Seizure-European Journal of Epilepsy最新文献

{"title":"Cardiac safety of low-dose ACTH therapy in infantile spasms: Evidence from electrocardiography and advanced echocardiography","authors":"Borakay Dilek ,&nbsp;Saylan Cevik Berna ,&nbsp;Unver Olcay ,&nbsp;Doganci Demet Deniz ,&nbsp;Gunes Sager Safiye ,&nbsp;Turkdogan Dilsad","doi":"10.1016/j.seizure.2025.10.020","DOIUrl":"10.1016/j.seizure.2025.10.020","url":null,"abstract":"<div><h3>Objective</h3><div>Infantile epileptic spasms syndrome (IESS) is a catastrophic epileptic encephalopathy of infancy. While adrenocorticotropic hormone (ACTH) remains the most effective first-line therapy, its cardiac safety profile, particularly at low doses, has not been systematically evaluated. This study aimed to investigate the effects of low-dose ACTH therapy on cardiac conduction and function using electrocardiography (ECG) and advanced echocardiography.</div></div><div><h3>Methods</h3><div>This prospective controlled study included 24 infants with IESS and 24 age- and sex-matched healthy controls. All patients received low-dose ACTH (Synacthen® Depot, intramuscular; 0.5 mg/kg if &lt; 10 kg, 1 mg/kg if ≥ 10 kg; 18 injections over 8 weeks). Serial 12-lead ECGs and echocardiographic assessments, including M-mode, Doppler, tissue Doppler imaging (TDI), and speckle-tracking strain, were performed at baseline and at 2, 4, and 6 months. Controls underwent single baseline assessments.</div></div><div><h3>Results</h3><div>No patient developed overt arrhythmia or hypertension during treatment. However, ECG analysis revealed progressive prolongation of PR, QRS, QT, QTc, Tp–Te, and Tp–Te-related ratios (p &lt; 0.001). Echocardiography demonstrated significant increases in LVEDD, LVESD, LV mass, and MPI, with impaired diastolic relaxation and progressive deterioration of longitudinal and circumferential strain (p &lt; 0.05). Subgroup analyses showed no significant differences among genetic, hypoxic-ischemic, and hypoxia-related etiologies.</div></div><div><h3>Conclusion</h3><div>Even short-term, low-dose ACTH therapy is associated with subclinical conduction abnormalities and myocardial dysfunction in IESS patients. Routine cardiac monitoring, including advanced imaging modalities, should be integrated into ACTH protocols. Multidisciplinary management and larger multicenter studies are warranted to clarify the long-term cardiovascular implications of ACTH therapy in IESS.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 268-274"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520657","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":"Characteristics of epilepsy associated with hemophagocytic lymphohistiocytosis","authors":"Xue Wang,&nbsp;Hongyan Bi,&nbsp;Yingying Zhao,&nbsp;Yongbo Zhang","doi":"10.1016/j.seizure.2025.11.003","DOIUrl":"10.1016/j.seizure.2025.11.003","url":null,"abstract":"<div><h3>Objective</h3><div>Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome frequently complicated by severe neurological manifestations, including epilepsy. This study aimed to characterize the clinical phenotype, identify risk factors, and determine outcomes specific to HLH-associated epilepsy.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of 76 patients with HLH, comparing those with epilepsy (<em>n</em> = 25) and those without (<em>n</em> = 51). Comprehensive clinical, laboratory, genetic, electroencephalogram, and neuroimaging data were analyzed.</div></div><div><h3>Results</h3><div>Patients with HLH-associated epilepsy were significantly younger and had a higher prevalence of primary HLH. They demonstrated a more severe inflammatory profile, marked by elevated ferritin, interleukin-6, and cerebrospinal fluid (CSF) pleocytosis. Multivariate analysis identified age ≤25 years, ferritin &gt;20,000 ng/mL, CSF pleocytosis, and evolution to cortical atrophy as independent risk factors for epilepsy. Neuroimaging revealed a characteristic \"enhancement-to-atrophy\" sequence, where acute contrast-enhancing lesions (64.0 % vs. 29.4 %) often progressed to cortical atrophy (56.0 % vs. 19.6 %), highlighting a trajectory from acute neuroinflammation to permanent structural injury. The epilepsy group had significantly poorer survival (median 19 vs. 23 months). Although systemic HLH remission was achieved, the majority of patients (68.0 %) developed refractory epilepsy, necessitating long-term antiseizure medication.