Epilepsia Open最新文献

{"title":"Real-world use of Cenobamate in pediatric drug-resistant epilepsy: A European multicenter retrospective study.","authors":"Konstantin L Makridis, Thomas Bast, Stéphane Auvin, Pavel Krsek, Matyas Ebel, Eva Breuer, Mira Beckhaus, Matúš Bašovský, Pavlína Danhofer, Ondřej Horák, Alessandro Orsini, Gonzalo Alonso Ramos Rivera, Hana Medřická, Steffen Syrbe, Angela M Kaindl","doi":"10.1002/epi4.70301","DOIUrl":"10.1002/epi4.70301","url":null,"abstract":"<p><p>Pediatric drug-resistant epilepsy (DRE) remains a significant clinical challenge, with few effective pharmacological options. This European multicenter retrospective study assessed the real-world efficacy, tolerability, and retention of off-label cenobamate (CNB) in 108 children and adolescents with DRE (median age: 13.83 years, range 3.9-19.8). Overall, 57/108 patients (52.8%) achieved a ≥50% seizure reduction, including 20/108 (18.5%) who were seizure-free during the documented interval between visits. The median monthly seizure frequency declined from 30 to 9. Median follow-up was 581.5 days (IQR 340,8; range 27-1160); 5 patients had follow-up ≤90 days and 10 had follow-up <180 days. In sensitivity analyses excluding patients with follow-up ≤90 days and <180 days, ≥50% responder rates were 54.4% and 56.1%, respectively. Concomitant ASM dose reductions and discontinuations occurred in 44% and 51% of patients, respectively, with the median ASM count declining from 3 to 2. Adverse events were documented in 57.4%, most frequently fatigue, vertigo, and behavioral symptoms. No cases of DRESS were reported. CNB retention at 12 months was 86.8% and was higher in patients without adverse events (93.5% vs. 81.6%, p = 0.0076). The initiation dose was most commonly 12.5 mg (0.25 mg/kg/day, IQR 0.12), with titration to a median maintenance dose of 3.57 mg/kg/day (IQR 1.95; range 0.3-10). These findings suggest that CNB is a generally well-tolerated and clinically effective adjunctive treatment in pediatric DRE, with the potential to reduce polypharmacy and support long-term adherence. Controlled prospective studies are needed to confirm these results and to establish safe, evidence-based use of CNB in children. PLAIN LANGUAGE SUMMARY: Many children and adolescents with drug-resistant epilepsy do not respond to available medications. In this European multicenter study, we evaluated cenobamate, used off label, in 108 young patients with severe epilepsy. More than half had their seizures reduced by at least 50%, and nearly one in five became seizure-free. Seizure frequency dropped markedly, and many patients could reduce other anti-seizure medications. Side effects were common but usually mild, and most patients continued treatment long term. These results suggest cenobamate may be a useful option in pediatric drug-resistant epilepsy, but prospective studies are needed to confirm safety and effectiveness.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1863-1870"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized controlled trial of a multimodality digital health intervention to aid the delivery of the modified ketogenic diet therapy for epilepsy: The Keto eCoach trial protocol.","authors":"Neha Kaul, Lucy Vivash, Susanna Chen, Lillian King, Hannah Johns, Leonid Churilov, Zhibin Chen, John-Paul Nicolo, Danielle Heaven, Ella Meredith, Ryan Ervine, Lisa Todd, Bernadette Zappa, Zanfina Ademi, Gopisankar Mohanannair Geethadevi, Michael Erlichster, Efstratios Skafidas, Terence J O'Brien, Patrick Kwan","doi":"10.1002/epi4.70345","DOIUrl":"10.1002/epi4.70345","url":null,"abstract":"<p><strong>Objective: </strong>Dietary therapy is an effective treatment for drug-resistant epilepsy; however, low adherence presents a significant barrier to use in the clinical setting. This study aims to evaluate a multimodality digital health intervention to overcome this barrier and improve outcomes in adults undertaking the modified ketogenic diet for epilepsy.</p><p><strong>Method: </strong>This is a two-arm, randomized, controlled trial. A total of 136 participants will be randomized 1:1 to receive the modified ketogenic diet as per standard clinical care, or with the addition of the multimodality digital health intervention for 12 weeks. The intervention will include three components: (1) digital diaries, (2) a novel, at-home, saliva-based ketone testing device, and (3) dynamic dietitian support.