Pub Date : 2025-09-10DOI: 10.1016/j.eplepsyres.2025.107661
Ioannis Karakis , Lidia MVR Moura , Nada Boualam , Martha Wetzel , David Howard
Objective
To provide updated estimates of the healthcare costs associated with epilepsy using large, state-based all-payer claims databases.
Methods
We conducted a retrospective cohort study using all-payer claims data from Colorado, Massachusetts, and Virginia for 2016–2019, including individuals enrolled in Medicare, Medicaid, and individual and small-group commercial plans. Individuals with epilepsy were identified using a validated claims-based algorithm and matched with non-epilepsy controls based on age and sex. The two groups' healthcare use and costs were compared using generalized linear regressions and adjusting for age, sex, insurance status, and comorbidities.
Results
The study included 150,808 adults with epilepsy in Colorado, 122,222 in Virginia, and 118,707 in Massachusetts. State-level estimates of annual costs for adults with epilepsy were between $28,000 and $34,000 (2021 U.S. dollars), whereas costs for matched controls were between $2900 and $6300. Adults with epilepsy incurred higher costs than matched controls across all types of care. Adjusted analyses revealed that costs attributable to epilepsy ranged from $12,000 to $31,000, depending on the covariates included.
Conclusion
Our study provides updated and comprehensive cost estimates for epilepsy from diverse U.S. states, demonstrating the utility of all-payer claims data to generate state-specific and aggregate estimates of epilepsy burden to guide interventions. This study confirms that epilepsy imposes a substantial economic burden on the healthcare system, with costs higher than previous estimates.
{"title":"The health care costs of epilepsy: Evidence from all-payer claims data","authors":"Ioannis Karakis , Lidia MVR Moura , Nada Boualam , Martha Wetzel , David Howard","doi":"10.1016/j.eplepsyres.2025.107661","DOIUrl":"10.1016/j.eplepsyres.2025.107661","url":null,"abstract":"<div><h3>Objective</h3><div>To provide updated estimates of the healthcare costs associated with epilepsy using large, state-based all-payer claims databases.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study using all-payer claims data from Colorado, Massachusetts, and Virginia for 2016–2019, including individuals enrolled in Medicare, Medicaid, and individual and small-group commercial plans. Individuals with epilepsy were identified using a validated claims-based algorithm and matched with non-epilepsy controls based on age and sex. The two groups' healthcare use and costs were compared using generalized linear regressions and adjusting for age, sex, insurance status, and comorbidities.</div></div><div><h3>Results</h3><div>The study included 150,808 adults with epilepsy in Colorado, 122,222 in Virginia, and 118,707 in Massachusetts. State-level estimates of annual costs for adults with epilepsy were between $28,000 and $34,000 (2021 U.S. dollars), whereas costs for matched controls were between $2900 and $6300. Adults with epilepsy incurred higher costs than matched controls across all types of care. Adjusted analyses revealed that costs attributable to epilepsy ranged from $12,000 to $31,000, depending on the covariates included.</div></div><div><h3>Conclusion</h3><div>Our study provides updated and comprehensive cost estimates for epilepsy from diverse U.S. states, demonstrating the utility of all-payer claims data to generate state-specific and aggregate estimates of epilepsy burden to guide interventions. This study confirms that epilepsy imposes a substantial economic burden on the healthcare system, with costs higher than previous estimates.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107661"},"PeriodicalIF":2.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060001","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}
Pub Date : 2025-09-09DOI: 10.1016/j.eplepsyres.2025.107662
Manav Jain , Laurel Charlesworth , Helen Driver , Gavin P. Winston , Lysa Boissé Lomax , Garima Shukla
Introduction
Persons with epilepsy (PWE) frequently contend with disrupted sleep related to multiple seizure related as well as other factors like medications and comorbidities. Such disturbances often lead to fragmented sleep, which can adversely affect quality of life and compromise seizure management. Previous
Although previous research has addressed conditions like sleep apnea and insomnia among PWE, less attention has been paid to periodic limb movements (PLMs), a requirement for diagnosis of the periodic limb movement disorder and also commonly observed in restless legs syndrome (RLS) as well as other conditions. This study aims to determine the prevalence and specific features of PLMs in PWE and to explore how these movements correlate with objective sleep measurements.
Methods
This investigation employed a retrospective chart review of consecutive adult patients diagnosed with epilepsy who underwent polysomnography at a tertiary-care sleep laboratory over a ten-year span. The control group consisted of individuals evaluated for possible obstructive sleep apnea, who were matched to cases based on age, sex, and the severity of sleep apnea. Patient records were initially identified using keywords related to “epilepsy” or “seizures.” Epilepsy diagnosis was confirmed through detailed chart review, which also yielded clinical details likety duration of epilepsy, seizure classification, and antiseizure medication usage. Sleep parameters such as sleep efficiency, spontaneous arousal index, periodic limb movement index, periodic limb movement with arousal index, and apnea-hypopnea index were extracted from archived polysomnography reports. The subsequent analysis was carried out using descriptive statistical methods using RStudio version 4.4.1.
Results
A total of 152 relevant patient records were found in the database. Of these, 61 patients with epilepsy (mean age 41.4 ± 17.2 years, including 31 females) met the inclusion criteria and were matched with 61 patients suspected for OSA. Within the epilepsy cohort, 43 patients experienced focal-onset epilepsy while 16 had generalized epilepsy. 25 patients were prescribed two or more antiseizure medications, and 12 were categorized as medically refractory. PLMs were detected in 23 % of patients with epilepsy compared to 26 % in the control group, with mean PLMI values of 6.1 ± 16.8 and 8.8 ± 20.7, respectively. The PLMAI was also similar between the two groups (0.5 ± 1.0 vs. 1.1 ± 2.4). Other sleep parameters, including the mean AHI (16.0 ± 20.0 in the epilepsy group vs. 19.7 ± 19.4 in the control group), did not exhibit significant differences between groups. Within the epilepsy cohort, the only factor linked to the presence of periodic limb movements was older age, with no observed association with seizure type, number of antiseizure medications, or seizure control.
