Epilepsy ResearchPub Date : 2025-09-02DOI: 10.1016/j.eplepsyres.2025.107655
Hakimeh Gavzan , Mohammad Sayyah , Tara Asgari , Mohammad Ali Mobaraki
{"title":"Docosahexaenoic acid provides a protective effect in amygdala-kindled rats by activating peroxisome proliferator-activated receptor α","authors":"Hakimeh Gavzan , Mohammad Sayyah , Tara Asgari , Mohammad Ali Mobaraki","doi":"10.1016/j.eplepsyres.2025.107655","DOIUrl":"10.1016/j.eplepsyres.2025.107655","url":null,"abstract":"<div><h3>Introduction</h3><div>Docosahexaenoic acid (DHA) is a bioactive fatty acid with safe and acceptable anti-seizure activity in clinical and animal studies. Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, with a high rate of drug resistance. The peroxisome proliferator-activated receptor α (PPARα) is expressed in the brain and plays a significant role in oxidative stress, energy homeostasis, and mitochondrial fatty acid metabolism. We aimed to evaluate the acute effect of DHA on the amygdala-kindled seizures and the role of PPARα in the DHA effect.</div></div><div><h3>Methods</h3><div>Male rats were kindled by repetitive daily electrical stimulation of the amygdala through a stimulating-recording electrode. DHA 1 mM (alone, or along with the PPARα antagonist GW6471, 2 and/or 4 μg/rat) was injected into the lateral cerebral ventricle of the kindled rats. The amygdala-kindled seizures were evoked 15 and 30 min after drug administration. The duration of after-discharges (ADD), generalized seizure behavior (S5D), and total seizure behavior (SD) were recorded.</div></div><div><h3>Results</h3><div>DHA significantly decreased ADD (<em>p</em> < 0.05), S5D (<em>p</em> < 0.05), SD (<em>p</em> < 0.05), and incidence of S5 (<em>p</em> < 0.05). GW6471 2 μg/rat did not change seizure parameters but at 4 μg/rat significantly increased ADD (<em>p</em> < 0.001). GW6471 2 μg/rat diminished the anticonvulsant effect of DHA.</div></div><div><h3>Conclusion</h3><div>Acute administration of DHA inhibits amygdala-kindled seizures by activating PPARα. Although PPARα is a nuclear receptor, it partly mediates the acute anti-seizure effect of DHA by rapid non-genomic changes in cellular function. This finding reveals another characteristic of the remarkable omega-3 fatty acid, DHA.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107655"},"PeriodicalIF":2.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988077","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":"Real world observational study investigating clinical effectiveness and safety of lacosamide in epilepsy: ULTIMATE study","authors":"Sanjay Bhaumik , S.C. Nemichandra , Divyam Sharma , Malini Gopinath , Yakshdeep Dave , Zahraan Qureshi , Krishnaprasad Korukonda , Girish Kulkarni","doi":"10.1016/j.eplepsyres.2025.107657","DOIUrl":"10.1016/j.eplepsyres.2025.107657","url":null,"abstract":"<div><h3>Objective</h3><div>Primary generalized tonic-clonic seizures (pGTCS) are often misdiagnosed and remain challenging to manage due to limited treatment options. Lacosamide (LCM), approved for focal-onset seizures and adjunctive pGTCS therapy, was evaluated for real-world effectiveness in Indian patients.</div></div><div><h3>Methods</h3><div>This real-world, multicenter, retrospective, observational, and non-interventional study was conducted across 124 centers in India following approval from a centralized institutional ethics committee. Data were analysed using descriptive and analytical statistical methods for continuous and categorical variables, utilizing SPSS version 29.0.1.0.</div></div><div><h3>Results</h3><div>The Full Analysis Set (FAS) included 685 patients (245 females, 35.77 %; 440 males, 64.23 %) with a mean age of 43.30 ± 11.87 years. Among them, 301 (43.94 %) had pGTCS and 384 (56.06 %) had FoS. Concomitant ASMs for pGTCS included LEV (68.44 %), VPA (21.93 %), and CBZ (13.62 %), while for FoS, LEV (47.14 %) was most common, followed by VPA (16.15 %) and CBZ (14.58 %).</div><div>At week 12, mean seizure frequency in pGTCS reduced from 3 to 1 (p < 0.0001), with 52.16 % achieving seizure freedom and a 66.78 % responder rate. LCM with LEV showed a two-fold higher responder rate than with other ASMs (OR: 2.3582, p = 0.0037). In FoS, 47.66 % achieved seizure freedom, with a 58.85 % responder rate. Moreover, when prescribed as monotherapy in FoS, LCM showed a 62.96 % responder rate. LCM was generally well tolerated across both groups, with no unexpected safety concerns observed during the study period.</div></div><div><h3>Conclusion</h3><div>This study demonstrated the effectiveness of LCM therapy in reducing seizure frequency and improving seizure control in Indian patients with epilepsy. LCM was well tolerated and remains potential therapeutic option either as monotherapy or as an adjuvant therapy in the management of FoS.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107657"},"PeriodicalIF":2.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018501","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}
