Epilepsia最新文献

{"title":"Improving the tolerability of antiseizure medications: When and how to use cenobamate and other new antiseizure medications","authors":"Gregory L. Krauss,&nbsp;Josemir W. Sander,&nbsp;William E. Rosenfeld","doi":"10.1111/epi.18304","DOIUrl":"10.1111/epi.18304","url":null,"abstract":"<p>Despite the introduction of newer antiseizure medications (ASMs) with improved safety profiles over the past several years, rates of treatment-related intolerable adverse events (AEs) for people with epilepsy have not changed substantially. Tolerability issues can potentially jeopardize optimal dosing and effectiveness, regimen adherence, and treatment retention with these newer medications. Long-term clinical studies, open-label extension studies, and postmarketing studies allow flexible dosing and adjustment of concomitant ASMs, which can help clinicians reduce treatment-related AEs and thus improve the retention and tolerability of these treatments. With newer effective treatments (e.g., lacosamide, eslicarbazepine, perampanel, brivaracetam, and most recently, cenobamate), the risk of AEs may be minimized by proactively adjusting concomitant ASMs that have known pharmacokinetic and/or pharmacodynamic drug interactions. Additional tolerability considerations should be made for specific populations, for example, more determined reductions in concomitant ASMs may be required to improve treatment tolerability in older people, and individuals with more refractory seizures may require higher doses. Strategies to improve the tolerability of effective ASMs further, including earlier add-on therapy and transition to, or initial, monotherapy should be investigated. Ongoing clinical studies in children and people with generalized tonic–clonic seizures of the most recent ASM addition, cenobamate, will further inform the safety profile of cenobamate and its potential utility as a broad-spectrum treatment option.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"66 S1","pages":"15-28"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Symptom network analysis of prefrontal seizures.","authors":"Christophe Gauld, Fabrice Bartolomei, Jean-Arthur Micoulaud-Franchi, Aileen McGonigal","doi":"10.1111/epi.18372","DOIUrl":"https://doi.org/10.1111/epi.18372","url":null,"abstract":"<p><strong>Objective: </strong>Prefrontal seizures pose significant challenges in accurately identifying the complex interactions between clinical manifestations and brain electrophysiological activities. This proof-of-concept study aims to propose a new approach to rigorously support electroclinical reasoning in the field of epilepsy.</p><p><strong>Methods: </strong>We analyzed stereoelectroencephalographic data from 42 patients with drug-resistant focal epilepsy, whose seizures involved prefrontal cortex at seizure onset. Semiological and brain activities features were scored by expert observers. We performed a symptom network analysis of semiological feature and a hybrid network analysis, coupling semiological features with network analysis of ictal brain activities. Centrality measures were used to identify the most influential features in the networks.</p><p><strong>Results: </strong>Our analysis identified impairment of consciousness as the most central feature in the semiological network. In the hybrid network, the anterior cingulate area (here incorporating Brodmann area [BA]-32 and/or rostral part of BA-24) emerged as the most central brain activity feature.</p><p><strong>Significance: </strong>By integrating semiological features with brain electrophysiological activities into hybrid networks, symptom network analysis offers an effective quantitative tool for examining the relationships between seizure semiology and brain activity correlates in prefrontal seizures. This study provides an opportunity to advance a novel approach to rigorously investigate the intricacies of electroclinical correlations, sustaining the development of dynamic models, on different series of focal epilepsies, larger cohorts, and semiological features automatically extracted by artificial intelligence, that better reflect the temporal and spatial complexities of seizure propagation in patients with complex seizures.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cenobamate efficacy in specific populations","authors":"Pavel Klein","doi":"10.1111/epi.18303","DOIUrl":"10.1111/epi.18303","url":null,"abstract":"<p>Most people with epilepsy are able to achieve good seizure control with currently available medications. However, despite the development of more than 20 new antiseizure medications (ASMs) over the past 30 years, approximately one third of patients (both pediatric and adult) are treatment-resistant and at risk of increased morbidity and mortality, including sudden unexpected death in epilepsy. The management of epilepsy in these populations can be complex. Metabolic differences in older people and pediatric patients can alter drug metabolism, increasing the risk of adverse drug effects. Comorbid conditions, potential or existing polypharmacy, and age-related physiological changes need to be considered when treating these patients. Rare developmental epileptic encephalopathies such as Lennox–Gastaut syndrome and Dravet syndrome are typically diagnosed in childhood and have proven to be refractory to treatment and to have high mortality rates. Here, we provide an overview of ASM use in patients with refractory epilepsy, in older patients, and in pediatric patients, with a focus on the efficacy outcomes, safety, and tolerability observed with a newer ASM, cenobamate.