Arjune Sen, Sofia Toniolo, Xin You Tai, Mary Akinola, Mkael Symmonds, Sergio Mura, Joanne Galloway, Angela Hallam, Jane Y. C. Chan, Ivan Koychev, Chris Butler, John Geddes, Gabriel Davis Jones, Younes Tabi, Raquel Maio, Eleni Frangou, Sharon Love, Sian Thompson, Rohan Van Der Putt, Sanjay G. Manohar, Rupert McShane, Masud Husain
<div> <section> <h3> Objective</h3> <p>To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure.</p> </section> <section> <h3> Methods</h3> <p>We performed a randomized, double-blind, placebo-controlled crossover pilot study in individuals with mild-to-moderate Alzheimer's disease. Electroencephalography was performed at baseline and those with active epileptiform discharges were excluded. Eligible participants were randomized to placebo for 12 weeks or an active arm of oral levetiracetam (4 weeks up-titration to levetiracetam 500 mg twice daily, 4 weeks maintained on this dose followed by 4 weeks down-titration to nil). Participants then crossed over to the other arm. The primary outcome was change in cognitive function assessed by the Oxford Memory Task, a task sensitive to hippocampal memory binding. Secondary outcomes included tolerability, other neuropsychological scales, and general questionnaires.</p> </section> <section> <h3> Results</h3> <p>Recruitment numbers were severely limited owing to restrictions from the COVID-19 pandemic at the time of the study. Eight participants completed both arms of the study (mean age 68.4 years [SD = 9.2]; 5 females [62.5%]). No participants withdrew from the study and there was no significant difference between reported side effects in the active levetiracetam or placebo arm. Measures of mood and quality of life were also not significantly different between the two arms based on participant or carer reports. In limited data analysis, there was no statistically significant difference between participants in the active levetiracetam and placebo arm on the memory task.</p> </section> <section> <h3> Significance</h3> <p>This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease who do not have a history of seizures and has no detrimental effect on mood or quality of life. Larger studies are needed to assess whether levetiracetam may have a positive effect on cognitive function in subsets of individuals with Alzheimer's disease.</p> </section> <section> <h3> Plain Language Summary</h3> <p>Abnormal electrical activity within the brain, such as is seen in seizures, might contribute to memory problems in people with dementia. We completed a clinical trial to see if an antiseizure medication, levetiracetam, could help with memory difficulties in people with A
{"title":"Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double-blind placebo-controlled crossover trial","authors":"Arjune Sen, Sofia Toniolo, Xin You Tai, Mary Akinola, Mkael Symmonds, Sergio Mura, Joanne Galloway, Angela Hallam, Jane Y. C. Chan, Ivan Koychev, Chris Butler, John Geddes, Gabriel Davis Jones, Younes Tabi, Raquel Maio, Eleni Frangou, Sharon Love, Sian Thompson, Rohan Van Der Putt, Sanjay G. Manohar, Rupert McShane, Masud Husain","doi":"10.1002/epi4.13070","DOIUrl":"10.1002/epi4.13070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a randomized, double-blind, placebo-controlled crossover pilot study in individuals with mild-to-moderate Alzheimer's disease. Electroencephalography was performed at baseline and those with active epileptiform discharges were excluded. Eligible participants were randomized to placebo for 12 weeks or an active arm of oral levetiracetam (4 weeks up-titration to levetiracetam 500 mg twice daily, 4 weeks maintained on this dose followed by 4 weeks down-titration to nil). Participants then crossed over to the other arm. The primary outcome was change in cognitive function assessed by the Oxford Memory Task, a task sensitive to hippocampal memory binding. Secondary outcomes included tolerability, other neuropsychological scales, and general questionnaires.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Recruitment numbers were severely limited owing to restrictions from the COVID-19 pandemic at the time of the study. Eight participants completed both arms of the study (mean age 68.4 years [SD = 9.2]; 5 females [62.5%]). No participants withdrew from the study and there was no significant difference between reported side effects in the active levetiracetam or placebo arm. Measures of mood and quality of life were also not significantly different between the two arms based on participant or carer reports. In limited data analysis, there was no statistically significant difference between participants in the active levetiracetam and placebo arm on the memory task.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease who do not have a history of seizures and has no detrimental effect on mood or quality of life. Larger studies are needed to assess whether levetiracetam may have a positive effect on cognitive function in subsets of individuals with Alzheimer's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Abnormal electrical activity within the brain, such as is seen in seizures, might contribute to memory problems in people with dementia. We completed a clinical trial to see if an antiseizure medication, levetiracetam, could help with memory difficulties in people with A","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2353-2364"},"PeriodicalIF":2.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dong Ah Lee, Junghae Ko, Sung-Tae Kim, Ho-Joon Lee, Kang Min Park
<div> <section> <h3> Objectives</h3> <p>This study aimed to investigate the differences in structural connectivity and glymphatic system function between patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) and healthy controls. Additionally, we analyzed the association between structural connectivity, glymphatic system function, and antiseizure medication (ASM) response.</p> </section> <section> <h3> Methods</h3> <p>We retrospectively enrolled patients with TLE and HS and healthy controls who underwent diffusion tensor imaging at our hospital. We assessed structural connectivity in patients with TLE and HS and healthy controls by calculating network measures using graph theory and evaluated glymphatic system function using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Patients with TLE and HS were categorized into two groups: ASM poor and good responders.