Epilepsia最新文献

{"title":"Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real-world study.","authors":"Emanuele Cerulli Irelli, Adolfo Mazzeo, Roberto H Caraballo, Marco Perulli, Patrick B Moloney, Javier Peña-Ceballos, Marica Rubino, Katarzyna M Mieszczanek, Andrea Santangelo, Laura Licchetta, Valentina De Giorgis, Gabriela Reyes Valenzuela, Susanna Casellato, Elisabetta Cesaroni, Francesca F Operto, Jana Domínguez-Carral, Alia Ramírez-Camacho, Alessandro Ferretti, Giuseppe Santangelo, Angel Aledo-Serrano, Andrea Rüegger, Maria M Mancardi, Giulia Prato, Antonella Riva, Luca Bergonzini, Duccio M Cordelli, Paolo Bonanni, Francesca Bisulli, Giancarlo Di Gennaro, Sara Matricardi, Pasquale Striano, Norman Delanty, Carla Marini, Domenica Battaglia, Carlo Di Bonaventura, Georgia Ramantani, Elena Gardella, Alessandro Orsini, Antonietta Coppola","doi":"10.1111/epi.18378","DOIUrl":"https://doi.org/10.1111/epi.18378","url":null,"abstract":"<p><strong>Objective: </strong>This real-world, retrospective, multicenter study aims to investigate the effectiveness of highly purified cannabidiol (CBD) in a large cohort of patients with epilepsy of genetic etiology due to an identified monogenic cause. Additionally, we examine the potential relationship between specific genetic subgroups and treatment response.</p><p><strong>Methods: </strong>This study was conducted across 27 epilepsy centers and included patients with monogenic epileptic disorders (pathogenic or likely pathogenic variants) who were treated with highly purified CBD for at least 3 months.</p><p><strong>Results: </strong>A total of 266 patients (135 females, 50.8%) with monogenic epilepsies were included with a median age at CBD initiation of 12 years (interquartile range [IQR] = 7-19) and a median follow-up duration of 17 months (IQR = 12-24). Overall, 77 different monogenic epilepsies have been included, with the most common genes being SCN1A (32.3%), TSC2 (13.5%), CDKL5, and MECP2 (4.5% each). The mean seizure reduction at the last follow-up was 38.6%, with 47.5% of patients achieving ≥50% seizure reduction and 7.4% achieving seizure freedom. The Clinical Global Impression scale indicated improvement in 65.8% of patients. The general linear mixed model revealed that a shorter maximum duration of seizure freedom before CBD initiation and a higher degree of intellectual disability were independently associated with lower CBD effectiveness. Conversely, no significant differences in seizure outcome were observed across different epilepsy syndromes (Lennox-Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex epilepsy, and other developmental and epileptic encephalopathy), between approved indications and off-label use, or between concomitant clobazam use or not.</p><p><strong>Significance: </strong>This study supports CBD as a potential treatment for monogenic epilepsies beyond its licensed indications, demonstrating comparable effectiveness between approved and off-label use and suggesting genetic subgroups with promising treatment responses.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691141","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":"Video-based detection of tonic-clonic seizures using a three-dimensional convolutional neural network.","authors":"Aidan Boyne, Hsiang J Yeh, Anthony K Allam, Brandon M Brown, Mohammad Tabaeizadeh, John M Stern, R James Cotton, Zulfi Haneef","doi":"10.1111/epi.18381","DOIUrl":"https://doi.org/10.1111/epi.18381","url":null,"abstract":"<p><strong>Objective: </strong>Seizure detection in epilepsy monitoring units (EMUs) is essential for the clinical assessment of drug-resistant epilepsy. Automated video analysis using machine learning provides a promising aid for seizure detection, with resultant reduction in the resources required for diagnostic monitoring. We employ a three-dimensional (3D) convolutional neural network with fully fine-tuned backbone layers to identify seizures from EMU videos.</p><p><strong>Methods: </strong>A two-stream inflated 3D-ConvNet architecture (I3D) classified video clips as a seizure or not a seizure. A pretrained action classifier was fine-tuned on 11 h of video containing 49 tonic-clonic seizures from 25 patients monitored at a large academic hospital (site A) using leave-one-patient-out cross-validation. Performance was evaluated by comparing model predictions to ground-truth annotations obtained from video-electroencephalographic review by an epileptologist on videos from site A and a separate dataset from a second large academic hospital (site B).