Epilepsy ResearchPub Date : 2025-08-31DOI: 10.1016/j.eplepsyres.2025.107645
Karin Daniele , Jaroslava Raudenská , Alena Javůrková
{"title":"Attention-deficit/hyperactivity disorder in adults with epilepsy: Preliminary prevalence and associated factors in a Czech sample","authors":"Karin Daniele , Jaroslava Raudenská , Alena Javůrková","doi":"10.1016/j.eplepsyres.2025.107645","DOIUrl":"10.1016/j.eplepsyres.2025.107645","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigated the prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in Czech adult people with epilepsy (PWE) and examined factors potentially contributing to the co-occurrence of these two conditions. Although previous research has consistently reported elevated rates of ADHD in epilepsy populations, data from adult samples in Czech Republic remain limited.</div></div><div><h3>Methods</h3><div>Fifty-six adults with epilepsy completed validated self-report questionnaires assessing ADHD symptoms (ASRS), anxiety (GAD-2), and depression (NDDIE-2). Epilepsy-related clinical factors, such as seizure frequency, anti-seizure medication (ASM), type of epilepsy and epilepsy duration, were also analyzed in relation to ADHD symptoms.</div></div><div><h3>Results</h3><div>A high prevalence of ADHD symptoms n = 25 (44.6 %) was found in the sample. No significant associations were observed between ADHD symptoms and epilepsy-related variables or depressive symptoms, but a regression model of clinical and sociodemographic variables can explain 34.2 % of the variance in ASRS scores (Adj. R² = 0.342), with only anxiety emerging as a significant predictor (β = 0.517, SE = 0.50, t = 3.23, p = .003).</div></div><div><h3>Conclusion</h3><div>These preliminary findings suggest a possible link between epilepsy and ADHD, which may be further explored in future research through shared emotional or neurobiological mechanisms. The results underscore the need for integrated screening approaches and further research into the co-occurrence of epilepsy and ADHD in adult populations.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107645"},"PeriodicalIF":2.0,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018503","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}
Epilepsy ResearchPub Date : 2025-08-30DOI: 10.1016/j.eplepsyres.2025.107647
Sami Aboumatar , Jay R. Gavvala , Zeenat Jaisani , Ruben Kuzniecky , Michael Privitera , Madeline Ring , William E. Rosenfeld , Jacob Pellinen
{"title":"Electrographic seizures on responsive neurostimulation: An early and objective measure of response to cenobamate","authors":"Sami Aboumatar , Jay R. Gavvala , Zeenat Jaisani , Ruben Kuzniecky , Michael Privitera , Madeline Ring , William E. Rosenfeld , Jacob Pellinen","doi":"10.1016/j.eplepsyres.2025.107647","DOIUrl":"10.1016/j.eplepsyres.2025.107647","url":null,"abstract":"<div><h3>Objectives</h3><div>Responsive neurostimulation (RNS) electrocorticographic (ECoG) data may have a role in objectively assessing the efficacy of add-on antiseizure medications (ASMs). This retrospective, multicenter, observational, 24-week study is the first to report the effects of cenobamate on RNS-detected events (RDE).</div></div><div><h3>Methods</h3><div>Patients included adults (≥18 years) with a history of recurrent focal seizures and implanted RNS who initiated adjunctive cenobamate ≥ 3 months after RNS implant between 4/1/20–12/15/23 and who received ≥ 2 weeks of cenobamate (≥50 mg/day). RDE (“long episodes,” “long episodes with saturation,” and “saturation”) obtained from the NeuroPace Patient Data Management System were reviewed to select only electrographic seizures (ESs) based on electrographic ictal patterns. RDEs and ESs were counted during the 8-week baseline period, every 2 weeks for 12 weeks after starting cenobamate, and at study end. The main outcome was percent change from baseline to the end of the 16-week treatment period (12 + weeks) for overall ESs, ESs ≥ 50 seconds, and ESs < 50 seconds. Patient-reported clinical seizure frequency was recorded when available.</div></div><div><h3>Results</h3><div>Thirty-seven patients (mean age 36.7 years) were included. Median cenobamate dose was 150 mg/day (range, 50–250 mg/day). There was a significant median percent reduction from baseline to the end of cenobamate treatment in ESs (94.4 %; p < 0.0001), ESs ≥ 50 s (100.0 %; p < 0.0001), and ESs < 50 s (100.0 %; p < 0.0001). Among patients with available seizure data (n = 24), median percent reduction in clinical seizures per 28 days from baseline to end of treatment was 72.2 % (p < 0.0001). Adverse events were reported in 27 % (10/37) of patients; dizziness, fatigue, and sleepiness were most reported.