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Corrigendum to "Long-term outcome and predictors of vagus nerve stimulation for drug-resistant epilepsy: Real-world evidence from the Korean National Hospital Consortium" [Epilepsy Res. 210 (2025) 107511 0920-1211].
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-17 DOI: 10.1016/j.eplepsyres.2025.107522
Seo-Young Lee, Hyesung Lee, Jae-Wook Cho, Kyung Wook Kang, Jong-Geun Seo, Jon Soo Kim, Joon-Won Kang, Daeyoung Kim, Young-Soo Kim, Sun Ah Choi, Jeonghoon Park, Ji Hoon Phi, Sang Ook Nam, Won Seop Kim, Jae-Moon Kim, Ki Joong Kim
{"title":"Corrigendum to \"Long-term outcome and predictors of vagus nerve stimulation for drug-resistant epilepsy: Real-world evidence from the Korean National Hospital Consortium\" [Epilepsy Res. 210 (2025) 107511 0920-1211].","authors":"Seo-Young Lee, Hyesung Lee, Jae-Wook Cho, Kyung Wook Kang, Jong-Geun Seo, Jon Soo Kim, Joon-Won Kang, Daeyoung Kim, Young-Soo Kim, Sun Ah Choi, Jeonghoon Park, Ji Hoon Phi, Sang Ook Nam, Won Seop Kim, Jae-Moon Kim, Ki Joong Kim","doi":"10.1016/j.eplepsyres.2025.107522","DOIUrl":"https://doi.org/10.1016/j.eplepsyres.2025.107522","url":null,"abstract":"","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":" ","pages":"107522"},"PeriodicalIF":2.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of the phenotype and functional alternations of three HCN1 variants in Chinese epilepsy patients
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-07 DOI: 10.1016/j.eplepsyres.2025.107521
Ziyao Han, Lingling Xie, Xiaorui Liu, Jiaxin Yang, Hanyu Luo, Ran Ding, Hengsheng Chen, Li Cheng, Zhixu Fang, Li Jiang

Purpose

To evaluate the electrophysiological properties of three HCN1 variant sites found in Chinese epileptic patients and to explore the potential relationship between genotype and phenotype.

Methods

We correlated clinical severity of three patients with HCN1 variants with whole-cell patch-clamp measurements of channel activity, channel expression detected by Western blot, and bioinformatics prediction of the damaging effects of each variant.

Results

Three patients with the variants p.L400P, p.D534H and p.M243delinsTL, showed different phenotypes, ranging from mild epilepsy to severe epileptic encephalopathy. Variants L400P and D534H were classified as pathogenic by all bioinformatics tools, and variant M243delinsTL was classified as a polymorphism by MutationTaster. The L400P and D534H variants showed significantly reduced current compared with that of the wild-type (WT), while the current density of M243delinsTL was similar to WT. The half-activation voltage (V1/2) of M243delinsTL variant was shifted in the hyperpolarizing direction when compared to the WT, and the slope factor (k) of activation of the M243delinsTL variant was significantly lower than that of the WT. The L400P variant was associated with a significantly higher activation time constant compared with that of the WT. In addition, quantitative detection of the FLAG-tagged HCN1 channel revealed that the expression level of the L400P variant was significantly decreased compared to WT.

