Pub Date : 2024-08-29DOI: 10.1016/j.seizure.2024.08.023
Yi Zhang , Ginger Qinghong Zeng , Ruodi Lu , Xiaofei Ye , Xiaochu Zhang
Sleep deprivation has been studied as a method to induce sleep before EEG testing to improve the diagnosis of epilepsy. However, the effectiveness of sleep deprivation in diagnosing epilepsy through EEG in humans showed conflicting findings in previous studies. This meta-analysis aimed to provide statistical evidence for the diagnostic value of sleep-deprived EEG in epilepsy. A systematic search of the Web of Science and PubMed databases identified 12 relevant studies from May 1997 to the present. These studies were included to examine the diagnostic value of sleep-deprived EEG in epilepsy and its associated clinical variables, such as patient age, duration of sleep deprivation, and EEG recording duration. The results of the random effects model did not show a significant overall diagnostic effect for sleep-deprived EEG in epilepsy, but revealed high heterogeneity among the studies. Notably, this heterogeneity was not accounted for by the clinical variables analyzed. Upon excluding outliers, a trend suggesting a modest diagnostic value of sleep-deprived EEG emerged. The high heterogeneity among studies indicates the need for a standardized protocol for sleep deprivation in future studies. Overall, while sleep deprivation may have a small positive effect on EEG-based epilepsy diagnosis, further research is needed to better understand its impact and optimize its use in clinical practice.
睡眠剥夺法是一种在脑电图测试前诱导睡眠以改善癫痫诊断的方法。然而,在以往的研究中,睡眠剥夺对通过脑电图诊断人类癫痫的有效性显示出相互矛盾的结果。本荟萃分析旨在为睡眠剥夺脑电图在癫痫诊断中的价值提供统计学证据。通过对 Web of Science 和 PubMed 数据库进行系统搜索,发现了 1997 年 5 月至今的 12 项相关研究。纳入这些研究是为了考察睡眠剥夺脑电图对癫痫的诊断价值及其相关临床变量,如患者年龄、睡眠剥夺持续时间和脑电图记录持续时间。随机效应模型的结果表明,睡眠剥夺脑电图对癫痫的总体诊断效果并不显著,但却显示出研究之间的高度异质性。值得注意的是,分析的临床变量并不能解释这种异质性。在排除异常值后,出现了一种趋势,表明睡眠剥夺脑电图具有适度的诊断价值。各研究之间的高度异质性表明,在未来的研究中需要对睡眠剥夺制定标准化方案。总之,虽然剥夺睡眠可能对基于脑电图的癫痫诊断有微小的积极影响,但仍需进一步研究,以更好地了解其影响并优化其在临床实践中的应用。
{"title":"The diagnostic value of sleep-deprived EEG in epilepsy: A meta-analysis","authors":"Yi Zhang , Ginger Qinghong Zeng , Ruodi Lu , Xiaofei Ye , Xiaochu Zhang","doi":"10.1016/j.seizure.2024.08.023","DOIUrl":"10.1016/j.seizure.2024.08.023","url":null,"abstract":"<div><p>Sleep deprivation has been studied as a method to induce sleep before EEG testing to improve the diagnosis of epilepsy. However, the effectiveness of sleep deprivation in diagnosing epilepsy through EEG in humans showed conflicting findings in previous studies. This meta-analysis aimed to provide statistical evidence for the diagnostic value of sleep-deprived EEG in epilepsy. A systematic search of the Web of Science and PubMed databases identified 12 relevant studies from May 1997 to the present. These studies were included to examine the diagnostic value of sleep-deprived EEG in epilepsy and its associated clinical variables, such as patient age, duration of sleep deprivation, and EEG recording duration. The results of the random effects model did not show a significant overall diagnostic effect for sleep-deprived EEG in epilepsy, but revealed high heterogeneity among the studies. Notably, this heterogeneity was not accounted for by the clinical variables analyzed. Upon excluding outliers, a trend suggesting a modest diagnostic value of sleep-deprived EEG emerged. The high heterogeneity among studies indicates the need for a standardized protocol for sleep deprivation in future studies. Overall, while sleep deprivation may have a small positive effect on EEG-based epilepsy diagnosis, further research is needed to better understand its impact and optimize its use in clinical practice.</p></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 211-216"},"PeriodicalIF":2.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.1016/j.seizure.2024.08.021
Heidrun Potschka
While late-onset epilepsies are characterized by a good pharmacoresponsiveness, a relevant subgroup of this patient population suffers from drug-refractory epilepsy with its impact on overall quality of life and a high risk of seizure-related injuries. Particular attention should be paid to accurate diagnosis and thorough exclusion of pseudoresistance. Challenges include the likelihood of multimorbidities and polypharmacotherapy in an elderly patient population. Network, cellular, molecular, and metabolic alterations associated with aging and age-related disorders have the potential to affect the intrinsic severity of late-onset epilepsies, neural network function, and the pharmacodynamics and pharmacokinetics of antiseizure medications (ASMs). Whereas age-related changes in pharmacokinetics tend to favor responsiveness to low doses, respective changes in network excitability and pharmacodynamics of ASMs are more likely to contribute to drug resistance. There are particular gaps in our knowledge of the mechanisms of drug resistance and the impact of influencing factors in this patient population. Therefore, experimental and clinical research needs to be intensified to advance our understanding of drug-resistant epilepsy in patients with late-onset epilepsies and to develop multivariate prediction algorithms. In this context, the heterogeneity of an elderly patient population should be taken into account, considering differences in etiology, comorbidities, co-medications, frailty, activity and environmental factors.
