Epilepsy Research最新文献

{"title":"Antiseizure medication discontinuation in pediatric epilepsy: Real-world insights","authors":"Deniz Menderes ,&nbsp;Salih Akbaş ,&nbsp;Esra Serdaroğlu ,&nbsp;Tuğba Hırfanoğlu ,&nbsp;Ayşe Serdaroğlu ,&nbsp;Ebru Arhan","doi":"10.1016/j.eplepsyres.2026.107742","DOIUrl":"10.1016/j.eplepsyres.2026.107742","url":null,"abstract":"<div><h3>Objective</h3><div>This retrospective study aimed to precisely characterize the factors necessitating antiseizure medication (ASM) discontinuation in pediatric epilepsy patients and to delineate drug-specific adverse event patterns based on monotherapy and polytherapy regimens.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed data from patients under 18 years of age, followed at a single Pediatric Neurology Clinic between January 2015 and September 2024. Discontinuation was defined as the cessation of a medication due to inadequate efficacy or intolerable adverse effects. Patient demographics, epilepsy classification, ASM regimen, treatment duration, and detailed reasons for discontinuation were collected for analysis.</div></div><div><h3>Results</h3><div>Out of 4578 pediatric epilepsy patients screened, ASM discontinuation was recorded in 169 cases (4 %). The discontinuation rate was higher in polytherapy (68/1373, 5 %) than in monotherapy (101/3205, 3 %). The most frequent compelling reasons for cessation were seizure persistence or worsening (48/169, 28 %) and psychiatric adverse effects (40/169, 24 %). Levetiracetam was overwhelmingly associated with psychiatric complaints (25/34, 74 %), while carbamazepine demonstrated a powerful correlation with the emergence of continuous spikes and waves during sleep (CSWS) like sleep-activated epileptiform EEG pattern (28/42, 67 %), leading to its withdrawal. The mean time to discontinuation was 8 ± 6 months.</div></div><div><h3>Conclusion</h3><div>Our real-world data confirms that persistent seizures and drug-induced psychiatric adverse effects are the dominant causes of ASM discontinuation in children. The particular correlations between levetiracetam and psychiatric issues, and carbamazepine and CSWS-like sleep-activated EEG pattern, highlight the critical necessity for highly individualized ASM selection and close clinical and electroencephalographic monitoring in pediatric practice.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"221 ","pages":"Article 107742"},"PeriodicalIF":2.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075798","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":"Antiseizure medication effects on sleep architecture in epilepsy: Glymphatic insights and implications for cognitive decline","authors":"Justyna Swierz ,&nbsp;Michael Doherty ,&nbsp;Sung Ji ,&nbsp;Jeffrey Iliff ,&nbsp;Yeilim Cho","doi":"10.1016/j.eplepsyres.2025.107730","DOIUrl":"10.1016/j.eplepsyres.2025.107730","url":null,"abstract":"<div><div>Disruptions in sleep architecture may contribute to cognitive decline in people with epilepsy (PWE), potentially through impaired glymphatic clearance. In this narrative review, we explore how antiseizure medications (ASMs) influence key sleep stages, particularly slow-wave sleep (SWS) and rapid eye movement (REM) sleep, and consider how these changes may intersect with glymphatic function and cognitive outcomes. SWS supports glymphatic clearance of interstitial waste, including neurotoxic solutes such as amyloid-β and tau. Some ASMs appear to enhance SWS, while others suppress it, suggesting the possibility of differential long-term cognitive effects. We propose that sleep disruption may represent an important but underappreciated factor linking epilepsy and neurocognitive decline. While sleep impairment in epilepsy is often attributed to seizures or interictal activity, ASM-induced alterations in sleep architecture may also play a role. However, this relationship remains largely theoretical and requires further experimental study. We also review the use of diffusion tensor image analysis along the perivascular space (DTI-ALPS) as an emerging imaging method to approximate glymphatic activity. Although DTI-ALPS provides a non-invasive proxy for perivascular water diffusivity, it does not directly measure glymphatic clearance and may be affected by factors such as partial volume effects. Its role in epilepsy research remains exploratory and