Epilepsy Research最新文献

{"title":"Reassessing anhedonia in Genetic Absence Epilepsy: Sucrose preference unaltered by spike-wave discharges in WAG/Rij rats","authors":"Maria Pupikina,&nbsp;Evgenia Sitnikova","doi":"10.1016/j.eplepsyres.2025.107683","DOIUrl":"10.1016/j.eplepsyres.2025.107683","url":null,"abstract":"<div><div>Anhedonia, characterized by reduced pleasure or interest, is linked to various neurological disorders, including genetic epilepsies. Previous studies in genetic rat models of absence epilepsy, such as WAG/Rij rats, have reported anhedonia-like behaviors. Here, we hypothesize that these behaviors depend on experimental factors rather than epilepsy itself. To test this, we conducted sucrose preference tests in WAG/Rij rats using different concentrations (2 % and 20 %), fasting durations (0 and 23 h), and test lengths (1 and 48 h). Rats underwent non-invasive electroencephalographic examination, which revealed typical 8–10 Hz spike-wave discharges (SWD) and a hallmark of absence epilepsy. In Experiment 1 (2 % sucrose), 59 symptomatic and 31 asymptomatic rats were tested at 6 and 12 months. In Experiment 2 (20 % sucrose), 34 rats were tested at 6 months. Surprisingly, there were no significant differences in sucrose preference or consumption between symptomatic and asymptomatic rats, indicating that absence epilepsy in WAG/Rij rats does not cause anhedonia. After a 23-h fast, female rats showed a lower preference for 20 % sucrose than males, suggesting that fasting conditions might introduce stress and metabolic differences that affect males and females differently. Both the 2 % and 20 % sucrose preference tests showed that symptomatic WAG/Rij rats did not exhibit anhedonia and had similar preferences to asymptomatic rats, regardless of concentration or fasting conditions. These findings challenge previous assumptions and emphasize the importance of considering methodological factors when interpreting rodent behavior.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107683"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardization of preclinical methodologies for discovery and validation of circulating microRNA biomarkers for post-traumatic epileptogenesis – Lessons learned from the EpiBioS4Rx Project 1","authors":"Noora Puhakka ,&nbsp;Mette Heiskanen ,&nbsp;Xavier Ekolle Ndode-Ekane ,&nbsp;Idrish Ali ,&nbsp;Cesar Santana-Gomez ,&nbsp;Shalini Das Gupta ,&nbsp;Meheli Banerjee ,&nbsp;Pedro Andrade ,&nbsp;Riikka Immonen ,&nbsp;Pablo Casillas-Espinosa ,&nbsp;Gregory Smith ,&nbsp;Rhys D. Brady ,&nbsp;Juliana Silva ,&nbsp;Emma Braine ,&nbsp;Matthew R. Hudson ,&nbsp;Glen R. Yamakawa ,&nbsp;Nigel C. Jones ,&nbsp;Sandy R. Shultz ,&nbsp;Neil G. Harris ,&nbsp;David K. Wright ,&nbsp;Asla Pitkänen","doi":"10.1016/j.eplepsyres.2025.107667","DOIUrl":"10.1016/j.eplepsyres.2025.107667","url":null,"abstract":"<div><h3>Objective</h3><div>To analyze the success of harmonization and standardization of plasma miRNA biomarker discovery and validation for post-traumatic epilepsy (PTE) in the EpiBioS4Rx international multicenter project.</div></div><div><h3>Methods</h3><div>Adult male Sprague-Dawley rats were randomized to lateral fluid-percussion-induced traumatic brain injury (TBI) or sham operation at three study sites (Finland, Australia, USA). Video-electroencephalogram (vEEG) was performed in the 7th post-injury month to detect spontaneous seizures. Tail vein plasma was collected at baseline and 48 h after TBI for microRNA (miRNA) analysis. Common data elements were generated to document and monitor pre-analytic activities, including housing conditions, post-injury care, blood sampling, plasma preparation, plasma quality, storage, and shipping. miRNA analysis was performed using droplet digital PCR (ddPCR) at one study site (Finland) with on-site standardized procedures.</div></div><div><h3>Results</h3><div>The 2-day miRNA levels were successfully measured in 85 % (209/245) of the rats included in the final analysis cohort. Exclusions were related to small sample volume, hemolysis, and failed RNA extraction for ddPCR. Most of the pre-analytical factors leading to sample exclusions were related to non-optimal plasma pipetting. We also recognized gaps in data entry and monitoring of personnel training.