</p><p><strong>Results: </strong>The model achieved a leave-one-patient-out cross-validation F1-score of .960 ± .007 (mean ± SD) and area under the receiver operating curve score of .988 ± .004 at site A. Evaluation on full videos detected all seizures (95% binomial exact confidence interval = 94.1%-100%), with median detection latency of 0.0 s (interquartile range = 0.0-3.0) from seizure onset. The site A model had an average false alarm rate of 1.81 alarms per hour, although 36 of the 49 videos (73.5%) had no false alarms. Evaluation at site B demonstrated generalizability of the architecture and training strategy, although cross-site evaluation (site A model tested on site B data and vice versa) resulted in diminished performance.</p><p><strong>Significance: </strong>Our model demonstrates high performance in the detection of epileptic seizures from video data using a fine-tuned I3D model and outperforms similar models identified in the literature. This study provides a foundation for future work in real-time EMU seizure monitoring and possibly for reliable, cost-effective at-home detection of tonic-clonic seizures.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691234","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":"Clinical implications of naming performance and seizure lateralization in bilingual children with epilepsy.","authors":"Melanie R Somekh, Mary Lou Smith, William S MacAllister, Nahal D Heydari, Robyn M Busch, Robert Fee, Christine Salinas, Marla J Hamberger","doi":"10.1111/epi.18373","DOIUrl":"https://doi.org/10.1111/epi.18373","url":null,"abstract":"<p><strong>Objective: </strong>Naming difficulty is a common symptom of left (i.e., language dominant) hemisphere epilepsy. As such, in the presurgical evaluation for drug-resistant epilepsy, which aims to localize the epileptogenic region, identification of a naming deficit typically implicates the left temporal region. However, the well-established finding of poor naming in those with left but not right (i.e., nondominant) hemisphere seizures in monolingual patients is unreliable in bilingual adults with epilepsy, despite proficiency in the language tested. We aimed to examine naming performance and its relation with seizure lateralization in bilingual children with epilepsy.</p><p><strong>Methods: </strong>This multisite study included 57 bilingual and 202 monolingual pediatric epilepsy patients, aged 6-17 years. All patients underwent neuropsychological evaluation including assessment of auditory and visual object naming in English.</p><p><strong>Results: </strong>In the context of age-appropriate English expressive vocabulary skills, bilingual children with epilepsy demonstrated significantly weaker auditory and visual naming than monolingual patients. Additionally, unlike monolingual patients, who showed poorer naming among those with left compared to those with right hemisphere seizures, bilingual children with unilateral left and right hemisphere seizures demonstrated similarly weak naming performances. Furthermore, naming score cutoffs failed to differentiate individual bilingual patients with left versus right hemisphere seizure onset as they did among monolingual patients.</p><p><strong>Significance: </strong>Despite conversational proficiency and normal English expressive vocabulary, the relation between seizure laterality and naming performance demonstrated in monolingual children with unilateral seizures was not observed in a comparable group of bilingual children. Consequently, poor naming performance in bilingual children with epilepsy may be misinterpreted, most seriously in those with nondominant hemisphere seizures, as scores may be erroneously interpreted to reflect dominant hemisphere seizure involvement, potentially leading to unnecessary invasive and costly procedures. Results suggest cautious interpretation of naming performance in bilingual children with epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691111","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":"Clinical phenotypic spectrum of NRXN1 microdeletions and their association with epilepsy: A systematic review and meta-analysis.","authors":"Xintong Guo, Chengzhe Wang, Dingju Long, Heyu Zhang, Sijing Yin, Xinxin Peng, Yicong Liu, Siqing Chen, Yue Liu, Wenyao Huang, Jinming Zhang, Jingjing Chen, Guanzhong Ni, Ziyi Chen","doi":"10.1111/epi.18337","DOIUrl":"https://doi.org/10.1111/epi.18337","url":null,"abstract":"<p><strong>Objective: </strong>NRXN1 microdeletions are associated with an increased genetic risk for various neuropsychiatric disorders, with diverse breakpoints complicating research, diagnosis, and treatment. This study aims to investigate the deletion rate and penetrance of NRXN1 microdeletions across different clinical phenotypes through meta-analysis while exploring their relationship with epilepsy and summarizing the characteristics of NRXN1 biallelic variations.