should be interpreted cautiously. To date, no study has directly examined the combined effects of ASMs, sleep structure, and glymphatic function in a single cohort. We outline opportunities for future research integrating neuroimaging, sleep assessment, and cognitive testing to better understand how sleep-targeted strategies might preserve brain health in epilepsy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107730"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938883","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":"Elevated thalamic blood flow in self-limited epilepsy with centrotemporal spikes","authors":"Niki Iasinovschi ,&nbsp;Elizabeth Tong ,&nbsp;Lucia Bicknell ,&nbsp;Fiona Mitchell Baumer","doi":"10.1016/j.eplepsyres.2025.107716","DOIUrl":"10.1016/j.eplepsyres.2025.107716","url":null,"abstract":"<div><div>Children with self-limited epilepsy syndrome with centrotemporal spikes (SeLECTS) exhibit altered thalamocortical connectivity, but whether thalamic function itself is abnormal remains unclear. We investigated whether thalamic blood flow, a marker of metabolism, differs between children with SeLECTS and controls, and examined the effects of spike distribution and antiseizure medications (ASMs) on thalamic perfusion. In this retrospective cohort study, we identified consecutive children with SeLECTS who underwent magnetic resonance imaging (MRI) for epilepsy evaluation (n = 44) and age- and sex-matched children who underwent MRI for non-epilepsy indications (n = 35). We quantified thalamic blood flow via manual segmentation of cerebral blood flow (CBF) sequences obtained from arterial spin labeling MRI. Clinical variables including sedation use during MRI, daily ASM use, and spike distribution (unilateral or bilateral) were extracted from medical records. Children with SeLECTS demonstrated elevated thalamic blood flow compared to controls, with the most pronounced differences in specific subgroups. Children with unilateral spikes showed the highest CBF, particularly in the thalamus contralateral to spike activity. ASM use significantly modulated thalamic blood flow: children taking oxcarbazepine showed the highest CBF, while those on levetiracetam had CBF similar to controls. Unmedicated children showed intermediate elevations. These findings demonstrate that elevated thalamic blood flow may be intrinsic to SeLECTS pathophysiology, with different ASMs producing distinct neurobiological effects. The differential medication effects may relate to their clinical efficacy and provide neurobiological rationale for treatment selection in this common childhood epilepsy syndrome.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107716"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693019","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":"A systematic review of highly purified cannabidiol in developmental and epileptic encephalopathies and complex treatment-resistant epilepsies: Changes in seizure frequency and adverse events","authors":"Antonietta Coppola ,&nbsp;Lisa Moore-Ramdin ,&nbsp;Marco Navetta ,&nbsp;Debopam Samanta","doi":"10.1016/j.eplepsyres.2026.107731","DOIUrl":"10.1016/j.eplepsyres.2026.107731","url":null,"abstract":"<div><h3>Objective</h3><div>The efficacy and safety of a highly purified plant-derived cannabidiol (CBD) oral solution (Epidiolex® [US]/Epidyolex® [EU], EPX) have been established for the treatment of seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. These conditions involve diverse etiologies, suggesting EPX may have broad utility across different seizure types. This systematic literature review (SLR) evaluated studies reporting CBD effectiveness and tolerability in patients with other developmental and epileptic encephalopathies (DEEs) and complex treatment-resistant epilepsies (TREs).</div></div><div><h3>Methods</h3><div>In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, an SLR was conducted in March 2024 using Embase, PubMed, and Cochrane libraries for publications on complex TREs, CBD, seizure outcomes, and adverse events (AEs). Results were narratively summarized according to epilepsy type.</div></div><div><h3>Results</h3><div>Seizure frequency-related changes were reported in 57 studies including 37 DEEs/TREs comprising 971 patients; most (n=33)(n = 33) were case reports/small case series. Most common diagnoses were focal/multifocal-onset epilepsy (n=401)(n = 401) and Angelman syndrome (n=188).