Epilepsia最新文献

{"title":"New onset refractory status epilepticus: Long-term outcomes beyond seizures.","authors":"Poul H Espino, Krista Eschbach, Leah J Blank, Mackenzie C Cervenka, Eyal Muscal, Raquel Farias-Moeller, Emily J Gilmore, Margaret T Gopaul, Hiba A Haider, Aurelie Hanin, Lawrence J Hirsch, Marissa A Kellogg, Gerhard Kluger, Soon-Tae Lee, Alexandria E Melendez-Zaidi, Vincent Navarro, Audrey C Oliger, Elena Pasini, Gitta Reuner, Cynthia M Sharpe, Zubeda B Sheikh, Leon Steigleder, Claude Steriade, Coral M Stredny, Adam Strzelczyk, Olga Taraschenko, Andreas van Baalen, Sarah A Vinette, Ronny Wickström, Nora W Wong, Jiyeoun Yoo, Teneille E Gofton","doi":"10.1111/epi.18267","DOIUrl":"https://doi.org/10.1111/epi.18267","url":null,"abstract":"<p><p>We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps. Subsequently, a consensus-building process was performed to prioritize and rank important LTO domains for further research. The prioritization of LTO domains was qualitative, enabling the expert panel to generate ideas, share opinions, and provide reasons for the rankings. A second round took place to allow expansion and agreement regarding specific details for each domain. Outcomes were classified into eight main domains: (1) Function: Neuropsychological, Neurological (other than seizures), and Psychiatric (mood and behavior); (2) Quality of Life; (3) Epilepsy; (4) Nonneurological (medical); (5) Social; (6) Caregiver Burden; (7) Long-Term Mortality; and (8) Health Care System Impact. In addition, the working group suggested obtaining outcome measures for each domain at 6 months and 1 year after discharge and annually thereafter until stability has been reached. There are no currently established time frames set for when LTO in NORSE begin or plateau, and previously there existed no consensus regarding which LTO should be considered. This consensus process identifies and recommends NORSE LTO domains that should be considered in future research studies to provide more consistent results that can be compared between studies. Survivors of NORSE should be evaluated serially and at fixed points over time to maximize our understanding of the recovery trajectory for all LTO domains. Establishing reliable and standardized data describing LTO (beyond seizures) after NORSE will support discussions with families during the acute stages, prognostication, the development of targeted management strategies for survivors, and future comparative research globally helping to identify biomarkers that may predict LTO.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of social determinants of health with first antiseizure medication prescription for patients with newly diagnosed epilepsy: A systematic review and meta-analysis.","authors":"Brian J Johnson, Katie E Jung, Megan A MacKenzie, Abdulsalam Bah, Nathalie Jetté, Nihal Mohamed, Leah J Blank","doi":"10.1111/epi.18277","DOIUrl":"https://doi.org/10.1111/epi.18277","url":null,"abstract":"<p><strong>Objective: </strong>To assess whether social determinants of health (SDOHs) are associated with the first antiseizure medication (ASM) prescribed for newly diagnosed epilepsy.</p><p><strong>Methods: </strong>The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed, and the protocol registered (CRD42023448998). Embase, Medline, and Web of Science were searched up to July 31, 2023. Two reviewers independently screened studies and reached mutual consensus for inclusion. Studies reporting the first ASM prescribed for patients with new epilepsy in all age groups, countries, and languages were eligible for inclusion. Review articles, conference abstracts, and studies with fewer than 15 participants were not eligible for inclusion. Studies were meta-analyzed using fixed-effects models. Quality assessment was performed using the Newcastle-Ottawa Scale.</p><p><strong>Results: </strong>Thirteen studies (total participants = 380,785) contained SDOH data and their association with the first ASM prescription after epilepsy diagnosis. Meta-analysis of studies with compatible data revealed that Black (pooled odds ratio [OR] .94, 95% confidence interval [CI] .90-.98) and Hispanic (pooled OR .89, 95% CI .82-.97) patients with U.S. Medicare/Medicaid had a lower odds of receiving a newer ASM compared to White patients. Three studies revealed that rural epilepsy patients had a lower odds of receiving new ASMs compared to urban patients (pooled OR .84, 95% CI .80-.89). The relationship between income levels and ASM prescription patterns differed across countries, highlighting inconsistencies that warrant further investigation. Among studies identified for inclusion, relatively few had combinable data, thereby limiting the scope of our meta-analysis to two SDOHs.