{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:14:34Z","timestamp":1793661274646,"version":"4.5.1"},"reference-count":110,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["602391"],"award-info":[{"award-number":["602391"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["952455"],"award-info":[{"award-number":["952455"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.ebiom.2025.105740","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T06:33:10Z","timestamp":1747117990000},"page":"105740","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex"],"prefix":"10.1016","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8120-0287","authenticated-orcid":false,"given":"Nicola","family":"Specchio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Di Micco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0676-4701","authenticated-orcid":false,"given":"Mirte","family":"Scheper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Curatolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/epi.13709","article-title":"ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology","volume":"58","author":"Scheffer","year":"2017","journal-title":"Epilepsia"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/brain\/awaa371","article-title":"Developmental and epileptic encephalopathies: what we do and do not know","volume":"144","author":"Specchio","year":"2021","journal-title":"Brain"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib3","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1152\/physrev.00063.2021","article-title":"Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum","volume":"103","author":"Guerrini","year":"2023","journal-title":"Physiol Rev"},{"key":"10.1016\/j.ebiom.2025.105740_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116476","article-title":"Twenty-first century antiepileptic drugs. An overview of their targets and synthetic approaches","volume":"272","author":"S\u00e1nchez","year":"2024","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.ebiom.2025.105740_bib5","doi-asserted-by":"crossref","DOI":"10.1177\/17562864231191000","article-title":"Pharmacological diversity amongst approved and emerging antiseizure medications for the treatment of developmental and epileptic encephalopathies","volume":"16","author":"Sills","year":"2023","journal-title":"Ther Adv Neurol Disord"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib6","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1001\/jamaneurol.2017.3949","article-title":"Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs","volume":"75","author":"Chen","year":"2018","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2025.105740_bib7","article-title":"Epilepsy","volume":"4","author":"Devinsky","year":"2018","journal-title":"Nat Rev Dis Prim"},{"issue":"9","key":"10.1016\/j.ebiom.2025.105740_bib8","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S1474-4422(22)00213-7","article-title":"Advances in the genetics and neuropathology of tuberous sclerosis complex: edging closer to targeted therapy","volume":"21","author":"Curatolo","year":"2022","journal-title":"Lancet Neurol"},{"issue":"11","key":"10.1016\/j.ebiom.2025.105740_bib9","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S2352-4642(24)00196-2","article-title":"The expanding field of genetic developmental and epileptic encephalopathies: current understanding and future perspectives","volume":"8","author":"Specchio","year":"2024","journal-title":"Lancet Child Adolesc Heal"},{"issue":"12","key":"10.1016\/j.ebiom.2025.105740_bib10","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/s41582-020-0409-4","article-title":"Impact of predictive, preventive and precision medicine strategies in epilepsy","volume":"16","author":"Nabbout","year":"2020","journal-title":"Nat Rev Neurol"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib11","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1007\/s13311-021-01122-6","article-title":"Precision therapy for epilepsy related to brain malformations","volume":"18","author":"D\u2019Gama","year":"2021","journal-title":"Neurotherapeutics"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib12","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13023-014-0182-9","article-title":"TOSCA \u2013 first international registry to address knowledge gaps in the natural history and management of tuberous sclerosis complex","volume":"9","author":"Kingswood","year":"2014","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13023-018-0870-y","article-title":"Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study","volume":"13","author":"Ebrahimi-Fakhari","year":"2018","journal-title":"Orphanet J Rare Dis"},{"issue":"9639","key":"10.1016\/j.ebiom.2025.105740_bib14","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0140-6736(08)61279-9","article-title":"Tuberous sclerosis","volume":"372","author":"Curatolo","year":"2008","journal-title":"Lancet"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.spen.2015.10.002","article-title":"Genotype\/phenotype correlations in tuberous