(n = 188). Overall, 47 studies reported seizure frequency reduction in ≥1≥ 1 patient; definitions/thresholds included seizure reduction (n = 18 studies; 20–100 % of patients) and mean/median percent seizure reduction (n = 8 studies; 12–99 % reduction). Twenty-two studies reported ≥ 1 patient was seizure-free for ≥ 48 days.</div><div>AEs experienced while taking CBD were generally mild or moderate and most commonly gastrointestinal, including diarrhea (17–50 %), decreased appetite (7–45 %), and vomiting (5–86 %).</div></div><div><h3>Conclusion</h3><div>CBD may reduce seizure frequency in patients with a range of DEEs and complex TREs. These findings support future studies in these populations.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107731"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009412","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":"Factors influencing pediatric epilepsy outcomes: Predictive variables and adherence to clinical practice guidelines","authors":"Vaibhav R. Suryawanshi ,&nbsp;Kavita Srivastava ,&nbsp;Anshu Priya ,&nbsp;Bhakti Sarangi ,&nbsp;Asavari Raut","doi":"10.1016/j.eplepsyres.2026.107738","DOIUrl":"10.1016/j.eplepsyres.2026.107738","url":null,"abstract":"<div><h3>Background</h3><div>Pediatric epilepsy constitutes significant challenges for long-term management in resource-limited settings. This study determined factors influencing epilepsy outcomes in children (predictive variables) and assessed adherence to clinical practice guidelines (CPG) and its effect on clinical outcomes, addressing the evidence gap in Indian settings.</div></div><div><h3>Methods</h3><div>We enrolled prospectively followed 170 children (&lt;18 years) diagnosed with epilepsy, treated and monitored at a tertiary-care university hospital from ‘January 2021 to December 2024’. Adherence to clinical practice guidelines (CPG) was assessed using ‘Indian Academy of Pediatrics’ and ‘American Epilepsy Society’ standards. Clinical outcomes were studied and classified as ‘favorable (seizure freedom)’ and ‘unfavorable (seizure recurrence at 6 months of ASM initiation AND/OR active epilepsy ≥1 year of ASM initiation AND/OR time to seizure freedom exceeding 15 months after ASM initiation)’. Factors predictive of unfavorable epilepsy outcomes were analyzed using multivariate regression, and the event probabilities were estimated using Kaplan–Meier analysis.</div></div><div><h3>Results</h3><div>Of 170 children, 117 (68.8 %) diagnosed with new‑onset epilepsy (NOE) and 53 (31.2 %) with drug‑resistant epilepsy (DRE). The median (IQR) age was 4.6 (3.1 – 11.5) years. Male preponderance was observed [93 (54.7 %)]. Overall adherence to CPG was 70 %, with deviations noted in 28.2 % of NOE cases and in 34 % of DRE cases. Seizure recurrence at 6 months of ASM initiation [82.4 % versus 64.7 %, P = 0.034] and active epilepsy for ≥ 1 year of ASM initiation [60.8 % versus 32.8 %, P = 0.001] was higher in CPG non-adherent group. Seizure freedom was observed in a total of 100 (58.8 %) children. Patients from CPG non-adherent group took longer (&gt;15 months) to gain seizure freedom (P &lt; 0.042). Of 11 studied factors predictive of unfavorable epilepsy outcomes, 2 factors in NOE and 5 factors in DRE achieved statistical significance. Kaplan-Meier analysis demonstrated increased hazards of unfavorable epilepsy outcomes in patients with DRE compared to NOE, (HR 2.3, 95 % CI 1.2–4.7, P = 0.0147).</div></div><div><h3>Conclusion</h3><div>Adherence to CPG was associated with favorable epilepsy outcomes, while non‑adherence predicted higher risk of seizure recurrence and prolonged active epilepsy. DRE cases demonstrated significantly greater risk of unfavorable epilepsy outcomes compared to NOE, underscoring the importance of guideline‑based management in optimizing pediatric epilepsy care.