Epilepsia最新文献

{"title":"Motor-associated thalamic nuclei are reduced in juvenile myoclonic epilepsy.","authors":"Aaron F Struck, Camille Garcia-Ramos, Vivek Prabhakaran, Veena Nair, Anusha Adluru, Santiago Philibert Rosas, Dace Almane, Nagesh Adluru, Jana E Jones, Bruce P Hermann","doi":"10.1111/epi.18571","DOIUrl":"https://doi.org/10.1111/epi.18571","url":null,"abstract":"<p><strong>Objective: </strong>This study was undertaken to determine the thalamic nuclei that are different between juvenile myoclonic epilepsy (JME) and healthy controls from the Juvenile Myoclonic Epilepsy Connectome Project and then to determine their relationship with other subcortical gray matter volumes, disease covariates, and motor performance.</p><p><strong>Methods: </strong>Sixty-two patients with JME and 41 age-matched controls (mean age = 20 years) were examined using T1-weighted images. Thalamic nuclei volumes were compared after normalization to total intracranial volume. The relationship between thalamic nuclei volumes and age, duration of epilepsy, number of antiseizure medications, and age at onset were examined using linear models with relative assessment of regressors. Correlation with other subcortical volumes was undertaken to identify a potential network effect. Nuclei volumes were related to a task of speeded fine-motor dexterity.</p><p><strong>Results: </strong>Ventral motor-associated thalamic nuclei (ventral anterior, ventral lateral anterior, and ventral lateral posterior) as well as one intralaminar nucleus (parafascicular) volumes were reduced in JME. These thalamic nuclei volume reductions were correlated with cerebellar and ventral diencephalon volume reductions. The reduction in thalamic volumes was associated with age (which differed from controls) in only the ventral thalamic nuclei. Duration of epilepsy also had an effect. JME was associated with decreased dominant and nondominant hand speeded dexterity, with greater deficits relative to reduction of thalamic nuclei volume than in controls. The findings suggest a baseline decrease in ventral thalamic volume with an inability to make efficiency gains because of disordered adolescent synaptic pruning.</p><p><strong>Significance: </strong>Motor-related ventral thalamic nuclei appear to be a core factor in JME pathogenesis. These motor-associated nuclei have known connections with premotor cortex, basal ganglion, and cerebellar pathways that are related to motor control. Their dysregulation may account for the myoclonus seen in JME and interictal motor effects. Further longitudinal investigation and comparison with other cohorts are needed. Targeted neuromodulation of JME may be possible.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world epilepsy monitoring with ultra-long-term subcutaneous electroencephalography: A 15-month prospective study.","authors":"Pedro F Viana, Jonas Duun-Henriksen, Andrea Biondi, Joel S Winston, Dean R Freestone, Andreas Schulze-Bonhage, Benjamin H Brinkmann, Mark P Richardson","doi":"10.1111/epi.18566","DOIUrl":"10.1111/epi.18566","url":null,"abstract":"<p><strong>Objective: </strong>Novel subcutaneous electroencephalography (sqEEG) systems enable prolonged, near-continuous cerebral monitoring in real-world conditions. Nevertheless, the feasibility, acceptability and overall clinical utility of these systems remain unclear. We report on the longest observational study using ultra-long-term sqEEG to date.</p><p><strong>Methods: </strong>We conducted a 15-month prospective, observational study including 10 adult people with treatment-resistant epilepsy. After device implantation, patients were asked to record sqEEG, to use an electronic seizure diary, and to complete acceptability and usability questionnaires. sqEEG seizures were annotated visually, aided by automated detection. Individualized temporal patterns of seizure occurrence were assessed via circadian circular statistics and via Fano factor analysis.