OBJECTIVE:Pediatric epilepsy surgery is well established, but contemporary global data on referral and presurgical evaluation practices are lacking. This International League Against Epilepsy (ILAE) Pediatric Epilepsy Surgery Task Force study provides an updated overview of current trends and regional differences. METHODS:Group-level data were collected from 61 epilepsy surgery programs (49 pediatric-only) across 29 countries and six continents, identified through ILAE networks, and included all children and adolescents treated in 2023 who underwent presurgical evaluation/epilepsy surgery. RESULTS:Group-level data were available for 2427 patients. Mean age at surgery was 9.1 ± 4.9 years; mean epilepsy duration was 5.3. At surgery, 3.2% were <1 year old (highest in Oceania: 5.1%), and 6.1% were nonpharmacoresistant (highest in Europe: 15.0%). Prior neurosurgery was reported in 14.2% (highest in North America: 28.8%), including 8.0% resections (6.1% for epilepsy, 1.5% for tumors; highest in Oceania: 16.5%), 2.3% disconnections (1.3% corpus callosotomy; highest in South America: 4.7%), and 4.2% neuromodulation (3.7% vagal nerve stimulation, .2% responsive neurostimulation, one deep brain stimulation; highest in North America: 12.2%). Developmental and epileptic encephalopathies (DEEs) at surgery included Lennox-Gastaut syndrome (7.4%), infantile epileptic spasms syndrome (5.1%), and DEE with spike-wave activation in sleep (1.5%). Presurgical investigations included fluorodeoxyglucose positron emission tomography (52.6%; highest in Oceania: 79.7%), genetic testing (46.8%; highest in Asia: 54.3%), magnetic resonance imaging (MRI) postprocessing (32.4%; highest in South America: 53.0%), functional MRI (fMRI; 15.2%; highest in North America: 40.3%), magnetoencephalography (11.9%; highest in North America: 39.3%), single photon emission computed tomography (9.6%; highest in North America: 22.2%), high-density electroencephalography (EEG; 1.9%; highest in Europe: 4.7%), source localization (1.6%; highest in Oceania: 7.6%), Wada test (1.2%; highest in North America: 3.5%), and EEG-fMRI (.5%; highest in Europe: 1.1%). SIGNIFICANCE:Despite some early surgeries, including in infancy and before pharmacoresistance, mean epilepsy duration before surgery remains >5 years. Reoperations are common, with resection more frequent than neuromodulation. Genetic testing in nearly half of patients reflects its growing relevance, and the high rate of DEEs underscores the complexity of surgical candidates.

Abstract Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two‐week‐long, on‐site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16–89) hours of intensive and dedicated clinical training, coordinated by 2–3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on‐site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post‐training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on‐site attendance by basic scientists in specialized clinical settings up‐scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. Plain Language Summary Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two‐week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long‐term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.

Executive functions are a set of high-level cognitive processes necessary for planning, organization, decision-making, self-control, and attention, and are carried out in the anterior frontal lobes. An impairment in executive functioning might present as difficulties in planning and organizing activities, in attention and concentration, in cognitive flexibility, impulsiveness, and working memory fragility. These might result in greater emotional and psychopathological difficulties and poorer academic performance. Self-limited epilepsy with centro-temporal spikes (SeLECTS), the most common epileptic syndrome occurring in the pediatric population, is characterized by seizure remission around puberty in most cases. However, despite the favorable seizure outcome, previous studies have suggested that executive function deficits might be present and persist after epilepsy remission. We conducted a scoping review to investigate the current knowledge on executive functioning in children with SeLECTS. Furthermore, we explored psychopathological and emotional dimensions and daily functioning in this population. Starting from two reviews published in 2021, we conducted a complementary search and included 41 articles, from which we analyzed clinical data, neuropsychological findings, and their respective correlations. Our results confirmed the possible presence of executive dysfunction in patients with SeLECTS in the domains of inhibition and cognitive flexibility. We also strengthen possible impairments in working memory and higher order executive functions. We confirmed the correlation between executive dysfunction and both early age at onset and high frequency of electroencephalogram abnormalities and observed a possible role for high seizure frequency, secondary bilateralization, and the use of anti-seizure medications. We also found a higher prevalence of psychopathological dimensions, most commonly attention deficit-hyperactivity disorder, compared with controls. Overall, our findings support the need for neuropsychological assessment in clinical practice for children with SeLECTS to characterize executive functioning and its impact on psychopathological and emotional dimensions, as well as academic performance.