Conclusions

Elucidation of the type and location of variant sites combined with the use of bioinformatics tools and patch-clamp techniques can improve our understanding of the clinical phenotype of epilepsy associated with HCN1 variants.
{"title":"Characterization of the phenotype and functional alternations of three HCN1 variants in Chinese epilepsy patients","authors":"Ziyao Han,&nbsp;Lingling Xie,&nbsp;Xiaorui Liu,&nbsp;Jiaxin Yang,&nbsp;Hanyu Luo,&nbsp;Ran Ding,&nbsp;Hengsheng Chen,&nbsp;Li Cheng,&nbsp;Zhixu Fang,&nbsp;Li Jiang","doi":"10.1016/j.eplepsyres.2025.107521","DOIUrl":"10.1016/j.eplepsyres.2025.107521","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the electrophysiological properties of three <em>HCN1</em> variant sites found in Chinese epileptic patients and to explore the potential relationship between genotype and phenotype.</div></div><div><h3>Methods</h3><div>We correlated clinical severity of three patients with <em>HCN1</em> variants with whole-cell patch-clamp measurements of channel activity, channel expression detected by Western blot, and bioinformatics prediction of the damaging effects of each variant.</div></div><div><h3>Results</h3><div>Three patients with the variants p.L400P, p.D534H and p.M243delinsTL, showed different phenotypes, ranging from mild epilepsy to severe epileptic encephalopathy. Variants L400P and D534H were classified as pathogenic by all bioinformatics tools, and variant M243delinsTL was classified as a polymorphism by MutationTaster. The L400P and D534H variants showed significantly reduced current compared with that of the wild-type (WT), while the current density of M243delinsTL was similar to WT. The half-activation voltage (V<sub>1/2</sub>) of M243delinsTL variant was shifted in the hyperpolarizing direction when compared to the WT, and the slope factor (k) of activation of the M243delinsTL variant was significantly lower than that of the WT. The L400P variant was associated with a significantly higher activation time constant compared with that of the WT. In addition, quantitative detection of the FLAG-tagged <em>HCN1</em> channel revealed that the expression level of the L400P variant was significantly decreased compared to WT.</div></div><div><h3>Conclusions</h3><div>Elucidation of the type and location of variant sites combined with the use of bioinformatics tools and patch-clamp techniques can improve our understanding of the clinical phenotype of epilepsy associated with <em>HCN1</em> variants.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"211 ","pages":"Article 107521"},"PeriodicalIF":2.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term outcome and predictors of vagus nerve stimulation for drug-resistant epilepsy: Real-world evidence from the Korean national hospital consortium
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.eplepsyres.2025.107511
Seo-Young Lee , Hyesung Lee , Jae-Wook Cho , Kyung Wook Kang , Jong-Geun Seo , Jon Soo Kim , Joon-Won Kang , Daeyoung Kim , Young-Soo Kim , Sun Ah Choi , Jeonghoon Park , Ji Hoon Phi , Sang Ook Nam , Won Seop Kim , Jae-Moon Kim , Ki Joong Kim , Korean National Hospital Consortium for VNS Outcome Study

Objective

This study aimed to assess the long-term outcome and prognostic factors of vagus nerve stimulation (VNS) for drug-resistant epilepsy (DRE) using real-world data.

Method

We included 189 DRE patients who underwent VNS implantation between 2005 and 2018 at nine national hospitals in Korea. Seizure-frequency data obtained quarterly one year before and after surgery and annually up to four years after surgery were collected from medical records. Health resource utilization trends over the four years preceding and following surgery were assessed through linkage with national health insurance data. We performed interrupted time series analysis to examine the trend in seizure frequency before and after one year following surgery.

Results

The seizure frequency exhibited a decreasing trend in 27.5 % and an increasing trend in 3.8 % during the first year following VNS implantation without a significant change in efficacy over the subsequent three years. Patients with focal spikes with secondary bilateral synchrony (SBS) in electroencephalography had a higher responder rate (adjusted odds ratio (aOR)= 3.06 [1.36–6.90]), whereas those with Lennox-Gastaut syndrome had a lower responder rate (aOR=0.38 [0.15–0.94]). One-year seizure-freedom was achieved in 6.0 % of patients at some point during the four-year follow-up. Over an eight-year period, the number of antiseizure medications (ASMs) tended to increase before surgery and remained at a median of 5 [4−6] after surgery. While the total medical and epilepsy-related costs tended to decrease after surgery, the ASM cost continued to increase.

Conclusion

VNS was substantially beneficial for one in four patients with DRE, offering the chance of seizure-freedom. However, the efficacy of VNS fell within the efficacy range of recently introduced medical treatments and did not lead to a decrease in the ASM burden. Focal spike with SBS is a potential biomarker for a favorable response to VNS.
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引用次数: 0
The significance of interictal electroencephalogram analysis based on the grand total electroencephalogram score in early assessment of cognitive impairment in epilepsy patients
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.eplepsyres.2025.107506
Honghua Chen, Lingli Ju, Yanyan Ji, Lihong Tao

Purpose

Epilepsy is a widespread neurological disorder that increases the risk of cognitive impairment (CI) or dementia. We aimed to assess the relationship between cognition and interictal electroencephalogram (EEG) in epilepsy patients, using the Grand Total EEG (GTE) score. Additionally, we investigated the GTE score's utility in the early detection of CI in these patients.

Methods

Data from 93 patients diagnosed with unexplained epilepsy at the Affiliated Hospital of Yangzhou University were analyzed. EEG recordings and cognitive evaluations were performed. Patients were categorized into three groups based on their Montreal Cognitive Assessment (MoCA) scores: normal cognitive (NC) group, mild cognitive impairment (MCI) group, and dementia group. The study included analysis of correlations between cognitive test results and clinical characteristics. Additionally, the influence of GTE scores and subscores on cognition was examined. Statistical analyses included one-way analysis of variance (ANOVA), Kruskal-Wallis H-test, Mann-Whitney U-test, Chi-square test, Spearman rank correlation analysis, and multiple linear regression.