</p><p><strong>Methods: </strong>For meta-analysis, a systematic review of published studies was conducted to calculate NRXN1 microdeletion rates and penetrance across different disorders, with comparisons to control groups. For systematic review, data from 401 cases across 57 studies were analyzed to compare microdeletion characteristics in patients with and without epilepsy, alongside a review of NRXN1 biallelic variation clinical features.</p><p><strong>Results: </strong>NRXN1 microdeletion carriers had a 3.20-fold higher disease risk compared to noncarriers. The deletion rate was elevated in patients with autism, schizophrenia, and Tourette syndrome relative to controls. Additionally, NRXN1 microdeletions were more prevalent in epilepsy patients with comorbidities than in those with epilepsy alone. Among epilepsy patients, 81.3% had comorbidities. Deletions involving exons 1-6 were more frequent in patients with epilepsy, of whom 71.42% were diagnosed with genetic generalized epilepsy (GGE). Among those with NRXN1 biallelic variations, 53.84% had epilepsy, and all experienced generalized seizures.</p><p><strong>Significance: </strong>Understanding genotype-phenotype associations in NRXN1 microdeletion-related diseases is critical for early diagnosis and management. Our study shows that NRXN1 microdeletions have been associated with various neuropsychiatric disorders and exhibit incomplete penetrance. In epilepsy, patients with NRXN1 microdeletions are associated with mental comorbidities and generalized seizure types, particularly involving exon 1-6 deletions, and are common in patients with GGE.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691126","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 surgery in Sturge-Weber syndrome with unilateral or bilateral asymmetric brain involvement: Boston Children's Hospital experience.","authors":"Michelle Y Chiu, Isabelle Iannotti, Matheus D Soldatelli, Mustafa Sahin, Katrina Boyer, Morgan E Ryan, Bo Zhang, Masanori Takeoka, Joseph R Madsen, Scellig Stone, Sanjay Prabhu, Anna L Pinto","doi":"10.1111/epi.18387","DOIUrl":"https://doi.org/10.1111/epi.18387","url":null,"abstract":"<p><strong>Objective: </strong>Sturge-Weber syndrome (SWS) is a neurocutaneous disorder caused by a somatic mosaic mutation in the GNAQ gene. Epilepsy is seen in 75%-80% of children with SWS, and they are at high risk of early onset seizures, status epilepticus, and drug-resistant epilepsy. Epilepsy surgery is an effective treatment, but timing and candidacy for epilepsy surgery remain controversial in this patient population. We examined the indications, trends, and outcomes of surgically treated patients with SWS at a large-volume tertiary pediatric hospital over >2 decades.</p><p><strong>Methods: </strong>This retrospective cohort study includes all patients who have a clinical diagnosis of SWS, underwent epilepsy surgery, and were followed by a neurologist at Boston Children's Hospital with clinic visit(s) between January 2000 and April 2022. Chart review and descriptive statistics were performed, and epilepsy characteristics and magnetic resonance imaging findings of the surgical cohort were compared with a nonsurgical SWS cohort.</p><p><strong>Results: </strong>Seventeen patients met the inclusion criteria, 12 with unilateral brain involvement (six right hemispheric) and five with bilateral asymmetric involvement. The average age at seizure onset was 7 months, and average age at first surgery was 29 months. Indication for epilepsy surgery was medically refractory epilepsy in all patients. Eleven hemispherectomies (seven anatomical, four functional) and six motor-sparing focal resections/disconnections were performed. After an average follow-up time of 7 years, Engel class I or II seizure outcome was achieved in 15 patients, including all five with bilateral asymmetric involvement. Five patients have discontinued antiseizure medications.