Seizure-European Journal of Epilepsy最新文献

{"title":"Efficacy and safety of cannabidiol in children with developmental and epileptic encephalopathies: A systematic review","authors":"Anna Saranti ,&nbsp;Pinelopi Dragoumi ,&nbsp;Konstantinos Pavlogiannis ,&nbsp;Evangelos Pavlou ,&nbsp;Dimitrios Zafeiriou","doi":"10.1016/j.seizure.2025.10.001","DOIUrl":"10.1016/j.seizure.2025.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Developmental and epileptic encephalopathies (DEEs) constitute rare epileptic conditions characterized by treatment-resistant seizures, neurodevelopmental delay, and various comorbidities. None of the currently available drugs have proven effective in suppressing epileptiform activity in those conditions.</div></div><div><h3>Objectives</h3><div>We aimed to assess the efficacy and safety of cannabidiol in children with DEEs through a systematic review.</div></div><div><h3>Methods</h3><div>We searched MEDLINE, Cochrane Central Register of Controlled Trials, trial registries, and reference lists of included studies. We conducted the last search on March 9, 2024. All study types investigating pharmaceutical cannabidiol in children with DEEs were considered eligible, with no language or date restrictions. Risk of bias was assessed using RoB2 and ROBINS-I V2.</div></div><div><h3>Results</h3><div>Of the 722 records identified, 14 met the inclusion criteria. The included studies varied in design and involved a total of 682 children. Cannabidiol was administered to a maximum dose of 50mg/kg/day. Almost all studies reported positive outcomes with cannabidiol, leading to a reduction of a 50% or above in seizure frequency in at least 20% of patients included in 11 studies. Adverse events were relatively common across studies and included somnolence, loss of appetite, diarrhea, fatigue, and increased serum aminotransferases. Most of them were mild to moderate and reversible.</div></div><div><h3>Conclusions</h3><div>Cannabidiol is generally well tolerated and has been shown to effectively reduce seizure frequency in children with DEEs whose seizures are refractory to concomitant antiepileptic medications. Future research should explore the long-term effects of cannabidiol on seizure control, developmental outcomes, and quality of life in this population.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 114-127"},"PeriodicalIF":2.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364361","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":"Sequential radiological manifestations in Dyke-Davidoff-Masson Syndrome-Comparison with recent systematic review.","authors":"Suat Yee Lee, Fatt Yang Chew","doi":"10.1016/j.seizure.2025.09.022","DOIUrl":"https://doi.org/10.1016/j.seizure.2025.09.022","url":null,"abstract":"","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145394819","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":"Efficacy of adjunctive cenobamate by focal seizure subtypes: a randomized, double-blind, placebo-controlled, multicenter study in a multinational Asian population","authors":"Xintong Wu ,&nbsp;Ling Chen ,&nbsp;Eunyeong Choe ,&nbsp;Kyoung Heo ,&nbsp;Seung Bong Hong ,&nbsp;Koji Iida ,&nbsp;Yong Heui Jeon ,&nbsp;Jiwon Jung ,&nbsp;Marc Kamin ,&nbsp;Kensuke Kawai ,&nbsp;Ji Hyun Kim ,&nbsp;Myung Won Kim ,&nbsp;Sang Kun Lee ,&nbsp;Sunita N Misra ,&nbsp;Jungshin Park ,&nbsp;William E Rosenfeld ,&nbsp;Tiancheng Wang ,&nbsp;Takamichi Yamamoto ,&nbsp;Peimin Yu ,&nbsp;Louis Ferrari","doi":"10.1016/j.seizure.2025.09.021","DOIUrl":"10.1016/j.seizure.2025.09.021","url":null,"abstract":"<div><h3>Objectives</h3><div>To assess the efficacy of adjunctive cenobamate by seizure subtype in Asian patients with uncontrolled focal epilepsy during a 24-week controlled study (NCT04557085 [C035]).</div></div><div><h3>Methods</h3><div>Adults 18–70 years old with ≥8 focal seizures (focal aware motor [FAM], focal impaired awareness [FIA], and/or focal to bilateral tonic-clonic [FBTC]) during an 8-week baseline, despite treatment with 1–3 antiseizure medications, were randomized 1:1:1:1 to receive placebo or cenobamate 100, 200, or 400 mg/day, starting at 12.5 mg/day and uptitrated at 2-week intervals. The study design included an 18-week titration phase and a 6-week maintenance phase. Median percent change from baseline in 28-day seizure frequency and responder rates for patients with FAM, FIA, and/or FBTC seizures were assessed during the maintenance phase and during a 12-week treatment period that combined the last 6 weeks of titration and the 6-week maintenance phase.