Pub Date : 2025-02-01DOI: 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 , Ineke A. van Rossum , Jorien van Hoey Smith , Frederik J. de Lange , Roland D. Thijs , 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&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}
Pub Date : 2025-02-01DOI: 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.
{"title":"4-Phenylbutyrate restored GABA uptake, mitigated seizures in SLC6A1 and SLC6A11 microdeletions/3p- syndrome: From cellular models to human patients","authors":"Melissa B. DeLeeuw , Wangzhen Shen , Xiaojuan Tian , Changhong Ding , Karishma Randhave , Jing-Qiong Kang","doi":"10.1016/j.eplepsyres.2025.107514","DOIUrl":"10.1016/j.eplepsyres.2025.107514","url":null,"abstract":"<div><h3>Background</h3><div>Haploinsufficient deletions of GABA transporter 1 (GAT-1)- encoding <em>SLC6A1</em>, and GABA transporter 3 (GAT-3)-encoding <em>SLC6A11</em> are implicated in epileptic syndromes. Despite their significance, the impact of these deletions has not been characterized. Our previous work on <em>SLC6A1</em> 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 <em>SLC6A1</em> mutation patients and 3p- syndrome patients carrying deletions of <em>SLC6A1</em> and <em>SLC6A11</em>. This study characterizes the functional impact of these deletions and assesses the urgent question of whether 3p- syndrome patients could benefit from this treatment.</div></div><div><h3>Methods</h3><div>Chromosomal microarray analysis identified a deletion affecting one allele of both <em>SLC6A1</em> and <em>SLC6A11</em> in two pediatric patients with 3p- syndrome. Clinical phenotyping included electroencephalogram (EEG) recordings and neurodevelopmental assessments. Functional characterization was conducted using <sup>3</sup>H-labeled GABA uptake assays and Western blotting in HEK293T cells, comparing haploinsufficient and missense variant models.</div></div><div><h3>Results</h3><div>The haploinsufficient GAT-1 and GAT-3 conditions demonstrated reduced GABA uptake and protein expression, comparable to known <em>SLC6A1</em> 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.</div></div><div><h3>Conclusions</h3><div>Haploinsufficiency of <em>SLC6A1</em> and <em>SLC6A11</em> 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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107514"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349038","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}
Pub Date : 2025-02-01DOI: 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.
{"title":"Use of benzodiazepines in patients with status epilepticus requiring second-line antiseizure medication treatment","authors":"Teemu Pöytäkangas , Pabitra Basnyat , Sirpa Rainesalo , Jukka Peltola , 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 < 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.</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}
Pub Date : 2025-02-01DOI: 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.
{"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 , 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","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 > 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}
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.
{"title":"Significant reduction of seizure frequency in patients with drug-resistant epilepsy by vagus nerve stimulation: Systematic review and meta-analysis","authors":"Malaisamy Muniyandi , Karthick Chelvanayagam , Sahil Abdul Salam , Sathishkumar Vadamalai , Kavitha Rajsekar , 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 > 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 > 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).</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}
{"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":"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}
Pub Date : 2025-02-01DOI: 10.1016/j.eplepsyres.2025.107509
Cory E. Kowalski , Warren S. Brown , Anne A.T. Nolty , Amanda Panos , Monika Jones , Lynn K. Paul
Background and aims
For young children with intractable epilepsy caused by congenital abnormalities or acquired cortical lesions, pediatric hemispherectomy surgery (pHS) may offer the only path to seizure remediation. Although some sensory and motor outcomes of pHS are highly predictable, the long-term cognitive and functional sequelae of pHS are far more variable. With the aim of identifying potential post-pHS intervention targets, the current study examined daily executive functioning and self-awareness in adults with pHS and broadly intact cognitive outcomes (indicated by average or above performance on intelligence tests).
Methods
This study used self- and informant-ratings on the Behavior Rating Inventory of Executive Functioning, Adult Version (BRIEF-A) everyday executive functioning in to evaluate adaptive behavior in 16 adults with pHS and Full-Scale IQ (FSIQ) of 77 or greater. Self- and informant-report results were compared to the normative sample, as was the proportion of participants with self vs. informant discrepancy scores of > 1 standard deviation.