</p><p><strong>Significance: </strong>Significant disparities exist in first-line ASM prescription for non-White and rural persons with epilepsy. There exist few data on other SDOHs including gender identity and socioeconomic background. Future work leveraging large data sets may reveal additional ASM prescription inequities. Developing care pathways to rectify known prescribing disparities may improve health equity among PWE.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsia – January 2025 Announcements","authors":"","doi":"10.1111/epi.18258","DOIUrl":"https://doi.org/10.1111/epi.18258","url":null,"abstract":"&lt;p&gt;\u0000 \u0000 &lt;b&gt;Epilepsy Workshop&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;16–17 January 2025&lt;/p&gt;&lt;p&gt;Egypt&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;14th ILAE School on Pre-Surgical Evaluation for Epilepsy and Epilepsy Surgery&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;20–24 January 2025&lt;/p&gt;&lt;p&gt;Brno, Czech Republic&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;15th Asian &amp; Oceanian Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;20–23 February 2025&lt;/p&gt;&lt;p&gt;New Delhi, India&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;18th Latin American Summer School on Epilepsy&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;7–15 March 2025&lt;/p&gt;&lt;p&gt;São Paulo, Brazil&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;7th ILAE School on EEG in the First Year of Life&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;26–27 April 2025&lt;/p&gt;&lt;p&gt;Sanya City, Hainan, China&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;ILAE School on Neuroimaging 2025&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;15–17 May 2025&lt;/p&gt;&lt;p&gt;Potsdam, Germany&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;5th African Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;16–18 May 2025&lt;/p&gt;&lt;p&gt;Lusaka, Zambia&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;15th ILAE School for Neuropathology and Neuroimaging in Epilepsy&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;31 July–3 August 2025&lt;/p&gt;&lt;p&gt;Campinas, São Paulo, Brazil&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;XVIII Workshop on Neurobiology of Epilepsy (WONOEP 2025)&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;25–29 August 2025&lt;/p&gt;&lt;p&gt;Portugal&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;36th International Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;30 August–3 September 2025&lt;/p&gt;&lt;p&gt;Lisbon, Portugal&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;16th European Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;5–9 September 2026&lt;/p&gt;&lt;p&gt;Athens, Greece&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;ILAE Eastern Mediterranean &amp; Africa webinaire (français)&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;14 January 2025&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;Acute Management of Functional/Dissociative Seizures&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;16 January 2025&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;ILAE Emergency Task Force Webinar: WHO Ukraine Health Cluster&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;28 January 2025&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;1er Congreso Latinoamericano de Epilepsias Genéticas 2025&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;8–10 January 2025&lt;/p&gt;&lt;p&gt;Santiago, Chile&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;3rd International Online Course on Pathogenesis of Epilepsy&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;27 February–29 May 2025&lt;/p&gt;&lt;p&gt;Online&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;World Neuroscience and Psychiatry Conference 2025 (WNPC25)&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;8–9 March 2025&lt;/p&gt;&lt;p&gt;Bangkok, Thailand&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;19th