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"66 S1","pages":"29-37"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy medication management: Addressing common treatment barriers to adopting cenobamate and other new antiseizure medications","authors":"William E. Rosenfeld","doi":"10.1111/epi.18305","DOIUrl":"10.1111/epi.18305","url":null,"abstract":"<p>Seizure freedom is an important therapeutic goal for people with epilepsy and is associated with improved quality of life and reduced morbidity and mortality. Yet despite the use of multiple antiseizure medications (ASMs; either as monotherapy or in combination), seizures persist in approximately one third of patients. Third-generation ASMs, such as lacosamide, eslicarbazepine, perampanel, and brivaracetam, have demonstrated good efficacy in terms of reductions in the frequency of focal seizures. The newest ASM, cenobamate, which is indicated for the treatment of focal seizures in adults, has demonstrated notable rates of seizure freedom for some patients with drug-resistant epilepsy. In long-term, open-label clinical studies of adjunctive cenobamate, between 18.4% and 36.3% of patients achieved seizure freedom for a consecutive ≥12-month duration, and 1-year retention rates ranged from 73% to 83%. This article reviews some of the potential treatment barriers encountered during the medication management of patients with epilepsy that may impede the use and optimization of newer ASMs like cenobamate. These include treatment complacency, inadequate trial of new adjunctive therapies (“last in, first out”), pitfalls of rational polytherapy, and restricting the use of newer drugs. Although treatment must always be tailored to the specific patient, clinicians should consider the potential benefits of newer therapies and continue to reassess and optimize ASM treatment to achieve the best outcomes for their patients.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"66 S1","pages":"38-48"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a discrete electrographic seizure detection algorithm for extended-duration, reduced-channel wearable EEG.","authors":"Tyler J Newton, Mitchell A Frankel, Zoë Tosi, Avidor B Kazen, Vamshi K Muvvala, Tobias Loddenkemper, Mark C Spitz, Laura Strom, Daniel Friedman, Mark J Lehmkuhle","doi":"10.1111/epi.18365","DOIUrl":"https://doi.org/10.1111/epi.18365","url":null,"abstract":"<p><strong>Objective: </strong>Reduced-channel wearable electroencephalography (EEG) may overcome the accessibility and patient comfort limitations of traditional ambulatory electrographic seizure monitoring during extended-duration use. Automated algorithms are necessary for review of extended-duration reduced-channel EEG, yet current clinical support software is designed only for full-montage recordings.</p><p><strong>Methods: </strong>The performance of a novel automated seizure detection algorithm for reduced-channel EEG (Epitel) was evaluated in a clinical validation study involving 50 participants (31 with seizures) with diverse demographic and seizure representation.</p><p><strong>Results: </strong>The algorithm demonstrated an event-level sensitivity of 86.2% (95% confidence interval [CI] = 79.5%-93.2%) and a false detection rate of .162 per hour (95% CI = .116-.221), which is comparable to the performance of current clinical software for full-montage EEG. Performance varied by electrographic seizure type, with 91.4% sensitivity for focal evolving to generalized seizures, 86.7% for generalized seizures, and 77.3% for focal seizures. The algorithm maintained robust performance in both pediatric participants aged 6-21 years (83% sensitivity) and adults aged 22+ years (90% sensitivity), as well as in ambulatory (80%) and epilepsy monitoring unit (EMU) monitoring environments (87.5%). The false detection rate in ambulatory monitoring environments (.290 false positive [FP] detections/h), all of which involved pediatric participants, was notably higher than in the EMU (.136 FP/h), indicating an area with clear need for improvement for unrestricted at-home monitoring. The algorithm's supplemental Confidence metric, designed to engender trust in the algorithm, showed a strong correlation with detection precision.