Epilepsy Research最新文献

{"title":"AI in ECG: Validating an ambulatory semiology labeller and predictor","authors":"Pooja Muralidharan ,&nbsp;Ravi Sankaran ,&nbsp;Perraju Bendapudi ,&nbsp;C. Santhosh Kumar ,&nbsp;A. Anand Kumar","doi":"10.1016/j.eplepsyres.2024.107403","DOIUrl":"10.1016/j.eplepsyres.2024.107403","url":null,"abstract":"<div><h3>Objectives</h3><p>Early prediction of epileptic seizures can help reduce morbidity and mortality. In this work, we explore using electrocardiographic (ECG) signal as input to a seizure prediction system and note that the performance can be improved by using selected signal processing techniques.</p></div><div><h3>Methods</h3><p>We used frequency domain analysis with a deep neural network backend for all our experiments in this work. We further analysed the effect of the proposed system for different seizure semiologies and prediction horizons. We explored refining the signal using signal processing to enhance the system's performance.</p></div><div><h3>Results</h3><p>Our final system using the Temple University Hospital’s Seizure (TUHSZ) corpus gave an overall prediction accuracy of 84.02 %, sensitivity of 87.59 %, specificity of 81.9 %, and an area under the receiver operating characteristic curve (AUROC) of 0.9112. Notably, these results surpassed the state-of-the-art outcomes reported using the TUHSZ database; all findings are statistically significant. We also validated our study using the Siena scalp EEG database. Using the frequency domain data, our baseline system gave a performance of 75.17 %, 79.17 %, 70.04 % and 0.82 for prediction accuracy, sensitivity, specificity and AUROC, respectively. After selecting the optimal frequency band of 0.8–15 Hz, we obtained a performance of 80.49 %, 89.51 %, 75.23 % and 0.89 for prediction accuracy, sensitivity, specificity and AUROC, respectively which is an improvement of 5.32 %, 10.34 %, 5.19 % and 0.08 for prediction accuracy, sensitivity, specificity and AUROC, respectively.</p></div><div><h3>Conclusions</h3><p>The seizure information in ECG is concentrated in a narrow frequency band. Identifying and selecting that band can help improve the performance of seizure detection and prediction.</p></div><div><h3>Significance</h3><p>EEG is susceptible to artefacts and is not preferred in a low-cost ambulatory device. ECG can be used in wearable devices (like chest bands) and is feasible for developing a low-cost ambulatory device for seizure prediction. Early seizure prediction can provide patients and clinicians with the required alert to take necessary precautions and prevent a fatality, significantly improving the patient’s quality of life.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"204 ","pages":"Article 107403"},"PeriodicalIF":2.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of an interpretable machine learning model for predicting post-stroke epilepsy","authors":"Yue Yu ,&nbsp;Zhibin Chen ,&nbsp;Yong Yang ,&nbsp;Jiajun Zhang ,&nbsp;Yan Wang","doi":"10.1016/j.eplepsyres.2024.107397","DOIUrl":"10.1016/j.eplepsyres.2024.107397","url":null,"abstract":"<div><h3>Background</h3><p>Epilepsy is a serious complication after an ischemic stroke. Although two studies have developed prediction model for post-stroke epilepsy (PSE), their accuracy remains insufficient, and their applicability to different populations is uncertain. With the rapid advancement of computer technology, machine learning (ML) offers new opportunities for creating more accurate prediction models. However, the potential of ML in predicting PSE is still not well understood. The purpose of this study was to develop prediction models for PSE among ischemic stroke patients.</p></div><div><h3>Methods</h3><p>Patients with ischemic stroke from two stroke centers were included in this retrospective cohort study. At the baseline level, 33 input variables were considered candidate features. The 2-year PSE prediction models in the derivation cohort were built using six ML algorithms. The predictive performance of these machine learning models required further appraisal and comparison with the reference model using the conventional triage classification information. The Shapley additive explanation (SHAP), based on fair profit allocation among many stakeholders according to their contributions, is used to interpret the predicted outcomes of the naive Bayes (NB) model.</p></div><div><h3>Results</h3><p>A total of 1977 patients were included to build the predictive model for PSE. The Boruta method identified NIHSS score, hospital length of stay, D-dimer level, and cortical involvement as the optimal features, with the receiver operating characteristic curves ranging from 0.709 to 0.849. An additional 870 patients were used to validate the ML and reference models. The NB model achieved the best performance among the PSE prediction models with an area under the receiver operating curve of 0.757. At the 20 % absolute risk threshold, the NB model also provided a sensitivity of 0.739 and a specificity of 0.720. The reference model had poor sensitivities of only 0.15 despite achieving a helpful AUC of 0.732. Furthermore, the SHAP method analysis demonstrated that a higher NIHSS score, longer hospital length of stay, higher D-dimer level, and cortical involvement were positive predictors of epilepsy after ischemic stroke.