Paediatric drug-resistant epilepsy (DRE) is associated with IQ deficits only partially explained by clinical seizure variables (for example, age of onset, seizure burden, seizure location). Given that intelligence depends on efficient large-scale brain networks, structural connectomics provides a complementary mechanistic framework for explaining residual IQ variance. We tested whether brain-network architecture explains additional IQ variance using global and network-averaged graph-theoretic metrics derived from streamline-count weighted diffusion MRI connectomes. Seventy-one children with DRE (50 focal epilepsy; 21 multifocal epilepsy) and 15 control participants underwent diffusion and T1-weighted MRI. For each participant, a 253 × 253 structural connectome was constructed, edge weights were defined as the number of streamlines, and graph metrics were computed using the Brain Connectivity Toolbox. Nodal metrics were averaged within Yeo's seven functional networks plus a Subcortical network. Associations with IQ were examined using correlations and general linear models (single-network and eight-predictor models). Finally, mediation analyses tested whether network metrics explained IQ differences between controls and children with DRE. Global metrics were not associated with IQ (all p > 0.05). Regionally, higher Salience-network betweenness centrality showed a nominal negative association with IQ in the multifocal subgroup (p = 0.040*, adjusted R2 = 0.142). In the eight-network GLM, higher nodal efficiency within the Default Mode Network (DMN) was positively associated with IQ (B = 122.406, p = .013), whereas higher nodal efficiency within the Subcortical Network was negatively associated with IQ (B = -51.942, p = .012). These regional associations did not survive Bonferroni correction. Exploratory mediation analyses suggested that opposing DMN and Subcortical Network effects partially accounted for the observed group difference in IQ. These findings are hypothesis-generating, as the regional associations with IQ were nominal and did not survive family-wise correction. Nevertheless, the mediation effects survived correction, highlighting opposing regional, rather than global, network alterations as candidate correlates of IQ variability in paediatric DRE.

Hemispherotomy is an established treatment for children with drug-resistant epilepsy. Recent reports have suggested a superiority of outcomes with the vertical approach compared to the traditional lateral approach. This study investigated whether an experienced epilepsy surgeon can safely transition from lateral peri-Sylvian to vertical parasagittal hemispherotomy, through evaluation of postoperative seizure freedom and associated outcomes. Thirty-six patients who underwent hemispherotomy by a single surgeon between 2016 and 2025 were analysed, 23 lateral peri-Sylvian and 13 vertical parasagittal. Pre-, peri- and postoperative findings were compared across the two techniques, with Pearson’s chi-squared, Fisher’s exact and Mann-Whitney U tests utilised where appropriate to detect significant differences. Patients with 1-year postoperative follow-up were split into chronological epochs. A binary logistic regression model compared seizure freedom by epoch whilst controlling for factors shown to predict seizure freedom. 90.9

