PURPOSE:The course of epilepsy in patients with tuberous sclerosis complex (TSC) is highly variable. Consistency of the epileptogenic zone is considered important in presurgical evaluation. The authors aimed to (1) assess consistency of ictal epileptogenic foci over time in patients with TSC, (2) evaluate concordance between interictal epileptiform abnormalities and ictal epileptogenic foci, and (3) identify determinants of ictal consistency. METHODS:This single-center retrospective, observational study included children with definite TSC and epilepsy with ≥2 ictal presurgical EEGs with an interval ≥1 year. In all EEGs, the regional localization of interictal and ictal epileptiform abnormalities was scored based on the EEG reports. All ictal epileptogenic foci were classified with an "ictal focus consistency score," according to one of the following subcategories: "single focus, consistent," "from unclear localization/diffuse or generalized to unifocal," "≥2 or more foci, each consistent," "≥2 foci of which at least one is consistent," "starting multifocal but at last EEG unifocal," and "multifocal changing otherwise." The primary end point was unifocal or multifocal consistency of ictal foci. The secondary end point was concordance between ictal epileptogenic foci and localization of interictal epileptiform abnormalities. The third end point involved an exploratory assessment of potential determinants of ictal consistency, including TSC variant, age at epilepsy onset, epileptic spasms, multiple seizure types, interictal multifocality, and tuber load. RESULTS:The authors included 45 patients with TSC with a median of 3 (interquartile range 2-4) ictal and 8 (interquartile range 5-10) interictal EEGs per patient. Median time between first and last ictal EEG was 28.4 months (19.0-60.3). Ictal foci were consistent over time in 11 patients (24.4%), of whom 9 had 1 consistent ictal focus. Nine other patients had a single consistent ictal focus on the first EEGs, but developed a second focus at the median age of 67.7 months. Of the 13 patients who later underwent surgery, 3 had a single focus, and only 2 of 13 had consistent ictal EEGs. The same three patients with a single focus over time were part of the seven postoperative seizure-free patients. All six nonseizure-free children had ictal multifocality. Interictal and ictal epileptogenic foci were discordant in 42 of 45 patients (93.3%). Exploratory analyses of potential determinants of ictal consistency suggested a negative association with interictal multifocality (risk ratio 0.32, 95% confidence interval 0.06-0.97, p = 0.04), which was not significant after adjustment for monitoring duration. CONCLUSIONS:Ictal epileptogenic foci are consistent in only 25% of the patients with TSC. Interictal epileptogenic foci are often discordant with ictal foci. This instability in the ictal epileptogenic focus might be explained by the presence of larger epileptogenic networks in TSC that undergo evolution over time. SIGNIFICANCE:The findings in this study could have important implications for presurgical evaluation in patients with TSC and might help to understand the cause of (late) surgical failure.

ObjectiveWe compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks.MethodsWe included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks.ResultsFewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0-29) compared to SPES-clinical (median: 10.0, range: 0-36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively rs=0.77, rs=0.70, rs=0.55, p<0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol.ConclusionsOur findings suggest that the number of effective network connections decreases, but network measures are only marginally affected.SignificanceThe primary network topology is preserved under propofol.

Background:There is limited evidence to support the currently suggested lamotrigine (LTG) therapeutic reference range of 2.5-15 mg/L for the treatment of seizures. The objective of this study was to evaluate the association of LTG plasma concentrations with the efficacy and toxicity of the treatment in patients with epilepsy. Methods:Patients whose LTG plasma concentration was measured between January 2013 and February 2022 were included. Efficacy was defined as seizure freedom for at least 6 months around the time of measured LTG concentration. Toxicity was defined as any LTG-related adverse drug effect documented in each patient's health record or when the reason for measuring the LTG concentration was toxicity. In addition, the dose-concentration relationship of LTG was assessed. Results:In total, 549 concentrations from 259 patients with epilepsy were included. The most common reasons for therapeutic drug monitoring were suspected inefficacy (39%) and pregnancy (21%). The LTG plasma concentration was not associated with efficacy (adjusted odds ratio = 0.94; 95% confidence interval, 0.85-1.04). The LTG plasma concentration was positively associated with the incidence of toxicity after adjusting for age, sex, and number of antiepileptic drugs (odds ratio = 1.11; 95% confidence interval, 1.04-1.19). The daily dose had a significant linear correlation with the LTG plasma concentration (P < 0.001). Conclusions:The LTG plasma concentration was associated with toxicity, whereas no association with efficacy was found. A reference range of 2.5-10 mg/L may be considered to decrease the risk of toxicity while maintaining similar efficacy. Therapeutic drug monitoring may be useful when LTG-related toxicity is suspected and in cases of pharmacokinetic changes (eg, pregnancy and concomitant use of interacting drugs) that can influence the LTG plasma concentration.