</p><p><strong>Significance: </strong>These results suggest that this algorithm can provide crucial support for review of extended-duration reduced-channel wearable EEG, enabling electrographic seizure monitoring with no restrictions on a person's daily life.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do the third-generation antiseizure medications provide the “magic bullet” for drug-resistant epilepsy? Focus on cenobamate","authors":"Patrick Kwan,&nbsp;Martin J. Brodie","doi":"10.1111/epi.18306","DOIUrl":"10.1111/epi.18306","url":null,"abstract":"&lt;p&gt;Achieving seizure freedom remains elusive for a substantial number of patients, particularly those designated as having drug-resistant epilepsy. Over the past 30 years, 24 new antiseizure medications (ASMs) have been developed and licensed in the United States and Europe, some of which offer improved safety and tolerability profiles.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; However, landmark studies conducted in Glasgow, Scotland, on individuals with newly diagnosed epilepsy have suggested that the proportion of patients with uncontrolled epilepsy has not decreased significantly during this time. In the most recent updated analysis of the Glasgow cohort,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; which included 1795 adolescents and adults who began ASM treatment between 1982 and 2012, the use of second-generation drugs increased from 21% in the first decade to 74% in the last. Despite this shift in availability and choice, the probability of achieving seizure freedom—defined as no seizures for at least the previous year—has remained unchanged across three consecutive decades. In this latest update, 64% of patients were seizure-free, a proportion identical to that reported in the earlier, smaller study undertaken in the same clinical setting and published in 2000.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; These findings were confirmed in a recent systematic review and meta-analysis of observational studies involving 10 109 children and adults with newly diagnosed epilepsy, published between 1995 and 2021.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; The pooled proportion of those achieving seizure freedom for 1 year at the last follow-up was 68% (95% confidence interval [CI]: 63%–72%), with outcomes not linked to the publication year or the earliest date of cohort recruitment. This lack of fundamental progress in treatment outcomes has underpinned the relentless search for the “magic bullet” that will result in long-term seizure freedom for the majority of people designated as having drug-resistant epilepsy.&lt;/p&gt;&lt;p&gt;The arrival of a number of third-generation ASMs over the past decade has sparked recent optimism that a breakthrough in epilepsy drug treatment may be on the horizon. These ASMs, omitting those limited to licensing for rare epilepsy syndromes, include lacosamide, eslicarbazepine, perampanel, brivaracetam, and cenobamate—listed in chronological order of approval. Among these, cenobamate arguably appears the most promising, as reviewed in this special supplement of articles.&lt;/p&gt;&lt;p&gt;In this supplement, Sperling and coworkers highlight the risks associated with uncontrolled seizures, particularly those with a focal onset leading to bilateral tonic–clonic seizures, which pose the highest risk for sudden unexpected death in epilepsy (SUDEP). They then summarize the impressive efficacy and tolerability of cenobamate in initial clinical trials and the high proportion of patients achieving seizure freedom, which was sustained in an open-label extension study. It is important to note that the reduction in seizu","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"66 S1","pages":"1-3"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain perfusion imaging by arterial spin labeling predicts postsurgical seizure freedom in pediatric focal lesional epilepsy: A pilot study.","authors":"Antonio Giulio Gennari, Luca Gaito, Dorottya Cserpan, Raimund Kottke, Niklaus Krayenbühl, Andrea Rüegger, Ruth O' Gorman Tuura, Georgia Ramantani","doi":"10.1111/epi.18375","DOIUrl":"https://doi.org/10.1111/epi.18375","url":null,"abstract":"<p><strong>Objective: </strong>This study was undertaken to determine whether integrating arterial spin labeling (ASL) perfusion imaging into presurgical planning improves postsurgical seizure outcomes in children with pharmacoresistant focal lesional epilepsy associated with focal cortical dysplasia (FCD) or low-grade epilepsy-associated tumors (LEATs).</p><p><strong>Methods: </strong>We retrospectively analyzed magnetic resonance imaging (MRI) scans from 18 children (median age = 4.8 years, interquartile range = 1.9-11.5) who underwent resection for FCD- or LEAT-associated pharmacoresistant epilepsy, with at least 1 year of follow-up. All patients underwent presurgical ASL imaging along with pre- and postsurgical structural MRI. Image postprocessing, including segmentation and coregistration, assessed the completeness of resection of the anatomical lesion and ASL-derived perfusion changes. DICE similarity scores measured the alignment of pre- to postsurgical segmentations, and the residue ratio assessed the percentage of presurgical segmentation remaining postresection. These metrics were then correlated with postsurgical seizure outcomes.