Epilepsia最新文献

{"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}

{"title":"MBOAT7 encephalopathy: Characterizing the neurology and epileptology.","authors":"Sebastian Ortiz De la Rosa, Valentina Rizzo, Robin-Tobias Jauss, Tobias Bartolomaeus, Maria Escolar, Geneviève Bernard, Ralitza Gavrilova, Rebecca Ahrens-Nicklas, Gabrielle Lemire, Kym M Boycott, Saadet Mercimek-Andrews, Paolo Prontera, Cinzia Costa, Bojana Rakic, Cornelius F Boerkoel, Stephanie Huynh, Linda Huh, Elliott Sherr, Emanuela Argilli, Juan Darío Ortigoza-Escobar, Didac Casas-Alba, Tania Nunes, David A Koolen, Konrad Platzer, Marianne S Khinchi, Elena Gardella, Christina D Fenger, Rikke S Møller, Allan Bayat","doi":"10.1111/epi.18376","DOIUrl":"https://doi.org/10.1111/epi.18376","url":null,"abstract":"<p><strong>Objective: </strong>Biallelic pathogenic MBOAT7 variants are associated with neurodevelopmental disorders, intellectual disability (ID), epilepsy, and neuropsychiatric disorders such as attention-deficit/hyperactivity disorder and autism spectrum disorders. We aimed to characterize the epilepsy phenotype in a cohort of patients affected by this syndrome.</p><p><strong>Methods: </strong>We describe epilepsy features, electroencephalography, magnetic resonance imaging (MRI) findings, antiseizure treatment response, and neurodevelopment of 15 patients with biallelic MBOAT7 variants.</p><p><strong>Results: </strong>All 15 patients had ID or developmental delay (DD). Twelve suffered from epilepsy, with mean age at seizure onset of 36 months (range = 2 months-6.5 years) and 10 of 12 showing signs of DD before seizure onset. Patients with epilepsy presented with focal motor seizures with impaired awareness (n = 3), focal tonic-clonic seizures and epileptic spasms (n = 1), focal to bilateral tonic-clonic seizures (n = 1), unknown onset bilateral tonic-clonic seizures (n = 2), myoclonic seizures (n = 4), myoclonic-atonic seizures (n = 1), atonic seizures (n = 1), tonic seizures (n = 1), and myoclonic absences (n = 2). Seizure freedom was achieved in 66.7% (8/12), with variable antiseizure treatment regimes. We reviewed electroencephalograms of the patients with epilepsy. Background activity was normal in 64%, whereas 36% had either a generalized or a focal slowing. Interictal epileptiform discharges (IEDs) were reported in 83%. Generalized spikes/polyspikes were found in 53%, multifocal IEDs in 23%, and parasagittal focal IEDs in 26%. The most frequent abnormal brain MRI findings, reported in 58% of patients, included high-intensity signal in T2 and fluid-attenuated inversion recovery (FLAIR) sequences in dentate nuclei and globus pallidus. Biallelic missense variants seemed to be associated with better cognitive and motor outcomes compared to truncating variants and in-frame deletions.</p><p><strong>Significance: </strong>Biallelic MBOAT7 variants are associated with global developmental impairment in all affected patients and epilepsy in the majority. The seizure semiology is heterogenous. One third of our cohort had persistent seizures despite treatment. The most frequent MRI findings were hyperintensities in T2/FLAIR sequences in dentate nuclei and globus pallidus.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673243","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":"Tailoring antiseizure treatment with a wearable device: A proof-of-concept study in absence epilepsy.","authors":"Jaiver Macea, Christos Chatzichristos, Miguel Bhagubai, Maarten De Vos, Wim Van Paesschen","doi":"10.1111/epi.18384","DOIUrl":"https://doi.org/10.1111/epi.18384","url":null,"abstract":"<p><strong>Objective: </strong>Typical absence seizures are underreported. We aimed to improve patient care using a wearable electroencephalograph (wEEG) at home and assess a machine learning (ML) pipeline for absence detection.</p><p><strong>Methods: </strong>Patients with typical absences used a wEEG device 12-24 h 1 week after antiseizure medication (ASM) adjustments. Three-hertz generalized spike-wave discharges (SWDs) ≥ 3 s were used as absence surrogates. After manual inspection, we used the results to guide medical treatment. The outcomes were seizure freedom, number of consecutive measurements without relapse, and side effects. Afterward, we used the ML pipeline on the recordings, and a neurologist reviewed the output. Review time and diagnostic performance were compared with manual inspection.</p><p><strong>Results: </strong>Nineteen patients (12 female, median age = 24 years) were followed for a median of 5 months (range = 1-12). The median recording time for each session was 21.3 h (range = 10-24). Fifteen patients (79%) were seizure-free during the last measurement, including seven of 11 (63%) diagnosed with refractory epilepsy. Ten patients relapsed after a median of 1-2 recordings (range = 1-6) without 3-Hz SWDs. Side effects occurred in 21% of patients. Manual file inspection identified 806 3-Hz SWDs of ≥3 s. The ML pipeline reduced a neurologist's median review time for 24-h wEEG from 27 (range = 10-45) to 4.3 min (range = .1-10), with a sensitivity, precision, F1-score, and false positives per hour of .8, .95, .87, and .007, respectively.