Objective: Intraoperative electrocorticography (ioECoG) during neurosurgery is influenced by anesthetics. In our center we stop the propofol to enable interpretation of ioECoG. We reported our clinical experience and evaluated awareness and hemodynamic changes during the propofol-free periods (PFP). Methods: We retrospectively included surgeries with paused propofol administration to record ioECoG (period: 2008-2019). Clinical reports were screened for symptoms of awareness. We compared mean arterial blood pressure (MAP; mmHg) and heart rate (HR;bpm) during PFP to baseline (ten minutes preceding PFP). An increase > 15% was defined as clinically relevant. The association between hemodynamic changes and clinical characteristics was analyzed using logistic regression models. Results: Propofol administration was paused 742 times in 352 surgeries (mean PFP duration 9 +/- 5 min). No signs of awareness were reported. MAP and HR increased > 15% in 54 and six PFPs. Five PFPs showed both MAP and HR increases. Prolonged PFP was associated with having MAP and HR increase during surgery (OR=1.18, 95%CI [1.12-1.26]). Conclusions: Signs of inadequate sedation depth were rare. MAP and HR increases were related to the length of PFP. Significance: We summarize 10 years of clinical experience with pausing propofol administration during epilepsy surgery to record ioECoG without evidence of awareness.

BACKGROUND AND OBJECTIVES:Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic method. We assessed the current evidence to use ioECoG-tailored epilepsy surgery for improving postsurgical outcome. METHODS:PubMed and Embase were searched for original studies reporting on ≥10 cases who underwent ioECoG-tailored surgery for epilepsy, with a follow-up of at least 6 months. We used a random-effects model to calculate the overall rate of patients achieving favorable seizure outcome (FSO), defined as Engel class I, ILAE class 1, or seizure-free status. Meta-regression was used to investigate potential sources of heterogeneity. We calculated the odds ratio (OR) for estimating variables on FSO:ioECoG vs non-ioECoG-tailored surgery (if included studies contained patients with non-ioECoG-tailored surgery), ioECoG-tailored epilepsy surgery in children vs adults, temporal (TL) vs extratemporal lobe (eTL), MRI-positive vs MRI-negative, and complete vs incomplete resection of tissue that generated interictal epileptiform discharges (IEDs). A Bayesian network meta-analysis was conducted for underlying pathologies. We assessed the evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS:Eighty-three studies (82 observational studies, 1 trial) comprising 3,631 patients with ioECoG-tailored surgery were included. The overall pooled rate of patients who attained FSO after ioECoG-tailored surgery was 74% (95% CI 71-77) with significant heterogeneity, which was predominantly attributed to pathologies and seizure outcome classifications. Twenty-two studies contained non-ioECoG-tailored surgeries. IoECoG-tailored surgeries reached a higher rate of FSO than non-ioECoG-tailored surgeries (OR 2.10 [95% CI 1.37-3.24]; p < 0.01; very low certainty). Complete resection of tissue that displayed IEDs in ioECoG predicted FSO better compared with incomplete resection (OR 3.04 [1.76-5.25]; p < 0.01; low certainty). We found insignificant difference in FSO after ioECoG-tailored surgery in children vs adults, TL vs eTL, or MRI-positive vs MRI-negative. The network meta-analysis showed that the odds of FSO was lower for malformations of cortical development than for tumors (OR 0.47 95% credible interval 0.25-0.87). DISCUSSION:Although limited by low-quality evidence, our meta-analysis shows a relatively good surgical outcome (74% FSO) after epilepsy surgery with ioECoG, especially in tumors, with better outcome for ioECoG-tailored surgeries in studies describing both and better outcome after complete removal of IED areas.