sclerosis complex","volume":"22","author":"Curatolo","year":"2015","journal-title":"Semin Pediatr Neurol"},{"key":"10.1016\/j.ebiom.2025.105740_bib16","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","article-title":"Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations","volume":"123","author":"Northrup","year":"2021","journal-title":"Pediatr Neurol"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/ajmg.c.31651","article-title":"Genetics, genomics, and genotype-phenotype correlations of TSC: insights for clinical practice","volume":"178","author":"Peron","year":"2018","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"10.1016\/j.ebiom.2025.105740_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.spen.2023.101086","article-title":"Updated genotype-phenotype correlations in TSC","volume":"47","author":"Curatolo","year":"2023","journal-title":"Semin Pediatr Neurol"},{"issue":"11","key":"10.1016\/j.ebiom.2025.105740_bib19","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1038\/s41436-019-0562-6","article-title":"Low-level mosaicism in tuberous sclerosis complex: prevalence, clinical features, and risk of disease transmission","volume":"21","author":"Giannikou","year":"2019","journal-title":"Genet Med"},{"key":"10.1016\/j.ebiom.2025.105740_bib20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2023\/4899372","article-title":"Targeted genomic sequencing of TSC1 and TSC2 reveals causal variants in individuals for whom previous genetic testing for tuberous sclerosis complex was normal","volume":"2023","author":"West","year":"2023","journal-title":"Hum Mutat"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/epi4.12286","article-title":"Epilepsy in tuberous sclerosis complex: findings from the TOSCA Study","volume":"4","author":"Nabbout","year":"2019","journal-title":"Epilepsia Open"},{"key":"10.1016\/j.ebiom.2025.105740_bib22","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yebeh.2017.02.007","article-title":"Influence of seizures on early development in tuberous sclerosis complex","volume":"70","author":"Capal","year":"2017","journal-title":"Epilepsy Behav"},{"key":"10.1016\/j.ebiom.2025.105740_bib23","doi-asserted-by":"crossref","first-page":"639","DOI":"10.3389\/fneur.2020.00639","article-title":"Autism and epilepsy in patients with tuberous sclerosis complex","volume":"11","author":"Specchio","year":"2020","journal-title":"Front Neurol"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib24","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/dmcn.14356","article-title":"Long-term cognitive outcomes in tuberous sclerosis complex","volume":"62","author":"Tye","year":"2020","journal-title":"Dev Med Child Neurol"},{"issue":"9","key":"10.1016\/j.ebiom.2025.105740_bib25","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1111\/epi.18069","article-title":"Have epilepsy outcomes changed for children with tuberous sclerosis complex in Queensland, Australia?","volume":"65","author":"Braun","year":"2024","journal-title":"Epilepsia"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib26","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/ana.26551","article-title":"Tubers affecting the fusiform face area are associated with autism diagnosis","volume":"93","author":"Cohen","year":"2023","journal-title":"Ann Neurol"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/ana.26778","article-title":"Early treatment with vigabatrin does not decrease focal seizures or improve cognition in tuberous sclerosis complex: the PREVeNT trial","volume":"95","author":"Bebin","year":"2024","journal-title":"Ann Neurol"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/14737175.2018.1428562","article-title":"mTOR dysregulation and tuberous sclerosis-related epilepsy","volume":"18","author":"Curatolo","year":"2018","journal-title":"Expert Rev Neurother"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib29","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/joa.12956","article-title":"New insights into a spectrum of developmental malformations related to mTOR dysregulations: challenges and perspectives","volume":"235","author":"M\u00fchlebner","year":"2019","journal-title":"J Anat"},{"issue":"Pt B","key":"10.1016\/j.ebiom.2025.105740_bib30","article-title":"Genetic pathogenesis of the epileptogenic lesions in Tuberous Sclerosis Complex: therapeutic targeting of the mTOR pathway","volume":"131","author":"Moavero","year":"2022","journal-title":"Epilepsy Behav"},{"key":"10.1016\/j.ebiom.2025.105740_bib31","doi-asserted-by":"crossref","DOI":"10.1093\/brain\/awad048","article-title":"Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy","author":"Aronica","year":"2023","journal-title":"Brain"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib32","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1038\/s41380-023-02402-7","article-title":"The role of TSC1 and TSC2 proteins in neuronal axons","volume":"29","author":"Karalis","year":"2024","journal-title":"Mol