World Congress on Controversies in Neurology&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;20–22 March 2025&lt;/p&gt;&lt;p&gt;Prague, Czech Republic&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;13th Trinationa","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"66 1","pages":"316-317"},"PeriodicalIF":6.6,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143115773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy and employment: A qualitative interview study with heads of human resources and occupational physicians in Austria - A call for legislative optimization according to the WHO Intersectoral Global Action Plan.","authors":"Markus Leitinger, Claudia Klampfer, Leonie Obermeyr, Kateriine Orav, Payam Tabaee Damavandi, Michael Alexa, Aljoscha Thomschewski, Julia Höfler, Fabio Rossini, Giorgi Kuchukhidze, Gudrun Kalss, Matthias Mauritz, Kai-Nicolas Poppert, Andreea Toma, Bernardo Crespo-Pimentel, Pilar Bosque-Varela, Teia Kobulashvili, Fabian Schwimmbeck, Eugen Trinka","doi":"10.1111/epi.18221","DOIUrl":"https://doi.org/10.1111/epi.18221","url":null,"abstract":"<p><strong>Objective: </strong>People with epilepsy (PWEs) often face difficulties in obtaining or keeping employment. To determine the views on this topic of the heads of human resources (HHRs) and occupational physicians (OCPs).</p><p><strong>Method: </strong>Twelve HHRs and five OCPs underwent a telephone interview concerning the opportunities and limitations of job applications for PWEs. The interviews were performed in May 2020, in the federal state of Salzburg, Austria, and they were analyzed using the qualitative method of content analysis (Kuckartz). The legal situation was investigated according to Global target 5.2 of the Intersectoral Global Action Plan (IGAP) on epilepsy and other neurological disorders 2022-2031 by WHO.</p><p><strong>Results: </strong>Employers were confident that employees with epilepsy could be managed well in a positive company culture and with first responders in place. The Austrian law predisposes to uncertainty among both employers and employees. In particular, it allows only retrospective juridical clarification of health-related questions in the job interview. The authors developed a classification system of workplaces, with \"D0\" (D-zero) meaning no health or financial danger, for example, office workers and \"D1\" posing still no health hazard but includes regular work with cash, for example, salespersons. \"D2\" means potential medical implications for the person with epilepsy or any other person at the workplace, for example, industrial worker. Measures taken to abandon the risk in D2 workplaces, for example, a total sheath for a machine, leads to reclassification as \"D2-0.\" With D2, OCPs evaluate the applicant's medical fitness for the job without disclosing medical details to the employer. The \"compartment model of medical information in the job application process\" guarantees that OCPs are the only persons who learn about the applicant's medical details.</p><p><strong>Significance: </strong>The practical and simple classification of workplaces according to the D-system, and the concept of making medical information accessible only to OCPs may diminish stigma and discrimination in the working world for PWEs.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonconvulsive status epilepticus in patients under intensive care: Should we view epilepsy as a sleep disorder?","authors":"Philippe Gélisse, Arielle Crespel","doi":"10.1111/epi.18274","DOIUrl":"https://doi.org/10.1111/epi.18274","url":null,"abstract":"<p><p>Nonconvulsive status epilepticus (NCSE) was initially described in patients with typical and atypical absence status epilepticus (ASE) characterized by states of confusion varying in severity and in focal epilepsies with or without alteration of consciousness. Continuous EEG monitoring of critically ill patients has further refined the classification of NCSE into two main categories: with coma and without coma. Hypnotic, soporific or somniferous epileptic seizures do not exist. On the contrary, patients usually awaken when seizures occur during sleep, and their eyes remain open during ASE. Excessive sleepiness and coma alone are not ictal signs but are observed in the postictal phase of convulsive seizures. On the other hand, excessive sleepiness evolving into coma is a