</p><p><strong>Results: </strong>Over a median duration of 438 days, 10 patients recorded a median 18.8 h/day, totaling 71 984 h of real-world sqEEG data. Adherence and acceptability remained high throughout the study. Although 754 sqEEG seizures were recorded across patients, more than half (52%) of these were not reported in the patient diary. Of the 140 (27%) diary reports not associated with an identifiable sqEEG seizure, the majority (68%) were reported as seizures with preserved awareness. The sqEEG to diary F1 agreement score was highly variable, ranging from .06 to .97. Patient-specific patterns of circadian seizure occurrence and seizure clustering were found, including several relevant discrepancies between sqEEG and diary.</p><p><strong>Significance: </strong>We demonstrate feasibility and high acceptability of ultra-long-term (months-years) sqEEG monitoring. These systems help provide real-world, more objective seizure counting compared to patient diaries. It is possible to objectively monitor individual temporal fluctuations of seizure occurrence.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WONOEP XVII appraisal: Targeting network excitability beyond the synapse -Neurotransmitter, ionic, and electro -diffusions.","authors":"Vincent Magloire, Marco de Curtis, Jeffrey Noebels, Gilles Huberfeld, Piotr Suffczynski, Vadym Gnatkovsky, Olga Tyurikova, Dominique Durand, David C Henshall, Cian McCafferty","doi":"10.1111/epi.18548","DOIUrl":"https://doi.org/10.1111/epi.18548","url":null,"abstract":"<p><p>Epilepsy affects approximately 1% of the population worldwide, and although medications are effective in the majority of cases, seizures persist in approximately 30% of patients. Despite the effort to develop new antiseizure drugs, the rate of pharmacoresistance in patients has not diminished over the past 3 decades. There is thus a real unmet need, and new approaches and therapeutic targets should be pursued. Seizures are caused by a change in neuronal excitability resulting in hyperexcitation and hypersynchronization of neurons, and modulating either intrinsic neuronal properties or synaptic transmission has been and still is the best way to reduce excitation and synchronization of the neuronal network. However, network excitability and synchronicity are also influenced by many extrasynaptic regulators. Extracellular diffusion of glutamate and γ-aminobutyric acid (GABA) and activation of their extrasynaptic receptors also participate in the generation of a hyperexcitable environment. Interestingly, even without synaptic transmission, neuronal activity can synchronize and propagate throughout the network via gap junctions, extracellular potassium ionic diffusion, and electric fields. In this review, we will discuss the recent advances in our understanding of how different extrasynaptic signaling mechanisms influence neuronal excitability and whether they could be candidate therapeutic targets to treat refractory epilepsy. This review emanated from the XVII Workshop on Neurobiology of Epilepsy meeting (Kilkea, Ireland) organized in 2023 by the Neurobiology Commission of the International League Against Epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy expands the phenotype of L-arginine:glycine amidinotransferase deficiency.","authors":"Alessandro Ferretti, Roberta Battini, Olga Gagliardo, Daniela Verrigni, Maria Beatrice Manca, Anna Rita Ferrari, Gerardo Salerno, Rosanna Boccia, Daniela Polese, Chiara Cocco, Stefania Zampogna, Giovanni Di Nardo, Melania Evangelisti, Jacopo Pagani, Oliviero Bruni, Andrea Romano, Marco Piastra, Maurizio Simmaco, Monica Rocco, Antonio Novelli, Claudia Carducci, Alessandro Bozzao, Pasquale Parisi","doi":"10.1111/epi.18565","DOIUrl":"https://doi.org/10.1111/epi.18565","url":null,"abstract":"<p><strong>Objective: </strong>L-arginine:glycine amidinotransferase (AGAT) deficiency is a rare autosomal recessive disorder affecting creatine biosynthesis, leading to developmental delay, intellectual disabilities, and myopathy. Unlike other creatine deficiency disorders, its link to epilepsy remains uncertain. This study presents the first reported epilepsy cases in AGAT deficiency, analyzing seizure patterns and response to creatine monohydrate supplementation.