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Epilepsy is associated with increased mortality. Cardiovascular disease confers a significant portion of this increased risk. Recently there is increased interest in the burden of cardiovascular mortality in people with epilepsy. This review discusses the most common cardiovascular risk factors and their association with epilepsy including obesity, diabetes mellitus, and hyperlipidemia. Hyperlipidemia related to the use of enzyme inducing anti-seizure medications is also discussed as a topic that is of particular importance to prescribers that have patients with comorbid cardiovascular risk and epilepsy. Heart rate variability (HRV) and its association with SUDEP is discussed as well as a contributor to vascular risk. Finally, the authors discuss a potential role for neurologists who treat epilepsy to engage closer with their patients cardiovascular risk factors using available tools such as a the ASCVD score calculator to determine the overall risk of mortality, as well as acting upon this information to guide treatment approaches integrating the information provided in this review.

Background and purpose: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of epilepsy mortality. All international guidance strongly advocates for clinicians working with people with epilepsy (PWE) to discuss SUDEP. Clinician views working with PWE in the UK and Norway on SUDEP counselling are compared. Methods: A cross‐sectional online mixed methodology survey of 17 Likert and free‐text response questions using validated themes was circulated via International League against Epilepsy/Epilepsy Specialist Nurses Association in the UK and International League against Epilepsy/Epilepsinet in Norway using a non‐discriminatory exponential snowballing technique leading to non‐probability sampling. Quantitative data were analysed using descriptive statistics and Mann–Whitney, Kruskal–Wallis, chi‐squared and Fisher's exact tests. Significance was accepted at p < 0.05. Thematic analysis was conducted on free‐text responses. Results: Of 309 (UK 197, Norway 112) responses, UK clinicians were more likely to have experienced an SUDEP (p < 0.001), put greater importance on SUDEP communication (p < 0.001), discuss SUDEP with all PWE particularly new patients (p < 0.001), have access and refer to bereavement support (p < 0.001) and were less likely to never discuss SUDEP (p < 0.001). Significant differences existed between both countries' neurologists and nurses in SUDEP counselling with UK clinicians generally being more supportive. UK responders were more likely to be able to identify bereavement support (p < 0.001). Thematic analysis highlighted four shared themes and two specific to Norwegians. Discussion: Despite all international guidelines stating the need/importance to discuss SUDEP with all PWE there remain hesitation, avoidance and subjectivity in clinicians having SUDEP‐related conversations, more so in Norway than the UK. Training and education are required to improve communication, engagement and decision making. [ABSTRACT FROM AUTHOR]

• The last decade witnessed a rapid increase in epilepsy mortality. • Mortality from epilepsy was higher in Black individuals and men. • Similar upward trends in the last decade have been observed across ages, genders, and ethnicities. • A comprehensive assessment of long-term trends in mortality from epilepsy holds significance for healthcare prioritization. The analysis of long-term trends of mortality from epilepsy has not been conducted, which is crucial for estimating the future burden of epilepsy. We therefore aimed to investigate the long-term trends of mortality from epilepsy in the United States from 1979 to 2021. The cause-of-death and demographic data were from the National Center for Health Statistics (1979–2021) and population estimates were from the US Census Bureau. We used the joinpoint regression model to analyze secular trends in the mortality of epilepsy spanning from 1979 to 2021. Age-adjusted mortality from epilepsy was assessed based on the year 2000 U.S. population data, stratified by age, sex, and race. The age-adjusted mortality from epilepsy increased from 0.78 per 100,000 population in 1979 to 1.01 per 100,000 population in 2021, with an average annual percent change (AAPC) of 0.58% (95% confidence interval [CI]: 0.45% - 0.72%). The overall age-adjusted mortality of epilepsy had been on the rise between 2011 and 2021. The mortality rate generally increases with age. The mortality of epilepsy was higher in the Afro-American people and men. The mortality of epilepsy in both sexes declined first and then increased, with AAPC 1.02% (95% CI: 0.88%, 1.23%) in women and 0.10% (95% CI: -0.002%, 0.21%) in men. Mortality in all races including White, Afro-American people, and other races individuals fell first and then rose. The AAPC of mortality in White, other races, and Afro-American people were 0.89% (95% CI: 0.79%, 1.02%), -0.87% (95% CI: -1.84%, 0.88%), and -0.31% (95% CI: -0.48%, -0.13%), respectively. Although the mortality rate from epilepsy has experienced a period of decline, it is worth noting that the last decade has seen a rapid increase. A comprehensive assessment of long-term trends in mortality from epilepsy holds significance for healthcare prioritization. [ABSTRACT FROM AUTHOR]

Epilepsy is associated with increased mortality. Cardiovascular disease confers a significant portion of this increased risk. Recently there is increased interest in the burden of cardiovascular mortality in people with epilepsy. This review discusses themost common cardiovascular risk factors and their association with epilepsy including obesity, diabetes mellitus, and hyperlipidemia. Hyperlipidemia related to the use of enzyme inducing anti-seizure medications is also discussed as a topic that is of particular importance to prescribers that have patients with comorbid cardiovascular risk and epilepsy. Heart rate variability (HRV) and its association with SUDEP is discussed as well as a contributor to vascular risk. Finally, the authors discuss a potential role for neurologists who treat epilepsy to engage closer with their patient's cardiovascular risk factors using available tools such as a the ASCVD score calculator to determine the overall risk ofmortality, as well as acting upon this information to guide treatment approaches integrating the information provided in this review. [ABSTRACT FROM AUTHOR]

Epilepsy is associated with increased mortality. Cardiovascular disease confers a significant portion of this increased risk. Recently there is increased interest in the burden of cardiovascular mortality in people with epilepsy. This review discusses the most common cardiovascular risk factors and their association with epilepsy including obesity, diabetes mellitus, and hyperlipidemia. Hyperlipidemia related to the use of enzyme inducing anti-seizure medications is also discussed as a topic that is of particular importance to prescribers that have patients with comorbid cardiovascular risk and epilepsy. Heart rate variability (HRV) and its association with SUDEP is discussed as well as a contributor to vascular risk. Finally, the authors discuss a potential role for neurologists who treat epilepsy to engage closer with their patient's cardiovascular risk factors using available tools such as a the ASCVD score calculator to determine the overall risk of mortality, as well as acting upon this information to guide treatment approaches integrating the information provided in this review.