Results

(1) There was a significant negative correlation between cognitive test scores and GTE scores. Strong negative correlations were found between cognition (MoCA) and the GTE score (ρ = −0.754, P < 0.001), as well as for the subscores "Diffuse Slow Activity" (ρ = −0.712, P < 0.001), "Frequency of Rhythmic Background Activity" (ρ = −0.490, P < 0.001), and "Paroxysmal Activity" (ρ = −0.565, P < 0.001). (2) Multiple linear regression analysis identified the GTE score, "Diffuse Slow Activity", "Paroxysmal Activity", age, and education as significant predictors of cognitive decline. (3) At a threshold of 4.5, the GTE score effectively differentiated between individuals with and without CI, demonstrating a sensitivity of 73.8 % and a specificity of 93.7 %.

Conclusion

The GTE score provides clinically valuable information for the early detection of CI in patients with epilepsy. As CI worsens in epilepsy patients, the GTE score, Diffuse Slow Activity, Frequency of Rhythmic Background Activity, and Paroxysmal Activity increase. Healthcare providers should focus on managing not only seizures but also interictal EEG abnormalities to prevent or mitigate the risk of CI.
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引用次数: 0
Novel insights regarding haemodynamics in focal seizures
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.eplepsyres.2025.107513
Boriana S. Gagaouzova , Ineke A. van Rossum , Jorien van Hoey Smith , Frederik J. de Lange , Roland D. Thijs , J. Gert van Dijk

Introduction

We explored the temporal patterns of haemodynamic parameters in four seizures of three patients using the log-ratio method.

Methods

We identified three subjects who experienced a seizure during a tilt table test: one had two focal impaired awareness seizures (FIAS, seizures#1 and#2), one had one FIAS (#3), and one had a focal to bilateral tonic-clonic seizure (fbTCS, seizure#4). Recordings included video, heart rate (HR) and continuous blood pressure (BP). We used the log-ratio method to determine the relative contributions of HR, stroke volume (SV), and total peripheral resistance (TPR) to mean arterial pressure (MAP). A 'phase' was defined as a temporary departure of MAP, HR, SV or TPR from baseline.

Results

BP showed a decrease in all four seizures. We observed one phase with synchronous events for all haemodynamic variables during seizures 1&2; seizure#3 showed one phase for MAP and TPR, three phases for HR, and only one for SV. Seizure#4 showed no autonomic involvement during the first minute of the focal seizure, after which MAP and HR showed an asynchronous triphasic course until the signal was lost when a tonic-clonic seizure occurred.

Conclusion

This chance sample illustrates that haemodynamic variables may change in different directions and asynchronously during focal seizures. We speculate that these complex autonomic patterns represent different ictal propagation pathways and that they may include ictal as well as corrective changes. BP decreased in all four seizures while the literature reports BP increases. As our patients were upright, not supine, we hypothesise that ictal haemodynamic changes impair normal control and are therefore likely to cause hypotension in the upright position.
{"title":"Novel insights regarding haemodynamics in focal seizures","authors":"Boriana S. Gagaouzova ,&nbsp;Ineke A. van Rossum ,&nbsp;Jorien van Hoey Smith ,&nbsp;Frederik J. de Lange ,&nbsp;Roland D. Thijs ,&nbsp;J. Gert van Dijk","doi":"10.1016/j.eplepsyres.2025.107513","DOIUrl":"10.1016/j.eplepsyres.2025.107513","url":null,"abstract":"<div><h3>Introduction</h3><div>We explored the temporal patterns of haemodynamic parameters in four seizures of three patients using the log-ratio method.</div></div><div><h3>Methods</h3><div>We identified three subjects who experienced a seizure during a tilt table test: one had two focal impaired awareness seizures (FIAS, seizures#1 and#2), one had one FIAS (#3), and one had a focal to bilateral tonic-clonic seizure (fbTCS, seizure#4). Recordings included video, heart rate (HR) and continuous blood pressure (BP). We used the log-ratio method to determine the relative contributions of HR, stroke volume (SV), and total peripheral resistance (TPR) to mean arterial pressure (MAP). A 'phase' was defined as a temporary departure of MAP, HR, SV or TPR from baseline.</div></div><div><h3>Results</h3><div>BP showed a decrease in all four seizures. We observed one phase with synchronous events for all haemodynamic variables during seizures 1&amp;2; seizure#3 showed one phase for MAP and TPR, three phases for HR, and only one for SV. Seizure#4 showed no autonomic involvement during the first minute of the focal seizure, after which MAP and HR showed an asynchronous triphasic course until the signal was lost when a tonic-clonic seizure occurred.</div></div><div><h3>Conclusion</h3><div>This chance sample illustrates that haemodynamic variables may change in different directions and asynchronously during focal seizures. We speculate that these complex autonomic patterns represent different ictal propagation pathways and that they may include ictal as well as corrective changes. BP decreased in all four seizures while the literature reports BP increases. As our patients were upright, not supine, we hypothesise that ictal haemodynamic changes impair normal control and are therefore likely to cause hypotension in the upright position.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107513"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
4-Phenylbutyrate restored GABA uptake, mitigated seizures in SLC6A1 and SLC6A11 microdeletions/3p- syndrome: From cellular models to human patients
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.eplepsyres.2025.107514
Melissa B. DeLeeuw , Wangzhen Shen , Xiaojuan Tian , Changhong Ding , Karishma Randhave , Jing-Qiong Kang

