Pub Date : 2025-11-03DOI: 10.1016/j.seizure.2025.11.002
Xintong Wu , Yangmei Chen , Li Feng , Xiong Han , Yanbing Han , Huapin Huang , Qifu Li , Xiaorong Liu , Liankun Ren , Yanping Sun , Qun Wang , Tiancheng Wang , Xiangqing Wang , Bo Xiao , Huiqin Xu , Peimin Yu , Hong Zhang , Guoxing Zhu , Suiqiang Zhu , Dong Zhou
Purpose
This guideline evaluated previous clinical studies that examined the use of third-generation antiseizure medications (ASMs) to treat epilepsy in order to provide treatment recommendations from a clinical practice perspective, thus aiming to enhance clinicians’ understanding of these drugs and improve the standardization of clinical treatment.
Methods
A systematic literature search was conducted to identify studies that examined third-generation ASMs. The included literature was rated using the 2011 Oxford Centre for Evidence-based Medicine (OCEBM) levels of evidence, and recommendations were formulated. The strength of the recommendations was determined based on the evidence level and drug safety profiles.
Results
This guideline examines 10 third-generation ASMs: pregabalin (PGB), rufamide (RFN), lacosamide (LCM), perampanel (PER), eslicarbazepine (ESL), brivaracetam (BRV), stripentol (STP), cannabidiol (CBD), cenobamate (CNB) and fenfluramine (FFA). Recommendations were developed for 13 clinical questions.
Conclusion
This guideline provides a detailed evaluation of the current evidence and treatment recommendations regarding third-generation ASMs. This guideline will help clinicians to better understand these medications and offer guidance for clinical practice.
{"title":"Clinical practice guidelines for the administration of third-generation anti-seizure medications","authors":"Xintong Wu , Yangmei Chen , Li Feng , Xiong Han , Yanbing Han , Huapin Huang , Qifu Li , Xiaorong Liu , Liankun Ren , Yanping Sun , Qun Wang , Tiancheng Wang , Xiangqing Wang , Bo Xiao , Huiqin Xu , Peimin Yu , Hong Zhang , Guoxing Zhu , Suiqiang Zhu , Dong Zhou","doi":"10.1016/j.seizure.2025.11.002","DOIUrl":"10.1016/j.seizure.2025.11.002","url":null,"abstract":"<div><h3>Purpose</h3><div>This guideline evaluated previous clinical studies that examined the use of third-generation antiseizure medications (ASMs) to treat epilepsy in order to provide treatment recommendations from a clinical practice perspective, thus aiming to enhance clinicians’ understanding of these drugs and improve the standardization of clinical treatment.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted to identify studies that examined third-generation ASMs. The included literature was rated using the 2011 Oxford Centre for Evidence-based Medicine (OCEBM) levels of evidence, and recommendations were formulated. The strength of the recommendations was determined based on the evidence level and drug safety profiles<strong>.</strong></div></div><div><h3>Results</h3><div>This guideline examines 10 third-generation ASMs: pregabalin (PGB), rufamide (RFN), lacosamide (LCM), perampanel (PER), eslicarbazepine (ESL), brivaracetam (BRV), stripentol (STP), cannabidiol (CBD), cenobamate (CNB) and fenfluramine (FFA). Recommendations were developed for 13 clinical questions.</div></div><div><h3>Conclusion</h3><div>This guideline provides a detailed evaluation of the current evidence and treatment recommendations regarding third-generation ASMs. This guideline will help clinicians to better understand these medications and offer guidance for clinical practice.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"134 ","pages":"Pages 13-26"},"PeriodicalIF":2.8,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.seizure.2025.11.001
Philippe Gélisse , Arielle Crespel , Pierre Genton , Charlotte Dravet
