Epilepsia Open最新文献

{"title":"Transcranial direct current stimulation treatment reduces, while repetitive transcranial magnetic stimulation treatment increases electroencephalography spike rates with refractory occipital lobe epilepsy: A case study.","authors":"Tine Tronrud, Marco Hirnstein, Tom Eichele, Eivind Kolstad, Lynn Marquardt","doi":"10.1002/epi4.70024","DOIUrl":"https://doi.org/10.1002/epi4.70024","url":null,"abstract":"<p><strong>Objective: </strong>Non-invasive brain stimulation has been suggested as an alternative/supplementary treatment for focal, refractory epilepsy. However, there are only a few studies and even fewer that directly compared transcranial direct current stimulation (tDCS) to repetitive transcranial magnetic stimulation (rTMS).</p><p><strong>Methods: </strong>We report the case of a 20-year-old female patient with persistent epileptiform discharges in the left occipital region consistent with focal status epilepticus. The patient received 20 min sessions of tDCS (2 mA) for five consecutive days, with the cathode over the left occipital region and the anode over the contralateral prefrontal lobe. After initial improvement, the patient's condition worsened again, and thus it was decided to treat her with rTMS (1 Hz, 1800 pulses), also for five consecutive days. Before and after each treatment, spike frequency was recorded with electroencephalography (EEG).</p><p><strong>Results: </strong>There was a significant decrease in spike frequency from pre- to post-tDCS treatment. Depending on the type of data analysis, there was either a near significant (p = 0.058, d = 0.51) or a significant (p < 0.001, d = 1.13) increase from pre- to post-rTMS treatment, and the patient reported a worsening of symptoms.</p><p><strong>Significance: </strong>The study adds to a growing body of evidence on non-invasive brain stimulation treatments in focal refractory epilepsy. On the one hand, we corroborate its usefulness. On the other hand, we highlight that non-invasive brain stimulation might inadvertently worsen symptoms. Future research needs to determine which method, with which parameters, for which patient is beneficial (and detrimental).</p><p><strong>Plain language summary: </strong>The study details the case of a patient suffering from epilepsy, located in the occipital region of the brain, who did not respond to several antiseizure medications. We treated with both transcranial direct current stimulation and repetitive transcranial magnetic stimulation. The transcranial direct current stimulation treatment resulted in a significant decrease in EEG spikes, yet the patient's condition worsened again after 2 weeks. We therefore used repetitive transcranial magnetic stimulation treatment, which, in fact, resulted in an increase in spike frequency. The results demonstrate both the potential benefits and risks of non-invasive brain stimulation as treatment in drug-resistant epilepsy.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729533","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":"Short-term sick leave due to epilepsy in the Swedish Prospective Regional Epilepsy Database and Biobank for Individualized Clinical Treatment (PREDICT).","authors":"Kerstin Andrén, David Larsson, Fredrik Asztély, Johan Zelano","doi":"10.1002/epi4.70029","DOIUrl":"https://doi.org/10.1002/epi4.70029","url":null,"abstract":"<p><strong>Objective: </strong>Epilepsy is associated with low socioeconomic standing and increases the risk of sick leave. Longer periods resulting in benefit payments are captured by administrative data, but the disease also entails a risk of repeated short sick leave periods, which have so far not been studied or quantified. The aim of this study was to describe the frequency of short sick leave in persons with epilepsy (PWE) and the characteristics of these PWE.</p><p><strong>Methods: </strong>A prospective multicenter study, Prospective Regional Epilepsy Database and Biobank for Individualized Clinical Treatment (PREDICT) project, based on medical records and yearly self-report questionnaires in 2020-2023. PWE from five neurology departments who were working, studying, or applying for work were included, and they reported the number of sick leave days the past year in the questionnaires. Socioeconomic data was retrieved from Statistics Sweden. Demographic and clinical factors were compared by chi-squared test, Fisher's exact test, or Mann-Whitney U-test.