Background

Haploinsufficient deletions of GABA transporter 1 (GAT-1)- encoding SLC6A1, and GABA transporter 3 (GAT-3)-encoding SLC6A11 are implicated in epileptic syndromes. Despite their significance, the impact of these deletions has not been characterized. Our previous work on SLC6A1 missense mutations prompted a clinical trial for Ravicti (NCT04937062), a glycerol formulation of 4-phenylbutyrate (PBA), for treatment-resistant epilepsy. We observed phenotypic overlap between trial-eligible SLC6A1 mutation patients and 3p- syndrome patients carrying deletions of SLC6A1 and SLC6A11. This study characterizes the functional impact of these deletions and assesses the urgent question of whether 3p- syndrome patients could benefit from this treatment.

Methods

Chromosomal microarray analysis identified a deletion affecting one allele of both SLC6A1 and SLC6A11 in two pediatric patients with 3p- syndrome. Clinical phenotyping included electroencephalogram (EEG) recordings and neurodevelopmental assessments. Functional characterization was conducted using 3H-labeled GABA uptake assays and Western blotting in HEK293T cells, comparing haploinsufficient and missense variant models.

Results

The haploinsufficient GAT-1 and GAT-3 conditions demonstrated reduced GABA uptake and protein expression, comparable to known SLC6A1 missense variants. Post-treatment EEGs showed a moderate reduction in epileptiform discharges following PBA administration, and patients exhibited improved motor function. However, varying degrees of cognitive impairments persisted.

Conclusions

Haploinsufficiency of SLC6A1 and SLC6A11 contributes to the epileptic phenotypes observed in 3p- syndrome, marking this as the first study to biochemically characterize the functional impact of these deletions. Treatment with PBA may provide therapeutic benefits, particularly for addressing seizures and motor deficits, though further exploration of PBA’s long-term effects in patients with 3p- syndrome is warranted.
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引用次数: 0
Use of benzodiazepines in patients with status epilepticus requiring second-line antiseizure medication treatment 苯二氮卓类药物在需要二线抗癫痫药物治疗的癫痫持续状态患者中的应用。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.eplepsyres.2025.107507
Teemu Pöytäkangas , Pabitra Basnyat , Sirpa Rainesalo , Jukka Peltola , Jukka T. Saarinen

Background

Status epilepticus (SE) is a life-threatening state that needs rapid and adequate treatment. Benzodiazepines (BZD) are used as a first-line treatment for SE, and if the desired effect is not achieved, second-line antiseizure medications are used.

Objective

To investigate whether the treatment with BZDs is performed adequately in patients with different subtypes of SE requiring second-line ASM treatment and, if not, to identify the factors influencing the suboptimal treatment.

Patients and methods

This is a retrospective single centre study from the patient register of Tampere University Hospital including patients over 16 years of age with a diagnosis of SE, seizure or epilepsy and who received intravenous (IV) ASM during a one-year period in 2015. Treatment was considered to be suboptimal if it was not in line with the latest European, Finnish or American guidelines.

Results

In total, 109 episodes were registered. The largest group was that with convulsive SE with 56 episodes, followed by postictal with 23 episodes, nonconvulsive status epilepticus (NCSE) with 22 episodes, and focal awareness SE (FASE) with eight episodes. Overall, in 77 % of the episodes, BZDs were administered, and in 43 % of the episodes, treatment was in line with guidelines. In the NCSE group, BZD was administered less often and was less often in line with the guidelines than in the CSE group (27.3 % vs. 89.3 %, p < 0.001 and 4.5 % vs. 55.4 %, p < 0.001). For FASE episodes, the concordance with the guidelines was low. After IV administration, the mean BZD dose was lower than that after buccal administration of midazolam (2.1 mg vs. 8.7 mg) or after rectal administration of diazepam (4.5 mg vs. 10.0 mg). Lorazepam was administered only via the IV route, with mean dosage of 2.6 mg. Clinical characteristics did not influence the dosing of BZDs.