Dit is een bewerking van een bijdrage in Medisch Contact over inzagerecht van patiënten in hun medisch dossier dat ander taalgebruik vereist van de behandelaar.

Background Electrical stimulation therapy for epilepsy patients is applied either to the epileptogenic region or to a larger network (e.g. with deep brain stimulation).Objective/hypothesis Responses to single pulse electrical stimuli (SPES) reveal potential stimulation sites that target the epileptogenic region for cortical network stimulation therapy.Methods We applied SPES to ten epilepsy patients who underwent intracranial electrocorticography recordings for pre-surgical evaluation. We detected cortico-cortical evoked potentials (CCEPs) in response electrodes after stimulating other pairs of electrodes, revealing effective connections. We calculated event-related spectral perturbation (ERSP) plots in all response electrodes after stimulating other electrode pairs. We detected interictal epileptic discharges (IEDs) before and after each single pulse and calculated the logarithmic IED ratio.We analyzed whether power suppression in the ERSP occurred in a response electrode when connected with the stimulus pair. We analyzed whether a larger change in IED ratio was accompanied by power suppression in the response electrode or when this electrode was connected with the stimulus pair.Results We found that SPES has a neuromodulatory effect measured as: 1) the relationship of a CCEP and power suppression, 2) a larger change in IED rate when a CCEP was present, 3) a decrease in IED rate when power suppression was observed.Conclusion(s) Results suggest that stimulation in an area connected to the epileptogenic region can modulate IEDs in this region. SPES might provide a template for localizing a stimulation site outside the epileptogenic region for electrical stimulation treatment of epilepsy.Highlights ### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis project was funded by the Dutch Epilepsy Fund (NEF 17-07).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethics committee of University Medical Center Utrecht 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.YesI 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).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll code is available at [https://github.com/dvanblooijs/CCEP\_suppressionPower\_Spikes][1]. Data will be available at [openneuro.org][2] when the study is published in a peer-reviewed journal. [1]: https://github.com/dvanblooijs/CCEP_suppressionPower_Spikes [2]: http://openneuro.org

Binnenkort zal klinisch technoloog Dorien van Blooijs promoveren op corticale netwerkstimulatie als behandeling voor epilepsie. De totstandkoming van haar REC2STIM- studie heeft veel voeten in de aarde gehad, maar levert opmerkelijke inzichten en resultaten op. Daarnaast heeft zij met de spin-off van dit project een geweldige bijdrage geleverd aan de fysiologische kennis over de hersenen. Haar promotietraject geeft een diverse inkijk in de problematiek van centrale-windingen-epilepsie, in het uitvoeren van klinische trials met medische apparatuur en in de toekomst van corticale hersenstimulatie bij epilepsie.