INTRODUCTION:Epilepsy affects 65 million people globally, with drug-resistant epilepsy (DRE) developing in 30% of patients. Neuromodulation therapies, such as deep brain stimulation (DBS), responsive neurostimulation (RNS), and vagus nerve stimulation (VNS) are attractive treatment options, but assessing efficacy is time consuming. Predictive biomarkers of treatment response may expedite assessment and pave the way for closed-loop strategies that optimize outcomes. This systematic review identifies scalp and intracranial electroencephalography (EEG)-derived biomarkers associated with clinical efficacy in invasive neuromodulation for DRE and explores the impact of preprocessing and methodologic variations on biomarker efficacy. MATERIALS AND METHODS:A systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, searching PubMed from 2004 to 2025 for human studies on EEG biomarkers post invasive neuromodulation for people with DRE. Inclusion criteria required ≥four participants, single neuromodulation modalities, and EEG-based measures linked to seizure outcomes. Exclusion criteria eliminated multimodal therapies, craniotomies, and non-English studies. Owing to heterogeneity, qualitative synthesis identified trends, supplemented by an exploratory logistic regression analysis assessing the preprocessing, methodologic, and biomarker type (node-level, edge-level, graph-theory metrics) impacts on biomarker efficacy. RESULTS:This review included 30 studies (2005-2024), covering DBS (n = 8), RNS (n = 7), and VNS (n = 15). Ten of 30 studies were of focal DRE; three of 30 studies were generalized DRE, and half of the included studies did not specify whether participants had focal or generalized epilepsy. Biomarkers spanned node-level (eg, interictal epileptiform discharges, spectral power, n = 14), edge-level (eg, phase-amplitude coupling, coherence, n = 13), and graph-theory metrics (n = 3). Key findings were as follows: 1) interictal epileptiform discharge (IED) rate reductions commonly correlate with seizure frequency reduction; 2) short-term changes in the aperiodic parameters appear to be predictive of longer-term clinical outcome; and 3) reduced synchronization is repeatedly associated with improved seizure outcomes across RNS, VNS, and some DBS contexts. Four studies reported early measures (intraoperative or ≤six months post implant) that predicted longer-term seizure outcomes. Exploratory logistic regression suggested nonsignificant trends favoring larger sample sizes, higher sampling rates, data normalization, and edge-level metrics; use of artifact-removal algorithms tended to reduce the likelihood of a reported significant association. All regression estimates were imprecise (nonsignificant, wide 95% CIs) CONCLUSION: In conclusion, EEG-derived biomarkers, particularly IEDs, aperiodic measures, and synchronization measures, show promise for predicting neuromodulation efficacy in DRE. Nonsignificant trends revealed through logistic regression analysis suggest that methodologic and preprocessing variations may influence biomarker predictive efficacy. We would recommend more comprehensive reporting of the signal processing protocols and biomarker performance to enable more robust causal inference.

OBJECTIVE:The thalamus is a key hub in seizure propagation, and its nuclei are emerging targets for neuromodulation. However, the contributions of individual nuclei to epileptic networks remain unclear, particularly in children, who are less studied than adults. We investigated structural and functional thalamic alterations across different pediatric focal epilepsies and their associations with clinical features and postsurgical outcomes. METHODS:We retrospectively studied children with temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and posterior quadrant epilepsy (PQE) and healthy controls. The thalamus was segmented into four nuclei groups (anterior, lateral, medial, pulvinar) using the THOMAS pipeline on T1-weighted magnetic resonance imaging (MRI) to estimate volumes. Functional connectivity was assessed with functional MRI using node strength, capturing total thalamic connectivity across the brain. We compared patients with controls and evaluated associations with hippocampal sclerosis, history of focal to bilateral tonic-clonic seizures, and postsurgical seizure freedom. RESULTS:Among 136 children with focal epilepsy (81 TLE, 36 FLE, 19 PQE; mean age = 13.0 years) and 70 controls (mean age = 13.4 years), ipsilateral thalamic volume reductions were observed in the following: anterior and lateral nuclei and pulvinar in TLE, anterior and lateral nuclei in FLE, and pulvinar in PQE (Cohen d = .52-.70, all Bonferroni-corrected p < .05). In contrast, medial nuclei volume increase was associated with history of seizure generalization (partial η2 = .06). Functional connectivity was bilaterally reduced across epilepsy groups (partial η2 = .03), most consistently in the pulvinar (Cohen d = .25-.68). Within TLE, hippocampal sclerosis was associated with increased anterior nucleus connectivity (partial η2 = .17), distinguishing it from other pathologies. SIGNIFICANCE:We demonstrate both shared and syndrome-specific thalamic abnormalities in pediatric focal epilepsy. Common patterns included ipsilateral thalamic volume loss, indicating cumulative disease burden, and reduced bilateral functional connectivity, particularly in the pulvinar, likely reflecting thalamocortical decoupling. These findings advance understanding of seizure networks beyond the epileptogenic zone and provide a foundation for personalized thalamic-targeted neuromodulation strategies.

