Epilepsia最新文献

{"title":"Optimizing pediatric status epilepticus management: The role of early midazolam infusion and adherence to clinical practice guidelines.","authors":"Anna Rosati, Patrizia Bartolotta, Carla Marini, Maria Cristina Mondardini, Duccio Maria Cordelli, Anna Fetta, Luca Bergonzini, Manuela L'Erario, Giulia Cannizzaro, Emmanuele Mongelli, Clarissa Tona, Stefano Sartori, Claudia Maria Bonardi, Fabrizio Chiusolo, Federico Vigevano, Nicola Specchio, Francesca Darra, Jacopo Proietti, Paolo Biban, Elisabetta Cesaroni, Alessandro Simonini, Francesca Izzo, Massimo Mastrangelo, Sara Olivotto, Silvia Maria Pulitanò, Domenica Immacolata Battaglia, Silvia Buratti, Emanuele Giacheri, Caterina Zanus, Paola Costa, Roberta Vittorini, Alessandra Conio, Angela Amigoni, Lucia Fusco","doi":"10.1111/epi.18455","DOIUrl":"https://doi.org/10.1111/epi.18455","url":null,"abstract":"<p><strong>Objective: </strong>This study was undertaken to describe a cohort of pediatric patients with status epilepticus (SE) in Italy over the past decade, focusing on the variability of treatment protocols among centers, adherence to guidelines, and potential predictors of refractoriness.</p><p><strong>Methods: </strong>This is a multicenter retrospective observational cohort study including patients aged 1 month to 18 years who experienced convulsive SE (CSE) between January 2010 and June 2022. Variables analyzed included age at CSE onset, etiology, and treatment.</p><p><strong>Results: </strong>We included 1374 CSE episodes in 1071 patients (median age = 3.3 years); 46% occurred in the first 3 years of life. The prominent etiology was remote symptomatic (32%). Resolution was obtained only with benzodiazepine administration in 19.2% of SE episodes. Phenytoin, phenobarbital, and midazolam by infusion were the drugs most frequently used. Maximum therapeutic response occurred with low-dose (<.2 mg/kg/h) midazolam infusion administered at an early stage, following a single dose of benzodiazepine or an antiseizure medication (ASM; 59%). Midazolam effectiveness decreased to 37% when it was used after multiple ASMs, even at high doses. CSE was refractory in 39% of cases. Predictors of refractoriness included nonadherence to current guidelines, type of CSE, and etiology.</p><p><strong>Significance: </strong>This study emphasizes that low-dose midazolam infusion, not requiring endotracheal intubation and administered at an early phase, appears to be effective in permanently stopping seizure and preventing the evolution toward a refractory CSE. Given its proven efficacy and widespread use in many hospitals, early midazolam infusion could be considered in the management of pediatric CSE. Adherence to treatment protocols, specific etiologies, and type of CSE are correlated with refractoriness; thus, when facing SE in infants, these factors should guide treatment protocol selection, including medication choice and timing.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076596","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":"Two-year outcomes of epicranial focal cortex stimulation in pharmacoresistant focal epilepsy.","authors":"Andreas Schulze-Bonhage, Martin Hirsch, Susanne Knake, Ann Mertens, Michael Rademacher, Elisabeth Kaufmann, Josua Kegele, Carolin Jenkner, Volker Coenen, Martin Glaser, Sergiu Groppa, Yaroslav Winter","doi":"10.1111/epi.18448","DOIUrl":"https://doi.org/10.1111/epi.18448","url":null,"abstract":"<p><strong>Objective: </strong>This study was undertaken to report on the long-term safety and efficacy of epicranial focal cortex stimulation (FCS) using the EASEE device as adjunctive neuromodulatory therapy in improving seizure control in adults with pharmacoresistant epilepsy originating from one predominant epileptogenic zone.</p><p><strong>Methods: </strong>Prospective open-label follow-up of patients from the EASEE II and PIMIDES I clinical trials was done for a period of 2 years after the epicranial implantation of the EASEE electrode and stimulator device.</p><p><strong>Results: </strong>Thirty-three patients underwent device implantation, and stimulation was activated in 32 patients. Of these, 26 patients continued stimulation up to 2-year follow-up and provided seizure diary data for efficacy analysis. The 50% responder rate at 2-year follow-up was 65.4% (95% confidence interval = 44.3-82.8), corresponding to a median seizure frequency reduction of 68%. Patients reported improved health-related quality of life. Tolerability was excellent, and there were no severe adverse events considered to be related to implantation or stimulation, nor were adverse effects on mood or cognition reported.</p><p><strong>Significance: </strong>Results of the 2-year follow-up show that epicranial FCS is well tolerated by patients while providing improved seizure control in the long term. It thus offers a minimally invasive treatment option for patients with a predominant epileptic focus.