Results
Both participants and informants reported each participants’ behaviors and executive functioning were largely commensurate with average range from test norms. On average, participants with pHS rated themselves as stronger than their peers at Self-Monitoring, possibly suggesting compensatory attention to issues surrounding their sensory-motor disabilities (e.g., hemiplegia and hemianopsia). Informant- and self-reports were generally consistent, with the exception of an elevated number of participants whose self-ratings indicated less impairment than informant-ratings on the Initiate subscale.
Conclusions
This study demonstrates that following pHS, adults with average (or higher) general cognition also exhibit daily executive functioning broadly commensurate with their peers, with the possible exceptions of elevated self-monitoring and greater likelihood of overestimating their initiation (compared to informant ratings).
{"title":"Daily executive functioning in adults with pediatric hemispherectomy","authors":"Cory E. Kowalski , Warren S. Brown , Anne A.T. Nolty , Amanda Panos , Monika Jones , Lynn K. Paul","doi":"10.1016/j.eplepsyres.2025.107509","DOIUrl":"10.1016/j.eplepsyres.2025.107509","url":null,"abstract":"<div><h3>Background and aims</h3><div>For young children with intractable epilepsy caused by congenital abnormalities or acquired cortical lesions, pediatric hemispherectomy surgery (pHS) may offer the only path to seizure remediation. Although some sensory and motor outcomes of pHS are highly predictable, the long-term cognitive and functional sequelae of pHS are far more variable. With the aim of identifying potential post-pHS intervention targets, the current study examined daily executive functioning and self-awareness in adults with pHS and broadly intact cognitive outcomes (indicated by average or above performance on intelligence tests).</div></div><div><h3>Methods</h3><div>This study used self- and informant-ratings on the Behavior Rating Inventory of Executive Functioning, Adult Version (BRIEF-A) everyday executive functioning in to evaluate adaptive behavior in 16 adults with pHS and Full-Scale IQ (FSIQ) of 77 or greater. Self- and informant-report results were compared to the normative sample, as was the proportion of participants with self vs. informant discrepancy scores of > 1 standard deviation.</div></div><div><h3>Results</h3><div>Both participants and informants reported each participants’ behaviors and executive functioning were largely commensurate with average range from test norms. On average, participants with pHS rated themselves as stronger than their peers at Self-Monitoring, possibly suggesting compensatory attention to issues surrounding their sensory-motor disabilities (e.g., hemiplegia and hemianopsia). Informant- and self-reports were generally consistent, with the exception of an elevated number of participants whose self-ratings indicated less impairment than informant-ratings on the Initiate subscale.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that following pHS, adults with average (or higher) general cognition also exhibit daily executive functioning broadly commensurate with their peers, with the possible exceptions of elevated self-monitoring and greater likelihood of overestimating their initiation (compared to informant ratings).</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107509"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002576","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}
Pub Date : 2025-02-01DOI: 10.1016/j.eplepsyres.2025.107512
Yu Chen , Shu-Nan Yang , Guan-Ling Fu , Xiao-Xuan Liu , Xin-Li Xiao , Xiao-Lin Wu , Feng Wu , Yan-Bing Ma , Sheng-Feng Ji , Jin-Song Zhou , Jian-Xin Liu
Mutations in methyl CpG binding protein 2 (MeCP2) are linked to Rett syndrome, in which epilepsy is one of the most well-described disorders. However, little is known about the specific role of MeCP2 during epileptogenesis. Our previous study has demonstrated that MeCP2 has a unique control on the development of mossy fiber sprouting (MFS) in the epileptic hippocampus. This study aimed to (1) examine whether MeCP2 affects spontaneous recurrent seizures (SRSs) and cognitive deficits in mice with pilocarpine-induced epilepsy, and (2) profile MeCP2’s downstream molecular events. In the dentate gyrus (DG), we found that over-expression or suppression of MeCP2 significantly reduced or increased the frequency, duration, and number of stage 5 seizures of SRSs during the chronic stage after the SE. Over-expression of MeCP2 improved cognitive deficits in TLE mice, while exacerbated cognitive performances were observed following MeCP2 knockdown. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-sequence analyses revealed that MeCP2-targeted genes have far‑reaching impacts on the pathophysiological events during epileptogenesis, including neuron differentiation, neurogenesis, axon guidance, and so on.