Background: Major depressive disorder remains a leading cause of disability. While subgenual cingulate cortex (sgCC) deep brain stimulation (DBS) shows promise for medically refractory depression, clinical outcomes have been heterogeneous, suggesting that individual differences in neural circuitry engagement may critically influence therapeutic efficacy. We aimed to define the electrophysiological signatures of sgCC efferent connectivity using single-pulse electrical stimulation (SPES) with intracranial stereo-EEG (sEEG) to inform rational targeting and physiological biomarkers for sgCC-DBS. Methods: In four patients undergoing clinically indicated sEEG for seizure mapping, SPES was delivered through sgCC pairs, while distributed brain stimulation-evoked potentials (BSEPs) were recorded across cortical and subcortical sites. Responses were characterized using Canonical Response Parameterization to extract reproducible waveforms and per-trial reliability. Results: sgCC stimulation elicited reproducible, spatially organized BSEPs across frontal, limbic, and paralimbic networks, aligning with known anatomical pathways. Frontal recruitment featured robust, lateralized orbitofrontal activation favoring the ipsilateral central, medial OFC and bilateral ventromedial prefrontal responses. Limbic effects demonstrated bilateral cingulate activation with stronger ipsilateral recruitment and lateralized amygdala and hippocampal responses. Paralimbic engagement included insular responses with subject-specific anterior predominance and bi-hemispheric temporal-polar slow-wave deflections. Conclusion: These findings provide direct electrophysiological evidence of distributed, lateralized sgCC divergent network connectivity in the human brain, offering physiologic confirmation of its role in affective circuitry. The observed topography and laterality have direct applications for sgCC-DBS targeting and implicate BSEP signatures as candidate biomarkers to guide patient-specific therapy.

OBJECTIVE:Determining patient-specific thalamic connectivity alterations may be an important step toward personalized surgical and neuromodulation strategies, but no data are available to support this concept in pediatric cohorts. This study investigated thalamocortical structural connectivity profiles in children with focal-onset epilepsy of different seizure-onset zones. METHODS:This neuroimaging, case-control study compared structural connectivity of four thalamic nuclei (anteroventral [AV], centromedian [CM], mediodorsal [MDPf], and pulvinar [PUL]) between 81 children who underwent surgery for focal-onset epilepsy (median age = 12.2 years) and 63 controls (median age = 12.8 years). Using preoperative 3-Tesla diffusion magnetic resonance imaging (dMRI), brain (Lausanne) and thalamic (THOMAS) parcellations combined with tractography generated structural connectomes based on streamline counts. Connectivity strength of each thalamic nucleus was calculated by summing the weights of each connecting brain region. RESULTS:Patients had higher structural connectivity strengths than controls of the thalamic nuclei (effect size (η2ₚ) = .072; p = .015), differentially involving nucleus regions, but there was no overall difference in nucleus volumes (η2ₚ < .000; p = .968). When comparing patient groups defined by seizure-onset zones, it emerged that reduced AV connectivity strength was specific to the hippocampal sclerosis group, whereas CM, MDPf, and PUL connectivity was similarly high in all the patient groups, including those with frontal or temporal lobe epilepsy. Patients who were seizure-free after surgery had a lower ipsilateral and a higher contralateral connectivity strength (η2ₚ = .111; p = .005) and volumes (η2ₚ = .073; p = .025) of thalamic nuclei compared to those who were not. SIGNIFICANCE:This study provides unique data suggesting that different pediatric focal epilepsies have distinct structural thalamocortical connectivity and volumetric profiles. The structural connectivity and volumetric asymmetries of the thalami have an association with postoperative seizure freedom. More studies are required to further understand the thalamic connectivity signatures that may have implications for precision surgical planning and neuromodulation targeting for focal-onset epilepsy.

BACKGROUND AND OBJECTIVES:Chiari 1 malformation (CM1) is a common MRI finding and a frequent reason for neurosurgical consultation. Although many studies have investigated surgical outcomes for patients with CM1, outcomes for those treated without surgery have been less frequently reported. The UK Chiari 1 Study reports the quality of life of adults and children with CM1 treated without surgery, 12 months after the first neurosurgical clinic visit. METHODS:The UK Chiari 1 Study was a prospective, multicenter cohort study of adults (≥16 years) and children (<16 years) with CM1. This was an observational study that did not alter the course of clinical care. Symptoms and quality-of-life data (using Short-Form 36 in adults and the Pediatric Quality of Life Inventory™ in children) were collected at baseline and 12 months after the first clinical review for all participants. RESULTS:One hundred ninety-two patients with CM1 (146 females; 148 adults) were studied at baseline, and 113 patients with CM1 treated without surgery were studied at a 12-month follow-up. Baseline quality-of-life scores in the study cohort were significantly lower in every domain compared with normative control data, in both adults and children. There were no decreases in quality-of-life subscores after 12 months in this cohort of adults and children with CM1 treated without surgery. Social functioning ( t = -40, P < .001) and bodily pain (t = -2.9; P = .03) Short-Form 36 scores showed improvements at 12 months in adult patients treated without surgery. CONCLUSION:This study demonstrates the stability of quality-of-life domains in adults and children with CM1 after 12 months who have been managed without surgery. Further studies are required to understand the determinants of poor quality of life in patients with CM1 and to investigate interventions for improving quality of life. There is a further need for robust comparison of surgical and nonsurgical management for patients with CM1.