Conclusions

BZDs were both underdosed and underused for all subtypes of SE. In particular, their use for NCSE was infrequent and suboptimal. The divergence from the guidelines was influenced especially by low IV dosages.
背景:癫痫持续状态(SE)是一种危及生命的状态,需要迅速和充分的治疗。苯二氮卓类药物(BZD)被用作SE的一线治疗,如果没有达到预期的效果,则使用二线抗癫痫药物。目的:探讨需要二线ASM治疗的不同SE亚型患者BZDs治疗是否充分,如果不充分,则确定影响治疗不理想的因素。患者和方法:这是一项回顾性单中心研究,来自坦佩雷大学医院的患者登记,包括16岁以上,诊断为SE、癫痫或癫痫,并在2015年接受静脉注射(IV) ASM的患者。如果治疗不符合最新的欧洲、芬兰或美国的指导方针,则被认为是次优治疗。结果:共登记109例。最大的组是惊厥性SE,共56次,其次是后惊厥性癫痫持续状态(NCSE),共23次,非惊厥性癫痫持续状态(NCSE) 22次,局灶性意识SE (FASE) 8次。总的来说,在77 %的发作中,给予bzd治疗,43 %的发作中,治疗符合指南。在NCSE组中,BZD的使用频率低于CSE组(27.3 % vs. 89.3% %,p )。结论:BZD在所有SE亚型中都是剂量不足和使用不足的。特别是,它们对NCSE的使用很少,而且不是最佳的。与指南的背离尤其受到低静脉注射剂量的影响。
{"title":"Use of benzodiazepines in patients with status epilepticus requiring second-line antiseizure medication treatment","authors":"Teemu Pöytäkangas ,&nbsp;Pabitra Basnyat ,&nbsp;Sirpa Rainesalo ,&nbsp;Jukka Peltola ,&nbsp;Jukka T. Saarinen","doi":"10.1016/j.eplepsyres.2025.107507","DOIUrl":"10.1016/j.eplepsyres.2025.107507","url":null,"abstract":"<div><h3>Background</h3><div>Status epilepticus (SE) is a life-threatening state that needs rapid and adequate treatment. Benzodiazepines (BZD) are used as a first-line treatment for SE, and if the desired effect is not achieved, second-line antiseizure medications are used.</div></div><div><h3>Objective</h3><div>To investigate whether the treatment with BZDs is performed adequately in patients with different subtypes of SE requiring second-line ASM treatment and, if not, to identify the factors influencing the suboptimal treatment.</div></div><div><h3>Patients and methods</h3><div>This is a retrospective single centre study from the patient register of Tampere University Hospital including patients over 16 years of age with a diagnosis of SE, seizure or epilepsy and who received intravenous (IV) ASM during a one-year period in 2015. Treatment was considered to be suboptimal if it was not in line with the latest European, Finnish or American guidelines.</div></div><div><h3>Results</h3><div>In total, 109 episodes were registered. The largest group was that with convulsive SE with 56 episodes, followed by postictal with 23 episodes, nonconvulsive status epilepticus (NCSE) with 22 episodes, and focal awareness SE (FASE) with eight episodes. Overall, in 77 % of the episodes, BZDs were administered, and in 43 % of the episodes, treatment was in line with guidelines. In the NCSE group, BZD was administered less often and was less often in line with the guidelines than in the CSE group (27.3 % vs. 89.3 %, p &lt; 0.001 and 4.5 % vs. 55.4 %, p &lt; 0.001). For FASE episodes, the concordance with the guidelines was low. After IV administration, the mean BZD dose was lower than that after buccal administration of midazolam (2.1 mg vs. 8.7 mg) or after rectal administration of diazepam (4.5 mg vs. 10.0 mg). Lorazepam was administered only via the IV route, with mean dosage of 2.6 mg. Clinical characteristics did not influence the dosing of BZDs.</div></div><div><h3>Conclusions</h3><div>BZDs were both underdosed and underused for all subtypes of SE. In particular, their use for NCSE was infrequent and suboptimal. The divergence from the guidelines was influenced especially by low IV dosages.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107507"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to "Significant reduction of seizure frequency in patients with drug-resistant epilepsy by vagus nerve stimulation: Systematic review and meta-analysis" [Epilepsy Res. 210 (2025) 107510].
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.eplepsyres.2025.107519
Malaisamy Muniyandi, Karthick Chelvanayagam, Sahil Abdul Salam, Sathishkumar Vadamalai, Kavitha Rajsekar, Rajeswari Ramachandran
{"title":"Corrigendum to \"Significant reduction of seizure frequency in patients with drug-resistant epilepsy by vagus nerve stimulation: Systematic review and meta-analysis\" [Epilepsy Res. 210 (2025) 107510].","authors":"Malaisamy Muniyandi, Karthick Chelvanayagam, Sahil Abdul Salam, Sathishkumar Vadamalai, Kavitha Rajsekar, Rajeswari Ramachandran","doi":"10.1016/j.eplepsyres.2025.107519","DOIUrl":"https://doi.org/10.1016/j.eplepsyres.2025.107519","url":null,"abstract":"","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":" ","pages":"107519"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term efficacy and safety of perampanel monotherapy in patients with newly diagnosed or currently untreated recurrent focal-onset seizures: Results from the open-label extension phase of FREEDOM (Study 342) perampanel单药治疗新诊断或目前未治疗的复发性局灶性癫痫患者的长期疗效和安全性:来自FREEDOM开放标签延长期的结果(研究342)。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.eplepsyres.2024.107494
Takamichi Yamamoto , Sung Chul Lim , Hirotomo Ninomiya , Yuichi Kubota , Won Chul Shin , Dong Wook Kim , Dong Jin Shin , Koji Iida , Taku Ochiai , Risa Matsunaga , Hidetaka Hiramatsu , Ji Hyun Kim