</p><p><strong>Results: </strong>Of the 288 included PWE, 76.4% (n = 220) stated not having stayed at home due to their epilepsy, 13.9% (n = 40) replied 1-5 days, 1.4% (n = 4) 6-10 days, and 8.3% (n = 27) >10 days. More recently diagnosed PWE reported more sick leave days. Short-term sick leave was more prevalent in those with seizures, with medication side effects, and in those with polytherapy. Demographic and socioeconomic factors did not differ between those with or without sick leave days. In the 184 participants who had replied to the questionnaire at the 1 and/or 2 years' follow-up, the distribution did not differ from the baseline report.</p><p><strong>Significance: </strong>Most PWE do not have short-term sick leave. Short-term sick leave was mainly seen in those with more difficult-to-treat or newly diagnosed epilepsy. Future studies should address if interventions like information about high-risk periods to patients and employers can improve psychosocial outcomes.</p><p><strong>Plain language summary: </strong>Epilepsy can impact work ability, potentially leading to longer sick leaves or disability pensions, but shorter absences are less studied and are not included in the national registries in Sweden. This study explores shorter work absences in epilepsy patients attending neurology clinics in western Sweden. A quarter of patients reported missed workdays, but 68% had no sick leave recorded in national registries. Those with poorly controlled or newly diagnosed epilepsy were more likely to take sick leave, offering insights for patients, healthcare providers, and employers about managing epilepsy in the workplace.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729528","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":"Self-stigma among people with epilepsy: Comparison between Germany and Japan.","authors":"Izumi Kuramochi, Takayuki Iwayama, Hiroaki Okajima, Satsuki Watanabe, Koji Matsuo, Haruo Yoshimasu, Christian G Bien, Christian Brandt, Anne Hagemann","doi":"10.1002/epi4.70005","DOIUrl":"https://doi.org/10.1002/epi4.70005","url":null,"abstract":"<p><strong>Objective: </strong>Epilepsy is a neurological disorder characterized by recurrent seizures, with prevalence and treatment availability varying across countries. Stigma associated with epilepsy significantly impacts the quality of life (QOL) of people with epilepsy (PWE). This study aimed to compare self-stigma, depressive symptoms, anxiety, and QOL in PWE treated at tertiary epilepsy centers in Germany and Japan. It also explored cultural differences influencing these experiences.</p><p><strong>Methods: </strong>Participants were recruited from the Bethel Epilepsy Center in Germany and the Comprehensive Epilepsy Centers at Saitama Medical University in Japan. Eligible participants were PWE aged 18 and above, receiving treatment at these facilities, meeting language requirements, and capable of providing informed consent. Data collection occurred from May 2022 to April 2023 using questionnaires assessing self-stigma (Epilepsy Self-Stigma Scale, ESSS), self-esteem, depressive symptoms, anxiety, knowledge, and QOL. Comparisons between Japanese and German samples and associations among variables were analyzed using t-tests, chi-square tests, and regression analyses.</p><p><strong>Results: </strong>PWE in Japan reported higher levels of self-stigma, depressive symptoms, and anxiety compared to those in Germany. Conversely, they demonstrated lower epilepsy knowledge, self-esteem, and overall health. Significant correlations emerged among variables; however, differences in ESSS scores remained significant in a multiple regression model, highlighting persistent cultural variances.</p><p><strong>Significance: </strong>The findings reveal marked differences in self-stigma and psychosocial factors between Japanese and German PWE. Japanese participants experienced higher self-stigma and psychological distress, potentially due to disparities in healthcare delivery systems, institutional frameworks, and social support structures. Healthcare providers should address these contextual factors in epilepsy care. Future studies should explore systemic influences on self-stigma through long-term, multi-center research in diverse healthcare settings to improve support for PWE globally.</p><p><strong>Plain language summary: </strong>This study compared how people with epilepsy treated in two tertiary epilepsy centers in Japan and Germany feel about their condition and themselves. The research found that Japanese patients felt more stigma (negative self-judgment) about having epilepsy and reported more feelings of depression and anxiety than German patients. They also knew less about epilepsy and felt less confident about themselves. These findings suggest that differences in healthcare systems and social attitudes between the two countries may affect how people cope with epilepsy, highlighting the need for better support systems in Japan.