</p> </section> <section> <h3> Results</h3> <p>We enrolled 55 patients with TLE and HS and 53 healthy controls. Of the 55 patients with TLE and HS, 39 were ASM poor responders, and 16 were ASM good responders. The assortativity coefficient in patients with TLE and HS was higher than that in healthy controls (0.004 vs. −0.007, <i>p</i> = 0.004), and the assortativity coefficient in ASM poor responders was lower than that in ASM good responders (−0.001 vs. −0.197, <i>p</i> = 0.003). The DTI-ALPS index in patients with TLE and HS was lower than that in healthy controls (1.403 vs. 1.709, <i>p</i> < 0.001); however, the DTI-ALPS index did not differ between ASM poor and good responders (1.411 vs. 1.385, <i>p</i> = 0.628). The DTI-ALPS index had a significant negative correlation with age in patients with TLE and HS (<i>r</i> = −0.267, <i>p</i> = 0.049).</p> </section> <section> <h3> Significance</h3> <p>We confirmed increased assortativity coefficient in structural connectivity and decreased DTI-ALPS index in patients with TLE and HS compared with healthy controls. Additionally, we demonstrated an association between decreased assortativity coefficient in structural connectivity and ASM poor response in patients with TLE patients and HS.</p> </section> <section> <h3> Plain Language Summary</h3> <p>This study investigates the relationship between brain connectivity changes and glymphatic system function with antiseizure medication response in patients with temporal lobe epilepsy and hippocampal sclerosis. The research reveals that these patien
研究目的本研究旨在探讨颞叶癫痫（TLE）和海马硬化症（HS）患者与健康对照组在结构连接性和脑 glymphatic 系统功能方面的差异。此外，我们还分析了结构连接、脑 glymphatic 系统功能和抗癫痫药物（ASM）反应之间的关联：我们回顾性地纳入了在本院接受弥散张量成像检查的TLE和HS患者以及健康对照组。我们利用图论计算网络度量，评估了TLE和HS患者以及健康对照组的结构连接性，并利用沿血管周围空间的弥散张量图像分析（DTI-ALPS）指数评估了甘液系统功能。TLE和HS患者被分为两组：结果：我们招募了 55 名 TLE 和 HS 患者以及 53 名健康对照者。在55名TLE和HS患者中，39人为ASM反应差者，16人为ASM反应良好者。TLE和HS患者的同种异体系数高于健康对照组（0.004 vs. -0.007，p = 0.004），而ASM不良反应者的同种异体系数低于ASM良好反应者（-0.001 vs. -0.197，p = 0.003）。TLE和HS患者的DTI-ALPS指数低于健康对照组（1.403 vs. 1.709，p）：我们证实，与健康对照组相比，TLE 和 HS 患者的结构连通性中的同源性系数增加，DTI-ALPS 指数降低。此外，我们还证实了颞叶癫痫和海马硬化症患者结构连通性的同位系数降低与 ASM 反应不佳之间的关联。白话摘要：本研究调查了颞叶癫痫和海马硬化症患者大脑连通性变化和甘油系统功能与抗癫痫药物反应之间的关系。研究发现，与健康人相比，这些患者的大脑连接性和脑 glymphatic 功能发生了改变。研究的一个重要发现是，特定的连通性测量（同位系数）与抗癫痫药物反应之间存在密切联系，这为癫痫治疗和未来研究方向提供了宝贵的启示。
{"title":"The association between structural connectivity and anti-seizure medication response in patients with temporal lobe epilepsy","authors":"Dong Ah Lee, Junghae Ko, Sung-Tae Kim, Ho-Joon Lee, Kang Min Park","doi":"10.1002/epi4.13076","DOIUrl":"10.1002/epi4.13076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to investigate the differences in structural connectivity and glymphatic system function between patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) and healthy controls. Additionally, we analyzed the association between structural connectivity, glymphatic system function, and antiseizure medication (ASM) response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively enrolled patients with TLE and HS and healthy controls who underwent diffusion tensor imaging at our hospital. We assessed structural connectivity in patients with TLE and HS and healthy controls by calculating network measures using graph theory and evaluated glymphatic system function using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Patients with TLE and HS were categorized into two groups: ASM poor and good responders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We enrolled 55 patients with TLE and HS and 53 healthy controls. Of the 55 patients with TLE and HS, 39 were ASM poor responders, and 16 were ASM good responders. The assortativity coefficient in patients with TLE and HS was higher than that in healthy controls (0.004 vs. −0.007, <i>p</i> = 0.004), and the assortativity coefficient in ASM poor responders was lower than that in ASM good responders (−0.001 vs. −0.197, <i>p</i> = 0.003). The DTI-ALPS index in patients with TLE and HS was lower than that in healthy controls (1.403 vs. 1.709, <i>p</i> < 0.001); however, the DTI-ALPS index did not differ between ASM poor and good responders (1.411 vs. 1.385, <i>p</i> = 0.628). The DTI-ALPS index had a significant negative correlation with age in patients with TLE and HS (<i>r</i> = −0.267, <i>p</i> = 0.049).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>We confirmed increased assortativity coefficient in structural connectivity and decreased DTI-ALPS index in patients with TLE and HS compared with healthy controls. Additionally, we demonstrated an association between decreased assortativity coefficient in structural connectivity and ASM poor response in patients with TLE patients and HS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>This study investigates the relationship between brain connectivity changes and glymphatic system function with antiseizure medication response in patients with temporal lobe epilepsy and hippocampal sclerosis. The research reveals that these patien","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2408-2418"},"PeriodicalIF":2.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andres Schulze-Bonhage, Bernhard Steinhoff, Mercedes Garcés, Martin Hirsch, Vicente Villanueva
Objective
To assess antiseizure effects of cenobamate, a new antiseizure medication with at least two mechanisms of action, in the rare, highly pharmacoresistant and progressive epilepsy syndrome related to Rasmussen's encephalitis.
Methods
Three patients from the epilepsy centers in Freiburg, Kork, and Valencia are reported with focal epilepsy which had been pharmacoresistant to more than 10 prior treatment regimens. Assessment included at least 1 year of follow-up after cenobamate introduction and included seizure frequency, seizure severity (in particular status epilepticus) and changes in co-medication.
Results
In the three patients, cenobamate add on treatment proved superior to all prior antiseizure and immunomodulatory treatments which had been individually applied. Not only were focal to bilateral tonic–clonic seizure completely controlled, but also focal motor status epilepticus no longer occurred. Co-medication could be reduced in all patients.
Significance
This case series in a rare and highly pharmacoresistant epilepsy syndrome suggests high efficacy of cenobamate add-on treatment for seizure control. This may be a valuable information in epilepsy related to Rasmussen encephalitis and calls for further elucidation of the mechanism involved in superior seizure control also compared to prior treatments including sodium channel blockers and benzodiazepines.
Plain Language Summary
Rasmussen's encephalitis is a rare type of epilepsy that gets worse over time and doesn't respond well to most seizure medications. We describe three patients who tried many treatments without much success, but when they added cenobamate to their treatment, it worked better than the other medications. This also let them lower the overall amount of medication they were taking.