Psychiatry"},{"key":"10.1016\/j.ebiom.2025.105740_bib33","doi-asserted-by":"crossref","DOI":"10.1038\/s41583-024-00805-1","article-title":"mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment","author":"Ravizza","year":"2024","journal-title":"Nat Rev Neurosci"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1093\/cercor\/bhs310","article-title":"Fetal brain mTOR signaling activation in tuberous sclerosis complex","volume":"24","author":"Tsai","year":"2014","journal-title":"Cereb Cortex"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1750-3639.2012.00616.x","article-title":"Fetal brain lesions in tuberous sclerosis complex: TORC1 activation and inflammation","volume":"23","author":"Prabowo","year":"2013","journal-title":"Brain Pathol"},{"key":"10.1016\/j.ebiom.2025.105740_bib36","doi-asserted-by":"crossref","first-page":"899","DOI":"10.3389\/fnins.2020.00899","article-title":"Progression of fetal brain lesions in tuberous sclerosis complex","volume":"14","author":"Gelot","year":"2020","journal-title":"Front Neurosci"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib37","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/ana.22696","article-title":"Altered inhibition in tuberous sclerosis and type IIb cortical dysplasia","volume":"71","author":"Talos","year":"2012","journal-title":"Ann Neurol"},{"issue":"23","key":"10.1016\/j.ebiom.2025.105740_bib38","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.150120","article-title":"Identifying the temporal electrophysiological and molecular changes that contribute to TSC-associated epileptogenesis","volume":"6","author":"Koene","year":"2021","journal-title":"JCI insight"},{"issue":"14","key":"10.1016\/j.ebiom.2025.105740_bib39","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1523\/JNEUROSCI.2260-18.2019","article-title":"mTOR hyperactivity levels influence the severity of epilepsy and associated neuropathology in an experimental model of tuberous sclerosis complex and focal cortical dysplasia","volume":"39","author":"Nguyen","year":"2019","journal-title":"J Neurosci"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib40","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/ana.21331","article-title":"Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex","volume":"63","author":"Zeng","year":"2008","journal-title":"Ann Neurol"},{"issue":"7","key":"10.1016\/j.ebiom.2025.105740_bib41","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1111\/epi.13031","article-title":"Intermittent dosing of rapamycin maintains antiepileptogenic effects in a mouse model of tuberous sclerosis complex","volume":"56","author":"Rensing","year":"2015","journal-title":"Epilepsia"},{"key":"10.1016\/j.ebiom.2025.105740_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2024.114874","article-title":"Modeling mTORopathy-related epilepsy in cultured murine hippocampal neurons using the multi-electrode array","volume":"379","author":"Heuvelmans","year":"2024","journal-title":"Exp Neurol"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib43","doi-asserted-by":"crossref","first-page":"7664","DOI":"10.1038\/s41467-023-42855-6","article-title":"Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years","volume":"14","author":"Huschner","year":"2023","journal-title":"Nat Commun"},{"issue":"7","key":"10.1016\/j.ebiom.2025.105740_bib44","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.21037\/tp-24-211","article-title":"Screening for biomarkers of tuberous sclerosis complex\u2013associated epilepsy: a bioinformatics analysis","volume":"13","author":"Sun","year":"2024","journal-title":"Transl Pediatr"},{"key":"10.1016\/j.ebiom.2025.105740_bib45","article-title":"Diagnosis of tuberous sclerosis in the prenatal period: a retrospective study of 240 cases and review of the literature","author":"Milon","year":"2024","journal-title":"Eur J Hum Genet"},{"issue":"7","key":"10.1016\/j.ebiom.2025.105740_bib46","doi-asserted-by":"crossref","DOI":"10.1002\/mgg3.1952","article-title":"Noninvasive prenatal diagnosis based on cell-free DNA for tuberous sclerosis: a pilot study","volume":"10","author":"Yang","year":"2022","journal-title":"Mol Genet Genomic Med"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib47","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1186\/s12887-023-04137-4","article-title":"Childhood tuberous sclerosis complex in southern Sweden: a paradigm shift in diagnosis and treatment","volume":"23","author":"Pearsson","year":"2023","journal-title":"BMC Pediatr"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/epi.17115","article-title":"The epilepsy-autism spectrum disorder phenotype in the era of molecular genetics and precision therapy","volume":"63","author":"Specchio","year":"2022","journal-title":"Epilepsia"},{"key":"10.1016\/j.ebiom.2025.105740_bib49","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pediatrneurol.2020.11.003","article-title":"Approach to preventive epilepsy treatment in tuberous sclerosis complex and current clinical practice in 23 countries","volume":"115","author":"S\u0142owi\u0144ska","year":"2021","journal-title":"Pediatr