Abstract Objective This study aimed to describe the characteristics of pediatric neurologists (PNs) in Latin America (LA) who attend to children and adolescents with epilepsy and convey to them the risk of sudden unexpected death in epilepsy (SUDEP). Methods Personal data and details of discussion of SUDEP with families, including relevance of SUDEP disclosure, frequency of such communication, perceived benefits and risks of disclosure, extent of training received on such disclosure, and professional experience with SUDEP, were collected through an online survey of PNs from LA. Their personal experience in carrying out this conversation was obtained through responses to an open question, further used to identify the main barriers. Results Of the 442 surveys received, 367 (83%) were analyzed. Most participants (73.8%) responded that the communication of SUDEP risk was relevant or very relevant; however, only 17.9% reported communicating it always or very frequently. Factors that increased the frequency of SUDEP communication included patients with higher levels of complexity (OR = 2.18, P = .003) and the physician's personal experience with SUDEP (OR = 2.305, P

SUMMARY: Almost a quarter of people with intellectual disabilities have epilepsy. This life-long condition adversely affects their health, safety and well-being and carries an increased risk of sudden unexpected death in epilepsy (SUDEP) in this population. This commentary considers what not only health and social services but also communities and people with intellectual disabilities themselves can do to improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to describe the characteristics of pediatric neurologists (PNs) in Latin America (LA) who attend to children and adolescents with epilepsy and convey to them the risk of sudden unexpected death in epilepsy (SUDEP). Methods: Personal data and details of discussion of SUDEP with families, including relevance of SUDEP disclosure, frequency of such communication, perceived benefits and risks of disclosure, extent of training received on such disclosure, and professional experience with SUDEP, were collected through an online survey of PNs from LA. Their personal experience in carrying out this conversation was obtained through responses to an open question, further used to identify the main barriers. Results: Of the 442 surveys received, 367 (83%) were analyzed. Most participants (73.8%) responded that the communication of SUDEP risk was relevant or very relevant; however, only 17.9% reported communicating it always or very frequently. Factors that increased the frequency of SUDEP communication included patients with higher levels of complexity (OR = 2.18, P =.003) and the physician's personal experience with SUDEP (OR = 2.305, P <.001). Direct questions from the family and avoiding scaring them about a rare outcome were the main motivations behind discussing and not discussing SUDEP, respectively. In the open question, respondents identified worries about the patient's ability to understand the information and cultural gaps as barriers. "Informing with the intention of improving adherence to treatment" and "establishing an empathic relationship" were significantly related. Further, the concept of "do not scare" was significantly related to "personal difficulties in discussing SUDEP." Significance: Although most PNs agree that communication about SUDEP is relevant, only a minority actually engages in it. Participants identified a lack of appropriate training in such communication as a barrier. A better understanding of communication expectations, education of health professionals, and communication techniques have a strong relevance in diminishing the gap between guidelines and practice. [ABSTRACT FROM AUTHOR]

Background: Sudden Unexpected Death in Epilepsy (SUDEP) is a complication of epilepsy responsible for approximately 1 death per 1000 patients. The literature has demonstrated minimal SUDEP disclosure between providers and patients, although patients have consistently reported desire to know about their risk. However, the majority of these studies has been conducted in Caucasian populations which did not seek to include lower socio-economic class individuals. Thus, the purpose of this study is to determine patient and provider attitudes regarding SUDEP disclosure at a community health center serving minority, predominantly Hispanic, patients., Methods: This cross-sectional study utilized surveys distributed to patients with epilepsy (n = 20), patients with diabetes (n = 20), those with no chronic disease (n = 20) and providers (n = 13). Online surveys were distributed to 13 providers whereas phone surveys were conducted for patients with epilepsy. In-person surveys were distributed to patients with diabetes and no chronic disease to serve as comparison groups. Surveys were available in both Spanish and English. Patient surveys consisted of demographic information and questions evaluating their current knowledge and preferences regarding disclosure of a potentially fatal disorder., Results: Twenty patients with epilepsy, 20 patients with diabetes, 20 patients without chronic diseases, and 9 providers responded to the online or in-person surveys. Of the patients with epilepsy, 90 % (n = 18/20) were Hispanic which was not significantly different from the comparison groups. 45 % (n = 9/20) believed they had a higher rate of death due to epilepsy with only 3 patients having heard of SUDEP prior to the survey, and only 1 learning this from a physician. All patients wanted to know everything there was to know regarding their condition, including a higher risk of unexpected death. Most patients (85%, n = 17/20) believe everyone with epilepsy should be informed of SUDEP and this information should come from their provider (90 %, n = 18/20). Results were similar for both comparison groups, except patients with diabetes unanimously desired to know about a theoretical risk of death at the time of diagnosis. Of the providers, 66.7% (n = 6/9) never discuss SUDEP, with the remaining 33.3% (n = 3/9) discussing SUDEP rarely. The primary reason for not discussing SUDEP was not knowing enough about it (66.7%, n = 5/9)., Conclusion: Almost all patients with epilepsy had no knowledge of SUDEP, yet desired to know this information within the first two visits. Providers in the primary care setting rarely discuss SUDEP, most often due to lack of knowledge. These results are very similar to those found in mainly white, higher socioeconomic populations and indicate that race should not be a barrier to SUDEP disclosure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Buchhalter serves as a paid consultant to the Epilepsy Foundation, Epilepsy Study Consortium, Biocodex Inc, Epilog Clouds of Care and UCB Inc. He receives research support from the Dravet Syndrome Foundation and serves as a co-chair for Partners Against Mortality in Epilepsy on a volunteer basis. No other authors have any declarations of competing interests.]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Seizures are a common clinical occurrence in high-grade glioma (HGG). While many studies have explored seizure incidence and prevalence in HGG, limited studies have examined the prognostic effect of seizures occurring in the post-diagnosis setting. This study aims to assess the impact of seizure presentation on HGG survival outcomes., Methods: Single-center retrospective review identified 950 patients with histologically-confirmed high-grade glioma. Seizure presentation was determined by clinical history and classified as early onset (occurring within 30 days of HGG presentation) or late onset (first seizure occurring after beginning HGG treatment). The primary outcome, hazard ratios for overall survival and progression-free survival, was assessed with multivariable Cox proportional-hazards models. IDH1 mutation status (assessed through immunohistochemistry) was only consistently available beginning in 2015; subgroup analyses were performed in the subset of patients with known IDH1 status., Results: Epileptic activity before (HR = 0.81, 95% CI = 0.68-0.96, P = 0.017) or after (HR = 0.74, 95% CI = 0.60-0.91, P = 0.005) HGG diagnosis associated with improved overall survival. Additionally, late seizure onset significantly associated with lower odds of achieving partial (OR = 0.25, 95% CI = 0.12-0.53, P = < 0.001) or complete (OR = 0.30, 95% CI = 0.18-0.50, P < 0.001) seizure control than patients with early seizure onset., Conclusions: Clinical seizures both at the time of diagnosis and later during the HGG treatment course are associated with improved overall survival. This association potentially persists for both IDH1-wildtype and IDH1-mutant patients, but further study is required., (© 2024. The Author(s).)