PURPOSE:MRI detection of subtle focal cortical dysplasia (FCD)-like abnormalities remains challenging in focal epilepsy. Higher signal-to-noise ratio and spatial resolution offered by ultra-high-field 7T MRI and surface-based graph-neural-network (GNN) analysis may improve detection of subtle cortical abnormalities. We evaluated whether combining 7T MRI with a surface-based GNN classifier improves lesion detection in focal epilepsy of suspected structural origin. METHODS:We analyzed paired 7T and 3T MRI datasets from 87 patients with focal epilepsy (78.1% pediatric) and 10 internal healthy control individuals. We processed T1-weighted and Fluid-Attenuated-Inversion-Recovery MRI using a surface-based framework and a pre-trained GNN classifier developed within the Multi-centre-Epilepsy-Lesion-Detection project. We compared classifier outputs with expert visual MRI assessment, clinical and surface electroencephalography (EEG) localization (all patients), stereo-EEG (ten patients) and histopathological (17 patients) findings. We evaluated diagnostic yield and lesion conspicuity, and performed within-subject comparisons between 7T and 3T. RESULTS:Following quality controls, we included 70 patients. The 7T MRI-based classifier identified lesion clusters concordant with visual 3T MRI and electroclinical localization in 25/37 (67.6%) MRI-positive patients, electroclinical-concordant clusters in 15/33 (45.4%) 3T MRI-negatives, stereo-EEG-concordant clusters in 7/10 (70.0%) patients and surgically-concordant clusters in 11/17 (64.7%). Among classifier-positive patients (40/70, 57.1%), 7T allowed detection of previously hidden lesions in 15/40 (37.5%) patients, and improved detection of known lesions in 11/40 (27.5%). CONCLUSION:Combining 7T MRI with surface-based GNN analysis improves detection and characterization of FCD-like abnormalities in focal epilepsy, particularly in patients with unrevealing 3T MRI, supporting the adoption of advanced neuroimaging in presurgical epilepsy assessment.

BACKGROUND:We evaluated the real-world efficacy, tolerability, treatment retention, and quality-of-life effects of cenobamate in paediatric drug-resistant epilepsy. METHODS:We retrospectively studied 78 paediatric patients with drug-resistant epilepsy treated with cenobamate for ≥ 3 months at a tertiary epilepsy centre. We assessed seizure frequency, adverse effects, cognitive/behavioural outcomes, and changes in concomitant antiseizure medications. The primary efficacy endpoint was a ≥ 50% reduction in seizure frequency. We assessed safety through reported adverse events and clinical improvement using the Clinical Global Impression-Improvement (CGI-I) scale. We used Kaplan-Meier analyses to assess responder rates and treatment retention over 18 months. RESULTS:A ≥ 50% seizure reduction was achieved in 67.9% of patients including 6.4% who became seizure-free. Polytherapy was simplified in 38% overall and in 56.6% of responders. Adverse events occurred in 43.6% of patients, were mostly mild, and led to discontinuation in only one patient (1.3%). CGI-I indicated clinical improvement in 24.4%. Kaplan-Meier analysis showed sustained response in 93% of initial responders at 18 months. Treatment retention remained high: 94.7% at 3 months, 89.6% at 12 months, and 86.8% at 18 months. Median follow-up was 12 months (range 3-18), with 60.3% followed for ≥ 12 months and 41% for the full 18 months. CONCLUSIONS:Our study confirms and extends recent evidence on the efficacy and favourable tolerability of cenobamate in paediatric drug-resistant epilepsy. We observed functional improvements and polytherapy simplification, suggesting broader therapeutic benefits. These findings warrant prospective validation in specific paediatric epilepsy syndromes and may help support regulatory approval for paediatric use.