</div></div><div><h3>Conclusions</h3><div>Our study demonstrates that conducting a successful plasma miRNA biomarker analysis requires procedural harmonization between laboratories, protocol standardization, inclusion and analysis of quality controls, training of researchers, and continuous monitoring of adherence to pre-agreed protocols.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107667"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Principal component analysis of antiseizure medication-induced hostility/aggression and factor analysis of levetiracetam using the food and drug administration adverse event reporting system","authors":"Ryuichiro Hosoya ,&nbsp;Kento Kitajima ,&nbsp;Koushirou Sogawa ,&nbsp;Daigo Ikegami ,&nbsp;Tomoko Terajima ,&nbsp;Hideaki Kato ,&nbsp;Masahiko Funada ,&nbsp;Hajime Kagaya ,&nbsp;Yoshihiro Uesawa","doi":"10.1016/j.eplepsyres.2025.107626","DOIUrl":"10.1016/j.eplepsyres.2025.107626","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy affects approximately 50 million people worldwide. Antiseizure medications (ASMs) are essential for seizure control. However, adverse psychiatric effects, particularly hostility and aggression, affect treatment adherence and the quality of life. The risk factors and mechanisms underlying these adverse effects remain unclear.</div></div><div><h3>Objective</h3><div>This study aimed to classify ASM-induced hostility/aggression using the Food and Drug Administration Adverse Event Reporting System (FAERS), a global pharmacovigilance database, focusing on the risk factors and onset patterns of levetiracetam-induced hostility/aggression.</div></div><div><h3>Methods</h3><div>The FAERS database (2004 Q1–2022 Q1) was analyzed to calculate the reporting odds ratios for ASM-induced hostility/aggression, which were classified using a principal component analysis. Levetiracetam-induced adverse effects and the associated independent risk factors were examined. Weibull distribution analysis was used to assess the time-to-onset patterns</div></div><div><h3>Results</h3><div>Principal component analysis identified eight ASM-induced adverse effects, including \"aggression,\" \"anger,” “homicidal ideation,\" and \"hostility.\" In those taking levetiracetam aged ≥ 12 years, male sex, younger age, and specific concomitant medications were independent risk factors for levetiracetam-induced adverse effects. Levetiracetam-induced adverse effects exhibited an early failure pattern, with a median onset of 4.5 days in patients aged ≥ 12 years and 1.5 days in those &lt; 12 years.</div></div><div><h3>Conclusion</h3><div>In this study, we classified ASM-induced hostility/aggression and estimated the risk factors for levetiracetam-induced adverse effects. In particular, we identified early-onset patterns and high-risk patient profiles. These findings are consistent with clinical observations and provide insight into the mechanisms underlying these adverse effects, which will contribute to proactive risk management and personalized treatment strategies.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107626"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of executive functions on quality of life in Pediatric Epilepsy: A cross-sectional study","authors":"Lena Mühe ,&nbsp;Elisabeth Kaufmann ,&nbsp;Mirjam N. Landgraf ,&nbsp;Moritz Tacke ,&nbsp;Christine Makowski ,&nbsp;Malin Zaddach ,&nbsp;Leonie Grosse ,&nbsp;Miriam Gerstner ,&nbsp;Robert Optiz ,&nbsp;Ingo Borggraefe","doi":"10.1016/j.eplepsyres.2025.107646","DOIUrl":"10.1016/j.eplepsyres.2025.107646","url":null,"abstract":"<div><h3>Background</h3><div>The EpiTrack Junior is a screening tool assessing executive function in children with epilepsy. This study aimed to investigate whether children and adolescents with epilepsy are at a higher risk of experiencing a reduced quality of life if they also reveal abnormal results reflecting executive dysfunction.