Sudden unexpected death in epilepsy (SUDEP) is responsible for most epilepsy-related deaths. It is mainly related to unwitnessed nocturnal convulsions, either focal to bilateral or generalised tonic-clonic seizures (TCS). Targeted preventive strategies are currently lacking as underlying mechanisms are largely unknown. Antiseizure medications (ASMs) modulate SUDEP risk through seizure reduction, but it is yet undetermined whether individual ASMs or other medications could also influence the internal SUDEP cascade. Seizure detection devices (SDD) may offer an alternative strategy by preventing TCS from being unwitnessed. Here, we critically evaluated the current evidence on the influence of ASMs, non-epilepsy concomitant drugs and SDD on SUDEP occurrence. We found no robust evidence for the effect of starting ASMs on SUDEP beyond TCS control, but we found some indications of a protective effect for polytherapy. We found no signs that specific ASMs exert a risk for SUDEP. One study suggested a possible protective effect of levetiracetam requiring further investigation. Only a few small studies addressed the association between non-epilepsy concomitant drugs and SUDEP, with no consistent effect for psychotropic medications and one more extensive study suggesting a lower risk among statin users. We only found indirect evidence indicating a protective effect for enhancing nocturnal supervision without explicitly addressing the impact of SDD on SUDEP occurrence. Further work is needed to explore the potential of ASMs and other interventions to modulate SUDEP risk, and they should accurately account for TCS frequency, polypharmacy and markers of non-adherence., (© 2024. The Author(s).)

Importance: Maternal epilepsy is associated with adverse pregnancy and neonatal outcomes. A better understanding of this condition and the associated risk of mortality and morbidity at the time of delivery could help reduce adverse outcomes., Objective: To determine the risk of severe maternal and perinatal morbidity and mortality among women with epilepsy., Design, Setting, Participants: This prospective population-based register study in Denmark, Finland, Iceland, Norway, and Sweden took place between January 1, 1996, and December 31, 2017. Data analysis was performed from August 2022 to November 2023. Participants included all singleton births at 22 weeks' gestation or longer. Births with missing or invalid information on birth weight or gestational length were excluded. The study team identified 4 511 267 deliveries, of which 4 475 984 were to women without epilepsy and 35 283 to mothers with epilepsy., Exposure: Maternal epilepsy diagnosis recorded before childbirth. Prenatal exposure to antiseizure medication (ASM), defined as any maternal prescription fills from conception to childbirth, was also examined., Main Outcomes and Measures: Composite severe maternal morbidity and mortality occurring in pregnancy or within 42 days postpartum and composite severe neonatal morbidity (eg, neonatal convulsions) and perinatal mortality (ie, stillbirths and deaths) during the first 28 days of life. Multivariable generalized estimating equations with logit-link were used to obtain adjusted odds ratios (aORs) and 95% CIs., Results: The mean (SD) age at delivery for women in the epilepsy cohort was 29.9 (5.3) years. The rate of composite severe maternal morbidity and mortality was also higher in women with epilepsy compared with those without epilepsy (36.9 vs 25.4 per 1000 deliveries). Women with epilepsy also had a significantly higher risk of death (0.23 deaths per 1000 deliveries) compared with women without epilepsy (0.05 deaths per 1000 deliveries) with an aOR of 3.86 (95% CI, 1.48-8.10). In particular, maternal epilepsy was associated with increased odds of severe preeclampsia, embolism, disseminated intravascular coagulation or shock, cerebrovascular events, and severe mental health conditions. Fetuses and infants of women with epilepsy were at elevated odds of mortality (aOR, 1.20; 95% CI, 1.05-1.38) and severe neonatal morbidity (aOR, 1.48; 95% CI, 1.40-1.56). In analyses restricted to women with epilepsy, women exposed to ASM compared with those unexposed had higher odds of severe maternal morbidity (aOR ,1.24; 95% CI, 1.10-1.48) and their neonates had an increased odd of mortality and severe morbidity (aOR, 1.37; 95% CI, 1.23-1.52)., Conclusion and Relevance: This multinational study shows that women with epilepsy were at considerably higher risk of severe maternal and perinatal outcomes and increased risk of death during pregnancy and postpartum. Maternal epilepsy and maternal use of ASM were associated with increased maternal morbidity and perinatal mortality and morbidity.

Introduction: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality., Patients and Methods: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014., Results: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26)., Discussion and Conclusion: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Ciccone reports grants from Daiichi-Sankyo; grants from Italfarmaco; and grants from Alexion Pharmaceuticals.Dr Paciaroni reports compensation from SANOFI-AVENTIS U.S. LLC for other services; compensation from PFIZER CANADA INC for other services; compensation from iRhythm Technologies for other services; compensation from Daiichi Sankyo Europe GmbH for other services; and compensation from Bristol-Myers Squibb for other services.The other Authors have nothing to disclose.