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691485","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":"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, Isha Puntambekar, Sallie Baxendale","doi":"10.1002/epi4.70027","DOIUrl":"https://doi.org/10.1002/epi4.70027","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Significance: </strong>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.</p><p><strong>Plain language summary: </strong>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 complaints that impair social function. Anxiety is also associated with problems that have an executive basis, while depression is associated with reports of losses from the core memory store. Recognizing these patterns may help clinicians identify the most effective interventions for these difficulties.</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":"143691489","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":"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, Bernhard J Steinhoff, Edouard Hirsch, Felix Rosenow, Arnaud Biraben, Rhys Thomas, Alessandro Lovera, Paola Lipone, Alessandro Comandini, Caroline Benoist, Elena Alvarez Baron, John Paul Leach, Karthinathan Thangavelu, Agnese Cattaneo","doi":"10.1002/epi4.70021","DOIUrl":"https://doi.org/10.1002/epi4.70021","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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%.</p><p><strong>Results: </strong>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.</p><p><strong>Significance: </strong>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.</p><p><strong>Plain language summary: </strong>This study involved patients with drug-resistant epilepsy, who had continued seizures despite using at least two antiseizure medications (ASMs). Patients received cenobamate (Ontozry) as epilepsy treatment during the Early Access Program (EAP) in France, Germany, and the United Kingdom. An EAP allows patients to receive promising new drugs under clinical supervision before they are commercially available. After 6 months from cenobamate start, 49.3% of patients had their seizures cut by half or more, and 13.6% became seizure-free. A total of 30.9% of patients had an undesirable reaction to cenobamate, mostly mild-to-moderate and resolved; the most frequent were asthenia, dizziness, and somnolence.</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":"143676744","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":"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, Prima Kristina Paola Quintay, Veeda Michelle Anlacan, Adrian Espiritu, Viel Mendoza","doi":"10.1002/epi4.70013","DOIUrl":"https://doi.org/10.1002/epi4.70013","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Significance: </strong>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.</p><p><strong>Plain language summary: </strong>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 cases.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Mei He, Xuan Luo, Hu Pan, Xiao Mao, Jinping Su","doi":"10.1002/epi4.13117","DOIUrl":"https://doi.org/10.1002/epi4.13117","url":null,"abstract":"<p><p>The COX4I1 is responsible for encoding a crucial component of cytochrome c oxidase, integral to electron transport in the mitochondrial respiratory chain. Mutations in COX4I1 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 COX4I1 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. PLAIN LANGUAGE SUMMARY: 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 COX4I1 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>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Jiuluan Lin, Jianjun Bai, Haixiang Wang, Bingqing Zhang, Qian Feng, Zhaohui Sun, Yiou Liu, Jing He, Xiancheng Song, Siyu Wang, Xiaoyan Liu, Wenjing Zhou","doi":"10.1002/epi4.70014","DOIUrl":"https://doi.org/10.1002/epi4.70014","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Two of the probands had COL4A1 variants and six had COL4A2 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).</p><p><strong>Significance: </strong>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.</p><p><strong>Plain language summary: </strong>In this case series of eight patients, epilepsy related to variants in the collagen type IV alpha 1/2 chain genes was characterized by drug-resistant localized seizures with an early onset, one-sided muscle weakness, and developmental delay. Neuroimaging revealed various brain abnormalities. Structural abnormalities outside the seizure-onset zone did not appear to affect surgical prognosis. Early surgical intervention in patients with well-defined seizure-onset zones improved seizure control and developmental outcomes.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}