</p></div><div><h3>Conclusions</h3><p>Our study confirmed the feasibility of applying the ML method to use easy-to-obtain variables for accurate prediction of PSE and provided improved strategies and effective resource allocation for high-risk patients. In addition, the SHAP method could improve model transparency and make it easier for clinicians to grasp the prediction model's reliability.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"205 ","pages":"Article 107397"},"PeriodicalIF":2.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morbidity Associated with Deviation from Pediatric Status Epilepticus Guidelines","authors":"Jillian Gregory ,&nbsp;Andrew Cohen ,&nbsp;Anya Cutler ,&nbsp;Alexa Craig","doi":"10.1016/j.eplepsyres.2024.107394","DOIUrl":"10.1016/j.eplepsyres.2024.107394","url":null,"abstract":"<div><p>Treatment guidelines for the management of pediatric status epilepticus (PSE) are often institution-specific. We aim to characterize deviation from our hospital-based PSE treatment guidelines, the total dosage of benzodiazepines administered, and the need for intubation. The study population included all patients with an ICD −10 code for PSE who required admission to the Pediatric Intensive Care Unit (PICU) from April 2019 to April 2022. There were 66 PICU admissions. All patients with concern for PSE and altered mental status are admitted to the PICU. The cohort was divided between those treated according to the PSE protocol (benzodiazepine dose (0.05 mg/kg- 0.2 mg/kg) versus those who had low dose (≤0.05 mg/kg) and high-dose benzodiazepine (&gt; 0.2 mg/kg) totals. The dosage was calculated as the total dose of benzodiazepines received pre-hospital and in the ED before intubation or transport. Forty-one (62 %) of patients received high-dose benzodiazepines (median 0.34 mg/kg [IQR 0.29–0.56], 19 (29 %) received recommended-dose benzodiazepines (median 0.13 mg/kg [IQR 0.09,0.15] and 6 (9 %) received low-dose (median 0.05 mg/kg [IQR 0.03,0.05]. The high-dose group was 15.9 (95 % CI = 3.7, 99.9) times more likely to be intubated controlling for the location of care (tertiary versus community hospital), and the age of the patient. The recommended-dose and low-dose groups required intubation with much less frequency.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"204 ","pages":"Article 107394"},"PeriodicalIF":2.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality of life during usual epilepsy care for anxiety or depression symptoms: Secondary patient-reported outcomes in a randomized trial of remote assessment methods","authors":"Heidi M. Munger Clary ,&nbsp;Beverly M. Snively ,&nbsp;Yaw Kumi-Ansu ,&nbsp;Halley B. Alexander ,&nbsp;James Kimball ,&nbsp;Pamela Duncan ,&nbsp;Kelly Conner ,&nbsp;Jerryl Christopher ,&nbsp;Paneeni Lohana ,&nbsp;Gretchen A. Brenes","doi":"10.1016/j.eplepsyres.2024.107396","DOIUrl":"10.1016/j.eplepsyres.2024.107396","url":null,"abstract":"<div><h3>Background and objectives</h3><p>Anxiety and depression are highly prevalent and impactful in epilepsy. American Academy of Neurology quality measures emphasize anxiety and depression screening and quality of life (QOL) measurement, yet usual epilepsy care QOL and anxiety/depression outcomes are poorly characterized. The main objective was to assess 6-month QOL, anxiety and depression during routine care among adults with epilepsy and baseline anxiety or depression symptoms; these were prespecified secondary outcomes within a pragmatic randomized trial of remote assessment methods.</p></div><div><h3>Methods</h3><p>Adults with anxiety or depression symptoms and no suicidal ideation were recruited from a tertiary epilepsy clinic via an electronic health record (EHR)-embedded process. Participants were randomized 1:1 to 6 month outcome collection via patient portal EHR questionnaires vs. telephone interview. This report focuses on an a priori secondary outcomes of the overall trial, focused on patient-reported health outcomes in the full sample. Quality of life, (primary health outcome), anxiety, and depression measures were collected at 3 and 6 months (Quality of Life in Epilepsy-10, QOLIE-10, Generalized Anxiety Disorder-7, Neurological Disorders Depression Inventory-Epilepsy). Change values and 95 % confidence intervals were calculated. In post-hoc exploratory analyses, patient-reported anxiety/depression management plans at baseline clinic visit and healthcare utilization were compared with EHR-documentation, and agreement was calculated using the kappa statistic.