</div></div><div><h3>Results</h3><div><em>N</em> = 519 patients were randomized (maintenance phase <em>n</em> = 446, 12-week period <em>n</em> = 478). During both periods assessed, numerically greater reductions vs placebo occurred across all cenobamate doses and seizure subtypes. For cenobamate 200 and 400 mg/day, maintenance-phase median seizure frequency reductions were 76 %-100 % across all seizure subtypes; seizure-free rates were up to 52.4 % (FAM), 57.5 % (FIA), and 75.0 % (FBTC). The most common cenobamate-related treatment-emergent adverse events (≥20 %) were dizziness and somnolence.</div></div><div><h3>Conclusions</h3><div>Cenobamate reduced all focal seizure subtypes in a generally dose-response manner in adult Asian patients, including maintenance-phase seizure frequency reductions of 76 %-100 %. Notably high seizure-free rates were observed for patients with FBTC seizures, an important contributor to morbidity/mortality in focal epilepsy patients.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 43-51"},"PeriodicalIF":2.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309813","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":"A proposal for a machine-learning algorithm for the prediction of seizure recurrence risk at 2 years after discontinuation of anti-seizure medications","authors":"Margherita Contento ,&nbsp;Bruno Bertaccini ,&nbsp;Martina Biggi ,&nbsp;Matteo Magliani ,&nbsp;Ylenia Failli ,&nbsp;Marco Paganini ,&nbsp;Luca Massacesi ,&nbsp;Eleonora Rosati","doi":"10.1016/j.seizure.2025.09.020","DOIUrl":"10.1016/j.seizure.2025.09.020","url":null,"abstract":"<div><h3>Background</h3><div>This article presents a novel method to create a scale for predicting the risk of seizure recurrence 2 years after discontinuation of anti-seizure medications (ASMs). The approach enables the development of a straightforward, easily calculable score scale with a clear-cut threshold to effectively identify high-risk patients.</div></div><div><h3>Methods</h3><div>Clinical and demographic features of epileptic patients who had discontinued their ASMs were incorporated into a customized R algorithm. This algorithm evaluated each covariate and its corresponding weight to determine the combination of weighted scores creating the scale with the highest accuracy for predicting seizure recurrence risk. Moreover, the algorithm generated a threshold that differentiates between low- and high-risk patients.</div></div><div><h3>Results</h3><div>In our dataset, the 10 covariates whose combination was associated with the scale with the maximized Youden index (0.51) selected by the algorithm were: “duration of epilepsy”, “duration of the seizure-free period on therapy”, “duration of ASM tapering”, “development delay”, “age at ASM withdrawal over 50 years”, “gender”, “age at ASM withdrawal over 40 years”, “structural etiology of epilepsy”, “failure of previous ASM discontinuations”, “age at seizure onset”; The sensitivity and specificity of the scale were 0.87 and 0.64 respectively. Scale scores above 5 identify high-risk patients.</div></div><div><h3>Conclusions</h3><div>This work does not aim to propose a definitive scale to predict the risk of seizure recurrence 2 years after discontinuation of ASMs. Rather, it introduces a data-driven tool to support the development of a scale with a clear-cut threshold, easily applicable in the clinical practice and understandable to patients.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 73-79"},"PeriodicalIF":2.8,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318728","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":"Developmental and epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS): Clinical and treatment insights from a cohort of 50 children","authors":"Ruzica Kravljanac ,&nbsp;Pasquale Striano ,&nbsp;Biljana Vucetic Tadic ,&nbsp;Jana Savkic Arsovic ,&nbsp;Luka Nikolic ,&nbsp;Jovana Bedjik ,&nbsp;Vladimir Oparnica ,&nbsp;Sofija Popović","doi":"10.1016/j.seizure.2025.09.019","DOIUrl":"10.1016/j.seizure.2025.09.019","url":null,"abstract":"<div><h3>Background</h3><div>Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS) is a rare and complex pediatric epilepsy syndrome characterized by cognitive and/or behavioral regression and nearly continuous spike-wave discharges during slow-wave sleep. D/EE-SWAS encompasses a spectrum of encephalopathies with heterogeneous etiologies and outcomes.</div></div><div><h3>Objective</h3><div>To assess etiology, clinical course, and treatment response in 50 children with D/EE-SWAS, with a focus on how underlying causes influence neuropsychological outcomes.