</p><p><strong>Results: </strong>The primary treatment benefit will be determined using the epilepsy desirability of outcome rank, a composite outcome measure co-designed with people living with drug-resistant epilepsy. Secondary outcomes will include seizure frequency, treatment retention, adverse events, psychiatric symptoms, quality of life, medication use, cost effectiveness, and acceptability of the intervention.</p><p><strong>Significance: </strong>The results of this trial will provide evidence on the effectiveness of using this innovative digital health intervention approach to improve treatment outcomes of dietary therapy for drug-resistant epilepsy.</p><p><strong>Ethics and dissemination: </strong>This study has received approval from the Alfred Hospital Human Research Ethics Committee (Reference No.: 723/23). The results will be disseminated via peer-reviewed publications and publicly available plain language summaries.</p><p><strong>Trial registration number: </strong>Australian New Zealand Clinical Trials Registry (ANZCTR, ACTRN12624000486527).</p><p><strong>Plain language summary: </strong>This trial aims to find out if a 12-week digital health program can improve treatment outcomes of people living with epilepsy. We will invite 136 people commencing on the modified ketogenic diet to be randomly assigned to the digital health program or standard clinic care. The treatment outcome will be assessed combining seizure frequency, side effects, and quality of life.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1718-1728"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Economic burden and cost determinants of epilepsy in Georgia: A longitudinal cost-of-illness study.","authors":"Sofia Kasradze, Tamar Jishkariani, Eka Burkadze, Ketevan Mamasakhlisi, Marika Megrelishvili, Josemir W Sander","doi":"10.1002/epi4.70337","DOIUrl":"10.1002/epi4.70337","url":null,"abstract":"<p><strong>Objective: </strong>To assess the economic burden, cost components, and individual-level determinants of outpatient epilepsy care in adults in Georgia.</p><p><strong>Methods: </strong>This longitudinal study of epilepsy-related costs in adults with active epilepsy attending a tertiary epilepsy centre in Tbilisi collected clinical and sociodemographic data over 6 months. Direct and indirect costs were analyzed using descriptive statistics and multivariate regression.</p><p><strong>Results: </strong>Median total epilepsy-related costs in 351 adults (median age 31 years; 44.4% male) for six months were USD 402.22 (IQR: 293.33-578.15), with a mean cost of USD 572.54 ± 789.29, indicating a highly skewed distribution. Direct medical costs, mainly antiseizure medications, accounted for 83.5% of the mean total. Costs were similar across urban and rural residents. In multivariable analysis, males incurred lower total costs than females (CR = 0.86; 95% CI: 0.74-0.99), employment in non-professional roles (CR = 1.47; 95% CI: 1.19-1.81), health insurance coverage (overall p = 0.010), epilepsy type (overall p = 0.014), monotherapy compared with polytherapy (CR = 0.75; 95% CI: 0.64-0.88), and greater seizure frequency (per additional seizure: CR = 1.08; 95% CI: 1.05-1.11). Age showed a weak inverse association with costs, whereas epilepsy duration and disability/social benefit status were not significant predictors. Most participants incurred costs below 40% of their six-month income, although a subset faced a disproportionately high financial burden.</p><p><strong>Significance: </strong>Epilepsy in Georgia imposes a significant economic burden on adults, driven mainly by medication costs, specialized services, and poor seizure control. This highlights the need for affordable therapies, optimized management, strengthened health system support, and expanded social protection. Future research needs to assess the long-term economic impact of drug-resistant epilepsy.</p><p><strong>Plain language summary: </strong>People with epilepsy often need lifelong treatment, but little is known about the financial burden of epilepsy in Georgia. We studied the cost of epilepsy care for 351 adults over six months. Most spending was on antiseizure medications and medical tests. People who had more seizures or needed more than one antiseizure medication had higher treatment costs. For most people, the cost of epilepsy care was not extremely high, but some experienced much greater expenses than others. Our findings show where the biggest costs come from and may help improve epilepsy care and make treatment more affordable in Georgia.