Epilepsia Open最新文献

{"title":"Epilepsy syndromes classification.","authors":"Elaine C Wirrell, Nicola Specchio, Rima Nabbout, Phillip L Pearl, Kate Riney","doi":"10.1002/epi4.70026","DOIUrl":"https://doi.org/10.1002/epi4.70026","url":null,"abstract":"<p><p>Epilepsy syndromes are distinct electroclinical entities which have been recently defined by the International League Against Epilepsy Nosology and Definitions Task Force. Each syndrome is associated with \"a characteristic cluster of clinical and EEG features, often supported by specific etiologic findings\". Syndromes often present in an age-dependent manner, carry both prognostic and treatment implications, and are associated with a specific range of comorbidities. Syndromes are most commonly identified in young children and are less frequent in adults. Syndrome identification assists clinicians in selecting the highest yield investigations, the most effective therapies, and allows them to give more accurate prognoses both with regards to seizure control and potential remission as well as expected, associated comorbidities. This review outlines how syndromes are organized and defined, highlighting the characteristic features of the more common entities. PLAIN LANGUAGE SUMMARY: Epilepsy syndromes are identifiable entities that are characterized by specific seizure type(s) and EEG findings. Identification of an epilepsy syndrome often provides a clue to the underlying cause, helps clinicians select the most effective treatments, and provides information on the likely outcome.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691472","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}

{"title":"Subjective memory complaints in people with epilepsy: Are there “signature” complaints associated with anxiety and depression?","authors":"Cassandra Trend,&nbsp;Isha Puntambekar,&nbsp;Sallie Baxendale","doi":"10.1002/epi4.70027","DOIUrl":"10.1002/epi4.70027","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;While there is a relatively weak association between cognitive complaints and performance on standardized tests of memory function, elevated levels of depression and anxiety are highly correlated with subjective memory complaints in people with epilepsy (PWE). The study examined whether there are “signature” constellations of memory complaints that are associated with anxiety and depression in PWE. If identified, these signatures may alert clinicians to the likelihood of mood playing a role when presented with these complaints in the neurology clinic.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Three hundred and seventy-five adults with epilepsy, mean age 37 (s.d. 12.8), completed a Subjective Memory Questionnaire (SMQ), rating how often they experienced 19 different types of memory difficulty. Frequencies ranged from never to more than once a day on a six-point scale. They also completed the Hospital Anxiety and Depression Scale.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A principal component analysis of responses on the SMQ revealed three primary factors. Factor 1 comprised items primarily related to verbal memory lapses in social settings such as forgetting people's names, repetition and rambling in conversation, and difficulties following the thread of a discussion. Factor 2 comprised items related to losses from the core store of memories such as failure to recognize close relatives, getting lost, and forgetting autobiographical details. Factor 3 related to organizational/attentional aspects of memory with an executive component. People who reported moderate/severe levels of anxiety and depression on the HADS reported a higher frequency of memory failures in the social domain than those with no mood disturbance. Anxiety was associated with memory complaints mediated by executive functions, while depression was associated with increased reports of losses from the core memory store.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Anxiety and depression are associated with different subjective memory complaints in people with epilepsy. Paying attention to the nature of these complaints may help in the management of these difficulties.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Anxiety and depression are associated with different patterns of memory complaints in people with epilepsy. In this study, we found that elevated levels of anxiety and depression are associated with memory co","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 3","pages":"758-767"},"PeriodicalIF":2.