{"title":"Efficacy of add-on Cenobamate treatment in refractory epilepsy due to Rasmussen's encephalitis","authors":"Andres Schulze-Bonhage, Bernhard Steinhoff, Mercedes Garcés, Martin Hirsch, Vicente Villanueva","doi":"10.1002/epi4.13060","DOIUrl":"10.1002/epi4.13060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess antiseizure effects of cenobamate, a new antiseizure medication with at least two mechanisms of action, in the rare, highly pharmacoresistant and progressive epilepsy syndrome related to Rasmussen's encephalitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three patients from the epilepsy centers in Freiburg, Kork, and Valencia are reported with focal epilepsy which had been pharmacoresistant to more than 10 prior treatment regimens. Assessment included at least 1 year of follow-up after cenobamate introduction and included seizure frequency, seizure severity (in particular status epilepticus) and changes in co-medication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the three patients, cenobamate add on treatment proved superior to all prior antiseizure and immunomodulatory treatments which had been individually applied. Not only were focal to bilateral tonic–clonic seizure completely controlled, but also focal motor status epilepticus no longer occurred. Co-medication could be reduced in all patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This case series in a rare and highly pharmacoresistant epilepsy syndrome suggests high efficacy of cenobamate add-on treatment for seizure control. This may be a valuable information in epilepsy related to Rasmussen encephalitis and calls for further elucidation of the mechanism involved in superior seizure control also compared to prior treatments including sodium channel blockers and benzodiazepines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Rasmussen's encephalitis is a rare type of epilepsy that gets worse over time and doesn't respond well to most seizure medications. We describe three patients who tried many treatments without much success, but when they added cenobamate to their treatment, it worked better than the other medications. This also let them lower the overall amount of medication they were taking.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2537-2545"},"PeriodicalIF":2.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Armen Sargsyan, Pablo M. Casillas-Espinosa, Dmitri Melkonian, Terence J. O'Brien, Gilles van Luijtelaar
<div> <section> <h3> Objective</h3> <p>Frequency properties of the EEG characteristics of different seizure types including absence seizures have been described for various rodent models of epilepsy. However, little attention has been paid to the frequency properties of individual spike–wave complexes (SWCs), the constituting elements characterizing the different generalized seizure types. Knowledge of their properties is not only important for understanding the mechanisms underlying seizure generation but also for the identification of epileptiform activity in various seizure types. Here, we compared the frequency properties of SWCs in different epilepsy models.</p> </section> <section> <h3> Methods</h3> <p>A software package was designed and used for the extraction and frequency analysis of SWCs from long-term EEG of four spontaneously seizing, chronic epilepsy models: a post-status epilepticus model of temporal lobe epilepsy, a lateral fluid percussion injury model of post-traumatic epilepsy, and two genetic models of absence epilepsy—GAERS and rats of the WAG/Rij strain. The SWCs within the generalized seizures were separated into fast (three-phasic spike) and slow (mostly containing the wave) components. Eight animals from each model were used (32 recordings, 104 510 SWCs in total). A limitation of our study is that the recordings were hardware-filtered (high-pass), which could affect the frequency composition of the EEG.</p> </section> <section> <h3> Results</h3> <p>We found that the three-phasic spike component was similar in all animal models both in time and frequency domains, their amplitude spectra showed a single expressed peak at 18–20 Hz. The slow component showed a much larger variability across the rat models.</p> </section> <section> <h3> Significance</h3> <p>Despite differences in the morphology of the epileptiform activity in different models, the frequency composition of the spike component of single SWCs is identical and does not depend on the particular epilepsy model. This fact may be used for the development of universal algorithms for seizure detection applicable to different rat models of epilepsy.</p> </section> <section> <h3> Plain Language Summary</h3> <p>There is a large variety between people with epilepsy regarding the clinical manifestations and the electroencephalographic (EEG) phenomena accompanying the epileptic seizures. Here, we show that one of the EEG signs of epilepsy, an epileptic spike, is universal, since
{"title":"A spike is a spike: On the universality of spike features in four epilepsy models","authors":"Armen Sargsyan, Pablo M. Casillas-Espinosa, Dmitri Melkonian, Terence J. O'Brien, Gilles van Luijtelaar","doi":"10.1002/epi4.13062","DOIUrl":"10.1002/epi4.13062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Frequency properties of the EEG characteristics of different seizure types including absence seizures have been described for various rodent models of epilepsy. However, little attention has been paid to the frequency properties of individual spike–wave complexes (SWCs), the constituting elements characterizing the different generalized seizure types. Knowledge of their properties is not only important for understanding the mechanisms underlying seizure generation but also for the identification of epileptiform activity in various seizure types. Here, we compared the frequency properties of SWCs in different epilepsy models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A software package was designed and used for the extraction and frequency analysis of SWCs from long-term EEG of four spontaneously seizing, chronic epilepsy models: a post-status epilepticus model of temporal lobe epilepsy, a lateral fluid percussion injury model of post-traumatic epilepsy, and two genetic models of absence epilepsy—GAERS and rats of the WAG/Rij strain. The SWCs within the generalized seizures were separated into fast (three-phasic spike) and slow (mostly containing the wave) components. Eight animals from each model were used (32 recordings, 104 510 SWCs in total). A limitation of our study is that the recordings were hardware-filtered (high-pass), which could affect the frequency composition of the EEG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the three-phasic spike component was similar in all animal models both in time and frequency domains, their amplitude spectra showed a single expressed peak at 18–20 Hz. The slow component showed a much larger variability across the rat models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Despite differences in the morphology of the epileptiform activity in different models, the frequency composition of the spike component of single SWCs is identical and does not depend on the particular epilepsy model. This fact may be used for the development of universal algorithms for seizure detection applicable to different rat models of epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>There is a large variety between people with epilepsy regarding the clinical manifestations and the electroencephalographic (EEG) phenomena accompanying the epileptic seizures. Here, we show that one of the EEG signs of epilepsy, an epileptic spike, is universal, since","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2365-2377"},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Objective</h3> <p>Gut microbiota can traverse into the brain, activate the vagus nerve, and modulate immune responses and inflammatory processes, thereby influencing the onset of epileptic seizures. However, research on oral microbiota and epilepsy remains limited, and observational studies have been inconsistent. We aim to estimate the potential links between oral microbiota and epilepsy and elucidate which specific oral microbes may directly influence the pathogenesis of epilepsy.