</div></div><div><h3>Significance</h3><div>Patients with uncontrolled seizures after RNS had a significant reduction in ESs and clinically reported seizures during adjunctive cenobamate treatment. Results from this analysis support the potential use of RNS ECoG data as an objective measure to supplement clinical data when determining cenobamate efficacy and may provide a strategy for monitoring responses to ASMs more generally in this population.</div></div><div><h3>Data Availability</h3><div>The data for the analyses described in this paper are available by request from the corresponding author or from SK Life Science, Inc., the company sponsoring the clinical development of cenobamate for the treatment of focal epilepsy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107647"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003869","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}
Epilepsy ResearchPub Date : 2025-08-26DOI: 10.1016/j.eplepsyres.2025.107644
Caleb Rhodes , Benjamin Rees , Holly Dubbs , Mollie Lesser , Lucas Morgan , Tim A. Benke , Alan Percy , Jeffrey L. Neul , Eric D. Marsh , for the NIH Rett and Related Disorders Natural History Study
{"title":"Natural history of epilepsy in FOXG1 Syndrome","authors":"Caleb Rhodes , Benjamin Rees , Holly Dubbs , Mollie Lesser , Lucas Morgan , Tim A. Benke , Alan Percy , Jeffrey L. Neul , Eric D. Marsh , for the NIH Rett and Related Disorders Natural History Study","doi":"10.1016/j.eplepsyres.2025.107644","DOIUrl":"10.1016/j.eplepsyres.2025.107644","url":null,"abstract":"<div><h3>Background</h3><div>FOXG1 syndrome is rare neurodevelopmental disorder with microcephaly, brain malformations, epilepsy, and cognitive and motor disabilities as major features. Knowledge of the clinical features is primarily from case series and a foundation sponsored registry. We expand insight into epilepsy in FOXG1 syndrome by examining longitudinal data from 94 individuals from a multi-site natural history study and local cohorts.</div></div><div><h3>Methods</h3><div>Clinical information on severity, seizure type, and seizure features was collected from 68 individuals enrolled in the Rett Syndrome and Related Disorders Natural History Study and extracted via retrospective chart review from 15 individuals seen at the Children’s Hospital of Philadelphia Rett Syndrome Center of Excellence and 11 individuals from Children’s Hospital of Colorado. Genotype-phenotype and other correlations were assessed using non- and semi-parametric analyses.</div></div><div><h3>Results</h3><div>78.7 % of participants had seizures, beginning at a median age of 1.0 years. Individuals were followed for a median of 4.9 years after first seizure onset. Taken independently, over 70 % of seizures were partial or tonic-clonic, occurred less than weekly, and lasted less than 5 min. 1/3 of seizures resolved in a median time and age of 1.1 and 3.3 years. Age had a weak non-linear association with average seizure frequency, and, for those with seizures, smaller head circumference correlated with increased disease severity.</div></div><div><h3>Conclusions</h3><div>We further characterize disease severity and epilepsy in FOXG1 syndrome and demonstrate that smaller head circumferences are associated with more severe disease and age is weakly non-linearly correlated with average seizure frequency. This information will improve clinical care and aid therapeutic development.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107644"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908471","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}
Epilepsy ResearchPub Date : 2025-08-26DOI: 10.1016/j.eplepsyres.2025.107643
Anca-Mihaela Vasilica , Jasneet Kaur Dhaliwal , Debayan Dasgupta , Aswin Chari , Sachit Shah , Dermot Mallon , Jane de Tisi , Anna Miserocchi , Andrew W. McEvoy , John S. Duncan
{"title":"Outcomes of surgically and non-surgically managed temporal encephalocoeles in the context of drug-resistant temporal lobe epilepsy: A retrospective single-centre case series","authors":"Anca-Mihaela Vasilica , Jasneet Kaur Dhaliwal , Debayan Dasgupta , Aswin Chari , Sachit Shah , Dermot Mallon , Jane de Tisi , Anna Miserocchi , Andrew W. McEvoy , John S. Duncan","doi":"10.1016/j.eplepsyres.2025.107643","DOIUrl":"10.1016/j.eplepsyres.2025.107643","url":null,"abstract":"<div><h3>Introduction</h3><div>Temporal encephalocoeles are a recognised cause of drug-resistant temporal lobe epilepsy (TLE), with uncertain associations to epileptogenesis and an unclear optimal management approach. Operative management, particularly resective temporal lobe surgery, has been proposed, but outcomes and decision-making criteria remain debated. This study aims to evaluate the outcomes of surgically and non-surgically managed patients with temporal encephalocoeles in the context of drug-resistant TLE, focusing on seizure freedom rates, postoperative complications and factors influencing management decisions.