Objective: Approximately 50 million people worldwide have epilepsy and 8-17% of the deaths in patients with epilepsy are attributed to sudden unexpected death in epilepsy (SUDEP). The goal of the present work was to establish a biomarker for SUDEP so that preventive treatment can be instituted., Approach: Seizure activity in patients with SUDEP and non-SUDEP was analyzed, specifically, the scalp EEG extracted muscle activity (SMA) and the average wavelet phase coherence (WPC) during seizures was computed for two frequency ranges (1-12 Hz, 13-30 Hz) to identify differences between the two groups., Main Results: Ictal SMA in SUDEP patients showed a statistically higher average WPC value when compared to non-SUDEP patients for both frequency ranges. Area under curve for a cross-validated logistic classifier was 81%., Significance: Average WPC of ictal SMA is a candidate biomarker for early detection of SUDEP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gravitis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Epilepsy is associated with significant mortality risk. There is limited research examining how traumatic brain injury (TBI) timing affects mortality in relation to the onset of epilepsy. We aimed to assess the temporal relationship between epilepsy and TBI regarding mortality in a cohort of post-9/11 veterans., Methods: This retrospective cohort study included veterans who received health care in the Defense Health Agency and the Veterans Health Administration between 2000 and 2019. For those diagnosed with epilepsy, the index date was the date of first antiseizure medication or first seizure; we simulated the index date for those without epilepsy. We created the study groups by the index date and first documented TBI: (1) controls (no TBI, no epilepsy), (2) TBI only, (3) epilepsy only, (4) TBI before epilepsy, (5) TBI within 6 months after epilepsy, and (6) TBI >6 months after epilepsy. Kaplan-Meier estimates of all-cause mortality were calculated, and log-rank tests were used to compare unadjusted cumulative mortality rates among groups compared to controls. Cox proportional hazard models were used to compute hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: Among 938 890 veterans, 27 436 (2.92%) met epilepsy criteria, and 264 890 (28.22%) had a TBI diagnosis. Mortality was higher for veterans with epilepsy than controls (6.26% vs. 1.12%; p < .01). Veterans with TBI diagnosed ≤6 months after epilepsy had the highest mortality hazard (HR = 5.02, 95% CI = 4.21-5.99) compared to controls, followed by those with TBI before epilepsy (HR = 4.25, 95% CI = 3.89-4.58), epilepsy only (HR = 4.00, 95% CI = 3.67-4.36), and TBI >6 months after epilepsy (HR = 2.49, 95% CI = 2.17-2.85). These differences were significant across groups., Significance: TBI timing relative to epilepsy affects time to mortality; TBI within 6 months after epilepsy or before epilepsy diagnosis was associated with earlier time to death compared to those with epilepsy only or TBI >6 months after epilepsy., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Dexmedetomidine (Dex), midazolam, and propofol are three distinct sedatives characterized by varying pharmacological properties. Previous literature has indicated the positive impact of each of these sedatives on ICU patients. However, there is a scarcity of clinical evidence comparing the efficacy of Dex, midazolam, and propofol in reducing mortality among people with epilepsy (PWE). This study aimed to assess the impact of Dex, midazolam, and propofol on the survival of PWE., Methods: The data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC)-IV database (version 2.0). PWE were categorized into Dex, midazolam, and propofol groups based on the intravenously administered sedatives. PWE without standard drug therapy were included in the control group. Comparative analyses were performed on the data among the groups., Results: The Dex group exhibited a significantly lower proportion of in-hospital deaths and a markedly higher in-hospital survival time compared to the midazolam and propofol groups (p < 0.01) after propensity score matching. Kaplan-Meier curves demonstrated a significant improvement in survival rates for the Dex group compared to the control group (p = 0.025). Analysis of Variance (ANOVA) revealed no significant differences in survival rates among the Dex, midazolam, and propofol groups (F = 1.949, p = 0.143). The nomogram indicated that compared to midazolam and propofol groups, Dex was more effective in improving the survival rate of PWE., Conclusion: Dex might improve the survival rate of PWE in the ICU compared to no standard drug intervention. However, Dex did not exhibit superiority in improving survival rates compared to midazolam and propofol., (© 2024. The Author(s).)

Background: Sudden unexpected death in epilepsy (SUDEP) is in most cases probably due to a fatal complication of tonic-clonic seizures and plays a significant role in the premature mortality of individuals with epilepsy. The reported risks of SUDEP vary considerably depending on the study population, so that an up-dated systematic review of SUDEP incidence including most recent studies is required to improve the estimated SUDEP risk and the counseling of individuals with epilepsy., Objective: To provide an overview of the current research landscape concerning SUDEP incidence across different patient populations and discuss potential conclusions and existing limitations., Material and Methods: A systematic literature review on SUDEP incidence was conducted in MEDLINE and EMBASE, supplemented by a manual search in June 2023. Out of a total of 3324 publications, 50 were reviewed for this study., Results: The analyzed studies showed significant heterogeneity concerning cohorts, study design and data sources. Studies conducted without specific criteria and relying on comprehensive registers indicated an incidence of 0.78-1.2 per 1000 patient-years. Research providing incidences across various age groups predominantly show an increase with age, peaking in middle age., Discussion: Due to varying methods of data collection and incidence calculation, comparing between studies is challenging. The association with age might be due to an underrepresentation of children, adolescents and patients over 60 years., Conclusion: Considering all age groups and types of epilepsy it is estimated that about 1 in 1000 individuals with epilepsy dies of SUDEP annually. With an assumed epilepsy prevalence of 0.6% in Germany, this could lead to more than one SUDEP case daily. Standardization of research methods is essential to gain more profound insights., (© 2024. The Author(s).)

Studies on epilepsy mortality in the United States are limited. We used the National Vital Statistics System Multiple Cause of Death data to investigate mortality rates and trends during 2011-2021 for epilepsy (defined by the International Classification of Diseases, 10th Revision, codes G40.0-G40.9) as an underlying, contributing, or any cause of death (i.e., either an underlying or contributing cause) for U.S. residents. We also examined epilepsy as an underlying or contributing cause of death by selected sociodemographic characteristics to assess mortality rate changes and disparities in subpopulations. During 2011-2021, the overall age-standardized mortality rates for epilepsy as an underlying (39 % of all deaths) or contributing (61 % of all deaths) cause of death increased 83.6 % (from 2.9 per million to 6.4 per million population) as underlying cause and 144.1 % (from 3.3 per million to 11.0 per million population) as contributing cause (P < 0.001 for both based on annual percent changes). Compared to 2011-2015, in 2016-2020 mortality rates with epilepsy as an underlying or contributing cause of death were higher overall and in nearly all subgroups. Overall, mortality rates with epilepsy as an underlying or contributing cause of death were higher in older age groups, among males than females, among non-Hispanic Black or non-Hispanic American Indian/Alaska Native persons than non-Hispanic White persons, among those living in the West and Midwest than those living in the Northeast, and in nonmetro counties compared to urban regions. Results identify priority subgroups for intervention to reduce mortality in people with epilepsy and eliminate mortality disparity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Objective: As autoimmune encephalitis (AE) often involves the mesial temporal structures which are known to be involved in both sudden unexpected death in epilepsy (SUDEP) and ictal asystole (IA), it may represent a good model to study the physiopathology of these phenomena. Herein, we systematically reviewed the occurrence of SUDEP and IA in AE., Methods: We searched 4 databases (MEDLINE, Scopus, Embase, and Web of Science) for studies published between database inception and December 20, 2022, according to the PRISMA guidelines. We selected articles reporting cases of definite/probable/possible/near-SUDEP or IA in patients with possible/definite AE, or with histopathological signs of AE., Results: Of 230 records assessed, we included 11 cases: 7 SUDEP/near-SUDEP and 4 IA. All patients with IA were female. The median age at AE onset was 30 years (range: 15-65), and the median delay between AE onset and SUDEP was 11 months; 0.9 months for IA. All the patients presented new-onset seizures, and 10/11 also manifested psychiatric, cognitive, or amnesic disorders. In patients with SUDEP, 2/7 were antibody-positive (1 anti-LGI1, 1 anti-GABABR); all IA cases were antibody-positive (3 anti-NMDAR, 1 anti-GAD65). Six patients received steroid bolus, 3 intravenous immunoglobulin, and 3 plasmapheresis. A pacemaker was implanted in 3 patients with IA. The 6 survivors improved after treatment., Discussion: SUDEP and IA can be linked to AE, suggesting a role of the limbic system in their pathogenesis. IA tends to manifest in female patients with temporal lobe seizures early in AE, highlighting the importance of early diagnosis and treatment., (© 2024. The Author(s).)