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076670","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-onset zone lateralization in temporal lobe epilepsy using 7T rs-fMRI: Direct comparison with 3T rs-fMRI.","authors":"Alfredo Lucas, Eli J Cornblath, Nishant Sinha, Lorenzo Caciagli, Peter Hadar, Ashley Tranquille, Joel M Stein, Sandhitsu Das, Kathryn A Davis","doi":"10.1111/epi.18447","DOIUrl":"https://doi.org/10.1111/epi.18447","url":null,"abstract":"<p><strong>Objective: </strong>Resting-state functional magnetic resonance imaging (rs-fMRI) at ultra-high field strengths (≥7T) is known to provide superior signal-to-noise to comparable acquisitions at lower field strengths. In this study, we provide a direct comparison of the seizure onset-zone (SOZ) lateralizing ability of 7T rs-fMRI and 3T rs-fMRI.</p><p><strong>Methods: </strong>We investigated a cohort of 70 patients with temporal lobe epilepsy (TLE). A paired cohort of 19 patients had 3T and 7T rs-fMRI acquisitions for direct comparison between the two field strengths. Forty-three patients had only 3T, and eight patients had only 7T rs-fMRI acquisitions. We quantified the functional connectivity between the hippocampus and other nodes within the default mode network (DMN) using seed-to-voxel connectivity, and measured how hippocampal-DMN connectivity could inform SOZ lateralization at 7T and 3T field strengths.</p><p><strong>Results: </strong>Differences in hippocampal-DMN connectivity ipsilateral and contralateral to the SOZ were significantly higher at 7T (Cohen's d = 0.51, p = 0.008) than at 3T (Cohen's d = 0.26, p = 0.68) when measured in the same subjects. We found that SOZ lateralization was superior at 7T (receiver-operating characteristic area under the curve [ROC AUC] = 0.97, 95% confidence interval [CI]: 0.92-1.00) than 3T (ROC AUC = 0.67, 95% CI: 0.36-0.98), for the same subjects scanned at both field strengths. Our findings were reproduced in extended cohorts of subjects scanned at either 3T or 7T. Our rs-fMRI findings at 7T, but not 3T, are consistent (Spearman ρ = 0.65, p = .01) with clinical fluorodeoxyglucose positron emission tomography (FDG-PET) lateralizing hypometabolism.</p><p><strong>Significance: </strong>We show superior SOZ lateralization in patients with TLE when using 7T relative to 3T rs-fMRI, supporting the adoption of high field strength functional imaging in the epilepsy presurgical evaluation.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076600","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":"Time to prerandomization seizure count design sufficiently assessed the safety and tolerability of perampanel for the treatment of focal seizures.","authors":"Wesley T Kerr, Leock Y Ngo, Liang Zhu, Anna Patten, Jocelyn Y Cheng, Lavanya Biju, Jacqueline A French","doi":"10.1111/epi.18460","DOIUrl":"https://doi.org/10.1111/epi.18460","url":null,"abstract":"<p><strong>Objective: </strong>In traditionally designed randomized clinical trials of antiseizure medications, participants take a blinded treatment for a prespecified number of weeks, irrespective of continued seizures. The alternative design time to prerandomization monthly seizure count (T-PSC) allows participants to end the blinded treatment after an individually prespecified number of seizures, which shortens exposure to placebo and ineffective treatment. Previous reanalyses have shown that T-PSC replicated the efficacy conclusions of trials; therefore, we evaluated whether T-PSC also could replicate tolerability and safety conclusions.</p><p><strong>Methods: </strong>We retrospectively applied the T-PSC design to analyze treatment-emergent adverse events (TEAEs) from three blinded, placebo-controlled trials of perampanel for focal onset seizures (NCT00699972, NCT00699582, NCT00700310). We evaluated the incidences of TEAEs, treatment-related TEAEs, serious TEAEs, and TEAEs that prompted medication adjustment compared to those observed during the full-length trial.</p><p><strong>Results: </strong>Of the 1480 participants in the three trials, 1093 experienced any TEAE, of whom 1006 (92%) had onset prior to T-PSC. When evaluating the differences in each type of TEAE for each dose of perampanel from placebo within each trial, there was no consistent pattern of under- or overestimation. Across the three studies, 23 of 79 (29%) serious TEAEs, most requiring hospitalization, occurred after T-PSC.</p><p><strong>Significance: </strong>Almost all TEAEs occurred before T-PSC. Similar conclusions regarding the tolerability and safety of perampanel would have been reached if the T-PSC design had been used. This suggests that the T-PSC design may potentially benefit participants by allowing earlier change from an ineffective treatment to an alternate treatment, which could reduce the risk of serious consequences of ineffective treatment, such as hospitalization.