{"title":"Periodic limb movements among persons with epilepsy: A retrospective polysomnographic study","authors":"Manav Jain , Laurel Charlesworth , Helen Driver , Gavin P. Winston , Lysa Boissé Lomax , Garima Shukla","doi":"10.1016/j.eplepsyres.2025.107662","DOIUrl":"10.1016/j.eplepsyres.2025.107662","url":null,"abstract":"<div><h3>Introduction</h3><div>Persons with epilepsy (PWE) frequently contend with disrupted sleep related to multiple seizure related as well as other factors like medications and comorbidities. Such disturbances often lead to fragmented sleep, which can adversely affect quality of life and compromise seizure management. Previous</div><div>Although previous research has addressed conditions like sleep apnea and insomnia among PWE, less attention has been paid to periodic limb movements (PLMs), a requirement for diagnosis of the periodic limb movement disorder and also commonly observed in restless legs syndrome (RLS) as well as other conditions. This study aims to determine the prevalence and specific features of PLMs in PWE and to explore how these movements correlate with objective sleep measurements.</div></div><div><h3>Methods</h3><div>This investigation employed a retrospective chart review of consecutive adult patients diagnosed with epilepsy who underwent polysomnography at a tertiary-care sleep laboratory over a ten-year span. The control group consisted of individuals evaluated for possible obstructive sleep apnea, who were matched to cases based on age, sex, and the severity of sleep apnea. Patient records were initially identified using keywords related to “epilepsy” or “seizures.” Epilepsy diagnosis was confirmed through detailed chart review, which also yielded clinical details likety duration of epilepsy, seizure classification, and antiseizure medication usage. Sleep parameters such as sleep efficiency, spontaneous arousal index, periodic limb movement index, periodic limb movement with arousal index, and apnea-hypopnea index were extracted from archived polysomnography reports. The subsequent analysis was carried out using descriptive statistical methods using RStudio version 4.4.1.</div></div><div><h3>Results</h3><div>A total of 152 relevant patient records were found in the database. Of these, 61 patients with epilepsy (mean age 41.4 ± 17.2 years, including 31 females) met the inclusion criteria and were matched with 61 patients suspected for OSA. Within the epilepsy cohort, 43 patients experienced focal-onset epilepsy while 16 had generalized epilepsy. 25 patients were prescribed two or more antiseizure medications, and 12 were categorized as medically refractory. PLMs were detected in 23 % of patients with epilepsy compared to 26 % in the control group, with mean PLMI values of 6.1 ± 16.8 and 8.8 ± 20.7, respectively. The PLMAI was also similar between the two groups (0.5 ± 1.0 vs. 1.1 ± 2.4). Other sleep parameters, including the mean AHI (16.0 ± 20.0 in the epilepsy group vs. 19.7 ± 19.4 in the control group), did not exhibit significant differences between groups. Within the epilepsy cohort, the only factor linked to the presence of periodic limb movements was older age, with no observed association with seizure type, number of antiseizure medications, or seizure control.</div></div><div><h3>Conclusions</h3><div>PLMs are a","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107662"},"PeriodicalIF":2.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085185","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}
Pub Date : 2025-09-06DOI: 10.1016/j.eplepsyres.2025.107660
Patricio S. Haro-Perez , Fausto A. Saltos-Ponce , Christopher D. Del Valle-Lascano , Ruthiar S. Cortes-Chiluiza , Jose E. Naranjo-Carrillo , Andrea Ortiz-Ordonez
Objective
To compare seizure outcomes and complication rates between magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) and resective surgery (RS) in patients with MRI-positive focal cortical dysplasia (FCD).
Methods
A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting seizure outcomes and complications in patients with MRI-positive FCD were included. Meta-analysis of the data was conducted using random effects models. Meta-regression explored associations between mean age at surgery and mean duration of epilepsy with seizure outcomes.
Results
Thirty-four studies were included, totaling 1162 patients for analysis. Engel I rates were 71.3 % for MRgLITT and 65.6 % for RS, with no difference between both arms (OR 1.11, 95 % CI 0.49–2.52; p = 0.79). Overall complication rates were similar (12 % vs. 11 %; RD: +1 %, 95 % CI, −7 % to +12 %; p = 0.84). MRgLITT had a significant higher rate of transient neurologic deficits (15 % vs. 6.4 %; RD: +8.6 %, 95 % CI, −0.6 % to +17.8 %; p = 0.012), while permanent deficits did not differ significantly (1.7 % vs. 4.4 %; RD: −3 %, 95 % CI, −6 % to +1 %; p = 0.30). In RS studies, mean age at surgery was not associated with seizure freedom (OR per 10 years 1.18, 95 % CI 0.77–1.79; p = 0.43), nor was mean epilepsy duration (OR per 5 years 1.05, 95 % CI 0.94–1.18; p = 0.343). Risk of bias was serious across studies. Across FCD type II RS studies, the pooled proportion of Engel I was 74.0 % (95 % CI 64.0–82.1; I² = 0.7 %).
Conclusion
In MRI-positive FCD, MRgLITT and RS yielded comparable seizure freedom and rates of permanent complications, but MRgLITT showed a higher risk of transient neurologic deficits. Study-level meta-regressions found no association between seizure freedom and mean age at surgery or epilepsy duration. Interpretation is limited by the indirect comparison, observational designs with serious risk of bias, and substantial heterogeneity in some analyses. Prospective, adequately powered head-to-head studies with standardized outcomes are needed to confirm these findings and guide surgical decision-making.