Lennox–Gastaut syndrome (LGS), one of the most severe childhood epileptic encephalopathies, was described stepwise in the United States and France. Gibbs (1938) and Gibbs et al. (1939) identified a characteristically slow spike-and-wave pattern, which they called the ‘petit mal variant,’ as opposed to typical spike-and-waves at 3 Hz observed in ‘petit mal.’ Shortly after participating in the description of this pattern, William G. Lennox reported children with 1) diffuse slow spike-and-waves, 2) mental deficiency, and 3) three seizure types with—myoclonic jerks—a variant of petit mal absences described as brief episodes of immobility—and drops of the head on the chest or of the whole body on the ground. Henri Gastaut arranged three symposia over six years in Marseille to discuss the entity conceptualized by Lennox. Charlotte Dravet’s medical dissertation (1965) was the basis of a paper published in Epilepsia by Gastaut et al. (1966), enriched with 50 new cases. Gastaut et al. proposed describing this epileptic syndrome under the name ‘Lennox syndrome.’ They preferred this designation over ‘petit mal variant’ because of the term's exclusive electroencephalographic significance that cannot be employed to designate a clinical syndrome. Furthermore, Henri Gastaut wanted to use the term ‘Lennox syndrome’ in the same manner as ‘West syndrome’ was used to describe infantile myoclonic encephalopathy with hypsarrhythmia. Margaret Lennox–Buchthal, daughter of William Lennox, co-chaired the second meeting dedicated to the concept developed by her father, held in Marseille in September 1966 and suggested that the syndrome be called the LGS in honor of her father’s first description, later confirmed and completed by the Marseille school. Nowadays, the clinical and EEG characteristics of the LGS are well-defined. The Marseille school stressed the importance of sleep electroencephalographic recording to highlight bilateral fast epileptic rhythms and axial tonic seizures. The eponym LGS should be restricted to a relatively homogeneous entity, clinical expression, and prognosis, with multiple possible etiologies.
lenox - gastaut综合征（LGS）是最严重的儿童癫痫性脑病之一，在美国和法国被逐步描述。吉布斯（1938）和吉布斯等人（1939）发现了一种典型的慢尖波模式，他们称之为“小畸形”，与“小畸形”中观察到的典型的3赫兹尖波模式相反。在参与描述这种模式后不久，威廉·g·伦诺克斯报告说，1)弥漫的慢尖波，2)智力缺陷，3)三种癫痫类型：肌阵挛性抽搐——一种被描述为短暂的不动的小症状的变体——头部下垂到胸部或整个身体落在地上。Henri Gastaut在六年内在马赛安排了三次专题讨论会，讨论Lennox概念化的实体。Charlotte Dravet的医学论文（1965年）是Gastaut et al.（1966年）发表在《癫痫病》上的一篇论文的基础，文中补充了50个新病例。Gastaut等人建议将这种癫痫综合征命名为“Lennox综合征”。他们更喜欢这个名称，而不是“小畸形变异”，因为该术语的专有脑电图意义不能用于指定临床综合征。此外，Henri Gastaut希望使用术语“Lennox综合征”，就像“West综合征”被用来描述伴有低心律失常的婴儿肌阵挛性脑病一样。Margaret Lennox- buchthal， William Lennox的女儿，共同主持了第二次会议，致力于由她父亲提出的概念，于1966年9月在马赛举行，并建议将该综合征称为LGS，以纪念她父亲的第一次描述，后来由马赛学校证实并完成。目前，LGS的临床特征和脑电图特征都很明确。马赛学派强调睡眠脑电图记录的重要性，以突出双侧快速癫痫节律和轴向强直性癫痫发作。LGS应该局限于一个相对同质的实体，临床表现和预后，有多种可能的病因。
{"title":"History of Lennox–Gastaut Syndrome: An electro-clinical voyage in search of an epileptic syndrome","authors":"Philippe Gélisse , Arielle Crespel , Pierre Genton , Charlotte Dravet","doi":"10.1016/j.seizure.2025.11.001","DOIUrl":"10.1016/j.seizure.2025.11.001","url":null,"abstract":"<div><div>Lennox<strong>–</strong>Gastaut syndrome (LGS), one of the most severe childhood epileptic encephalopathies, was described stepwise in the United States and France. Gibbs (1938) and Gibbs <em>et al</em>. (1939) identified a characteristically slow spike-and-wave pattern, which they called the ‘<em>petit mal variant,</em>’ as opposed to typical spike-and-waves at 3 Hz observed in ‘<em>petit mal.</em>’ Shortly after participating in the description of this pattern, William G. Lennox reported children with 1) diffuse slow spike-and-waves, 2) mental deficiency, and 3) three seizure types with—myoclonic jerks—a variant of petit mal absences described as brief episodes of immobility—and drops of the head on the chest or of the whole body on the ground. Henri Gastaut arranged three symposia over six years in Marseille to discuss the entity conceptualized by Lennox. Charlotte Dravet’s medical dissertation (1965) was the basis of a paper published in <em>Epilepsia</em> by Gastaut <em>et al.</em> (1966), enriched with 50 new cases. Gastaut <em>et al</em>. proposed describing this epileptic syndrome under the name ‘<em>Lennox syndrome.