</div></div><div><h3>Methods</h3><div>We screened patients for executive dysfunction using the clinical test tool EpiTrack Junior. To assess health-related quality of life (HRQoL), the German children’s and parents’ version of KINDL questionnaire was used. The KINDL scores (total score and dimensions scores) of patients with and without clinically conspicuous values were compared (≤ 28 and &gt; 29, respectively). In addition, the exact EpiTrack Junior point scores were correlated with the KINDL total score and the scores of all KINDL dimensions.</div></div><div><h3>Results</h3><div>In this study 112 (mean age = 11.72, SD = 3.6) patients with epilepsy and their parents were included. Patients with executive dysfunctions (EpiTrack Junior values ≤ 28) scored significantly poorer in the QoL categories ‘family’ and ‘social environment’ than patients without. In the ‘family’ dimension, the child-report revealed the following data: z = -2.759; adjusted <em>p-</em>value: 0.042, and in the ‘friends’ dimension, parent-reports yielded the following data: z = -3.645; adjusted <em>p</em>-value: 0.007. In contrast, the 'self-esteem' dimension in the children's version showed significantly higher values in patients with executive dysfunctions than for those without: z = -2.524; adjusted <em>p-</em>value: 0.042. No significant differences between patients with and without executive dysfunctions were found for the overall quality of life (as assessed by the KINDL 'total score') as well as for the other dimensions (school, physical and emotional well-being).</div></div><div><h3>Conclusions</h3><div>No differences were found in the overall quality of life between patients with and without executive dysfunction. Nevertheless, executive dysfunction appeared to have a negative impact on some areas of life, such as family and friends, and was a predictor of increased self-esteem.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107646"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histological and electrophysiological effects of sulbactam and valproate in the PTZ-induced epileptic rat model","authors":"Yun-Ju Hsieh ,&nbsp;Fang-Chia Chang ,&nbsp;Chiung-Hui Liu ,&nbsp;Yi-Tse Hsiao ,&nbsp;Wen-Chieh Liao ,&nbsp;Ru-Yin Tsai ,&nbsp;Ciptasari Prabawanti ,&nbsp;Chih-Li Lin ,&nbsp;Ching-Sui Hung ,&nbsp;Ying-Jui Ho","doi":"10.1016/j.eplepsyres.2025.107676","DOIUrl":"10.1016/j.eplepsyres.2025.107676","url":null,"abstract":"<div><div>An imbalance between excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) neurotransmitters is a key mechanism in epilepsy. Astrocytic glutamate transporter-1 (GLT-1) helps reuptake glutamate in the synaptic cleft to maintain glutamate concentration and prevent neuronal hyperactivity. Sulbactam (SUL), a β-lactam drug, increases GLT-1 expression. Valproate (VPA) is a first-line antiepileptic drug. The current study evaluated the effects of SUL and VPA on histology and electroencephalography in a pentylenetetrazol (PTZ)-induced epilepsy rat model.</div><div>Male Wistar rats received intraperitoneal injection of PTZ (20–35 mg/kg, every other day) for 25 days (13 injections in total) to establish an epilepsy model. From day 26, saline, SUL (50 or 150 mg/kg), VPA (50 mg/kg), or a combination of SUL and VPA was intraperitoneally administered daily for 25 days. Electroencephalography recordings were taken on day 46 or 47. Brains were used for histological analyses.</div><div>Electrophysiological results indicated that during the PTZ challenge session, the epilepsy group had significantly more spikes and seizures and higher delta, theta, and beta power compared with the control group. SUL at 150 mg/kg and the combination of SUL (50 mg/kg) and VPA (50 mg/kg) significantly reduced the numbers of spikes and seizures. SUL at both 50 and 150 mg/kg and the combination of SUL (50 mg/kg) and VPA (50 mg/kg) significantly inhibited the increase in delta, theta, and beta power. In terms of histology, the epilepsy group exhibited lower neuronal density in the hippocampus, lower GLT-1 expression in astrocytes, lower GABAergic density, and hyperactivity in the subthalamic nucleus. These neurophysiological impairments were restored by treatment with SUL and a combination of SUL and VPA. The results suggest that SUL increases GLT-1 expression in astrocytes and the number of GABAergic neurons, indicating it holds potential as an antiepileptic treatment.