目的比较磁共振引导下激光间质热治疗（MRgLITT）和切除手术（RS）治疗mri阳性局灶性皮质发育不良（FCD）患者的癫痫发作结局和并发症发生率。方法按照系统评价和荟萃分析首选报告项目（PRISMA）指南进行系统评价。研究报告了mri阳性FCD患者的癫痫发作结果和并发症。采用随机效应模型对数据进行meta分析。meta回归探讨了手术时平均年龄和平均癫痫持续时间与癫痫发作结果之间的关系。结果纳入34项研究，共1162例患者。MRgLITT的Engel I率为71.3 %，RS为65.6% %，两组间无差异（OR 1.11, 95 % CI 0.49-2.52; p = 0.79）。总并发症发生率相似（12 % vs 11 %;RD: +1 %,95 % CI， - 7 %至+12 %；p = 0.84）。MRgLITT瞬变率显著高于神经赤字(15 % 6.4 vs %;理查德·道金斯:+ 8.6 %,95 % CI, 17.8−0.6 % + %;p = 0.012),而永久赤字没有显著差异(1.7 % 4.4 vs %;理查德·道金斯:−3 %,95 % CI,−6 % + 1 %;p = 0.30)。在RS研究中，手术时的平均年龄与癫痫发作自由无关（OR每10年1.18,95 % CI 0.77-1.79; p = 0.43），平均癫痫持续时间也无关（OR每5年1.05,95 % CI 0.94-1.18; p = 0.343）。所有研究的偏倚风险都很严重。在FCD II型RS研究中，Engel I的合并比例为74.0 %（95 % CI 64.0-82.1; I²= 0.7 %）。结论在mri阳性FCD患者中，MRgLITT和RS的癫痫发作自由度和永久性并发症发生率相当，但MRgLITT显示出更高的短暂性神经功能障碍风险。研究水平的meta回归发现癫痫发作自由度与手术时的平均年龄或癫痫持续时间之间没有关联。解释受到间接比较、具有严重偏倚风险的观察性设计和某些分析中的实质性异质性的限制。需要前瞻性的、具有标准化结果的充分有力的头对头研究来证实这些发现并指导手术决策。
{"title":"A comparison between magnetic resonance-guided laser interstitial thermal therapy and resective surgery for drug-resistant epilepsy in patients with MRI-positive focal cortical dysplasia: A systematic review and meta-analysis","authors":"Patricio S. Haro-Perez , Fausto A. Saltos-Ponce , Christopher D. Del Valle-Lascano , Ruthiar S. Cortes-Chiluiza , Jose E. Naranjo-Carrillo , Andrea Ortiz-Ordonez","doi":"10.1016/j.eplepsyres.2025.107660","DOIUrl":"10.1016/j.eplepsyres.2025.107660","url":null,"abstract":"<div><h3>Objective</h3><div>To compare seizure outcomes and complication rates between magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) and resective surgery (RS) in patients with MRI-positive focal cortical dysplasia (FCD).</div></div><div><h3>Methods</h3><div>A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting seizure outcomes and complications in patients with MRI-positive FCD were included. Meta-analysis of the data was conducted using random effects models. Meta-regression explored associations between mean age at surgery and mean duration of epilepsy with seizure outcomes.</div></div><div><h3>Results</h3><div>Thirty-four studies were included, totaling 1162 patients for analysis. Engel I rates were 71.3 % for MRgLITT and 65.6 % for RS, with no difference between both arms (OR 1.11, 95 % CI 0.49–2.52; p = 0.79). Overall complication rates were similar (12 % vs. 11 %; RD: +1 %, 95 % CI, −7 % to +12 %; p = 0.84). MRgLITT had a significant higher rate of transient neurologic deficits (15 % vs. 6.4 %; RD: +8.6 %, 95 % CI, −0.6 % to +17.8 %; p = 0.012), while permanent deficits did not differ significantly (1.7 % vs. 4.4 %; RD: −3 %, 95 % CI, −6 % to +1 %; p = 0.30). In RS studies, mean age at surgery was not associated with seizure freedom (OR per 10 years 1.18, 95 % CI 0.77–1.79; p = 0.43), nor was mean epilepsy duration (OR per 5 years 1.05, 95 % CI 0.94–1.18; p = 0.343). Risk of bias was serious across studies. Across FCD type II RS studies, the pooled proportion of Engel I was 74.0 % (95 % CI 64.0–82.1; I² = 0.7 %).</div></div><div><h3>Conclusion</h3><div>In MRI-positive FCD, MRgLITT and RS yielded comparable seizure freedom and rates of permanent complications, but MRgLITT showed a higher risk of transient neurologic deficits. Study-level meta-regressions found no association between seizure freedom and mean age at surgery or epilepsy duration. Interpretation is limited by the indirect comparison, observational designs with serious risk of bias, and substantial heterogeneity in some analyses. Prospective, adequately powered head-to-head studies with standardized outcomes are needed to confirm these findings and guide surgical decision-making.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107660"},"PeriodicalIF":2.0,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044612","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}
Pub Date : 2025-09-05DOI: 10.1016/j.eplepsyres.2025.107646
Lena Mühe , Elisabeth Kaufmann , Mirjam N. Landgraf , Moritz Tacke , Christine Makowski , Malin Zaddach , Leonie Grosse , Miriam Gerstner , Robert Optiz , Ingo Borggraefe
Background
The EpiTrack Junior is a screening tool assessing executive function in children with epilepsy. This study aimed to investigate whether children and adolescents with epilepsy are at a higher risk of experiencing a reduced quality of life if they also reveal abnormal results reflecting executive dysfunction.
Methods
We screened patients for executive dysfunction using the clinical test tool EpiTrack Junior. To assess health-related quality of life (HRQoL), the German children’s and parents’ version of KINDL questionnaire was used. The KINDL scores (total score and dimensions scores) of patients with and without clinically conspicuous values were compared (≤ 28 and > 29, respectively). In addition, the exact EpiTrack Junior point scores were correlated with the KINDL total score and the scores of all KINDL dimensions.
Results
In this study 112 (mean age = 11.72, SD = 3.6) patients with epilepsy and their parents were included. Patients with executive dysfunctions (EpiTrack Junior values ≤ 28) scored significantly poorer in the QoL categories ‘family’ and ‘social environment’ than patients without. In the ‘family’ dimension, the child-report revealed the following data: z = -2.759; adjusted p-value: 0.042, and in the ‘friends’ dimension, parent-reports yielded the following data: z = -3.645; adjusted p-value: 0.007. In contrast, the 'self-esteem' dimension in the children's version showed significantly higher values in patients with executive dysfunctions than for those without: z = -2.524; adjusted p-value: 0.042. No significant differences between patients with and without executive dysfunctions were found for the overall quality of life (as assessed by the KINDL 'total score') as well as for the other dimensions (school, physical and emotional well-being).