INTRODUCTION:Telemedicine has gained increasing prominence in healthcare services, with neuropsychological tele-assessment emerging as a promising tool for evaluating and monitoring cognitive functions remotely, even in clinical conditions with mild vulnerabilities. Despite its growing application in adults, its use in pediatric clinical contexts remains understudied. Among pediatric disorders, Self-limited epilepsy with centrotemporal spikes (SeLECTs) may feature subtle neuropsychological deficits, particularly in higher order cognitive processes such as Executive Functions (EF), and in learning skills. Early tele-neuropsychological assessment can help delineate the neuropsychological profile in this population. METHOD:The feasibility of a fully remote neuropsychological assessment protocol in children with SeLECTs was examined. Forty-seven children (aged 6-13) were recruited, of whom 43 underwent the assessment. Two online sessions via Google Meet and web-based platforms (TeleFE battery), to assess children's cognitive and executive functioning were conducted. Clinicians evaluated the children's engagement and parents completed remote questionnaires addressing academic performances, EF-related behaviors, and feasibility of the procedure. RESULTS:The protocol demonstrated high feasibility and acceptability, with participants' strong compliance and no major technical issues. Descriptive analyses highlighted the presence of vulnerabilities in executive functioning and school achievement in children with SeLECTs. DISCUSSION:These findings support the clinical relevance of remote neuropsychological assessment in pediatric epilepsy, offering a scalable and accessible tool to enhance care.

Objective Neonatal developmental and epileptic encephalopathy with movement disorder and arthrogryposis (NDEEMA) represents the most severe end of the gain-of-function (GOF) SCN1A disorder spectrum. Sporadic cases of congenital arthrogryposis have also been reported in individuals with SCN2A-, SCN3A-, and SCN8A-related developmental and epileptic encephalopathy. Here, we investigated whether NDEEMA occurs in other brain-expressed sodium channelopathies and characterized its features.Methods Individuals with the clinical phenotype of NDEEMA were identified through internal databases, an international network of epileptologists and geneticists, and the literature. Their clinical and genetic information was analyzed. A literature survey was conducted to review studies describing the functional effects of the pathogenic variants.Results Of 46 NDEEMA individuals, 25 harbored variants in SCN1A, 13 in SCN2A, one in SCN3A, and seven in SCN8A. Thirty-five different pathogenic/likely pathogenic missense variants were identified, all of which clustered in evolutionary conserved paralogous NaV positions. Five individuals died in utero. Thirty-nine of 41 (95%) liveborn individuals developed neonatal epilepsy with tonic seizures and/or apnea. Thirty-one individuals tried sodium channel blockers, of whom 21 (68%) experienced seizure reduction. All individuals for whom information was available developed movement disorders, with myoclonus, dystonia, and tremor being the most common features. Literature review of functional studies revealed that nine NDEEMA variants, and the corresponding paralogues of 16 additional NDEEMA variants, have been biophysically characterized as GOF.Significance This study expands the phenotype of NDEEMA from SCN1A to its paralogue sodium channel genes expressed in the brain: SCN2A, SCN3A, and SCN8A.

OBJECTIVE:Quantitative assessment of extent of tissue resection following epilepsy surgery requires accurate delineation of the resection cavity on postoperative magnetic resonance imaging (MRI). Current methods for resection cavity masking are time-consuming and labor-intensive, and existing automated approaches exhibit variable segmentation accuracy, particularly on extratemporal resections. We developed MELD-PostOp, a deep learning tool trained and evaluated on a large, heterogeneous cohort to automatically segment resection cavities. METHODS:The study included 1.5- and 3T postoperative three-dimensional T1-weighted MRI images from the Multicentre Epilepsy Lesion Detection (MELD) project (nsubjects = 969, 27 centers) and from the EPISURG dataset (n = 133). The cohort included children and adults, alongside a range of resection locations, pathologies, and MRI characteristics. Resection cavities were individually segmented in 285 subjects and used to train an nnU-Net prototype model. The prototype model was used to generate an additional 680 resection masks, which were subsequently quality-controlled, edited, and combined with the original 285 to train the final MELD-PostOp model (n = 965). A Stratified Test Cohort (n = 50) and Independent Test Cohort (n = 87) were withheld for model evaluation. Performance was evaluated using Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), number of predicted clusters, and inference runtime, and compared against established tools (Epic-CHOP, ResectVol, and RESSEG). RESULTS:MELD-PostOp achieved a median DSC of .85 and HD95 of 3.61 on the combined test cohort, outperforming Epic-CHOP (DSC .69, HD95 9.67), ResectVol (DSC .66, HD95 15.05), and RESSEG (DSC .43, HD95 32.67), with significant improvements seen in both temporal and especially extratemporal resections. The model detected 98.5% (135/137) of resection cavities. MELD-PostOp runtime was 17 s per MRI, compared to 612 s (ResectVol), 3205 s (Epic-CHOP), and 4 s (RESSEG). MELD-PostOp performance remained high across clinical and imaging subgroups (median DSC > .8). SIGNIFICANCE:MELD-PostOp is an open-source research tool that provides an accurate, efficient, and generalizable solution for postoperative resection cavity segmentation using only postoperative MRI scans.