Objective

FREEDOM (Study 342; NCT03201900) assessed the long-term treatment effect of perampanel monotherapy in adolescent and adult patients (12–74 years of age) with untreated focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS).

Methods

In the Core Study, after a 4-week Pretreatment Phase, perampanel was up-titrated to 4 mg/day during a 6-week Titration Period followed by a 26-week Maintenance Period. Patients experiencing seizure(s) during the 4-mg/day Maintenance Period could have perampanel up-titrated to 8 mg/day over 4 weeks then could enter the 26-week 8-mg/day Maintenance Period. Patients could enter Extension to continue treatment upon the completion of the Core Study. Seizure-freedom rates, time to seizure recurrence or withdrawal since the initiation of maintenance treatment, and safety outcomes were assessed.

Results

In FREEDOM, 89 patients who received ≥ 1 perampanel dose were included for safety assessments (Safety Analysis Set), and 73 of them entered the 4-‍‍‍mg/day Maintenance Period (the modified Intent-to-Treat Analysis set) with 21 patients having perampanel up-titrated to 8 mg/day; 46 patients entered Extension with 38 patients completing. Overall, 42/89 (47.2 %) patients had cumulative exposure to perampanel for > 52 weeks. Among patients who entered Extension, 52.2 % (n = 24/46; 95 % confidence interval [CI] 36.9, 67.1) remained seizure free for 52 weeks at perampanel 4 mg/day and 67.4 % (n = 31/46; 95 % CI 52.0, 80.5) at 4–8 mg/day. The cumulative probabilities of seizure recurrence and withdrawal at 4–8 mg/day over 52 weeks were 28.9 % (95 % CI 19.0, 42.4) and 43.8 % (95 % CI 33.4, 55.9), respectively. Treatment-emergent adverse events (TEAEs) occurred in 74/89 (83.1 %) patients, with 9/89 (10.1 %) discontinuing because of TEAEs. Dizziness occurred in 34/89 (38.2 %) patients and was the most common event.