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076604","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":"No association between histopathology and neurophysiology in surgical specimens from pediatric focal epilepsy patients.","authors":"Nicolás von Ellenrieder, Mariam Alrashid, Kenneth Myers, Bradley Osterman, Elisabeth Simard-Tremblay, Jason Karamchandani, Marie-Christine Guiot, Jean Gotman, Roy W R Dudley","doi":"10.1111/epi.18459","DOIUrl":"https://doi.org/10.1111/epi.18459","url":null,"abstract":"<p><strong>Objective: </strong>Focal epilepsy is caused by focal brain pathologies sometimes with involvement of surrounding or distant tissue. However, within the epileptogenic zone (EZ), which can be resected to cure epilepsy, the contribution of histopathological cells to epileptogenicity remains unknown. We hypothesized that areas showing neurophysiological biomarkers of epileptogenicity would more often contain histopathological cells compared to areas without such biomarkers.</p><p><strong>Methods: </strong>Pediatric epilepsy patients with nonlesional magnetic resonance imaging (MRI), or with lesions with unclear borders, underwent stereoelectroencephalographic (SEEG) exploration followed by resective surgery of the suspected EZ. Tissue specimens were taken from locations where the SEEG contacts had been, using intraoperative MRI-guided precise neuronavigation. Then, we explored the association between histopathology and rates of interictal epileptic discharges, ripples, and fast ripples (FRs), and the channels of the seizure onset zone (SOZ).</p><p><strong>Results: </strong>The association between histopathology and ictal/interictal activity was low and not statistically significant in 260 specimens from 20 surgeries. Rates of interictal events were slightly lower for pathological samples than in normal tissue (low effect size, Cliff |d| < .15, p > .1). The classification accuracy of tissue as normal or pathological based on interictal activity/SOZ was low (accuracy ≤ 54%). As a secondary outcome, SEEG events were excellent predictors of surgical outcome, FRs leading to perfect prediction (20/20).</p><p><strong>Significance: </strong>Histopathological tissue initiates epileptogenicity in focal epilepsy. However, our findings suggest that the EZ is not strictly a histopathological entity but a hybrid of abnormal cells and normal-appearing cells. Thus, SEEG events are biomarkers of epileptogenicity and not histopathology. Resecting of electrophysiological biomarkers of epileptogenicity may be more important than resecting all histopathology.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076512","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":"Status epilepticus in older adults: A critical review.","authors":"Matthew R Woodward, Michael J Armahizer, Tina I Wang, Neeraj Badjatia, Emily L Johnson, Emily J Gilmore","doi":"10.1111/epi.18453","DOIUrl":"https://doi.org/10.1111/epi.18453","url":null,"abstract":"<p><p>Older adults (≥60 years of age) have the highest incidence of status epilepticus (SE) among adults and experience the highest morbidity and mortality. SE incidence increases with age in adulthood. A recent study from Austria estimated an incidence of 89.6/100 000 and 67.6/100 000 person-years adjusted for age and sex in women and men aged >60 years, respectively, compared to 18.1/100 000 in adults aged <60 years. In-hospital mortality associated with SE increases fourfold from the 3rd to 9th decade of life. There are multiple important considerations unique to older adults. Etiologies, including ischemia, hemorrhage, and neoplasm, are more common in older adults and are independently associated with poorer outcomes. Important physiological changes of aging affect both the pharmacokinetics and pharmacodynamics of established treatments for SE. Pharmacology studies have shown differences in sensitivity to benzodiazepines and benzodiazepine elimination, as well as greater unpredictability of antiseizure medications such as phenytoin. Older adults have been largely underrepresented in high-quality randomized clinical trials of SE treatment relative to the incidence of SE in this population. The Established Status Epilepticus Treatment Trial published a post hoc analysis of older adults that showed similar efficacy of treatments, although many older trials did not stratify by age, limiting the opportunity to recognize age-related differences in efficacy and safety. Future research should be aimed at investigating treatment selection and dosing in older adults with SE.