</div></div><div><h3>Significance</h3><div>HLH-associated epilepsy constitutes a severe clinical entity driven by intense neuroinflammation, which frequently results in irreversible brain damage. Early identification of its hallmark features, including young age, extreme hyperferritinemia, CSF pleocytosis, and the distinctive \"enhancement-to-atrophy\" neuroimaging sequence, is crucial for prompt intervention and long-term neurological management.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 275-280"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520658","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":"2025-12-01","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":"Enhancing diagnostic yield in functional seizures: A narrative review, design and implementation of a novel ictal testing battery for video telemetry","authors":"Elisaveta Sokolov ,&nbsp;Rohan Kandasamy ,&nbsp;Michael Kinney ,&nbsp;Nigel Lyttle ,&nbsp;Mahinda Yogarajah ,&nbsp;Beate Diehl","doi":"10.1016/j.seizure.2025.10.012","DOIUrl":"10.1016/j.seizure.2025.10.012","url":null,"abstract":"<div><div>Evaluation of behavioural impairment during functional seizures (FS) is critical for medical decision making, including accurate diagnosis, and future management recommendations. To date this type of behavioural evaluation in the setting of FS in an inpatient telemetry unit has not been closely reviewed. Here we perform a narrative review of the literature examining ictal testing and how best to improve diagnostic yield in the context of FS. We propose a novel ictal testing battery to obtain the most pertinent clinical information in people with functional seizures (PWFS). We then applied this novel ictal testing battery to patients as part of a service improvement project and compared it with the standard procedures in the video telemetry (VT) unit. This demonstrated significant improvement (Student’s T-Statistic of 2.284 and a p-value of 0.014) in the amount of FS-specific information extracted as identified in the review, suggesting that such a battery is useful and can be utilised in the VT setting.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 242-250"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477347","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":"Genotypic and phenotypic analysis of epilepsy associated with NPRL2/NPRL3 genes","authors":"Song Su ,&nbsp;Hongwei Zhang ,&nbsp;Qi Zhang ,&nbsp;Fen Zhao ,&nbsp;Wandong Hu ,&nbsp;Yong Liu ,&nbsp;Fang Fang","doi":"10.1016/j.seizure.2025.10.023","DOIUrl":"10.1016/j.seizure.2025.10.023","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Summary and analysis of clinical phenotypes, genotypes, and their correlations in epilepsy patients associated with NPRL2 and NPRL3 gene variants.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Retrospective analysis and statistical investigation of clinical phenotypes and genotype-phenotype correlations in children with NPRL2/NPRL3 gene variants, combining clinical data from Shandong University Affiliated Children’s Hospital and Beijing Children’s Hospital, Capital Medical University, with literature review.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our institution collected 8 epilepsy patients with NPRL2 variants, and 32 additional cases were identified from the literature, resulting in a total cohort of 40 patients. Among the available clinical data, 20 patients (54.3 %) were male and 16 (45.7 %) were female. The median age of seizure onset was 21.0 months (2.5–55.0 months). Twenty-five distinct variant types were identified, with nonsense variants (8/25, 32.0 %) being the most prevalent. Focal seizures were observed in 26 patients (75.8 %). Cortical developmental abnormalities Malformations of Cortical Development (MCD) were present in 15 patients (51.7 %), normal cortical structure in 12 (41.4 %), tumor in 1 (3.4 %), and hippocampal sclerosis in 1 (3.4 %). Regarding treatment, 18 patients (69.2 %) had drug-resistant epilepsy (DRE), while seizures were pharmacologically controlled