Objective Quantitative assessment of extent of tissue resection following epilepsy surgery requires accurate delineation of the resection cavity on postoperative MRI. Current methods for resection cavity masking are time-consuming and labour-intensive, while existing automated approaches exhibit variable segmentation accuracy, particularly on extra-temporal resections. We developed MELD-PostOp, a deep learning tool trained and evaluated on a large, international, heterogeneous cohort to automatically segment resection cavities. Methods The study included 1.5 and 3T postoperative 3D T1-weighted MRI images from the Multicentre Epilepsy Lesion Detection (MELD) project (nsubjects=969, 27 centres) and from the EPISURG dataset (n=133). The cohort included both children and adults, alongside a range of resection locations, pathologies, and MRI characteristics. Resection cavities were individually segmented in 285 subjects and used to train an nnU-Net prototype model. The prototype model was used to generate an additional 680 resection masks, which were subsequently quality-controlled, edited and then combined with the original 285 to train the final MELD-PostOp model (n=965). A Stratified (STC; n=50) and Independent Test Cohort (ITC; n=87) were masked and withheld for model evaluation. Performance was evaluated using Dice Similarity Coefficient (DSC), 95th percentile Hausdorff distance (HD95), number of predicted clusters and inference runtime; and compared against established tools (Epic-CHOP and ResectVol). Results MELD-PostOp achieved a median DSC of 0.85 and HD95 of 3.61 on the combined test cohort, outperforming Epic-CHOP (DSC 0.68, HD95 9.54) and ResectVol (DSC 0.66, HD95 12.07), with significant improvements seen in both temporal and especially extra-temporal resections. The model detected 99% (135/137) of resection cavities. MELD-PostOp runtime was 17s per MRI, compared to 612s (ResectVol) and 3205s (Epic-CHOP). MELD-PostOp performance remained high across clinical and imaging subgroups (median DSC > 0.8). Significance MELD-PostOp provides an accurate, efficient and generalisable solution for postoperative resection cavity segmentation using only postoperative MRI scans. This open-source tool facilitates large-scale quantitative analysis to define what tissue is essential to resect for optimal epilepsy surgical outcomes. ### Competing Interest Statement Alexander G. Weil is a consultant for Monteri. Kate Davis is an advisory board member for NeuroPace, Rapport Therapeutics, Mosaica Therapeutics, UCB. ### Clinical Protocols ### Funding Statement JS, MR and KW are supported by Wellcome Trust (301991/Z/23/Z) and Epilepsy Research Institute UK (P2208). SA is supported by Epilepsy Research Institute UK(P2208). TJO is supported by NHMRC Investigator Grants (APP1176426 & APP2034258). HX is supported by National Institute of Child Health and Human Development (P50HD105328-01). NTC is supported by the National Institute Of Neurological Disorders And Stroke and the National Institutes of Health (Award Number K23NS131522). AGW and AH are supported by Canadian Institute for Health Research , Fonds de recherche du Quebec - Sante, Savoy Foundation, Department of surgery at Universite de Montreal, CHU Sainte-Justine Foundation. AI is supported by grants from the Fogarty International Center, National Institutes of Health, National Institutes of Aging (R01 AG057234, R01 AG075775, R01 AG21051, R01 AG083799, CARDS-NIH, R01 AG057234), Alzheimer's Association (SG-20-725707), Rainwater Charitable Foundation, ANID/FONDECYT Regular (1250091 and 1210176 and 1220995), ANID/PIA/ANILLOS ACT210096, JPI JPND-Care, DISCeRN 2025, FONDEF ID20I10152,ANID/FONDAP 15150012; Wellcome Trust (BRAIN-CLIMA 335293/Z/25/Z), and CliCBrain (Horizon ID: 101236426; DOI 10.3030/101236426, Marie Skłodowska-Curie Actions - MSCA). AC is supported by NIHR & GOSH BRC. MHE is supported by The Sigrid Juselius Foundation. RJP is supported by NIHR & GOSH Children's Charity. CLY is supported by CNPQ (445340/2024-0/; 313263/2025-6). FC is supported by Sao Paulo Research Foundation (FAPESP) grants 2013/07559-3 and 2021/12956-8. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of any of the funders. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study used anonymised MRI data collected as part of the Multi-centre Epilepsy Lesion Detection (MELD) Focal Epilepsies project (https://meldproject.github.io/), which has Health Research Authority ethical approval (IRAS: 301863) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data sharing of the MELD Focal Epilepsies dataset is restricted as consent was not obtained from participants for public sharing of data. EPISURG dataset is available at:https://rdr.ucl.ac.uk/articles/dataset/EPISURG\_a\_dataset\_of\_postoperative\_magnetic\_resonance\_images\_MRI\_for\_quantitative\_analysis\_of\_resection\_neurosurgery\_for\_refractory_epilepsy/9996158?file=26153588 All code for model design, development and statistical analyses alongside the MELD-PostOp model is available at: https://github.com/MELDProject/MELD-PostOp/tree/main