</p><p><strong>Significance: </strong>Outcomes after epilepsy surgery in children with SWS are robust and durable, with a low rate of complications. Both functional hemispherectomy and focal resections are effective in carefully selected patients, and patients with bilateral asymmetric involvement may have favorable outcomes.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691223","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":"Increased Na_V1.2 expression and its interaction with CaM contribute to the hyperexcitability induced by prolonged inhibition of CaMKII.","authors":"Hongyue Liang, Ling Qin, Rui Feng, Jaehoon Shim, Xuan Huang, Xiaoxue Xu, Dongyi Zhao, Zhiyi Yu, Tomasz Boczek, Meixuan Li, Yu Tong, Junwei Huang, Qinghua Gao, Li Wang, Xinyu Cao, Dongxin Liu, Ke Du, Jianjun Xu, Yue Zhao, Wuyang Wang, Corey Ray Seehus, Weidong Zhao, Feng Guo","doi":"10.1111/epi.18377","DOIUrl":"https://doi.org/10.1111/epi.18377","url":null,"abstract":"<p><strong>Objective: </strong>Dysfunction of calcium/calmodulin (CaM)-dependent kinase II (CaMKII) has been involved in hyperexcitability-related disorders including epilepsy. However, the relationship between CaMKII and neuronal excitability remains unclear.</p><p><strong>Methods: </strong>Neuronal excitability was detected in vivo and in vitro by electroencephalography (EEG), patch clamp and multi-electrode array (MEA), respectively. Next, we assessed the currents of voltage-gated sodium channels (VGSCs) by patch clamp, and  mRNA and protein expressions of VGSCs were determined by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot, respectively. Meanwhile, the association between the nuclear receptor subfamily 4 group A member 2 (NR4A2) and promoters of Scn2a, was determined by chromatin immunoprecipitation (ChIP)-qPCR. In addition, we utilized co-immunoprecipitation (Co-IP), immunofluorescence labeling, and pull-down to determine the interaction between VGSCs and CaM.</p><p><strong>Results: </strong>Prolonged CaMKII inhibition by KN93, an inhibitor of CaMKII, for 24 h and CaMKII knockdown induced more seizure-like events in Wistar rats, TRM rats and C57BL/6 mice, and led to hyperexcitability in primary hippocampal neurons and human induced-pluripotent stem cell (hiPSC)-derived cortical neurons. In addition, prolonged CaMKII inhibition resulted in elevated persistent sodium current (I_NaP)/transient sodium current (I_NaT) and increased mRNA and protein expressions of Na_V1.2. Meanwhile, prolonged CaMKII inhibition by KN93 decreased NR4A2 expression and contributed to a transcriptional repression role of NR4A2 in Scn2a regulation, leading to increased Na_V1.2 expression. Moreover, an increased interaction between Na_V1.2 and CaM was attributable to enhanced binding of CaM to the isoleucine-glutamine (IQ) domain at the C-terminus of the Na_V1.2 channel, which may also lead to the potentiation in I_NaP/I_NaT and channel activity. Furthermore, a peptide that antagonized CaM binding to Na_V1.2 IQ domain (ACNp) rescued hyperexcitability following prolonged CaMKII inhibition.</p><p><strong>Significance: </strong>We unveiled that prolonged CaMKII inhibition induced hyperexcitability through increasing the expression of Na_V1.2 and its association with CaM. Thus, our study uncovers a novel signaling mechanism by which CaMKII maintains appropriate neuronal excitability.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677016","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":"Comparison of lacosamide, levetiracetam, and valproate as second-line therapy in adult status epilepticus: Analysis of a large cohort.","authors":"Cecil D Hahn, Jan Novy, Andrea O Rossetti","doi":"10.1111/epi.18380","DOIUrl":"https://doi.org/10.1111/epi.18380","url":null,"abstract":"<p><p>We compared the efficacy of lacosamide to other frequently used second-line anti-seizure medications (ASMs) for adult status epilepticus (SE) by conducting a retrospective analysis of an institutional SE registry between January 2013 and December 2022. Clinical outcomes assessed at discharge were categorized as return to baseline, new disability, or death; we also considered SE termination after the second-line ASM and the need for mechanical ventilation. Potential confounders included the Status Epilepticus Severity Score (STESS), sex, adequacy of initial