in 8 (30.8 %). Thirteen patients underwent epilepsy surgery, and 8 achieved postoperative seizure freedom. Our institution collected 11 epilepsy patients with NPRL3 variants, combined with 145 cases reported in the literature, totaling 156 cases. A total of 67 variant sites and 6 variant types were identified, with frameshift variants (20/67, 29.9 %) being the most common. The cohort included 87 males (60 %) and 58 females (40 %), with a median age of onset of 48.0 months (12.0–120.0 months). Focal seizures were observed in 95 patients (79.2 %). MRI results showed normal findings in 69 patients (63.3 %) and MCD in 38 (34.9 %), including 30 cases of focal cortical dysplasia (FCD). DRE was reported in 52 patients (54.2 %), with 20 achieving seizure control through monotherapy. Twenty-nine patients underwent surgical resection, and 15 (51.7 %) achieved postoperative seizure freedom. Among 4 drug-resistant epilepsy patients treated with ketogenic diet therapy (KDT), 2 showed no response, 1 achieved seizure control, and 1 experienced recurrence after discontinuing KDT and undergoing surgery. Five patients received rapamycin therapy, with 4 showing no improvement. Comparative analysis between MCD and non-MCD groups revealed significant differences in age of onset and proportion of drug-resistant epilepsy (&lt;em&gt;P&lt;/em&gt; = 0.001, 0.033, and &lt; 0.001, respectively). When comparing NPRL2 and NPRL3 variant cohorts, significant differences were observed in age of onset (&lt;em&gt;P&lt;/em&gt; = 0.030) and presence of MCD (&lt;em&gt;P&lt;/em&gt; = 0.046). No significant differences were fou","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 208-218"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460426","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":"Fragile balance: Managing bone health in people with intellectual disability and epilepsy, an english multi-site study","authors":"Rachel Menon ,&nbsp;Charlotte Young ,&nbsp;Madeline Dale ,&nbsp;Matthew Allen ,&nbsp;Joanne McCabe ,&nbsp;Sarah Badger ,&nbsp;Myles Appleyard ,&nbsp;Georgios Mousailidis ,&nbsp;Rachel Newman ,&nbsp;Caryn Jory ,&nbsp;Joanne Hammett ,&nbsp;Abigail Swift ,&nbsp;Coryn Jones ,&nbsp;Indermeet Sawhney ,&nbsp;Robert Winterhalder ,&nbsp;Lance Watkins ,&nbsp;Rohit Shankar","doi":"10.1016/j.seizure.2025.10.018","DOIUrl":"10.1016/j.seizure.2025.10.018","url":null,"abstract":"<div><h3>Background</h3><div>People with intellectual disability (ID) experience poorer health outcomes than the general population, with epilepsy and polypharmacy contributing to further risks. Bone health is a neglected area, despite the established association between antiseizure medications (ASMs), (especially those cautioned by the UK Medicines and Healthcare products Regulatory Agency (MHRA)), and reduced bone mineral density. We aimed to evaluate prescribing practices, fracture risk, and bone health management in adults with ID and epilepsy attending specialist ID services.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted across three English specialist ID epilepsy services between August 2021–August 2022. Data were collected from case-note review, including ASM prescribing, falls and fracture history, bone health monitoring, and protective treatments. Descriptive statistics, Chi-squared and Mann-Whitney U tests were conducted. Logistic regression was used to examine associations between ASM use and fracture risk.</div></div><div><h3>Results</h3><div>Of 484 adults analysed almost all (97%) were prescribed ≥1 ASM, with 18% receiving four or more and 63% receiving at least one MHRA-cautioned ASM. Over 25% on MHRA-cautioned ASMs had a history of fractures, yet 38% received no bone-protective treatment. Patients with severe-profound ID were prescribed significantly more ASMs than those with mild-moderate ID. Each additional ASM increased fracture risk by 37%, and each additional MHRA-cautioned ASM by 43%.</div></div><div><h3>Conclusions</h3><div>Adults with ID and epilepsy are frequently exposed to polypharmacy, including bone health–compromising ASMs, yet bone health monitoring and treatment remain suboptimal. Targeted strategies and ID-specific guidance are urgently required to reduce fracture risk and improve outcomes in this vulnerable group.