</p> </section> <section> <h3> Methods</h3> <p>A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to OM and epilepsy in East Asian individuals. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighed mode methods, were utilized. Sensitivity analysis, including Cochrane's <i>Q</i> test, MR-Egger intercept test, and leave-one-out analysis, was applied to confirm the robustness of results.</p> </section> <section> <h3> Results</h3> <p>Among the 3117 bacterial taxa examined, we observed that 14 OM, like <i>s_Streptococcus_mitis, s_Streptococcus_pneumoniae,</i> and <i>s_Haemophilus,</i> were positively associated with epilepsy, while 7 OM, like <i>g_Fusobacterium</i> and <i>g_Aggregatibacter,</i> were negatively related to epilepsy. The MR-Egger intercept suggested that no evidence of horizontal pleiotropy was observed (<i>p</i> > 0.05). The leave-one-out analysis validated the robustness of the results.</p> </section> <section> <h3> Significance</h3> <p>This study underscores the effect of OM on epilepsy, suggesting potential mechanisms between the OM and epilepsy. Further investigation into the potential role of the OM is needed to enhance our in-depth understanding of the pathogenesis of epilepsy.</p> </section> <section> <h3> Plain Language Summary</h3> <p>Previous research has demonstrated that the microbiota may influence the onset of epileptic seizures. We applied 3117 oral microbiota from the newest publicly available database of East Asian populations. Mendelian randomization analysis was utilized to estimate the causal relationship between oral microbiota and epilepsy. Our results showed that a causal effect exists between 21 oral microbiota and epilepsy. We provided genetic evidence for risk assessment and early intervention in ep
{"title":"Causal relationship between oral microbiota and epilepsy risk: Evidence from Mendelian randomization analysis in East Asians","authors":"Chenyang Zhao, Fei Chen, Qiong Li, Wei Zhang, Lixiu Peng, Chaoyan Yue","doi":"10.1002/epi4.13074","DOIUrl":"10.1002/epi4.13074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Gut microbiota can traverse into the brain, activate the vagus nerve, and modulate immune responses and inflammatory processes, thereby influencing the onset of epileptic seizures. However, research on oral microbiota and epilepsy remains limited, and observational studies have been inconsistent. We aim to estimate the potential links between oral microbiota and epilepsy and elucidate which specific oral microbes may directly influence the pathogenesis of epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to OM and epilepsy in East Asian individuals. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighed mode methods, were utilized. Sensitivity analysis, including Cochrane's <i>Q</i> test, MR-Egger intercept test, and leave-one-out analysis, was applied to confirm the robustness of results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 3117 bacterial taxa examined, we observed that 14 OM, like <i>s_Streptococcus_mitis, s_Streptococcus_pneumoniae,</i> and <i>s_Haemophilus,</i> were positively associated with epilepsy, while 7 OM, like <i>g_Fusobacterium</i> and <i>g_Aggregatibacter,</i> were negatively related to epilepsy. The MR-Egger intercept suggested that no evidence of horizontal pleiotropy was observed (<i>p</i> > 0.05). The leave-one-out analysis validated the robustness of the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This study underscores the effect of OM on epilepsy, suggesting potential mechanisms between the OM and epilepsy. Further investigation into the potential role of the OM is needed to enhance our in-depth understanding of the pathogenesis of epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Previous research has demonstrated that the microbiota may influence the onset of epileptic seizures. We applied 3117 oral microbiota from the newest publicly available database of East Asian populations. Mendelian randomization analysis was utilized to estimate the causal relationship between oral microbiota and epilepsy. Our results showed that a causal effect exists between 21 oral microbiota and epilepsy. We provided genetic evidence for risk assessment and early intervention in ep","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2419-2428"},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha Weber, Johannes Jungilligens, Selma Aybek, Stoyan Popkirov
<div> <section> <h3> Objective</h3> <p>Dissociative seizures are paroxysmal disruptions of awareness and behavioral control in the context of affective arousal. Alterations in stress-related endocrine function have been demonstrated, but the timescale of dissociation suggests that the central locus coeruleus (LC) noradrenergic system is likely pivotal. Here, we investigate whether LC activation at rest is associated with altered brain network dynamics.</p> </section> <section> <h3> Methods</h3> <p>A preliminary co-activation pattern (CAP) analysis of resting-state functional magnetic resonance imaging (fMRI) in 14 patients with dissociative seizures and 14 healthy controls was performed by using the LC as a seeding region. The red nucleus served as a control condition. Entry rates, durations, and state transition probabilities of identified CAPs were calculated. Analyses were corrected for demographic, technical, and clinical confounders including depression and anxiety.</p> </section> <section> <h3> Results</h3> <p>Three LC-related CAPs were identified, with the dominant two showing inverse activations and deactivations of the default mode network and the attention networks, respectively. Analysis of transition probabilities between and within the three CAPs revealed higher state persistence in patients compared to healthy controls for both CAP2<sub>LC</sub> (Cohen's <i>d</i> = −0.55; <i>p</i> = 0.01) and CAP3<sub>LC</sub> (Cohen's <i>d</i> = −0.57; <i>p</i> = 0.01). The control analysis using the red nucleus as a seed yielded similar CAPs, but no significant between-group differences in transition probabilities.</p> </section> <section> <h3> Significance</h3> <p>Higher state persistence of LC-CAPs in patients with dissociative seizures generates the novel hypothesis that arousal-related impairments of network switching might be a candidate neural mechanism of dissociation.</p> </section> <section> <h3> Plain Language Summary</h3> <p>Dissociative seizures often arise during high affective arousal. The locus coeruleus is a brain structure involved in managing such acute arousal states. We investigated whether the activity of the locus coeruleus correlates with activity in other regions of the brain (which we refer to as “brain states”), and whether those brain states were different between patients with dissociative seizures and healthy controls. We found that patients tended to stay in certain locus coeruleus-dependent brain states instead of swit