Objective: People with epilepsy (PWE) may be at an increased risk of severe COVID-19. It is important to characterize this risk to inform PWE and for future health and care planning. We assessed whether PWE were at higher risk of being hospitalized with, or dying from, COVID-19., Methods: We performed a retrospective cohort study using linked, population-scale, anonymized electronic health records from the SAIL (Secure Anonymised Information Linkage) databank. This includes hospital admission and demographic data for the complete Welsh population (3.1 million) and primary care records for 86% of the population. We identified 27 279 PWE living in Wales during the study period (March 1, 2020 to June 30, 2021). Controls were identified using exact 5:1 matching (sex, age, and socioeconomic status). We defined COVID-19 deaths as having International Classification of Diseases, 10th Revision (ICD-10) codes for COVID-19 on death certificates or occurring within 28 days of a positive SARS-CoV-2 polymerase chain reaction (PCR) test. COVID-19 hospitalizations were defined as having a COVID-19 ICD-10 code for the reason for admission or occurring within 28 days of a positive SARS-CoV-2 PCR test. We recorded COVID-19 vaccinations and comorbidities known to increase the risk of COVID-19 hospitalization and death. We used Cox proportional hazard models to calculate hazard ratios., Results: There were 158 (.58%) COVID-19 deaths and 933 (3.4%) COVID-19 hospitalizations in PWE, and 370 (.27%) deaths and 1871 (1.4%) hospitalizations in controls. Hazard ratios for COVID-19 death and hospitalization in PWE compared to controls were 2.15 (95% confidence interval [CI] = 1.78-2.59) and 2.15 (95% CI = 1.94-2.37), respectively. Adjusted hazard ratios (adjusted for comorbidities) for death and hospitalization were 1.32 (95% CI = 1.08-1.62) and 1.60 (95% CI = 1.44-1.78)., Significance: PWE are at increased risk of being hospitalized with, and dying from, COVID-19 when compared to age-, sex-, and deprivation-matched controls, even when adjusting for comorbidities. This may have implications for prioritizing future COVID-19 treatments and vaccinations for PWE., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: This study was undertaken to characterize changes in health care utilization and mortality for people with epilepsy (PWE) during the COVID-19 pandemic., Methods: We performed a retrospective study using linked, individual-level, population-scale anonymized health data from the Secure Anonymised Information Linkage databank. We identified PWE living in Wales during the study "pandemic period" (January 1, 2020-June 30, 2021) and during a "prepandemic" period (January 1, 2016-December 31, 2019). We compared prepandemic health care utilization, status epilepticus, and mortality rates with corresponding pandemic rates for PWE and people without epilepsy (PWOE). We performed subgroup analyses on children (<18 years old), older people (>65 years old), those with intellectual disability, and those living in the most deprived areas. We used Poisson models to calculate adjusted rate ratios (RRs)., Results: We identified 27 279 PWE who had significantly higher rates of hospital (50.3 visits/1000 patient months), emergency department (55.7), and outpatient attendance (172.4) when compared to PWOE (corresponding figures: 25.7, 25.2, and 87.0) in the prepandemic period. Hospital and epilepsy-related hospital admissions, and emergency department and outpatient attendances all reduced significantly for PWE (and all subgroups) during the pandemic period. RRs [95% confidence intervals (CIs)] for pandemic versus prepandemic periods were .70 [.69-.72], .77 [.73-.81], .78 [.77-.79], and .80 [.79-.81]. The corresponding rates also reduced for PWOE. New epilepsy diagnosis rates decreased during the pandemic compared with the prepandemic period (2.3/100 000/month cf. 3.1/100 000/month, RR = .73, 95% CI = .68-.78). Both all-cause deaths and deaths with epilepsy recorded on the death certificate increased for PWE during the pandemic (RR = 1.07, 95% CI = .997-1.145 and RR = 2.44, 95% CI = 2.12-2.81). When removing COVID deaths, RRs were .88 (95% CI = .81-.95) and 1.29 (95% CI = 1.08-1.53). Status epilepticus rates did not change significantly during the pandemic (RR = .95, 95% CI = .78-1.15)., Significance: All-cause non-COVID deaths did not increase but non-COVID deaths associated with epilepsy did increase for PWE during the COVID-19 pandemic. The longer term effects of the decrease in new epilepsy diagnoses and health care utilization and increase in deaths associated with epilepsy need further research., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Excess mortality due to epilepsy is greatest among young adults. However, the relative proportions of sudden unexpected death in epilepsy (SUDEP) and other epilepsy‐related causes of death are not well defined. We prospectively adjudicated cause of death in all 18‐ to 45‐year‐olds with a history of seizure/epilepsy who underwent medicolegal investigation in San Diego County between 2014 and 2017. We identified 108 decedents with definite or probable epilepsy; 62% died from an epilepsy‐related cause. SUDEP accounted for 42.6% (N = 46) of deaths, which were usually unwitnessed deaths, at home in bed. Other frequent causes of death were drug overdose (N = 23), suicide (N = 8), trauma (N = 8), and drowning (N = 6). SUDEP autopsies were similar to those of decedents from other causes. Most deaths in young adults with epilepsy that undergo medico‐legal investigation are epilepsy‐related, and SUDEP is the leading cause. Improved seizure control can potentially save many lives. [ABSTRACT FROM AUTHOR]