Epilepsy associated with periventricular nodular heterotopia (PVNH) frequently begins in childhood and often proves refractory to medication. Surgical management is challenging, as lesions are frequently deep-seated or bilateral, and seizure onset often involves networks extending beyond the heterotopic tissue itself, with the precise contribution of the nodules varying between patients. This systematic review synthesises all available evidence on neurosurgical and invasive interventions for childhood-onset PVNH-associated epilepsy, focusing on outcomes and prognostic factors. We conducted a PRISMA 2020-compliant systematic review searching PubMed/MEDLINE, Scopus, and Web of Science from inception to 13 December 2025. Eligible studies reported neurosurgical interventions in patients with MRI- or histopathology-confirmed PVNH whose epilepsy began before age 18, with outcomes reported using Engel or ILAE classification. Two reviewers independently screened and extracted data. Methodological quality was appraised using GRADE. Findings were synthesised narratively due to the inherent heterogeneity of the included studies. Thirty studies comprising 134 patients met our inclusion criteria. Excellent outcomes, defined as seizure freedom or auras only, were achieved in 50.7% (n = 68), with 76.9% (n = 103) experiencing meaningful benefit, defined as at least a 50% reduction in seizure frequency. Outcomes were better in unilateral than bilateral PVNH (75.9%vs 33.8%, p < 0.001) and with complete rather than incomplete nodule removal (72.9%vs 25.0%, p < 0.001). Permanent morbidity was 10.4% (n = 14), predominantly visual field deficits. Invasive EEG-guided approaches can achieve seizure freedom in around half of children with PVNH-related epilepsy, with outcomes strongly predicted by laterality. As with all subgroup comparisons in this review, reported p-values reflect effect size across pooled retrospective cohorts rather than formal hypothesis testing. Minimally invasive ablation appears effective and safe, while neuromodulation offers palliation where curative treatment is not feasible. Evidence remains limited by retrospective study designs and small sample sizes, and prospective multicentre data are needed.

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

Introduction This study aimed to gather UK clinician, patient, and carer perspectives on vagus nerve stimulation (VNS) and deep brain stimulation (DBS) to inform the design of clinical trials comparing these treatments for drug-resistant epilepsy (DRE). Research Question To assess stakeholder views on these treatments and their willingness to participate in a clinical trial comparing VNS and DBS for DRE. Methods Two surveys were conducted: one for clinicians in neurology, neurophysiology, and neurosurgery, and another for patients/carers. The estimated response rates were 2.7% and 0.008% for the surveys respectively. Results Among the 32 clinician responses all agreed VNS has a role in treating DRE, as did 94% for DBS. While 84% felt VNS had sufficient evidence for routine use, only 23% said the same for DBS. Median minimum age for treatment consideration was 5 years for VNS and 8 years for DBS. Clinicians agreed on the proposed trial's scientific validity (median Likert score 4/5) and interest in efficacy comparison (5/5); 72% would refer patients for the trial. Of the 38 patient/carer responses, 13% had VNS. Around one-third would consider VNS (32%) or DBS (34%). Concerns included procedure anxiety, side effects, and battery changes. While 53% were willing to enter the proposed trial, 84% preferred to choose their treatment.Key outcomes identified included seizure reduction, seizure freedom, quality of life, and SUDEP risk. Discussion and Conclusion Clinician, patient, and carer insights highlight the need for robust evidence on VNS and DBS efficacy. These findings will guide future trials in managing DRE.

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.