</div></div><div><h3>Methods</h3><div>A retrospective, single-centre study was conducted based on all adult TLE patients with temporal encephalocoeles encountered between March 2017 and August 2023. Patients were classified into three groups: those discussed at an epilepsy surgery multidisciplinary team (MDT) meeting and managed surgically (surgical group), those discussed at an MDT and managed non-surgically (non-surgical group) and those radiologically identified by reporting neuroradiologists but not discussed at MDT (radiologically diagnosed group). Clinical, electrophysiological, radiological and surgical data were compared across the groups, including radiological features of raised intracranial pressure (ICP) that have been postulated as a cause for temporal encephaloceles.</div></div><div><h3>Results</h3><div>We included 24 adult patients with temporal encephalocoeles: eight in the surgical group, eight in the non-surgical group and eight in the radiologically diagnosed group. The mean age at diagnosis was 39.3 ± 13.6 years and clinical features were comparable across groups. Operative management was decided by an experienced epilepsy surgery MDT, involving resection of the anterior temporal pole with (4/8, 50 %) or without (50 %) mesial temporal structures, resulted in a seizure freedom rate of 87.5 %. In contrast, no patient in the non-surgical or radiologically diagnosed groups achieved seizure freedom (0 %). Postoperative complications included one patient who developed hydrocephalus and required a ventriculoperitoneal shunt, and another who developed a pseudomeningocoele. Radiological markers of raised ICP were broadly similar across the groups, with the exception of increased optic nerve sheath diameter in the non-surgical group (p = 0.032).</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that excellent post-operative outcomes are achievable with temporal lobe resections. A standardised presurgical evaluation pathway and management protocol are essential to ensure timely identification of temporal encephalocoeles on imaging, facilitating preoperative planning and optimising surgical outcomes. CSF hydrodynamic disturbances may occur after surgery for encephaloceles and individualised evaluation is therefore crucial to select the most appropriate management approach.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107643"},"PeriodicalIF":2.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908470","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}
Epilepsy ResearchPub Date : 2025-08-22DOI: 10.1016/j.eplepsyres.2025.107641
Stephanie DeGasperis, Rajesh RamachandranNair, Kevin C. Jones, Robyn Whitney
{"title":"SYNGAP-1 developmental and epileptic encephalopathy: Utility of corpus callosotomy and neuromodulation","authors":"Stephanie DeGasperis, Rajesh RamachandranNair, Kevin C. Jones, 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 > 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 > 50 % seizure reduction. Two children (n = 2/15, 13.3 %) underwent VNS then CC, 1 had a > 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 > 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":"2025-08-22","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}
Epilepsy ResearchPub Date : 2025-08-21DOI: 10.1016/j.eplepsyres.2025.107642
Ryan Budde , Laura RoaFiore , Pedro Irazoqui
{"title":"High density probes reveal medullary seizure and rapid medullary shutdown in a model of fatal apnea in seizure","authors":"Ryan Budde , Laura RoaFiore , Pedro Irazoqui","doi":"10.1016/j.eplepsyres.2025.107642","DOIUrl":"10.1016/j.eplepsyres.2025.107642","url":null,"abstract":"<div><div>Objective: Sudden unexpected death in epilepsy (SUDEP) is suggested to be a cardiorespiratory collapse that occurs shortly after a seizure. The impacts of seizure on medullary respiratory control remain poorly understood. Prior work in rats suggests that reflexive apneas are highly fatal during seizure but well tolerated otherwise. These reflexes share network connectivity in the medulla, particularly the caudal solitary nucleus (NTS) and ventral respiratory column (VRC), and possibly other intermediate structures. We sought to observe the activity in these regions in fatal ictal apneas. Methods: We collected data from urethane anesthetized long evans rats. To record neural activity we used either 125 <em>µ</em>m silver wire in the caudal NTS or a Neuropixel 1.0 probe along a dorsoventral trajectory that spanned the caudal NTS to the VRC. We additionally recorded cardiorespiratory activity via several methods. We induced a reflexive apnea – the diving reflex – by nasal irrigation of cold water for several seconds, which produces a period of apnea, then gasping, and then a gradual return to eupnea. We repeated several trials while the animal was healthy and subsequently induced continuous seizure activity with kainate and repeated the reflexes, which are ultimately fatal