目的：解离性癫痫发作是在情感唤醒背景下意识和行为控制的阵发性中断。应激相关内分泌功能的改变已得到证实，但解离发作的时间尺度表明，中央区小脑去甲肾上腺素能系统可能起着关键作用。在此，我们研究了LC在静息状态下的激活是否与大脑网络动力学的改变有关：方法：以 LC 为播种区域，对 14 名分离性癫痫发作患者和 14 名健康对照者的静息态功能磁共振成像（fMRI）进行了初步的共激活模式（CAP）分析。红色核作为对照条件。计算了已识别 CAP 的进入率、持续时间和状态转换概率。分析对人口、技术和临床混杂因素（包括抑郁和焦虑）进行了校正：结果：发现了三种与低密度脂蛋白胆固醇相关的 CAPs，其中最主要的两种分别表现为默认模式网络和注意力网络的反向激活和失活。对三个CAP之间和内部的转换概率分析显示，与健康对照组相比，患者的CAP2LC（Cohen's d = -0.55；p = 0.01）和CAP3LC（Cohen's d = -0.57；p = 0.01）的状态持续性更高。以红色细胞核为种子进行对照分析的结果与 CAP 相似，但过渡概率在组间无显著差异：意义：解离性癫痫发作患者的 LC-CAPs 状态持续性较高，这提出了一个新的假设，即与唤醒相关的网络切换障碍可能是解离的一种候选神经机制。脑室小叶是参与管理这种急性唤醒状态的大脑结构。我们研究了局部小脑的活动是否与大脑其他区域的活动（我们称之为 "大脑状态"）相关，以及解离性癫痫发作患者与健康对照组之间的大脑状态是否有所不同。我们发现，患者倾向于停留在某些依赖于脑皮质的大脑状态，而不是在这些状态之间切换。这可能与患者在癫痫发作时意识丧失和大脑功能紊乱（"解离"）有关。
{"title":"Locus coeruleus co-activation patterns at rest show higher state persistence in patients with dissociative seizures: A Pilot Study","authors":"Samantha Weber, Johannes Jungilligens, Selma Aybek, Stoyan Popkirov","doi":"10.1002/epi4.13050","DOIUrl":"10.1002/epi4.13050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Dissociative seizures are paroxysmal disruptions of awareness and behavioral control in the context of affective arousal. Alterations in stress-related endocrine function have been demonstrated, but the timescale of dissociation suggests that the central locus coeruleus (LC) noradrenergic system is likely pivotal. Here, we investigate whether LC activation at rest is associated with altered brain network dynamics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A preliminary co-activation pattern (CAP) analysis of resting-state functional magnetic resonance imaging (fMRI) in 14 patients with dissociative seizures and 14 healthy controls was performed by using the LC as a seeding region. The red nucleus served as a control condition. Entry rates, durations, and state transition probabilities of identified CAPs were calculated. Analyses were corrected for demographic, technical, and clinical confounders including depression and anxiety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three LC-related CAPs were identified, with the dominant two showing inverse activations and deactivations of the default mode network and the attention networks, respectively. Analysis of transition probabilities between and within the three CAPs revealed higher state persistence in patients compared to healthy controls for both CAP2<sub>LC</sub> (Cohen's <i>d</i> = −0.55; <i>p</i> = 0.01) and CAP3<sub>LC</sub> (Cohen's <i>d</i> = −0.57; <i>p</i> = 0.01). The control analysis using the red nucleus as a seed yielded similar CAPs, but no significant between-group differences in transition probabilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Higher state persistence of LC-CAPs in patients with dissociative seizures generates the novel hypothesis that arousal-related impairments of network switching might be a candidate neural mechanism of dissociation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Dissociative seizures often arise during high affective arousal. The locus coeruleus is a brain structure involved in managing such acute arousal states. We investigated whether the activity of the locus coeruleus correlates with activity in other regions of the brain (which we refer to as “brain states”), and whether those brain states were different between patients with dissociative seizures and healthy controls. We found that patients tended to stay in certain locus coeruleus-dependent brain states instead of swit","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2331-2341"},"PeriodicalIF":2.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew J. Zillgitt, Eric R. Mong, Angelique M. Manasseh, Hannah C. Guider, Nour Baki, Michael D. Staudt
<div> <section> <h3> Objective</h3> <p>Temporal lobe encephaloceles (TLEN) have been implicated as a cause of temporal lobe epilepsy (TLE), the treatment which is primarily surgical; however, there is no clear consensus on the optimal surgical approach, because it is unclear whether TLE related to TLEN can be addressed by a restricted encephalocele resection or if a more extensive resection is required. The aim of the current article is to report the clinical and electrophysiological profile of patients with TLE secondary to TLEN who underwent stereotactic electroencephalography (SEEG) implantation to identify the epileptogenic network.</p> </section> <section> <h3> Methods</h3> <p>A retrospective review was performed of patients with TLE related to TLEN who underwent SEEG implantation. Medical charts were reviewed for demographic data, the results of noninvasive and invasive investigations, and operative details. Surgical outcomes were based on Engel classification with at least 6 months follow-up.</p> </section> <section> <h3> Results</h3> <p>Nine patients were identified. The mean age at epilepsy onset was 28 years (range, 15–41 years), and 7/9 patients were female. Scalp EEG revealed interictal epileptiform activity most often maximum in the frontotemporal and/or temporal regions. A discrete TLEN was often not identified on initial imaging, but was identified during re-review or at the time of surgery. Seizure onset zones during SEEG were localized to the mesial temporal structures, the temporal pole, or both. One patient became seizure-free following SEEG and another refused further surgery. Of the 7 patients who underwent epilepsy surgery, 5/7 underwent an anterior temporal lobectomy—surgical outcomes were favorable, with 5/7 achieving Engel I outcomes.</p> </section> <section> <h3> Significance</h3> <p>Invasive SEEG monitoring demonstrated ictal onsets may not be restricted to the TLEN, and often the temporal pole and mesial structures are involved at seizure onset. Ictal propagation patterns vary significantly, which may be related to the underlying pathology and explain the variability in semiology. These findings may inform surgical treatment options.</p> </section> <section> <h3> Plain language summary</h3> <p>Temporal lobe encephaloceles can cause intractable epilepsy, although their presence may be missed on routine imaging. The management of encephaloceles is primarily surgical; however, the optimal surgical approach can be unclear. I
{"title":"Exploration of epileptic networks in temporal lobe encephaloceles with stereotactic EEG: Electroclinical characteristics and surgical outcomes","authors":"Andrew J. Zillgitt, Eric R. Mong, Angelique M. Manasseh, Hannah C. Guider, Nour Baki, Michael D. Staudt","doi":"10.1002/epi4.13063","DOIUrl":"10.1002/epi4.13063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Temporal lobe encephaloceles (TLEN) have been implicated as a cause of temporal lobe epilepsy (TLE), the treatment which is primarily surgical; however, there is no clear consensus on the optimal surgical approach, because it is unclear whether TLE related to TLEN can be addressed by a restricted encephalocele resection or if a more extensive resection is required. The aim of the current article is to report the clinical and electrophysiological profile of patients with TLE secondary to TLEN who underwent stereotactic electroencephalography (SEEG) implantation to identify the epileptogenic network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective review was performed of patients with TLE related to TLEN who underwent SEEG implantation. Medical charts were reviewed for demographic data, the results of noninvasive and invasive investigations, and operative details. Surgical outcomes were based on Engel classification with at least 6 months follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nine patients were identified. The mean age at epilepsy onset was 28 years (range, 15–41 years), and 7/9 patients were female. Scalp EEG revealed interictal epileptiform activity most often maximum in the frontotemporal and/or temporal regions. A discrete TLEN was often not identified on initial imaging, but was identified during re-review or at the time of surgery. Seizure onset zones during SEEG were localized to the mesial temporal structures, the temporal pole, or both. One patient became seizure-free following SEEG and another refused further surgery. Of the 7 patients who underwent epilepsy surgery, 5/7 underwent an anterior temporal lobectomy—surgical outcomes were favorable, with 5/7 achieving Engel I outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Invasive SEEG monitoring demonstrated ictal onsets may not be restricted to the TLEN, and often the temporal pole and mesial structures are involved at seizure onset. Ictal propagation patterns vary significantly, which may be related to the underlying pathology and explain the variability in semiology. These findings may inform surgical treatment options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain language summary</h3>\u0000 \u0000 <p>Temporal lobe encephaloceles can cause intractable epilepsy, although their presence may be missed on routine imaging. The management of encephaloceles is primarily surgical; however, the optimal surgical approach can be unclear. I","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2395-2407"},"PeriodicalIF":2.