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1786-1800"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13468731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte subtype-specific alterations in the dentate gyrus of individuals with mesial temporal lobe epilepsy.","authors":"Chiara Lötzsch, Jakob Johann Schmidt, Daniel Delev, Roland Coras, Ingmar Blümcke, Ruth Beckervordersandforth","doi":"10.1002/epi4.70324","DOIUrl":"10.1002/epi4.70324","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Epilepsy affects approximately 50 million people worldwide and, although primarily attributed to neuronal dysfunction, increasing evidence highlights a critical role of glial cells, particularly astrocytes, in the pathophysiological mechanisms. Mesial temporal lobe epilepsy (MTLE), the most common form of drug-resistant epilepsy, is frequently associated with hippocampal sclerosis (HS) and pronounced astrogliosis. Given the limited efficacy of current anti-seizure medication (ASM) and the side effects of surgical hippocampus removal, there is a need for more specific and effective therapies that potentially address non-neuronal mechanisms. Astrocytes, with their inherent heterogeneity, are key candidates for such approaches due to their role in regulating and maintaining neuronal activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;To investigate subtype-specific astrocyte alterations in MTLE, we performed immunofluorescence analyses of human dentate gyrus (DG) tissue from MTLE patients (HS1, HS2, and noHS according to the International League Against Epilepsy (ILAE) consensus classification of HS in temporal lobe epilepsy) and postmortem controls. We analyzed the expression and spatial distribution of selected functionally relevant astrocytic proteins, including glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), excitatory amino acid transporter 2 (EAAT2), and aquaporin-4 (AQP4).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In control tissue, astrocyte subtypes, characterized by combinatorial expression of GFAP, GS, EAAT2, and AQP4, displayed distinct, layer-specific protein expression profiles across the DG compartments. While the subtype identities were largely preserved in MTLE, localization and expression levels of GFAP, EAAT2, and AQP4 were dramatically altered, suggesting functional deficits in glutamate transport and water homeostasis. Since GS expression was unaffected by MTLE, it served as a proxy to quantify the number of astrocytes. In contrast to existing reports, we found that astrocyte numbers did not differ between control and MTLE patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Significance: &lt;/strong&gt;Our findings demonstrate that astrocyte reactivity in MTLE is not uniform but occurs in a subtype- and region-specific manner. This highlights astrocyte heterogeneity as an important feature of MTLE pathology and underscores the need to consider astrocyte diversity in understanding disease mechanisms and developing precision medicine-based therapeutic strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;Epilepsy is usually studied as a disease of nerve cells, but support cells, called astrocytes, are also involved. We studied brain tissue from patients with a common form of drug-resistant epilepsy and found that different groups of astrocytes showed distinct changes in proteins that help control brain activity and water movement in the brain. Although the overall number of astrocytes did not change compared with postmortem contr","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1651-1667"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of anti-neural antibodies and autoimmune epilepsy in focal epilepsy of unknown etiology: An observational study in a Singaporean cohort.","authors":"Seong Jin Park, Jeanne May May Tan, Xuejuan Peng, Patricia Yut Wan Wong, Karine Su Shan Tay, Angelia Swee Hoon Koe, Janis Siew Noi Tye, Josiah Yui Huei Chai, Pei Xuan Koh, Yee Leng Tan, Sheila Srinivasan, Ngai Kun Loh, Nigel Choon Kiat Tan, Kevin Tan, Tianrong Yeo","doi":"10.1002/epi4.70327","DOIUrl":"10.1002/epi4.70327","url":null,"abstract":"<p><strong>Objective: </strong>Autoimmune epilepsy (AES) is increasingly recognized as a condition in patients with epilepsy of unknown etiology. Early immunotherapy improves outcomes; however, data on its prevalence and the frequency of anti-neural/neuronal antibodies in Asian populations remain scarce. Herein, we aim to (1) evaluate the frequency of serum anti-neuronal/neural antibodies, (2) compare the clinical characteristics between seropositive and seronegative patients, and (3) explore the clinical utility of the ACES (Antibodies Contributing to Focal Epilepsy Signs and Symptoms) score in diagnosing AES in a cohort of Singaporean patients with focal epilepsy of unknown etiology.