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world effectiveness and tolerability of cenobamate in drug-resistant epilepsy: A retrospective analysis of the patients included into the Early Access Programs (EAP) in Germany, France, and United Kingdom","authors":"Sylvain Rheims,&nbsp;Bernhard J. Steinhoff,&nbsp;Edouard Hirsch,&nbsp;Felix Rosenow,&nbsp;Arnaud Biraben,&nbsp;Rhys Thomas,&nbsp;Alessandro Lovera,&nbsp;Paola Lipone,&nbsp;Alessandro Comandini,&nbsp;Caroline Benoist,&nbsp;Elena Alvarez Baron,&nbsp;John Paul Leach,&nbsp;Karthinathan Thangavelu,&nbsp;Agnese Cattaneo","doi":"10.1002/epi4.70021","DOIUrl":"10.1002/epi4.70021","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Investigate real-world outcomes in drug-resistant epilepsy (DRE) patients treated with cenobamate as adjunctive treatment to other antiseizure medications (ASMs) within the Early Access Programs (EAP) in Germany, France, and the United Kingdom.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;DRE adults with uncontrolled focal-onset seizures were included from 19 hospitals participating in the EAP in this retrospective study. Data were sourced from clinical records. Participants were evaluated at baseline, 1 months, and 3 months from cenobamate start, and 3, 6, and 12 months after maintenance. The primary effectiveness endpoint was the 50% responder rate, defined as the reduction in seizure frequency ≥50%.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Data were collected from 298 patients who received at least one dose of cenobamate; efficacy was evaluated on 216 patients with seizure data available. At baseline, the median epilepsy duration was 22.2 years, and 41.9% of patients had previous epilepsy surgery, including vagus nerve stimulation, with a median of nine previously failed ASMs. The median number of seizures/month was 8.8. After 3 months of maintenance, the 50% responder rate (primary endpoint) was 49.3%; the median percentage seizure reduction from baseline was 49.1%. A total of 100%, ≥90%, and ≥75% seizures reduction were reported in 13.6%, 20.0%, and 33.6% of patients, respectively. Both the responder rate and the median percentage seizure reduction steadily increased during the observation period. At 6-month maintenance, the seizure-free rate was 24.2%. The retention rate assessed by Kaplan–Meier decreased from 96.6% at 1-month cenobamate start to 69.7% at 12-month maintenance. Adverse Drug Reactions (ADRs) to cenobamate occurred in 30.9% of patients, with asthenia, dizziness, and somnolence being the most frequent; the majority were mild-to-moderate and resolved during the observation period; three patients (1.0%) experienced a total of seven serious ADRs, all during titration.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this study, cenobamate demonstrated to be an effective option for people with uncontrolled epilepsy even after multiple failed ASMs or failure of epilepsy surgery.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study involved patients with drug-resistant epilepsy, who had continued seizures despite using at least two antiseizure medications (ASMs). Pati","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 3","pages":"736-748"},"PeriodicalIF":2.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing is everything: The effect of early-life seizures on developing neuronal circuits subserving spatial memory.","authors":"Gregory L Holmes","doi":"10.1002/epi4.70023","DOIUrl":"https://doi.org/10.1002/epi4.70023","url":null,"abstract":"<p><p>Spatial memory, the aspect of memory involving encoding and retrieval of information regarding one's environment and spatial orientation, is a complex biological function incorporating multiple neuronal networks. Hippocampus-dependent spatial memory is not innate and emerges during development in both humans and rodents. For spatial memory to occur, the hippocampus forms highly associative networks integrating external inputs conveying multi-sensory, proprioceptive, contextual, and emotional information onto internally generated dynamics. Hippocampal cognitive maps are produced by sequences of transient ordered neuronal activations that represent not only spatial information but also the temporal order of events in a memory episode. This patterned activity fine-tunes synaptic connectivity of the network and drives the emergence of specific firing necessary for spatial memory. In the rodent hippocampus, there is a sequence of spontaneous activities that are precisely timed, starting with early sharp waves progressing to theta and gamma oscillations, place and grid cell firing, and sharp wave-ripples that must occur for spatial memory to develop. Whereas normal activity patterns are required for circuit maturation, aberrant neuronal activity