INTRODUCTION:Deep Brain Stimulation (DBS) of the thalamus for drug-resistant epilepsy (DRE) is an emerging treatment modality. This systematic review and meta-analysis sought to evaluate the efficacy of stimulating different targets within the thalamus. METHODS:A systematic search of four databases was conducted. Rates for overall seizure reduction (SR), responder rate (RR ≥50 % SR), and seizure freedom (SF) were evaluated at a minimum time point of 12 months post-stimulation commencement in the anterior (ANT) and centro-median (CMN) thalamic nuclei. Subgroup analyses for a minimum 24 months follow up, sensitivity analyses, and funnel plots to assess for publication bias were also performed. Risk of bias was assessed using the ROBINS-I tool. RESULTS:Fourty-nine articles met the inclusion criteria. The mean seizure reduction (SR) across 21 studies was 62.31 % (95 % CI: 55.99-68.62, p < 0.01). Specifically, SR was 64.28 % for ANT (95 % CI: 57.55-71.01, p < 0.01) and 69.11 % for CMN (95 % CI: 58.14-80.09, p < 0.01). Meta-analyses of 41 ANT studies and 12 CMN studies reported a response rate (RR) of 61.51 % (95 % CI: 54.11-68.9, p < 0.01) and 69.09 % (95 % CI: 54.01-84.16, p < 0.01), respectively. Overall seizure freedom (SF) was 3.57 % % for ANT (95 % CI: 1.86-5.28, p = 0.45) and 1.32 % for CMN(95 % CI: 0-4.45, p = 0.81). For ANT, RR was 67.63 % (95 % CI: 61.04-74.23) for follow-up periods longer than 24 months, and 44.05 % (95 % CI: 26.73-61.38) for periods shorter than 24 months. The SF rate for ANT was 3 % (95 % CI: 1-4 %) for follow-up under 12 months. For CMN, RR was 70 % (95 % CI: 53-87 %) for periods over 24 months, and 68 % (95 % CI: 31-100 %) for periods under 24 months. The SF rate for CMN was 1 % (95 % CI: 0-4 %) for periods under 12 months. There was no strong evidence of publication bias based on funnel plot analysis, and results were consistent across sensitivity analyses. Insufficient data precluded meta-analysis for other nuclei. CONCLUSION:These findings demonstrate efficacy of ANT and CMN DBS for patients with DRE, defined by responder rate and seizure reduction. Further research is required to optimize patient selection, predict individual response, and assess non-seizure related outcomes.

Cortico-cortical evoked potentials (CCEPs) are an active electrophysiological technique used during intracranial electroencephalography to evaluate the effective connectivity and influence of therapeutic stimulation between distinct cortical regions and pinpoint epileptogenic zones (EZs) in patients with epilepsy. Various methodologies have been implemented to analyze CCEPs and characterize the epileptogenic networks for EZ localization. Despite its promise, their interpretation remains challenging due to the large volumes of spatially and temporally complex data generated. Early studies focused largely on qualitative descriptors and predefined, semi-quantitative features such as waveform morphology and peak latencies. However, these methods are limited by the significant heterogeneity in CCEP waveform conformations across patients and cortical regions. The specific technique used for extraction of features, such as the spectral band power and root mean squared values, remains open to empirical refinement, as does choice of appropriate latency windows, with no consensus reached regarding the optimal approach. Graph theoretical metrics such as degree centrality, betweenness centrality, and clustering coefficients can provide a rich representation of epileptogenic network connectivity. However, these metrics are often abstract and difficult to interpret in a clinical setting or to the non-expert, and their neuroscientific substrates remains poorly understood. The lack of standardization in stimulation protocol and data-processing pipelines has further contributed to inconsistency in reported findings. Emerging machine learning approaches have been increasingly applied to CCEP data, offering a more data-driven and potentially generalizable way to identify electrophysiological biomarkers of the epileptogenic effective connectivity. In this article, we discuss qualitative, quantitative, and spectral features; network-analytical metrics; and more recently, data driven methodologies aimed at improving the interpretability and clinical utility of CCEP data.