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107738"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972764","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":"Hospitalisation burden among persons with epilepsy attending an outpatient neuroscience specialist clinic in Singapore","authors":"Anushika Raheja ,&nbsp;Zhibin Tan ,&nbsp;Kaavya Narasimhalu","doi":"10.1016/j.eplepsyres.2026.107736","DOIUrl":"10.1016/j.eplepsyres.2026.107736","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy carries significant clinical and socioeconomic burden, largely driven by hospitalisations. Although hospitalisation rates are well described internationally, data from Asia remain limited. We aimed to quantify hospitalisation rates among persons with epilepsy (PwE) attending an outpatient neuroscience specialist clinic in Singapore and assess whether anti-seizure medication (ASM) polytherapy is associated with hospitalisation.</div></div><div><h3>Methods</h3><div>This exploratory secondary analysis included PwE enrolled in a prospective cohort at a tertiary adult neurology clinic in Singapore from August 2020 to December 2022, and followed up to mid-July 2025. Polytherapy was defined as concurrent use of ≥ 2 ASMs. Incidence rate ratios (IRRs) were calculated and multivariate logistic regression identified factors associated with hospitalisation.</div></div><div><h3>Results</h3><div>A total of 54 PwE were followed up at the outpatient neuroscience specialist clinic for a median of 3.5 years (range 2.6–4.6). The incidence rates of all-cause hospitalisations and seizure-related hospitalisations was 0.679 hospitalisations per person-year (95 % CI: 0.401 – 1.150) and 0.189 hospitalisations per person-year (95 % CI: 0.071 – 0.501), respectively. PwE on polytherapy had significantly higher incidence rates of all-cause (incidence rate ratio, IRR 3.45, 95 % CI 1.24 – 9.90, <em>p</em> = 0.021) and epilepsy-related hospitalisation (IRR 7.59, 95 % CI 1.76 – 32.7, <em>p</em> = 0.007). On multivariate analysis, PwE on polytherapy had a higher risk of at least one all-cause hospitalisation (OR = 5.952, 95 % CI 1.504 – 23.553, <em>p</em> = 0.011) during the study period.</div></div><div><h3>Conclusion</h3><div>We report hospitalisation incidence in PwE in Singapore for the first time and describe our finding that ASM polytherapy is associated with all-cause hospitalisations. These findings may help plan further studies on the morbidity of epilepsy and how it may be better addressed.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107736"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972841","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":"Sexual and developmental variability of spike-wave discharges in the taiep rat: A model of H-ABC leukodystrophy","authors":"Carmen Cortes ,&nbsp;Juan M. Ibarra-Hernández ,&nbsp;Gilles van Luijtelaar ,&nbsp;Jose R. Eguibar","doi":"10.1016/j.eplepsyres.2026.107733","DOIUrl":"10.1016/j.eplepsyres.2026.107733","url":null,"abstract":"<div><div><em>Taiep</em> rat has a leukodystrophy caused by a tubulinopathy affecting the β-tubulin 4 A (TUBB4A) gene characterized by hypomyelination and progressive demyelination of the central nervous system. In magnetic resonance imaging <em>taiep</em> rats showed hypomyelination and atrophy of the putamen and cerebellum that resemble human leukodystrophy named hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). In addition, <em>taiep</em> rat has spike-wave discharges (SWDs) in the electroencephalogram (EEG) associated with behavioral interruption of the ongoing activity. This study aims to analyze the characteristics and circadian distribution of SWDs in both sexes throughout the first year of life. We chronically implanted male and female <em>taiep</em> rats aged 3, 6, 9, and 12 months with electrodes in the cerebral cortex, neck muscles, and right eye orbit for 24-hour video-EEG recordings. Offline, we analyzed the number, mean and total duration of SWDs, the latency of the first SWD, and the spectral content using Fast Fourier Transform. A cosinor analysis was applied to 24-hour data to describe circadian distributions of SWD number and mean duration. In both sexes, the number, mean, and total duration of SWDs increased with age; onset occurred earlier in males at 3 months with respect to females that have SWDs at 6 months. The acrophase of the mean duration rhythm was delayed in females. These findings indicate a sexual dimorphism in the SWDs expression and timing during the circadian cycle. In both sexes, the interspike frequency of SWDs was 6.31 showing no change with age, suggesting similar thalamo-cortical circuit properties across all groups. In conclusion, these results clearly demonstrate that hypomyelination and demyelination