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 50 children diagnosed with D/EE-SWAS at our center between 2005 and 2023. Patients were grouped into three etiological categories: self-limited focal epilepsies (SeLFE, n=19), structural brain abnormalities (n=18), and genetic causes (n=7). EEG features, cognitive and behavioral changes, and treatment responses were evaluated.</div></div><div><h3>Results</h3><div>Corticosteroids (80.9%), clobazam (55.8%), levetiracetam (54.1%), and sulthiame (52.9%) were the most effective treatments. SeLFE patients experienced shorter SWAS duration and better outcomes, while those with structural etiologies had more prolonged discharges and poorer responses. All patients showed cognitive and behavioral regression, with severity modulated by etiology.</div></div><div><h3>Conclusion</h3><div>D/EE-SWAS is a spectrum disorder with variable severity and prognosis depending on etiology. Early recognition and tailored treatment, especially in children with SeLFE, are essential to mitigate neurocognitive decline. This large single-center cohort provides new insights into the therapeutic challenges and outcome variability in D/EE-SWAS.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 20-28"},"PeriodicalIF":2.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271024","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, cardiovascular health, and all-cause mortality among adults: A cohort study","authors":"Rui Zhong ,&nbsp;Baoli Zhong ,&nbsp;Kezhong Zhang","doi":"10.1016/j.seizure.2025.09.018","DOIUrl":"10.1016/j.seizure.2025.09.018","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular disease is a common comorbidity in people with epilepsy and has been closely associated with mortality risk. This study was undertaken to investigate the associations between epilepsy, cardiovascular health and all-cause mortality risk among US adults using population-level data.</div></div><div><h3>Methods</h3><div>National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2018 were used. A total of 12,818 participants aged ≥ 18 years with complete data on epilepsy, cardiovascular health and mortality were included. Weighted logistic regression analysis models were used to explore the association between epilepsy and cardiovascular health. Weighted cox proportional hazard regression models were used to assess the associations of epilepsy and cardiovascular health with all-cause mortality.</div></div><div><h3>Results</h3><div>Among 12,818 participants, there were 112 participants with epilepsy and 555 deaths (a median follow-up of 49 months) were recorded. Epilepsy was significantly associated with low cardiovascular health after full adjustment. Sensitivity analyses suggested that this association remained significant after excluding individuals with history of cardiovascular disease. Epilepsy and low cardiovascular health were both associated with an increased risk of all-cause mortality. Furthermore, the association between epilepsy and increased mortality risk was partly mediated by cardiovascular health.</div></div><div><h3>Conclusions</h3><div>People with epilepsy have an increased risk of poor cardiovascular health and all-cause mortality compared with population controls. Poor cardiovascular health partly mediated the impact of epilepsy on mortality risk. Our findings emphasize the importance of cardiovascular health management in the clinical care of people with epilepsy.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 37-42"},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304278","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 in the context of forensic psychiatry: The relationship between epilepsy, violence and criminal responsibility","authors":"Barış Kılıç Demir ,&nbsp;Selma Çilem Kızılpınar ,&nbsp;Elif Banu Söker","doi":"10.1016/j.seizure.2025.09.017","DOIUrl":"10.1016/j.seizure.2025.09.017","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to describe the sociodemographic, clinical, and criminal characteristics of forensic psychiatry patients with epilepsy and to examine the relationship between epilepsy and seizures, criminal responsibility, and violence.</div></div><div><h3>Materials and Methods</h3><div>The study included 1235 patients who had completed inpatient treatment in a high-security forensic psychiatry unit. Within the total sample, 48 individuals diagnosed with epilepsy were assessed in terms of sociodemographic, clinical, and criminal variables, and their characteristics were compared to those of the overall sample.