during seizure. Results: Seizure activity confounds many established methods of analyzing high-density single unit data such as provided by Neuropixels probes, and so our analyses focus on averaging responses over larger anatomical regions (120 <em>µ</em>m) covering small populations of neurons. Seizure produces broad increases in neuronal activity across the medullary tract, which by itself is not dangerous. Ictal reflexive apneas were broadly more inhibitory (producing a reduction in firing rate) than they were preictally, and fatal ictal responses resulted in a very rapid shutdown of all medullary activity. We only rarely observed ictal central apneas (apneas with no apparent stimuli), but when we did they were apparently safe, always survived, and produced no significant change in network activity (neither increase nor decrease). Conclusions: These data support the theory that central apnea events in seizure are relatively safe as we observed they produce little change in the medullary tract network, while stimuli-induced-reflexive-apneas are dangerous because they produce profound quieting across respiratory centers. Our data suggest that seizure spreads to this medullary tract at approximately the same rate and intensity as forebrain, as previously described in this model. These data are supportive of SUDEP mechanisms involving brainstem inhibition as a primary cause, such as spreading depolarization waves. These findings likely extend beyond nasal irrigation to any sensory reflexive apnea caused by airway irritation of any kind, and may bear relevance to similar deaths seen in infants.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107642"},"PeriodicalIF":2.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890017","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}
Epilepsy ResearchPub Date : 2025-08-13DOI: 10.1016/j.eplepsyres.2025.107640
Syeda Amrah Hashmi , Mark Quigg , Anelyssa D’Abreu , Carol Manning , Jaideep Kapur , Ifrah Zawar
{"title":"Co-morbid seizures in frontotemporal dementia: What do they tell us?","authors":"Syeda Amrah Hashmi , Mark Quigg , Anelyssa D’Abreu , Carol Manning , Jaideep Kapur , 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 < 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":"2025-08-13","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}
Epilepsy ResearchPub Date : 2025-08-09DOI: 10.1016/j.eplepsyres.2025.107639
Herbert Peeples , Emily Achter , Christopher Dieyi , Keshia Maughn
{"title":"Health care burden of access barriers to epilepsy care in the United States: A claims-based analysis of payer channels","authors":"Herbert Peeples , Emily Achter , Christopher Dieyi , Keshia Maughn","doi":"10.1016/j.eplepsyres.2025.107639","DOIUrl":"10.1016/j.eplepsyres.2025.107639","url":null,"abstract":"<div><h3>Objective</h3><div>To describe access challenges, barriers to antiseizure medications (ASMs), and impact of ASM formulary policies for patients with epilepsy (PWE).</div></div><div><h3>Methods</h3><div>Observational study of de-identified claims from an all-payer claims database (2014–2021) and a formulary/payer policy database. Adults prescribed ≥ 1 ASM following initial epilepsy diagnosis, with continuous medical/pharmacy benefits, were included. Demographic characteristics, proximity to/use of a neurology health care professional (HCP), health care resource utilization (HCRU), and costs were assessed.</div></div><div><h3>Results</h3><div>In total, 35,351, 33,339, and 24,722 PWE with commercial, Medicare, and Medicaid insurance, respectively, were included. The Medicare group was older, had a higher comorbidity index score, more males, and fewer non-White and Hispanic individuals versus other groups. Most (> 58 %) commercially-insured PWE had coverage to all six first-generation ASMs examined, six to 12 second-generation ASMs, and all four third-generation ASMs; coverage rates were higher for Medicaid while data for Medicare were incomplete. Most commercial and Medicaid PWE had no access requirements to first-generation ASMs; approximately two-thirds and half of patients had access requirements for second- and third-generation ASMs, respectively. Although > 90 % of PWE used a neurology HCP during follow-up, only about one-third lived within proximity. Of PWE with formulary data (N = 77,787), > 80 % and < 8.0 % were prescribed second- and third-generation ASMs, respectively. There were no clear patterns in epilepsy-related HCRU/cost.</div></div><div><h3>Conclusions</h3><div>Data revealed difficulties in neurologist access and predominant use of second-generation ASMs, despite access restrictions for many PWE, suggesting obstacles in accessing treatment and specialist care.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107639"},"PeriodicalIF":2.0,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890018","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}