</p><p><strong>Results: </strong>Fourteen (78%) patients achieved seizure freedom, and 13 (72%) had complete lesion resection. Qualitative analysis showed that complete inclusion of the perfusion changes within the resection cavity significantly correlated with seizure freedom (p = .009), whereas complete resection of the anatomical lesion did not (p = .57). Quantitative analysis indicated that higher alignment of the perfusion changes with the resection cavity, measured by the DICE score, was significantly associated with seizure freedom (p = .043), whereas alignment between lesion and resection was not (p = .44). Larger residual perfusion volumes significantly correlated with seizure recurrence (p = .008).</p><p><strong>Significance: </strong>Incorporating ASL perfusion imaging into presurgical evaluation may better delineate the epileptogenic zone, potentially improving postsurgical seizure outcomes. These findings support ASL as a valuable complementary tool in surgical planning for pharmacoresistant pediatric focal lesional epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of adjunctive cenobamate in people with focal-onset epilepsy: Interim results after 24-week observational period from the BLESS study.","authors":"Simona Lattanzi, Fedele Dono, Giuseppe d'Orsi, Alfredo D'Aniello, Mariangela Panebianco, Paolo Bonanni, Carlo Di Bonaventura, Elisa Montalenti, Antonio Gambardella, Federica Ranzato, Giada Pauletto, Elena Tartara, Angela La Neve, Francesca Bisulli, Giampaolo Vatti, Patrizia Pulitano, Claudio Liguori, Giovanni Assenza, Alfonso Giordano, Pietro Pignatta, Vincenzo Belcastro, Michela Cecconi, Simone Beretta, Chiara Pizzanelli, Marianna Pezzella, Massimo Gangitano, Maurizio Elia, Rosaria Renna, Catello Vollono, Angelo Pascarella, Luciana Tramacere, Giovanni De Maria, Daniela Audenino, Maria Pia Pasolini, Loretta Giuliano, Rosita Galli, Gionata Strigaro, Monica Puligheddu, Angelo Labate, Pietro Penza, Stefano Quadri, David Stokelj, Giovanni Boero, Elisa Fallica, Monica Santo Sabato, Giovanni Falcicchio, Nicoletta Foschi, Michela Procaccini, Valentina Villano, Gabriele Camattari, Fabiano Mele, Barbara Roncari, Giancarlo Di Gennaro","doi":"10.1111/epi.18357","DOIUrl":"https://doi.org/10.1111/epi.18357","url":null,"abstract":"<p><strong>Objective: </strong>Cenobamate is an antiseizure medication (ASM) with a dual mechanism of action that was recently approved for the treatment of focal seizures in adults. This analysis aimed to describe the outcomes at 12 and 24 weeks after starting cenobamate therapy in a real-world setting.</p><p><strong>Methods: </strong>BLESS [NCT05859854] is an ongoing, observational, retrospective and prospective cohort study to evaluate the real-world effectiveness and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy. Subgroup analysis was performed in subjects with 2 to 3 previous ASMs (early users) and those with >3 previous ASMs (late users).</p><p><strong>Results: </strong>The second interim analysis of the BLESS study included 388 participants with a median (interquartile range) age of 43.0 (31.0-54.0) years. They had a median of 6.0 (4.0-9.0) prior ASMs and a median of 7.2 (3.0-20.6) monthly seizures at baseline. The median monthly seizure frequency was reduced by 59.9% (19.2%-87.3%) from baseline to 24 weeks; 229 (59.0%) subjects had a ≥50% seizure frequency reduction, and 44 (11.3%) showed sustained seizure freedom. The proportion of participants taking ≤2 concomitant ASMs increased from 217 (56.5%) at baseline to 239 (65.7%) at 24 weeks. Among the early users (n = 76, 19.6%), the median reduction in monthly seizure frequency at 24 weeks was 78.0% (50.0-97.1%), and 76.3% of subjects had a ≥50% response rate. The frequency of adverse drug reactions (ADRs) was 5.3% and 23.4% in early and late users. The most frequent ADRs were somnolence, dizziness, and balance disorder; after the occurrence of ADRs, 63.5% of participants maintained the prescribed dose, and 5.2% permanently discontinued treatment.</p><p><strong>Significance: </strong>Cenobamate was effective in reducing seizure frequency in a real-world setting and showed a manageable safety profile. The treatment with cenobamate also reduced the burden of concomitant ASMs in both early and late users.