</em>’ They preferred this designation over ‘<em>petit mal variant</em>’ because of the term's exclusive electroencephalographic significance that cannot be employed to designate a clinical syndrome. Furthermore, Henri Gastaut wanted to use the term ‘<em>Lennox syndrome</em>’ in the same manner as ‘<em>West syndrome</em>’ was used to describe infantile myoclonic encephalopathy with hypsarrhythmia. Margaret Lennox–Buchthal, daughter of William Lennox, co-chaired the second meeting dedicated to the concept developed by her father, held in Marseille in September 1966 and suggested that the syndrome be called the LGS in honor of her father’s first description, later confirmed and completed by the Marseille school. Nowadays, the clinical and EEG characteristics of the LGS are well-defined. The Marseille school stressed the importance of sleep electroencephalographic recording to highlight bilateral fast epileptic rhythms and axial tonic seizures. The eponym LGS should be restricted to a relatively homogeneous entity, clinical expression, and prognosis, with multiple possible etiologies.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 251-260"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.seizure.2025.07.009
Rachana Mehta , Ranjana Sah
{"title":"Comment on “Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep: A single tertiary center experience”","authors":"Rachana Mehta , Ranjana Sah","doi":"10.1016/j.seizure.2025.07.009","DOIUrl":"10.1016/j.seizure.2025.07.009","url":null,"abstract":"","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"132 ","pages":"Pages 194-195"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145528841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous research highlights the impact of chronic health conditions on parents of children with health conditions, including epilepsy, however thus far there has not been a qualitative synthesis of the parental experience of caring for a child with epilepsy. This review aims to synthesise the available literature to gain greater insight into how parents experience their child’s condition and to identify gaps in current healthcare provision.
Methods: a
systematic literature search of five electronic databases identified 14 papers which included data regarding the parental experience of caring for a child with epilepsy. A thematic analysis method was used to synthesise these papers.
Results
Four main themes were identified: 1) prolonged uncertainty, 2) a 24-7 condition, 3) a multitude of losses and 4) facing societal stigma.
Conclusions
The synthesis identified that parents face a range of experiences and emotions whilst caring for their child with epilepsy. Recommendations for how healthcare and third sector services can support parents further to help them cope with their experience are provided.
{"title":"Parents' experiences of caring for a child with epilepsy: a systematic review of qualitative research and thematic synthesis","authors":"Amy Breed , Bridget Hanley , Candice Walton , Craig D. Murray","doi":"10.1016/j.seizure.2025.10.025","DOIUrl":"10.1016/j.seizure.2025.10.025","url":null,"abstract":"<div><h3>Purpose</h3><div>Previous research highlights the impact of chronic health conditions on parents of children with health conditions, including epilepsy, however thus far there has not been a qualitative synthesis of the parental experience of caring for a child with epilepsy. This review aims to synthesise the available literature to gain greater insight into how parents experience their child’s condition and to identify gaps in current healthcare provision.</div></div><div><h3>Methods: a</h3><div>systematic literature search of five electronic databases identified 14 papers which included data regarding the parental experience of caring for a child with epilepsy. A thematic analysis method was used to synthesise these papers.</div></div><div><h3>Results</h3><div>Four main themes were identified: 1) prolonged uncertainty, 2) a 24-7 condition, 3) a multitude of losses and 4) facing societal stigma.</div></div><div><h3>Conclusions</h3><div>The synthesis identified that parents face a range of experiences and emotions whilst caring for their child with epilepsy. Recommendations for how healthcare and third sector services can support parents further to help them cope with their experience are provided.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 232-241"},"PeriodicalIF":2.8,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.seizure.2025.10.024
Iván Sánchez Fernández , Ellen C. Broekhuizen , Alex S. Aguirre Bonilla , Daan A. Pijs , Jurriaan M. Peters
Purpose
To describe the utilization of epilepsy surgery in children with tuberous sclerosis complex (TSC), its evolution over the years, and the factors that predict epilepsy surgery use.