</p><p><strong>Methods: </strong>This was a cross-sectional, observational, single-center study performed at the National Neuroscience Institute (NNI), Singapore. Patients with focal epilepsy of unknown etiology were prospectively recruited. Serum samples were tested using both cell-based (CBA) and immunohistochemistry (IHC)-based tissue assays. Patients were classified into definite, probable, and possible AES based on antibody positivity. Clinical characteristics, MRI and EEG findings, and ACES scores were analyzed.</p><p><strong>Results: </strong>One-hundred-and-twenty patients were included. Nine patients (7.50%) were seropositive on IHC, while 2 patients (1.67%) were positive on CBA (1 with concomitant IHC positivity, 1 without). In total, 10 patients (8.33%) were seropositive on IHC and/or CBA. Seropositivity was associated with female sex, autoimmune and psychiatric comorbidities, behavioral changes, speech problems, abnormal MRI brain, medial temporal T2/FLAIR hyperintensities, and ACES ≥2. AUC of ACES for seropositivity was 0.878; sensitivity and specificity were 60.0% and 96.4% respectively at a cutoff of ≥2.</p><p><strong>Significance: </strong>The frequency of specific, well-characterized anti-neural/neuronal antibodies in focal epilepsy of unknown etiology is low in Singapore. Distinct clinico-radiological features, in particular those that comprise the ACES score, were useful in identifying AES. Their presence should prompt antibody testing to confirm the diagnosis of AES for earlier immunotherapy.</p><p><strong>Plain language summary: </strong>This study performed in Singapore investigated autoimmune epilepsy in people who have focal epilepsy with no clear cause. Researchers tested blood samples for antibodies linked to autoimmune epilepsy and compared clinical features between patients with and without these antibodies. Out of 120 patients, 10 had positive antibody tests-they were more often female, more likely to have autoimmune or psychiatric conditions, behavior or speech problems, and abnormal brain MRI findings. An ACES score of 2 or more was useful for identifying patients with antibodies. Using these clinical features can help clinicians decide who should be tested and treated earlier.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1677-1691"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroclinical classification of idiopathic generalized epilepsy syndromes at initial evaluation: A prospective multicenter study.","authors":"Omar Nawfal, Heba Samara, Wassim Nasreddine, Fatima Jaafar, Mahasen Reda, Tarek Halabi, Ahmad Beydoun","doi":"10.1002/epi4.70349","DOIUrl":"10.1002/epi4.70349","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To determine the extent to which electroclinical information available at initial evaluation allows classification of idiopathic generalized epilepsy (IGE) syndromes, and to assess the contributions of seizure semiology and age at seizure onset to early syndromic diagnosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We prospectively analyzed a cohort of patients with new-onset seizures who underwent a structured clinical evaluation, including detailed history-taking, 3-h video-EEG, and epilepsy-protocol MRI. Seizure semiology was assessed at three levels: index seizure, initial seizure type, and seizure types identified at initial evaluation. Syndromic classification followed International League Against Epilepsy criteria. Final electroclinical diagnosis, established after longitudinal follow-up, served as reference. Within patients ultimately diagnosed with one of the four IGE syndromes, baseline data were used to determine whether the final syndrome could be assigned at initial evaluation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 2699 patients evaluated, 498 (18.4%) met criteria for genetic generalized epilepsy, of whom 401 (80.5%) were classified as having one of the IGE syndromes. Based on initial evaluation, the correct syndrome could be assigned in 366 patients (91.3%), whereas 7 (1.7%) would have been misclassified and 28 (7.0%) were not assignable. Non-assignability was confined to absence epilepsies, reflecting overlap between childhood (CAE) and juvenile absence epilepsy (JAE), whereas misclassification occurred only in juvenile myoclonic epilepsy (JME) presenting with isolated generalized tonic-clonic (GTC) seizures. Classification based on the index seizure alone showed limited accuracy (63.6%), whereas incorporation of seizure types identified through structured history improved classification to 95.0%. Myoclonic seizures were highly specific for JME, whereas absence and GTC seizures required integration with additional features. Age at seizure onset strongly differentiated CAE from JAE (AUC 0.935).