during development can have major adverse consequences, disrupting the development of spatial memory. Seizures during infancy, involving massive bursts of synchronized network activity, result in impaired spatial memory when animals are tested as adolescents or adults. This impaired spatial memory is accompanied by alterations in theta and gamma oscillations and spatial and temporal coding of place cells. Conversely, enhancement of oscillatory activity following early-life seizures can improve cognitive impairment. The plasticity of developing oscillatory activity in the immature brain provides exciting opportunities for therapeutic intervention in childhood epilepsy. PLAIN LANGUAGE SUMMARY: Children with epilepsy often struggle with memory and learning challenges. Research has shown that seizures can interfere with the brain's natural rhythms, which are crucial for these processes. Seizures in children are particularly harmful because they disrupt the development of brain connections, which are still growing and maturing during this critical time. Exciting new studies in both animals and humans suggest that using electrical or magnetic stimulation to adjust these brain rhythms can help restore memory and learning abilities. This breakthrough offers hope for improving the lives of children with epilepsy.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663132","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}

{"title":"Prevalence and factors associated with seizures among patients with dementia: A retrospective clinic-based study","authors":"Liz Edenberg Quiles,&nbsp;Prima Kristina Paola Quintay,&nbsp;Adrian Espiritu,&nbsp;Viel Mendoza,&nbsp;Veeda Michelle Anlacan","doi":"10.1002/epi4.70013","DOIUrl":"10.1002/epi4.70013","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Chronic diseases associated with aging, such as dementia and seizures, are expected to rise significantly in the Philippines' growing elderly population. This study aims to determine the frequency, demographic characteristics, and clinical profile of dementia patients who developed new-onset seizures in an outpatient setting.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This descriptive, retrospective, cumulative prevalence study included 245 patients diagnosed with dementia at a tertiary hospital in Manila from February 2010 to February 2020, according to DSM-5 criteria. Patients were stratified into those who developed seizures and those who did not. Data on demographics, type, dementia severity, comorbidities, and seizure characteristics were collected and analyzed using descriptive statistics, bivariate, and multivariate logistic regression analyses.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The study included 245 dementia patients, of whom 10 (4.1%) developed seizures, with a higher likelihood observed in those with severe dementia. Most patients were diagnosed with Alzheimer's disease, and seizures were mostly seen in individuals between the ages of 65 and 79. The majority of the seizures were classified as generalized (50%). Compared to mild cases, patients with moderate dementia are about 1.5 times more likely to experience seizures, whereas patients with severe dementia are about 10 times more likely to experience seizures compared to patients with mild dementia. The association is statistically significant for severe cases of dementia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study revealed that 4.1% of Filipino patients diagnosed with dementia in an outpatient setting at a tertiary hospital developed new-onset seizures. Seizures were mostly reported in patients with severe Alzheimer's disease. Conventional understanding of seizures among patients with dementia is important to identify features and predictors to provide efficient management among these patients to possibly improve their quality of life.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;With the aging Filipino population, there is an expected rise in chronic diseases such as dementia and seizures. This study looked at dementia patients in an outpatient setting over 10 years and found that 4.1% developed seizures. Most patients had Alzheimer's disease, and seizures were more common in severe dementia case","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 3","pages":"717-724"},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound heterozygosity of a De novo 16q24.1 deletion and missense mutation in COX4I1 leads to developmental regression, intellectual disability, and seizures","authors":"Zhen Liu,&nbsp;Mei He,&nbsp;Xuan Luo,&nbsp;Hu Pan,&nbsp;Xiao Mao,&nbsp;Jinping