Epilepsy is an archetypal brain network disorder characterized by recurrent seizures and associated psychological, cognitive and behavioural sequelae. Progressive brain network dysfunction may contribute to poorer outcomes following treatment, but this has never been tested in humans. In this structural connectomics pilot study, we assess whether there is progressive brain network dysfunction in a cohort of 23 children undergoing repeated multi-shell diffusion tensor imaging as part of their pre-surgical evaluation of focal epilepsy prior to epilepsy surgery. We analyse global and nodal graph metrics and thalamocortical connectivity, comparing the longitudinal changes to a cross-sectional cohort of 57 healthy controls. We identify no robust longitudinal changes in global or nodal network properties over a median of 1.15 years between scans. We also do not identify robust longitudinal changes in thalamic connectivity between scans. On sensitivity analyses, we identify increases in weighted degree at higher scales of brain parcellation and a decrease in the proportion of nodes with a low participation coefficient, suggesting progressive increases in intermodular connections. These findings of no or subtle structural longitudinal brain network changes over a relatively short timeframe indicate that either there are no progressive structural brain network changes over time in epilepsy or the changes appear over longer timescales. Larger studies with longer timeframes between scans may help clarify these findings.

Understanding healthy human brain function is crucial to identify and map pathological tissue within it. Whilst previous studies have mapped intracranial EEG (icEEG) from non-epileptogenic brain regions, they often neglect age and sex effects. Further, they are limited by small sample sizes due to the modality’s invasive nature. This study substantially expands the subject pool compared to existing literature, to create a multi-centre, normative map of brain activity which considers the effects of age, sex and recording hospital. Using interictal icEEG recordings from n = 502 subjects across 15 centres, we constructed a normative map of non-pathological brain activity by regressing age and sex on relative band power in five frequency bands. A linear mixed model was implemented to account for the hospital effect. Variable importance was assessed using standard statistical measures, and regression coefficients (and their standard errors) were analysed at both whole-brain and regional scales. Recording hospital significantly impacted normative icEEG maps in all frequency bands, and age was a more influential predictor of band power than sex. The age effect varied by frequency band, but no spatial patterns were observed at the region-specific level. Certainty about regression coefficients was also frequency band specific and moderately impacted by sample size. The concept of a normative map is well-established in neuroscience research and particularly relevant to the icEEG modality, which does not allow healthy control baselines. Our key results regarding the hospital site and age effect guide future work utilising normative maps in icEEG.

Objectives Computer-assisted planning (CAP) allows faster SEEG planning and improves grey matter sampling, orthogonal drilling angles to the skull, reduces risk scores and minimises intracerebral electrode length. Incorporating prior SEEG trajectories enhances CAP planning, refining output with centre-specific practices. This study significantly expands on the previous work, compares priors libraries between two centres, and describes differences between SEEG in adults and children in these centres. Methods 98 adults and 61 children who underwent SEEG implantation as part of epilepsy surgery investigations were included. Priors libraries were created for each population, clustered by target regions and subdivided by cortical approaches. The libraries were coregistered and quantitatively and qualitatively compared. Results The average number of implanted electrodes per patient was higher in paediatric patients than adults (13.6 vs 8.0). Paediatric implantations focused more on the insula than adult implantations (38.0 % vs 13.5 %), with similar proportions of electrodes implanted in the temporal and parietal lobes, and a higher proportion of adult electrodes in the frontal and orbitofrontal regions (40.6 % vs 24.0 %). Correspondence between the priors libraries was high. We present an example of a complex insular implantation planned with paediatric spatial priors and illustrate resultant SEEG recordings. Discussion The use of centre-specific spatial priors allows the incorporation of surgeon-specific and unit-specific preferences into automated planning. We compare implantation styles between a paediatric and an adult centre, discussing similarities and differences. This tool allows centres to compare practice and represents an effective way to analyse implantation strategies that is agnostic to method of implantation.