Conclusions
No differences were found in the overall quality of life between patients with and without executive dysfunction. Nevertheless, executive dysfunction appeared to have a negative impact on some areas of life, such as family and friends, and was a predictor of increased self-esteem.
{"title":"Influence of executive functions on quality of life in Pediatric Epilepsy: A cross-sectional study","authors":"Lena Mühe , Elisabeth Kaufmann , Mirjam N. Landgraf , Moritz Tacke , Christine Makowski , Malin Zaddach , Leonie Grosse , Miriam Gerstner , Robert Optiz , Ingo Borggraefe","doi":"10.1016/j.eplepsyres.2025.107646","DOIUrl":"10.1016/j.eplepsyres.2025.107646","url":null,"abstract":"<div><h3>Background</h3><div>The EpiTrack Junior is a screening tool assessing executive function in children with epilepsy. This study aimed to investigate whether children and adolescents with epilepsy are at a higher risk of experiencing a reduced quality of life if they also reveal abnormal results reflecting executive dysfunction.</div></div><div><h3>Methods</h3><div>We screened patients for executive dysfunction using the clinical test tool EpiTrack Junior. To assess health-related quality of life (HRQoL), the German children’s and parents’ version of KINDL questionnaire was used. The KINDL scores (total score and dimensions scores) of patients with and without clinically conspicuous values were compared (≤ 28 and > 29, respectively). In addition, the exact EpiTrack Junior point scores were correlated with the KINDL total score and the scores of all KINDL dimensions.</div></div><div><h3>Results</h3><div>In this study 112 (mean age = 11.72, SD = 3.6) patients with epilepsy and their parents were included. Patients with executive dysfunctions (EpiTrack Junior values ≤ 28) scored significantly poorer in the QoL categories ‘family’ and ‘social environment’ than patients without. In the ‘family’ dimension, the child-report revealed the following data: z = -2.759; adjusted <em>p-</em>value: 0.042, and in the ‘friends’ dimension, parent-reports yielded the following data: z = -3.645; adjusted <em>p</em>-value: 0.007. In contrast, the 'self-esteem' dimension in the children's version showed significantly higher values in patients with executive dysfunctions than for those without: z = -2.524; adjusted <em>p-</em>value: 0.042. No significant differences between patients with and without executive dysfunctions were found for the overall quality of life (as assessed by the KINDL 'total score') as well as for the other dimensions (school, physical and emotional well-being).</div></div><div><h3>Conclusions</h3><div>No differences were found in the overall quality of life between patients with and without executive dysfunction. Nevertheless, executive dysfunction appeared to have a negative impact on some areas of life, such as family and friends, and was a predictor of increased self-esteem.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107646"},"PeriodicalIF":2.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018500","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}
Pub Date : 2025-09-04DOI: 10.1016/j.eplepsyres.2025.107656
Zheng-Dong Lim , Nur Asyiqin Syafiqa Abdullah , Kheng-Seang Lim , Paul Chi-Lui Ho , Alina Arulsamy , Si-Lei Fong , Hui-Yin Yow
Drug-resistant epilepsy (DRE) is characterized by the failure to attain sustained seizure freedom despite adequate trials of two antiseizure medication (ASM) regimens that are well tolerated and appropriately chosen and administered, either as monotherapies or in combination. Despite being a cornerstone of epilepsy treatment, ASMs are ineffective in achieving seizure remission in nearly one-third of patients, who are consequently classified as having DRE. This systematic review aims to determine potential metabolic biomarkers and pathways linked to DRE, which could inform personalized treatment and optimize therapeutic outcomes. A comprehensive search of databases, namely Medline, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) based on predefined inclusion and exclusion criteria yielded 29 eligible studies after full-text screening. The risk of bias from these studies was reviewed using the Office of Health Assessment and Translation (OHAT) risk of bias rating tool. Key information, including study groups, sample size, model types, and main findings were tabulated. Several metabolites were identified, including amino acids (glycine, glutamate, isoleucine), organic acids (lactate), and glucose, which may serve as potential biomarkers for DRE. MetaboAnalyst 6.0 pathway analysis identified the alanine, aspartate and glutamate metabolism, as well as phenylalanine, tyrosine and tryptophan biosynthesis pathways, emerged with significant impact score (≥0.5, p < 0.05). The findings highlight the promising role of these metabolites and pathways as predictive biomarkers for DRE and potential therapeutic targets for novel drug development.
