OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.

Department of Circuit Theory Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

Department of Clinical Psychology 2nd Faculty of Medicine Charles University and Motol University Hospital full member of the European Reference Network EpiCARE Prague Czech Republic

Department of Neurosurgery 2nd Faculty of Medicine Charles University and Motol University Hospital full member of the European Reference Network EpiCARE Prague Czech Republic

Department of Pathology and Molecular Medicine 2nd Faculty of Medicine Charles University and Motol University Hospital full member of the European Reference Network EpiCARE Prague Czech Republic

Department of Pediatric Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital full member of the European Reference Network EpiCARE Prague Czech Republic

Department of Pediatrics Martin University Hospital Jessenius Faculty of Medicine in Martin Martin Slovak Republic

Department of Radiology 2nd Faculty of Medicine Charles University and Motol University Hospital full member of the European Reference Network EpiCARE Prague Czech Republic

Department of Water Resources and Environmental Modeling Faculty of Environmental Sciences Czech University of Life Sciences Prague Prague Czech Republic

Zobrazit více v PubMed

Blumcke I, Spreafico R, Haaker G, Coras R, Kobow K, Bien CG, et al. Histopathological findings in brain tissue obtained during epilepsy surgery. N Engl J Med. 2017;377(17):1648–1656. PubMed

Garner GL, Streetman DR, Fricker JG, Bui NE, Yang C, Patel NA, et al. Focal cortical dysplasia as a cause of epilepsy: the current evidence of associated genes and future therapeutic treatments. Interdisciplinary Neurosurg. 2022;30:101635.

Hong S‐J, Bernhardt BC, Caldairou B, Hall JA, Guiot MC, Schrader D, et al. Multimodal MRI profiling of focal cortical dysplasia type II. Neurology. 2017;88(8):734–742. PubMed PMC

Kuruvilla A, Flink R. Focal fast rhythmic epileptiform discharges on scalp EEG in a patient with cortical dysplasia. Seizure. 2002;11(5):330–334. PubMed

Noachtar S, Bilgin Ö, Rémi J, Chang N, Midi I, Vollmar C, et al. Interictal regional polyspikes in noninvasive EEG suggest cortical dysplasia as etiology of focal epilepsies. Epilepsia. 2008;49(6):1011–1017. PubMed

Guerrini R, Duchowny M, Jayakar P, Krsek P, Kahane P, Tassi L, et al. Diagnostic methods and treatment options for focal cortical dysplasia. Epilepsia. 2015;56(11):1669–1686. PubMed

Lim JS, Kim W, Kang H‐C, Kim SH, Park AH, Park EK, et al. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy. Nat Med. 2015;21(4):395–400. PubMed

Baldassari S, Ribierre T, Marsan E, Adle‐Biassette H, Ferrand‐Sorbets S, Bulteau C, et al. Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta Neuropathol. 2019;138(6):885–900. PubMed PMC

Straka B, Hermanovska B, Krskova L, Zamecnik J, Vlckova M, Balascakova M, et al. Genetic testing for malformations of cortical development. Neurology Genetics. 2022;8(5):e200032. PubMed PMC

Widdess‐Walsh P, Diehl B, Najm I. Neuroimaging of focal cortical dysplasia. J Neuroimaging. 2006;16(3):185–196. PubMed

Hauptman JS, Mathern GW. Surgical treatment of epilepsy associated with cortical dysplasia: 2012 update. Epilepsia. 2012;53(s4):98–104. PubMed

Wang ZI, Alexopoulos AV, Jones SE, Jaisani Z, Najm IM, Prayson RA. The pathology of magnetic‐resonance‐imaging‐negative epilepsy. Mod Pathol. 2013;26(8):1051–1058. PubMed

Coras R, Holthausen H, Sarnat HB. Focal cortical dysplasia type 1. Brain Pathol. 2021;31(4):e12964. PubMed PMC

Janca R, Jezdik P, Ebel M, Kalina A, Kudr M, Jahodova A, et al. Distinct patterns of interictal intracranial EEG in focal cortical dysplasia type I and II. Clin Neurophysiol. 2023;151:10–17. PubMed