{"title":"The aging brain and late onset drug-refractory epilepsies.","authors":"Heidrun Potschka","doi":"10.1016/j.seizure.2024.08.021","DOIUrl":"https://doi.org/10.1016/j.seizure.2024.08.021","url":null,"abstract":"<p><p>While late-onset epilepsies are characterized by a good pharmacoresponsiveness, a relevant subgroup of this patient population suffers from drug-refractory epilepsy with its impact on overall quality of life and a high risk of seizure-related injuries. Particular attention should be paid to accurate diagnosis and thorough exclusion of pseudoresistance. Challenges include the likelihood of multimorbidities and polypharmacotherapy in an elderly patient population. Network, cellular, molecular, and metabolic alterations associated with aging and age-related disorders have the potential to affect the intrinsic severity of late-onset epilepsies, neural network function, and the pharmacodynamics and pharmacokinetics of antiseizure medications (ASMs). Whereas age-related changes in pharmacokinetics tend to favor responsiveness to low doses, respective changes in network excitability and pharmacodynamics of ASMs are more likely to contribute to drug resistance. There are particular gaps in our knowledge of the mechanisms of drug resistance and the impact of influencing factors in this patient population. Therefore, experimental and clinical research needs to be intensified to advance our understanding of drug-resistant epilepsy in patients with late-onset epilepsies and to develop multivariate prediction algorithms. In this context, the heterogeneity of an elderly patient population should be taken into account, considering differences in etiology, comorbidities, co-medications, frailty, activity and environmental factors.</p>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 10.1016/j.seizure.2024.08.020
Kirsty H T Phillips , Karalyn Patterson , Christopher R Butler , Emma Woodberry , Matthew A Lambon Ralph , Thomas E Cope
Despite the recognition that epilepsy can substantially disrupt memory, there are few published accounts of whether and how this disruption varies across different types of memory and/or different types of epilepsy. This review explores four main questions: (1) Are working, episodic and semantic memory differentially affected by epilepsy? (2) Do various types of epilepsy, and their treatment, have different, specifiable effects on memory? (3) Are the usual forms of neuropsychological assessments of memory – many or most designed for other conditions – appropriate for patients with epilepsy? (4) How can research on epilepsy contribute to our understanding of the neuroscience of memory?
We conclude that widespread and multifactorial problems are seen in working memory in all patient groups, while patients with temporal lobe epilepsy seem particularly prone to episodic memory deficit, and those with frontal lobe epilepsy to executive function deficits that may in turn impair semantic control. Currently, it is difficult to make individual patient predictions about likely memory deficits based on seizure aetiology and type, but it is possible to guide and tailor neuropsychological assessments in an individualised way. We make recommendations for future directions in validating and optimising neuropsychological assessments, and consider how to approach effective shared decision making about the pros and cons of seizure treatment strategies, especially at crucial educational stages such as adolescence.