Background Epileptic encephalopathy with spike -wave activation in sleep (EE-SWAS) is a rare syndrome associated with cognitive and behavioural regression. On the basis of mostly small observational and retrospective studies, corticosteroids and clobazam are often considered the most effective treatments for this syndrome. We aimed to compare cognitive outcomes of children with EE-SWAS 6 months after starting treatment with either corticosteroids or clobazam. Methods We did a multicentre, randomised controlled trial at eight tertiary referral centres for rare epilepsies in seven European countries. Children were eligible to participate if they were aged 2-12 years, were diagnosed with EE-SWAS within 6 months before inclusion, and had not been treated with corticosteroids or clobazam previously. Participants were randomly assigned (1:1) to treatment with corticosteroids (either continuous treatment with 1-2 mg/kg per day of prednisolone orally or pulse treatment with 20 mg/kg per day of methylprednisolone intravenously for 3 days every 4 weeks) or clobazam (0 center dot 5-1 center dot 2 mg/kg per day orally). The primary outcome was cognitive functioning after 6 months of treatment, which was assessed by either the intelligence quotient (IQ) responder rate (defined as improvement of >= 11 center dot 25 IQ points) or the cognitive sum score responder rate (defined as improvement of >= 0 center dot 75 points). Safety was assessed by number of adverse events and serious adverse events. Data were analysed in the intention -to -treat population, which included all children as randomised who had primary outcome data available at 6 months. The trial is registered with the Dutch Trial Register, Toetsingonline, NL43510.041.13, and the ISRCTN registry, ISRCTN42686094. The trial was terminated prematurely because enrolment of the predefined number of 130 participants was deemed not feasible. Findings Between July 22, 2014, and Sept 3, 2022, 45 children were randomly assigned to either corticosteroids (n=22) or clobazam (n=23); two children assigned clobazam dropped out before 6 months and were excluded from the intentionto -treat analysis. At the 6 -month assessment, an improvement of 11 center dot 25 IQ points or greater was reported for five (25%) of 20 children assigned corticosteroids versus zero (0%) of 18 assigned clobazam (risk ratio [RR] 10 center dot 0, 95% CI 1 center dot 2-1310 center dot 4; p=0 center dot 025). An improvement of 0 center dot 75 points or more in the cognitive sum score was recorded for one (5%) of 22 children assigned corticosteroids versus one (5%) of 21 children assigned clobazam (RR 1 center dot 0, 95% CI 0 center dot 1-11 center dot 7, p=0 center dot 97). Adverse events occurred in ten (45%) of 22 children who received corticosteroids, most frequently weight gain, and in 11 (52%) of 21 children who received clobazam, most often fatigue and behavioural disturbances. Occurrence of adverse events did not differ between groups (RR 0 center dot 8, 95% CI 0 center dot 4-1 center dot 4; p=0 center dot 65). Serious adverse events occurred in one child in the corticosteroid group (hospitalisation due to laryngitis) and in two children in the clobazam group (hospitalisation due to seizure aggravation, and respiratory tract infection). No deaths were reported. Interpretation The trial was terminated prematurely, and the target sample size was not met, so our findings must be interpreted with caution. Our data indicated an improvement in IQ outcomes with corticosteroids compared with clobazam treatment, but no difference was seen in cognitive sum score. Our findings strengthen those from previous uncontrolled studies that support the early use of corticosteroids for children with EE-SWAS. Copyright (c) 2023 Elsevier Ltd. All rights reserved.

Brain surgery is the only curative treatment for people with focal epilepsy, but it is unclear whether this induces active disease in multiple sclerosis (MS). This creates a barrier to evaluate MS patients for epilepsy surgery. We present two cases of successful epilepsy surgery in patients with pharmacoresistant epilepsy and stable MS and give an overview of the existing literature. (1) a 28-year-old woman with seizures arising from a right basal temporo-occipital ganglioglioma was seizure-free after surgery, without MS relapse but with one new MS lesion postsurgically. (2) a 46-year-old woman with seizures arising from a natalizumab-associated progressive multifocal leukoencephalopathy (PML) lesion in the right frontal lobe was seizure-free after surgery preceded by extraoperative subdural electrocorticography, with new subclinical MS lesions. We are the first to report brain surgery in a PML survivor. Both patients stabilized radiologically after initiating second-line therapies. Successful epilepsy surgery can substantially increase the quality of life in patients with pharmacoresistant epilepsy and MS. With increasing survival rates of brain tumors and PML, the risk-benefit ratio of epilepsy surgery compared to a potential MS relapse after surgery becomes critically important. Shared decision-making is valuable for balancing the risks related to both diseases.