Kimura N, Takahashi Y, Shigematsu H, Imai K, Ikeda H, Ootani H, et al. Risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia. Brain Dev. 2019;41(1):77–84. PubMed

Kwon HE, Eom S, Kang H‐C, Lee JS, Kim SH, Kim DS, et al. Surgical treatment of pediatric focal cortical dysplasia. Neurology. 2016;87(9):945–951. PubMed

Veersema TJ, van Schooneveld MMJ, Ferrier CH, van Eijsden P, Gosselaar PH, van Rijen PC, et al. Cognitive functioning after epilepsy surgery in children with mild malformation of cortical development and focal cortical dysplasia. Epilepsy Behav. 2019;94:209–215. PubMed

Fujimoto A, Enoki H, Niimi K, Nozaki T, Baba S, Shibamoto I, et al. Epilepsy in patients with focal cortical dysplasia may be associated with autism spectrum disorder. Epilepsy Behav. 2021;120:107990. PubMed

Tahta A, Turgut M. Focal cortical dysplasia: etiology, epileptogenesis, classification, clinical presentation, imaging, and management. Childs Nerv Syst. 2020;36(12):2939–2947. PubMed

Bell GS, Sander JW. CPD—education and self‐assessment the epidemiology of epilepsy: the size of the problem. Seizure: European Journal of Epilepsy. Elsevier BV; 2001. p. 306–316. PubMed

Mühlebner A, Gröppel G, Dressler A, Reiter‐Fink E, Kasprian G, Prayer D, et al. Epilepsy surgery in children and adolescents with malformations of cortical development—outcome and impact of the new ILAE classification on focal cortical dysplasia. Epilepsy Res. 2014;108(9):1652–1661. PubMed

Choi SA, Kim SY, Kim H, Kim WJ, Kim H, Hwang H, et al. Surgical outcome and predictive factors of epilepsy surgery in pediatric isolated focal cortical dysplasia. Epilepsy Res. 2018;139:54–59. PubMed

Cossu M, Fuschillo D, Bramerio M, Galli C, Gozzo F, Pelliccia V, et al. Epilepsy surgery of focal cortical dysplasia–associated tumors. Epilepsia. 2013;54(s9):115–122. PubMed

Krsek P, Pieper T, Karlmeier A, Hildebrandt M, Kolodziejczyk D, Winkler P, et al. Different presurgical characteristics and seizure outcomes in children with focal cortical dysplasia type I or II. Epilepsia. 2009;50(1):125–137. PubMed

Holthausen H, Coras R, Tang Y, Bai L, Wang I, Pieper T, et al. Multilobar unilateral hypoplasia with emphasis on the posterior quadrant and severe epilepsy in children with FCD ILAE type 1A. Epilepsia. 2021;63(1):42–60. PubMed

Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, 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. PubMed

Najm I, Lal D, Alonso Vanegas M, Cendes F, Lopes‐Cendes I, Palmini A, et al. The ILAE consensus classification of focal cortical dysplasia: an update proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia. 2022;63(8):1899–1919. PubMed PMC

Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–521. PubMed PMC

Bayley N. Bayley scales of infant and toddler development. Third ed. San Antonio: Pearson; 2005.

Wechsler D. Wechsler preschool and primary scale of intelligence. 4th ed. San Antonio: Pearson; 2013.

Wechsler D. Wechslerova inteligenční škála pro děti. Hogrefe Testcentrum, Praha: WISC‐III; 2002.

Wechsler D. Wechslerova inteligenční škála pro dospelé. Hogrefe Testcentrum, Praha: WAIS‐III; 2010.

Torres F. Atlas and classification of electroencephalography. Pediatr Neurol. 2000;22(4):332.