Abstract Background Sudden Unexpected Death in Epilepsy (SUDEP) is a significant cause of death in childhood epilepsy, and causes considerable concern to patients and their families. Despite this, the condition remains poorly understood. This systematic review investigates the risk factors, pathophysiology, and circumstances associated with childhood SUDEP. It aimed to explore the etiology of SUDEP and inform clinicians approaching SUDEP risk disclosure. Methods A structured electronic database search of MEDLINE, CENTRAL, EMBASE, and ISI web of science was conducted. Studies were included if they described clinical details of one or more patients, aged 18 years of age and below, who had SUDEP. Two reviewers independently reviewed each article for data extraction and quality assessment. Results Information on 108 cases of pediatric SUDEP was extracted from 22 included studies. These comprised five cohort studies, four retrospective case control studies, seven case series, and five case reports. Factors that appeared to be linked to pediatric SUDEP included those associated with severe epilepsy (early age of onset, high seizure frequency, intellectual impairment and developmental delay, multiple antiepileptic drug therapy, and structural abnormalities). The majority of included studies was noncomparative and had significant risk of bias. Conclusions There is currently insufficient evidence to determine the etiology of pediatric SUDEP. Current best practice to prevent pediatric SUDEP is to optimize the management of epilepsy. A national SUDEP registry would provide invaluable high-quality data and insights into modifiable risk factors, genetic predispositions, and novel prevention strategies. Highlights • Very little is known about the pathophysiology, risk factors and circumstances associated with childhood SUDEP. • In this systematic review, 22 studies were included with information on 108 cases of pediatric SUDEP. • Factors which appeared to be linked to pediatric SUDEP included those associated with severe epilepsy. • This is the first systematic review of childhood SUDEP in the literature, drawn from analysis of the largest compilation of pediatric SUDEP cases. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is considered one of the most burdensome neurologic diseases by the World Health Organization due to the high risk of morbidity and mortality. Few studies have investigated the epidemiology of idiopathic epilepsy in Sub-Saharan Africa (SSA). This study aims to characterize the disease burden of epilepsy among the older population in SSA via a large international database., Methods: Descriptive epidemiological data from the Global Burden of Disease (GBD) database was collected for idiopathic epilepsy in all regions of SSA. The "older" population was defined as 55 years of age and above. The variables of interest included mortality, incidence, prevalence, and disability-adjusted life years (DALYs) rates per one hundred thousand populations., Results: The average mortality rate was highest in Western SSA (6.34 per 100,000), and all regions were significantly higher than the global average (p < 0.001). DALYs and incidence rates of idiopathic epilepsy in all regions of SSA were significantly higher than the global averages (p < 0.01). Globally, the older population had a significantly higher mortality rate than the younger population (2.78 vs 1.62, respectively; p < 0.01). The older population had a higher mortality rate than the younger population in each region of SSA (p < 0.01). Conversely, for DALYs, the younger population had a higher disease burden than the older population globally and in each region of SSA (p < 0.01)., Conclusion: This study is the first to examine the epidemiologic profile of idiopathic epilepsy in the older population in SSA. Our results indicate that, when compared with the global population, older adults in SSA suffer a greater disease burden and mortality. This study reports the immense need for increased resources and awareness regarding epilepsy in the elderly population of Africa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have seemed to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: There is little evidence to guide the choice of antiseizure medication (ASM) for patients with poststroke epilepsy. Theoretical concerns about detrimental effects of ASMs on survival exist. Enzyme-inducing drugs could interfere with secondary stroke prevention. The US Food and Drug Administration recently issued a safety announcement about the potential proarrhythmic properties of lamotrigine., Objective: To investigate whether mortality varies with specific ASMs among patients with poststroke epilepsy., Design, Setting, and Participants: A cohort study was conducted using individual-level data from linked registers on all adults in Sweden with acute stroke from July 1, 2005, to December 31, 2010, and subsequent onset of epilepsy before December 31, 2014. A total of 2577 patients receiving continuous ASM monotherapy were eligible for the study. Data were analyzed between May 27, 2019, and April 8, 2021., Exposures: The dispensed ASM (Anatomical Therapeutic Chemical code N03A) determined exposure status, and the first dispensation date marked the start of treatment., Main Outcomes and Measures: The primary outcome, all-cause death, was analyzed using Cox proportional hazards regression with carbamazepine as the reference. Cardiovascular death (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I0-I99 as the underlying cause) was assessed using Fine-Gray competing risk regression models., Results: A total of 2577 patients (1400 men [54%]; median age, 78 years [IQR, 69-85 years]) were included. The adjusted hazard ratio of all-cause death compared with carbamazepine was 0.72 (95% CI, 0.60-0.86) for lamotrigine, 0.96 (95% CI, 0.80-1.15) for levetiracetam, 1.40 (95% CI, 1.23-1.59) for valproic acid, 1.16 (95% CI, 0.88-1.51) for phenytoin, and 1.16 (95% CI, 0.81-1.66) for oxcarbazepine. The adjusted hazard ratio of cardiovascular death compared with carbamazepine was 0.76 (95% CI, 0.61-0.95) for lamotrigine, 0.77 (95% CI, 0.60-0.99) for levetiracetam, 1.40 (95% CI, 1.19-1.64) for valproic acid, 1.02 (95% CI, 0.71-1.47) for phenytoin, and 0.71 (95% CI, 0.42-1.18) for oxcarbazepine., Conclusions and Relevance: This cohort study's findings suggest differences in survival between patients treated with different ASMs for poststroke epilepsy. Patients receiving lamotrigine monotherapy had significantly lower mortality compared with those receiving carbamazepine. The opposite applied to patients prescribed valproic acid, who had a higher risk of cardiovascular and all-cause death. Levetiracetam was associated with a reduced risk of cardiovascular death compared with carbamazepine, but there was no significant difference in overall mortality.

Competing Interests: Disclosure. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. Our studies are supported by the following grants: FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo); CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Estado de Minas Gerais.

