Epilepsia Open最新文献

{"title":"Interim analysis of the long-term efficacy and safety of azetukalner in an ongoing open-label extension study following a phase 2b clinical trial (X-TOLE) in adults with focal epilepsy","authors":"Jacqueline A. French, Roger J. Porter, Emilio Perucca, Martin J. Brodie, Michael A. Rogawski, Cynthia Harden, Jenny Qian, Constanza Luzon Rosenblut, Christopher Kenney, Gregory N. Beatch, X-TOLE Study Group","doi":"10.1002/epi4.70015","DOIUrl":"10.1002/epi4.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To report interim data from an ongoing, open-label extension (OLE) of a Phase 2b study (X-TOLE) of azetukalner in adults with focal onset seizures (FOS) receiving 1–3 antiseizure medications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible participants enrolled in the 7-year OLE at 20 mg azetukalner once daily with food. Long-term seizure outcomes included median percentage change (MPC) in monthly (28 days) FOS frequency from the double-blind phase (DBP) baseline and achievement of ≥50%, ≥75%, ≥90%, and 100% seizure reductions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>285 participants completed the DBP, and 275 (96.5%) enrolled in the OLE. At the 24-month interim analysis (September 5, 2023), 182 participants had been treated for ≥12 months and 165 for ≥24 months; 152 (55.3%) continued in the study. The median (range) treatment duration in the OLE was 26.3 (0.1–46.6) months. MPC reduction was 83.2% at 24 months in the OLE vs. DBP baseline. For all participants who entered the OLE, 56.4% (155/275) and 44.4% (122/275) achieved a ≥50% seizure reduction, 28.4% (78/275) and 19.6% (54/275) achieved a ≥90% seizure reduction, and 22.2% (61/275) and 14.9% (41/275) achieved seizure freedom (100% seizure reduction) for any consecutive ≥6- and ≥12-month period, respectively. For those who reached ≥24 months in the OLE, seizure freedom was achieved by 34.5% (57/165) and 23.6% (39/165) for any consecutive ≥6- and ≥12-month period, respectively. The majority of treatment-emergent adverse events (TEAEs) were mild or moderate. The most common TEAEs were dizziness (21.8%), headache (15.3%), coronavirus infection (15.3%), somnolence (12.7%), fall (12.7%), and memory impairment (10.9%). Serious AEs were reported in 35 (12.7%) participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>The efficacy demonstrated by azetukalner in reducing FOS seizure frequency in the DBP was sustained in this interim analysis. Azetukalner was generally well tolerated, with no new safety signals compared to the DBP. These data suggest sustained long-term efficacy and safety of azetukalner in a difficult-to-treat population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>This long-term study assessed the safety and efficacy of azetukalner to treat focal seizures. Patients taking azetukalner daily with food for about 2 years had far fewer focal seizures with azetukalner than before taking the medication. For those who ha","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"539-548"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins' protective effects on focal epilepsy are independent of LDL-C","authors":"Zhen Sun,&nbsp;Jing Zhang,&nbsp;Yulong Li,&nbsp;Miao Tuo,&nbsp;Limin Yu,&nbsp;Yun Wang,&nbsp;Yanping Sun","doi":"10.1002/epi4.70008","DOIUrl":"10.1002/epi4.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study evaluates the potential protective effects of statins against epilepsy, focusing on their differential impacts on focal and generalized epilepsy. It investigates the role of statins through the HMGCR gene and associated low-density lipoprotein (LDL) cholesterol levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A two-sample Mendelian randomization (MR) and summary-data-based MR (SMR) approach were employed using genetic instruments from genome-wide association studies (GWASs) and expression quantitative trait loci (eQTLs). Subgroup analyses examined focal and generalized epilepsy, with sensitivity tests, including MR-Egger regression and MR-PRESSO, to assess horizontal pleiotropy and robustness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SMR analysis found no significant association between HMGCR expression and epilepsy risk across subtypes (<i>p</i> &gt; 0.05). However, inverse-variance-weighted MR (IVW-MR) showed that elevated LDL cholesterol mediated by HMGCR was linked to an increased risk of focal epilepsy (OR = 1.251, 95% CI = 1.135–1.378). No such association was observed for generalized epilepsy. Statins showed promise in reducing post-stroke epilepsy risk, likely through anti-inflammatory and neuroprotective effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>The findings suggest that statins' protective effects may be subtype-specific, particularly in post-stroke