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Significance: &lt;/strong&gt;Electroclinical classification of IGE syndromes is frequently achievable at initial evaluation when based on seizure semiology and age at onset. When classification is not possible, limitations follow predictable electroclinical patterns, supporting a structured, history-driven diagnostic approach.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;This study examined how accurately doctors can identify specific types of generalized epilepsy when patients are first evaluated. Among 401 patients with generalized epilepsy, the correct epilepsy syndrome could be identified in more than 90% at the first visit. Looking beyond the first seizure and asking about all seizure types together with age at seizure onset greatly improved diagnosis. While some overlap exists between specific types (like childhood versus juvenile absence epilepsy), a thorough clinical evaluation from the start provides relia","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1841-1852"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DECREASE study: A European pool-analysis of patients with significant reductions in concomitant antiseizure medications in cenobamate Early Access Programs.","authors":"Vicente Villanueva, Simona Lattanzi, Javier Peña-Ceballos, Rhys H Thomas, Juan Rodríguez-Uranga, Zsófia Jordán, Bernhard J Steinhoff, Randi von Wrede, Norman Delanty, Patrick B Moloney, Roberta Roberti, Giovanni Boero, Laura Canafoglia, Nicola Specchio, Antonio Gambardella, Edoardo Ferlazzo, Francesca Felicia Operto, Elena Tartara, Hester Garratt, Dániel Fabó, Asier Gómez-Ibáñez, Gustavo Torres-Gaona, Yulia Novitskaya, Rainer Surges, Kevin Hampel, Andreas Schulze-Bonhage","doi":"10.1002/epi4.70344","DOIUrl":"10.1002/epi4.70344","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the effectiveness and tolerability of cenobamate in patients with a significant reduction in concomitant antiseizure medication (ASM) in European cenobamate Early Access Programs (EAPs).</p><p><strong>Method: </strong>Anonymized patient data from real-world studies/registries associated with European cenobamate EAPs were pooled. Patients were included if they had significantly reduced their concomitant drug load (i.e., converted to cenobamate monotherapy or reduced from multiple to one concomitant ASM) between baseline and the last visit. Effectiveness, tolerability, and dosage of cenobamate were evaluated. Responses according to therapeutic regimen at last visit were studied.</p><p><strong>Results: </strong>Of 694 patients within cenobamate EAPs, 75 (10.7%) met the inclusion criteria (mean age 39.5 years [range 19-65]). At baseline, the median number of prior ASMs was 10 (interquartile range [IQR] 6-13); 46 patients (61.3%) were taking two, 23 (30.7%) were taking three, and six (8%) were taking four concomitant ASMs at baseline. At the last visit, seven patients (9.3%) were converted to monotherapy and 68 (90.7%) were receiving one concomitant ASM. The median cenobamate dosage at last visit was 300 mg (IQR 200-350). Median cenobamate follow-up was 22 months; 73 patients (97%) had at least 1 year of follow-up and one discontinued cenobamate at 1 year. Twenty-five patients (33.3%) were seizure-free at last visit; 51 (68%) had a ≥50% reduction in seizure frequency. The seizure-freedom rate was numerically, but not significantly, higher in patients converted to monotherapy (57.1%) versus those receiving one concomitant ASM (30.9%; p = 0.16). Cenobamate plus clobazam was the most effective combination. Adverse events (AEs) were reported in 55/75 patients (73.3%); the most common were somnolence (30.7%), dizziness/vertigo (28%), and fatigue (26.7%). No AEs led to treatment discontinuation.</p><p><strong>Significance: </strong>Cenobamate demonstrated good effectiveness and tolerability in a population of patients within European EAPs who achieved a significant reduction of concomitant ASM.</p><p><strong>Plain language summary: </strong>People with highly drug-resistant epilepsy often need to take several antiseizure medications at the same time. Combined data from European Early Access Programs show that about 10% of people treated with cenobamate were able to stop all other antiseizure medications or reduce treatment to cenobamate plus one other medication. Despite this simplification of treatment, one-third of these patients became seizure-free and more than two-thirds experienced at least a 50% reduction in seizure frequency. Within this group, no patients stopped cenobamate because of side effects.