Neurol"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib50","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/epi4.12652","article-title":"The state of pediatric tuberous sclerosis complex epilepsy care: results from a national survey","volume":"7","author":"Whitney","year":"2022","journal-title":"Epilepsia Open"},{"issue":"12","key":"10.1016\/j.ebiom.2025.105740_bib51","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1111\/epi.16379","article-title":"Scalp EEG spikes predict impending epilepsy in TSC infants: a longitudinal observational study","volume":"60","author":"Wu","year":"2019","journal-title":"Epilepsia"},{"issue":"7","key":"10.1016\/j.ebiom.2025.105740_bib52","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S1474-4422(15)00069-1","article-title":"Neurological and neuropsychiatric aspects of tuberous sclerosis complex","volume":"14","author":"Curatolo","year":"2015","journal-title":"Lancet Neurol"},{"issue":"8","key":"10.1016\/j.ebiom.2025.105740_bib53","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/acn3.51128","article-title":"Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?","volume":"7","author":"Moavero","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"key":"10.1016\/j.ebiom.2025.105740_bib54","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.pediatrneurol.2024.06.012","article-title":"Drug-resistant epilepsy in tuberous sclerosis complex is associated with TSC2 genotype: more findings from the preventing epilepsy using vigatrin (PREVeNT) trial","volume":"159","author":"Farach","year":"2024","journal-title":"Pediatr Neurol"},{"issue":"9","key":"10.1016\/j.ebiom.2025.105740_bib55","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/s41436-020-0823-4","article-title":"TSC2 pathogenic variants are predictive of severe clinical manifestations in TSC infants: results of the EPISTOP study","volume":"22","author":"Og\u00f3rek","year":"2020","journal-title":"Genet Med"},{"key":"10.1016\/j.ebiom.2025.105740_bib56","doi-asserted-by":"crossref","DOI":"10.1016\/j.gene.2023.147566","article-title":"Mild TSC phenotype and non-penetrance associated with a frameshift variant in TSC2 prompts caution in evaluating pathogenicity of frameshift variants","volume":"877","author":"Farach","year":"2023","journal-title":"Gene"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib57","doi-asserted-by":"crossref","first-page":"332","DOI":"10.3390\/genes15030332","article-title":"The genetics of tuberous sclerosis complex and related mTORopathies: current understanding and future directions","volume":"15","author":"Man","year":"2024","journal-title":"Genes (Basel)"},{"key":"10.1016\/j.ebiom.2025.105740_bib58","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.pediatrneurol.2020.07.015","article-title":"Epilepsy risk prediction model for patients with tuberous sclerosis complex","volume":"113","author":"Farach","year":"2020","journal-title":"Pediatr Neurol"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib59","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/dmcn.15073","article-title":"Evolution of electroencephalogram in infants with tuberous sclerosis complex and neurodevelopmental outcome: a prospective cohort study","volume":"64","author":"De Ridder","year":"2022","journal-title":"Dev Med Child Neurol"},{"issue":"5","key":"10.1016\/j.ebiom.2025.105740_bib60","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/ana.21037","article-title":"Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation","volume":"60","author":"Jansen","year":"2006","journal-title":"Ann Neurol"},{"key":"10.1016\/j.ebiom.2025.105740_bib61","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.pediatrneurol.2024.09.014","article-title":"Severe epilepsy in an individual with a TSC2 R905Q variant prompting late diagnosis in affected family members","volume":"161","author":"Man","year":"2024","journal-title":"Pediatr Neurol"},{"issue":"8","key":"10.1016\/j.ebiom.2025.105740_bib62","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1111\/epi.16284","article-title":"Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex","volume":"60","author":"Davis","year":"2019","journal-title":"Epilepsia"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib63","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/ana.26015","article-title":"Tuber locations associated with infantile spasms map to a common brain network","volume":"89","author":"Cohen","year":"2021","journal-title":"Ann Neurol"},{"key":"10.1016\/j.ebiom.2025.105740_bib64","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejrad.2024.111800","article-title":"Prediction of epileptogenicity in patients with tuberous sclerosis complex using multimodal cerebral MRI","volume":"181","author":"Li","year":"2024","journal-title":"Eur J Radiol"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib65","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/08830738060210020901","article-title":"Tuberous sclerosis complex: correlation of magnetic resonance imaging (MRI) findings with comorbidities","volume":"21","author":"Wong","year":"2006","journal-title":"J Child