cardinal sign of metabolic/toxic encephalopathies with triphasic waves evolving to burst suppression patterns and ultimately to cerebral inactivity and death. NCSE alone does not directly cause coma. Comas are related to the underlying etiology, patient age and comorbidities, as well as the administration of intravenous sedative drugs to control epileptic seizures. In cases of severe brain injury, NCSE can explain the failure to awaken after the withdrawal of anesthetics and is only an aggravating factor of the neurological condition. In typical ASE, which is characterized by sustained, rhythmic, bilateral, synchronous and unreactive discharges with evolving spatiotemporal patterns (the best example of NCSE), there is no vigilance impairment. This contrasts with metabolic/toxic encephalopathies, which exhibit monomorphic generalized periodic discharges in which patients may become comatose and die. The extended concept of NCSE in comatose patients may lead to an inflated assessment of NCSE, implying a potentially worse prognosis compared to convulsive status epilepticus.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-based analysis of status epilepticus management and outcome: A cohort study.","authors":"Andria Tziakouri, Jan Novy, Andrea O Rossetti","doi":"10.1111/epi.18266","DOIUrl":"https://doi.org/10.1111/epi.18266","url":null,"abstract":"<p><p>Status epilepticus (SE) is a neurological emergency with significant morbidity and mortality. The role of sex as a factor influencing the characteristics, treatment, and outcomes of SE has been scarcely addressed. This study investigates this variable regarding the clinical management and outcome among adult patients with SE. We retrospectively analyzed the Centre Hospitalier Universitaire Vaudois (CHUV) Status Epilepticus Registry (SERCH) over a 10-year period, including 961 SE episodes in 831 patients (56.82% male; 43.18% female), excluding post-axonic cases. There were no statistically significant differences in age, potentially fatal etiology, or pre-treatment consciousness impairment between sexes. Male patients were slightly younger (mean age 61 vs 64 years, p =.03), had a higher prevalence of prior seizures (54.76% vs 47.9%, p = .04), and were more likely to present with generalized convulsive SE (51.5% vs 41%), whereas female patients exhibited a higher frequency of focal unaware SE (31.7% vs 22.1%, global p = .02). Treatment strategies were similar across sexes, with benzodiazepines as first-line therapy in over 80% of cases, levetiracetam being the most frequently prescribed second-line treatment, followed by valproate and lacosamide. Development of refractory SE was comparable between sexes (54% in both, p = .92); outcomes at discharge were also similar. SE refractoriness and return to baseline conditions remained similar after multivariable adjustment for potential confounders. Overall, our results suggest comparable SE management, treatment responsiveness and outcomes between men and women.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seizure outcomes after resection of temporal encephalocele in patients with drug-resistant epilepsy: A systematic review and meta-analysis.","authors":"Hamza Khoudari, Mohammad Alabbas, Steven Tobochnik, Jorge Burneo, Benjamin Cox, Hernan Nicolas Lemus","doi":"10.1111/epi.18264","DOIUrl":"https://doi.org/10.1111/epi.18264","url":null,"abstract":"<p><strong>Objective: </strong>Temporal encephaloceles (TEs) are seen in patients with drug-resistant epilepsy (DRE); yet they are also common incidental findings. Variability in institutional pre-surgical epilepsy practices and interpretation of epileptogenic network localization contributes to bias in existing epilepsy cohorts with TE, and therefore the relevance of TE in DRE remains controversial. We sought to estimate effect sizes and sample sizes necessary to demonstrate clinically relevant improvements in seizure outcome with different surgical approaches.</p><p><strong>Methods: </strong>We searched Medline, Embase, and Cochrane to identify studies reporting the outcomes of epilepsy surgery after 12 months in patients with DRE and TE. The main outcome was seizure freedom or favorable seizure outcome. We also assessed the rates of seizure freedom among patients with DRE, TE, and the following covariables: use of intracranial electroencephalography (iEEG), side of the encephalocele, sex, and type of surgical resection (anterior temporal lobectomy [ATL] vs lesionectomy). Random-effects meta-analysis was used to calculate the proportion of patients attaining seizure outcomes.