Seizure cycles in paediatric epilepsy

Multiday cyclic patterns underlying the timing of seizures are well-established in adults with epilepsy and are critical to the development of seizure risk forecasting models. As cycles underpinning these models are yet to be explored in paediatric cohorts, the current study applies methods drawn from seizure risk forecasting to identify and compare multiday seizure cycles between paediatric and adult cohorts. This is followed by the first validation of personalised forecasts of seizure likelihood in a paediatric cohort. Multiday seizure cycles were extracted retrospectively from 325 (71 paediatric) electronic seizure diary users (more than 28 days of app use) with confirmed epilepsy. Cycles were grouped (k-means clustering), and seizure cycles quantified (synchronisation index), with significant cycles identified by Rayleigh test of periodicity ( p <0.05). Wilcoxon rank-sum test assessed differences in prevalence and strength of cycle groups between paediatric and adult cohorts. 34,402 seizures (paediatric: M =101, SD =103, adult: M =107, SD =156) were analysed and seizure cycles were grouped according to circadian (0.5-1.5 days), about-weekly (2-12 days), about-fortnightly (13-22 days) and about-monthly (23-32 days) periodicities. Significant cycles were identified in each cycle group, with no differences in prevalence or cycle strength between paediatric and adult cohorts for any multiday cycle group. Similar effects were observed across clinical and demographic features (sex, epilepsy-type, medication). These multiday patterns formed the basis for cycle-based estimates of seizure likelihood. Receiver operating characteristic (area under the curve: AUC) was applied and demonstrated that these seizure forecasts performed better than chance (i.e. shuffled seizure times). Multiday seizure cycles are therefore similar in paediatric and adult cohorts, and this study provides the first validation of cycle-based seizure risk forecasting models as a promising approach for paediatric epilepsy. ### Competing Interest Statement H.K., P.J.K., R.E.S., E.S.N., D.E., D.F. and M.J.C. have employment or a financial interest in Seer Medical Pty. Ltd. The remaining authors have no conflicts of interest. ### Funding Statement This research was supported by NHMRC Investigator Grant (1178220), My Seizure Gauge Grant (Epilepsy Foundation of America) and the BioMedTech Horizons 3 program (initiative of MTPConnect). Funding partners were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. ### 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: Ethics committee of St Vincent's Hospital Melbourne gave ethical approval for this work. 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 study are available upon reasonable request to the authors.