{"title":"Does epilepsy differentially affect different types of memory?","authors":"Kirsty H T Phillips , Karalyn Patterson , Christopher R Butler , Emma Woodberry , Matthew A Lambon Ralph , Thomas E Cope","doi":"10.1016/j.seizure.2024.08.020","DOIUrl":"10.1016/j.seizure.2024.08.020","url":null,"abstract":"<div><p>Despite the recognition that epilepsy can substantially disrupt memory, there are few published accounts of whether and how this disruption varies across different types of memory and/or different types of epilepsy. This review explores four main questions: (1) Are working, episodic and semantic memory differentially affected by epilepsy? (2) Do various types of epilepsy, and their treatment, have different, specifiable effects on memory? (3) Are the usual forms of neuropsychological assessments of memory – many or most designed for other conditions – appropriate for patients with epilepsy? (4) How can research on epilepsy contribute to our understanding of the neuroscience of memory?</p><p>We conclude that widespread and multifactorial problems are seen in working memory in all patient groups, while patients with temporal lobe epilepsy seem particularly prone to episodic memory deficit, and those with frontal lobe epilepsy to executive function deficits that may in turn impair semantic control. Currently, it is difficult to make individual patient predictions about likely memory deficits based on seizure aetiology and type, but it is possible to guide and tailor neuropsychological assessments in an individualised way. We make recommendations for future directions in validating and optimising neuropsychological assessments, and consider how to approach effective shared decision making about the pros and cons of seizure treatment strategies, especially at crucial educational stages such as adolescence.</p></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 217-225"},"PeriodicalIF":2.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1059131124002437/pdfft?md5=c5f668e018c15654330c5ae192f3d279&pid=1-s2.0-S1059131124002437-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146686","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}
The objective of this study is to characterize the electro-clinical phenotype of individuals affected by the rare PPP3CA gene-related developmental and epileptic encephalopathy (DEE).
Methods
We provide a detailed electro-clinical description of four previously unreported subjects, with unremarkable structural brain MRI and a normal screening for inborn errors of metabolism, who carry pathogenic variants within the regulatory domain of the PPP3CA gene, which encodes for calcineurin. We also conducted a literature review via PubMed and SCOPUS (up to December 2023) to collect all the studies reporting clinical details of subjects with PPP3CA pathogenic variants within the regulatory domain.
Results
Our in-depth investigation reveals two distinct electro-clinical phenotypes with unique interictal and ictal patterns. Pathogenic variants within the calmodulin-binding domain result in childhood-onset epilepsy with focal and generalized seizures, developmental and intellectual impairments. Pathogenic variants within the regulatory domain lead to early onset drug-resistant severe epilepsy and potentially fatal outcomes. Comparative analysis with existing literature corroborates the notion that truncating mutations, prevalent in the regulatory domain but also possible in the calmodulin-binding domain, consistently associate with more profound disabilities and drug-resistant epilepsy.
Conclusion
Our study emphasizes the critical role of pathogenic variants’ type and location on the severity of PPP3CA-related DEE. We also speculate, based on peculiar EEG patterns, on potential pathophysiological mechanisms involving calcineurin dysfunction and calcium homeostasis. In order to improve our understanding of this rare DEE, we need both collaborative efforts to gather larger cohorts and further experimental studies.
目的:本研究旨在描述受罕见的 PPP3CA 基因相关发育性癫痫脑病(DEE)影响的个体的电-临床表型:方法:我们对以前未报道过的四例受试者进行了详细的电-临床描述,这四例受试者的脑部核磁共振成像(MRI)结构均无异常,先天性代谢异常筛查结果也正常,但他们携带了编码钙神经蛋白的 PPP3CA 基因调控域内的致病变体。我们还通过PubMed和SCOPUS(截至2023年12月)进行了文献综述,收集了所有报告PPP3CA基因调控域致病变体受试者临床细节的研究:我们的深入研究发现了两种不同的电临床表型,它们具有独特的发作间期和发作模式。钙调蛋白结合域的致病变异导致儿童发病型癫痫,伴有局灶性和全身性癫痫发作、发育和智力障碍。调节结构域中的致病变异会导致早发性耐药性严重癫痫,并可能造成致命后果。与现有文献的比较分析证实,截短突变(主要发生在调节结构域,但也可能发生在钙调素结合结构域)始终与更严重的残疾和耐药性癫痫有关:我们的研究强调了致病变异的类型和位置对 PPP3CA 相关 DEE 严重程度的关键作用。我们还根据特殊的脑电图模式推测了涉及钙神经蛋白功能障碍和钙平衡的潜在病理生理机制。为了提高我们对这种罕见 DEE 的认识,我们需要共同努力收集更多的队列并开展进一步的实验研究。