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107676"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SYNGAP-1 developmental and epileptic encephalopathy: Utility of corpus callosotomy and neuromodulation","authors":"Stephanie DeGasperis,&nbsp;Rajesh RamachandranNair,&nbsp;Kevin C. Jones,&nbsp;Robyn Whitney","doi":"10.1016/j.eplepsyres.2025.107641","DOIUrl":"10.1016/j.eplepsyres.2025.107641","url":null,"abstract":"<div><h3>Introduction</h3><div>Variants in <em>SYNGAP1</em> cause a rare childhood-onset developmental and epileptic encephalopathy (DEE). Limited reports describe palliative surgical procedures such as corpus callosotomy (CC) and vagus nerve stimulation (VNS) in <em>SYNGAP1</em>-related DEE.</div></div><div><h3>Methods</h3><div>A retrospective chart review of de-identified medical records from the SynGAP Research Fund Citizen Health Database (Citizen) who underwent CC and/or VNS was conducted. This was supplemented with one child from our centre. Details related to epilepsy, comorbidities, genetics, electroencephalogram/neuroimaging findings and treatment response are summarized.</div></div><div><h3>Results</h3><div>We identified 185 children with likely pathogenic/pathogenic variants in <em>SYNGAP1</em>; 156 had epilepsy (n = 156/185, 84.3 %). Fifteen children had palliative procedures (15/156, 9.6 %). Eleven children had VNS (n = 11/15, 73.3 %), and the median follow-up was 3.3 years (IQR 5.6, 3.3). Seven children had an initial &gt; 50 % seizure reduction (n = 7/11, 63.6 %), 2 had worsening (n = 2/11, 18.2 %), 1 had no change (n = 1/11, 9.1 %), and 1 had an unknown response (n = 1/11, 9.1 %). VNS response was sustained in 3 children (3/11, 27.3 %). Two children (n = 2/15, 13.3 %) had CC only with a mean follow-up of 3.1 years; 1 became seizure-free, and the other had &gt; 50 % seizure reduction. Two children (n = 2/15, 13.3 %) underwent VNS then CC, 1 had a &gt; 50 % overall seizure reduction, and one had minimal change; mean follow up from CC was 3.1 years. One child from our centre had a sustained &gt; 80 % seizure reduction (1.5 years) following CC at 7 years.</div></div><div><h3>Conclusion</h3><div>The effect of VNS was variable and sustained in less children over time. CC appeared to be more effective in the few treated. Larger cohorts are required to confirm these findings in <em>SYNGAP1</em>-related DEE.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107641"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends, prescribing patterns and projections of antiseizure drug use in Europe","authors":"Lilly Josephine Bindel,&nbsp;Roland Seifert","doi":"10.1016/j.eplepsyres.2025.107689","DOIUrl":"10.1016/j.eplepsyres.2025.107689","url":null,"abstract":"<div><h3>Purpose</h3><div>Epilepsy represents a significant global burden, with antiseizure drugs (ASDs) essential for treatment. This study examines past and recent trends in ASD consumption in 11 European countries, forecasts future developments, analyses Anatomical Therapeutic Chemical Classification (ATC) subgroup use, and offers an initial assessment of treatment sufficiency.</div></div><div><h3>Methods</h3><div>Publicly available consumption data were collected for ATC group N03A and its subgroups. Past trends in defined daily doses per 1000 inhabitants per day (DID) were analysed, and projections to 2030 were made using Auto Regressive Integrated Moving Average (ARIMA) models. For each country, treatment coverage relative to epilepsy prevalence was estimated.</div></div><div><h3>Results</h3><div>In 2023, ASD consumption ranged from 6.9 to 14.0 DID, with varying past and projected trends. The most commonly and increasingly used subgroup was miscellaneous (e.g. levetiracetam). Other subgroup distributions differed across countries, with most showing declines. The analysed countries of Northern Europe had the highest use and share of miscellaneous drugs, while Southern and Eastern Europe showed greater use of barbiturates and benzodiazepines. Adjusted treatment coverage revealed potential undertreatment in several countries, particularly in Eastern Europe.