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1812-1824"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond seizure freedom: Reframing recovery in epilepsy.","authors":"Giancarlo Di Gennaro, Andrea Tomasini","doi":"10.1002/epi4.70341","DOIUrl":"10.1002/epi4.70341","url":null,"abstract":"","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1894-1896"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of fenfluramine in Dravet syndrome: The impact of patient clinical characteristics.","authors":"Rima Nabbout, Joseph Sullivan, Stéphane Auvin, J Helen Cross, Orrin Devinsky, Antonio Gil-Nagel, Renzo Guerrini, Kelly G Knupp, M Scott Perry, Rocío Sánchez-Carpintero, An-Sofie Schoonjans, Ingrid E Scheffer, Nicola Specchio, Adam Strzelczyk, James Wheless, Elaine C Wirrell, Diego Morita, Patrick Healy, Mélanie Langlois, Amélie Lothe, Lieven Lagae","doi":"10.1002/epi4.70340","DOIUrl":"10.1002/epi4.70340","url":null,"abstract":"<p><strong>Objective: </strong>To assess the efficacy and safety of fenfluramine in patients with Dravet syndrome (DS) stratified by age, number of previously attempted antiseizure medications (ASMs), and SCN1A pathogenic variant status.</p><p><strong>Methods: </strong>In this post hoc analysis, data from three randomized controlled trials (RCTs) in patients with DS (2-18 years) were pooled and stratified by age (<4; ≥4 years), number of previous ASMs (1-3; 4-6; ≥7), and SCN1A pathogenic variant status (SCN1A+; SCN1A-). Stratified groups were assessed and compared with the pooled placebo group (change in monthly convulsive seizure frequency [MCSF], longest convulsive seizure-free interval, and Clinical Global Impression-Improvement [CGI-I] scale scores rated by parents/caregivers and investigators), and safety (treatment-emergent adverse events [TEAEs]: frequency, days to onset, and proportion resolved).</p><p><strong>Results: </strong>Among 348 patients included in the RCTs, 216 were randomized to fenfluramine (0.7 mg/kg/day, n = 88; 0.4 mg/kg/day [with stiripentol], n = 43; 0.2 mg/kg/day, n = 85) and 132 to placebo. Compared with placebo, fenfluramine treatment (all doses combined) resulted in greater MCSF reductions, greater increases in longest convulsive seizure-free intervals, and a higher proportion of parents/caregivers and investigators reporting clinically meaningful improvement (\"Much Improved\", \"Very Much Improved\") on CGI-I scores across all stratified groups. CGI-I scores were consistent across fenfluramine doses in most stratified groups, but patients with the fewest number of previous ASMs had the greatest frequency of clinically meaningful improvement on investigator-rated CGI-I scores. Safety outcomes were similar across all strata. Most TEAEs resolved by end-of-study.</p><p><strong>Significance: </strong>Fenfluramine treatment was associated with improved seizure outcomes and global functioning compared with placebo regardless of age, number of previous ASMs, and SCN1A status in patients with DS. Fenfluramine was well-tolerated; no new safety signals were identified. Further studies with larger sample sizes (including adults) and a priori inferential analyses of stratified groups are warranted.</p><p><strong>Plain language summary: </strong>Patients with Dravet syndrome struggle with seizures and everyday life. In three studies, patients aged 2-18 years received fenfluramine or placebo (sugar pill). Fenfluramine lowered seizures without many side effects. Researchers combined results from these studies to see how fenfluramine worked in different patient groups based on age, number of previous medications, and a gene called SCN1A. They looked at seizure reduction and whether doctors felt patients had improved. In all groups, fenfluramine worked better than placebo, with similar side effects. Researchers believe fenfluramine helped these patients, but some groups were small, so these results need to be confirmed.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1692-1705"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response: Rethinking GABAergic therapy in neonatal seizures: Beyond Scylla and Charybdis.","authors":"Kerry W Thompson, Lucie Suchomelova, Claude G Wasterlain","doi":"10.1002/epi4.70280","DOIUrl":"10.1002/epi4.70280","url":null,"abstract":"","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1888-1889"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}