</p><p><strong>Results: </strong>We identified 332 studies, of which 15 (282 patients) met inclusion criteria for meta-analysis. Seizure-freedom rate was 65% (95% confidence interval [CI] 53-76), whereas the favorable outcome rate was 78% (95% CI 70-85). There was no significant interstudy heterogeneity. Patients with TE undergoing iEEG (risk ratio [RR] 0.80, 95% CI 0.74-0.87) had a lower chance of a favorable seizure outcome. A power analysis estimated a sample size of 28 932 patients with TE (13 764 with ATL) necessary to determine a significant difference in seizure freedom between limited resection and ATL.</p><p><strong>Significance: </strong>Retrospective cohort studies demonstrate good outcomes after TE resection regardless of the extent of resection. Prohibitively large sample sizes necessary to observe outcome differences between surgical approaches and presurgical predictors indicate that improved biomarkers and mechanistic understanding of TE epileptogenicity are needed.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct peripheral pro-inflammatory profile associated with tuberous sclerosis complex and epilepsy.","authors":"Renaud Balthazard, Rose-Marie Drouin-Engler, Samuel Bertrand, Faycal Zine-Eddine, Jimmy Li, Olivier Tastet, Audrey Daigneault, Victoria H Mamane, Gloria Gabrielle Ortega-Delgado, Alina Maria Sreng Flores, Daniel E Kaufmann, Philippe Major, Andrew A House, Laurent Létourneau-Guillon, Nathalie Arbour, Mark R Keezer, Catherine Larochelle","doi":"10.1111/epi.18261","DOIUrl":"https://doi.org/10.1111/epi.18261","url":null,"abstract":"<p><strong>Objective: </strong>Tuberous sclerosis complex (TSC) is a monogenetic disorder associated with sustained mechanistic target of rapamycin (mTOR) activation, leading to heterogeneous clinical manifestations. Epilepsy and renal angiomyolipoma are the most important causes of morbidity in adult people with TSC (pwTSC). mTOR is a key player in inflammation, which in turn could influence TSC-related clinical manifestations. Reliable biomarkers are lacking to monitor and predict evolution and response to treatment for epilepsy in pwTSC. Inflammation has been implicated in epileptogenesis in non-TSC-related epilepsy. We aimed to characterize the relation between markers of neuroglial activation/injury, markers of peripheral inflammation, and active epilepsy in pwTSC to identify accessible biomarkers and potential new therapeutic targets.</p><p><strong>Methods: </strong>We performed a cross-sectional study to investigate markers of central nervous system (CNS) (neurofilament light [NfL] and glial fibrillary acidic protein [GFAP]) and peripheral (45 cytokines) inflammation in the peripheral blood of pwTSC (n = 46) vs age- and sex-matched healthy controls (HCs) (n = 26). In pwTSC, markers associated with active epilepsy (n = 23/46) were compared to non-TSC epilepsy controls (n = 18). Observations on markers of neuroglial activation/injury (GFAP, NfL) were confirmed in an independent TSC cohort (n = 45; 69% with active epilepsy).</p><p><strong>Results: </strong>We report that TSC is characterized by elevated serum levels of marker of astrogliosis (GFAP), pro-inflammatory molecules (interleukin 1β [IL-1β], CXCL8) and trophic factor (epidermal growth factor [EGF]) compared to HCs and to non-TSC-related epilepsy controls. Among pwTSC, renal angiomyolipoma presence and size was associated with IL-15. It is notable that active epilepsy in pwTSC was associated with higher levels of GFAP compared to pwTSC without epilepsy, which was confirmed in an external validation cohort, and with elevated levels of pro-inflammatory cytokines (IL-17A, IL-17C, tumor necrosis factor α [TNF-α]), not significantly related to seizure activity or treatment with mTOR inhibitor. These associations remained significant after adjusting for age and sex.</p><p><strong>Significance: </strong>These results suggest that key inflammatory mediators could contribute to epileptogenesis and represent novel biomarkers and therapeutic targets in TSC.