耐药癫痫（DRE）的特点是，尽管对两种抗癫痫药物（ASM）方案进行了充分的试验，但仍未能实现持续的癫痫发作自由，这两种抗癫痫药物（ASM）方案具有良好的耐受性，并且可以作为单一疗法或联合疗法进行适当的选择和施用。尽管asm是癫痫治疗的基石，但在近三分之一的患者中，asm对癫痫发作的缓解是无效的，因此这些患者被归类为DRE。本系统综述旨在确定与DRE相关的潜在代谢生物标志物和途径，从而为个性化治疗提供信息并优化治疗结果。综合检索数据库，即Medline， Web of Science和Cochrane Central Register of Controlled Trials (Central)，基于预定义的纳入和排除标准，在全文筛选后获得29项符合条件的研究。使用健康评估和翻译办公室（OHAT）偏倚风险评级工具对这些研究的偏倚风险进行了审查。关键信息，包括研究组、样本量、模型类型和主要发现被制成表格。鉴定出几种代谢物，包括氨基酸（甘氨酸、谷氨酸、异亮氨酸）、有机酸（乳酸）和葡萄糖，它们可能作为DRE的潜在生物标志物。MetaboAnalyst 6.0通路分析发现丙氨酸、天冬氨酸和谷氨酸代谢，以及苯丙氨酸、酪氨酸和色氨酸的生物合成通路，出现显著影响评分（≥0.5,p <； 0.05）。这些发现强调了这些代谢物和途径作为DRE的预测性生物标志物和新药开发的潜在治疗靶点的有希望的作用。
{"title":"Exploring metabolic biomarkers and pathways in pharmacoresistant epilepsy: A systematic review","authors":"Zheng-Dong Lim , Nur Asyiqin Syafiqa Abdullah , Kheng-Seang Lim , Paul Chi-Lui Ho , Alina Arulsamy , Si-Lei Fong , Hui-Yin Yow","doi":"10.1016/j.eplepsyres.2025.107656","DOIUrl":"10.1016/j.eplepsyres.2025.107656","url":null,"abstract":"<div><div>Drug-resistant epilepsy (DRE) is characterized by the failure to attain sustained seizure freedom despite adequate trials of two antiseizure medication (ASM) regimens that are well tolerated and appropriately chosen and administered, either as monotherapies or in combination. Despite being a cornerstone of epilepsy treatment, ASMs are ineffective in achieving seizure remission in nearly one-third of patients, who are consequently classified as having DRE. This systematic review aims to determine potential metabolic biomarkers and pathways linked to DRE, which could inform personalized treatment and optimize therapeutic outcomes. A comprehensive search of databases, namely Medline, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) based on predefined inclusion and exclusion criteria yielded 29 eligible studies after full-text screening. The risk of bias from these studies was reviewed using the Office of Health Assessment and Translation (OHAT) risk of bias rating tool. Key information, including study groups, sample size, model types, and main findings were tabulated. Several metabolites were identified, including amino acids (glycine, glutamate, isoleucine), organic acids (lactate), and glucose, which may serve as potential biomarkers for DRE. MetaboAnalyst 6.0 pathway analysis identified the alanine, aspartate and glutamate metabolism, as well as phenylalanine, tyrosine and tryptophan biosynthesis pathways, emerged with significant impact score (≥0.5, p < 0.05). The findings highlight the promising role of these metabolites and pathways as predictive biomarkers for DRE and potential therapeutic targets for novel drug development.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107656"},"PeriodicalIF":2.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044611","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}
Pub Date : 2025-09-02DOI: 10.1016/j.eplepsyres.2025.107655
Hakimeh Gavzan , Mohammad Sayyah , Tara Asgari , Mohammad Ali Mobaraki
Introduction
Docosahexaenoic acid (DHA) is a bioactive fatty acid with safe and acceptable anti-seizure activity in clinical and animal studies. Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, with a high rate of drug resistance. The peroxisome proliferator-activated receptor α (PPARα) is expressed in the brain and plays a significant role in oxidative stress, energy homeostasis, and mitochondrial fatty acid metabolism. We aimed to evaluate the acute effect of DHA on the amygdala-kindled seizures and the role of PPARα in the DHA effect.
Methods
Male rats were kindled by repetitive daily electrical stimulation of the amygdala through a stimulating-recording electrode. DHA 1 mM (alone, or along with the PPARα antagonist GW6471, 2 and/or 4 μg/rat) was injected into the lateral cerebral ventricle of the kindled rats. The amygdala-kindled seizures were evoked 15 and 30 min after drug administration. The duration of after-discharges (ADD), generalized seizure behavior (S5D), and total seizure behavior (SD) were recorded.
Results
DHA significantly decreased ADD (p < 0.05), S5D (p < 0.05), SD (p < 0.05), and incidence of S5 (p < 0.05). GW6471 2 μg/rat did not change seizure parameters but at 4 μg/rat significantly increased ADD (p < 0.001). GW6471 2 μg/rat diminished the anticonvulsant effect of DHA.
Conclusion
Acute administration of DHA inhibits amygdala-kindled seizures by activating PPARα. Although PPARα is a nuclear receptor, it partly mediates the acute anti-seizure effect of DHA by rapid non-genomic changes in cellular function. This finding reveals another characteristic of the remarkable omega-3 fatty acid, DHA.
{"title":"Docosahexaenoic acid provides a protective effect in amygdala-kindled rats by activating peroxisome proliferator-activated receptor α","authors":"Hakimeh Gavzan , Mohammad Sayyah , Tara Asgari , Mohammad Ali Mobaraki","doi":"10.1016/j.eplepsyres.2025.107655","DOIUrl":"10.1016/j.eplepsyres.2025.107655","url":null,"abstract":"<div><h3>Introduction</h3><div>Docosahexaenoic acid (DHA) is a bioactive fatty acid with safe and acceptable anti-seizure activity in clinical and animal studies. Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, with a high rate of drug resistance. The peroxisome proliferator-activated receptor α (PPARα) is expressed in the brain and plays a significant role in oxidative stress, energy homeostasis, and mitochondrial fatty acid metabolism. We aimed to evaluate the acute effect of DHA on the amygdala-kindled seizures and the role of PPARα in the DHA effect.</div></div><div><h3>Methods</h3><div>Male rats were kindled by repetitive daily electrical stimulation of the amygdala through a stimulating-recording electrode. DHA 1 mM (alone, or along with the PPARα antagonist GW6471, 2 and/or 4 μg/rat) was injected into the lateral cerebral ventricle of the kindled rats. The amygdala-kindled seizures were evoked 15 and 30 min after drug administration. The duration of after-discharges (ADD), generalized seizure behavior (S5D), and total seizure behavior (SD) were recorded.</div></div><div><h3>Results</h3><div>DHA significantly decreased ADD (<em>p</em> < 0.05), S5D (<em>p</em> < 0.05), SD (<em>p</em> < 0.05), and incidence of S5 (<em>p</em> < 0.05). GW6471 2 μg/rat did not change seizure parameters but at 4 μg/rat significantly increased ADD (<em>p</em> < 0.001). GW6471 2 μg/rat diminished the anticonvulsant effect of DHA.</div></div><div><h3>Conclusion</h3><div>Acute administration of DHA inhibits amygdala-kindled seizures by activating PPARα. Although PPARα is a nuclear receptor, it partly mediates the acute anti-seizure effect of DHA by rapid non-genomic changes in cellular function. This finding reveals another characteristic of the remarkable omega-3 fatty acid, DHA.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107655"},"PeriodicalIF":2.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988077","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}
Primary generalized tonic-clonic seizures (pGTCS) are often misdiagnosed and remain challenging to manage due to limited treatment options. Lacosamide (LCM), approved for focal-onset seizures and adjunctive pGTCS therapy, was evaluated for real-world effectiveness in Indian patients.
