OBJECTIVES: Timely referral and efficient presurgical evaluation are important to optimize postoperative seizure and developmental outcomes in epilepsy surgery patients. We aimed to identify determinants of time intervals from epilepsy diagnosis to referral to specialized centers and epilepsy surgery in children with malformations of cortical development (MCDs) and low-grade epilepsy-associated tumors (LEATs). METHODS: We performed a retrospective cohort study in 3 European centers, including children with MCD or LEAT who underwent epilepsy surgery between 2010 and 2020. Primary endpoints were (1) time interval between epilepsy diagnosis and referral for presurgical evaluation, (2) duration of presurgical evaluation trajectory, and (3) time from diagnosis to surgery. The secondary endpoint was postoperative seizure outcome. In our primary analysis, we performed a multivariable Cox proportional hazards analysis and used histopathological diagnosis, age at first seizure, presence of developmental delay, 1st seizure classification, initial EEG and MRI findings, duration until drug resistance, and family history as covariates. RESULTS: Of the 507 children included, 259 (51%) had an MCD and 248 (49%) had a LEAT. Earlier drug resistance and the presence of an MR-visible epileptogenic lesion were associated with shorter times from diagnosis to referral and surgery, and later onset of seizures was associated with a shorter time to surgery. LEAT was associated with a shorter presurgical evaluation and shorter time to surgery. An older age at surgery, shorter time from diagnosis to surgery, and a histopathological diagnosis of FCDII and LEAT were all independently associated with better postoperative seizure outcome. SIGNIFICANCE: Epilepsy surgery was performed earlier in children with MR-visible lesions and early drug resistance, particularly those with LEAT, and a shorter duration to epilepsy surgery was associated with better seizure outcomes. Many patients were initially considered MRI-negative in the referring center, highlighting the importance of early referral, epilepsy-dedicated MRI protocols, and experienced neuroradiologists. Increasing awareness of timely referral and surgery benefits is crucial for improving outcomes. PLAIN LANGUAGE SUMMARY: Children with severe focal structural epilepsy who have not responded to medication often benefit from surgery, especially when they are referred early. This study of 507 children found that certain factors-such as visible brain abnormalities on the first MRI, especially a specific type of brain tumor (LEAT), early signs of drug resistance, and seizures starting later in childhood-were linked to shorter times from diagnosis to surgery and that shorter time to surgery was linked to better seizure outcomes. Many children whose initial MRIs appeared to be normal were later found to have an epileptogenic brain lesion when examined at specialized centers. Early referral, advanced imaging, and expert evaluation are key to improving postsurgical outcomes.

Department of Child Neurology Brain Center University Medical Center Utrecht The Netherlands

Department of Paediatric Neurology Motol Epilepsy Center 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

UCL NIHR BRC Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children London UK

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;377:1648–1656. PubMed

Cross JH, Jayakar P, Nordli D, Delalande O, Duchowny M, Wieser HG, et al. Proposed criteria for referral and evaluation of children for epilepsy surgery: recommendations of the subcommission for pediatric epilepsy surgery. Epilepsia. 2006;47:952–959. PubMed

Lamberink HJ, Otte WM, Blümcke I, Braun KPJ, Aichholzer M, Amorim I, et al. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study. Lancet Neurol. 2020;19:748–757. PubMed

Casadei CH, Carson KW, Mendiratta A, Bazil CW, Pack AM, Choi H, et al. All‐cause mortality and SUDEP in a surgical epilepsy population. Epilepsy Behav. 2020;108:107093. PubMed PMC

Téllez‐Zenteno JF, Dhar R, Hernandez‐Ronquillo L, Wiebe S. Long‐term outcomes in epilepsy surgery: antiepileptic drugs, mortality, cognitive and psychosocial aspects. Brain. 2007;130:334–345. PubMed

Braun KPJ, Cross JH. Pediatric epilepsy surgery: the earlier the better. Expert Rev Neurother. 2018;18(4):261–263. PubMed

Chen J, Chen X, Huang C, Zhu H, Hou Z, An N, et al. Predictors of seizure recurrence in patients with surgery for focal cortical dysplasia: pairwise and network meta‐analysis and trial sequential analysis. Childs Nerv Syst. 2019;26:753–767. PubMed

Ko A, Kim SH, Kim SH, Park EK, Shim KW, Kang HC, et al. Epilepsy surgery for children with low‐grade epilepsy‐associated tumors: factors associated with seizure recurrence and cognitive function. Pediatr Neurol. 2019;91:50–56. PubMed

Jehi L, Yardi R, Chagin K, Tassi L, Russo GL, Worrell G, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283–290. PubMed

Sanders MW, Van der Wolf I, Jansen FE, Aronica E, Helmstaedter C, Racz A, et al. Outcome of epilepsy surgery in MRI‐negative patients without histopathologic abnormalities in the resected tissue. Neurology. 2024;102(4):e208007. PubMed PMC

Bjellvi J, Olsson I, Malmgren K, Wilbe Ramsay K. Epilepsy duration and seizure outcome in epilepsy surgery: a systematic review and meta‐analysis. Neurology. 2019;93(2):e159–e166. PubMed PMC

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

Engel J, van Ness PC, Rasmussen TB, Ojemann LM. Outcome with respect to epileptic seizures. In: Engel J, editor. Surgical treatment of the epilepsies. New York, NY: Raven Press; 1993. p. 609–621.

Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, 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;51:1069–1077. PubMed

Wiebe S. Definition of drug‐resistant epilepsy: is it evidence based? Epilepsia. 2013;54(Suppl 2):9–12. PubMed

Jetté N, Sander JW, Keezer MR. Surgical treatment for epilepsy: the potential gap between evidence and practice. Lancet Neurol. 2016;15(9):982–994. PubMed

Jehi L, Jette N, Kwon CS, Josephson CB, Burneo JG, Cendes F, 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. PubMed PMC

Gupta A, Chirla A, Wyllie E, Lachhwani DK, Kotagal P, Bingaman WE. Pediatric epilepsy surgery in focal lesions and generalized electroencephalogram abnormalities. Pediatr Neurol. 2007;37(1):8–15. PubMed

Ka A, Taher A, D'Souza S, Barnes EH, Gupta S, Troedson C, et al. Predictors of longitudinal seizure outcomes after epilepsy surgery in childhood. Epilepsy Behav Rep. 2022;19:100561. PubMed PMC

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

Freitag H, Tuxhorn I. Cognitive function in preschool children after epilepsy surgery: rationale for early intervention. Epilepsia. 2005;46(4):561–567. PubMed