SE treatment, treatment delay, and potentially fatal etiology. Over 10 years, 961 adult SE episodes were analyzed; 868 were treated with the following second-line ASMs: 413 levetiracetam (47.6%), 110 valproate (12.7%), and 75 lacosamide (8.6%), as well as lower rates of 18 other ASMs including benzodiazepines (not further analyzed). Univariable analysis identified STESS, treatment delay, and adequacy of initial SE treatment as potential confounders. On multivariable analysis adjusting for these variables, patients with episodes treated with second-line lacosamide, levetiracetam, or valproate demonstrated statistically equivalent rates of seizure cessation, need for mechanical ventilation, and clinical outcomes at hospital discharge. We conclude that lacosamide appears to represent a reasonable alternative to levetiracetam and valproate, and warrants consideration for inclusion in future randomized controlled trials for control of SE.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676991","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":"Long-term seizure and psychosocial outcomes of patients with ring chromosome 20 syndrome: A cohort study of 47 cases.","authors":"Kentaro Tokumoto, Takuji Nishida, Hitoshi Ikeda, Hiroko Ikeda, Norihiko Kawaguchi, Satoshi Mizutani, Tokito Yamaguchi, Hideyuki Ohtani, Etsuko Yamazaki, Naotaka Usui, Katsumi Imai, Yushi Inoue","doi":"10.1111/epi.18370","DOIUrl":"https://doi.org/10.1111/epi.18370","url":null,"abstract":"<p><strong>Objective: </strong>We retrospectively investigated a cohort of patients with ring chromosome 20 syndrome (r20), aiming to provide information on the prognosis of r20 regarding seizures, cognitive function, comorbidities, and social living.</p><p><strong>Methods: </strong>Patients diagnosed with r20 in our hospital were identified, and clinical data were extracted from medical records. We used the following seizure outcome classification: favorable seizure outcome, a condition in which seizures do not interfere with daily life, including no seizures, subclinical discharges, sleep seizures or mild focal aware seizures; poor seizure outcome, a condition in which seizures interfere with daily life. Clinical variables were compared between favorable and poor seizure outcome groups.</p><p><strong>Results: </strong>Forty-seven patients (64% female) were studied. Mean age ± standard deviation (SD) at epilepsy onset was 7.5 ± 3.7 (range 1-15) years. Mosaicism rate was 33 ± 24% (range 1%-97%). Fourteen patients (30%) were classified in the favorable seizure outcome group and 33 (70%) in the poor seizure outcome group. Multivariable analysis identified lower mosaicism rate and higher rate of lamotrigine use as independent factors associated with a favorable seizure outcome. The most effective drug was lamotrigine (69%), followed by valproate (43%) and other sodium channel blockers. Intellectual disability was present in 27 patients (57%), autism spectrum disorder in 8 (17%), and psychiatric symptoms in 10 (21%). Of 30 adult patients, 7 (23%) were employed, 5 (17%) were employed previously but unemployed at the last follow-up, 3 (10%) were employed as disabled, 6 (20%) received employment support, 3 (10%) were college students, and 6 (20%) had no employment history. Twenty-five patients (83%) lived with their families. Two patients (7%) were married.</p><p><strong>Significance: </strong>In 30% of r20 patients, drug treatment improved seizures to a degree minimally disruptive to daily life. Lamotrigine use was associated with favorable seizure outcome. Social constraints in employment, residence, and marriage were significant, indicating the need for comprehensive epilepsy care.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677035","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":"Medication-resistant epilepsy is associated with a unique gut microbiota signature.","authors":"Antonella Riva, Eray Sahin, Greta Volpedo, Noemi Teresa Catania, Isabel Venara, Valentina Biagioli, Ganna Balagura, Elisabetta Amadori, Carmen De Caro, Emanuele Cerulli Irelli, Carlo Di Bonaventura, Federico Zara, Osman Ugur Sezerman, Emilio Russo, Pasquale Striano","doi":"10.1111/epi.18367","DOIUrl":"https://doi.org/10.1111/epi.18367","url":null,"abstract":"<p><strong>Objective: </strong>Dysfunction of the microbiota-gut-brain axis is emerging as a new pathogenic mechanism in epilepsy, potentially impacting on medication response and disease outcome. We investigated the composition of the gut microbiota in a cohort of medication-resistant (MR) and medication-sensitive (MS) pediatric patients with epilepsy.