{"title":"PPP3CA gene-related developmental and epileptic encephalopathy: Expanding the electro-clinical phenotype","authors":"Jacopo Favaro , Alessandro Iodice , Margherita Nosadini , Francesca Asta , Irene Toldo , Claudio Ancona , Elena Cavaliere , Maria Federica Pelizza , Gianluca Casara , Lucio Parmeggiani , Stefano Sartori","doi":"10.1016/j.seizure.2024.08.017","DOIUrl":"10.1016/j.seizure.2024.08.017","url":null,"abstract":"<div><h3>Purpose</h3><div>The objective of this study is to characterize the electro-clinical phenotype of individuals affected by the rare PPP3CA gene-related developmental and epileptic encephalopathy (DEE).</div></div><div><h3>Methods</h3><div>We provide a detailed electro-clinical description of four previously unreported subjects, with unremarkable structural brain MRI and a normal screening for inborn errors of metabolism, who carry pathogenic variants within the regulatory domain of the PPP3CA gene, which encodes for calcineurin. We also conducted a literature review via PubMed and SCOPUS (up to December 2023) to collect all the studies reporting clinical details of subjects with PPP3CA pathogenic variants within the regulatory domain.</div></div><div><h3>Results</h3><div>Our in-depth investigation reveals two distinct electro-clinical phenotypes with unique interictal and ictal patterns. Pathogenic variants within the calmodulin-binding domain result in childhood-onset epilepsy with focal and generalized seizures, developmental and intellectual impairments. Pathogenic variants within the regulatory domain lead to early onset drug-resistant severe epilepsy and potentially fatal outcomes. Comparative analysis with existing literature corroborates the notion that truncating mutations, prevalent in the regulatory domain but also possible in the calmodulin-binding domain, consistently associate with more profound disabilities and drug-resistant epilepsy.</div></div><div><h3>Conclusion</h3><div>Our study emphasizes the critical role of pathogenic variants’ type and location on the severity of PPP3CA-related DEE. We also speculate, based on peculiar EEG patterns, on potential pathophysiological mechanisms involving calcineurin dysfunction and calcium homeostasis. In order to improve our understanding of this rare DEE, we need both collaborative efforts to gather larger cohorts and further experimental studies.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 253-261"},"PeriodicalIF":2.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1059131124002413/pdfft?md5=fc608179af8966489c3473977ada7034&pid=1-s2.0-S1059131124002413-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299520","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}
Pub Date : 2024-08-24DOI: 10.1016/j.seizure.2024.08.018
Iván Sánchez Fernández, Taha Fathima Khan, Amanda Romeu, Tahir Sheikh, Alcy Torres, Rinat Jonas, Laurie Douglass
Objective
To describe the prescription patterns of home, non-intravenous rescue benzodiazepines (non-IV-rBZDs) for febrile seizures and the factors associated with their prescription.
Methods
Retrospective descriptive study using the MarketScan Commercial Database, a large database of employer-sponsored privately insured patients in the United States. We used data from January 1st 2006 to December 31st 2022. We studied patients with febrile seizures as the main code for the healthcare encounter (identified with International Classification of Diseases codes) with age from 6 months to 5 years of age and with at least 1 month of follow-up.
Results
There were a total of 82,835 patients [median (p25-p75) age 1.0 (1.0–2.0) years, 56.7 % males] with at least one febrile seizure, of whom 9,737 (11.8 %) filled at least one non-IV-rBZD prescription. Among the 9,737 patients who filled at least one prescription, the median (p25-p75) time from first febrile seizure to non-IV-rBZD prescription was 27 (2–186) days. Among the factors known at the time of the first febrile seizure, complex febrile seizure (OR: 3.51, 95 % CI: 3.24–3.79), and an initial inpatient hospitalization for febrile seizure (OR: 3.53, 95 % CI: 3.29–3.79) were the factors most strongly associated with filling a non-IV-rBZD prescription. In contrast, sex, rural patient's residence, and salary employment (versus other employment class) were not independently associated with filling a non-IV-rBZD prescription. Among the factors known at the end of follow-up, complex febrile seizures, type of initial encounter, and an eventual diagnosis of epilepsy were major independent factors associated with filling a non-IV-rBZD prescription.
Conclusion
Only approximately 12 % of children with a febrile seizure filled a prescription for a home non-IV-rBZD. The major factors independently associated with prescription were complex febrile seizure, hospital admission, recurrent febrile seizures, and an eventual diagnosis of epilepsy.