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986560","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":"Topographical map of subjective states evoked by focal seizures and electrical stimulation of the human insula.","authors":"Anna Duong, Alvand Daliri, Alexandra Montavont, Erica Leah Von Stein, Eric K van Staalduinen, Sofia Pantis, Guénot Marc, Sylvain Rheims, Vivek Buch, Laure Mazzola, Josef Parvizi","doi":"10.1111/epi.18433","DOIUrl":"https://doi.org/10.1111/epi.18433","url":null,"abstract":"<p><strong>Objective: </strong>The goal of this study was to investigate how the topographical map of human subjective experiences induced by intracranial electrical stimulation (iES) compares to the map of subjective auras experienced by patients during seizures involving the same cortical areas (here, the insular cortex).</p><p><strong>Methods: </strong>We recruited 14 patients with insular epilepsies confirmed with intracranial electroencephalography in the United States (N = 7) and France (N = 7). We identified insular regions involved early in seizures (i.e., presumed seizure-onset zones [SOZs]), and documented the auras reported by each patient. Data from subjective reports of auras were then compared with subjective reports during insular iES in 10 of the 14 patients with confirmed insular seizures and in 17 other patients with stimulation of normal insular sites (previously reported by our group).</p><p><strong>Results: </strong>Epileptic auras reported by patients with seizures involving the insula were largely categorized as visceral, pain/temperature, or non-painful/non-temperature bodily sensations. We observed a striking similarity between the topographical maps of auras during insular seizures and the subjective states induced by the stimulation of the same insular regions (either identified as epileptic or not-epileptic).</p><p><strong>Significance: </strong>Our findings may guide informed clinical decision-making in patients with similar ictal semiology and insular lesions identified on magnetic resonance imaging. On the basis of our findings, we conclude that (1) electrically evoked and seizure-induced subjective symptoms are similar when the presumed SOZ involves the insula; (2) the topography of subjective experiences evoked by insular iES and seizures is largely anatomically consistent across subjects; and (3) stimulation of radiographically abnormal brain tissue seems to cause symptoms that are similar and reliable compared to the ones evoked by the stimulation of the same site in subjects without structural insular abnormalities. The extent to which these findings can be generalized to other cortical regions and networks remains to be determined.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973184","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":"Incidence of sudden unexpected death in epilepsy in New Zealand: A prospective population-wide, 2-year study.","authors":"Peter S Bergin, Sunayana Sasikumar, Erica Beilharz, Charley Glenn, Robert Scragg","doi":"10.1111/epi.18452","DOIUrl":"https://doi.org/10.1111/epi.18452","url":null,"abstract":"<p><strong>Objective: </strong>This study was undertaken to determine the incidence of sudden unexpected death in epilepsy (SUDEP) in New Zealand.</p><p><strong>Methods: </strong>We attempted to prospectively identify all people with epilepsy (PWE) in New Zealand who died from SUDEP after August 1, 2019. Information about the patients' death and epilepsy was recorded in the EpiNet database. Two neurologists (P.S.B. and S.S.) reviewed each case and determined the SUDEP category. The national censuses for 2018 and 2023 were used as the denominator population.</p><p><strong>Results: </strong>Records for 440 PWE who died between August 1, 2019 and July 31, 2021 were reviewed. We concluded that 103 people died from definite, definite plus, probable, probable plus, or resuscitated SUDEP (hereafter referred to as SUDEP). Possible SUDEP was diagnosed in 54. The crude incidence of SUDEP was 10.7 (95% confidence interval [CI] = 8.7-12.9)/1 million person-years. If the prevalence of active epilepsy in New Zealand was 5.49/1000 people, then the incidence of SUDEP in PWE was 1.93 (95% CI = 1.46-2.55) per 1000 person-years. If possible cases are included, the crude incidence of SUDEP was 16.2 (95% CI = 13.8-18.9) per 1 million person-years, and in PWE was 2.94 (95% CI = 2.23-3.89) per 1000 person-years. Sixty-five patients were male, and 38 were female (incidence rate ratio [IRR] = 1.75, 95% CI = 1.18-2.63, p = .005). The rate of SUDEP was lower among Asian people living in New Zealand compared with New Zealand European people (IRR = .33, 95% CI = .10-.83, p = .015). There was a trend toward a higher incidence in Māori and Pacific peoples. Employment status was known for 62 people, of whom 23 were unemployed.</p><p><strong>Significance: </strong>The incidence of SUDEP in New Zealand in PWE (1.93/1000 person-years) is higher than usually reported for high-income countries, although there is uncertainty regarding the prevalence of epilepsy in New Zealand. We suspect the actual incidence of SUDEP worldwide is higher than is usually reported.