focal epilepsy. Further research is needed to elucidate underlying mechanisms and optimize their therapeutic potential in epilepsy management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Statins, drugs typically used to manage cholesterol, may also lower the risk of developing certain types of epilepsy, especially post-stroke focal epilepsy, by reducing inflammation and protecting brain cells. The research found no clear effect of statins on generalized epilepsy or epilepsy caused by other factors. These results could aid in creating better treatments for epilepsy in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"521-528"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency-specific network changes in mesial temporal lobe epilepsy: Analysis of chronic and transient dysfunctions in the temporo-amygdala-orbitofrontal network using magnetoencephalography","authors":"Tomotaka Ishizaki,&nbsp;Satoshi Maesawa,&nbsp;Takahiro Suzuki,&nbsp;Miki Hashida,&nbsp;Yoshiki Ito,&nbsp;Hiroyuki Yamamoto,&nbsp;Takafumi Tanei,&nbsp;Jun Natsume,&nbsp;Minoru Hoshiyama,&nbsp;Ryuta Saito","doi":"10.1002/epi4.70018","DOIUrl":"10.1002/epi4.70018","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Mesial temporal lobe epilepsy (MTLE) is associated with disruptions in the temporo-amygdala-orbitofrontal (TAO) network, a key component of the limbic system. We aimed to investigate TAO network alterations in patients with MTLE using magnetoencephalography (MEG), which overcomes susceptibility artifacts that limit functional MRI analysis of the orbitofrontal cortex.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Nine seizure-free patients with MTLE post-temporal lobectomy and nine age- and sex-matched healthy controls were recruited. Preoperative MEG data were collected and segmented into frequency bands ranging from delta to ripple to assess functional connectivity (FC) between the bilateral hippocampi and TAO network.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Patients with MTLE exhibited increased FC between the affected hippocampus and amygdala across all frequency bands. Additionally, FC between the affected hippocampus and the medial prefrontal cortex (mPFC), orbitofrontal gyrus (OFG), and amygdala was elevated in the gamma and ripple bands compared with healthy controls. Conversely, FC between the healthy hippocampus and mPFC decreased in the alpha and beta bands. Furthermore, FC within the TAO network fluctuated before and after epileptic spikes; there was a decrease in the delta band between the bilateral hippocampi and the amygdala, OFG, and thalamus, whereas FC between the hippocampus and mPFC increased in the alpha, beta, and ripple bands.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;These findings suggest the formation of an abnormal network involving the affected hippocampus and the TAO network, particularly in the gamma–ripple bands, indicating epilepsy-induced network disruptions. Reduced FC in the healthy hippocampus and the TAO network may reflect frontal lobe dysfunction related to emotion and cognition. Additionally, both chronic and transient FC changes observed via MEG may contribute to the cognitive and psychiatric impairments experienced by patients with MTLE. This study highlights the significance of frequency-specific network alterations in understanding MTLE's pathophysiology and its impact on limbic system functions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain language summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In mesial temporal lobe epilepsy, there may be abnormal connectivity between the hippocampus and the limbic system, which is involved in memory, cognition, and emotion. The changes in connectivity obs","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"557-570"},"PeriodicalIF":2.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy following neonatal encephalopathy—Future directions","authors":"Carol M. Stephens,&nbsp;Jacopo Proietti,&nbsp;Sean R. Mathieson,&nbsp;Vicki Livingstone,&nbsp;Brian McNamara,&nbsp;Niamh McSweeney,&nbsp;Olivia O'Mahony,&nbsp;Brian H. Walsh,&nbsp;Deirdre M. Murray,&nbsp;Geraldine B. Boylan","doi":"10.1002/epi4.70011","DOIUrl":"10.1002/epi4.70011","url":null,"abstract":"<p>We appreciate the thoughtful review of our publication in the recent correspondence from Lucia Fusco.<span>^{1, 2}</span> Our study investigated the incidence of later epilepsy in full term infants with neonatal encephalopathy (NE) who underwent continuous conventional electroencephalography (cEEG) monitoring during the neonatal period. A secondary objective was to identify potential predictors of later epilepsy. While our sixteen-year study period provided valuable insights into long term outcomes, we acknowledge the inherent limitations of its retrospective design.