Epilepsia最新文献

{"title":"The gut microbiome associated with LGI1-antibody encephalitis.","authors":"Edmund Gilbert, Sophie Binks, Valentina Damato, Christopher Uy, Paula Colmenero, Mark Kelly, Mohamed Ibrahim Khalil, Marcus O'Brien, Marcus J Claesson, John F Cryan, Norman Delanty, Sarosh R Irani, Gianpiero L Cavalleri","doi":"10.1111/epi.18556","DOIUrl":"https://doi.org/10.1111/epi.18556","url":null,"abstract":"<p><strong>Objective: </strong>Autoimmune encephalitis is a cause of brain inflammation characterized by auto-antibodies, which target cell surface neuronal proteins and lead to neuronal dysfunction. The most common form is associated with auto-antibodies to leucine-rich glioma-inactivated 1 (LGI1) protein, the presentation of which includes frequent focal seizures. The exact cause of these auto-antibodies remains unknown, but established predispositions include overrepresented human leukocyte antigen (HLA) alleles. Yet, these HLA alleles are themselves common in the healthy ancestry-matched population. One potential etiological hypothesis is that an environmental trigger, such as the gut microbiome, interacts with a genetically predisposed individual.</p><p><strong>Methods: </strong>To investigate this, we studied 42 patients with LGI1-antibody encephalitis (LGI1-Ab-E) and 27 familial/environmentally matched controls, and performed metagenomic shotgun sequencing, to describe the compositional and functional differences in the gut microbiome.</p><p><strong>Results: </strong>We observed that LGI1-Ab-E gut microbiomes exhibited a significant reduction in the ratio of Firmicutes (or Bacillota) and Bacteroidetes phyla, which is associated with the dosage of HLA susceptibility allele count in patients with LGI1-Ab-E. Furthermore, we identified differences in functional gene profiles in the gut microbiome that led to a reduction of neuroinflammatory protective short-chain fatty acids (SCFAs) in LGI1-Ab-E patients.</p><p><strong>Significance: </strong>Taken together, our results suggest that a compositional shift in the gut microbiome of LGI1-Ab-E associates with a neuroinflammatory state, possibly through the reduction of SCFA production. Our study highlights the potential of the gut microbiome to explain some of the complex condition and unravel etiological questions. Validation studies with greater sample sizes are recommended.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How often do caregivers attend their child when a seizure detection device alerts for a nocturnal major motor seizure?","authors":"Anemoon T Bosch, Franciscus S S Leijten, Roland D Thijs","doi":"10.1111/epi.18534","DOIUrl":"https://doi.org/10.1111/epi.18534","url":null,"abstract":"<p><strong>Objective: </strong>Development in seizure detection devices has focused mainly on detection performance. Yet, in order to serve their function in preventing harmful situations and even sudden unexpected death in epilepsy (SUDEP), caregivers need to respond to seizure alarms. This aspect has not been studied so far. We therefore determined caregiver attendance in response to an alarm from a seizure detection device in a real-world family home setting and evaluated the determinants affecting this rate.</p><p><strong>Methods: </strong>We examined caregiver attendance using video recordings from the PROMISE trial, a home-based study designed to determine the performance of the NightWatch seizure detection device. Attendance was recorded when a caregiver approached the child within 15 min after the alarm. We evaluated attendance to each true alarm, and we randomly selected one false alarm of the same subject, if available, to evaluate attendance as well. We also collected several child- and alarm-related determinants, which we analyzed for effect on attendance using a generalized estimated equation (GEE).</p><p><strong>Results: </strong>We included 461 true positive alarms for 31 children and matched them to 311 false alarms. The overall attendance rate for true positive alarms was 64%, with a median individual attendance rate of 100% per child. The individual attendance rate to false alarms (median 50%) was significantly lower when comparing the response to true positive alarms (p < .001). Nine caregivers always responded to alarms regardless of their nature, whereas two never attended to any alarm. The presence of seizure-related sounds (odds ratio [OR] 7.73, 95% confidence interval [CI] 3.74-15.96) and having a lower seizure frequency (OR 0.37, 95% CI 0.19-0.75) were associated with higher attendance rates.</p><p><strong>Significance: </strong>We found that rates of attendance to nocturnal major motor seizure alarms were generally high, although variation existed among caregivers. These findings highlight the need for counseling when implementing seizure detection devices in epilepsy care.