</p><p><strong>Methods: </strong>Children with epilepsy of genetic and presumed genetic etiologies were evaluated clinically and subgrouped into MR and MS. Age-matched healthy controls (HCs) were also recruited. A food diary was used to evaluate nutritional habits, and the Rome IV questionnaire was used to record gastrointestinal symptoms. The microbiota composition was assessed in stool samples through 16S rRNA. α-Diversity (AD) and β-diversity (BD) were calculated, and differential abundance analysis was performed using linear multivariable models (significance: p.adj < .05).</p><p><strong>Results: </strong>Forty-one patients (MR:MS = 20:21) with a mean age of 7.2 years (±4.6 SD) and 27 age-matched HCs were recruited. No significant differences in AD were found when comparing patients and HCs. Significant positive correlation was found between AD and age (Chao1 p.adj = .0004, Shannon p.adj = .0004, Simpson p.adj = .0028). BD depicted a different bacterial profile in the epilepsy groups compared to HCs (MS vs. HC: Bray-Curtis F = 1.783, p = .001; Jaccard F = 1.24, p = .001; MR vs. HC: Bray-Curtis F = 2.24, p = .001; Jaccard F = 1.364, p = .001). At the genus level, the epilepsy groups were characterized by a significant increase in Hungatella (MS vs. HC: +4.95 log₂ change; MR vs. HC: +6.72 log₂ change); the [Eubacterium] siraeum group changed between the MR and MS subgroups.</p><p><strong>Significance: </strong>Epileptic patients display unique gut metagenomic signatures compared to HCs. Moreover, a different ratio of the butyrate-producing [Eubacterium] siraeum group suggests dissimilarities between patients based on the response to antiseizure medications.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677061","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":"Mitochondrial respiration defects in lymphoblast cell lines from patients with Dravet syndrome.","authors":"Anna G Figueroa, Ruth E Fulton, Rajeswari Banerji, Kelly G Knupp, Manisha N Patel","doi":"10.1111/epi.18382","DOIUrl":"https://doi.org/10.1111/epi.18382","url":null,"abstract":"<p><strong>Objective: </strong>Dravet syndrome (DS) is a developmental and epileptic encephalopathy with early life intractable seizures and lifelong comorbidities. There is growing evidence linking energy metabolism to DS, from mitochondrial respiration deficits in skeletal muscle and fibroblasts from children with DS to responsiveness to ketogenic diets. Lymphoblast cell lines (LCLs) have revealed metabolic alterations in neurological disorders, suggesting their utility for studying systemic bioenergetics. In this pilot study, we used LCLs from patients with DS to evaluate energy metabolism.</p><p><strong>Methods: </strong>LCLs were established from eight children with DS (DS-LCLs) and sex-/age-matched controls (control-LCLs). Extracellular flux analysis measured glycolytic function, mitochondrial respiration, and fatty acid oxidation (FAO). High-resolution respirometry was used to determine sites of mitochondrial respiration defects. Mitochondrial content and membrane potential were analyzed using high-content screening methods.</p><p><strong>Results: </strong>DS-LCLs exhibit impaired bioenergetics, characterized by deficiencies in mitochondrial respiration with 25% lower baseline and adenosine triphosphate-linked respiration. Similarly, maximal mitochondrial capacity was 26% lower, leading to a 40% decrease in respiratory reserves. They exhibit a metabolic shift toward FAO, indicated by increased endogenous fatty acid utilization to counter cellular stress. Mitochondrial oxygen flux was impaired, with greatest deficiency in complex I, and reduced complex II activity. Leak respiration, mitochondrial content, membrane potential, and glycolytic function were unaffected.</p><p><strong>Significance: </strong>LCLs from patients with DS reveal reduced mitochondrial respiratory capacity. These preliminary findings may enhance our understanding of energy metabolism in DS pathogenesis. Beyond helping identify new therapies, this model may noninvasively serve as a surrogate for evaluating metabolic function throughout a patient's life.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677062","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}