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p> Translational Epilepsy Summer School 2024 </p><p>21–25 October 2024</p><p>Subang Jaya, Malaysia</p><p> ASEPA SEEG Workshop and DIXI SEEG Course </p><p>October 30 to November 3, 2024</p><p>Bangkok, Thailand</p><p> Pediatric Epilepsy Surgery: From basics to advancements </p><p>November 7–10, 2024</p><p>Cochin, India</p><p> 7th East Mediterranean Epilepsy Congress </p><p>12–15 December 2024</p><p>Baghdad, Iraq</p><p> 14th ILAE School on Pre-Surgical Evaluation for Epilepsy and Epilepsy Surgery </p><p>January 20–24, 2025</p><p>Brno, Czech Republic</p><p> 15th Asian & Oceanian Epilepsy Congress </p><p>February 20–23, 2025</p><p>New Delhi, India</p><p> 5th African Epilepsy Congress </p><p>May 1–31, 2025</p><p>Africa</p><p> XVIII Workshop on Neurobiology of Epilepsy (WONOEP 2025) </p><p>August 25–29, 2025</p><p>Portugal</p><p> 36th International Epilepsy Congress </p><p>August 30 to September 3, 2025</p><p>Lisbon, Portugal</p><p> 16th European Epilepsy Congress </p><p>5–9 September 2026</p><p>Athens, Greece</p><p> Approach to Difficult to Treat Epilepsies </p><p>3 October 2024</p><p> Webinaire éducatif sur l'épilepsie en français </p><p>8 October 2024</p><p> How to talk about SUDEP </p><p>23 October 2024</p><p> ILAE e-Forum: Optimal timing for epilepsy surgery </p><p>November 25, 2024</p><p> Chirurgie de l’epilépsie </p><p>1–2 October 2024</p><p>Tunisia</p><p> 26èmes Journées Françaises de l'Epilepsie </p><p>October 8–11, 2024</p><p>Marseille, France</p><p> Epilepsy Training Course </p><p>October 10–11, 2024</p><p>Medan, Indonesia</p><p> Cours épilepsie et EEG pour les médecins de première ligne </p><p>October 11–12, 2024</p><p>Sfax, Tunisie</p><p> Cairo – Epilepsy Workshop </p><p>October 16, 2024</p><p>Cairo, Egypt</p><p> Epilepsy Training Course </p><p>October 18–20, 2024</p><p>Douala, Cameroon</p><p> 2ème Journée de la Société Malienne des Neurosciences </p><p>19 October 2024</p><p>Bamako, Mali</p><p> 2024 ILAE British Branch Annual Scientific Meeting </p><p>October 21–23, 2024</p><p>Liverpool, UK</p><p> SEEG Course 2024 </p><p>October 31 to November 2, 2024</p><p>Thailand</p><p> 2nd Annual Canadian Paediatric SEEG Conference </p><p>November 1–3, 2024</p><p>London, Ontario, Canada</p><p> Epilepsy Society of Australia Annual Scientific Meeting 2024 </p><p>November 6–8, 2024</p><p>Hobart, Tasmania, Australia</p><p> 2nd Advanced Course on the Ph
{"title":"Epilepsia open—October 2024 announcements","authors":"","doi":"10.1002/epi4.13059","DOIUrl":"https://doi.org/10.1002/epi4.13059","url":null,"abstract":"<p>\u0000 Translational Epilepsy Summer School 2024\u0000 </p><p>21–25 October 2024</p><p>Subang Jaya, Malaysia</p><p>\u0000 ASEPA SEEG Workshop and DIXI SEEG Course\u0000 </p><p>October 30 to November 3, 2024</p><p>Bangkok, Thailand</p><p>\u0000 Pediatric Epilepsy Surgery: From basics to advancements\u0000 </p><p>November 7–10, 2024</p><p>Cochin, India</p><p>\u0000 7th East Mediterranean Epilepsy Congress\u0000 </p><p>12–15 December 2024</p><p>Baghdad, Iraq</p><p>\u0000 14th ILAE School on Pre-Surgical Evaluation for Epilepsy and Epilepsy Surgery\u0000 </p><p>January 20–24, 2025</p><p>Brno, Czech Republic</p><p>\u0000 15th Asian & Oceanian Epilepsy Congress\u0000 </p><p>February 20–23, 2025</p><p>New Delhi, India</p><p>\u0000 5th African Epilepsy Congress\u0000 </p><p>May 1–31, 2025</p><p>Africa</p><p>\u0000 XVIII Workshop on Neurobiology of Epilepsy (WONOEP 2025)\u0000 </p><p>August 25–29, 2025</p><p>Portugal</p><p>\u0000 36th International Epilepsy Congress\u0000 </p><p>August 30 to September 3, 2025</p><p>Lisbon, Portugal</p><p>\u0000 16th European Epilepsy Congress\u0000 </p><p>5–9 September 2026</p><p>Athens, Greece</p><p>\u0000 Approach to Difficult to Treat Epilepsies\u0000 </p><p>3 October 2024</p><p>\u0000 Webinaire éducatif sur l'épilepsie en français\u0000 </p><p>8 October 2024</p><p>\u0000 How to talk about SUDEP\u0000 </p><p>23 October 2024</p><p>\u0000 ILAE e-Forum: Optimal timing for epilepsy surgery\u0000 </p><p>November 25, 2024</p><p>\u0000 Chirurgie de l’epilépsie\u0000 </p><p>1–2 October 2024</p><p>Tunisia</p><p>\u0000 26èmes Journées Françaises de l'Epilepsie\u0000 </p><p>October 8–11, 2024</p><p>Marseille, France</p><p>\u0000 Epilepsy Training Course\u0000 </p><p>October 10–11, 2024</p><p>Medan, Indonesia</p><p>\u0000 Cours épilepsie et EEG pour les médecins de première ligne\u0000 </p><p>October 11–12, 2024</p><p>Sfax, Tunisie</p><p>\u0000 Cairo – Epilepsy Workshop\u0000 </p><p>October 16, 2024</p><p>Cairo, Egypt</p><p>\u0000 Epilepsy Training Course\u0000 </p><p>October 18–20, 2024</p><p>Douala, Cameroon</p><p>\u0000 2ème Journée de la Société Malienne des Neurosciences\u0000 </p><p>19 October 2024</p><p>Bamako, Mali</p><p>\u0000 2024 ILAE British Branch Annual Scientific Meeting\u0000 </p><p>October 21–23, 2024</p><p>Liverpool, UK</p><p>\u0000 SEEG Course 2024\u0000 </p><p>October 31 to November 2, 2024</p><p>Thailand</p><p>\u0000 2nd Annual Canadian Paediatric SEEG Conference\u0000 </p><p>November 1–3, 2024</p><p>London, Ontario, Canada</p><p>\u0000 Epilepsy Society of Australia Annual Scientific Meeting 2024\u0000 </p><p>November 6–8, 2024</p><p>Hobart, Tasmania, Australia</p><p>\u0000 2nd Advanced Course on the Ph","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 5","pages":"2003-2005"},"PeriodicalIF":2.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epi4.13059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesca Furia, Katrine M. Johannesen, Claudia M. Bonardi, Roberto Previtali, Angel Aledo-Serrano, Massimo Mastrangelo, Jacopo Favaro, Silvia Masnada, Valentina di Micco, Jacopo Proietti, Pierangelo Veggiotti, Guido Rubboli, Gaetano Cantalupo, Kern Olofsson, Rikke S. Møller, Elena Gardella