affect the expression and circadian dynamics of SWDs in both sexes throughout development in <em>taiep</em> rats. In conclusion, <em>taiep</em> rats had a leukodystrophy associated to spike-wave discharges and behavioral arrest that are absence-like epilepsy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107733"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972842","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":"Evaluating the impact of cenobamate in the management in patients with drug resistant focal epilepsy – A retrospective real world observational study of patients attending NHS Greater Glasgow and Clyde","authors":"M. Taha ,&nbsp;L. Stephen ,&nbsp;S. Nichol ,&nbsp;S. Yule ,&nbsp;S. MacBride-Stewart ,&nbsp;AD Marshall ,&nbsp;CA Heath","doi":"10.1016/j.eplepsyres.2025.107717","DOIUrl":"10.1016/j.eplepsyres.2025.107717","url":null,"abstract":"<div><h3>Introduction</h3><div>Cenobamate (CNB) is the latest ASM to be licensed in the UK as an adjunctive treatment for adults with focal epilepsy. Early clinical trials have been encouraging with up to 50.4 % of patients showing a 50 % improvement at 12 weeks and 71 % were still receiving Cenobamate at 48 months. Regulatory studies of this nature provide useful information, but real-world data is often more informative.</div><div>Since Scottish Medicine Consortium approval in 2022, we have been collecting audit data on outcomes from patients receiving cenobamate.</div></div><div><h3>Methods</h3><div>Adult patients were included if they received at least one prescription for cenobamate between March 2022 and April 2024 and had at least 12 months of data available before their first prescription.</div><div>Patients dispensed cenobamate were identified from the national Prescribing Information System (PIS) to ensure complete patient capture.</div><div>A manual review of electronic patient records was undertaken. The primary outcome of interest was change in seizure frequency on a stable dose. Secondary outcomes included epilepsy-related admissions, changes in ASMs and healthcare resource utilisation costs.</div></div><div><h3>Results</h3><div>145 patients received at least 1 CNB prescription, 144 of whom had reached an endpoint. 94/144 (65.2 %) had a favourable response. The median length of treatment was 655 days (range 180–922 days), with a median dose of 150 mg/d (range 25–400 mg/d). The median number of previous ASM was 5 (1−13).</div><div>48/145 (33.1 %) discontinued CNB – 35 due to adverse effects, 6 due to lack of efficacy. 2 patients died.</div><div>Early analysis suggest a reduction in Health care resource use although long term follow up is required.</div></div><div><h3>Conclusion</h3><div>These results offer insights for clinicians regarding the real-world effectiveness, retention rates, and healthcare cost implications of CNB therapy in a cohort consisting largely of patients with severe drug resistant epilepsy. Further studies are ongoing to assess the efficacy of CNB when used earlier and also to provide a comprehensive assessment of health care resource use in this real world settings.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107717"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665355","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":"4-Phenylbutyrate rescues neurobehavioral phenotypes in SLC6A1-related encephalopathy","authors":"Karishma Randhave,&nbsp;Kirill Zavalin,&nbsp;Jing-Qiong Kang","doi":"10.1016/j.eplepsyres.2025.107708","DOIUrl":"10.1016/j.eplepsyres.2025.107708","url":null,"abstract":"<div><div>Developmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in <em>SLC6A1</em>, encoding γ-aminobutyric acid (GABA) transporter 1 (GAT-1), present with seizures and severe comorbidities including cognitive impairment, developmental delay, motor difficulties, and social deficits. Current therapies focus on seizure reduction but do not address the disabling neurobehavioral symptoms. We previously showed that 4-phenylbutyrate (PBA), known as a chemical chaperone and histone deacetylase inhibitor, restores GAT-1 function and reduces seizures in both mouse models and humans with <em>SLC6A1</em> variants. Here, we tested whether PBA can improve neurobehavioral deficits in the <em>Slc6a1</em>^+/S295L knock-in mouse model of DEE besides seizure mitigation. Longitudinal behavioral analysis