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAC-FOS: A novel translational concordance framework identifies preclinical seizure models with highest predictive validity for clinical focal onset seizures.","authors":"Lyndsey L Anderson, Kristopher M Kahlig, Melissa L Barker-Haliski, Lillian G Matthews, Hamish D Toop, Brian Hannigan, Jacqueline French, H Steve White, Marcio Souza, Steven Petrou","doi":"10.1111/epi.18592","DOIUrl":"https://doi.org/10.1111/epi.18592","url":null,"abstract":"<p><strong>Objective: </strong>Central to the development of novel antiseizure medications (ASMs) is testing of antiseizure activity in preclinical models. Although various well-established models exist, their predictive validity across the spectrum of clinical epilepsies has been less clear. We sought to establish the translational concordance of commonly used preclinical models to define models with the highest predictive clinical validity for focal onset seizures (FOS).</p><p><strong>Methods: </strong>The Praxis Analysis of Concordance (PAC) framework was implemented to assess the translational concordance between preclinical and clinical ASM response for 32 US Food and Drug Administration-approved ASMs. Preclinical ASM responses in historically used seizure models were collected. Protective indices based on reported median tolerability and median efficacy values were calculated for each ASM in each preclinical model. A weighted scale representing relative antiseizure effect was used to grade preclinical ASM response for each seizure model. Data depth was further scored based on the number of evaluated ASMs with publicly available data. Established reports of clinical ASM use in patients with FOS were similarly evaluated, and a weighted scale representing prescribing patterns and perceived efficacy was used to grade clinical ASM response. To assess the predictive validity of preclinical models, a unified translational scoring matrix was developed to assign a concordance score spanning the spectrum from complete discordance (-1) to complete concordance (1) between preclinical and clinical ASM responses. Scores were summed and normalized to generate a global translational concordance score.</p><p><strong>Results: </strong>The preclinical models with the highest translational concordance and greatest data depth for FOS were rodent maximal electroshock seizure (MES), mouse audiogenic seizure, mouse 6 Hz (32 mA), and rat amygdala kindling.</p><p><strong>Significance: </strong>The PAC-FOS framework highlights mouse MES, mouse audiogenic, and mouse 6 Hz (32 mA) as three acute seizure models consistently demonstrating high predictive validity for FOS. We provide a pragmatic decision tree approach to support efficient resource utilization for novel ASM discovery for FOS.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early seizure freedom with [¹⁸F]fluorodopa positron emission tomography response after isocitrate dehydrogenase inhibition with vorasidenib: First case report.","authors":"Roberta Rudà, Francesco Bruno, Alessia Pellerino, Edoardo Pronello, Michela Zotta, Silvia Morbelli","doi":"10.1111/epi.18593","DOIUrl":"https://doi.org/10.1111/epi.18593","url":null,"abstract":"<p><p>Vorasidenib, a dual isocitrate dehydrogenase 1/2 (IDH1/2) inhibitor, showed superior efficacy in prolonging progression-free survival and time to next intervention in IDH-mutant grade 2 gliomas. This case is part of an ongoing institutional study exploring the impact of vorasidenib on seizure control and the potential of [¹⁸F]fluorodopa (F-DOPA) positron emission tomography (PET) to detect treatment response earlier than magnetic resonance imaging (MRI). A 52-year-old patient with grade 2 IDH-mutant 1p19q-codeleted oligodendroglioma and persistent postoperative seizures received vorasidenib. He achieved early seizure freedom from the first month of therapy without any change of antiseizure medication (ASM). At 3 and 6 months after treatment, MRI showed stable disease (with a slight progressive reduction in tumor volume), whereas F-DOPA PET revealed a significant decrease in tracer uptake starting from the third month, which was confirmed at 6 months, corresponding to a partial response according to PET Response Assessment in Neuro-Oncology 1.0 criteria. This is the first report of an IDH-mutant grade 2 glioma patient achieving early seizure control and metabolic response on F-DOPA PET after vorasidenib. It highlights the potential of vorasidenib for seizure management and the value of F-DOPA PET for early treatment assessment. Further studies are required to evaluate long-term seizure control and potential reduction of ASM in IDH-mutant low-grade gliomas treated with vorasidenib.