</div></div><div><h3>Conclusion</h3><div>ASD use has shifted in subgroup patterns without a uniform trend in total volume, with strong regional differences. Evaluating treatment adequacy remains challenging due to non-epilepsy indications. The increase in miscellaneous use appears to be driven by broader applications rather than substitution for older ASDs. Evidence suggests a north-to-south-east gradient, with more rational use in Northern Europe. These disparities likely reflect systemic determinants. The ATC system’s limitations reduce interpretative capability.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107689"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-morbid seizures in frontotemporal dementia: What do they tell us?","authors":"Syeda Amrah Hashmi ,&nbsp;Mark Quigg ,&nbsp;Anelyssa D’Abreu ,&nbsp;Carol Manning ,&nbsp;Jaideep Kapur ,&nbsp;Ifrah Zawar","doi":"10.1016/j.eplepsyres.2025.107640","DOIUrl":"10.1016/j.eplepsyres.2025.107640","url":null,"abstract":"<div><h3>Objectives</h3><div>Comorbid seizures occur in 2–11 % of frontotemporal dementia(FTD). Despite the high risk for seizures, the risk factors, clinical characteristics, and seizure outcomes in FTD patients with comorbid seizures remain understudied.</div></div><div><h3>Methods</h3><div>All patients who presented to our hospital from 5/1/2011–4/30/2024 with a clinical diagnosis of FTD were included and subclassified into behavioral-variant FTD(bvFTD), sematic-variant-primary-progressive-aphasia(svPPA), or non-fluent-primary-progressive-aphasia(nfPPA). Demographics, comorbidities, dementia characteristics, and seizure characteristics were obtained from electronic medical records. Patients were classified into those with(FTD+SZ) or without(FTD-SZ) clinically-diagnosed seizures. Seizure outcome was categorized as uncontrolled, controlled on anti-seizure-medications(ASMs), or self-resolving if resolved without ASMs. Data were analyzed using Pearson’s Chi-squared, Fisher Exact, or t-tests.</div></div><div><h3>Results</h3><div>Of 317 FTD patients(average age of dementia onset=64.18<u>+</u>9.07years,46.37 % female]), 24(7.6 %) reported seizures. FTD+SZ were more likely to have anxiety(FTD+SZ=7(29.17 %),FTD-SZ= 35(11.95 %),p = 0.0392).Traumatic brain injury(TBI) was the only risk factor for seizures(FTD+SZ=6(25 %),FTD-SZ= 18(6 %),p &lt; 0.001). BvFTD was the most common subtype in FTD+SZ(54.17 %). Focal seizures were more common(50 %) than generalized (29.17 %), with temporal-lobe epilepsy(TLE) being the most common subtype of focal seizures(42 %). Levetiracetam was the most frequently used ASM(38.1 %). Seizures had a favorable prognosis, with 87.5 % achieving seizure control through ASMs, and seizures self-resolving in the rest. FTD+SZ were more likely to be older at death(FTD+SZ=78.63years,FTD-SZ=71.37,p = 0.03966).</div></div><div><h3>Significance</h3><div>The prevalence of comorbid seizures in FTD at our single-center is 7.6 %. They were most common in bvFTD, primarily focal, with TLE as the predominant subtype. Anxiety was more prevalent with comorbid seizures. Most achieved seizure control on ASMs. FTD+SZ were older at death. These findings address a critical gap, guiding diagnosis, management, and future research.