</p></div><div><h3>Results</h3><p>Overall, 30 participants (15 per group) were recruited and analyzed, of mean age 42.5 years, with 60 % women. Mean 6-month change in QOLIE-10 overall was 2.0(95 % CI −6.8, 10.9), and there were no significant differences in outcomes between the EHR and telephone groups. Mean anxiety and depression scores were stable across follow-up (all 95 % CI included zero). Outcomes were similar regardless of whether an anxiety or depression action plan was documented. During the baseline interview, most participants with clinic visit EHR documentation indicating action to address anxiety and/or depression reported not being offered a treatment(7 of 12 with action plan, 58 %), and there was poor agreement between patient report and EHR documentation (kappa=0.22). Healthcare utilization was high: 40 % had at least one hospitalization or emergency/urgent care visit reported and/or identified via EHR, but a third (4/12) failed to self-report an EHR-identified hospitalization/urgent visit.</p></div><div><h3>Discussion</h3><p>Over 6 months of usual care among adults with epilepsy and anxiety or depression symptoms, there was no significant average improvement in quality of life or anxiety/depression, suggesting a need for interventions to enhance routine neurology care and achieve quality of life improvement for this group.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"204 ","pages":"Article 107396"},"PeriodicalIF":2.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141400290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rat strain differences in seizure frequency and hilar neuron loss after systemic treatment with pilocarpine","authors":"Kristina Junghans ,&nbsp;Megan Wyeth ,&nbsp;Paul S. Buckmaster","doi":"10.1016/j.eplepsyres.2024.107384","DOIUrl":"10.1016/j.eplepsyres.2024.107384","url":null,"abstract":"<div><p>At least 3 months after systemic treatment with pilocarpine to induce status epilepticus, Long-Evans and Sprague-Dawley rats were video-EEG monitored for seizures continuously for 1 month. Rats were then perfused, hippocampi were processed for Nissl staining, and hilar neurons were quantified. Seizure frequency in Long-Evans rats was 1/10th of that in Sprague-Dawley rats, and more variable. Hilar neuron loss was also less severe in Long-Evans rats. However, there was no correlation between hilar neuron loss and seizure frequency in either strain. The low and variable seizure frequency suggests limited usefulness of pilocarpine-treated Long-Evans rats for some epilepsy experiments.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"204 ","pages":"Article 107384"},"PeriodicalIF":2.2,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and tolerability of classical and polyunsaturated fatty acids ketogenic diet in controlling paediatric refractory epilepsy – A randomized study","authors":"Subhasree Ray ,&nbsp;Janak Nathan ,&nbsp;Meena Godhia","doi":"10.1016/j.eplepsyres.2024.107395","DOIUrl":"10.1016/j.eplepsyres.2024.107395","url":null,"abstract":"<div><h3>Objectives</h3><p>To measure and compare the efficacy and tolerability of a classical ketogenic diet (CKD) and a polyunsaturated fatty acids ketogenic diet (PUFAKD) in managing childhood refractory epilepsy. Efficacy was assessed by measuring the change in seizure frequency at 3, 6, 9, and 12 months within and between groups. The percentage reduction in seizures at &lt;50 %, 50–90 %, &gt;90 %, and 100 % was also measured. Tolerability was assessed and compared by recording adverse events - vomiting, nausea, lethargy, and constipation.</p></div><div><h3>Methods</h3><p>52 children, aged 2–10 years, were randomized, 25 in the CKD group and 27 in the PUFAKD group. Fat: carbohydrate + protein ratio of 2.2:1–4:1 was maintained in both diets; the PUFAKD group only used unsaturated fats with an omega 3: omega 6 ratio of 1:2.8. Ketone levels were measured using keto-dipsticks, with 4+ and 4++ (80–160 mg/dL) being the most optimal values.</p></div><div><h3>Results</h3><p>A significant decrease (p=0.001) in seizures was observed (n=52), with no significant difference (p=0.537) between the two groups. The mean seizure reduction was 71.1 %, with no significant difference (p=0.488) in both groups. The mean compliance rate was 78.3 % (n=52). A statistically significant linear trend existed between a higher compliance rate and a greater reduction in seizures (p = 0.042, Z=4.039) among all children (n=52). Nausea (p=0.033) and vomiting (p=0.014) occurred more in PUFAKD than in CKD.</p></div><div><h3>Conclusion</h3><p>No significant difference was seen in seizure reduction between the two groups. Compliance correlates with a greater seizure reduction. Despite similar seizure reduction rates, the novel PUFAKD exhibited poorer compliance and more pronounced adverse effects compared to CKD. CKD remained a superior choice over the novel PUFAKD in the management of paediatric refractory epilepsy. More controlled trials with varying PUFA compositions are recommended for long-term evaluations.