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is there really evidence for neurodegeneration in Dravet syndrome? Commentary on the publication by Selvarajah et al.","authors":"Sanjay M Sisodiya, Simona Balestrini, Samuel F Berkovic, Kailash P Bhatia, Lisa M Clayton, J Helen Cross, Claire Eldred, Antonio Gambardella, Renzo Guerrini, Rima Nabbout, Adam Strzelczyk, Galia Wilson, Ingrid E Scheffer","doi":"10.1111/epi.18582","DOIUrl":"https://doi.org/10.1111/epi.18582","url":null,"abstract":"","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence demands action: An invitation to share the burden of proof.","authors":"Danielle M Andrade, Anne T Berg, Arunan Selvarajah, Andrea Sabo, Carolina Gorodetsky, Paula Marques, Ilakkiah Chandran, Miles Thompson, Quratulain Zulfiqar Ali, Mary Pat McAndrews, Maria Carmela Tartaglia, Victor S T Lira, Linda Huh, Mary Connolly, Arezoo Rezazadeh, Farah Qaiser, Tadeu A Fantaneanu, Monica Duong, Karen Barboza, Lysa Boissé Lomax, Luciana Inuzuka Nakaharada, Jack Arbinuch, Mariana Espindola, Eliana Garzon, Gianluca Sorrento, Mary Anne Meskis, Nicole Villas, Veronica Hood, Marta Gonzalez, Elena Cardenal-Muñoz, Jose Angel Aibar, Lauraine McKenna, Christine Linehan, Ryan Yuen, Babak Taati, Alfonso Fasano, Orrin Devinsky, Kette Valente","doi":"10.1111/epi.18583","DOIUrl":"https://doi.org/10.1111/epi.18583","url":null,"abstract":"","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy-heart syndrome: Back to the future!","authors":"Guilherme L Fialho, Katia Lin","doi":"10.1111/epi.18597","DOIUrl":"https://doi.org/10.1111/epi.18597","url":null,"abstract":"","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Org 34167 rescues voltage dependence of mutant channels and normalizes hyperexcitability in HCN1 epilepsy.","authors":"Lauren E Bleakley, Chaseley E McKenzie, Khaing Phyu Aung, Ming S Soh, James Spyrou, Ian C Forster, Christopher A Reid","doi":"10.1111/epi.18585","DOIUrl":"https://doi.org/10.1111/epi.18585","url":null,"abstract":"<p><strong>Objective: </strong>Developmental and epileptic encephalopathies (DEEs) are severe neurological conditions typically caused by pathogenic genetic variants. Variants in HCN1 can cause DEE by disrupting channel voltage sensitivity, leading to cation \"leak.\" Even with current best-available medications, most patients with DEE struggle to achieve seizure control, and current treatments do not address major clinical morbidities of DEE. We aimed to study the capability of the small molecule Org 34167 to address phenotypes of HCN1 DEE.</p><p><strong>Methods: </strong>Org 34167 is a blood-brain barrier-permeable, broad-spectrum HCN channel modulator. We used a range of assays at biophysical, cellular, network, and behavioral levels to explore the potential of Org 34167 as a precision medicine for HCN1 DEE.</p><p><strong>Results: </strong>Org 34167 rescued voltage dependence of HCN1 channels carrying a range of pathogenic DEE variants in the Xenopus oocyte expression system, significantly reducing cation \"leak.\" In layer V pyramidal neurons from the Hcn1^M249L knock-in mouse model of HCN1 DEE, Org 34167 significantly reduced \"leak\" current, hyperpolarized the resting membrane potential, increased input resistance, and caused a right-shift in rheobase, indicating reduced excitability. In vivo, Org 34167 caused a significant reduction in interictal spiking on electrocorticography in Hcn1^M249L mice and normalized performance in several behavioral assays. However, tremors emerged at therapeutic doses.</p><p><strong>Significance: </strong>Our data provide strong proof-of-concept that a small molecule that rectifies a channel deficit caused by HCN1 pathogenic variants can correct cellular and consequently behavioral phenotypes of HCN1 DEE. The emergence of tremors is likely due the broad-spectrum nature of Org 34167 block. Therefore, more selective HCN1 modulators are needed to improve efficacy and reduce side-effects. Org 34167 acts as an exemplar of a brain-penetrant HCN modulator that can be used as a template for further drug development focused on greater HCN1 selectivity.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurocognitive, behavioral, and treatment burden as key predictors of parental stress in pediatric epilepsy.","authors":"Cinzia Correale, Mattia Mercier, Simona Cappelletti, Nicola Pietrafusa, Chiara Falamesca, Elisabetta Collalti, Giusy Carfi' Pavia, Costanza Calabrese, Marina Trivisano, Luca De Palma, Francesca Cirulli, Nicola Specchio","doi":"10.1111/epi.18580","DOIUrl":"https://doi.org/10.1111/epi.18580","url":null,"abstract":"<p><strong>Objective: </strong>Parental stress in pediatric epilepsy is often linked to seizure-related factors. However, less is known about the contribution of child cognitive functioning, behavioral symptoms, and treatment complexity to caregiver burden. This study aimed to investigate how these variables, along with sociodemographic factors, predict perceived parental stress.