Younger adults with epilepsy have an increased mortality. Some deaths are seizure-related, for example, sudden unexpected death in epilepsy (SUDEP), whereas others, for example, suicide, have multiple causes, including adverse effects of the treatment on mood. In this retrospective population-based study of all Danish persons with epilepsy aged 18 to 49 years during 2007 to 2009 we evaluated the risk of death from seizures and suicide. SUDEP comprised 82.7% of all seizure-related death. Younger adults with epilepsy had an 8.3-fold increased risk of death from seizure-related causes compared with suicide. This underpins the importance of effective seizure control in preventing premature death. ANN NEUROL 2021;90:983-987., (© 2021 American Neurological Association.)

Objective: To evaluate severe maternal morbidity (SMM) among patients with epilepsy and patients without epilepsy., Methods: We retrospectively examined SMM using linked birth certificate and maternal hospital discharge records in California between 2007 and 2012. Epilepsy present at delivery admission was the exposure and was subtyped into generalized, focal and other less specified, or unspecified. The outcomes were SMM and nontransfusion SMM from delivery up to 42 days' postpartum, identified using Centers for Disease Control and Prevention indicators. Multivariable logistic regression models were used to adjust for confounders, which were selected a priori. We also estimated the association between epilepsy and SMM independent of comorbidities by using a validated obstetric comorbidity score. Severe maternal morbidity indicators were then compared using the same multivariable logistic regression models., Results: Of 2,668,442 births, 8,145 (0.3%) were to patients with epilepsy; 637 (7.8%) had generalized, 6,250 (76.7%) had focal or other less specified, and 1,258 (15.4%) had unspecified subtypes. Compared with patients without epilepsy, patients with epilepsy had greater odds of SMM (4.3% vs 1.4%, adjusted odds ratio [aOR] 2.91, 95% CI 2.61-3.24) and nontransfusion SMM (2.9% vs 0.7%, aOR 4.16, 95% CI 3.65-4.75). Epilepsy remained significantly associated with increased SMM and nontransfusion SMM after additional adjustment for the obstetric comorbidity score, though the effects were attenuated. When grouped by organ system, all SMM indicators were significantly more common among patients with epilepsy-most notably those related to hemorrhage and transfusion., Conclusion: Severe maternal morbidity was significantly increased in patients with epilepsy, and SMM indicators across all organ systems contributed to this., Competing Interests: Financial Disclosure Kimford J. Meador disclosed that money was paid to his institution by Eisai Inc. and Sunovion Pharmaceuticals. The Epilepsy Study Consortium pays Kimford J. Meador's university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals. Thomas F. McElrath disclosed receiving compensation from Hoffman—LaRoche, NxPreatal, Comanche Biopharma, and Momenta Pharmaceuticals, Inc. for serving on their scientific advisory boards in work that is unrelated to the present analysis. Deirdre J. Lyell disclosed receiving funds from Bloomlife (stock options for consulting, unrelated to this work). She also received payment from SMFM and UCSF for lectures. The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: To determine the risk of mortality and causes of death in persons with late-onset epilepsy (LOE) compared to those without epilepsy in a community-based sample, adjusting for demographics and comorbid conditions., Methods: This is an analysis of the prospective Atherosclerosis Risk in Communities study, initiated in 1987-1989 among 15,792 mostly Black and White men and women in 4 US communities. We used Centers for Medicare & Medicaid Services fee-for-service claims codes to identify cases of incident epilepsy starting at or after age 67. We used Cox proportional hazards analysis to identify the hazard of mortality associated with LOE and to adjust for demographics and vascular risk factors. We used death certificate data to identify dates and causes of death., Results: Analyses included 9,090 participants, of whom 678 developed LOE during median 11.5 years of follow-up after age 67. Participants who developed LOE were at an increased hazard of mortality compared to those who did not, with adjusted hazard ratio 2.39 (95% confidence interval 2.12-2.71). We observed excess mortality due to stroke, dementia, neurologic conditions, and end-stage renal disease in participants with compared to without LOE. Only 4 deaths (1.1%) were directly attributed to seizure-related causes., Conclusions: Persons who develop LOE are at increased risk of death compared to those without epilepsy, even after adjusting for comorbidities. The majority of this excess mortality is due to stroke and dementia., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Epilepsy, a neuronal disorder has affected 1% of the world's population. Almost 35-40% of these patients get resistant to available anti-epileptic drugs (AEDs). Recent studies have shown the role of inflammation in the pathophysiology of epilepsy and a combination of anti-inflammatory and antiepileptic drugs could prove beneficial against epileptic seizures. Therefore, we aimed to examine the effect of levetiracetam (LEV) and diclofenac sodium (DFS) combination on pilocarpine (PLC) induced epileptic seizures in mice. Mice were divided into control and treatment groups. LEV alone and in combination with DFS was given for 3 days. On 3rd day after administering the required drugs, pilocarpine challenge was given intraperitoneally. Then, behavioral changes were observed for 90 minutes, including latency to first seizure, continuous seizures, duration of continuous seizures, and survival rate. Results showed significant improvement in the latencies to first (P<0.001) and continuous seizures (P<0.05), duration of the continuous seizure (p=0.001), and survival rate (P<0.01) in the combination treatment group as compared to the control or individual drug treatment groups. DFS enhances the efficacy of LEV, however, further mechanistic studies will be required to conclude if DFS can be given in combination with LEV for epilepsy treatment.

Objective: Sudden unexpected death in epilepsy (SUDEP) is a significant cause of mortality in epilepsy. The aim of this study is to evaluate the validity of the SUDEP-7 inventory and its components as tools for predicting SUDEP risk, and to develop and validate an improved inventory., Methods: The study included 28 patients who underwent video-electroencephalography (EEG) monitoring and later died of SUDEP, and 56 age- and sex-matched control patients with epilepsy. The SUDEP-7 score, its individual components, and an alternative inventory were examined as predictors of SUDEP., Results: SUDEP-7 scores were significantly higher among SUDEP patients compared with controls, both at time of admission (p = 0.024) and most recent follow-up (p = 0.016). SUDEP-7 scores declined only among controls, who demonstrated reduced seizure frequency. Seizure freedom after epilepsy surgery was also associated with survival. Several components of the SUDEP-7 inventory were independently associated with higher risk of SUDEP, including more than three generalized tonic-clonic (GTC) seizures (p = 0.002), one or more GTC seizures (p = 0.001), or one or more seizures of any type within the last year (p = 0.013), and intellectual disability (p = 0.031). In stepwise regression models, SUDEP-7 scores did not enhance the prediction of SUDEP over either GTC seizure frequency or seizure frequency alone. A novel SUDEP-3 inventory comprising GTC seizure frequency, seizure frequency, and intellectual disability (p < 0.001) outperformed the SUDEP-7 inventory (p = 0.010) in predicting SUDEP., Significance: Our findings demonstrate the limitations of the SUDEP-7 inventory. We propose a new three-item SUDEP-3 inventory, which predicts SUDEP better than the SUDEP-7., (© 2021 International League Against Epilepsy.)