Conclusions

Patients with untreated FOS (with or without FBTCS) are able to maintain seizure freedom for up to 52 weeks with perampanel monotherapy at a dose of 4–8 mg/day. The tolerability profile was manageable, and the safety profile was consistent with previous findings.
目的:FREEDOM(研究342;NCT03201900)评估了perampanel单药治疗未经治疗的局灶性癫痫(FOS)青少年和成人患者(12-74岁)的长期治疗效果,伴有或不伴有局灶性或双侧强直-阵挛性癫痫(FBTCS)。方法:在核心研究中,经过4周的预处理阶段,在6周的滴定期和26周的维持期中,perampanel的滴定量增加到4 mg/天。在4mg /天维持期发生癫痫发作的患者可以在4周内将perampanel的滴度提高到8 mg/天,然后进入26周的8mg /天维持期。患者可在核心研究完成后进入延伸期继续治疗。评估癫痫发作自由率、癫痫复发或自维持治疗开始后停药的时间以及安全性结果。结果:在FREEDOM试验中,89例接受≥ 1 perampanel剂量的患者被纳入安全性评估(安全性分析集),其中73例进入4-‍‍‍mg/天维持期(改进的意向治疗分析集),其中21例perampanel上调至8 mg/天;46例患者进入延长期,38例患者完成。总体而言,42/89(47.2% %)患者累积暴露于perampanel的时间为bb0 52周。在进入延长期的患者中,52.2% % (n = 24/46;95 %可信区间[CI] 36.9, 67.1)在perampanel 4 mg/天和67.4 % (n = 31/46;95 % CI 52.0, 80.5), 4-8 mg/天。在52周内,4-8 mg/天的发作复发和停药的累积概率分别为28.9 %(95 % CI 19.0, 42.4)和43.8 %(95 % CI 33.4, 55.9)。74/89例(83.1 %)患者出现治疗不良事件(teae), 9/89例(10.1 %)患者因teae停止治疗。眩晕发生率为34/89(38.2 %),是最常见的事件。结论:未经治疗的FOS(伴有或不伴有FBTCS)患者能够在4-8 mg/天的perampanel单药治疗下维持长达52周的癫痫发作自由。耐受性是可控的,安全性与之前的研究结果一致。
{"title":"Long-term efficacy and safety of perampanel monotherapy in patients with newly diagnosed or currently untreated recurrent focal-onset seizures: Results from the open-label extension phase of FREEDOM (Study 342)","authors":"Takamichi Yamamoto ,&nbsp;Sung Chul Lim ,&nbsp;Hirotomo Ninomiya ,&nbsp;Yuichi Kubota ,&nbsp;Won Chul Shin ,&nbsp;Dong Wook Kim ,&nbsp;Dong Jin Shin ,&nbsp;Koji Iida ,&nbsp;Taku Ochiai ,&nbsp;Risa Matsunaga ,&nbsp;Hidetaka Hiramatsu ,&nbsp;Ji Hyun Kim","doi":"10.1016/j.eplepsyres.2024.107494","DOIUrl":"10.1016/j.eplepsyres.2024.107494","url":null,"abstract":"<div><h3>Objective</h3><div>FREEDOM (Study 342; NCT03201900) assessed the long-term treatment effect of perampanel monotherapy in adolescent and adult patients (12–74 years of age) with untreated focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS).</div></div><div><h3>Methods</h3><div>In the Core Study, after a 4-week Pretreatment Phase, perampanel was up-titrated to 4 mg/day during a 6-week Titration Period followed by a 26-week Maintenance Period. Patients experiencing seizure(s) during the 4-mg/day Maintenance Period could have perampanel up-titrated to 8 mg/day over 4 weeks then could enter the 26-week 8-mg/day Maintenance Period. Patients could enter Extension to continue treatment upon the completion of the Core Study. Seizure-freedom rates, time to seizure recurrence or withdrawal since the initiation of maintenance treatment, and safety outcomes were assessed.</div></div><div><h3>Results</h3><div>In FREEDOM, 89 patients who received ≥ 1 perampanel dose were included for safety assessments (Safety Analysis Set), and 73 of them entered the 4-‍‍‍mg/day Maintenance Period (the modified Intent-to-Treat Analysis set) with 21 patients having perampanel up-titrated to 8 mg/day; 46 patients entered Extension with 38 patients completing. Overall, 42/89 (47.2 %) patients had cumulative exposure to perampanel for &gt; 52 weeks. Among patients who entered Extension, 52.2 % (n = 24/46; 95 % confidence interval [CI] 36.9, 67.1) remained seizure free for 52 weeks at perampanel 4 mg/day and 67.4 % (n = 31/46; 95 % CI 52.0, 80.5) at 4–8 mg/day. The cumulative probabilities of seizure recurrence and withdrawal at 4–8 mg/day over 52 weeks were 28.9 % (95 % CI 19.0, 42.4) and 43.8 % (95 % CI 33.4, 55.9), respectively. Treatment-emergent adverse events (TEAEs) occurred in 74/89 (83.1 %) patients, with 9/89 (10.1 %) discontinuing because of TEAEs. Dizziness occurred in 34/89 (38.2 %) patients and was the most common event.</div></div><div><h3>Conclusions</h3><div>Patients with untreated FOS (with or without FBTCS) are able to maintain seizure freedom for up to 52 weeks with perampanel monotherapy at a dose of 4–8 mg/day. The tolerability profile was manageable, and the safety profile was consistent with previous findings.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107494"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Significant reduction of seizure frequency in patients with drug-resistant epilepsy by vagus nerve stimulation: Systematic review and meta-analysis 迷走神经刺激对耐药癫痫患者癫痫发作频率的显著降低:系统回顾和荟萃分析。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.eplepsyres.2025.107510
Malaisamy Muniyandi , Karthick Chelvanayagam , Sahil Abdul Salam , Sathishkumar Vadamalai , Kavitha Rajsekar , Rajeswari Ramachandran

Background

Epilepsy is a major neurological disorder, typically managed with Anti-Seizure Medication (ASM). Nevertheless, a substantial 30 % of patients did not respond satisfactorily to ASMs, classifying their condition as Drug-Resistant Epilepsy (DRE). Vagus Nerve Stimulation (VNS) was recommended as a potential solution.

Objective

To evaluate clinical efficacy of VNS on patients with DRE in reduction of seizures through a systematic review and meta-analysis using a random effects model.

Methods

A systematic search was done from PubMed, ScienceDirect, Cochrane Library and Google Scholar databases on observational studies and randomized controlled trials (RCTs) for the clinical effectiveness of VNS among DRE patients. A meta-analysis was performed to obtain the pooled estimate of the clinical effectiveness of VNS in terms of seizure reduction and the odds ratio (OR) for patients achieving > 50 % seizure reduction. Heterogeneity was assessed using visual inspection of forest plots and I2 statistic.