</p><p>The main strength of our study is that all infants underwent cEEG monitoring during the neonatal period, which remains the gold standard for neonatal seizure detection.<span>³</span></p><p>Our study highlights the importance of cEEG monitoring in infants with NE and its potential role in predicting later epilepsy. Future research should focus on prospective studies in larger cohorts incorporating cEEG monitoring alongside advanced neuroimaging and extended genetic analysis.</p><p>CMS is a PhD candidate funded by the Health Research Board (CDA-2018-008) This research was also supported by a Wellcome Trust Innovator Award (209325/Z/17/Z) and partly supported by Merck's Life Science Community Engagement Programme—Scientific Research. No role was played by the funder/sponsor in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.</p><p>None of the authors has any conflict of interest to disclose. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"656-657"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative EEG signatures in patients with and without epilepsy development after a first seizure","authors":"Marysol Segovia-Oropeza,&nbsp;Erik Hans Ulrich Rauf,&nbsp;Ev-Christin Heide,&nbsp;Niels K. Focke","doi":"10.1002/epi4.13128","DOIUrl":"10.1002/epi4.13128","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Diagnosing epilepsy after a first unprovoked seizure in the absence of visible epileptogenic lesions and interictal epileptiform discharges (IED) in the electroencephalogram (EEG) is challenging. Quantitative EEG analysis and functional connectivity (FC) have shown promise in identifying patterns across epilepsy syndromes. Hence, we retrospectively investigated whether there were differences in FC (imaginary part of coherency) and spectral band power in non-lesional, IED-free, unmedicated patients after a first unprovoked seizure in contrast to controls. Further, we investigated if there were differences between the patients who developed epilepsy and those who remained with a single seizure for at least 6 months after the first seizure.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We used 240 s of resting-state EEG (19 channels) recordings of patients (&lt;i&gt;n&lt;/i&gt; = 41) after a first unprovoked seizure and age and sex-matched healthy controls (&lt;i&gt;n&lt;/i&gt; = 46). Twenty-one patients developed epilepsy (epilepsy group), while 20 had no further seizures during follow-up (single-seizure group). We computed source-reconstructed power and FC in five frequency bands (1 ± 29 Hz). Group differences were assessed using permutation analysis of linear models.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Patients who developed epilepsy showed increased theta power and FC, increased delta power, and decreased delta FC compared to healthy controls. The single-seizure group exhibited reduced beta-1 FC relative to the control group. In comparison with the single-seizure group, patients with epilepsy demonstrated elevated delta and theta power and decreased delta FC.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Source-reconstructed data from routine EEGs identified distinct network patterns between non-lesional, IED-free, unmedicated patients who developed epilepsy and those who remained with a single seizure. Increased delta and theta power, along with decreased delta FC, could be a potential epilepsy biomarker. Further, decreases in beta-1 FC after a single seizure may point toward a protective mechanism for patients without further seizures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;After a first seizure, some people develop epilepsy, while others do not. We looked at brain activity in people who had a seizure but showed no clear signs of epilepsy. By comparing those who later developed epilepsy to thos","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"427-440"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.13128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of ubiquitin C–terminal hydrolase (UCH-L1) and protein S100B in differentiating patients with epileptic and psychogenic non-epileptic seizures – Pilot study","authors":"Biljana Dapic Ivancic,&nbsp;Zeljka Petelin Gadze,&nbsp;Lana Ganoci,&nbsp;Petra Nimac Kozina,&nbsp;Dunja Rogic,&nbsp;Maja Zivkovic","doi":"10.1002/epi4.13130","DOIUrl":"10.1002/epi4.13130","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Psychogenic non-epileptic seizures (PNES) are functional neurological disorders that are often misdiagnosed and treated as epileptic seizures (ES). Video-electroencephalography (v-EEG) is the gold standard for differentiating ES from PNES. However, blood biomarkers provide a faster and more accessible methodology, particularly for unwitnessed events. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and protein S100B are key biomarkers released following neuronal and glial damage. Previous experimental and clinical studies have shown increased postictal serum and cerebrospinal fluid (CSF) levels of UCH-L1 and S100B in patients with ES.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This prospective cohort pilot study compared postictal serum levels of UCH-L1 and S100B proteins in subjects with ES to those with PNES, aiming to identify specific biomarkers for distinguishing these conditions. To exclude confounding factors, the inclusion criteria required normal magnetic resonance (MR) findings of the brain. Strict timing of blood sampling and v-EEG monitoring were used for diagnosing PNES. The study included 32 subjects with epilepsy, 36 with PNES, and 30 healthy controls.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A significant difference in postictal UCH-L1 levels was observed among the groups. Subjects with ES had significantly higher postictal UCH-L1 levels (pg/mL) compared to those with PNES (&lt;i&gt;p&lt;/i&gt; = 0.049) and healthy controls (&lt;i&gt;p&lt;/i&gt; = 0.029). No significant differences were found between PNES subjects and healthy controls (&lt;i&gt;p&lt;/i&gt; = 0.756). Postictal protein S100B levels did not differ significantly between the groups (&lt;i&gt;p&lt;/i&gt; = 0.515).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study confirms the potential of postictal UCH-L1 levels as a biomarker for distinguishing ES from PNES. However, it also raises questions about the utility of protein S100B as a biomarker in epilepsy. Given the pilot nature of this study, UCH-L1 cannot yet be adopted for clinical use due to the small sample size, as statistical significance may have been driven by a subset of eight patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study evaluated two potential biomarkers, UCH-L1 and S100B, to differentiate ES from PNES in clinical practice. Our findings showed elevated postictal UCH-L1 levels in subjects with epilepsy compared to those with PNES, while no significant differences in S100B ","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"441-449"},"PeriodicalIF":2.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.13130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voxel-based and surface-based cortical morphometric MRI applications for identifying the epileptogenic zone: A narrative review","authors":"Jacob Bunyamin,&nbsp;Benjamin Sinclair,&nbsp;Meng Law,&nbsp;Patrick Kwan,&nbsp;Terence J. O'Brien,&nbsp;Andrew Neal","doi":"10.1002/epi4.70012","DOIUrl":"10.1002/epi4.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Approximately 40% of patients with drug-resistant epilepsy referred for surgical evaluation have no epileptogenic lesion on MRI (MRI-negative). MRI-negative epilepsy is associated with poorer seizure freedom prognosis and has therefore motivated the development of structural post-processing methods to “convert” MRI-negative to MRI-positive cases. In this article, we review the principles, advances, and challenges of voxel- and surface-based cortical morphometric MRI techniques in detecting the epileptogenic zone. The ground truth for the presumed epileptogenic zone in imaging studies can be classified into lesion-based (MRI lesion mask or histopathology) or epileptogenicity-based ground truth (anatomical-electroclinical correlations or resections that lead to seizure freedom). Voxel-based techniques are reported to have a 13%–97% concordance rate, while surface-based techniques have 67%–92% compared to lesion-based ground truths. Epileptogenicity-based ground truth may be more relevant in the case of MRI-negative cases; however, the sensitivity and concordance rate (voxel-based technique 7.1%–66.7%, and surface-based technique 62%) are limited by the reliance on scalp EEG and qualitative analysis of seizure-onset pattern. The use of stereo-EEG and quantitative EEG analysis may fill this gap to evaluate the correlation between cortical morphometry results and electrophysiological epileptogenic biomarkers of the epileptogenic zone and help improve the yield of structural post-processing tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Locating the epileptogenic zone (the brain area that is responsible for seizure generation) is important to diagnose and plan epilepsy treatments. An abnormal brain imaging (MRI) result can help clinical decision-making; however, around 40% of patients have normal MRI results (MRI-negative). We are reviewing the potential of two advanced MRI methods (voxel- and surface-based cortical morphometry) to localize the epileptogenic zone in the presence or absence of visible MRI abnormalities. We also describe the current challenge of applying the above methods in daily clinical practice and propose using advanced brain recording analysis to aid this translation process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"380-397"},"PeriodicalIF":2.