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ENX-101, a GABA_A receptor α2,3,5-selective positive allosteric modulator, displays antiseizure effects in rodent seizure and epilepsy models.","authors":"Jordi Serrats, Krishna C Vadodaria, William Brubaker, Melissa Barker-Haliski, H Steve White, Alexis Evrard, Corinne Roucard, Eve Taylor, Kimberly E Vanover, Stephen Cunningham, Vikram Sudarsan, Michael A Rogawski","doi":"10.1111/epi.18340","DOIUrl":"https://doi.org/10.1111/epi.18340","url":null,"abstract":"<p><strong>Objective: </strong>γ-Aminobutyric acid type A (GABA_A) receptor positive allosteric modulators (PAMs) that lack α-subunit selectivity, including benzodiazepines such as diazepam, exhibit antiseizure actions in animal models and in humans. ENX-101 is a deuterated analog of the ⍺2,3,5-selective GABA_A receptor PAM L-838,417. The purpose of this study was to characterize the α-subunit selectivity of ENX-101 and evaluate its antiseizure potential in preclinical seizure and epilepsy models.</p><p><strong>Methods: </strong>ENX-101 potentiation of GABA chloride current responses in cells expressing recombinant GABA_A receptors were evaluated using an automated patch clamp assay. Antiseizure effects of ENX-101 were examined in the mouse 6 Hz test at 32 and 44 mA, amygdala kindled rats, and Genetic Absence Epilepsy Rat from Strasbourg (GAERS).</p><p><strong>Results: </strong>ENX-101 displayed partial PAM activity with respect to diazepam at GABA_A receptors containing α2, α3, or α5 subunits but did not enhance GABA responses of GABA_A receptors containing α1 subunits. ENX-101 (30, 100, and 300 mg/kg, i.p.) and diazepam protected most animals in the 6 Hz model at 32 mA but was less effective at 44 mA. In amygdala kindled rats, ENX-101 (1-100 mg/kg, p.o.) reduced behavioral seizure severity and afterdischarge duration in a dose-dependent manner. ENX-101 (0.075-100 mg/kg, p.o.) caused dose-dependent, persistent (>130 min) inhibition of spontaneous spike-and-wave discharges (SWDs) in GAERS, whereas diazepam transiently inhibited discharges. ENX-101 did not cause motor impairment, as measured by performance in the rotarod assay.</p><p><strong>Significance: </strong>ENX-101 is an α2,α3,α5-selective GABA_A receptor PAM that has high potency and partial efficacy. The drug is highly effective in rodent seizure and epilepsy models. ENX-101 is most potent in the GAERS model of absence epilepsy, and active in the 6 Hz model and amygdala kindled rats. These results demonstrate that a partial, subtype-selective GABA_A receptor PAM has activity in translationally validated preclinical epilepsy screening models. Clinical evaluation of ENX-101 as a treatment for focal and generalized epilepsies is warranted.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scoping review of single-item global rating scales utilized in epilepsy research: Patterns of use, challenges, and recommendations.","authors":"Ann Subota, Mandavi Kashyap, Yasamin Mahjoub, Guillermo Delgado-García, Colin B Josephson, Samuel Wiebe","doi":"10.1111/epi.18333","DOIUrl":"https://doi.org/10.1111/epi.18333","url":null,"abstract":"<p><p>SIGRs (single-item global ratings) are gaining popularity among clinicians and health researchers as efficient tools to assess patient-reported outcomes. There has been no systematic assessment of domains explored, methodological aspects, and validation efforts of SIGRs in epilepsy. We aimed to critically appraise and provide recommendations on the use and reporting of SIGRs in epilepsy research. We performed a systematic scoping review using the Joanna Briggs Institute's recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) method was used to search five electronic databases (MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane Register of Controlled Trials) from 1980 to present day. We included English-language studies utilizing SIGRs that assessed health aspects (concept) in people with epilepsy of all ages (participants), in all settings (context), containing ≥30 patients, and using SIGRs with continuous or categorical responses in any study design. Abstract and full-text review was conducted independently by two reviewers; disagreements were resolved through consensus. Standardized data abstraction was used. Of 16 417 citations, we included 289 studies, involving 114 584 patients who underwent 747 unique measurements using SIGRs. Use increased over time; 30% were published in the last 4 years, and 51% used 1 SIGR (range 1-23 SIGRs). Commonly assessed domains were overall health (24.2%) and seizure-related aspects (23.5%), whereas 37% measured perceived change. Most studies used SIGRs descriptively (80.1%). Numerous SIGR formats were used (most commonly Likert-like, 73.3%). Ad hoc SIGRs without validation occurred frequently (45.6%). Stem questions were absent in 9.5% of measures, and only 6.5% reported SIGR measurement properties. SIGRs are widely used and increasingly prevalent in epilepsy research to assess diverse domains across various formats. However, many SIGRs suffer from poor reporting and methodological limitations. We provide a comprehensive catalog of SIGRs and offer recommendations to improve their use in research and clinical practice.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}