OBJECTIVE:To characterize the neuropsychological profile and social cognition, particularly Theory of Mind (ToM), in 45 children and adolescents with temporal lobe epilepsy (TLE) compared with 56 age, gender, and schooling-matched healthy controls. Within the original sample, we also evaluated a subgroup of patients who underwent epilepsy surgery, compared with those who were not surgically treated. METHODS:This is a prospective controlled study conducted between October 2020 and November 2022 at one center. We analyzed the study results for children (8-12 years old) and adolescents (13-18 years old) separately. We used univariate inferential statistical analyses (ANOVA or Kruskal-Wallis) and linear or logistic regression analyses. RESULTS:We observed significant impairments in cognitive functions, social cognition, and ToM in children with TLE compared with controls, as confirmed also by logistic regression analyses. Conversely, we found lower scores in adolescents with TLE compared with controls only in the sub-components of the Verbal Fluency test and Recognition of behaviors in the social situations test. Regression analyses adjusted for epilepsy-related variables confirmed that children exhibit more severe neuropsychological and sociocognitive impairments than adolescents. ToM abilities were impaired in children who had been treated surgically compared with those who had not. This finding could be due to epilepsy-related factors, such as earlier onset and longer disease duration, ablation of anatomic structures involved in ToM, or both. SIGNIFICANCE:A comprehensive neuropsychological and psychosocial assessment, including TOM, is recommended for children with TLE, especially if they are surgical candidates, to ensure timely psychoeducative and rehabilitative interventions. PLAIN LANGUAGE SUMMARY:Social cognition and ToM allow understanding of one's own and others' thoughts and feelings. These skills are often impaired in children and adolescents with temporal lobe epilepsy (TLE). We compared the neuropsychological and social profiles of young people with TLE to healthy peers and examined differences between those who underwent epilepsy surgery and those who did not. Children with TLE showed significant impairments in cognitive functions, social cognition, and ToM, with surgically treated children facing greater ToM challenges. Our findings highlight the need for comprehensive neuropsychological and psychosocial assessments to provide timely support for children with TLE.

Epilepsy surgery in language areas is challenged by the intricacies of presurgical workup and surgical planning. In recent decades, the view of language-related circuitry has shifted from being localized in a few cortical centers to a distributed, dynamically interconnected system, increasing complexity. In this framework, neuropsychology, functional neuroimaging and neurophysiological assessments play an essential role in minimizing the risk of language deficits. A comprehensive preoperative neuropsychological assessment is essential for providing a baseline against which to compare postoperative performance, as well as for helping to define functional deficit and epileptogenic zones. Functional magnetic resonance imaging (fMRI) represents a fundamental noninvasive alternative to the traditional Wada test for determining hemispheric language lateralization and localization. Resting state fMRI (rs-fMRI) may offer a compelling alternative, particularly in populations where task performance is difficult or unreliable. The role of Stereo-electroencephalography (Stereo-EEG) and the intracerebral electrical stimulations (ES) is pivotal for both the identification of the epileptogenic zone and the mapping of eloquent cortices. The use of all available cortical stimulation methods, combined with test batteries targeting different language subdomains and designed to avoid the induction of post-discharges, appears to be the optimal approach for maximizing patient safety. The preservation of language function also relies on highly specific intraoperative mapping techniques, primarily employed in cooperative patients during awake craniotomy. Likewise, cortico-cortical evoked potentials could represent a valuable "task-free" neurophysiological alternative. Surgical strategies involving language areas vary from focal resections to larger lobar, multilobar or hemispheric procedures. Minimally invasive options such as Stereo-EEG-guided radiofrequency thermocoagulation (RF-TC) and laser interstitial thermal therapy (LITT) have broadened therapeutic possibilities. Selection depends on EZ accessibility and extent. Modern epilepsy surgery within language-eloquent areas increasingly relies on integrated multimodal approaches. Future directions include the use of machine learning to analyze large postoperative datasets and predict long-term functional and seizure outcomes.