</div></div><div><h3>Results</h3><div>The prevalence of epilepsy was 3.79% (n=48). No significant difference was found between the groups of forensic psychiatry patients with a diagnosis of epilepsy and forensic psychiatry patients without a diagnosis of epilepsy in terms of self-destructive behaviour, suicide attempt, history of imprisonment, non-documented offense, and index offense severity (respectively p=0.598, p=0.840, p=0.907, p=0.479, p=0.343). The epilepsy group had a higher rate of non-violent offences, and no patients had committed severe violent offences. There were two patients (4.1%) in whom the index offence was associated with epilepsy and seizures.</div></div><div><h3>Conclusion</h3><div>The prevalence of epilepsy in the forensic psychiatry patient group was higher than in the general population. The predominance of non-violent offenses among the epilepsy group, the absence of any serious violent offense in this group, and the minority in other violence-related indicators provides important evidence against stigmatisation based on exaggerated associations between epilepsy and violence. The high comorbidity rates of epilepsy and intellectual disability underscore the need for developing special treatment programmes and approaches.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 1-7"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271025","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":"Early point-of-care EEG in acute stroke: Prevalence and predictive factors of early post-stroke status epilepticus (e-PSSE)","authors":"Giovanni Furlanis ,&nbsp;Edoardo Ricci ,&nbsp;Miloš Ajčević ,&nbsp;Stefania Pavan ,&nbsp;Katerina Iscra ,&nbsp;Gabriele Prandin ,&nbsp;Michele Malesani ,&nbsp;Emanuele Vincis ,&nbsp;Laura Mancinelli ,&nbsp;Federica Palacino ,&nbsp;Magda Quagliotto ,&nbsp;Gianpiero Farina ,&nbsp;Giulia Mazzon ,&nbsp;Marinella Tomaselli ,&nbsp;Paola Caruso ,&nbsp;Marcello Naccarato ,&nbsp;Paolo Manganotti","doi":"10.1016/j.seizure.2025.09.016","DOIUrl":"10.1016/j.seizure.2025.09.016","url":null,"abstract":"<div><h3>Purpose</h3><div>Status epilepticus (SE) is a severe complication of acute stroke (AS), with an incidence of approximately 1.5 %. This study aimed to investigate the prevalence of early post-stroke status epilepticus (e-PSSE) in a real-world stroke cohort using point-of-care EEG within the first 72 h after admission and identify the clinical and laboratory factors associated with its onset during the acute phase.</div></div><div><h3>Methods</h3><div>Clinical, laboratory and radiological data of 647 consecutive patients with AS assessed with point-of-care EEG were retrospectively analyzed. EEG was evaluated for the diagnosis of e-PSSE according to the International Federation of Clinical Neurophysiology criteria. Data of AS patients with PSSE were compared with those without PSSE. Multivariate logistic regression analysis was conducted to identify factors associated with the onset of PSSE.</div></div><div><h3>Results</h3><div>The median age of the cohort was 78 (68–83) and the median NIHSS at admission was 7 (2–11). Early PSSE was found in 27 (4.2 %) of 647 included patients. Multivariate analysis showed that female sex (OR=1.039, <em>p</em> = 0.011), chronic kidney disease (OR=1.052, <em>p</em> = 0.018), hemorrhagic stroke (OR=1.075, <em>p</em> &lt; 0.001), a higher neutrophil to lymphocyte ratio (NLR) (OR=1.005, <em>p</em> = 0.001) and NIHSS at admission (OR=1.004, <em>p</em> = 0.002) were significantly associated with the onset of PSSE.</div></div><div><h3>Conclusion</h3><div>This study highlights the critical role of early EEG assessment in detecting e-PSSE, with an incidence of 4.2 %. Moreover, our findings identify female sex, a history of CKD, higher NIHSS scores, hemorrhagic stroke, and the NLR as independent predictors of PSSE in the acute phase.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 8-15"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271026","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":"Fenfluramine treatment beyond dravet and lennox-gastaut syndromes - A retrospective study suggesting a novel use in genetic, developmental and epileptic encephalopathies (DEEs)","authors":"Amy Urbina Lopez ,&nbsp;Robin T Varughese ,&nbsp;Candice Marti ,&nbsp;Aizara Ermekbaeva ,&nbsp;Poduri Annapurna ,&nbsp;Kothare Sanjeev ,&nbsp;Yash Shah","doi":"10.1016/j.seizure.2025.09.013","DOIUrl":"10.1016/j.seizure.2025.09.