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"204 ","pages":"Article 107395"},"PeriodicalIF":2.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141402065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of short-lasting and ictal spike-and-wave discharges in around-the-ears EEG recordings in children with absence epilepsy","authors":"Silvano R. Gefferie ,&nbsp;Pauly P.W. Ossenblok ,&nbsp;Christoph S. Dietze ,&nbsp;Armen Sargsyan ,&nbsp;Mireille Bourez-Swart ,&nbsp;Arn M.J.M. van den Maagdenberg ,&nbsp;Roland D. Thijs","doi":"10.1016/j.eplepsyres.2024.107385","DOIUrl":"10.1016/j.eplepsyres.2024.107385","url":null,"abstract":"<div><h3>Purpose</h3><p>Long-term ambulatory EEG recordings can improve the monitoring of absence epilepsy in children, but signal quality and increased review workload are a concern. We evaluated the feasibility of around-the-ears EEG arrays (cEEGrids) to capture 3-Hz short-lasting and ictal spike-and-wave discharges and assessed the performance of automated detection software in cEEGrids data. We compared patterns of bilateral synchronisation between short-lasting and ictal spike-and-wave discharges.</p></div><div><h3>Methods</h3><p>We recruited children with suspected generalised epilepsy undergoing routine video-EEG monitoring and performed simultaneous cEEGrids recordings. We used ASSYST software to detect short-lasting 3-Hz spike-and-wave discharges (1–3 s) and ictal spike-and-wave discharges in the cEEGrids data. We assessed data quality and sensitivity of cEEGrids for spike-and-wave discharges in routine EEG. We determined the sensitivity and false detection rate for automated spike-and-wave discharge detection in cEEGrids data. We compared bihemispheric synchrony across the onset of short-lasting and ictal spike-and-wave discharges using the mean phase coherence in the 2–4 Hz frequency band.</p></div><div><h3>Results</h3><p>We included nine children with absence epilepsy (median age = 11 y, range 8–15 y, nine females) and recorded 4 h and 27 min of cEEGrids data. The recordings from seven participants were suitable for quantitative analysis, containing 82 spike-and-wave discharges. The cEEGrids captured 58 % of all spike-and-wave discharges (median individual sensitivity: 100 %, range: 47–100 %). ASSYST detected 82 % of all spike-and-wave discharges (median: 100 %, range: 41–100 %) with a false detection rate of 48/h (median: 6/h, range: 0–154/h). The mean phase coherence significantly increased during short-lasting and ictal spike-and-wave discharges in the 500-ms pre-onset to 1-s post-onset interval.</p></div><div><h3>Conclusions</h3><p>cEEGrids are of variable quality for monitoring spike-and-wave discharges in children with absence epilepsy. ASSYST could facilitate the detection of short-lasting and ictal spike-and-wave discharges with clear periodic structures but with low specificity. A similar course of bihemispheric synchrony between short-lasting and ictal spike-and-wave discharges indicates that cortico-thalamic driving may be relevant for both types of spike-and-wave discharges.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"204 ","pages":"Article 107385"},"PeriodicalIF":2.2,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0920121124001001/pdfft?md5=b553e9c7988a898d9a0b96aaf905c52f&pid=1-s2.0-S0920121124001001-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retention rate of vagus nerve stimulation for the treatment of drug-resistant epilepsy: A single-centre, retrospective study.","authors":"Astrid Durez ,&nbsp;Tom Theys ,&nbsp;Johannes van Loon ,&nbsp;Wim Van Paesschen","doi":"10.1016/j.eplepsyres.2024.107383","DOIUrl":"https://doi.org/10.1016/j.eplepsyres.2024.107383","url":null,"abstract":"<div><p>The aim of this single-centre, retrospective, observational study was to evaluate long-term effectiveness of vagus nerve stimulation (VNS) in drug-resistant epilepsy (DRE) by using retention rate as a surrogate measure for seizure reduction. We included all patients with DRE, treated at the adult neurology department of the University Hospitals Leuven and who started VNS therapy from January 1, 1994, until May 1, 2021, with follow-up data cutoff on January 1, 2023. Retention rate of VNS was defined as the percentage of patients who maintain VNS at established time points. We estimated cumulative retention rate and battery replacement rate and correlated these with seizure reduction, using Kaplan-Meier analysis. Statistical analysis of potential predictors of VNS outcome (age, sex and epilepsy duration at implantation) was performed using mono- and multivariate analyses. VNS was started in 110 patients with DRE, with a mean follow-up of 8.7 years (SD 6.5). VNS was discontinued in 55 patients (50%), with ineffectiveness as the main reason for discontinuation (98%). The battery was replaced at least once in 42 patients (38%). Estimated retention rates were 70%, 52%, 45% and 33% after 5, 10, 15 and 20 years, respectively. Estimated first battery replacement rates were 16%, 42% and 47% after 5, 10 and 15 years, respectively. Both estimates showed a statistically significant correlation with seizure reduction. No independent predictors of long-term outcome of VNS were found. This is the first long-term study using retention rate of VNS to assess effectiveness. VNS is a well-tolerated therapy, but retention rates decline with long follow-up.