{"title":"Prescription patterns of home rescue benzodiazepines for febrile seizures","authors":"Iván Sánchez Fernández, Taha Fathima Khan, Amanda Romeu, Tahir Sheikh, Alcy Torres, Rinat Jonas, Laurie Douglass","doi":"10.1016/j.seizure.2024.08.018","DOIUrl":"10.1016/j.seizure.2024.08.018","url":null,"abstract":"<div><h3>Objective</h3><p>To describe the prescription patterns of home, non-intravenous rescue benzodiazepines (non-IV-rBZDs) for febrile seizures and the factors associated with their prescription.</p></div><div><h3>Methods</h3><p>Retrospective descriptive study using the MarketScan Commercial Database, a large database of employer-sponsored privately insured patients in the United States. We used data from January 1st 2006 to December 31st 2022. We studied patients with febrile seizures as the main code for the healthcare encounter (identified with International Classification of Diseases codes) with age from 6 months to 5 years of age and with at least 1 month of follow-up.</p></div><div><h3>Results</h3><p>There were a total of 82,835 patients [median (p<sub>25</sub>-p<sub>75</sub>) age 1.0 (1.0–2.0) years, 56.7 % males] with at least one febrile seizure, of whom 9,737 (11.8 %) filled at least one non-IV-rBZD prescription. Among the 9,737 patients who filled at least one prescription, the median (p<sub>25</sub>-p<sub>75</sub>) time from first febrile seizure to non-IV-rBZD prescription was 27 (2–186) days. Among the factors known at the time of the first febrile seizure, complex febrile seizure (OR: 3.51, 95 % CI: 3.24–3.79), and an initial inpatient hospitalization for febrile seizure (OR: 3.53, 95 % CI: 3.29–3.79) were the factors most strongly associated with filling a non-IV-rBZD prescription. In contrast, sex, rural patient's residence, and salary employment (versus other employment class) were not independently associated with filling a non-IV-rBZD prescription. Among the factors known at the end of follow-up, complex febrile seizures, type of initial encounter, and an eventual diagnosis of epilepsy were major independent factors associated with filling a non-IV-rBZD prescription.</p></div><div><h3>Conclusion</h3><p>Only approximately 12 % of children with a febrile seizure filled a prescription for a home non-IV-rBZD. The major factors independently associated with prescription were complex febrile seizure, hospital admission, recurrent febrile seizures, and an eventual diagnosis of epilepsy.</p></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 197-203"},"PeriodicalIF":2.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 10.1016/j.seizure.2024.08.016
Thandar Aung , Jin Bo , William Bingaman , Imad Najm , Andreas Alexopoulos , Juan C. Bulacio
Objective
We aimed to analyze seizure outcomes and define ictal onset with intracranial electroencephalography (ICEEG) in patients with polymicrogyria (PMG)-related drug-resistant epilepsy (DRE), considering surrounding cortex and extent of surgical resection.
Methods
Retrospective study of PMG-diagnosed patients (2001 to June 2018) at a single epilepsy center was performed. Primary outcome was complete seizure freedom (SF), based on Engel classification with follow-up of ≥ 1 year. Univariate analyses identified predictive clinical variables, later integrated into multivariate Cox proportional hazards models.
Results
Thirty-five patients with PMG-related DRE (19 adults/16 pediatric: 20 unilateral/15 bilateral) were studied. In surgical group (n = 23), 52 % achieved SF (mean follow-up:47 months), whereas none in non-resective treatment group (n = 12) attained SF (mean follow-up:39.3 months) (p = 0.002). In surgical group, there were no significant differences in SF, based on the laterality of the PMG [uni or bilateral,p = 0.35], involvement of perisylvian region(p = 0.714), and extent of the PMG resection [total vs. partial,p = 0.159]. Patients with ictal ICEEG onset in both PMG and non-PMG cortices, and those limited to non- PMG cortices had a greater chance of achieving SF compared to those limited to the PMG cortices.
Conclusion
Resective surgery guided by ICEEG for defining the epileptogenic zone (EZ), in DRE patients with PMG, leads to favorable seizure outcomes. ICEEG-guided focal surgical resection(s) may lead to SF in patients with bilateral or extensive unilateral PMG. ICEEG aids in EZ localization within and/or outside the MRI-identified PMG. Complete removal of PMG identified on MRI does not guarantee SF. Hence, developing preimplantation hypotheses based on epileptogenic networks evaluation during presurgical assessment is crucial in this patient population.