Aim Delirium, a clinical manifestation of acute encephalopathy, is often unrecognised. An important electroencephalography (EEG) characteristic of acute encephalopathy is polymorphic delta activity (PDA), which can be detected automatically. We aimed to study whether automated assessment of PDA in unselected EEG could detect acute encephalopathy that presents clinically as delirium.Methods We assessed PDA in 145 elderly patients using the first 96 seconds of unselected single-channel EEG (Fp2-Pz). We compared fully automated PDA detection with visual inspection by EEG experts. Additionally, we tested its performance as a delirium monitor by comparing PDA detection with a standardized delirium assessment by a clinical expert panel.Results PDA detection showed an area under the receiver operating characteristic (AUC) of 0.86 (95%CI 0.81–0.90) compared to EEG experts. When compared with the delirium classification of clinical experts, PDA detection achieved an AUC of 0.78 (95%CI 0.71–0.85). PDA detection correlated with the likelihood of delirium, its severity and the levels of attention and consciousness (all p<0.001).Conclusion Automated PDA detection in unselected, single-channel EEG can classify acute encephalopathy clinically presenting as delirium.Significance A fully automated EEG algorithm can assist in the recognition of delirium.### Competing Interest StatementArjen JC Slooter is a non-salaried advisor for Prolira, a start-up company that develops an EEG-based delirium monitor. Any (future) profits from EEG-based delirium monitoring will be used for future scientific research only. Frans SS Leijten is also a non-salaried advisor and holds shares in Prolira. None of the other authors reports any conflicts of interest. The sponsor and Prolira, had no role in the study design, data analysis, data interpretation, or the decision to submit for publication.### Clinical TrialNCT02404181### Funding StatementThis work was funded by European Union Horizon 2020 [grant number 820555].### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study design was approved prior to patient enrolment by the local ethical committee of University Medical Center Utrecht (protocol 13-634)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.YesI 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).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors* AUC : Area Under the receiver operating Characteristic BMI : Body Mass Index CAM-ICU : Confusion Assessment Method in the ICU CAM-S : Confusion Assessment Method-Severity CI : Confidence Interval DSM-5 : Diagnostic and Statistical Manual of Mental Disorders fifth DRS-R-98 : Delirium Rating Scale Revised-98 EEG : Electroencephalogram IQR : Interquartile range MMSE : Mini-Mental State Examination NPV : Negative Predictive Value NRS : Numeric Rating Scale PPV : Positive Predictive Value RASS : Richmond Agitation and Sedation Scale ROC : Receiver Operating Characteristic-curve SD : Standard Deviation TIA : Transient Ischemic Attack

The structure of the human connectome develops from childhood throughout adolescence to middle age, but how this affects the speed of neuronal signaling is not well described. To understand the maturation process of transmission speed across the connectome, we stimulated electrocorticographic (ECoG) electrode pairs in 75 human subjects of 4 to 51 years old. We then measured the latency of cortico-cortical evoked responses in other electrodes. Each year, responses got faster, until transmission speed reached a minimum latency at the age of 29-44 years old. Responses during middle age were about two times faster compared to childhood. These increases in speed were observed in both long- and short-range connections between and within frontal, central, parietal, and temporal areas. These findings indicate that long-range and short-range communication between brain regions increase in efficiency well throughout adolescence.

Objective: We retrospectively assessed the localizing value of patient-history-based semiology (PHS), video-based semiology (VS), long-term monitoring video electroencephalography (LTM-VEEG) and interictal high resolution electric source imaging (HR-ESI) in the presurgical workup of patients with tuberous sclerosis complex (TSC). Methods: Data from 24 consecutive TSC surgical candidates who underwent both HR-ESI and LTM-VEEG was retrospectively collected. PHS and VS were analyzed to hypothesize the symptomatogenic zone localization. LTM-VEEG and HR-ESI localization results were extracted from the diagnostic reports. Localizing value was compared between modalities, taken the resected/disconnected area of surgical patients in consideration. HR-ESI's impact on the epileptogenic zone hypothesis and surgical workup was evaluated. Results: Semiology, interictal EEG, ictal EEG and HR-ESI were localizing in 25%, 54%, 63% and 79% of patients. Inter-modality concordance ranged between 33-89%. In good surgical outcome patients, PHS, VS, interictal EEG, ictal EEG and HR-ESI showed concordance with resected area in 1/9 (11%), 0/9 (0%), 4/9 (44%), 3/9 (33%) and 6/9 patients (67%). HR-ESI positively impacts clinical management in 50% of patients. Conclusions: In presurgical evaluation of TSC patients, semiology often has limited localizing value. Presurgical work-up benefits from HR-ESI. Significance: Our findings may advice future presurgical epilepsy workup of TSC patients with the ultimate aim to improve outcome. (C) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.

The neuroscience community increasingly uses the Brain Imaging Data Structure (BIDS) to organize data, extending from MRI to electrophysiology data. While automated tools and workflows are developed that help organize MRI data from the scanner to BIDS, these workflows are lacking for clinical intracranial EEG (iEEG data). We present a practical workflow on how to organize full clinical iEEG epilepsy data into BIDS. We present electrophysiological datasets recorded from twelve subjects who underwent intracranial monitoring followed by resective epilepsy surgery at the University Medical Center Utrecht, the Netherlands, and became seizure-free after surgery. These data include intraoperative electrocorticography recordings from six patients, long-term electrocorticography recordings from three patients and stereo-encephalography recordings from three patients. We describe the 6 steps in the pipeline that are essential to structure the data from these clinical iEEG recordings into BIDS and the challenges during this process. These proposed workflow enable centers performing clinical iEEG recordings to structure their data to improve accessibility, reusability and interoperability of clinical data.

