. Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES). Epilepsia 2009; 50 (06) 1517-1524
• 163 Morikawa T, Seino M, Watanabe Y. et al. Clinical relevance of continuous spike-waves during slow wave sleep. In: Manelis S, Bental E, Loeber J, Dreifuss F. eds. Advances in Epileptology. New York, NY: Raven Press; 1989: 359-363
• 164 Sánchez Fernández I, Loddenkemper T, Peters JM, Kothare SV. Electrical status epilepticus in sleep: clinical presentation and pathophysiology. Pediatr Neurol 2012; 47 (06) 390-410
• 165 Tassinari CA, Rubboli G, Volpi L. et al. Encephalopathy with electrical status epilepticus during slow sleep or ESES syndrome including the acquired aphasia. Clin Neurophysiol 2000; 111 (Suppl. 02) S94-S102
• 166 Scheltens-de Boer M. Guidelines for EEG in encephalopathy related to ESES/CSWS in children. Epilepsia 2009; 50 (Suppl. 07) 13-17
• 167 Tassinari CA, Michelucci R, Forti A. et al. The electrical status epilepticus syndrome. Epilepsy Res Suppl 1992; 6: 111-115
• 168 Chan S, Pressler R, Boyd SG, Baldeweg T, Cross JH. Does sleep benefit memory consolidation in children with focal epilepsy?. Epilepsia 2017; 58 (03) 456-466
• 169 Glennon JM, Weiss-Croft L, Harrison S, Cross JH, Boyd SG, Baldeweg T. Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy. Epilepsia 2016; 57 (09) 1436-1442
• 170 Wodeyar A, Chinappen D, Mylonas D. et al. Thalamic epileptic spikes disrupt sleep spindles in patients with epileptic encephalopathy. Brain 2024; 147 (08) 2803-2816
• 171 Sánchez Fernández I, Takeoka M, Tas E. et al. Early thalamic lesions in patients with sleep-potentiated epileptiform activity. Neurology 2012; 78 (22) 1721-1727
• 172 Lemke JR, Lal D, Reinthaler EM. et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet 2013; 45 (09) 1067-1072
• 173 Lesca G, Rudolf G, Bruneau N. et al. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction. Nat Genet 2013; 45 (09) 1061-1066
• 174 Carvill GL, Regan BM, Yendle SC. et al. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nat Genet 2013; 45 (09) 1073-1076
• 175 Kessi M, Xiong J, Wu L. et al. Rare copy number variations and predictors in children with intellectual disability and epilepsy. Front Neurol 2018; 9: 947
• 176 van den Munckhof B, van Dee V, Sagi L. et al. Treatment of electrical status epilepticus in sleep: a pooled analysis of 575 cases. Epilepsia 2015; 56 (11) 1738-1746
• 177 Baumer FM, McNamara NA, Fine AL. et al. Treatment practices and outcomes in continuous spike and wave during slow wave sleep: a multicenter collaboration. J Pediatr 2021; 232: 220-228.e3
• 178 Inutsuka M, Kobayashi K, Oka M, Hattori J, Ohtsuka Y. Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders. Brain Dev 2006; 28 (05) 281-286
• 179 Sánchez Fernández I, Peters JM, An S. et al. Long-term response to high-dose diazepam treatment in continuous spikes and waves during sleep. Pediatr Neurol 2013; 49 (03) 163-170.e4
• 180 Francois D, Roberts J, Hess S, Probst L, Eksioglu Y. Medical management with diazepam for electrical status epilepticus during slow wave sleep in children. Pediatr Neurol 2014; 50 (03) 238-242
• 181 Vega C, Sánchez Fernández I, Peters J. et al. Response to clobazam in continuous spike-wave during sleep. Dev Med Child Neurol 2018; 60 (03) 283-289
• 182 Buzatu M, Bulteau C, Altuzarra C, Dulac O, Van Bogaert P. Corticosteroids as treatment of epileptic syndromes with continuous spike-waves during slow-wave sleep. Epilepsia 2009; 50 (Suppl. 07) 68-72
• 183 Veggiotti P, Pera MC, Teutonico F, Brazzo D, Balottin U, Tassinari CA. Therapy of encephalopathy with status epilepticus during sleep (ESES/CSWS syndrome): an update. Epileptic Disord 2012; 14 (01) 1-11