Neurol"},{"key":"10.1016\/j.ebiom.2025.105740_bib66","article-title":"Developing forebrain synapses are uniquely vulnerable to sleep loss","author":"Gay","year":"2023","journal-title":"bioRxiv"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib67","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/0387-7604(94)00118-H","article-title":"Sleep disorders in tuberous sclerosis: a polysomnographic study","volume":"17","author":"Bruni","year":"1995","journal-title":"Brain Dev"},{"key":"10.1016\/j.ebiom.2025.105740_bib68","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ejpn.2022.03.010","article-title":"Sleep in children with refractory epilepsy and epileptic encephalopathies: a systematic review of literature","volume":"38","author":"Proost","year":"2022","journal-title":"Eur J Paediatr Neurol"},{"issue":"10","key":"10.1016\/j.ebiom.2025.105740_bib69","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmg.2022.104573","article-title":"Genotype\/phenotype correlation in 123 Chinese patients with tuberous sclerosis complex","volume":"65","author":"Ng","year":"2022","journal-title":"Eur J Med Genet"},{"key":"10.1016\/j.ebiom.2025.105740_bib70","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jpeds.2021.02.060","article-title":"Fetal brain magnetic resonance imaging findings predict neurodevelopment in children with tuberous sclerosis complex","volume":"233","author":"Hulshof","year":"2021","journal-title":"J Pediatr"},{"key":"10.1016\/j.ebiom.2025.105740_bib71","article-title":"Accumulated seizure burden predicts neurodevelopmental outcome at 36 months of age in patients with tuberous sclerosis complex","author":"Ihnen","year":"2024","journal-title":"Epilepsia"},{"issue":"5\u20136","key":"10.1016\/j.ebiom.2025.105740_bib72","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1177\/08830738241248685","article-title":"Abnormality of early white matter development in tuberous sclerosis complex and autism spectrum disorder: longitudinal analysis of diffusion tensor imaging measures","volume":"39","author":"Srivastava","year":"2024","journal-title":"J Child Neurol"},{"issue":"8","key":"10.1016\/j.ebiom.2025.105740_bib73","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines10081838","article-title":"miRNAs and isomiRs: serum-based biomarkers for the development of intellectual disability and autism spectrum disorder in tuberous sclerosis complex","volume":"10","author":"Scheper","year":"2022","journal-title":"Biomedicines"},{"issue":"6","key":"10.1016\/j.ebiom.2025.105740_bib74","doi-asserted-by":"crossref","DOI":"10.3390\/jcm8060788","article-title":"Early clinical predictors of autism spectrum disorder in infants with tuberous sclerosis complex: results from the EPISTOP study","volume":"8","author":"Moavero","year":"2019","journal-title":"J Clin Med"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib75","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1007\/s10803-019-04326-0","article-title":"EEG spectral features in sleep of autism spectrum disorders in children with tuberous sclerosis complex","volume":"50","author":"Cook","year":"2020","journal-title":"J Autism Dev Disord"},{"issue":"5","key":"10.1016\/j.ebiom.2025.105740_bib76","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1111\/epi.16892","article-title":"Early epileptiform EEG activity in infants with tuberous sclerosis complex predicts epilepsy and neurodevelopmental outcomes","volume":"62","author":"De Ridder","year":"2021","journal-title":"Epilepsia"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib77","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s11689-019-9293-x","article-title":"Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder","volume":"11","author":"Prohl","year":"2019","journal-title":"J Neurodev Disord"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib78","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1093\/cercor\/bhz233","article-title":"The connectivity fingerprint of the fusiform gyrus captures the risk of developing autism in infants with tuberous sclerosis complex","volume":"30","author":"Scherrer","year":"2020","journal-title":"Cereb Cortex"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib79","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ejpn.2009.03.003","article-title":"Early control of seizures improves long-term outcome in children with tuberous sclerosis complex","volume":"14","author":"Bombardieri","year":"2010","journal-title":"Eur J Paediatr Neurol"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib80","article-title":"Vigabatrin inhibits seizures and mTOR pathway activation in a mouse model of tuberous sclerosis complex","volume":"8","author":"Zhang","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib81","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/ana.25956","article-title":"Prevention of epilepsy in infants with tuberous sclerosis complex in the EPISTOP trial","volume":"89","author":"Kotulska","year":"2021","journal-title":"Ann Neurol"},{"issue":"12","key":"10.1016\/j.ebiom.2025.105740_bib82","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1111\/epi.17099","article-title":"Adjunctive