{"title":"Seizure outcome in drug-resistant epilepsy in the setting of polymicrogyria","authors":"Thandar Aung , Jin Bo , William Bingaman , Imad Najm , Andreas Alexopoulos , Juan C. Bulacio","doi":"10.1016/j.seizure.2024.08.016","DOIUrl":"10.1016/j.seizure.2024.08.016","url":null,"abstract":"<div><h3>Objective</h3><p>We aimed to analyze seizure outcomes and define ictal onset with intracranial electroencephalography (ICEEG) in patients with polymicrogyria (PMG)-related drug-resistant epilepsy (DRE), considering surrounding cortex and extent of surgical resection.</p></div><div><h3>Methods</h3><p>Retrospective study of PMG-diagnosed patients (2001 to June 2018) at a single epilepsy center was performed. Primary outcome was complete seizure freedom (SF), based on Engel classification with follow-up of ≥ 1 year. Univariate analyses identified predictive clinical variables, later integrated into multivariate Cox proportional hazards models.</p></div><div><h3>Results</h3><p>Thirty-five patients with PMG-related DRE (19 adults/16 pediatric: 20 unilateral/15 bilateral) were studied. In surgical group (<em>n</em> = 23), 52 % achieved SF (mean follow-up:47 months), whereas none in non-resective treatment group (<em>n</em> = 12) attained SF (mean follow-up:39.3 months) (<em>p</em> = 0.002). In surgical group, there were no significant differences in SF, based on the laterality of the PMG [uni or bilateral,<em>p</em> = 0.35], involvement of perisylvian region(<em>p</em> = 0.714), and extent of the PMG resection [total vs. partial,<em>p</em> = 0.159]. Patients with ictal ICEEG onset in both PMG and non-PMG cortices, and those limited to non- PMG cortices had a greater chance of achieving SF compared to those limited to the PMG cortices.</p></div><div><h3>Conclusion</h3><p>Resective surgery guided by ICEEG for defining the epileptogenic zone (EZ), in DRE patients with PMG, leads to favorable seizure outcomes. ICEEG-guided focal surgical resection(s) may lead to SF in patients with bilateral or extensive unilateral PMG. ICEEG aids in EZ localization within and/or outside the MRI-identified PMG. Complete removal of PMG identified on MRI does not guarantee SF. Hence, developing preimplantation hypotheses based on epileptogenic networks evaluation during presurgical assessment is crucial in this patient population.</p></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 226-234"},"PeriodicalIF":2.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 10.1016/j.seizure.2024.08.009
Emanuele Bartolini , Anna Rita Ferrari , Filippo Maria Santorelli , Carmen Salluce , Guja Astrea , Gemma Marinella , Francesca Maria Agostina Papoff , Alessandro Orsini , Roberta Battini
Background
Patients with genetic deficiency of the adaptor protein complex 4 (AP-4) exhibit earlyonset developmental delay, spastic diplegia, intellectual disability, speech impairment. The phenotype overlaps with other hereditary spastic paraplegias and cerebral palsies. Febrile seizures are common at onset. Epilepsy has been described in more than half of cases, arising in early infancy often with status epilepticus, but no typical seizure semiology or electroencephalographic features have been identified thus far.
Purpose
We aimed to specifically investigate the epileptological characteristics of the syndrome to unveil possible biomarkers of seizure development and prognosis in AP-4 deficiency.
Methods
Observational cohort study on patients with bi-allelic pathogenic variants in AP-4 subunits and epilepsy. We focused on the seizure semiology, electroencephalographic characteristics and response to antiseizure medications.
Results
Patients harboured pathogenic variants in AP4S1 (n = 5) or AP4M1 (n = 1). The phenotype included spastic paraparesis, intellectual disability, speech/language impairment, microcephaly, and MRI evidence of hypoplasia of the corpus callosum. In 66 % of the patients, febrile seizures preceded the onset of epilepsy, which spanned from infancy to adolescence (range=14 months-13 years). Absences (66 %) and focal motor seizures (50 %) were common. No patient met the criteria for drug-resistance. Peculiar electroencephalographic features arose after the epilepsy onset and persisted at long-term follow-up: bilateral and asynchronous focal discharges combined with independent diffuse spike-wave-discharges (100 %) and reflex abnormalities (66 %).
Conclusion
In AP-4 complex disease, epilepsy could arise beyond early infancy, until adolescence, with variable combination of generalized and focal seizures. The prognosis was favourable. We observed a common electroencephalographic signature - combined focal/generalized and reflex abnormalities - which may constitute a biomarker of AP-4 deficiency with epilepsy, applicable to inform genetic testing and disentangle the differential diagnosis.