</p><p><strong>Methods: </strong>We retrospectively analyzed two AGAT-deficient probands identified through a national collaboration. Biochemical assessments of creatine and guanidinoacetate (GAA) levels in plasma and urine were performed using electrospray ionization tandem mass spectrometry and high-performance liquid chromatography methods. Brain magnetic resonance spectroscopy was conducted to evaluate cerebral creatine levels pre- and postsupplementation.</p><p><strong>Results: </strong>Both probands carried the homozygous c.446G>A, p.(Trp149Ter) mutation in GATM, classified as pathogenic. The first, diagnosed at birth and treated with creatine from 4 months, had normal psychomotor development but developed focal epilepsy at 6 years, controlled with carbamazepine. The second, diagnosed at 5 years, presented with psychomotor delay, behavioral disturbances, and nocturnal seizures with unknown origin from age 4 years, later developing focal tonic seizures while awake. Initially the proband was unresponsive to carbamazepine; seizure control was achieved with valproate and lacosamide. Definitive conclusions on the role of creatine supplementation in epilepsy associated with AGAT deficiency cannot be drawn, as it was not modified after seizure onset in the first proband and introduced only after seizure control in the second.</p><p><strong>Significance: </strong>This study presents the first cases of epilepsy in AGAT deficiency, suggesting its prevalence may be underestimated. AGAT-related epilepsy appears to be part of the associated developmental encephalopathy, with focal seizures and minimal impact on psychomotor development. In AGAT deficiency, epilepsy is not linked to GAA accumulation as in other creatine deficiency disorders but rather to low brain creatine levels, which may affect γ-aminobutyric acidergic neurotransmission and seizure thresholds. The role of creatine supplementation in seizure control warrants further investigation.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping electrophysiological connectivity of pulvinar in seizure propagation and neuromodulation.","authors":"Yuan Yao, Xiu Wang, Baotian Zhao, Wenhan Hu, Liang Wang, Xiaoqiu Shao, Zhihao Guo, Bowen Yang, Zilin Li, Du Cai, Xiuliang Fan, Josef Parvizi, Kai Zhang, Chao Zhang","doi":"10.1111/epi.18537","DOIUrl":"https://doi.org/10.1111/epi.18537","url":null,"abstract":"<p><strong>Objective: </strong>The pulvinar is increasingly recognized as a promising target for neuromodulation in drug-resistant epilepsy (DRE). Despite growing interest, empirical evidence substantiating the efficacy and mechanism of its deep brain stimulation (DBS) in patients with epilepsy remains scarce. This study endeavors to address this knowledge gap by investigating the electrophysiological properties of pulvinar.</p><p><strong>Methods: </strong>We enrolled 35 patients with DRE who underwent stereoelectroencephalography with electrodes extended to the pulvinar and analyzed the pulvinar's involvement in seizures originating from different brain lobes. Repeated single electrical pulse stimulation (RSEPS) was employed to map the connectivity of the pulvinar. We also evaluated the effect of pulvinar DBS on interictal epileptic discharges within the epileptogenic zone.</p><p><strong>Results: </strong>We observed that greater involvement of the pulvinar exists in temporal lobe epilepsy, with the medial pulvinar (PuM) showing stronger engagement. Findings with RSEPS highlighted significant connections from the PuM to parietal, occipital, and temporal regions, as well as robust connections from the mesial temporal lobes to PuM. Lastly, we found high-frequency stimulation (140-150 Hz) of PuM significantly reduced interictal epileptic discharges.</p><p><strong>Significance: </strong>Our study supports emerging evidence for pulvinar involvement in seizure propagation. The data with RSEPS also map PuM causal connectivity in the human brain. Although the clinical utility of pulvinar neuromodulation in patients with DRE remains to be determined by prospective clinical trials, our findings provide a convincing link between PuM neuromodulation and the reduction of epileptic activity.