revealed deficits in motor reflexes, locomotion, and sleep correlating patient comorbidities. <em>Slc6a1</em>^+/S295L mice exhibited prolonged righting reflexes in neonates and reduced locomotion at 1 month of age. In home cage monitoring, <em>Slc6a1</em>^+/S295L mice traveled less distance at 1 and 7 months; spent less time hanging at 1, 7, and 10 months; and showed changes in sleep patterns at 7 and 10 months. Acute treatment with intraperitoneal PBA (100 mg/kg/day for 7 days) improved travel at 1 month (27 %) and hanging at 1 month (35 %) and 7 months (24 %). Chronic oral PBA treatment (100 mg/kg/day for 28 days) at 7 months further improved hanging (56 %) and travel (16 %). Both acute and chronic PBA treatments increased sleep in the mutant mouse. These results demonstrate that PBA not only reduces seizures but also mitigates comorbidities including motor and behavioral outcomes in <em>SLC6A1</em> DEE, supporting its potential as a disease-modifying therapy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107708"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741721","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":"Epilepsy and stroke: A mendelian Randomization study","authors":"Siyuan Chen ,&nbsp;Madison Crago ,&nbsp;Alain Lekoubou","doi":"10.1016/j.eplepsyres.2025.107714","DOIUrl":"10.1016/j.eplepsyres.2025.107714","url":null,"abstract":"<div><h3>Background</h3><div>Observational studies have established a relationship between stroke and epilepsy. While most studies have reported an increased risk of epilepsy following a stroke, fewer have concluded that a diagnosis of epilepsy increases the risk of future strokes. Precisely describing the causal relationship between epilepsy and stroke has clinical and public health implications.</div></div><div><h3>Methods</h3><div>We performed a two-sample Mendelian Randomization (MR) to analyze the relationship between epilepsy and stroke. We identified genetic instruments from the Stroke Multiancestry Genome-Wide Association Study [GCST005838 (67,162 cases and 454,450 controls)] and the International League Against Epilepsy Consortium on Complex Epilepsies [Generalized epilepsy: GCST007343 (n_case=3769, n_control=29677), Focal epilepsy: GCST007352 (n_case=9671, n_control=29677)]. We used a significance threshold of p-value &lt;5 × 10⁽⁻⁵⁾ for genetic instrument identification. We included the following epilepsy phenotypes: generalized epilepsy (GE), focal epilepsy (FE), childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized epilepsy with tonic-clonic seizures (GTCS), focal epilepsy with hippocampal sclerosis (focal HS), and focal lesion-negative epilepsy. Linkage disequilibrium (LD) reference panel of 1000 Genome Project pruning with Pearson correlation <span><math><msup><mrow><mi>r</mi></mrow><mrow><mn>2</mn></mrow></msup></math></span> &lt; 0.2 was applied to ensure that the analysis is restricted to independent variants. We used Steiger filtering for reverse causality and Z-scores for generalized epilepsy and focal epilepsy. We employed the following methods for causal effect estimation: inverse-variance weighted (IVW), MR-Egger, MR-RAPS, and MRPRESSO.</div></div><div><h3>Results</h3><div>For the association between GE and stroke (GE&gt; stroke), stroke and GE (stroke &gt; GE), FE and stroke (FE&gt;stroke), and stroke and FE (stroke&gt;FE), the number of SNPs was respectively 253, 213, 187, and 210. GE was associated with an increased risk of stroke [IVW, 95 % confidence interval: 0.058 (0.028–0.088)], and stroke was also associated with an increased risk of GE [IVW: 0.059 (0.026–0.092)]. FE was associated with an increased risk of stroke [IVW: 0.066 (0.029–0.102)] and stroke was associated with an increased risk of FE [IVW: 0.037(0.005–0.068)]. The analysis by epilepsy subtypes revealed an increased risk only among patients with stroke and for the following epilepsy subtypes: JAE, CAE, Focal HS, and Focal lesion negative epilepsy.</div></div><div><h3>Conclusion</h3><div>Our findings support a bidirectional relationship between stroke and epilepsy. Studies on post-stroke epilepsy should account for this bidirectional relationship.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107714"},"PeriodicalIF":2.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827121","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}