{"title":"Combined generalized and focal epilepsy with reflex features in Adaptor protein complex 4-associated hereditary spastic paraplegias: A cohort observational study","authors":"Emanuele Bartolini , Anna Rita Ferrari , Filippo Maria Santorelli , Carmen Salluce , Guja Astrea , Gemma Marinella , Francesca Maria Agostina Papoff , Alessandro Orsini , Roberta Battini","doi":"10.1016/j.seizure.2024.08.009","DOIUrl":"10.1016/j.seizure.2024.08.009","url":null,"abstract":"<div><h3>Background</h3><p>Patients with genetic deficiency of the adaptor protein complex 4 (AP-4) exhibit earlyonset developmental delay, spastic diplegia, intellectual disability, speech impairment. The phenotype overlaps with other hereditary spastic paraplegias and cerebral palsies. Febrile seizures are common at onset. Epilepsy has been described in more than half of cases, arising in early infancy often with status epilepticus, but no typical seizure semiology or electroencephalographic features have been identified thus far.</p></div><div><h3>Purpose</h3><p>We aimed to specifically investigate the epileptological characteristics of the syndrome to unveil possible biomarkers of seizure development and prognosis in AP-4 deficiency.</p></div><div><h3>Methods</h3><p>Observational cohort study on patients with bi-allelic pathogenic variants in AP-4 subunits and epilepsy. We focused on the seizure semiology, electroencephalographic characteristics and response to antiseizure medications.</p></div><div><h3>Results</h3><p>Patients harboured pathogenic variants in AP4S1 (<em>n</em> = 5) or AP4M1 (<em>n</em> = 1). The phenotype included spastic paraparesis, intellectual disability, speech/language impairment, microcephaly, and MRI evidence of hypoplasia of the corpus callosum. In 66 % of the patients, febrile seizures preceded the onset of epilepsy, which spanned from infancy to adolescence (range=14 months-13 years). Absences (66 %) and focal motor seizures (50 %) were common. No patient met the criteria for drug-resistance. Peculiar electroencephalographic features arose after the epilepsy onset and persisted at long-term follow-up: bilateral and asynchronous focal discharges combined with independent diffuse spike-wave-discharges (100 %) and reflex abnormalities (66 %).</p></div><div><h3>Conclusion</h3><p>In AP-4 complex disease, epilepsy could arise beyond early infancy, until adolescence, with variable combination of generalized and focal seizures. The prognosis was favourable. We observed a common electroencephalographic signature - combined focal/generalized and reflex abnormalities - which may constitute a biomarker of AP-4 deficiency with epilepsy, applicable to inform genetic testing and disentangle the differential diagnosis.</p></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 186-193"},"PeriodicalIF":2.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1016/j.seizure.2024.08.013
Kaiyi Kang , Yuxin Wu , Hui Gan , Baohui Yang , Han Xiao , Difei Wang , Hanli Qiu , Xinyu Dong , Haotian Tang , Xuan Zhai
Focal cortical dysplasia (FCD) is a structural lesion that is the most common anatomical lesion identified in children, and the second most common in adults with drug-resistant focal-onset epilepsy. These lesions vary in size, location, and histopathological manifestations. FCDs are classified into three subtypes associated with loss-of-function mutations in PI3K/AKT, TSC1/TSC2, RHEB, and DEPDC/NPRL2/NPRL3. During the decades of research into FCD, experimental models have played an irreplaceable role in the research design of studies investigating disease pathogenesis, pathophysiology, and treatment. Further, the establishment of FCD experimental models has moved the field forward by (1) revealing the cellular processes and signaling pathways underlying FCD pathogenesis and (2) varying the methods and materials to study the function of FCD proteins. Currently, FCD experimental models are predominantly murine, with each model providing unique insights into FCD lesions. This review briefly summarizes the pathology and molecular functions of FCD, further comparing the available modeling methods and indexes, as well as the utilization of models, followed by an analysis of the similarities, advantages, and disadvantages between these models and human FCD.