Methods
Retrospective descriptive study using the Pediatric Health Information System (PHIS) database between 2004 and 2024. Our main outcome was the proportion of children with TSC and drug-resistant epilepsy who received epilepsy surgery. We adjusted for potential confounders with a generalized estimating equation.
Results
2769 children had TSC and drug-resistant epilepsy (53 % males, median (p25-p75) age at first diagnosis of drug-resistant epilepsy: 5.2 (2.2–11.1) years). 802 (29.0 %) children underwent a total of 955 epilepsy surgeries. 307 (32.1 %) children had lobectomy, 599 (62.7 %) children had other excision of brain tissue, 61 (6.4 %) children had laser interstitial thermal therapy, 24 (2.5 %) children had intracranial neuromodulation, and 13 (1.4 %) children had hemispherectomy. Although the absolute number of epilepsy surgeries increased among children with long follow-up, the number of epilepsy surgeries per person-year decreased over the years. Although the cost during the epilepsy surgery admission is high [median (p25-p75): $72,415 ($44,734-$116,353), the healthcare cost per person-year after epilepsy surgery substantially decreased compared to prior to surgery [$9550 ($3408-$22,134) versus $28,268 ($15,936-$46,851)]. Black race, American Indian race, and public insurance were major factors which decreased the probability of receiving epilepsy surgery.
Conclusion
The proportion of children with TSC and drug-resistant epilepsy who receive epilepsy surgery is low, especially in marginalized populations, and has not increased over the years. Healthcare resource utilization may decrease after epilepsy surgery.
{"title":"Evolution in the use of epilepsy surgery in tuberous sclerosis complex. Analysis of the Pediatric Health Information System over two decades","authors":"Iván Sánchez Fernández , Ellen C. Broekhuizen , Alex S. Aguirre Bonilla , Daan A. Pijs , Jurriaan M. Peters","doi":"10.1016/j.seizure.2025.10.024","DOIUrl":"10.1016/j.seizure.2025.10.024","url":null,"abstract":"<div><h3>Purpose</h3><div>To describe the utilization of epilepsy surgery in children with tuberous sclerosis complex (TSC), its evolution over the years, and the factors that predict epilepsy surgery use.</div></div><div><h3>Methods</h3><div>Retrospective descriptive study using the Pediatric Health Information System (PHIS) database between 2004 and 2024. Our main outcome was the proportion of children with TSC and drug-resistant epilepsy who received epilepsy surgery. We adjusted for potential confounders with a generalized estimating equation.</div></div><div><h3>Results</h3><div>2769 children had TSC and drug-resistant epilepsy (53 % males, median (p<sub>25</sub>-p<sub>75</sub>) age at first diagnosis of drug-resistant epilepsy: 5.2 (2.2–11.1) years). 802 (29.0 %) children underwent a total of 955 epilepsy surgeries. 307 (32.1 %) children had lobectomy, 599 (62.7 %) children had other excision of brain tissue, 61 (6.4 %) children had laser interstitial thermal therapy, 24 (2.5 %) children had intracranial neuromodulation, and 13 (1.4 %) children had hemispherectomy. Although the absolute number of epilepsy surgeries increased among children with long follow-up, the number of epilepsy surgeries per person-year decreased over the years. Although the cost during the epilepsy surgery admission is high [median (p<sub>25</sub>-p<sub>75</sub>): $72,415 ($44,734-$116,353), the healthcare cost per person-year after epilepsy surgery substantially decreased compared to prior to surgery [$9550 ($3408-$22,134) versus $28,268 ($15,936-$46,851)]. Black race, American Indian race, and public insurance were major factors which decreased the probability of receiving epilepsy surgery.</div></div><div><h3>Conclusion</h3><div>The proportion of children with TSC and drug-resistant epilepsy who receive epilepsy surgery is low, especially in marginalized populations, and has not increased over the years. Healthcare resource utilization may decrease after epilepsy surgery.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 281-288"},"PeriodicalIF":2.8,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.seizure.2025.10.026
Mia Tuft , Karl O. Nakken
Objective
Norwegian legislators have for centuries discriminated people with epilepsy. This article specifically addresses the Norwegian marriage laws, and we discuss possible explanations for the discrimination.