• 184 Wirrell E, Ho AW, Hamiwka L. Sulthiame therapy for continuous spike and wave in slow-wave sleep. Pediatr Neurol 2006; 35 (03) 204-208
• 185 Fine AL, Wirrell EC, Wong-Kisiel LC, Nickels KC. Acetazolamide for electrical status epilepticus in slow-wave sleep. Epilepsia 2015; 56 (09) e134-e138
• 186 Wilson RB, Eliyan Y, Sankar R, Hussain SA. Amantadine: a new treatment for refractory electrical status epilepticus in sleep. Epilepsy Behav 2018; 84: 74-78
• 187 Arts WF, Aarsen FK, Scheltens-de Boer M, Catsman-Berrevoets CE. Landau-Kleffner syndrome and CSWS syndrome: treatment with intravenous immunoglobulins. Epilepsia 2009; 50 (Suppl. 07) 55-58
• 188 Nikanorova M, Miranda MJ, Atkins M, Sahlholdt L. Ketogenic diet in the treatment of refractory continuous spikes and waves during slow sleep. Epilepsia 2009; 50 (05) 1127-1131
• 189 Van Lierde A. Therapeutic data. In: Beaumanoir A, Bureau M, Deonna T, Mira L, Tassinari CA. eds. Continuous Spikes and Waves during Slow Sleep. London: John Libbey; 1995: 225-227
• 190 Snead III OC, Hosey LC. Exacerbation of seizures in children by carbamazepine. N Engl J Med 1985; 313 (15) 916-921
• 191 Fejerman N, Caraballo R, Tenembaum SN. Atypical evolutions of benign localization-related epilepsies in children: are they predictable?. Epilepsia 2000; 41 (04) 380-390
• 192 Callenbach PM, Bouma PA, Geerts AT. et al. Long term outcome of benign childhood epilepsy with centrotemporal spikes: Dutch Study of Epilepsy in Childhood. Seizure 2010; 19 (08) 501-506
• 193 Downes M, Greenaway R, Clark M. et al. Outcome following multiple subpial transection in Landau-Kleffner syndrome and related regression. Epilepsia 2015; 56 (11) 1760-1766
• 194 Guerrini R, Genton P, Bureau M. et al. Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus. Neurology 1998; 51 (02) 504-512
• 195 Praline J, Hommet C, Barthez MA. et al. Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes. Epilepsia 2003; 44 (11) 1434-1440
• 196 Rossi PG, Parmeggiani A, Posar A, Scaduto MC, Chiodo S, Vatti G. Landau-Kleffner syndrome (LKS): long-term follow-up and links with electrical status epilepticus during sleep (ESES). Brain Dev 1999; 21 (02) 90-98
• 197 Brunklaus A, Dorris L, Zuberi SM. Comorbidities and predictors of health-related quality of life in Dravet syndrome. Epilepsia 2011; 52 (08) 1476-1482
• 198 Berg AT, Kaat AJ, Zelko F, Wilkening G. Rare diseases–rare outcomes: assessing communication abilities for the developmental and epileptic encephalopathies. Epilepsy Behav 2022; 128: 108586
• 199 van der Veen S, Tse GTW, Ferretti A. et al. Movement disorders in patients with genetic developmental and epileptic encephalopathies. Neurology 2023; 101 (19) e1884-e1892
• 200 Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA. The expanding spectrum of movement disorders in genetic epilepsies. Dev Med Child Neurol 2020; 62 (02) 178-191
• 201 Turner SJ, Brown A, Arpone M, Anderson V, Morgan AT, Scheffer IE. Dysarthria and broader motor speech deficits in Dravet syndrome. Neurology 2017; 88 (08) 743-749
• 202 Chieffo D, Ricci D, Baranello G. et al. Early development in Dravet syndrome; visual function impairment precedes cognitive decline. Epilepsy Res 2011; 93 (01) 73-79
• 203 Licheni SH, Mcmahon JM, Schneider AL, Davey MJ, Scheffer IE. Sleep problems in Dravet syndrome: a modifiable comorbidity. Dev Med Child Neurol 2018; 60 (02) 192-198
• 204 Hagebeuk EE, van den Bossche RA, de Weerd AW. Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene. Dev Med Child Neurol 2013; 55 (05) 480-484
• 205 Minderhoud CA, Postma A, Jansen FE. et al. Gastrointestinal and eating problems in SCN1A-related seizure disorders. Epilepsy Behav 2023; 146: 109361