</p><p><strong>Significance: </strong>Home-based wEEG allows patient monitoring after ASM adjustments, improving absence seizure management. The ML-based pipeline performed well and was crucial in reducing review time.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673259","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":"Parallel transmit 7T MRI for adult epilepsy pre-surgical evaluation.","authors":"Krzysztof Klodowski, Minghao Zhang, Jian P Jen, Daniel J Scoffings, Robert Morris, Victoria Lupson, Franck Mauconduit, Aurélien Massire, Vincent Gras, Nicolas Boulant, Christopher T Rodgers, Thomas E Cope","doi":"10.1111/epi.18353","DOIUrl":"https://doi.org/10.1111/epi.18353","url":null,"abstract":"<p><strong>Objective: </strong>To implement parallel transmit (pTx) 7T magnetic resonance imaging (MRI) in the pre-surgical evaluation of 3T-negative patients with drug-resistant focal epilepsy, and to compare quality to conventional single transmit (specifically, circularly polarized [CP]) 7T MRI.</p><p><strong>Methods: </strong>We implemented a comparative protocol comprising both pTx and CP 7T MRI in consecutive adult candidates for epilepsy surgery who had negative or equivocal 3T MRI imaging. Here we report the outcomes from the first 31 patients. We acquired pTx and CP T₁, T₂, fluid-attenuated inversion recovery (FLAIR) and edge-enhancing gradient echo (EDGE) images, all in the same three-dimensional (3D) 0.8 mm isotropic space. Two-dimensional (2D) high-resolution T₂ and T₂*-weighted sequences were acquired only in CP mode due to current technological limitations. Two neuroradiologists, a neurologist, and a neurosurgeon made independent, blinded quality and preference ratings of pTx vs CP images. Quantitative methods were used to assess signal dropout.</p><p><strong>Results: </strong>7T revealed previously-unseen structural lesions in nine patients (29%), confirmed 3T-equivocal lesions in four patients (13%), and disproved 3T-equivocal lesions in four patients (13%). Lesions were better visualized on pTx than CP in 57% of cases, and never better visualized on CP. Clinical management was altered by 7T in 18 cases (58%). Nine cases were offered surgical resection and one laser interstitial thermal therapy (LITT). Three cases were removed from the surgical pathway because of bilateral or extensive lesions. Five cases were offered stereo-electroencephalography (sEEG) with better targeting (in three because the 7T lesion was deemed equivocal by the multi-disciplinary team (MDT), and in two because the lesion was extensive). Blinded comparison confirmed significantly better overall quality of pTx FLAIR images (F(2, 184) = 13.7, p = 2.88 × 10^-6), whereas pTx MP2RAGE images were subjectively non-inferior and had improved temporal lobe coverage with quantitatively less signal drop-out.</p><p><strong>Significance: </strong>pTx-7T is implementable in a clinical pathway, changed management in 58% of patients where 3T + FDG-PET had not enabled resection, and is superior to single transmit 7T MRI.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669429","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":"Toward molecular phenotyping of temporal lobe epilepsy by spatial omics.","authors":"Isabeau Vermeulen, Ronny Mohren, Micca Neusinger, Tobias A Dancker, Michiel Vandenbosch, Jan Beckervordersandforth, Benjamin Balluff, Rianna P Van der Hel, Olaf E M G Schijns, Govert Hoogland, Kim Rijkers, Berta Cillero-Pastor","doi":"10.1111/epi.18366","DOIUrl":"https://doi.org/10.1111/epi.18366","url":null,"abstract":"<p><strong>Objective: </strong>In temporal lobe epilepsy (TLE), detection of the epileptogenic zone predicts a good surgical outcome. When submitted to ¹⁸F-fluorodeoxyglucose positron emission tomography (PET), some patients display lateralized, focal hypometabolism in the temporal lobe (PET+), whereas others appear normometabolic (PET-). However, the mechanism behind this metabolic difference remains unclear. This study aimed to identify differential molecular mechanisms in these patient subtypes.</p><p><strong>Methods: </strong>Neocortical and hippocampal biopsies of TLE patients (n = 3 PET+, n = 3 PET-) and nonepileptic postmortem controls (n = 3) were analyzed for lipid distribution using mass spectrometry imaging (MSI). Laser capture microdissection of the neocortical gray matter and hippocampal cornu ammonis and dentate gyrus was guided by MSI-derived lipid profiles and histological annotations. Dissected areas were then subjected to liquid chromatography- tandem mass spectrometry-based label-free quantitative proteomic analysis.</p><p><strong>Results: </strong>MSI showed distinct lipid profiles, namely, phosphatidylserines were more abundant in PET+ samples in both the neocortex and hippocampus. Proteomic analysis showed significant differences between TLE and nonepileptic postmortem controls involving pathways in neuron excitability and neurotransmitter transporters, which were upregulated in TLE. Compared to PET-, all PET+ specimens displayed significantly dysregulated calcium signaling. Additionally, the neocortex of PET+ patients showed a shift from mitochondrial to cytosolic (cytoplasm of the cell) processes, whereas the hippocampus was characterized by a disruption of glycosylation and polyamine metabolism.