Su","doi":"10.1002/epi4.13117","DOIUrl":"10.1002/epi4.13117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The <i>COX4I1</i> is responsible for encoding a crucial component of cytochrome c oxidase, integral to electron transport in the mitochondrial respiratory chain. Mutations in <i>COX4I1</i> can result in a rare autosomal recessive disorder characterized by growth retardation, slow weight gain, microcephaly, and potentially, hematologic symptoms such as Fanconi anemia or neurological impairments including developmental regression and severe epilepsy. In this study, we report the first case of COX4I1 deficiency in China, identified in a 6-year-old boy. The patient exhibited developmental regression, epilepsy, low body weight, microcephaly, generalized muscle hypotonia, and progressive cerebral atrophy, but without hematologic damage or short stature. Compound heterozygosity for a de novo 16q24.1 deletion and a P152T missense mutation in the <i>COX4I1</i> was detected. The P152T missense mutation is previously reported in patients with similar clinical manifestations. Additionally, we provide the first instance of progressive brain atrophy observed through MRI in a COX4I1 deficiency patient, broadening our understanding of the mutation spectrum and clinical phenotype of this genetic disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>We discovered the first case of COX4I1 deficiency in China, identified in a 6-year-old boy. The patient exhibited developmental regression, epilepsy, low body weight, microcephaly, generalized muscle hypotonia, and progressive cerebral atrophy, but without hematologic damage or short stature. Compound heterozygosity for a de novo 16q24.1 deletion and a P152T missense mutation in the <i>COX4I1</i> was detected. Additionally, we provide the first instance of progressive brain atrophy observed through MRI in a COX4I1 deficiency patient, broadening our understanding of the mutation spectrum and clinical phenotype of this genetic disorder.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 3","pages":"942-947"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.13117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype and surgical management of drug-resistant epilepsy in patients with COL4A1 and COL4A2 variants","authors":"Jie Shi,&nbsp;Jiuluan Lin,&nbsp;Jianjun Bai,&nbsp;Haixiang Wang,&nbsp;Bingqing Zhang,&nbsp;Qian Feng,&nbsp;Zhaohui Sun,&nbsp;Yiou Liu,&nbsp;Jing He,&nbsp;Xiancheng Song,&nbsp;Siyu Wang,&nbsp;Xiaoyan Liu,&nbsp;Wenjing Zhou","doi":"10.1002/epi4.70014","DOIUrl":"10.1002/epi4.70014","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To summarize the clinical features of collagen type IV alpha 1/2 chain (COL4A)1/2-related epilepsy and the seizure outcomes of patients undergoing epilepsy surgery.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We retrospectively analyzed the clinical, electroencephalography, and neuroimaging data; genetic characteristics; surgical details; and prognosis of 8 patients (4 boys) treated for COL4A1/2-related epilepsy at Tsinghua University Yuquan Hospital.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Two of the probands had &lt;i&gt;COL4A1&lt;/i&gt; variants and six had &lt;i&gt;COL4A2&lt;/i&gt; variants. Four of the variants were de novo. Prenatal abnormalities consisted of intrauterine growth retardation and ventriculomegaly. Three patients had a low birth weight, and one had perinatal retinal hemorrhage. The median age of seizure onset was 8 months, with 75% (6/8) experiencing epilepsy before age 1. Status epilepticus occurred in 38% (3/8) of patients. All patients experienced focal seizures, and 50% (4/8) had focal epileptic spasms. Hemiparesis was observed in 88% (7/8) of patients, and all 8 had developmental delays. The median number of anti-seizure drugs was 5, and all patients had drug-resistant epilepsy. Seven patients had seizures localized to one of the posterior quadrants, consistent with the magnetic resonance imaging features of blurring of the gray-white matter junction and positron emission tomography features of metabolic abnormalities. Other neuroimaging features included bilateral mild white matter abnormalities; unilateral porencephaly near the basal ganglia; ventriculomegaly; focal cerebral calcification; contralateral schizencephaly; and contralateral cortical thickening and cerebellar abnormalities. Six patients underwent unilateral posterior quadrant disconnection, five (83%) of whom had no recurrence for at least 11 months and experienced developmental improvement. No surgical complications were reported. Pathological examination revealed malformations of cortical development in all six surgical cases (five with focal cortical dysplasia [FCD] type Ia and one with FCD type II).