BACKGROUND:It is unclear whether the underutilisation of the UK Children's Epilepsy Surgery Service (CESS) can be attributed to regional referral differences. This study develops a mapping tool to visualise CESS referrals, identifying any regional disparities and exploring the relationship between referrals and deprivation. Mapping posterior urethral valve (PUV) surgery referrals demonstrates the utility of this model for other health conditions. METHODS:Accepted CESS referrals within the catchment area of one centre between April 2017 and March 2022 were recorded in the Orion registry (n = 291). PUV referrals to one tertiary centre in the same region, between January 2013 and June 2023, were mapped using the same model (n = 212). RESULTS:Referral incidences per integrated care board (ICB) were calculated and visualised with choropleth maps. Pearson's correlation coefficient identified any relationship between referral incidence and population-weighted ICB deprivation scores. CESS referral incidence ranged from 30.06 to 39.9 per million under-18s. PUV referral incidence ranged from 12.0 to 46.9 per million under-18 males, yielding a statistically significant difference in variability between the two groups (p = 0.04). Referral incidence was independent of deprivation (p = 0.29 and p = 0.13, respectively). CONCLUSION:There is equity in CESS referrals within the region. The mapping tool is widely applicable, providing visually representable referral data without being patient-identifiable.

This study aimed to identify factors influencing brain volumes at term-equivalent age (TEA) in preterm infants with post-haemorrhagic ventricular dilatation (PHVD) and explore how these volumes, and other factors, correlate with neurodevelopmental outcome (NDO). A retrospective cohort study of 84 infants with PHVD managed on a standardised pathway at a single centre between 2012 and 2020. Brain volumes were measured from TEA MRI scans in 31 infants. NDO was assessed at one and two years. Primary analyses included the 31 infants with measured brain volumes. Sensitivity analysis included all 84 infants using multiple imputation for missing brain volumes. Sepsis (-12.75mL, 95 Understanding associations of independent variables with NDO is essential to evaluate the impact of neurosurgical interventions. - Among infants with post-haemorrhagic ventricular dilatation: - Sepsis was associated with smaller cerebellar volumes at term-equivalent age. - Intubation and inotrope use were associated with smaller deep grey matter volumes at term-equivalent age. - Larger deep grey matter volume at term-equivalent age was associated with improved neurodevelopmental outcome at two years.

Introduction Temporal encephalocoeles are a recognised cause of drug-resistant temporal lobe epilepsy (TLE), with uncertain associations to epileptogenesis and an unclear optimal management approach. Operative management, particularly resective temporal lobe surgery, has been proposed, but outcomes and decision-making criteria remain debated. This study aims to evaluate the outcomes of surgically and non-surgically managed patients with temporal encephalocoeles in the context of drug-resistant TLE, focusing on seizure freedom rates, postoperative complications and factors influencing management decisions. Methods A retrospective, single-centre study was conducted based on all adult TLE patients with temporal encephalocoeles encountered between March 2017 and August 2023. Patients were classified into three groups: those discussed at an epilepsy surgery multidisciplinary team (MDT) meeting and managed surgically (surgical group), those discussed at an MDT and managed non-surgically (non-surgical group) and those radiologically identified by reporting neuroradiologists but not discussed at MDT (radiologically diagnosed group). Clinical, electrophysiological, radiological and surgical data were compared across the groups, including radiological features of raised intracranial pressure (ICP) that have been postulated as a cause for temporal encephaloceles. Results We included 24 adult patients with temporal encephalocoeles: eight in the surgical group, eight in the non-surgical group and eight in the radiologically diagnosed group. The mean age at diagnosis was 39.3 ± 13.6 years and clinical features were comparable across groups. Operative management was decided by an experienced epilepsy surgery MDT, involving resection of the anterior temporal pole with (4/8, 50 %) or without (50 %) mesial temporal structures, resulted in a seizure freedom rate of 87.5 %. In contrast, no patient in the non-surgical or radiologically diagnosed groups achieved seizure freedom (0 %). Postoperative complications included one patient who developed hydrocephalus and required a ventriculoperitoneal shunt, and another who developed a pseudomeningocoele. Radiological markers of raised ICP were broadly similar across the groups, with the exception of increased optic nerve sheath diameter in the non-surgical group (p = 0.032). Conclusion Our study demonstrates that excellent post-operative outcomes are achievable with temporal lobe resections. A standardised presurgical evaluation pathway and management protocol are essential to ensure timely identification of temporal encephalocoeles on imaging, facilitating preoperative planning and optimising surgical outcomes. CSF hydrodynamic disturbances may occur after surgery for encephaloceles and individualised evaluation is therefore crucial to select the most appropriate management approach.