Network-based biomarkers in background electroencephalography in childhood epilepsies – A scoping review and narrative synthesis

Background Brain network analysis is an emerging field of research that could lead to the development, testing and validation of novel biomarkers for epilepsy. This could shorten the diagnostic uncertainty period, improve treatment, decrease seizure risk and lead to better management. This scoping review summarises the current state of electroencephalogram (EEG)-based network abnormalities for childhood epilepsies. The review assesses the overall robustness, potential generalizability, strengths, and limitations of the methodological frameworks of the identified research studies. Methods PRISMA guidelines for Scoping Reviews and the PICO framework was used to guide this review. Studies that evaluated candidate network-based features from EEG in children were retrieved from four international indexing databases (Cochrane Central / Embase / Medline / PsycINFO). Each selected study design, intervention characteristics, methodological design, potential limitations, and key findings were analysed. Results Of 2,959 studies retrieved nine were included. Studies used a group-level based comparison (e.g. based on a statistical test) or a classification-based method (e.g. based on a statistical model, such as a decision tree). A common limitation was the small sample-sizes (limiting further subgroup or confounder analysis) and the overall heterogeneity in epilepsy syndromes and age groups. Conclusion The heterogeneity of included studies (e.g. study design, statistical framework, outcome metrics) highlights the need for future studies to adhere to standardized frameworks (e.g. STARD) in order to develop standardized and robust methodologies. This would enable rigorous comparisons between studies, which is critical in assessing the potential of network-based approaches in developing novel biomarkers for childhood epilepsies. ### Competing Interest Statement KM is an employee of Neuronostics; WW and JT are co-founders, directors and share-holders of Neuronostics. RS holds joint grants with the co-founders of Neuronostics and is a member of the Neuronostics advisory board. Further, RS has received Honoria, institutional and research support from LivaNova, UCB, Eisai, Veriton Pharma, Bial, Angelini, UnEEG and Jazz/GW pharma outside the submitted work. He holds grants from NIHR AI, SBRI and other funding bodies all outside this work. LJ and AW declare no competing interests. ### Funding Statement This scoping review was funded with support from SBRI Healthcare: SBRIH23P1016 and UKRI (EPSRC): EP/T027703/1. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes 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 All data produced in the present work are contained in the manuscript