<p><i>SCN8A</i> encodes the voltage-gated sodium channel subunit Nav1.6, which is expressed in the brain.<span><sup>1</sup></span> Neuronal hyperexcitability, seizures, and neurocognitive problems are the result of impaired Nav1.6 channel inactivation.<span><sup>2, 3</sup></span> Pathogenic variants in the <i>SCN8A</i> gene are frequently related to epilepsy, ranging from self-limiting epilepsies<span><sup>4, 5</sup></span> to severe developmental and epileptic encephalopathies (DEE)<span><sup>6</sup></span> often refractory to anti-seizure medications (ASM).<span><sup>7-9</sup></span> Gardella and Møller described for the first time the phenotypic spectrum of <i>SCN8A</i>-related disorders detailing the distinguishing features of different sub-phenotypes.<span><sup>4-6, 10</sup></span></p><p>Epileptic seizures and sleep quality have a complex bidirectional relationship; in people with DEE, comorbidities such as intellectual disability, attention deficit, and movement disorder add complexity to this interaction.<span><sup>11, 12</sup></span> Significant sleep disturbances are often observed in patients with DEE, causing major disruption to their quality of life.<span><sup>13</sup></span> Although sleep disturbances are frequently reported in patients with genetic epilepsies, only few studies exploring this issue have been performed.<span><sup>14-17</sup></span></p><p>Studies in <i>SCN8A</i> as well as <i>SCN1A</i> mice models showed sleep disturbances, such as increased NREM and decreased REM sleep.<span><sup>18, 19</sup></span> Additionally, the mice displayed altered circadian rhythm of corticosterone secretion, with lowered and flattened diurnal level, indicating hypofunctioning hypothalamic–pituitary–adrenal (HPA) axis, and suggesting a sodium channels' role in sleep regulation.<span><sup>18, 19</sup></span></p><p>Our study aims to characterize the prevalence and nature of sleep disturbance in patients with different <i>SCN8A-</i>related disorders.</p><p>We enrolled patients with <i>SCN8A</i>-related disorders through a network of physicians and caregivers in Europe and in the USA (14 centers). We included all patients with pathogenic <i>SCN8A</i> variants, with available electro-clinical data, and excluded patients with <i>SCN8A</i> variants of uncertain significance and the ones who did not accept to participate in the study. We reviewed their medical history including demographic and genetic data, epilepsy features, cognitive and motor development, and relevant comorbidities. Information about seizures (types, frequency, and timing—specifically wakefulness versus sleep predominance), seizure control, and medications (anti-seizure and sleep medications) were obtained through a semi-structured spreadsheet.</p><p>Since the <i>SCN8A</i> phenotypic spectrum is extremely heterogeneous, using phenotypic subgroups is of pivotal importance. As we previously described based on large cohort studies,<span><sup>6, 10</sup></span> the patients were divi
{"title":"Sleep disturbances in SCN8A-related disorders","authors":"Francesca Furia, Katrine M. Johannesen, Claudia M. Bonardi, Roberto Previtali, Angel Aledo-Serrano, Massimo Mastrangelo, Jacopo Favaro, Silvia Masnada, Valentina di Micco, Jacopo Proietti, Pierangelo Veggiotti, Guido Rubboli, Gaetano Cantalupo, Kern Olofsson, Rikke S. Møller, Elena Gardella","doi":"10.1002/epi4.13042","DOIUrl":"10.1002/epi4.13042","url":null,"abstract":"<p><i>SCN8A</i> encodes the voltage-gated sodium channel subunit Nav1.6, which is expressed in the brain.<span><sup>1</sup></span> Neuronal hyperexcitability, seizures, and neurocognitive problems are the result of impaired Nav1.6 channel inactivation.<span><sup>2, 3</sup></span> Pathogenic variants in the <i>SCN8A</i> gene are frequently related to epilepsy, ranging from self-limiting epilepsies<span><sup>4, 5</sup></span> to severe developmental and epileptic encephalopathies (DEE)<span><sup>6</sup></span> often refractory to anti-seizure medications (ASM).<span><sup>7-9</sup></span> Gardella and Møller described for the first time the phenotypic spectrum of <i>SCN8A</i>-related disorders detailing the distinguishing features of different sub-phenotypes.<span><sup>4-6, 10</sup></span></p><p>Epileptic seizures and sleep quality have a complex bidirectional relationship; in people with DEE, comorbidities such as intellectual disability, attention deficit, and movement disorder add complexity to this interaction.<span><sup>11, 12</sup></span> Significant sleep disturbances are often observed in patients with DEE, causing major disruption to their quality of life.<span><sup>13</sup></span> Although sleep disturbances are frequently reported in patients with genetic epilepsies, only few studies exploring this issue have been performed.<span><sup>14-17</sup></span></p><p>Studies in <i>SCN8A</i> as well as <i>SCN1A</i> mice models showed sleep disturbances, such as increased NREM and decreased REM sleep.<span><sup>18, 19</sup></span> Additionally, the mice displayed altered circadian rhythm of corticosterone secretion, with lowered and flattened diurnal level, indicating hypofunctioning hypothalamic–pituitary–adrenal (HPA) axis, and suggesting a sodium channels' role in sleep regulation.<span><sup>18, 19</sup></span></p><p>Our study aims to characterize the prevalence and nature of sleep disturbance in patients with different <i>SCN8A-</i>related disorders.</p><p>We enrolled patients with <i>SCN8A</i>-related disorders through a network of physicians and caregivers in Europe and in the USA (14 centers). We included all patients with pathogenic <i>SCN8A</i> variants, with available electro-clinical data, and excluded patients with <i>SCN8A</i> variants of uncertain significance and the ones who did not accept to participate in the study. We reviewed their medical history including demographic and genetic data, epilepsy features, cognitive and motor development, and relevant comorbidities. Information about seizures (types, frequency, and timing—specifically wakefulness versus sleep predominance), seizure control, and medications (anti-seizure and sleep medications) were obtained through a semi-structured spreadsheet.</p><p>Since the <i>SCN8A</i> phenotypic spectrum is extremely heterogeneous, using phenotypic subgroups is of pivotal importance. As we previously described based on large cohort studies,<span><sup>6, 10</sup></span> the patients were divi","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2186-2197"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicola Specchio, Stéphane Auvin, Adam Strzelczyk, Francesco Brigo, Vicente Villanueva, Eugen Trinka
Status epilepticus (SE) is a life-threatening emergency with high morbidity and mortality. In people with epilepsy, the management of SE is focused on early medical treatment. Stiripentol is a third-generation antiseizure medication (ASM) approved for refractory generalized tonic–clonic seizures in Dravet syndrome. The aim of this systematic review was to evaluate the effectiveness and safety of stiripentol in reducing the incidence of SE in patients with Dravet syndrome or any epilepsy characterized by recurrent SE. The PubMed and Cochrane databases were systematically searched, and gray literature was hand-searched. Search results were screened by title and abstract; studies with data on the effect of stiripentol on SE outcomes, including the cessation of SE, reduction in number of SE episodes, or reduction in hospitalizations, were included. Of 66 records identified, 17 studies were eligible for inclusion, of which 15 were human studies (n = 474; aged 1.1–78 years), and two were animal experiments. Results of retrospective or prospective observational studies showed that stiripentol as add-on therapy to ASMs such as clobazam or valproate reduced the incidence of SE in patients with Dravet syndrome or other developmental and epileptic encephalopathies (DEEs). A mean of 68% of patients (range 41%–100%) had a ≥50% reduction in SE episodes from baseline, and 26%–100% of patients (mean 77%) became SE-free after stiripentol initiation. Moreover, this review found stiripentol, used as acute treatment, may also be effective for the cessation of super-refractory SE, but data are limited to three retrospective case series. Stiripentol was generally well-tolerated. In conclusion, stiripentol reduces the incidence of SE episodes in patients with Dravet syndrome and potentially other DEEs, and it promotes cessation of super-refractory SE in patients with and without a history of seizures.