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tremor as an intrinsic feature of juvenile myoclonic epilepsy.","authors":"Alessia Giugno, Francesco Fortunato, Ilaria Sammarra, Miriam Sturniolo, Enrico Fratto, Iolanda Martino, Rita Nisticò, Antonio Gambardella","doi":"10.1111/epi.18268","DOIUrl":"https://doi.org/10.1111/epi.18268","url":null,"abstract":"<p><p>We aim to understand whether tremor may be an intrinsic feature of juvenile myoclonic epilepsy (JME) and whether individuals with JME plus tremor experience a different disease course. Thirty-one individuals with JME plus tremor (17 females, mean age = 33.9 ± 13.8 years) and 30 age of onset- and gender-matched subjects with JME (21 females, mean age = 26.8 ± 11.2 years) prospectively underwent clinical and neurophysiologic assessment, including tremor assessment and somatosensory evoked potentials (SEPs). All JME plus tremor subjects experienced postural and action tremor affecting bilateral upper limbs. Nine of 31 individuals (29%) with tremor were never exposed to valproate (VPA), and 14 of 31 (45.2%) were not using VPA at the time of clinical evaluation. Twelve of 31 (38.7%) patients with JME plus tremor were drug-resistant compared to four of 30 (13.3%) with JME (p = .024). The JME plus tremor subjects had higher numbers of previous childhood absence epilepsy (n = 6/31 [19.4%]), interictal epileptiform discharges (n = 30/31 [96.8%]), photosensitivity (n = 8/31 [25.8%]), and psychiatric comorbidities (n = 12/31 [38.7%]). Six of 31 (19.4%) individuals with JME plus tremor had giant SEPs (1/30, 3.3% with JME; p = .05, chi-squared test). The clinical features and decreased sensorimotor inhibition in the JME plus tremor group suggest that tremor might be a marker of disease severity rather than an epiphenomenon of VPA exposure.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cenobamate as add-on treatment for SCN8A developmental and epileptic encephalopathy.","authors":"Cathrine E Gjerulfsen, Madeleine J Oudin, Francesca Furia, Sopio Gverdtsiteli, Cecilie Johannessen Landmark, Marina Trivisano, Simona Balestrini, Renzo Guerrini, Angel Aledo-Serrano, Ricardo Morcos, Roberto Previtali, Pierangelo Veggiotti, Emilia Ricci, Guido Rubboli, Elena Gardella, Rikke S Møller","doi":"10.1111/epi.18257","DOIUrl":"https://doi.org/10.1111/epi.18257","url":null,"abstract":"<p><strong>Objectives: </strong>Developmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. High doses of sodium channel blockers are typically used to treat SCN8A-DEE caused by gain-of-function (GoF) variants. However, seizures are often drug resistant, and only a few patients achieve seizure freedom. In this retrospective study, the effect of cenobamate was assessed in patients with SCN8A-DEE.</p><p><strong>Methods: </strong>Across multiple centers and through collaborations with SCN8A patient advocacy organizations, patients with SCN8A-DEE treated with cenobamate for ≥6 months were identified. Data were obtained from patients' caregivers or treating physicians through a (Research Electronic Data Capture) REDCap survey. The functional effect of the SCN8A variants was obtained from the literature or assessed by prediction tools.</p><p><strong>Results: </strong>Twelve patients (3-25 years of age (median 8 years), 9 females) with presumed GoF SCN8A variants were treated with cenobamate for a mean period of 17 months (range 6-42 months). Countable motor seizures were meaningfully reduced in 10 of 12 patients (83%). Six patients experienced a seizure reduction above 70%, of which two achieved seizure freedom. In addition, two patients achieved a reduction in seizures ranging between 50% and 70%. An increase in seizure-free days per patient was also reported. Rescue medication was decreased in six of seven patients (85%) in need. Furthermore, 80% of patients reported non-seizure-related improvements, which included increased alertness, better sleep, and improved muscle tone. Adverse effects were reported by 50% of patients, and half resolved spontaneously or through the reduction of concomitant antiseizure medications.</p><p><strong>Significance: </strong>Our data suggest that cenobamate is a promising and safe treatment for SCN8A-DEE, even during early childhood. As a potential precision approach to treatment, cenobamate significantly reduced seizure burden and improved non-seizure-related symptoms. These positive outcomes may also be achieved in patient cohorts with GoF variants in other voltage-gated sodium channel genes.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}