everolimus therapy for tuberous sclerosis complex-associated refractory seizures: results from the postextension phase of EXIST-3","volume":"62","author":"Franz","year":"2021","journal-title":"Epilepsia"},{"key":"10.1016\/j.ebiom.2025.105740_bib83","doi-asserted-by":"crossref","first-page":"951","DOI":"10.2147\/TCRM.S145630","article-title":"Everolimus for the treatment of refractory seizures associated with tuberous sclerosis complex (TSC): current perspectives","volume":"15","author":"Overwater","year":"2019","journal-title":"Ther Clin Risk Manag"},{"issue":"7","key":"10.1016\/j.ebiom.2025.105740_bib84","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S2352-4642(18)30099-3","article-title":"Adjunctive everolimus for children and adolescents with treatment-refractory seizures associated with tuberous sclerosis complex: post-hoc analysis of the phase 3 EXIST-3 trial","volume":"2","author":"Curatolo","year":"2018","journal-title":"Lancet Child Adolesc Heal"},{"issue":"10","key":"10.1016\/j.ebiom.2025.105740_bib85","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1111\/dmcn.15265","article-title":"Prenatal diagnosis and intervention improve developmental outcomes and epilepsy prognosis in children with tuberous sclerosis complex","volume":"64","author":"Wang","year":"2022","journal-title":"Dev Med Child Neurol"},{"issue":"8","key":"10.1016\/j.ebiom.2025.105740_bib86","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nm1788","article-title":"Reversal of learning deficits in a Tsc2+\/- mouse model of tuberous sclerosis","volume":"14","author":"Ehninger","year":"2008","journal-title":"Nat Med"},{"issue":"21","key":"10.1016\/j.ebiom.2025.105740_bib87","doi-asserted-by":"crossref","first-page":"5422","DOI":"10.1523\/JNEUROSCI.0955-08.2008","article-title":"Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function","volume":"28","author":"Meikle","year":"2008","journal-title":"J Neurosci"},{"issue":"8","key":"10.1016\/j.ebiom.2025.105740_bib88","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1212\/WNL.0b013e318247ca8d","article-title":"Everolimus alters white matter diffusion in tuberous sclerosis complex","volume":"78","author":"Tillema","year":"2012","journal-title":"Neurology"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib89","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.nbd.2011.08.024","article-title":"Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin","volume":"45","author":"Carson","year":"2012","journal-title":"Neurobiol Dis"},{"issue":"6","key":"10.1016\/j.ebiom.2025.105740_bib90","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.ejpn.2018.06.007","article-title":"Short-term safety of mTOR inhibitors in infants and very young children with tuberous sclerosis complex (TSC): multicentre clinical experience","volume":"22","author":"Krueger","year":"2018","journal-title":"Eur J Paediatr Neurol"},{"issue":"19","key":"10.1016\/j.ebiom.2025.105740_bib91","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1056\/NEJMc1800352","article-title":"Maternal sirolimus therapy for fetal cardiac rhabdomyomas","volume":"378","author":"Barnes","year":"2018","journal-title":"N Engl J Med"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105740_bib92","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/pd.5613","article-title":"Fetal cardiac rhabdomyomas treated with maternal sirolimus","volume":"40","author":"Pluym","year":"2020","journal-title":"Prenat Diagn"},{"issue":"16","key":"10.1016\/j.ebiom.2025.105740_bib93","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241612886","article-title":"Three-Year follow-up after intrauterine mTOR inhibitor administration for fetus with TSC-associated rhabdomyoma","volume":"24","author":"Ma\u00e1sz","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"5","key":"10.1016\/j.ebiom.2025.105740_bib94","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1002\/epi4.13013","article-title":"Long-term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3-year results from the cannabidiol expanded access program","volume":"9","author":"Weinstock","year":"2024","journal-title":"Epilepsia Open"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib95","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/epi4.12529","article-title":"The epileptogenic zone in children with tuberous sclerosis complex is characterized by prominent features of focal cortical dysplasia","volume":"6","author":"Hulshof","year":"2021","journal-title":"Epilepsia Open"},{"key":"10.1016\/j.ebiom.2025.105740_bib96","doi-asserted-by":"crossref","DOI":"10.1016\/j.jns.2021.117506","article-title":"Seizure outcome after epilepsy surgery in tuberous sclerosis complex: results and analysis of predictors from a multicenter study","volume":"427","author":"Vannicola","year":"2021","journal-title":"J Neurol Sci"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib97","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/brain\/awz411","article-title":"Resective epilepsy surgery in tuberous sclerosis