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 189-194"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439945","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":"Visualizing diagnostic delays in functional/dissociative seizures using the referral odyssey plot: A retrospective cohort study","authors":"Kazutoshi Konomatsu ,&nbsp;Yosuke Kakisaka ,&nbsp;Maimi Ogawa ,&nbsp;Mayu Fujikawa ,&nbsp;Makoto Ishida ,&nbsp;Takafumi Kubota ,&nbsp;Kazushi Ukishiro ,&nbsp;Nobukazu Nakasato ,&nbsp;Masashi Aoki ,&nbsp;Kazutaka Jin","doi":"10.1016/j.seizure.2025.10.009","DOIUrl":"10.1016/j.seizure.2025.10.009","url":null,"abstract":"<div><h3>Background</h3><div>Functional/dissociative seizures (FDS) are often misdiagnosed as epilepsy, leading to delays in appropriate interventions. Although certain factors are associated with diagnostic delays, the overall referral trajectory remains unclear. This study aimed to illustrate the diagnostic journey with a novel visual approach, the “referral odyssey plot,” and to depict patient pathways and identify factors associated with referral delays and diagnosis.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 50 patients diagnosed with documented FDS at Tohoku University Hospital (2014–2024). All patients underwent comprehensive inpatient evaluation, including long-term video-electroencephalogram monitoring, brain MRI, and psychosocial assessment. Four milestones were defined: seizure onset (T1), first non-epileptologist visit (T2), first epileptologist consultation (T3), and epilepsy monitoring unit admission (T4). Diagnostic pathways were visualized using a referral odyssey plot. Associations between variables and intervals were analyzed using Spearman’s correlation, Friedman test, Mann–Whitney <em>U</em> test, and Kruskal–Wallis test.</div></div><div><h3>Results</h3><div>The median total delay (T1–T4) was 51 months (interquartile range: IQR, 83.8). The longest delay occurred between T2 and T3 (median, 41 months; IQR, 74.8) and strongly correlated with total delay (ρ=0.95, <em>p</em> &lt; 0.001). Younger age at onset and a family history of epilepsy were significantly associated with longer T2–T3 intervals. Seizure worry scores were negatively correlated with T1–T2 intervals.</div></div><div><h3>Conclusion</h3><div>Referral delay to an epileptologist was the main contributor to prolonged diagnosis of FDS. The referral odyssey plot visualized individual trajectories and bottlenecks, supporting earlier specialist referrals. These findings highlight the need for timely access to epileptologists experienced in the comprehensive evaluation of epilepsy and FDS.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 61-67"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318885","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":"2025-12-01","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":"Novel PAK1 variants related to a variable phenotypic spectrum ranging from mild developmental delay to infantile epileptic spasms syndrome","authors":"Ting Wang ,&nbsp;Shijia Ouyang ,&nbsp;Dongfang Zou ,&nbsp;Zeyong Dong ,&nbsp;Zeshi Tan ,&nbsp;Haipo Yang ,&nbsp;Jianxiang Liao ,&nbsp;Dezhi Cao ,&nbsp;Yuehua Zhang","doi":"10.1016/j.seizure.2025.10.010","DOIUrl":"10.1016/j.seizure.2025.10.010","url":null,"abstract":"<div><h3>Objective</h3><div>To identify the novel variants and explore the new phenotypes of patients with <em>PAK1</em>-related disorder.</div></div><div><h3>Methods</h3><div>Five patients with <em>PAK1</em> variants were identified by whole-exon sequencing. Damaging effects of variants were analyzed using protein modelling.