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Fenfluramine (FFA), an amphetamine derivative, was historically used as an appetite suppressant but was discontinued for its association with valvular heart disease and pulmonary hypertension. More recently, significant results in randomized trials demonstrated promising seizure reduction properties. Further research led to FDA approval for usage of FFA in children aged two years and older with Dravet syndrome (DS) in 2020 and Lennox-Gastaut syndrome (LGS) in 2022 [<span><span>1</span></span>,<span><span>2</span></span>]. Considering FFA’s success in these populations, we aimed to characterize the extent of its efficacy related to drug-resistant epilepsy in individuals with genetic developmental and/or epileptic encephalopathies (DEEs). We hypothesized similar rates of improvement (at least 25 % seizure reduction) as the LGS and DS studies.</div></div><div><h3>Methods</h3><div>After Institutional Review Board approval, a systematic retrospective chart review was conducted of pediatric patients with DEE receiving clinical care in Boston Children’s Hospital, Cohen Children’s Medical Center, and Our Lady of the Lake Children’s Hospital-Baton Rouge systems who were placed on FFA after July 1, 2020. Self-reported seizure frequency and side effects were extracted. Reduction in monthly seizure frequency was the primary outcome investigated. Related-Samples Wilcoxon Signed Rank Test was performed to evaluate mean difference in seizure frequency pre-and-post-FFA treatment. The patients in this sample were on FFA for a duration of 23.5 ± 15.1 months.</div></div><div><h3>Results</h3><div>There were 20 children with epilepsy of diverse etiologies (excluding LGS and DS) who were placed on FFA and met our inclusion criteria. A statistically significant (<em>p</em> = 0.02) decrease in seizure frequency in days per month was found, with a mean reduction of 4.6 days per month. For generalized seizure types, there was a median reduction of 7 days per month. Some children responded more dramatically than others with 95 % seizure reduction in our two children with apneic seizures and tuberous sclerosis. Nine of twenty children observed had at least 50 % seizure reduction, 8 of which had at least 75 % seizure reduction. Additionally, the safety profile of FFA was similar as the one reported in the studies done on patients with DS and LGS.</div></div><div><h3>Conclusions</h3><div>This retrospective report suggests that FFA may be an effective add-on therapeutic option in children with rare, genetic epilepsies where efficacy was notable early on in drug initiation and titration. A trial of FFA for drug-resistant seizures may be considered to assess efficacy in the DEE population beyond DS and LGS.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 161-166"},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145379564","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":"Biallelic ACSF3 variants with combined malonic and methylmalonic acidemia and associated developmental epileptic encephalopathy phenotype: A novel genotype-phenotype correlation","authors":"JuleLayne Curry ,&nbsp;Emily Bonkowski ,&nbsp;Heather Mefford ,&nbsp;James Wheless ,&nbsp;Nitish Chourasia","doi":"10.1016/j.seizure.2025.09.015","DOIUrl":"10.1016/j.seizure.2025.09.015","url":null,"abstract":"<div><h3>Purpose</h3><div>Combined malonic and methylmalonic acidemia (CMAMMA) is a rare genetic disorder caused by biallelic variants in the acyl-CoA synthetase family member 3 (<em>ACSF3</em>) gene (Witkowski et al., 2011) and is associated with elevated levels of malonic acid (MA) and methylmalonic acid (MMA) in urine (Sloan et al., 2011). CMAMMA is generally considered a benign disorder, with recent descriptions of potential neuropsychiatric symptoms in children (Levtova et al., 2019). We expand the phenotype by describing a case of severe developmental and epileptic encephalopathy with a CMAMMA-associated Lennox-Gastaut Syndrome (LGS) phenotype and comorbid neuropsychiatric abnormalities.</div></div><div><h3>Methods and Results</h3><div>An 8-year-old boy with CMAMMA, referred to our clinic’s neurogenetic center, presented with refractory epilepsy and severe neurobehavioral symptoms. His epilepsy consisted of tonic, atonic, and generalized tonic-clonic seizures with electroclinical features consistent with LGS. The patient had comorbid autism, aggression, and intellectual disability with a history of developmental regression. Genetic testing confirmed pathogenic biallelic <em>ACSF3</em> variants, and urine organic acid testing showed elevated levels of MA and MMA in urine.</div></div><div><h3>Conclusion</h3><div>This case suggests that CMAMMA can lead to severe epilepsy and a neuropsychiatric phenotype, expanding the clinical spectrum of the disorder.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 16-19"},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271022","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}