OBJECTIVE:Epilepsy surgery is a standard treatment for drug-resistant epilepsy, resulting in seizure freedom in a significant number of cases. Although frequently performed for low-grade brain tumors, it is rarely considered for high-grade tumors, despite the impact of chronic epilepsy on quality of life and cognition. METHODS:This retrospective multicenter study across 43 European centers evaluated epilepsy surgery outcomes in children with high-grade brain tumors (World Health Organization grades III and IV). Two cohorts of patients younger than 25 years were studied: (1) those undergoing epilepsy surgery after tumor resection (n = 14) and (2) those initially suspected of low-grade lesions but diagnosed with high-grade brain tumors postsurgery (n = 11). RESULTS:Eighty percent of patients achieved seizure freedom 1 year after last epilepsy surgery: 71% in Cohort 1 and 91% in Cohort 2. Eighty-four percent were free of disabling seizures (Engel IA-D) after a median follow-up period of 4.3 years (range = 1-15.9 years). No surgery-related deaths occurred. Thirty-two percent of children experienced persistent morbidity, including motor dysfunction, visual impairment, persistent seizures, cognitive deficits, and hydrocephalus. SIGNIFICANCE:Epilepsy surgery is effective for medically refractory epilepsy in children with high-grade central nervous system tumors and should be considered early, as seizure freedom is achieved in the majority of patients. Despite involving numerous epilepsy centers, only 25 patients were recruited, indicating that this method is rarely considered for high-grade brain tumor patients with medically refractory epilepsy.

We conducted a systematic review and meta‐analysis of the ictal semiology associated with supplementary motor area (SMA) and pre‐supplementary motor area (pre‐SMA) epilepsy, to summarize current knowledge of related anatomo‐clinical correlations in the context of presurgical evaluation. We conducted the review and reported its results according to the Preferred Reporting Items for Systematic Review and Meta‐Analysis statement (PRISMA). We searched PubMed and Embase using relevant keywords related to the SMA and pre‐SMA localization, seizure semiology, and scalp electroencephalography (EEG) or stereo‐EEG. The risk of bias was evaluated using the QUADAS2 score. Twenty articles were included, with extractable data from 37 patients. We analyzed the included studies and extracted data on the presence of 12 different symptoms. We then performed a meta‐analysis of the proportion of patients with each symptom. The most frequently reported ictal feature in SMA epilepsy was asymmetric tonic posturing, observed in 47% of cases. Automatisms (25%) and versive seizures (23%) were also common, while loss of consciousness occurred in 19% of patients. Sensory phenomena (11%) and speech arrest/inhibition (10%) were less frequent. Other features, including symmetric tonic posturing, elementary motor signs, hyperkinetic patterns, affective phenomena, grimacing, and negative motor phenomena, were rarely observed. Little evidence is available on the distinct involvement of the pre‐SMA. Although asymmetric tonic posturing appears to be the most common feature of SMA epilepsy, it occurs in fewer than 50% of patients and the level of evidence of this association remains low. The same semiological feature may result from the rapid propagation to adjacent or connected regions; hence, semiology should always be interpreted in the context of a multimodal evaluation. Stereo‐EEG investigation remains crucial when EEG and imaging are inconclusive or conflicting.