</p><p><strong>Methods: </strong>We conducted a cross-sectional study including 117 children with epilepsy and 149 caregivers. Cognitive functioning was classified through standardized assessments; behavioral symptoms were evaluated using the Child Behavior Checklist (CBCL); and parental stress was measured with the Parenting Stress Index-Short Form (PSI-SF). Clinical variables included epilepsy etiology, seizure control, drug resistance, and medication regimen. Group comparisons and regression models were used to explore predictors of stress.</p><p><strong>Results: </strong>Higher stress levels were observed among parents of children with moderate intellectual disability, compared to those with normal cognition. Clinical-range behavioral symptoms-especially internalizing problems-were significantly associated with elevated stress across PSI domains. Parents of children receiving polytherapy or with drug-resistant epilepsy reported higher levels of dysfunctional parent-child interaction. Lower educational attainment was also linked to greater stress. Although no stress differences emerged by caregiver gender, most participants were mothers. Notably, elevated Defensing Responding scores suggested a potential underreporting of caregiver burden.</p><p><strong>Significance: </strong>These findings indicate that child cognitive and behavioral characteristics, along with treatment complexity, play a greater role in parental stress than core epilepsy variables alone. It is notable that, the tendency to underreport stress may obscure caregiver needs, especially in clinical settings relying solely on self-report measures. Routine caregiver screening and multimodal assessment strategies-including interviews and observations-should be integrated into epilepsy care pathways. Supporting caregiver well-being is essential to sustaining family functioning. It aligns with the priorities outlined in the World Health Organization (WHO) Intersectoral Global Action Plan (IGAP), which highlights caregiver support as a key pillar of person- and family-centered care for neurological conditions.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association study of ADORA2A gene polymorphisms with adverse drug reactions to valproic acid and oxcarbazepine in the treatment of children with epilepsy.","authors":"Xixuan Wang, Jiahao Zhu, Xi Li, Hanbing Xia, Jieluan Lu, Yaodong He, Xianhuan Shen, Jianping Zhang, Xiaomei Fan, Wenzhou Li","doi":"10.1111/epi.18587","DOIUrl":"https://doi.org/10.1111/epi.18587","url":null,"abstract":"<p><strong>Objective: </strong>Adenosine, a purine nucleotide, is implicated in various brain disorders. Our previous study identified a correlation between ADORA2A variants and epilepsy susceptibility. However, it remains unclear whether ADORA2A genetic polymorphisms affect the outcomes of antiseizure medication (ASM) therapy. This study aimed to investigate the association between ADORA2A gene polymorphisms and the efficacy and adverse drug reactions (ADRs) of ASM.</p><p><strong>Methods: </strong>In this study, 278 children with epilepsy treated with ASM were retrospectively recruited. Among them, 208 children received valproic acid (VPA), 113 received oxcarbazepine (OXC), and 43 received a combination of VPA and OXC. The ADORA2A rs2298383 polymorphism was genotyped using the Sequenom MassArray system. Additionally, putative targets and pathways associated with ADORA2A in ADRs induced by ASM were identified through protein-protein interaction, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology functional enrichment analysis.</p><p><strong>Results: </strong>The ADORA2A rs2298383 polymorphism was not significantly associated with drug responsiveness in children with epilepsy. However, the rs2298383 TT genotype was potentially protective against VPA-induced weight gain (p = .006) but may have increased the likelihood of OXC-induced cutaneous ADRs (p = .030). Furthermore, bioinformatic analysis revealed that nine target genes associated with VPA-induced weight gain were primarily involved in the \"positive regulation of mitogen-activated protein kinase cascade,\" \"calcium signaling pathway,\" and \"cyclic adenosine monophosphate signaling pathway\" pathways/processes.</p><p><strong>Significance: </strong>This study demonstrates that ADORA2A gene polymorphisms can assist in predicting the impact of ASM on outcomes in children with epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}