Abstract Objective To assess the performance of a multimodal seizure detection device, first tested in adults (sensitivity 86%, PPV 49%), in a pediatric cohort living at home or residential care. Methods In this multicenter, prospective, video‐controlled cohort‐study, nocturnal seizures were detected by heartrate and movement changes in children with epilepsy and intellectual disability. Participants with a history of >1 monthly major motor seizure wore Nightwatch bracelet at night for 3 months. Major seizures were defined as tonic–clonic, generalized tonic >30 s, hyperkinetic, or clusters (>30 min) of short myoclonic or tonic seizures. The video of all events (alarms and nurse diaries) and about 10% of whole nights were reviewed to classify major seizures, and minor or no seizures. Results Twenty‐three participants with focal or generalized epilepsy and nightly motor seizures were evaluated during 1511 nights, with 1710 major seizures. First 1014 nights, 4189 alarms occurred with average of 1.44/h, showing average sensitivity of 79.9% (median 75.4%) with mean PPV of 26.7% (median 11.1%) and false alarm rate of 0.2/hour. Over 90% of false alarms in children was due to heart rate (HR) part of the detection algorithm. To improve this rate, an adaptation was made such that the alarm was only triggered when the wearer was in horizontal position. For the remaining 497 nights, this was tested prospectively, 384 major seizures occurred. This resulted in mean PPV of 55.5% (median 58.1%) and a false alarm rate 0.08/h while maintaining a comparable mean sensitivity of 79.4% (median 93.2%). Significance Seizure detection devices that are used in bed which depend on heartrate and movement show similar sensitivity in children and adults. However, children do show general higher false alarm rate, mostly triggered while awake. By correcting for body position, the false alarms can be limited to a level that comes close to that in adults.

Background: In epilepsy patients, cortical electrical stimulation is therapeutically applied in the seizure onset zone (SOZ) to reduce seizures. However, in patients with epilepsy arising from the primary motor cortex (M1), stimulation can result in undesired muscle contractions or loss of motor control. We postulate that seizure frequency reduction can also be obtained by cortical network stimulation in a site outside M1 with a connection to the SOZ in M1. Methods: Patients with electroclinical seizures suspected to arise from M1 were selected. SOZ was delineated during chronic intracranial EEG monitoring. Using Single Pulse Electrical Stimulation, the underlying effective corticocortical network was determined and a site for stimulation was selected that was connected to the SOZ. One subdural strip was implanted on top of the SOZ, and one on the stimulus location. A subcutaneous neurostimulator (Activa PC+S, Medtronic), capable of recording and closed-loop stimulation, was connected to both strips. Seizure data was collected for three to five months and used to optimize a seizure detection algorithm. After this, closed-loop cortical network stimulation was applied during seven to nine months. Results: In five subjects (two females, mean age 34 years, range: 21-51 years), a neurostimulation system was implanted. One subject was seizure free for 17 months post-implantation without applying any electrical stimulation. Two subjects were responders with a mean seizure frequency reduction of 73%. In two subjects, seizure frequency was reduced by on average 35%. Discussion: In this clinical trial with five subjects suffering from refractory epilepsy arising in M1, seizure frequency was reduced with electrical stimulation in all subjects. This is a proof of concept showing that closed-loop cortical network stimulation can reduce seizure frequency as equal to direct SOZ stimulation in non-primary motor epilepsy.### Competing Interest StatementThe authors have declared no competing interest.### Clinical TrialNCT04158531### Funding StatementResearch reported in this publication was supported by EpilepsieNL under Award Number NEF17-07 (DvB) and NEF19-12 (DvB, SB).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The REC2Stim (Rational Extra-eloquent Closed-loop Cortical Stimulation) study was approved by the ethics committee at the University Medical Center Utrecht and the national Dutch Health and Youth Care Inspectorate, in accordance with the Declaration of Helsinki (2013). This study was registered with clinicaltrials.gov ([NCT04158531][1]). 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.YesI 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).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04158531&atom=%2Fmedrxiv%2Fearly%2F2023%2F11%2F12%2F2023.11.11.23298410.atom