Neurodegenerative Langerhans cell histiocytosis (ND-LCH) is a potentially devastating complication of LCH. We analyzed the natural history and the long-term outcome of patients with ND-LCH enrolled in the Italian LCH registry. ND-LCH was diagnosed in 63 of 637 patients with LCH (10%). Overall, at ND-LCH diagnosis 60% (38/63) patients were asymptomatic, 24% (15/63) had mild clinical manifestations including abnormal neurological examination and/or evoked potentials, and 16% (10/63) had overt symptoms. Brain magnetic resonance imaging (MRI) showed progressive structural changes in 13 of 63 (21%) patients over a median time of 1.5 years. Clinical ND-LCH developed after a median of 2.5 years since ND-LCH diagnosis. Thirty of 63 patients (17 pauci-symptomatic, 11 symptomatic, two asymptomatic but with severe brain MRI) received treatment, and 17 of 30 (57%) were stable or improved at the last follow-up). Thirty-three of 63 patients (mostly asymptomatic) were not treated and 31 of 33 (94%) remained stable through follow-up. At univariable analysis, the risk of developing overt clinical symptoms increased with LCH reactivations (odds ratio [OR]=6.40; P=0.018), severe brain MRI abnormalities at ND-LCH diagnosis (OR=10.40; P<0.001), and MRI findings worsening during follow-up (OR=10.25; P=0.001). The association of overt neurodegeneration with reactivations and MRI findings worsening was confirmed at multivariable analysis (OR=8.15; P=0.040; and OR=7.31; P=0.034, respectively). In conclusion, asymptomatic patients presenting with mild radioneuroimaging lesions at ND-LCH onset remained stable during follow-up; conversely, a history of LCH reactivation and worsening of brain MRI findings were associated with the appearance of overt clinical symptoms. These results may lay the basis for patients selection for treatment and different monitoring strategies.

Epilepsy with myoclonic-atonic seizures, formerly myoclonic-astatic epilepsy or Doose syndrome, accounts for 1-2.2% of childhood-onset epilepsies. We investigated genetic determinants, long-term clinical outcomes and prognostic indicators in a large cohort using homogeneous inclusion criteria. We studied 60 patients (26.7% female), mean age 14.5 years (±9.1, range 3.2-41), followed between 1986 and 2024 at two paediatric neurology centres. Average follow-up was 11.7 years. Inclusion criteria were seizure onset between 6 months and 8 years, generalized 2-6 Hz spike-wave discharges and video-EEG documented myoclonic-atonic, myoclonic seizures or both. We analysed clinical, EEG, neuroimaging, neuropsychological and genetic data obtained with next-generation sequencing. We used χ² test, t-test, Log-rank test, Cox regression, population-averaged logistic models and Benjamini-Yekutieli procedure to identify predictors of seizure outcome, intellectual disability and other neurodevelopmental comorbidities. We observed myoclonic-atonic seizures in 55/60 (91.7%), tonic-vibratory seizures in 44/60 (73.4%), absence seizures in 30/60 (50%), myoclonic seizures without post-myoclonic atonia in 25/60 (42%) and non-convulsive status epilepticus in 13/60 (21.7%). A 'stormy' onset occurred in 26/60 patients (43.3%). The most effective drugs were valproate, ethosuximide, benzodiazepines and phenobarbital, used in different combinations, whereas the newer drugs offered no benefit. Long-term outcomes were variable. Thirty-seven patients (61.7%) achieved seizure freedom after 5.1 years on average. We observed drug resistance in 23/60 patients (38.3%) and intellectual disability in 35/60 (58.3%). One adult patient died (mortality rate 1.80/1000-person-years). Attention deficit hyperactivity disorder was the most common comorbidity (24/60, 40%). 'Stormy' onset did not predict a worse prognosis. Global developmental delay at epilepsy onset was associated with drug resistance (P = 0.004, Q = 0.064) and with intellectual disability (P = 0.003, Q = 0.048). We found pathogenic variants in 15/39 (38.5%) patients undergoing next-generation sequencing, including four genes novel for this syndrome (KMT2E; POGZ; SHANK3; YWHAG), with exome sequencing yielding higher diagnostic rates than gene panels. Epilepsy with myoclonic-atonic seizures is a complex syndrome with diverse genetic causes and variable seizure severity and outcomes. Our findings expand its genetic landscape and highlight the prognostic value of prompt overall neurodevelopmental assessment at clinical onset. Whole exome sequencing should be prioritized for early diagnosis and counselling.