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HD-EEG source imaging with simultaneous SEEG recording in drug-resistant epilepsy.","authors":"Shenglin Hao, Haifeng Zhao, Ziyi Feng, Wei Liu, Chao Zhang, Hang Ping, Qiang Zhou, Bomin Sun, Shikun Zhan, Chunyan Cao","doi":"10.1111/epi.18552","DOIUrl":"https://doi.org/10.1111/epi.18552","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to assess the complementary role of high-density electroencephalography (HD-EEG)-based electrical source imaging (ESI) in localizing the seizure-onset zone (SOZ) during ictal events and the irritative zone (IZ) during the interictal period, using simultaneous acquired stereo-EEG (SEEG) recordings as a reference. In addition, we investigated the relationship of ictal cortical source activity with their scalp and intracranial EEG correlates, focusing on factors influencing ESI accuracy.</p><p><strong>Methods: </strong>We enrolled 29 patients with drug-resistant epilepsy who underwent simultaneous HD-EEG and SEEG recordings. ESI was performed on ictal and interictal discharges of HD-EEG identified via SEEG, and localization accuracy was assessed relative to SEEG-defined sources. A linear mixed-effects model was applied to examine the influence of source depth and spike power on ESI accuracy. Concordance between ictal ESI and SEEG localizations was analyzed, along with associations with post-surgical outcomes.</p><p><strong>Results: </strong>Synchronized rhythmic discharges, ranging from 1.95 to 8.77 Hz (mean 5.34 ± 2.14 Hz), but not the low-amplitude fast rhythms in SEEG were mandatory as references for ictal ESI. Ictal ESI periods (14.07 ± 4.62 mm) demonstrated significantly better localization accuracy than interictal ESI periods (17.38 ± 4.16 mm), with a shorter Euclidean distance between ESI dipoles and SEEG contacts. Both ictal spike power and source depth significantly influenced ESI accuracy. Patients with superficial or high-power discharges showed more precise localization. Concordant ictal ESI and SEEG results predicted favorable surgical outcomes (p = .006, n = 28).</p><p><strong>Significance: </strong>Ictal ESI provides superior localization performance compared to interictal ESI. SEEG-informed analysis of ictal scalp EEG provides critical insights into SOZ characteristics, including location, depth, and spatial complexity. Simultaneous HD-EEG and SEEG recordings enhance the understanding of epileptogenic networks and support surgical decision-making in drug-resistant epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enantioselective comparative analysis of the anticonvulsant potency of fenfluramine and norfenfluramine in mice.","authors":"Yara Sheeni, Natalia Erenburg, Dinorah Barasch, Tawfeeq Shekh-Ahmad, Emilio Perucca, Meir Bialer","doi":"10.1111/epi.18542","DOIUrl":"https://doi.org/10.1111/epi.18542","url":null,"abstract":"<p><strong>Objective: </strong>The in vivo effects of fenfluramine result from the combined actions of four active molecular entities (l-fenfluramine, d-fenfluramine, and the corresponding enantiomers of the primary metabolite norfenfluramine). Each of these compounds has different properties, with cardiovascular toxicity risk being ascribed primarily to the d-enantiomers. To determine whether l-fenfluramine or l-norfenfluramine is a better candidate for development as an enantiomerically pure antiseizure medication, we investigated dose-response and brain/plasma concentration-response relationships for each of the four individual enantiomers in mice.</p><p><strong>Methods: </strong>Antiseizure activity was evaluated in the maximal electroshock (MES) model at the time of peak effect. Neurotoxicity was assessed by determining minimal motor impairment (MMI) in the rotarod test. Median effective dose (ED₅₀), median toxic dose (TD₅₀), median effective concentration (EC₅₀), and median toxic concentration (TC₅₀) in plasma and brain were estimated from dose- and concentration-response curves after administration of each individual enantiomer. Protective indexes (PIs) were estimated based on dose (TD₅₀/ED₅₀) and plasma/brain concentrations (TC₅₀/EC₅₀).</p><p><strong>Results: </strong>The four enantiomers differed in antiseizure potency and neurotoxic activity. d-Norfenfluramine had the highest potency, but it also had the highest toxicity and the lowest PI. Differences in antiseizure potency and toxicity estimated from plasma and brain concentrations were more prominent than those estimated based on dose. l-Fenfluramine had greater potency than d-fenfluramine and l-norfenfluramine, and was overall the compound with the highest PI (6.3 based on dose, 41.6 based on plasma concentrations, and 39.2 based on brain concentrations).