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975238","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":"The human photosensitive epilepsy model for clinical proof-of-principle trials of novel antiseizure medications: 2. Analysis of drug trials and predictive value of the model.","authors":"Wolfgang Löscher, Dorothée Kasteleijn-Nolst Trenité","doi":"10.1111/epi.18444","DOIUrl":"https://doi.org/10.1111/epi.18444","url":null,"abstract":"<p><p>Clinical development of novel antiseizure medications (ASMs) would benefit from an early proof of principle (POP) model. The photosensitivity model, which uses the photoparoxysmal electroencephalographic response (PPR) as a surrogate of seizures, is currently the only human model that allows POP trials of investigational compounds after a single drug administration. Typically, trials in this model are performed as single-blinded, placebo-controlled phase IIa POP studies, evaluating a range of doses in small groups of epilepsy patients. In the second part of this review, based on the background information provided in Part 1, we analyze the outcome of all published trials performed over roughly 50 years. Many of the 35 drugs tested in the model were also examined in traditional add-on trials in patients with epilepsy, thus allowing analysis of the predictivity of the model. Drugs were categorized into three groups: drugs that suppressed PPR; drugs that exerted no effect on PPR; and drugs that increased PPR, indicating a proconvulsant effect. For the vast majority of drugs, the model correctly predicted the drugs' activity during long-term studies in patients with different types of epilepsy, including focal onset epilepsies. For some investigational compounds, the model detected proconvulsant activity that had not been observed in preclinical animal experiments and phase I studies in healthy volunteers, demonstrating the value of the model for adverse event assessment in patients with epilepsy. Limitations of the model are that it does not predict the extent of drug resistance of patients' seizures during chronic administration or efficacy differentiation of the novel drug from existing ASMs. Photosensitive POP trials are a useful tool to quantitatively predict drug efficacy and in aiding dose selection for subsequent larger phase IIb trials with chronic drug administration.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992457","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":"Seizures influence sleep macrostructure and the sleep-wake circadian rhythm in Dravet syndrome.","authors":"Alberto Cossu, Jacopo Proietti, Ludovica Ghobert, Livia Rinaldi, Bernardo Dalla Bernardina, Francesca Darra, Gaetano Cantalupo","doi":"10.1111/epi.18451","DOIUrl":"https://doi.org/10.1111/epi.18451","url":null,"abstract":"<p><strong>Objective: </strong>Dravet syndrome (DS) is a developmental and epileptic encephalopathy with a wide spectrum of comorbidities comprising sleep disorders, reported in up to 85% of cases. For this, a sleep study is recommended in patients with a sleep complaint. However, no data are available on sleep architecture in DS or on the impact of seizures on sleep quality and macrostructure. We aim to investigate the impact of epileptic phenomena on sleep in DS.</p><p><strong>Methods: </strong>In this study, we report seizure type and frequency, seizures during sleep, and concomitant antiseizure medications (ASMs) of 30 patients with clinical diagnosis of DS and confirmed SCN1A pathogenic variant. We obtained 62 whole-night polygraphic sleep recordings (PSGs) and analyzed sleep stages duration, number of arousal events (AEs), arousal index (AI), and number and number/hour of AEs preceded by interictal epileptiform discharges (IEDs; IED-related arousals [IRAs]). In a subgroup of patients, actigraphic recordings and caregiver-reported Sleep Disturbance Scale for Children (SDSC) questionnaires were collected.</p><p><strong>Results: </strong>Mean age at PSG was 9.9 years (range = 1.2-20.8). Mean sleep efficiency was 92.9%, mean AI was 4.2, and the mean IRA index was .5. Patients with tonic seizures during sleep had shorter rapid eye movement sleep duration (p < .05), and those with convulsive seizures during sleep had shorter N3 duration (p < .05). Higher IRA index was also associated with lower total N3 duration (p < .05). In the recordings obtained during treatment with fenfluramine, IRAs were absent (p < .05) or less abundant (p < .05). The actigraphy parameters showed unstable sleep and correlated with PSG-derived data.</p><p><strong>Significance: </strong>Our study shows a significant effect of epileptic phenomena on sleep macrostructure in DS. Motor seizures and IEDs influence slow wave sleep, which could be one of the mechanisms that sustain encephalopathy in DS. Interestingly, fenfluramine seems to have a protective effect on this mechanism, both by stabilizing sleep and as an ASM.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970311","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}