Plain Language Summary
Status epilepticus (SE) is a life-threatening, long-lasting seizure occurring in patients with/without epilepsy. This article analyzed 15 published studies that investigated the effects and safety of the anti-seizure medication stiripentol for preventing SE in epilepsy patients (prevention) or stopping an SE episode (cessation), and two animal studies that investigated how stiripentol works. In epilepsy patients, stiripentol halved the number of SE episodes in 41–100% of patients, 26–100% of patients became SE-free, and stiripentol was considered to be well tolerated. In patients with/without epilepsy, stiripentol may stop the SE episode after other drugs like anesthetics have not worked.
癫痫状态（SE）是一种危及生命的急症，发病率和死亡率都很高。对于癫痫患者来说，SE 的治疗重点在于早期药物治疗。斯替潘托是一种第三代抗癫痫药物（ASM），已被批准用于治疗德雷维综合征的难治性全身强直-阵挛发作。本系统综述的目的是评估斯奇潘托在降低德雷维综合征或任何以复发性 SE 为特征的癫痫患者 SE 发生率方面的有效性和安全性。我们对 PubMed 和 Cochrane 数据库进行了系统检索，并对灰色文献进行了手工检索。根据标题和摘要对检索结果进行筛选；纳入了有关斯奇潘托对 SE 结果（包括 SE 停止、SE 发作次数减少或住院次数减少）影响的研究数据。在确定的 66 条记录中，有 17 项研究符合纳入条件，其中 15 项为人类研究（n = 474；年龄 1.1-78 岁），2 项为动物实验。回顾性或前瞻性观察研究的结果表明，在氯巴扎铵或丙戊酸钠等 ASMs 的基础上加用司立潘妥，可降低德雷维综合征或其他发育性和癫痫性脑病（DEEs）患者 SE 的发病率。平均68%的患者（41%-100%）的SE发作次数比基线减少了≥50%，26%-100%的患者（平均77%）在开始使用司立潘妥后不再出现SE。此外，该综述还发现，作为急性治疗使用的斯利潘托也可有效阻止超难治性SE，但数据仅限于三个回顾性病例系列。施替潘托的耐受性普遍良好。总之，斯替潘托可降低德雷维综合征患者和其他可能患有德雷维综合征的患者的SE发作率，并可促进有癫痫发作史和无癫痫发作史的患者停止超级难治性SE。白话摘要：癫痫状态（SE）是一种危及生命、持续时间较长的癫痫发作，多发于癫痫患者/无癫痫患者。本文分析了 15 项已发表的研究，这些研究调查了抗癫痫药物斯奇潘托对预防癫痫患者癫痫发作（预防）或停止癫痫发作（停止）的效果和安全性，以及两项调查斯奇潘托如何发挥作用的动物实验。在癫痫患者中，41%-100%的患者使用斯奇潘托后SE发作次数减少了一半，26%-100%的患者不再发作SE，并且认为斯奇潘托具有良好的耐受性。对于患有/不患有癫痫的患者，在麻醉剂等其他药物不起作用后，斯奇潘托可能会阻止癫痫发作。
{"title":"Efficacy and safety of stiripentol in the prevention and cessation of status epilepticus: A systematic review","authors":"Nicola Specchio, Stéphane Auvin, Adam Strzelczyk, Francesco Brigo, Vicente Villanueva, Eugen Trinka","doi":"10.1002/epi4.13036","DOIUrl":"10.1002/epi4.13036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Status epilepticus (SE) is a life-threatening emergency with high morbidity and mortality. In people with epilepsy, the management of SE is focused on early medical treatment. Stiripentol is a third-generation antiseizure medication (ASM) approved for refractory generalized tonic–clonic seizures in Dravet syndrome. The aim of this systematic review was to evaluate the effectiveness and safety of stiripentol in reducing the incidence of SE in patients with Dravet syndrome or any epilepsy characterized by recurrent SE. The PubMed and Cochrane databases were systematically searched, and gray literature was hand-searched. Search results were screened by title and abstract; studies with data on the effect of stiripentol on SE outcomes, including the cessation of SE, reduction in number of SE episodes, or reduction in hospitalizations, were included. Of 66 records identified, 17 studies were eligible for inclusion, of which 15 were human studies (<i>n</i> = 474; aged 1.1–78 years), and two were animal experiments. Results of retrospective or prospective observational studies showed that stiripentol as add-on therapy to ASMs such as clobazam or valproate reduced the incidence of SE in patients with Dravet syndrome or other developmental and epileptic encephalopathies (DEEs). A mean of 68% of patients (range 41%–100%) had a ≥50% reduction in SE episodes from baseline, and 26%–100% of patients (mean 77%) became SE-free after stiripentol initiation. Moreover, this review found stiripentol, used as acute treatment, may also be effective for the cessation of super-refractory SE, but data are limited to three retrospective case series. Stiripentol was generally well-tolerated. In conclusion, stiripentol reduces the incidence of SE episodes in patients with Dravet syndrome and potentially other DEEs, and it promotes cessation of super-refractory SE in patients with and without a history of seizures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Status epilepticus (SE) is a life-threatening, long-lasting seizure occurring in patients with/without epilepsy. This article analyzed 15 published studies that investigated the effects and safety of the anti-seizure medication stiripentol for preventing SE in epilepsy patients (prevention) or stopping an SE episode (cessation), and two animal studies that investigated how stiripentol works. In epilepsy patients, stiripentol halved the number of SE episodes in 41–100% of patients, 26–100% of patients became SE-free, and stiripentol was considered to be well tolerated. In patients with/without epilepsy, stiripentol may stop the SE episode after other drugs like anesthetics have not worked.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2017-2036"},"PeriodicalIF":2.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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