Methods
This real-world, multicenter, retrospective, observational, and non-interventional study was conducted across 124 centers in India following approval from a centralized institutional ethics committee. Data were analysed using descriptive and analytical statistical methods for continuous and categorical variables, utilizing SPSS version 29.0.1.0.
Results
The Full Analysis Set (FAS) included 685 patients (245 females, 35.77 %; 440 males, 64.23 %) with a mean age of 43.30 ± 11.87 years. Among them, 301 (43.94 %) had pGTCS and 384 (56.06 %) had FoS. Concomitant ASMs for pGTCS included LEV (68.44 %), VPA (21.93 %), and CBZ (13.62 %), while for FoS, LEV (47.14 %) was most common, followed by VPA (16.15 %) and CBZ (14.58 %).
At week 12, mean seizure frequency in pGTCS reduced from 3 to 1 (p < 0.0001), with 52.16 % achieving seizure freedom and a 66.78 % responder rate. LCM with LEV showed a two-fold higher responder rate than with other ASMs (OR: 2.3582, p = 0.0037). In FoS, 47.66 % achieved seizure freedom, with a 58.85 % responder rate. Moreover, when prescribed as monotherapy in FoS, LCM showed a 62.96 % responder rate. LCM was generally well tolerated across both groups, with no unexpected safety concerns observed during the study period.
Conclusion
This study demonstrated the effectiveness of LCM therapy in reducing seizure frequency and improving seizure control in Indian patients with epilepsy. LCM was well tolerated and remains potential therapeutic option either as monotherapy or as an adjuvant therapy in the management of FoS.
{"title":"Real world observational study investigating clinical effectiveness and safety of lacosamide in epilepsy: ULTIMATE study","authors":"Sanjay Bhaumik , S.C. Nemichandra , Divyam Sharma , Malini Gopinath , Yakshdeep Dave , Zahraan Qureshi , Krishnaprasad Korukonda , Girish Kulkarni","doi":"10.1016/j.eplepsyres.2025.107657","DOIUrl":"10.1016/j.eplepsyres.2025.107657","url":null,"abstract":"<div><h3>Objective</h3><div>Primary generalized tonic-clonic seizures (pGTCS) are often misdiagnosed and remain challenging to manage due to limited treatment options. Lacosamide (LCM), approved for focal-onset seizures and adjunctive pGTCS therapy, was evaluated for real-world effectiveness in Indian patients.</div></div><div><h3>Methods</h3><div>This real-world, multicenter, retrospective, observational, and non-interventional study was conducted across 124 centers in India following approval from a centralized institutional ethics committee. Data were analysed using descriptive and analytical statistical methods for continuous and categorical variables, utilizing SPSS version 29.0.1.0.</div></div><div><h3>Results</h3><div>The Full Analysis Set (FAS) included 685 patients (245 females, 35.77 %; 440 males, 64.23 %) with a mean age of 43.30 ± 11.87 years. Among them, 301 (43.94 %) had pGTCS and 384 (56.06 %) had FoS. Concomitant ASMs for pGTCS included LEV (68.44 %), VPA (21.93 %), and CBZ (13.62 %), while for FoS, LEV (47.14 %) was most common, followed by VPA (16.15 %) and CBZ (14.58 %).</div><div>At week 12, mean seizure frequency in pGTCS reduced from 3 to 1 (p < 0.0001), with 52.16 % achieving seizure freedom and a 66.78 % responder rate. LCM with LEV showed a two-fold higher responder rate than with other ASMs (OR: 2.3582, p = 0.0037). In FoS, 47.66 % achieved seizure freedom, with a 58.85 % responder rate. Moreover, when prescribed as monotherapy in FoS, LCM showed a 62.96 % responder rate. LCM was generally well tolerated across both groups, with no unexpected safety concerns observed during the study period.</div></div><div><h3>Conclusion</h3><div>This study demonstrated the effectiveness of LCM therapy in reducing seizure frequency and improving seizure control in Indian patients with epilepsy. LCM was well tolerated and remains potential therapeutic option either as monotherapy or as an adjuvant therapy in the management of FoS.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107657"},"PeriodicalIF":2.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018501","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}
Pub Date : 2025-08-31DOI: 10.1016/j.eplepsyres.2025.107645
Karin Daniele , Jaroslava Raudenská , Alena Javůrková
Objective
This study investigated the prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in Czech adult people with epilepsy (PWE) and examined factors potentially contributing to the co-occurrence of these two conditions. Although previous research has consistently reported elevated rates of ADHD in epilepsy populations, data from adult samples in Czech Republic remain limited.
Methods
Fifty-six adults with epilepsy completed validated self-report questionnaires assessing ADHD symptoms (ASRS), anxiety (GAD-2), and depression (NDDIE-2). Epilepsy-related clinical factors, such as seizure frequency, anti-seizure medication (ASM), type of epilepsy and epilepsy duration, were also analyzed in relation to ADHD symptoms.
Results
A high prevalence of ADHD symptoms n = 25 (44.6 %) was found in the sample. No significant associations were observed between ADHD symptoms and epilepsy-related variables or depressive symptoms, but a regression model of clinical and sociodemographic variables can explain 34.2 % of the variance in ASRS scores (Adj. R² = 0.342), with only anxiety emerging as a significant predictor (β = 0.517, SE = 0.50, t = 3.23, p = .003).
Conclusion
These preliminary findings suggest a possible link between epilepsy and ADHD, which may be further explored in future research through shared emotional or neurobiological mechanisms. The results underscore the need for integrated screening approaches and further research into the co-occurrence of epilepsy and ADHD in adult populations.