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early rehabilitation and improved outcomes in patients with status epilepticus: Evidence from cases presenting to the emergency department","authors":"Hidetaka Onda,&nbsp;Shoji Yokobori","doi":"10.1002/epi4.70017","DOIUrl":"10.1002/epi4.70017","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Status epilepticus (SE) is a common neurological emergency characterized by prolonged or recurrent seizures that can cause permanent brain damage. Although these seizures can be controlled with appropriate treatment, SE is associated with poor outcomes and a high mortality rate. SE can cause physical, cognitive, and psychological complications at every stage of treatment. Understanding the treatment of SE and its outcomes is important both clinically and socially. Intensive care unit-acquired weakness and post-intensive care syndrome are significant issues in survivors of SE. This study aimed to determine if early rehabilitation in the intensive care unit can improve outcomes in patients with SE, given the limited options for intervention after hospitalization.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This observational study was approved by our ethics committee (B-2023-654) and included 1039 adult patients brought to our center with SE between 2011 and 2023. The patients were divided into a prospectively enrolled rehabilitation intervention group, in which rehabilitation was initiated within 24 h after admission post-2022, and a retrospective non-intervention group from before that time. We examined the current status of these patients to determine the value of ultra-acute rehabilitation and factors associated with favorable outcomes in these patients. The primary outcome was the proportion of patients with a Glasgow Outcome Scale score of 5 at discharge.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The average age was 52.3 years, with 619 cases aged 65 years or older. Mortality was 2.5%, and 519 patients achieved a Glasgow Outcome Scale score of 5. Rehabilitation initiated within 24 h of hospitalization did not significantly affect the length of hospital stay but did increase home discharge rates and functional independence, particularly in older patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study provides a systematic and insightful observational analysis suggesting that early rehabilitation may be associated with improved outcomes in patients with status epilepticus (SE). Further validation and investigation are required.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;When patients experience the severe epileptic condition known as status epilepticus, they are often admitted to the intensive care unit (ICU), where their chances of recovery can be poor. However, this ","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"549-556"},"PeriodicalIF":2.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiofrequency thermocoagulation in focal epilepsy: A retrospective cohort study","authors":"Alejandra Vasquez,&nbsp;Karimul Islam,&nbsp;Madeline R. Cross,&nbsp;Kai J. Miller,&nbsp;Jamie J. Van Gompel,&nbsp;Brian Nils Lundstrom,&nbsp;Anthony L. Fine","doi":"10.1002/epi4.70009","DOIUrl":"10.1002/epi4.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RFTC) has been increasingly used as diagnostic and therapeutic approach for drug-resistant focal epilepsies (DREs). We aimed to describe seizure outcomes of RFTC before and after further neurosurgical intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective single-institution case series of patients who underwent SEEG-RFTC. The primary outcome was Engel class I–IV classification ([responders Engel I–III and non-responders Engel IV]) at last follow-up after RFTC and prior to further neurosurgical intervention (open surgical resection, laser ablation, and neuromodulation).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-five patients (median age 18.9 years) with DRE were included. The median follow-up time after RFTC was 7.2 months, including 20 patients who underwent further intervention (median follow-up time of 7.3 months) and 5 without intervention (median of 3.5 months). From the patients who had further intervention, 17 (85%) underwent surgical procedure (laser ablation 53%, open surgical resection 47%) (median 4.4 months) and 3 (15%) had responsive neurostimulators placed (median 6.9 months). Prior to further intervention (median follow-up 3.5 months after RFTC), 12 (48%) patients were classified as responders (12% Engel class I, 16% class II, and 20% class III) and 13 (52%) as non-responders. Following