</p><p><strong>Significance: </strong>These findings are relevant in determining which enantiomer is most suitable for clinical development as a stereoselectively pure follow-up compound to the marketed racemic fenfluramine, and indicate that l-fenfluramine has superior antiseizure activity over l-norfenfluramine in the MES model. This study also illustrates the limitations of relying solely on dose-response curves, and the added value of assessing concentration-response relationships.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term efficacy and safety of cannabidiol in patients with treatment-resistant focal epilepsies treated in the Expanded Access Program.","authors":"Anup D Patel, Jerzy P Szaflarski, Paul D Lyons, Michael Boffa, Teresa Greco, Timothy B Saurer, Karthik Rajasekaran, Kelly C Simontacchi, Elizabeth A Thiele","doi":"10.1111/epi.18496","DOIUrl":"https://doi.org/10.1111/epi.18496","url":null,"abstract":"<p><strong>Objective: </strong>Cannabidiol (CBD) treatment was associated with long-term seizure reduction in patients with various treatment-resistant epilepsies who participated in the CBD Expanded Access Program. A phase 3 trial showed CBD effectively treats tuberous sclerosis complex (TSC)-associated seizures, which are primarily of focal origin. However, the effectiveness of CBD in non-TSC focal epilepsies is not well reported. Here, we evaluate CBD treatment outcomes among patients with a variety of focal epilepsies, including TSC.</p><p><strong>Methods: </strong>Patients received plant-derived highly purified CBD (Epidiolex; 100 mg/mL oral solution) doses starting at 2-10 mg/kg/day and titrated up to each patient's limit or to a maximum of 25-50 mg/kg/day. CBD effectiveness was assessed by the median percentage change from baseline in monthly frequency of focal and total seizures and by responder rates through 144 weeks of treatment. Safety data were reported for the full follow-up period.</p><p><strong>Results: </strong>Of 140 patients with focal epilepsies, 33 (24%) had TSC and 107 (76%) had other focal epilepsies, including cortical dysplasia (14%), frontal lobe epilepsy (10%), and malformation of cortical development (9%). Median age was 11.9 years (range = 2-31) in the TSC group and 17.8 years (range = 2-73) in the non-TSC group. Median CBD daily dose was comparable between TSC and non-TSC groups (25 and 23 mg/kg/day, respectively). CBD treatment was associated with a median reduction from baseline of 51%-87% in focal seizures and 44%-87% in total seizures in the TSC group and 46%-75% and 45%-71% in the non-TSC group, respectively. Responder rates were similar for both groups. Adverse events occurred in 91% of the TSC group and 96% of the non-TSC group.</p><p><strong>Significance: </strong>Open-label CBD treatment was associated with sustained seizure reduction through 144 weeks, with a consistent safety profile in patients with treatment-resistant focal epilepsies, regardless of epilepsy type.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comorbidities in the mouse model of temporal lobe epilepsy induced by intrahippocampal kainate.","authors":"Loan Samalens, Camille Beets, Clothilde Courivaud, Philippe Kahane, Antoine Depaulis","doi":"10.1111/epi.18553","DOIUrl":"https://doi.org/10.1111/epi.18553","url":null,"abstract":"<p><strong>Objective: </strong>Mesial temporal lobe epilepsy (MTLE) is generally associated with cognitive and psychiatric comorbidities. Here we examined whether similar comorbidities are observed in mice injected with kainate in the dorsal hippocampus, a model known to recapitulate many features of human MTLE, and if these comorbidities are sex dependent.</p><p><strong>Methods: </strong>Male and female C57BL/6 mice were unilaterally injected with kainate in the dorsal hippocampus (KA-MTLE), and hippocampal paroxysmal discharges were recorded over 2 months. Behavioral tests assessed food intake (Novelty Palatable Food Intake test), well-being (Nesting), impulsivity (Marbles test), depression-related behavior (Splash test), spatial learning and memory (Barnes maze), working memory (Y-maze), motor coordination (Climbing Cage test), locomotion and activity (Open Field), and anxiety-like behavior (Elevated Plus Maze). Body weight and estrous cycle were also monitored and compared to saline-injected mice (sham).