</div></div><div><h3>Results</h3><div>In this study, 5 patients were identified with 5 de novo <em>PAK1</em> variants, including p.Ile312Ser, p.Asp407Asn, p.Met453Thr, p.Leu470Pro, and p.Ile476Thr. All variants were missense, and one of which was a mosaic variant (Leu470Pro), with a variant allele fraction of 13.4 % (13/97). Four of five patients with <em>PAK1</em> variants had epilepsy, the seizure types included focal seizures, generalized tonic-clonic seizure and epileptic spasms. One patient diagnosed with infantile epileptic spasms syndrome (IESS). Four patients had macrocephaly. One patient only had mild developmental delay (DD) and normal head circumference. All missense variants identified in this study were predicted to be “damaging” by multiple in silico tools and to alter the hydrogen bonds with surrounding residues and/or protein stability. Notably, the variant Asp407Asn associated with a milder phenotype is predicted to have increased hydrogen bonds with ATP in contrast to our other reported variants. Spatial and temporal expression analysis showed that <em>PAK1</em> had three peak expressions in infant, adolescent and early adult brain subregions. Collectively, in our study (<em>n</em> = 5) and published studies (<em>n</em> = 11), all variants were missense variants. <em>PAK1</em>-related disorders encompass a wide phenotypic spectrum, including macrocephaly, epilepsy and DD/intellectual disability (ID). Seizures were observed in 81.25 % (13/16) of patients, and 53.8 % (7/13) patients with epilepsy had febrile seizure.</div></div><div><h3>Conclusions</h3><div>All variants of <em>PAK1</em>-related disorders were missense variants. In this study, five de novo variants were included, and Leu470Pro was the first reported mosaic variant in <em>PAK1. PAK1</em>-related disorders encompass a wide phenotypic spectrum, including macrocephaly, epilepsy and DD/ID. IESS is a rare newly recognized phenotype of <em>PAK1</em>-related epilepsy. More than half of patients with epilepsy had febrile seizure.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 88-95"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349577","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":"Predicting oxcarbazepine-induced hyponatremia in adult epilepsy patients: A multicenter machine learning analysis using real-world CDM data","authors":"Gucheol Jung ,&nbsp;JaeHyeok Lee ,&nbsp;Sung-Min Gho ,&nbsp;YoungMi Han ,&nbsp;ByungKwan Choi ,&nbsp;Jae Wook Cho ,&nbsp;Jiyoung Kim ,&nbsp;Gha-hyun Lee","doi":"10.1016/j.seizure.2025.10.004","DOIUrl":"10.1016/j.seizure.2025.10.004","url":null,"abstract":"<div><h3>Purpose</h3><div>Oxcarbazepine (OXC) is a widely used antiseizure medication (ASM) associated with hyponatremia. This study aimed to assess the prevalence and risk factors for OXC-induced severe hyponatremia using machine learning (ML) models applied to multicenter real-world data standardized within the Observational Medical Outcomes Partnership–Common Data Model (OMOP–CDM).</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study using OMOP-CDM data from two tertiary hospitals in South Korea. Adult epilepsy patients prescribed OXC were included, and severe hyponatremia was defined as a serum sodium concentration ≤128 mmol/L. Two prediction experiments were conducted: (1) single-institution training and external validation of an XGBoost model; and (2) multicenter training and evaluation of five machine learning algorithms, including XGBoost, random forest, support vector machine, logistic regression, and naïve Bayes. SHAP (SHapley Additive exPlanations) values were used for model interpretation.</div></div><div><h3>Results</h3><div>Among 2253 patients, the prevalence of severe hyponatremia was 8.4%. In Experiment 1, XGBoost showed strong internal performance (AUROC 0.82) but decreased external performance (AUROC 0.72). In Experiment 2, XGBoost trained on multicenter data achieved the highest AUROC (0.83) and F1-score (0.41), outperforming other models. SHAP analysis identified key predictors including valproate use, diuretics, high OXC dosage, age, and stroke history. Additional medications such as beta-blockers, calcium channel blockers, hypnotics, and other ASMs (e.g., levetiracetam, pregabalin, lacosamide) also contributed to risk.</div></div><div><h3>Conclusion</h3><div>XGBoost demonstrated robust predictive performance for OXC-induced severe hyponatremia using multicenter CDM data. SHAP-based interpretation revealed clinically relevant risk factors, supporting the implementation of personalized monitoring strategies in epilepsy care.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"133 ","pages":"Pages 167-174"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410622","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}