目的调查捷克成年癫痫患者（PWE）注意力缺陷/多动障碍（ADHD）症状的患病率，并探讨可能导致这两种情况同时发生的因素。尽管先前的研究一直报道癫痫人群中多动症的发病率升高，但捷克共和国成人样本的数据仍然有限。方法56例成人癫痫患者完成了评估ADHD症状（ASRS）、焦虑（GAD-2）和抑郁（NDDIE-2）的有效自我报告问卷。分析癫痫相关临床因素，如癫痫发作频率、抗癫痫药物（ASM）、癫痫类型和癫痫持续时间与ADHD症状的关系。结果本组儿童ADHD患病率较高，分别为 = 25（44.6% %）。ADHD症状与癫痫相关变量或抑郁症状之间没有明显的关联，但临床和社会人口学变量的回归模型可以解释ASRS评分中34.2% %的方差（Adj. R²= 0.342），只有焦虑是一个显著的预测因子（β = 0.517, SE = 0.50, t = 3.23,p = .003）。结论这些初步发现提示癫痫与ADHD之间可能存在联系，未来的研究可以通过共同的情绪或神经生物学机制进一步探索这一联系。这些结果强调需要综合筛查方法，并进一步研究成人人群中癫痫和ADHD的共发情况。
{"title":"Attention-deficit/hyperactivity disorder in adults with epilepsy: Preliminary prevalence and associated factors in a Czech sample","authors":"Karin Daniele , Jaroslava Raudenská , Alena Javůrková","doi":"10.1016/j.eplepsyres.2025.107645","DOIUrl":"10.1016/j.eplepsyres.2025.107645","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigated the prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in Czech adult people with epilepsy (PWE) and examined factors potentially contributing to the co-occurrence of these two conditions. Although previous research has consistently reported elevated rates of ADHD in epilepsy populations, data from adult samples in Czech Republic remain limited.</div></div><div><h3>Methods</h3><div>Fifty-six adults with epilepsy completed validated self-report questionnaires assessing ADHD symptoms (ASRS), anxiety (GAD-2), and depression (NDDIE-2). Epilepsy-related clinical factors, such as seizure frequency, anti-seizure medication (ASM), type of epilepsy and epilepsy duration, were also analyzed in relation to ADHD symptoms.</div></div><div><h3>Results</h3><div>A high prevalence of ADHD symptoms n = 25 (44.6 %) was found in the sample. No significant associations were observed between ADHD symptoms and epilepsy-related variables or depressive symptoms, but a regression model of clinical and sociodemographic variables can explain 34.2 % of the variance in ASRS scores (Adj. R² = 0.342), with only anxiety emerging as a significant predictor (β = 0.517, SE = 0.50, t = 3.23, p = .003).</div></div><div><h3>Conclusion</h3><div>These preliminary findings suggest a possible link between epilepsy and ADHD, which may be further explored in future research through shared emotional or neurobiological mechanisms. The results underscore the need for integrated screening approaches and further research into the co-occurrence of epilepsy and ADHD in adult populations.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107645"},"PeriodicalIF":2.0,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018503","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}
Pub Date : 2025-08-30DOI: 10.1016/j.eplepsyres.2025.107647
Sami Aboumatar , Jay R. Gavvala , Zeenat Jaisani , Ruben Kuzniecky , Michael Privitera , Madeline Ring , William E. Rosenfeld , Jacob Pellinen
Objectives
Responsive neurostimulation (RNS) electrocorticographic (ECoG) data may have a role in objectively assessing the efficacy of add-on antiseizure medications (ASMs). This retrospective, multicenter, observational, 24-week study is the first to report the effects of cenobamate on RNS-detected events (RDE).
Methods
Patients included adults (≥18 years) with a history of recurrent focal seizures and implanted RNS who initiated adjunctive cenobamate ≥ 3 months after RNS implant between 4/1/20–12/15/23 and who received ≥ 2 weeks of cenobamate (≥50 mg/day). RDE (“long episodes,” “long episodes with saturation,” and “saturation”) obtained from the NeuroPace Patient Data Management System were reviewed to select only electrographic seizures (ESs) based on electrographic ictal patterns. RDEs and ESs were counted during the 8-week baseline period, every 2 weeks for 12 weeks after starting cenobamate, and at study end. The main outcome was percent change from baseline to the end of the 16-week treatment period (12 + weeks) for overall ESs, ESs ≥ 50 seconds, and ESs < 50 seconds. Patient-reported clinical seizure frequency was recorded when available.
Results
Thirty-seven patients (mean age 36.7 years) were included. Median cenobamate dose was 150 mg/day (range, 50–250 mg/day). There was a significant median percent reduction from baseline to the end of cenobamate treatment in ESs (94.4 %; p < 0.0001), ESs ≥ 50 s (100.0 %; p < 0.0001), and ESs < 50 s (100.0 %; p < 0.0001). Among patients with available seizure data (n = 24), median percent reduction in clinical seizures per 28 days from baseline to end of treatment was 72.2 % (p < 0.0001). Adverse events were reported in 27 % (10/37) of patients; dizziness, fatigue, and sleepiness were most reported.
Significance
Patients with uncontrolled seizures after RNS had a significant reduction in ESs and clinically reported seizures during adjunctive cenobamate treatment. Results from this analysis support the potential use of RNS ECoG data as an objective measure to supplement clinical data when determining cenobamate efficacy and may provide a strategy for monitoring responses to ASMs more generally in this population.
Data Availability
The data for the analyses described in this paper are available by request from the corresponding author or from SK Life Science, Inc., the company sponsoring the clinical development of cenobamate for the treatment of focal epilepsy.