{"title":"Pathophysiological mechanisms underlying the development of focal cortical dysplasia and their association with epilepsy: Experimental models as a research approach","authors":"Kaiyi Kang , Yuxin Wu , Hui Gan , Baohui Yang , Han Xiao , Difei Wang , Hanli Qiu , Xinyu Dong , Haotian Tang , Xuan Zhai","doi":"10.1016/j.seizure.2024.08.013","DOIUrl":"10.1016/j.seizure.2024.08.013","url":null,"abstract":"<div><p>Focal cortical dysplasia (FCD) is a structural lesion that is the most common anatomical lesion identified in children, and the second most common in adults with drug-resistant focal-onset epilepsy. These lesions vary in size, location, and histopathological manifestations. FCDs are classified into three subtypes associated with loss-of-function mutations in PI3K/AKT, TSC1/TSC2, RHEB, and DEPDC/NPRL2/NPRL3. During the decades of research into FCD, experimental models have played an irreplaceable role in the research design of studies investigating disease pathogenesis, pathophysiology, and treatment. Further, the establishment of FCD experimental models has moved the field forward by (1) revealing the cellular processes and signaling pathways underlying FCD pathogenesis and (2) varying the methods and materials to study the function of FCD proteins. Currently, FCD experimental models are predominantly murine, with each model providing unique insights into FCD lesions. This review briefly summarizes the pathology and molecular functions of FCD, further comparing the available modeling methods and indexes, as well as the utilization of models, followed by an analysis of the similarities, advantages, and disadvantages between these models and human FCD.</p></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 176-185"},"PeriodicalIF":2.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1016/j.seizure.2024.08.014
Nicholas Huerta , Mengyang Lu , Bobbie J. Henry-Barron , Mackenzie C. Cervenka , Tanya J.W. McDonald
Purpose
This study investigated factors associated with improved seizure control in adults with epilepsy following a modified Atkins diet (MAD).
Methods
Follow-up data collected from participants enrolled in a prospective study between March 2016 and November 2023 was analyzed. Demographic and clinical differences between diet responders and non-responders were evaluated. MAD response was defined as ≥ 50 % reduction in seizure frequency from baseline.
Results
MAD use led to clinical response in 48 % of study participants with 2–3 month follow-up and in 56 % of study participants with 6 month follow-up. No significant differences were found for gender, age at diet initiation, age at epilepsy diagnosis, or for number of current or past medications tried. However, a significant relationship emerged between epilepsy type and diet response at 6 months with a response of 100 % seen in adults with generalized epilepsy and a response of only 42 % in adults with focal epilepsy (p = 0.004). Those who responded to the diet showed non-significant increases in many of the measured lipid biomarkers. Levels of apolipoprotein-B and small low-density lipoprotein particles showed significant increases from baseline after 3 months in responders compared to non-responders (p = 0.004 and 0.049, respectively).
Conclusions
These findings support the continued use of MAD particularly for seizure management in adults with generalized epilepsy and highlight potential mechanisms of clinical response involving lipoprotein and energy metabolism.
{"title":"Factors associated with seizure response in adults with epilepsy on a modified Atkins diet","authors":"Nicholas Huerta , Mengyang Lu , Bobbie J. Henry-Barron , Mackenzie C. Cervenka , Tanya J.W. McDonald","doi":"10.1016/j.seizure.2024.08.014","DOIUrl":"10.1016/j.seizure.2024.08.014","url":null,"abstract":"<div><h3>Purpose</h3><p>This study investigated factors associated with improved seizure control in adults with epilepsy following a modified Atkins diet (MAD).</p></div><div><h3>Methods</h3><p>Follow-up data collected from participants enrolled in a prospective study between March 2016 and November 2023 was analyzed. Demographic and clinical differences between diet responders and non-responders were evaluated. MAD response was defined as ≥ 50 % reduction in seizure frequency from baseline.</p></div><div><h3>Results</h3><p>MAD use led to clinical response in 48 % of study participants with 2–3 month follow-up and in 56 % of study participants with 6 month follow-up. No significant differences were found for gender, age at diet initiation, age at epilepsy diagnosis, or for number of current or past medications tried. However, a significant relationship emerged between epilepsy type and diet response at 6 months with a response of 100 % seen in adults with generalized epilepsy and a response of only 42 % in adults with focal epilepsy (<em>p</em> = 0.004). Those who responded to the diet showed non-significant increases in many of the measured lipid biomarkers. Levels of apolipoprotein-B and small low-density lipoprotein particles showed significant increases from baseline after 3 months in responders compared to non-responders (<em>p</em> = 0.004 and 0.049, respectively).</p></div><div><h3>Conclusions</h3><p>These findings support the continued use of MAD particularly for seizure management in adults with generalized epilepsy and highlight potential mechanisms of clinical response involving lipoprotein and energy metabolism.</p></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 147-151"},"PeriodicalIF":2.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}