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107640"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered synaptic functions in a humanized mouse model of down syndrome (TcMAC21): Implications for seizure susceptibility","authors":"Li-Rong Shao ,&nbsp;Carl E. Stafstrom","doi":"10.1016/j.eplepsyres.2025.107686","DOIUrl":"10.1016/j.eplepsyres.2025.107686","url":null,"abstract":"<div><div>It is not understood why children with Down syndrome (DS, trisomy of chromosome 21) have an increased risk of seizures, including infantile spasms and tonic-clonic seizures. Using a novel humanized mouse model of DS (TcMAC21), we recently showed that TcMAC21 mice express an increased propensity to infantile spasms and demonstrate an increased neocortical synaptic excitation-to-inhibition ratio. To understand the pathophysiology of DS that may predispose animals to increased seizure susceptibility, we investigated 1) kainic-acid receptor (KAR)-mediated excitation, 2) gamma-aminobutyric acid receptors A and B (GABA_AR and GABA_BR)-mediated inhibition, and 3) synaptojanin 1 (SYNJ1) function in TcMAC21 mice, as genes encoding KAR, GABA_BR and SYNJ1 are among those triplicated in DS. Layer V neocortical neurons were recorded using whole-cell patch-clamp recordings to test KAR, GABA_AR, GABA_BR, and SYNJ functions. TcMAC21 neurons responded to focal KA application with significantly larger currents than control euploid neurons. GABA_AR-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) were less frequent in TcMAC21 than in euploid neurons while sIPSC amplitudes remained unchanged. Bath application of a GABA_BR agonist, baclofen, caused similar hyperpolarization in TcMAC21 and euploid neurons. During repetitive synaptic stimulation, excitatory postsynaptic currents (EPSCs) in TcMAC21 neurons decayed slower and to a lesser extent than control euploid neurons, indicating less transmitter depletion (i.e., enhanced synaptic vesicle trafficking). These data provide the first physiological evidence for gain-of-function of KAR and SYNJ1, and altered GABA-mediated synaptic function in TcMAC21 mice, and may represent some important DS-specific mechanisms of seizure pathogenesis.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107686"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145323836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and tolerability of perampanel as first add-on treatment in pediatric patients with focal and generalized epilepsy","authors":"Bárbara Blanco Martínez,&nbsp;Elena Arce Portillo,&nbsp;María Muñoz Cabeza,&nbsp;Mercedes López Lobato,&nbsp;Beatriz Muñoz Cabello,&nbsp;Marta Correa Vela,&nbsp;Laura González Hernández,&nbsp;Carmen Cortés Jiménez,&nbsp;Olga Alonso Luengo","doi":"10.1016/j.eplepsyres.2025.107690","DOIUrl":"10.1016/j.eplepsyres.2025.107690","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare the effectiveness and safety of perampanel as first add-on vs. late add-on therapy in children with focal or generalized epilepsy.</div></div><div><h3>Methods</h3><div>Retrospective, single-center study conducted between March 2022 and April 2023, including children ≥ 4 years with focal an generalized epilepsy who started treatment with perampanel in November 2020 or later. Patients were classified into two groups: perampanel as first and as late add-on treatment. Effectiveness and safety data were collected at 3, 6, and 12 months after starting treatment. Primary outcomes were responder rates, seizure-freedom rates, and worsening.</div></div><div><h3>Results</h3><div>57 patients (45.6 % women) with a mean (SD) age of 8.8 (±3.5) years were included; 27 in the first and 30 in the late add-on group. Effectiveness was consistently higher throughout visits in patients receiving perampanel as first vs. late add-on treatment, with higher response rates (12 months, 95.0 % vs. 55.6 %, <em>p</em> = 0.003), higher seizure-freedom rates (12 months, 65 % vs. 37.0 %, <em>p</em> = 0.058), and fewer patients with worsening (12 months, 0 % vs. 12.8 %, <em>p</em> = 0.031). Retention rates remained high in both groups throughout visits. Sixteen patients discontinued treatment. Reasons were lack of effectiveness, which was more frequent in the late vs. first add-on group, with few patients discontinuing due to adverse events.</div></div><div><h3>Conclusion</h3><div>The improved effectiveness outcomes of perampanel used as first vs. late add-on therapy in a pediatric population and the favorable safety outcomes support its use as first add-on therapy in pediatric patients with focal and generalized epilepsy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107690"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}