Bernasconi A, Cendes F, Theodore WH, Gill RS, Koepp MJ, Hogan RE, et al. Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: a consensus report from the international league against epilepsy neuroimaging task force. Epilepsia. 2019;60(6):1054–1068. PubMed

Colliot O, Antel SB, Naessens VB, Bernasconi N, Bernasconi A. In vivo profiling of focal cortical dysplasia on high‐resolution MRI with computational models. Epilepsia. 2006;47(1):134–142. PubMed

Krsek P, Maton B, Korman B, Pacheco‐Jacome E, Jayakar P, Dunoyer C, et al. Different features of histopathological subtypes of pediatric focal cortical dysplasia. Ann Neurol. 2008;63(6):758–769. PubMed

Schuch F, Walger L, Schmitz M, David B, Bauer T, Harms A, et al. An open presurgery MRI dataset of people with epilepsy and focal cortical dysplasia type II. Scientific Data. 2023;10(1):475. PubMed PMC

Thomas BA, Cuplov V, Bousse A, Mendes A, Thielemans K, Hutton BF, et al. PETPVC: a toolbox for performing partial volume correction techniques in positron emission tomography. Phys Med Biol. 2016;61(22):7975–7993. PubMed

Janca R, Tomasek M, Kalina A, Marusic P, Krsek P, Lesko R. Automated identification of Stereoelectroencephalography contacts and measurement of factors influencing accuracy of frame Stereotaxy. IEEE J Biomed Health Inform. 2023;27(7):3326–3336. PubMed

Wieser HG, Blume WT, Fish D, Goldensohn E, Hufnagel A, King D, et al. Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia. 2001;42(2):282–286. PubMed

Janca R, Jahodova A, Hlinka J, Jezdik P, Svobodova L, Kudr M, et al. Ictal gamma‐band interactions localize ictogenic nodes of the epileptic network in focal cortical dysplasia. Clin Neurophysiol. 2021;132(8):1927–1936. PubMed

Janca R, Krsek P, Jezdik P, Cmejla R, Tomasek M, Komarek V, et al. The sub‐regional functional organization of neocortical irritative epileptic networks in pediatric epilepsy. Front Neurol. 2018;9:184. PubMed PMC

Yao K, Duan Z, Zhou J, Li L, Zhai F, Dong Y, et al. Clinical and immunohistochemical characteristics of type II and type I focal cortical dysplasia. Oncotarget. 2016;7(47):76415–76422. PubMed PMC

Guerrini R, Barba C. Focal cortical dysplasia: an update on diagnosis and treatment. Expert Rev Neurother. 2021;21(11):1213–1224. PubMed

Baud MO, Perneger T, Rácz A, Pensel MC, Elger C, Rydenhag B, et al. European trends in epilepsy surgery. Neurology. 2018;91:2. PubMed

Novak V, Maulisova A, Jezdik P, Benova B, Belohlavkova A, Liby P, et al. Generalized quasiperiodic epileptiform activity in sleep is associated with cognitive impairment in children with drug‐resistant focal lesional epilepsy. Epilepsia. 2019;60(11):2263–2276. PubMed

Beattie JF, Koch SA, Bolden LB, Thompson MD. Neuropsychological consequences of sleep disturbance in children with epilepsy. Epilepsy Behav. 2016;57:118–123. PubMed

Choi SA, Kim KJ. Focal cortical dysplasia in pediatric epilepsy. Annals Child Neurol. 2019;27(4):93–104.

Tassi L, Garbelli R, Colombo N, Bramerio M, Russo GL, Deleo F, et al. Type I focal cortical dysplasia: surgical outcome is related to histopathology. Epileptic Disord. 2010;12(3):181–191. PubMed

Blümcke I, Coras R, Busch RM, Morita‐Sherman M, Lal D, Prayson R, et al. Toward a better definition of focal cortical dysplasia: an iterative histopathological and genetic agreement trial. Epilepsia. 2021;62(6):1416–1428. PubMed

Jesus‐Ribeiro J, Pires LM, Melo JD, Ribeiro IP, Rebelo O, Sales F, et al. Genomic and epigenetic advances in focal cortical dysplasia types I and II: a scoping review. Front Neurosci. 2021;14:580357. PubMed PMC