</p><p><strong>Results: </strong>We observed reduced environmental care (Nesting) but no changes in self-care (Splash test) or impulsivity (Marbles test) in KA-MTLE mice. Spatial memory (Barnes maze) was unaffected, although less efficient strategies were used by these mice. Working memory (Y-maze) remained similar to that of shams. No motor impairments were observed (Climbing Cage test, Open Field), but KA-MTLE mice displayed increased activity without anxiety-like behavior. They gained more weight, while their palatable food intake did not differ from shams, and females showed longer estrous cycles. Death that might correspond to sudden unexpected death in epilepsy (SUDEP) occurred in 10% and 3% of epileptic male and female mice, respectively, vs 0% in shams.</p><p><strong>Significance: </strong>Our results suggest that KA-MTLE mice display several features (hyperactivity, reduced well-being, subtle cognitive changes) evocative of an attention disorder associated with hyperactivity (attention-deficit/hyperactivity disorder [ADHD]), often described in young patients with MTLE. Along with the increase in body weight and the occurrence of SUDEP, our data further validate this mouse model to study the physiopathology of MTLE and develop treatments for both seizures and associated comorbidities.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seizure forecasting by tracking cortical response to electrical stimulation.","authors":"Petroula Laiou, Zeljko Kraljevic, Antonio Valentin, Sharon Jewell, Pedro F Viana, Chirag Mehra, Richard J B Dobson, Andreas Schulze-Bonhage, Matthias Dümpelmann, Timothy J Denison, Joel S Winston, Mark P Richardson","doi":"10.1111/epi.18518","DOIUrl":"https://doi.org/10.1111/epi.18518","url":null,"abstract":"<p><strong>Objective: </strong>Seizure unpredictability is a significant burden in the lives of people with epilepsy. Previously published approaches to seizure forecasting analyzed intracranial electroencephalography (iEEG) recordings and showed that seizures can be forecast above chance levels. Although passive observation of the brain might provide some insights, repeated active perturbation of the cortex and measuring the cortical response may provide more direct information about time-varying cortical excitability. The aim of this study is to investigate whether seizures can be forecast by stimulating the cortex via intracranial electrodes and measuring cortical response from the iEEG.</p><p><strong>Methods: </strong>We studied a cohort of eight patients with treatment-resistant epilepsy who were admitted to King's College Hospital for presurgical evaluation with iEEG. During their stay, they underwent prolonged single-pulse electrical stimulation for ~1 day. Stimuli were delivered every 5 min to a constant pair of electrodes, and all patients experienced at least one clinical seizure during the period of stimulation. We extracted quantitative features from the iEEG post-stimulus response and developed a LR algorithm to estimate the seizure likelihood at each stimulus. To evaluate the algorithm's performance, we used improvement over chance (IoC), sensitivity, time spent in warning, and Brier Skill Score. We also compared performance with seizure prediction based on passive observation of iEEG.</p><p><strong>Results: </strong>In seven of eight patients, seizures could be forecast using the post-stimulus response above chance levels (average IoC: 0.74). In comparison, the seizure forecasting performance based on passive (unstimulated) iEEG was less good (average IoC: 0.54).</p><p><strong>Significance: </strong>These results suggest that cortical response to electrical stimulation may aid in the development of seizure forecasting algorithms as well as in the design of novel implantable devices that deliver electrical stimulation to control seizures.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}