</p><p><strong>Significance: </strong>The applied spatial omics approach demonstrated localized molecular differences between metabolic subtypes of TLE patients. These findings may further specify these TLE subtypes and provide leads for targeted treatment.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662878","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":"De novo TANC2 variants caused developmental and epileptic encephalopathy and epilepsy.","authors":"Sheng Luo, Wen-Jun Zhang, Mi Jiang, Rong-Na Ren, Lei Liu, Yu-Lan Li, Wen-Hui Liu, Peng-Yu Wang, Yu-Jie Gu, Li-Zhi Chen, Li-Ping Shen, Yang Tian, Xiao-Rong Liu, Yong-Hong Yi, Wei-Ping Liao, Peng Zhou","doi":"10.1111/epi.18358","DOIUrl":"https://doi.org/10.1111/epi.18358","url":null,"abstract":"<p><strong>Objective: </strong>The TANC2 gene encodes a scaffolding synaptic protein with essential roles in synaptic transmission. This study aims to explore the association between TANC2 and epilepsy and the mechanism underlying phenotypic variation.</p><p><strong>Methods: </strong>Trio-based exome sequencing was performed in patients with epilepsy from the China Epilepsy 1.0 cohort. The association between TANC2 and epilepsy was validated with a Drosophila model. The role of TANC2 in development was investigated by single-cell RNA sequencing in cerebral organoids and spatiotemporal expression across brain regions.</p><p><strong>Results: </strong>De novo TANC2 variants were identified in six unrelated cases, including four null and two missense variants. The six variants were classified as \"pathogenic\"/\"likely pathogenic,\" according to the American College of Medical Genetics and Genomics guidelines. Patients with null variants exhibited severe phenotypes, including three with epilepsy and neurodevelopmental disorders (NDDs) and one with developmental and epileptic encephalopathy (DEE). In contrast, the patients with missense variants presented with only epilepsy. Genotype-phenotype correlation analysis revealed that variants associated with epilepsy and NDD were mostly null variants, whereas the missense variants were associated with NDD or epilepsy. NDD-associated missense variants exhibited more severe damage effects, compared with the epilepsy-associated missense variants. Functional studies in Drosophila suggested that knockdown TANC2 led to increased susceptibility to seizure-like behavior. TANC2 expresses highly in the brain, with three peaks in early fetal, infancy, and adulthood, coinciding with the onset ages of patients. Specifically, TANC2 exhibited the highest expression in the early fetal stage, indicating its vital role in early development. Single-cell RNA sequencing revealed an extensive expression of TANC2 in neurons in 1-month-old cerebral organoids, suggesting its vital role in neurodevelopment.</p><p><strong>Significance: </strong>This study suggested TANC2 as a causative gene of epilepsy and DEE. The phenotypic spectrums of TANC2 potentially ranged from early lethality, DEE, epilepsy with NDD, NDD, to mild epilepsy, depending on the damaging effects caused by variants.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662875","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":"Seizure freedom and reducing the risk of sudden unexpected death in patients with focal epilepsy treated with cenobamate or other antiseizure medications","authors":"Michael R. Sperling,&nbsp;William E. Rosenfeld,&nbsp;John Watson,&nbsp;Pavel Klein","doi":"10.1111/epi.18307","DOIUrl":"10.1111/epi.18307","url":null,"abstract":"<p>People with epilepsy who have uncontrolled seizures are at increased risk of all-cause mortality, injuries, comorbidities, mood and psychosocial disorders, and diminished quality of life. For those with focal epilepsy, focal to bilateral tonic–clonic seizures (FBTCS) pose the greatest risk for sudden unexpected death in epilepsy (SUDEP), a leading cause of premature mortality in people with epilepsy. Cenobamate is a third-generation antiseizure medication with demonstrated efficacy in controlling focal seizures, including FBTCS, in people with drug-resistant epilepsy. Treatment with cenobamate in clinical trials was associated with a reduction in all-cause mortality to a rate statistically indistinguishable from that seen in the general population, and SUDEP rates were lower than expected. As FBTCS are associated with the highest risk of death, prevention of this seizure type is especially important, and physicians should continue to try new therapies to prevent these seizures. A shared decision-making model should be used when interacting with patients and their care providers to achieve and maintain seizure control and maximize treatment outcomes.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"66 S1","pages":"4-14"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}