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The results of this case series suggest that early surgical intervention in patients with COL4A1/2-related epilepsy with well-defined epileptogenic zones may improve seizure control and developmental outcomes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this case serie","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 3","pages":"725-735"},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bromodomain-containing protein 2 gene polymorphism among patients with photosensitive epilepsy in Indonesia","authors":"Diah Kurnia Mirawati,&nbsp;Muhana Fawwazy Ilyas,&nbsp;Muhammad Hafizhan,&nbsp;Stefanus Erdana Putra,&nbsp;Suroto Suroto,&nbsp;Subandi Subandi,&nbsp;Rivan Danuaji,&nbsp;Pepi Budianto,&nbsp;Yetty Hambarsari,&nbsp;Baarid Luqman Hamidi,&nbsp;Hanindia Riani Prabaningtyas,&nbsp;Ervina Arta Jayanti Hutabarat,&nbsp;Ira Ristinawati,&nbsp;Teddy Tejomukti,&nbsp;Raden Andi Ario Tedjo,&nbsp;Faris Khairuddin Syah","doi":"10.1002/epi4.70019","DOIUrl":"10.1002/epi4.70019","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Genetic-associated epilepsy in the Indonesian population is rarely discussed, and no study was specifically studied about photosensitive epilepsy. The fundamental goal of this research endeavor was to evaluate whether the single nucleotide polymorphism (SNP) of the Bromodomain-Containing Protein 2 (BRD2) gene gives vulnerability to photosensitive epilepsy among Indonesian descent.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This observational case–control study includes patients of Indonesian descent with Javanese ancestry. Clinical and neurophysiological data, along with electroencephalographic (EEG) recordings, were used to diagnose epilepsy and photosensitive epilepsy. Blood samples were collected and analyzed for BRD2 gene SNPs (rs206781, rs188245, and rs15912) using polymerase chain reaction (PCR), electrophoresis, and the Sanger sequencing method.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study included 27 participants, consisting of 17 patients in the epilepsy group (nine patients with photosensitive epilepsy and eight patients without photosensitive epilepsy) and 10 patients in the non-epilepsy group. Significant statistical differences were found in genotype (rs206781, &lt;i&gt;p&lt;/i&gt; = 0.008 and rs188245, &lt;i&gt;p&lt;/i&gt; = 0.004) and allele frequencies (rs206781, &lt;i&gt;p&lt;/i&gt; &lt; 0.001 and rs188245, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) of the BRD2 gene in Indonesian descent with Javanese race patients diagnosed with photosensitive epilepsy and in those without this condition.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our study corroborates the observation that genetic diversity within the BRD2 locus (rs206781 and rs188245) is associated with PE in Indonesian descendants of the Javanese race. To acquire a complete knowledge of the development of photosensitive epilepsy, further polymorphism studies at other SNP locations or genes are necessary.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study investigated whether genetic differences in the BRD2 gene were linked to photosensitive epilepsy (a type of epilepsy triggered by visual stimuli like flashing lights) in individuals of Indonesian Javanese descent. We analyzed deoxyribonucleic acid (DNA) samples from patients with epilepsy, including those with photosensitive epilepsy, and found that certain variations in the BRD2 gene were significantly more common in people with photosensitive epilepsy. These findings imply that genetic factors, speci","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"571-580"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interim analysis of the long-term efficacy and safety of azetukalner in an ongoing open-label extension study following a phase 2b clinical trial (X-TOLE) in adults with focal epilepsy","authors":"Jacqueline A. French,&nbsp;Roger J. Porter,&nbsp;Emilio Perucca,&nbsp;Martin J. Brodie,&nbsp;Michael A. Rogawski,&nbsp;Cynthia Harden,&nbsp;Jenny Qian,&nbsp;Constanza Luzon Rosenblut,&nbsp;Christopher Kenney,&nbsp;Gregory N. Beatch,&nbsp;X-TOLE Study Group","doi":"10.1002/epi4.70015","DOIUrl":"10.1002/epi4.70015","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To report interim data from an ongoing, open-label extension (OLE) of a Phase 2b study (X-TOLE) of azetukalner in adults with focal onset seizures (FOS) receiving 1–3 antiseizure medications.