OBJECTIVE:To study the current practice of epilepsy surgery in Italy and the relative impact of coronavirus disease 2019 (COVID-19) pandemic on it. METHODS:We launched a survey through the Italian National Virtual Epilepsy Institute, to identify centers with epilepsy surgery programs and collect data on the current preoperative and surgical practices. We reported changes in surgical volumes and complications and seizure outcomes between 2018 and 2022, that is, before and after the COVID-19 pandemic in Italy. RESULTS:A total of 21 of the 26 surveyed centers (80.7%) responded. Eleven centers (52.4%) reported having an established epilepsy surgery program, with most performing complex procedures, such as multilobar, disconnective, and hemispheric interventions. However, only a few carry out minimally invasive surgeries. Presurgical evaluation protocols vary across centers, but in keeping with international standards. Globally, 618 surgeries were performed in children and 621 in adults (total 1239) between 2018 and 2022. The most frequent type of surgery was unilobar extratemporal lobectomy for children (38.7%, p < 0.0001) and unilobar temporal lobectomy for adults (63.3%, p < 0.0001). Hemispheric surgeries were more frequent in children than in adults (11.5% vs 2.1%, p = 0.001), whereas interventions in unrevealing magnetic resonance (MRI) cases were more frequent in adults than in children (p = 0.030). At the onset of COVID-19outbreak in Italy (March 2020), we observed a significant decrease in the total number of operations compared to 2019, especially for hemispheric interventions (p = 0.027). Surgical volumes resumed in 2021, particularly for temporal lobe epilepsies and in adult cohorts. Surgical complications increased significantly in 2020 (Incidence Rate Ratio [IRR] = 13.13), whereas seizure outcome did not change significantly between 2018 and 2022. SIGNIFICANCE:Advanced pre- and postsurgical evaluation protocols are currently implemented across Italy, with a great variability between centers. Starting in 2021, epilepsy surgery volumes have regained their pre-pandemic levels, albeit with a slight loss of complexity, whereas seizure outcome has remained stable.

OBJECTIVE:This study was undertaken to prospectively assess the frequency and type of psychiatric disorders (PDs) in pediatric surgical candidates and evaluate the effects of epilepsy surgery on their psychopathological profile. METHODS:This is a prospective controlled study. Psychopathology was assessed using both diagnostic interviews and questionnaires completed by clinicians, parents, and whenever possible, patients, at baseline (T0) and 1 year after surgery in operated patients (T1) and 1 year after the first evaluation in a control group of nonoperated patients (T1). A "global assessment measure" was developed to integrate the results of the interviews, and the questionnaires were administered to multiple informants, at both T0 and T1. Descriptive statistics and multivariable analyses were performed for all outcomes. An ordinal logistic regression model was estimated to analyze the correlation between surgical treatment and possible changes in psychopathology at T1. RESULTS:At T0, 103 children (42 females, mean age at first evaluation = 9.5 ± 3.92 years) with lesional epilepsy were included in the study. Thirty-two patients (31.07%) had at least one PD, and 17 (16.5%) had more than one PD of any type. Sixty-two (60.2%) of 103 patients were enrolled for the T1 phase of the study, of whom 39 underwent epilepsy surgery. The ordinal logistic model revealed that patients who underwent surgery and achieved Engel class I outcome were 17.57 times (p = .047) more likely to experience improvement in their psychopathological profile than those who were not operated on and continued to experience seizures. SIGNIFICANCE:This prospective controlled study demonstrates a high prevalence of PD in pediatric surgical candidates and a correlation between successful surgery and reduced PD burden. An integrated approach encompassing diagnostic interviews and questionnaires, and accounting for potential disagreement between multiple informants, is essential for carefully assessing psychiatric comorbidities in children with drug-resistant seizures.

Stereo-EEG is not just a diagnostic examination but a complex methodology, requiring an accurate synthesis of many data (anatomical, clinical, neurophysiological, cognitive, metabolic, and genetic). The implantation scheme is decided based on a hypothesis (or hypotheses) of epileptogenic zone localization. Subsequently, intracerebral electrical stimulation is used to define the extent of highly functional cortical regions and to reproduce the clinical symptoms and signs associated with seizures. Finally, stereo-EEG-guided thermocoagulation is used, with the dual purpose of stopping/reducing the seizures and determining the prognosis of possible resective (curative) surgery. The centers in Italy that use stereo-EEG derive from the French school of Bancaud and Talairach. Nevertheless, each one has interpreted, on the basis of its own specificity and talent, a new methodology and philosophy of implantation. The present work presents the state of the art of stereo-EEG use in Italy, with detail of the stereo-EEG program of the Munari center in Milano, as well as those of Florence, Bologna and Rome.