Methods
At the library in the faculty of law at the University of Oslo, we have performed a historical search in Norwegian marriage laws and their preparatory works.
Results
The last law change that regulated epilepsy and marriage was passed in 1969. Before this, those with epilepsy had to disclose the disease before marriage, and if such information was withheld, the marriage could be annulled.
Significance
The laws that restricted people with epilepsy from marrying were based on long standing official discrimination due to an overestimation of heredity and/or simply lack of knowledge. We suspect that the discriminatory laws had roots in old theories about eugenics.
{"title":"Epilepsy and marriage - the story of the abolition of laws that discriminated people with epilepsy in Norway","authors":"Mia Tuft , Karl O. Nakken","doi":"10.1016/j.seizure.2025.10.026","DOIUrl":"10.1016/j.seizure.2025.10.026","url":null,"abstract":"<div><h3>Objective</h3><div>Norwegian legislators have for centuries discriminated people with epilepsy. This article specifically addresses the Norwegian marriage laws, and we discuss possible explanations for the discrimination.</div></div><div><h3>Methods</h3><div>At the library in the faculty of law at the University of Oslo, we have performed a historical search in Norwegian marriage laws and their preparatory works.</div></div><div><h3>Results</h3><div>The last law change that regulated epilepsy and marriage was passed in 1969. Before this, those with epilepsy had to disclose the disease before marriage, and if such information was withheld, the marriage could be annulled.</div></div><div><h3>Significance</h3><div>The laws that restricted people with epilepsy from marrying were based on long standing official discrimination due to an overestimation of heredity and/or simply lack of knowledge. We suspect that the discriminatory laws had roots in old theories about eugenics.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"134 ","pages":"Pages 8-12"},"PeriodicalIF":2.8,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.seizure.2025.10.022
Yinhui Chen , Cizheng Zeng , Chengzhu Luo , Binglong Huang , Siqi Chen , Wenhao Deng , Shaocong Lan , Chengyan Li
Objective
To investigate genetic factors in pediatric refractory epilepsy using trio-whole exome sequencing (trio-WES) and to evaluate the impact of genetic diagnosis on treatment optimization.
Methods
Participants diagnosed with refractory epilepsy were recruited between September 2021 and June 2024. Clinical phenotypes were systematically assessed, and trio-WES was performed to facilitate precision medicine approaches.
Results
Pathogenic (P) or likely pathogenic (LP) variants were identified in 42.9% (36/84) of participants. Single-nucleotide variants (SNVs) accounted for a diagnostic yield of 36.9% (31/84), and copy number variations (CNVs) for 7.1% (6/84), with one participant (1.2%, 1/84) harbored both variant types. Key clinical features in the cohort included infantile seizure onset (42.9%), developmental delay (70.2%), facial dysmorphisms (10.7%), and hypotonia (38.1%). Genetic diagnostic yields differed significantly based on age of seizure onset and neurodevelopmental status. A total of 33 P/LP SNVs were identified across 22 genes, among which 27.3% (9/33) were occurred in ion channel genes. Following genetic diagnosis, 19.0% of participants showed a favorable response to targeted therapies, accompanied by a significant reduction in annual medical expenditures for these participants.
Conclusion
Trio-WES is a valuable diagnostic tool for refractory epilepsy, achieving a diagnostic yield of 42.9%. Our findings support the clinical utility of genetic testing in enabling precise diagnosis, guiding therapy selection, improving outcomes, and reducing healthcare costs.