{"title":"Effects of MeCP2 on chronic seizures and cognitive function in mice with temporal lobe epilepsy","authors":"Yu Chen , Shu-Nan Yang , Guan-Ling Fu , Xiao-Xuan Liu , Xin-Li Xiao , Xiao-Lin Wu , Feng Wu , Yan-Bing Ma , Sheng-Feng Ji , Jin-Song Zhou , Jian-Xin Liu","doi":"10.1016/j.eplepsyres.2025.107512","DOIUrl":"10.1016/j.eplepsyres.2025.107512","url":null,"abstract":"<div><div>Mutations in methyl CpG binding protein 2 (MeCP2) are linked to Rett syndrome, in which epilepsy is one of the most well-described disorders. However, little is known about the specific role of MeCP2 during epileptogenesis. Our previous study has demonstrated that MeCP2 has a unique control on the development of mossy fiber sprouting (MFS) in the epileptic hippocampus. This study aimed to (1) examine whether MeCP2 affects spontaneous recurrent seizures (SRSs) and cognitive deficits in mice with pilocarpine-induced epilepsy, and (2) profile MeCP2’s downstream molecular events. In the dentate gyrus (DG), we found that over-expression or suppression of MeCP2 significantly reduced or increased the frequency, duration, and number of stage 5 seizures of SRSs during the chronic stage after the SE. Over-expression of MeCP2 improved cognitive deficits in TLE mice, while exacerbated cognitive performances were observed following MeCP2 knockdown. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-sequence analyses revealed that MeCP2-targeted genes have far‑reaching impacts on the pathophysiological events during epileptogenesis, including neuron differentiation, neurogenesis, axon guidance, and so on.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107512"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028333","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}
Pub Date : 2025-02-01DOI: 10.1016/j.eplepsyres.2025.107517
Sonali Singh , Karim Mithani , Ayako Ochi , Hiroshi Otsubo , Rohit Sharma , Suvasini Sharma , Lauren Sham , Shelly Weiss , George M. Ibrahim , Elizabeth Donner , Puneet Jain
Background
Direct cortical electrical stimulation remains the gold standard for delineation of the primary motor cortex in patients with drug-resistant epilepsy (DRE) undergoing epilepsy surgery evaluation
Objective
This study aimed to explore the efficacy and safety of functional motor mapping through Stereo-EEG (SEEG) electrode contacts in children with DRE at our institute.
Methods
We performed a retrospective analysis of children who underwent SEEG evaluation and functional cortical mapping via bipolar electrical stimulation at our institution between July 2020 and June 2024. Detailed clinical, radiological and neurophysiological variable were extracted; qualitative and quantitative variables were summarized using appropriate descriptive statistics.
Results
A total of 29 patients underwent functional cortical motor mapping via SEEG with the mean age of 12.5 years (standard deviation, 4.1). Stimulation was performed using 50 Hz bipolar electrical stimulation. Succesful motor mapping was reported in 28 patients (96.6 %). The median lowest current threshold for a motor response was 2 mA. The spectrum of motor responses reported included: tonic/dystonic (26), clonic (6), and jerk/jitteriness (1). Afterdischarges were noted in 14 patients (48.3 %) and seizures were seen in 5 patients (17.2 %).
Conclusions
SEEG guided electrical stimulation of motor cortex is feasible and safe for functional cortical mapping in children with epilepsy.