Results

A total of 1023 articles were retrieved from the electronic search. After removing duplicates, non-relevance and non-availability of efficacy data, 28 articles were included in the final analysis. Of these, 9 are RCTs and 19 are observational studies. The pooled estimate of > 50 % seizure reduction was 0.46 (95 % CI: 0.40–0.51) and the pooled estimate of the OR comparing > 50 % vs ≤ 50 % seizure reduction was 0.76 (95 % CI: 0.44–1.29).

Conclusion

Our meta-analysis showed that 46 % of DRE patients have experienced ≥ 50 % seizure reduction with VNS treatment. It should be considered in patients in whom ASM has failed or who continue to experience seizures after medication.
背景:癫痫是一种主要的神经系统疾病,通常使用抗癫痫药物(ASM)进行治疗。然而,高达30% %的患者对抗痉挛药物反应不满意,将其归类为耐药癫痫(Drug-Resistant Epilepsy, DRE)。迷走神经刺激(VNS)被推荐为潜在的解决方案。目的:采用随机效应模型,通过系统评价和meta分析,评价VNS对DRE患者减少癫痫发作的临床疗效。方法:系统检索PubMed、ScienceDirect、Cochrane Library和b谷歌Scholar数据库的观察性研究和随机对照试验(rct),研究VNS对DRE患者的临床疗效。我们进行了一项荟萃分析,以获得VNS在减少癫痫发作方面的临床有效性的汇总估计,以及达到> 50% %癫痫发作减少的患者的优势比(OR)。采用森林样地目视检验和I2统计量评价异质性。结果:电子检索共检索到文献1023篇。在剔除重复、不相关和不可获得的疗效数据后,28篇文献被纳入最终分析。其中9项为随机对照试验,19项为观察性研究。> 50 %与≤ 50 %癫痫发作减少的合并估计为0.46(95 % CI: 0.40-0.51), > 50 %与≤ 50 %癫痫发作减少的合并估计OR为0.76(95 % CI: 0.44-1.29)。结论:我们的荟萃分析显示,46% %的DRE患者在VNS治疗后癫痫发作减少≥ 50% %。对于ASM失败或服药后仍有癫痫发作的患者,应考虑使用它。
{"title":"Significant reduction of seizure frequency in patients with drug-resistant epilepsy by vagus nerve stimulation: Systematic review and meta-analysis","authors":"Malaisamy Muniyandi ,&nbsp;Karthick Chelvanayagam ,&nbsp;Sahil Abdul Salam ,&nbsp;Sathishkumar Vadamalai ,&nbsp;Kavitha Rajsekar ,&nbsp;Rajeswari Ramachandran","doi":"10.1016/j.eplepsyres.2025.107510","DOIUrl":"10.1016/j.eplepsyres.2025.107510","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy is a major neurological disorder, typically managed with Anti-Seizure Medication (ASM). Nevertheless, a substantial 30 % of patients did not respond satisfactorily to ASMs, classifying their condition as Drug-Resistant Epilepsy (DRE). Vagus Nerve Stimulation (VNS) was recommended as a potential solution.</div></div><div><h3>Objective</h3><div>To evaluate clinical efficacy of VNS on patients with DRE in reduction of seizures through a systematic review and meta-analysis using a random effects model.</div></div><div><h3>Methods</h3><div>A systematic search was done from PubMed, ScienceDirect, Cochrane Library and Google Scholar databases on observational studies and randomized controlled trials (RCTs) for the clinical effectiveness of VNS among DRE patients. A meta-analysis was performed to obtain the pooled estimate of the clinical effectiveness of VNS in terms of seizure reduction and the odds ratio (OR) for patients achieving &gt; 50 % seizure reduction. Heterogeneity was assessed using visual inspection of forest plots and I<sup>2</sup> statistic.</div></div><div><h3>Results</h3><div>A total of 1023 articles were retrieved from the electronic search. After removing duplicates, non-relevance and non-availability of efficacy data, 28 articles were included in the final analysis. Of these, 9 are RCTs and 19 are observational studies. The pooled estimate of &gt; 50 % seizure reduction was 0.46 (95 % CI: 0.40–0.51) and the pooled estimate of the OR comparing &gt; 50 % vs ≤ 50 % seizure reduction was 0.76 (95 % CI: 0.44–1.29).</div></div><div><h3>Conclusion</h3><div>Our meta-analysis showed that 46 % of DRE patients have experienced ≥ 50 % seizure reduction with VNS treatment. It should be considered in patients in whom ASM has failed or who continue to experience seizures after medication.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107510"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Epilepsy Research
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