{"title":"Transforming refractory epilepsy management: Trio-WES for enhanced genetic diagnosis and prognosis in children","authors":"Yinhui Chen , Cizheng Zeng , Chengzhu Luo , Binglong Huang , Siqi Chen , Wenhao Deng , Shaocong Lan , Chengyan Li","doi":"10.1016/j.seizure.2025.10.022","DOIUrl":"10.1016/j.seizure.2025.10.022","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate genetic factors in pediatric refractory epilepsy using trio-whole exome sequencing (trio-WES) and to evaluate the impact of genetic diagnosis on treatment optimization.</div></div><div><h3>Methods</h3><div>Participants diagnosed with refractory epilepsy were recruited between September 2021 and June 2024. Clinical phenotypes were systematically assessed, and trio-WES was performed to facilitate precision medicine approaches.</div></div><div><h3>Results</h3><div>Pathogenic (P) or likely pathogenic (LP) variants were identified in 42.9% (36/84) of participants. Single-nucleotide variants (SNVs) accounted for a diagnostic yield of 36.9% (31/84), and copy number variations (CNVs) for 7.1% (6/84), with one participant (1.2%, 1/84) harbored both variant types. Key clinical features in the cohort included infantile seizure onset (42.9%), developmental delay (70.2%), facial dysmorphisms (10.7%), and hypotonia (38.1%). Genetic diagnostic yields differed significantly based on age of seizure onset and neurodevelopmental status. A total of 33 P/LP SNVs were identified across 22 genes, among which 27.3% (9/33) were occurred in ion channel genes. Following genetic diagnosis, 19.0% of participants showed a favorable response to targeted therapies, accompanied by a significant reduction in annual medical expenditures for these participants.</div></div><div><h3>Conclusion</h3><div>Trio-WES is a valuable diagnostic tool for refractory epilepsy, achieving a diagnostic yield of 42.9%. Our findings support the clinical utility of genetic testing in enabling precise diagnosis, guiding therapy selection, improving outcomes, and reducing healthcare costs.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 224-231"},"PeriodicalIF":2.8,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.seizure.2025.10.023
Song Su , Hongwei Zhang , Qi Zhang , Fen Zhao , Wandong Hu , Yong Liu , Fang Fang
<div><h3>Objective</h3><div>Summary and analysis of clinical phenotypes, genotypes, and their correlations in epilepsy patients associated with NPRL2 and NPRL3 gene variants.</div></div><div><h3>Methods</h3><div>Retrospective analysis and statistical investigation of clinical phenotypes and genotype-phenotype correlations in children with NPRL2/NPRL3 gene variants, combining clinical data from Shandong University Affiliated Children’s Hospital and Beijing Children’s Hospital, Capital Medical University, with literature review.</div></div><div><h3>Results</h3><div>Our institution collected 8 epilepsy patients with NPRL2 variants, and 32 additional cases were identified from the literature, resulting in a total cohort of 40 patients. Among the available clinical data, 20 patients (54.3 %) were male and 16 (45.7 %) were female. The median age of seizure onset was 21.0 months (2.5–55.0 months). Twenty-five distinct variant types were identified, with nonsense variants (8/25, 32.0 %) being the most prevalent. Focal seizures were observed in 26 patients (75.8 %). Cortical developmental abnormalities Malformations of Cortical Development (MCD) were present in 15 patients (51.7 %), normal cortical structure in 12 (41.4 %), tumor in 1 (3.4 %), and hippocampal sclerosis in 1 (3.4 %). Regarding treatment, 18 patients (69.2 %) had drug-resistant epilepsy (DRE), while seizures were pharmacologically controlled in 8 (30.8 %). Thirteen patients underwent epilepsy surgery, and 8 achieved postoperative seizure freedom. Our institution collected 11 epilepsy patients with NPRL3 variants, combined with 145 cases reported in the literature, totaling 156 cases. A total of 67 variant sites and 6 variant types were identified, with frameshift variants (20/67, 29.9 %) being the most common. The cohort included 87 males (60 %) and 58 females (40 %), with a median age of onset of 48.0 months (12.0–120.0 months). Focal seizures were observed in 95 patients (79.2 %). MRI results showed normal findings in 69 patients (63.3 %) and MCD in 38 (34.9 %), including 30 cases of focal cortical