complex: a nationwide multicentre retrospective study from China","volume":"143","author":"Liu","year":"2020","journal-title":"Brain"},{"key":"10.1016\/j.ebiom.2025.105740_bib98","doi-asserted-by":"crossref","DOI":"10.1016\/j.eplepsyres.2024.107422","article-title":"Impact of seizure onset zone and intracranial electroencephalography ictal characteristics on epilepsy surgery outcomes in tuberous sclerosis complex","volume":"205","author":"Miecznikowski","year":"2024","journal-title":"Epilepsy Res"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib99","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/epi.16410","article-title":"Epileptogenicity in tuberous sclerosis complex: a stereoelectroencephalographic study","volume":"61","author":"Neal","year":"2020","journal-title":"Epilepsia"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib100","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1684\/epd.2021.1253","article-title":"Surgery for drug-resistant tuberous sclerosis complex-associated epilepsy: who, when, and what","volume":"23","author":"Specchio","year":"2021","journal-title":"Epileptic Disord"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib101","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1227\/neu.0000000000002214","article-title":"Epilepsy surgery in young children with tuberous sclerosis complex: a novel hybrid multimodal surgical approach","volume":"92","author":"Ravindra","year":"2023","journal-title":"Neurosurgery"},{"issue":"4","key":"10.1016\/j.ebiom.2025.105740_bib102","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3171\/2024.4.PEDS2481","article-title":"Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex","volume":"34","author":"Sadeghzadeh","year":"2024","journal-title":"J Neurosurg Pediatr"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105740_bib103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.euroneuro.2018.11.1107","article-title":"Neuroplasticity-related correlates of environmental enrichment combined with physical activity differ between the sexes","volume":"29","author":"Kokras","year":"2019","journal-title":"Eur Neuropsychopharmacol"},{"key":"10.1016\/j.ebiom.2025.105740_bib104","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/978-3-031-75980-2_6","article-title":"Environmental enrichment and epigenetic changes in the brain: from the outside to the deep inside","volume":"108","author":"Torres","year":"2025","journal-title":"Subcell Biochem"},{"key":"10.1016\/j.ebiom.2025.105740_bib105","doi-asserted-by":"crossref","DOI":"10.1016\/j.beproc.2023.104915","article-title":"Which form of environmental enrichment is most effective in rodent models of autism?","volume":"211","author":"Caires","year":"2023","journal-title":"Behav Processes"},{"issue":"10","key":"10.1016\/j.ebiom.2025.105740_bib106","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1111\/dmcn.14182","article-title":"Early environmental influences on the development of children's brain structure and function","volume":"61","author":"Miguel","year":"2019","journal-title":"Dev Med Child Neurol"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib107","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1097\/IYC.0000000000000160","article-title":"Improving developmental abilities in infants with tuberous sclerosis complex: a pilot behavioral intervention study","volume":"33","author":"McDonald","year":"2020","journal-title":"Infants Young Child"},{"key":"10.1016\/j.ebiom.2025.105740_bib108","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.omtm.2019.08.003","article-title":"Long-term therapeutic efficacy of intravenous AAV-mediated hamartin replacement in mouse model of tuberous sclerosis type 1","volume":"15","author":"Prabhakar","year":"2019","journal-title":"Mol Ther Methods Clin Dev"},{"issue":"2","key":"10.1016\/j.ebiom.2025.105740_bib109","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abb1703","article-title":"Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin","volume":"7","author":"Cheah","year":"2021","journal-title":"Sci Adv"},{"key":"10.1016\/j.ebiom.2025.105740_bib110","article-title":"CRISPR-Cas9-Mediated correction of TSC2 pathogenic variants in iPSCs from patients with tuberous sclerosis complex type 2","author":"Guo","year":"2024","journal-title":"Cris J"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396425001847?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396425001847?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T16:16:45Z","timestamp":1762618605000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396425001847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":110,"alternative-id":["S2352396425001847"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2025.105740","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanistic strategies for secondary prevention of developmental and epileptic encephalopathy in children with tuberous sclerosis complex","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2025.105740","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"105740"}}