• 206 Clayton LM, Azadi B, Eldred C, Wilson G, Robinson R, Sisodiya SM. Feeding difficulties and gastrostomy in Dravet syndrome: a UK-wide survey and 2-center experience. Neurol Clin Pract 2024; 14 (03) e200288
• 207 Reynolds C, King MD, Gorman KM. The phenotypic spectrum of SCN2A-related epilepsy. Eur J Paediatr Neurol 2020; 24: 117-122
• 208 Schreiber JM, Tochen L, Brown M. et al. A multi-disciplinary clinic for SCN8A-related epilepsy. Epilepsy Res 2020; 159: 106261
• 209 Weckhuysen S, Ivanovic V, Hendrickx R. et al; KCNQ2 Study Group. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology 2013; 81 (19) 1697-1703
• 210 Blumkin L, Suls A, Deconinck T. et al. Neonatal seizures associated with a severe neonatal myoclonus like dyskinesia due to a familial KCNQ2 gene mutation. Eur J Paediatr Neurol 2012; 16 (04) 356-360
• 211 Soldovieri MV, Freri E, Ambrosino P. et al. Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy. Pharmacol Res 2020; 160: 105200
• 212 Bonardi CM, Heyne HO, Fiannacca M. et al. KCNT1-related epilepsies and epileptic encephalopathies: phenotypic and mutational spectrum. Brain 2021; 144 (12) 3635-3650
• 213 Olson HE, Demarest ST, Pestana-Knight EM. et al. Cyclin-dependent kinase-like 5 deficiency disorder: clinical review. Pediatr Neurol 2019; 97: 18-25
• 214 Klein KM, Yendle SC, Harvey AS. et al. A distinctive seizure type in patients with CDKL5 mutations: hypermotor-tonic-spasms sequence. Neurology 2011; 76 (16) 1436-1438
• 215 Knight EMP, Amin S, Bahi-Buisson N. et al; Marigold Trial Group. Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial. Lancet Neurol 2022; 21 (05) 417-427
• 216 Devinsky O, King L, Schwartz D, Conway E, Price D. Effect of fenfluramine on convulsive seizures in CDKL5 deficiency disorder. Epilepsia 2021; 62 (07) e98-e102
• 217 Samanta D. PCDH19-related epilepsy syndrome: a comprehensive clinical review. Pediatr Neurol 2020; 105: 3-9
• 218 Coughlin II CR, Gospe Jr SM. Pyridoxine-dependent epilepsy: current perspectives and questions for future research. Ann Child Neurol Soc 2023; 1 (01) 24-37
• 219 van Karnebeek CD, Tiebout SA, Niermeijer J. et al. Pyridoxine-dependent epilepsy: an expanding clinical spectrum. Pediatr Neurol 2016; 59: 6-12
• 220 Alghamdi M, Bashiri FA, Abdelhakim M. et al. Phenotypic and molecular spectrum of pyridoxamine-5′-phosphate oxidase deficiency: a scoping review of 87 cases of pyridoxamine-5′-phosphate oxidase deficiency. Clin Genet 2021; 99 (01) 99-110
• 221 Olson HE, Kelly M, LaCoursiere CM. et al. Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression. Ann Neurol 2017; 81 (03) 419-429
• 222 Wolf B. Biotinidase deficiency: “if you have to have an inherited metabolic disease, this is the one to have”. Genet Med 2012; 14 (06) 565-575
• 223 Van Hove JL, Vande Kerckhove K, Hennermann JB. et al. Benzoate treatment and the glycine index in nonketotic hyperglycinaemia. J Inherit Metab Dis 2005; 28 (05) 651-663
• 224 Alemzadeh R, Gammeltoft K, Matteson K. Efficacy of low-dose dextromethorphan in the treatment of nonketotic hyperglycinemia. Pediatrics 1996; 97 (6 Pt 1): 924-926
• 225 Coughlin II CR, Swanson MA, Kronquist K. et al. The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT. Genet Med 2017; 19 (01) 104-111
• 226 Leary LD, Wang D, Nordli Jr DR, Engelstad K, De Vivo DC. Seizure characterization and electroencephalographic features in Glut-1 deficiency syndrome. Epilepsia 2003; 44 (05) 701-707
• 227 Pons R, Collins A, Rotstein M, Engelstad K, De Vivo DC. The spectrum of movement disorders in Glut-1 deficiency. Mov Disord 2010; 25 (03) 275-281
• 228 Pong AW, Geary BR, Engelstad KM, Natarajan A, Yang H, De Vivo DC. Glucose transporter type I deficiency syndrome: epilepsy phenotypes and outcomes. Epilepsia 2012; 53 (09) 1503-1510