dysplasia (FCD). DRE was reported in 52 patients (54.2 %), with 20 achieving seizure control through monotherapy. Twenty-nine patients underwent surgical resection, and 15 (51.7 %) achieved postoperative seizure freedom. Among 4 drug-resistant epilepsy patients treated with ketogenic diet therapy (KDT), 2 showed no response, 1 achieved seizure control, and 1 experienced recurrence after discontinuing KDT and undergoing surgery. Five patients received rapamycin therapy, with 4 showing no improvement. Comparative analysis between MCD and non-MCD groups revealed significant differences in age of onset and proportion of drug-resistant epilepsy (<em>P</em> = 0.001, 0.033, and < 0.001, respectively). When comparing NPRL2 and NPRL3 variant cohorts, significant differences were observed in age of onset (<em>P</em> = 0.030) and presence of MCD (<em>P</em> = 0.046). No significant differences were fou
{"title":"Genotypic and phenotypic analysis of epilepsy associated with NPRL2/NPRL3 genes","authors":"Song Su , Hongwei Zhang , Qi Zhang , Fen Zhao , Wandong Hu , Yong Liu , Fang Fang","doi":"10.1016/j.seizure.2025.10.023","DOIUrl":"10.1016/j.seizure.2025.10.023","url":null,"abstract":"<div><h3>Objective</h3><div>Summary and analysis of clinical phenotypes, genotypes, and their correlations in epilepsy patients associated with NPRL2 and NPRL3 gene variants.</div></div><div><h3>Methods</h3><div>Retrospective analysis and statistical investigation of clinical phenotypes and genotype-phenotype correlations in children with NPRL2/NPRL3 gene variants, combining clinical data from Shandong University Affiliated Children’s Hospital and Beijing Children’s Hospital, Capital Medical University, with literature review.</div></div><div><h3>Results</h3><div>Our institution collected 8 epilepsy patients with NPRL2 variants, and 32 additional cases were identified from the literature, resulting in a total cohort of 40 patients. Among the available clinical data, 20 patients (54.3 %) were male and 16 (45.7 %) were female. The median age of seizure onset was 21.0 months (2.5–55.0 months). Twenty-five distinct variant types were identified, with nonsense variants (8/25, 32.0 %) being the most prevalent. Focal seizures were observed in 26 patients (75.8 %). Cortical developmental abnormalities Malformations of Cortical Development (MCD) were present in 15 patients (51.7 %), normal cortical structure in 12 (41.4 %), tumor in 1 (3.4 %), and hippocampal sclerosis in 1 (3.4 %). Regarding treatment, 18 patients (69.2 %) had drug-resistant epilepsy (DRE), while seizures were pharmacologically controlled in 8 (30.8 %). Thirteen patients underwent epilepsy surgery, and 8 achieved postoperative seizure freedom. Our institution collected 11 epilepsy patients with NPRL3 variants, combined with 145 cases reported in the literature, totaling 156 cases. A total of 67 variant sites and 6 variant types were identified, with frameshift variants (20/67, 29.9 %) being the most common. The cohort included 87 males (60 %) and 58 females (40 %), with a median age of onset of 48.0 months (12.0–120.0 months). Focal seizures were observed in 95 patients (79.2 %). MRI results showed normal findings in 69 patients (63.3 %) and MCD in 38 (34.9 %), including 30 cases of focal cortical dysplasia (FCD). DRE was reported in 52 patients (54.2 %), with 20 achieving seizure control through monotherapy. Twenty-nine patients underwent surgical resection, and 15 (51.7 %) achieved postoperative seizure freedom. Among 4 drug-resistant epilepsy patients treated with ketogenic diet therapy (KDT), 2 showed no response, 1 achieved seizure control, and 1 experienced recurrence after discontinuing KDT and undergoing surgery. Five patients received rapamycin therapy, with 4 showing no improvement. Comparative analysis between MCD and non-MCD groups revealed significant differences in age of onset and proportion of drug-resistant epilepsy (<em>P</em> = 0.001, 0.033, and < 0.001, respectively). When comparing NPRL2 and NPRL3 variant cohorts, significant differences were observed in age of onset (<em>P</em> = 0.030) and presence of MCD (<em>P</em> = 0.046). No significant differences were fou","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 208-218"},"PeriodicalIF":2.8,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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