neurosurgical intervention, 17 (68%) patients were followed for a median time of 2.7 months and 3 were lost to follow-up. Of eight initial RFTC responders, 87.5% and 12.5% had Engel classes I and III, respectively. Of nine who were non-responders, 33% had Engel class I, 22% II and III, and 44% IV outcomes following further intervention. No neurologic complications were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>SEEG-guided RFTC is a well-tolerated procedure and a beneficial diagnostic approach prior to further neurosurgical interventions in patients with DRE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>SEEG-guided RFTC is a well-tolerated procedure and in the patients who experienced initial seizure reduction (<i>n</i> = 8), subsequent neurosurgical intervention (surgery or neuromodulation) led to favorable seizure outcomes (87.5% seizure freedom and 12.5% worthwhile seizure improvement).</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"529-538"},"PeriodicalIF":2.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and tolerability of low versus standard daily doses of antiseizure medications in newly diagnosed focal epilepsy. A multicenter, randomized, single-blind, non-inferiority trial (STANDLOW)","authors":"Giorgia Giussani,&nbsp;Elisa Bianchi,&nbsp;Edoardo Carlando,&nbsp;Jacopo Cosimo DiFrancesco,&nbsp;Payam Tabaee Damavandi,&nbsp;Francesco Pasini,&nbsp;Giulia Pederzoli,&nbsp;Stefania Filipponi,&nbsp;Alessandra Gaiani,&nbsp;Luca Massacesi,&nbsp;Eleonora Rosati,&nbsp;Ginevra Giovannelli,&nbsp;Teresa Anna Cantisani,&nbsp;Michela Cecconi,&nbsp;Rossella Papetti,&nbsp;Monica Brioschi,&nbsp;Francesco Aruta,&nbsp;Elio Clemente Agostoni,&nbsp;Francesco Paladin,&nbsp;Filippo Dainese,&nbsp;Marco Longoni,&nbsp;Bartolini Yerma,&nbsp;Sara Gasparini,&nbsp;Umberto Aguglia,&nbsp;Edoardo Ferlazzo,&nbsp;Roberto Cantello,&nbsp;Gionata Strigaro,&nbsp;Marta Maschio,&nbsp;Dario Benincasa,&nbsp;Angela La Neve,&nbsp;Giovanni Falcicchio,&nbsp;Alfonso Giordano,&nbsp;Lara Buttarelli,&nbsp;Gabriele Enia,&nbsp;Maurizio Leone,&nbsp;Carlo Ferrarese,&nbsp;Ettore Beghi,&nbsp;Simone Beretta","doi":"10.1002/epi4.70016","DOIUrl":"10.1002/epi4.70016","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The STANDLOW trial investigated whether first-line antiseizure monotherapy with low doses has a similar efficacy to standard doses, but with fewer adverse events, improved quality of life, and reduced costs for the National Health System.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Multicenter, randomized, parallel-arm, single-blind, non-inferiority trial, comparing low dose versus standard dose of antiseizure medications (carbamazepine, levetiracetam, valproate, zonisamide, oxcarbazepine, topiramate, lamotrigine, gabapentin, lacosamide) in adults with newly diagnosed focal epilepsy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The intention-to-treat (ITT) population consisted of 58 randomized patients, 29 in the low dose arm and 29 in the standard dose arm, 27 (46.6%) females and 31 (53.4%) males, with an age between 18 and 87 years (median 54.9, IQR 32–71). The seizure type was focal impaired awareness seizures in 44 (75.9%) and focal aware seizures in 14 (24.1%). Etiology was unknown in 43 (74.1%) and structural in 15 (25.9%). At study entry, EEG was epileptiform in 28 (48.2%) and seizure frequency was low (≤2 seizures/month) in 41 (70.7%). The estimated relapse proportions at 12 months were 47% for the low dose and 48% for the standard dose, with a difference of 1% (95% CI: −30%; 27%). At the end of the study visit (12 months of follow-up, or immediately after seizure relapse or study withdrawal for other reasons, whichever came first), no differences in the number or severity of adverse events or quality of life measures were observed between the two treatment groups. The total drug-related costs over the entire study period were lower in the low dose arm (median per participant 253 € versus 475 € in the standard dose arm).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Although the efficacy of low doses versus standard doses appeared similar, non-inferiority could not be demonstrated due to slow recruitment and premature termination of the trial. Although statistically inconclusive, our findings suggest that a low dose of antiseizure medications may be considered as a first-line option in adult patients with a new diagnosis of focal epilepsy of unknown etiology and low seizure frequency.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aimed to see if low doses of anti-seizure medications (ASMs) could be as effective as standard doses in treating adults with newly diagnosed ","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"10 2","pages":"643-653"},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}