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Eligible participants enrolled in the 7-year OLE at 20 mg azetukalner once daily with food. Long-term seizure outcomes included median percentage change (MPC) in monthly (28 days) FOS frequency from the double-blind phase (DBP) baseline and achievement of ≥50%, ≥75%, ≥90%, and 100% seizure reductions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;285 participants completed the DBP, and 275 (96.5%) enrolled in the OLE. At the 24-month interim analysis (September 5, 2023), 182 participants had been treated for ≥12 months and 165 for ≥24 months; 152 (55.3%) continued in the study. The median (range) treatment duration in the OLE was 26.3 (0.1–46.6) months. MPC reduction was 83.2% at 24 months in the OLE vs. DBP baseline. For all participants who entered the OLE, 56.4% (155/275) and 44.4% (122/275) achieved a ≥50% seizure reduction, 28.4% (78/275) and 19.6% (54/275) achieved a ≥90% seizure reduction, and 22.2% (61/275) and 14.9% (41/275) achieved seizure freedom (100% seizure reduction) for any consecutive ≥6- and ≥12-month period, respectively. For those who reached ≥24 months in the OLE, seizure freedom was achieved by 34.5% (57/165) and 23.6% (39/165) for any consecutive ≥6- and ≥12-month period, respectively. The majority of treatment-emergent adverse events (TEAEs) were mild or moderate. The most common TEAEs were dizziness (21.8%), headache (15.3%), coronavirus infection (15.3%), somnolence (12.7%), fall (12.7%), and memory impairment (10.9%). Serious AEs were reported in 35 (12.7%) participants.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The efficacy demonstrated by azetukalner in reducing FOS seizure frequency in the DBP was sustained in this interim analysis. Azetukalner was generally well tolerated, with no new safety signals compared to the DBP. These data suggest sustained long-term efficacy and safety of azetukalner in a difficult-to-treat population.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This long-term study assessed the safety and efficacy of azetukalner to treat focal seizures. Patients taking azetukalner daily with food for about 2 years had far fewer focal seizures with azetukalner than before taking the medication. For those who ha","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"539-548"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins' protective effects on focal epilepsy are independent of LDL-C","authors":"Zhen Sun,&nbsp;Jing Zhang,&nbsp;Yulong Li,&nbsp;Miao Tuo,&nbsp;Limin Yu,&nbsp;Yun Wang,&nbsp;Yanping Sun","doi":"10.1002/epi4.70008","DOIUrl":"10.1002/epi4.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study evaluates the potential protective effects of statins against epilepsy, focusing on their differential impacts on focal and generalized epilepsy. It investigates the role of statins through the HMGCR gene and associated low-density lipoprotein (LDL) cholesterol levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A two-sample Mendelian randomization (MR) and summary-data-based MR (SMR) approach were employed using genetic instruments from genome-wide association studies (GWASs) and expression quantitative trait loci (eQTLs). Subgroup analyses examined focal and generalized epilepsy, with sensitivity tests, including MR-Egger regression and MR-PRESSO, to assess horizontal pleiotropy and robustness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SMR analysis found no significant association between HMGCR expression and epilepsy risk across subtypes (<i>p</i> &gt; 0.05). However, inverse-variance-weighted MR (IVW-MR) showed that elevated LDL cholesterol mediated by HMGCR was linked to an increased risk of focal epilepsy (OR = 1.251, 95% CI = 1.135–1.378). No such association was observed for generalized epilepsy. Statins showed promise in reducing post-stroke epilepsy risk, likely through anti-inflammatory and neuroprotective effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>The findings suggest that statins' protective effects may be subtype-specific, particularly in post-stroke focal epilepsy. Further research is needed to elucidate underlying mechanisms and optimize their therapeutic potential in epilepsy management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Statins, drugs typically used to manage cholesterol, may also lower the risk of developing certain types of epilepsy, especially post-stroke focal epilepsy, by reducing inflammation and protecting brain cells. The research found no clear effect of statins on generalized epilepsy or epilepsy caused by other factors. These results could aid in creating better treatments for epilepsy in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"521-528"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}