{"title":"SEEG guided mapping of primary motor cortex in children with epilepsy","authors":"Sonali Singh , Karim Mithani , Ayako Ochi , Hiroshi Otsubo , Rohit Sharma , Suvasini Sharma , Lauren Sham , Shelly Weiss , George M. Ibrahim , Elizabeth Donner , Puneet Jain","doi":"10.1016/j.eplepsyres.2025.107517","DOIUrl":"10.1016/j.eplepsyres.2025.107517","url":null,"abstract":"<div><h3>Background</h3><div>Direct cortical electrical stimulation remains the gold standard for delineation of the primary motor cortex in patients with drug-resistant epilepsy (DRE) undergoing epilepsy surgery evaluation</div></div><div><h3>Objective</h3><div>This study aimed to explore the efficacy and safety of functional motor mapping through Stereo-EEG (SEEG) electrode contacts in children with DRE at our institute.</div></div><div><h3>Methods</h3><div>We performed a retrospective analysis of children who underwent SEEG evaluation and functional cortical mapping via bipolar electrical stimulation at our institution between July 2020 and June 2024. Detailed clinical, radiological and neurophysiological variable were extracted; qualitative and quantitative variables were summarized using appropriate descriptive statistics.</div></div><div><h3>Results</h3><div>A total of 29 patients underwent functional cortical motor mapping via SEEG with the mean age of 12.5 years (standard deviation, 4.1). Stimulation was performed using 50 Hz bipolar electrical stimulation. Succesful motor mapping was reported in 28 patients (96.6 %). The median lowest current threshold for a motor response was 2 mA. The spectrum of motor responses reported included: tonic/dystonic (26), clonic (6), and jerk/jitteriness (1). Afterdischarges were noted in 14 patients (48.3 %) and seizures were seen in 5 patients (17.2 %).</div></div><div><h3>Conclusions</h3><div>SEEG guided electrical stimulation of motor cortex is feasible and safe for functional cortical mapping in children with epilepsy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107517"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064696","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}
Pediatric status epilepticus (SE) is a life-threatening, time-sensitive neurological emergency. The adequate treatment of pediatric patients with SE is challenging, especially when the principles of time are considered. Various clinical trials and studies [especially one of the most important randomized controlled trials of the present time, ‘ESETT (Established Status Epilepticus Treatment Trial)’] compared the effectiveness of 3 antiseizure medications (ASMs) in patients with SE, providing robust evidence for clinical practice. Meticulous analysis of care delivery is an essential component as far as optimal management of pediatric SE is concerned. We performed an evidence-based comprehensive review on documented non-compliance and deviations from standard-treatment guidelines (STGs), focusing on time-elapsed from pediatric SE onset to ASM administration and escalation to subsequent classes. We have found significant gaps in real-world clinical practice. A literature review and a pooled-analysis of 12 studies on pediatric SE showed prehospital time to SE treatment was 29.5 minutes. Time to EMS arrival and hospital admission was 23 minutes and 48 minutes, respectively. Time-elapsed from SE onset to first-line ASM administration was 25.5 minutes, compared to evidence-based guidelines recommended time of 5–10 minutes. Similar delays were also observed in second- and third-line ASM administration. We have reviewed the factors affecting time-delays and impact on clinical outcomes. This review also highlights quality-improvement avenues that may help in improvising time for SE treatment and associated outcomes in pediatrics.
{"title":"Tenets of timing: An evidence based comprehensive review on time-lag in the management of pediatric status epilepticus and its effect on clinical outcomes","authors":"Vaibhav R. Suryawanshi , Kavita Srivastava , Asavari Raut , Bhakti Sarangi","doi":"10.1016/j.eplepsyres.2025.107518","DOIUrl":"10.1016/j.eplepsyres.2025.107518","url":null,"abstract":"<div><div>Pediatric status epilepticus (SE) is a life-threatening, time-sensitive neurological emergency. The adequate treatment of pediatric patients with SE is challenging, especially when the principles of time are considered. Various clinical trials and studies [especially one of the most important randomized controlled trials of the present time, ‘ESETT (Established Status Epilepticus Treatment Trial)’] compared the effectiveness of 3 antiseizure medications (ASMs) in patients with SE, providing robust evidence for clinical practice. Meticulous analysis of care delivery is an essential component as far as optimal management of pediatric SE is concerned. We performed an evidence-based comprehensive review on documented non-compliance and deviations from standard-treatment guidelines (STGs), focusing on time-elapsed from pediatric SE onset to ASM administration and escalation to subsequent classes. We have found significant gaps in real-world clinical practice. A literature review and a pooled-analysis of 12 studies on pediatric SE showed prehospital time to SE treatment was 29.5 minutes. Time to EMS arrival and hospital admission was 23 minutes and 48 minutes, respectively. Time-elapsed from SE onset to first-line ASM administration was 25.5 minutes, compared to evidence-based guidelines recommended time of 5–10 minutes. Similar delays were also observed in second- and third-line ASM administration. We have reviewed the factors affecting time-delays and impact on clinical outcomes. This review also highlights quality-improvement avenues that may help in improvising time for SE treatment and associated outcomes in pediatrics.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"210 ","pages":"Article 107518"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104484","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}
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