{"title":"Electrographic seizures on responsive neurostimulation: An early and objective measure of response to cenobamate","authors":"Sami Aboumatar , Jay R. Gavvala , Zeenat Jaisani , Ruben Kuzniecky , Michael Privitera , Madeline Ring , William E. Rosenfeld , Jacob Pellinen","doi":"10.1016/j.eplepsyres.2025.107647","DOIUrl":"10.1016/j.eplepsyres.2025.107647","url":null,"abstract":"<div><h3>Objectives</h3><div>Responsive neurostimulation (RNS) electrocorticographic (ECoG) data may have a role in objectively assessing the efficacy of add-on antiseizure medications (ASMs). This retrospective, multicenter, observational, 24-week study is the first to report the effects of cenobamate on RNS-detected events (RDE).</div></div><div><h3>Methods</h3><div>Patients included adults (≥18 years) with a history of recurrent focal seizures and implanted RNS who initiated adjunctive cenobamate ≥ 3 months after RNS implant between 4/1/20–12/15/23 and who received ≥ 2 weeks of cenobamate (≥50 mg/day). RDE (“long episodes,” “long episodes with saturation,” and “saturation”) obtained from the NeuroPace Patient Data Management System were reviewed to select only electrographic seizures (ESs) based on electrographic ictal patterns. RDEs and ESs were counted during the 8-week baseline period, every 2 weeks for 12 weeks after starting cenobamate, and at study end. The main outcome was percent change from baseline to the end of the 16-week treatment period (12 + weeks) for overall ESs, ESs ≥ 50 seconds, and ESs < 50 seconds. Patient-reported clinical seizure frequency was recorded when available.</div></div><div><h3>Results</h3><div>Thirty-seven patients (mean age 36.7 years) were included. Median cenobamate dose was 150 mg/day (range, 50–250 mg/day). There was a significant median percent reduction from baseline to the end of cenobamate treatment in ESs (94.4 %; p < 0.0001), ESs ≥ 50 s (100.0 %; p < 0.0001), and ESs < 50 s (100.0 %; p < 0.0001). Among patients with available seizure data (n = 24), median percent reduction in clinical seizures per 28 days from baseline to end of treatment was 72.2 % (p < 0.0001). Adverse events were reported in 27 % (10/37) of patients; dizziness, fatigue, and sleepiness were most reported.</div></div><div><h3>Significance</h3><div>Patients with uncontrolled seizures after RNS had a significant reduction in ESs and clinically reported seizures during adjunctive cenobamate treatment. Results from this analysis support the potential use of RNS ECoG data as an objective measure to supplement clinical data when determining cenobamate efficacy and may provide a strategy for monitoring responses to ASMs more generally in this population.</div></div><div><h3>Data Availability</h3><div>The data for the analyses described in this paper are available by request from the corresponding author or from SK Life Science, Inc., the company sponsoring the clinical development of cenobamate for the treatment of focal epilepsy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107647"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003869","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}
Pub Date : 2025-08-26DOI: 10.1016/j.eplepsyres.2025.107644
Caleb Rhodes , Benjamin Rees , Holly Dubbs , Mollie Lesser , Lucas Morgan , Tim A. Benke , Alan Percy , Jeffrey L. Neul , Eric D. Marsh , for the NIH Rett and Related Disorders Natural History Study
Background
FOXG1 syndrome is rare neurodevelopmental disorder with microcephaly, brain malformations, epilepsy, and cognitive and motor disabilities as major features. Knowledge of the clinical features is primarily from case series and a foundation sponsored registry. We expand insight into epilepsy in FOXG1 syndrome by examining longitudinal data from 94 individuals from a multi-site natural history study and local cohorts.
Methods
Clinical information on severity, seizure type, and seizure features was collected from 68 individuals enrolled in the Rett Syndrome and Related Disorders Natural History Study and extracted via retrospective chart review from 15 individuals seen at the Children’s Hospital of Philadelphia Rett Syndrome Center of Excellence and 11 individuals from Children’s Hospital of Colorado. Genotype-phenotype and other correlations were assessed using non- and semi-parametric analyses.
Results
78.7 % of participants had seizures, beginning at a median age of 1.0 years. Individuals were followed for a median of 4.9 years after first seizure onset. Taken independently, over 70 % of seizures were partial or tonic-clonic, occurred less than weekly, and lasted less than 5 min. 1/3 of seizures resolved in a median time and age of 1.1 and 3.3 years. Age had a weak non-linear association with average seizure frequency, and, for those with seizures, smaller head circumference correlated with increased disease severity.
Conclusions
We further characterize disease severity and epilepsy in FOXG1 syndrome and demonstrate that smaller head circumferences are associated with more severe disease and age is weakly non-linearly correlated with average seizure frequency. This information will improve clinical care and aid therapeutic development.
{"title":"Natural history of epilepsy in FOXG1 Syndrome","authors":"Caleb Rhodes , Benjamin Rees , Holly Dubbs , Mollie Lesser , Lucas Morgan , Tim A. Benke , Alan Percy , Jeffrey L. Neul , Eric D. Marsh , for the NIH Rett and Related Disorders Natural History Study","doi":"10.1016/j.eplepsyres.2025.107644","DOIUrl":"10.1016/j.eplepsyres.2025.107644","url":null,"abstract":"<div><h3>Background</h3><div>FOXG1 syndrome is rare neurodevelopmental disorder with microcephaly, brain malformations, epilepsy, and cognitive and motor disabilities as major features. Knowledge of the clinical features is primarily from case series and a foundation sponsored registry. We expand insight into epilepsy in FOXG1 syndrome by examining longitudinal data from 94 individuals from a multi-site natural history study and local cohorts.</div></div><div><h3>Methods</h3><div>Clinical information on severity, seizure type, and seizure features was collected from 68 individuals enrolled in the Rett Syndrome and Related Disorders Natural History Study and extracted via retrospective chart review from 15 individuals seen at the Children’s Hospital of Philadelphia Rett Syndrome Center of Excellence and 11 individuals from Children’s Hospital of Colorado. Genotype-phenotype and other correlations were assessed using non- and semi-parametric analyses.</div></div><div><h3>Results</h3><div>78.7 % of participants had seizures, beginning at a median age of 1.0 years. Individuals were followed for a median of 4.9 years after first seizure onset. Taken independently, over 70 % of seizures were partial or tonic-clonic, occurred less than weekly, and lasted less than 5 min. 1/3 of seizures resolved in a median time and age of 1.1 and 3.3 years. Age had a weak non-linear association with average seizure frequency, and, for those with seizures, smaller head circumference correlated with increased disease severity.</div></div><div><h3>Conclusions</h3><div>We further characterize disease severity and epilepsy in FOXG1 syndrome and demonstrate that smaller head circumferences are associated with more severe disease and age is weakly non-linearly correlated with average seizure frequency. This information will improve clinical care and aid therapeutic development.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107644"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908471","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}
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