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"203 ","pages":"Article 107383"},"PeriodicalIF":2.2,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0920121124000986/pdfft?md5=cd1c56dd24652243d1da00a23c936101&pid=1-s2.0-S0920121124000986-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An analysis of suicidal and self-injurious behavior reports with antiseizure medications in the FDA adverse event database","authors":"Mokshal H. Porwal ,&nbsp;Abrahim N. Razzak ,&nbsp;Vinay Kumar ,&nbsp;Ahmed Z. Obeidat ,&nbsp;Umesh Sharma","doi":"10.1016/j.eplepsyres.2024.107382","DOIUrl":"10.1016/j.eplepsyres.2024.107382","url":null,"abstract":"<div><h3>Background</h3><p>Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior.</p></div><div><h3>Methods</h3><p>Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of “suicidal and self-injurious behavior” were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as “Epilepsy”. Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control.</p></div><div><h3>Results</h3><p>Significant relative operating ratio, ROR (greater than 1, p&lt;0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286).</p></div><div><h3>Conclusions</h3><p>Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"203 ","pages":"Article 107382"},"PeriodicalIF":2.2,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conventional and novel anti-seizure medications reveal a particular role for GABAA in a North Sea progressive myoclonus Epilepsy Drosophila model","authors":"Sjoukje S. Polet ,&nbsp;Tom J. de Koning ,&nbsp;Roald A. Lambrechts ,&nbsp;Marina A.J. Tijssen ,&nbsp;Ody C.M. Sibon ,&nbsp;Jenke A. Gorter","doi":"10.1016/j.eplepsyres.2024.107380","DOIUrl":"10.1016/j.eplepsyres.2024.107380","url":null,"abstract":"<div><h3>Objective</h3><p>North Sea Progressive Myoclonus Epilepsy (NS-PME) is a rare genetic disorder characterized by ataxia, myoclonus and seizures with a progressive course. Although the cause of NS-PME is known, namely a homozygous mutation in the <em>GOSR2</em> gene (c.430 G&gt;T; p. Gly144Trp), sufficient treatment is lacking. Despite combinations of on average 3–5 anti-seizure medications (ASMs), debilitating myoclonus and seizures persist. Here we aimed to gain insight into the most effective anti-convulsive target in NS-PME by evaluating the individual effects of ASMs in a NS-PME Drosophila model.</p></div><div><h3>Method</h3><p>A previously generated <em>Drosophila</em> model for NS-PME was used displaying progressive heat-sensitive seizures. We used this model to test 1. a first-generation ASM (sodium barbital), 2. common ASMs used in NS-PME (clonazepam, valproic acid, levetiracetam, ethosuximide) and 3. a novel third-generation ASM (ganaxolone) with similar mode of action to sodium barbital. Compounds were administered by adding them to the food in a range of concentrations. After 7 days of treatment, the percentage of heat-induced seizures was determined and compared to non-treated but affected controls.</p></div><div><h3>Results</h3><p>As previously reported in the NS-PME <em>Drosophila</em> model, sodium barbital resulted in significant seizure suppression, with increasing effect at higher dosages. Of the commonly prescribed ASMs, clonazepam and ethosuximide resulted in significant seizure suppression, whereas both valproic acid and levetiracetam did not show any changes in seizures. Interestingly, ganaxolone did result in seizure suppression as well.</p></div><div><h3>Conclusion</h3><p>Of the six drugs tested, three of the four that resulted in seizure suppression (sodium barbital, clonazepam, ganaxolone) are primary known for their direct effect on GABA_A receptors. This suggests that GABA_A could be a potentially important target in the treatment of NS-PME. Consequently, these findings add rationale to the exploration of the clinical effect of ganaxolone in NS-PME and other progressive myoclonus epilepsies.</p></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"203 ","pages":"Article 107380"},"PeriodicalIF":2.2,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0920121124000950/pdfft?md5=c82ecc1fddb81e79646e0079f2d4ca9a&pid=1-s2.0-S0920121124000950-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141030058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}