Objective: We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE)., Patients and Methods: We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference., Results: Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06-2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years., Conclusions: Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.

Objective: The aim of the study is to examine the incidence and risk factors for death among neonates who developed neonatal seizures (NS) in an ethnically distinctive community with high consanguinity rate in Israel., Methods: Retrospective study was conducted at a single institution on data between January 2001 and January 2016. All neonates diagnosed with NS developed up to age 28 days were included. Mortality was defined as death within the first year of life., Results: Of all 69,460 neonates born during the study period, 118 (1.7 per 1,000 live births) developed NS; 35 (29.7%) died within the first year while 83 (70.3%) survived. The leading causes of death were developmental brain malformation (31.4%), genetic/metabolic (20%), hypoxic ischemic encephalopathy (20%), intracranial hemorrhage (11.4%) and infections (11.4%). Any consanguinity between the parents was found in 18 and 14.6% among the survivors and deceased groups, respectively ( p  = 0.24). Developmental brain malformations that lead to death were present in 3.6 and 31.4% in the survivors and deceased groups, respectively ( p  = 0.001; relative risk 8.70; 95% confidence interval 2.58-29.27). Stepwise backward logistic regression analysis revealed that developmental brain malformations ( p  < 0.0001), use of more than one antiepileptic medication ( p  = 0.006), and multiorgan failure ( p  = 0.004) were significant risk factors that predicted death., Conclusion: The results of the current study show that developmental brain malformations that cause NS were the leading risk factor for death., Competing Interests: All authors have indicated they have no potential conflicts of interest to disclose., (Thieme. All rights reserved.)

Objective: This study sought to understand issues facing people with epilepsy (PWE) during the lockdown period of the COVID-19 pandemic in the United States., Methods: We conducted a cross-sectional study using a 20-question survey that used SeziureTracker.com, sent to eligible PWE and their caregivers on May 6th, 2020. Questions about demographics and medical history were used to calculate COVID mortality risk odds ratios (OR) compared to a low baseline risk group., Results: In total, 505 responses were collected. Of these, 71% reported no change in seizure rates and 25% reported an increase in seizures, which they attributed primarily to disrupted sleep (63%) and decreased exercise (42%). Mortality risks from COVID-19 had median OR of 1.67, ranging 1.00-906.98. Fear about hospitalization (53%) and concern for loved ones (52%) were prominent concerns. Of the respondents, 5% reported stopping or reducing anti-seizure medications due to problems communicating with doctors, access or cost. Lower-risk COVID patients reported more fear of hospitalization (55% versus 38%, p<0.001) and anxiety about medication access (43% versus 28%, p=0.03) compared with higher-risk COVID patients. Increased anxiety was reported in 47%, and increased depression in 28%. Ten percent without generalized convulsions and 8% with did not know anything about epilepsy devices (VNS, RNS, DBS)., Significance: The COVID-19 pandemic presents unique challenges to PWE, including increased seizure rates, problems with access and cost of life-saving medications. Those with lower COVID-19 risk may have been marginalized more than those with higher risk. Efforts to protect PWE during major public health emergencies should take these findings into account.

Objective: Sudden unexpected death in epilepsy (SUDEP) is a diagnosis of exclusion; the definition includes individuals with epilepsy who die suddenly without an identifiable toxicological or anatomical cause of death. Limited data suggest underidentification of SUDEP as the cause of death on death certificates. Here, we evaluate the autopsy-reported cause of death in a population-based cohort of SUDEP cases., Methods: Case summaries of forensic autopsies conducted in Ontario, Canada between January 2014 and June 2016 were retrospectively screened using a language processing script for decedents with a history of epilepsy or seizures. After manual review for potential SUDEP cases, two neurologists independently examined the autopsy reports and classified deaths by Nashef criteria. Demographic characteristics and consideration by the forensic pathologist of the role of epilepsy, seizure, and SUDEP in death were summarized., Results: One hundred and eight Definite, 34 Definite Plus, and 22 Possible SUDEP cases were identified. Seventy-five percent of Definite/Definite Plus SUDEP cases identified by the neurologists were attributed to SUDEP, epilepsy, or seizure disorder in the autopsy report. There was a significant association between the proportion of cases listed in the autopsy report as SUDEP, epilepsy, or seizure disorder and neurologists' SUDEP classification (86% of Definite, 38% of Definite Plus, 0% of Possible). Age was significantly associated with SUDEP classification; Definite cases were younger than Definite Plus, which were younger than Possible SUDEP cases., Significance: Most SUDEP cases identified by neurologists were classified concordantly by forensic pathologists in Ontario, Canada; however, concordance decreased with increased case complexity. Although the role of epilepsy/seizures was considered in most Definite/Definite Plus cases, this study highlights the need for autopsy report review of potential SUDEP cases in research studies and assessments of the public health burden of SUDEP. The relationship between age and SUDEP classification has important public health implications; SUDEP incidence may be underappreciated in older adults., (© 2021 International League Against Epilepsy.)

Objective: To determine the incidence of epilepsy and subsequent 5-year mortality among older adults, as well as characteristics associated with mortality., Methods: This was a retrospective cohort study of Medicare beneficiaries age 65 or above with at least 2 years enrollment before January 2009. Incident epilepsy cases were identified in 2009 using ICD-9-CM code-based algorithms; death was assessed through 2014. Cox regression models examined the association between 5-year mortality and incident epilepsy, and whether mortality differed by sociodemographic characteristics or comorbid disorders., Results: Among the 99,990 of 33,615,037 beneficiaries who developed epilepsy, most were White (79.7%), female (57.3%), urban (80.5%), and without Medicaid (71.3%). The 5-year mortality rate for incident epilepsy was 62.8% (62,838 deaths). In multivariable models, lower mortality was associated with female sex (adjusted hazards ratio [AHR] 0.85, 95% confidence interval [CI] 0.84-0.87), Asian race (AHR 0.82, 95% CI 0.76-0.88), and Hispanic ethnicity (AHR 0.81, 95% CI 0.76-0.84). Hazard of death increased with comorbid disease burden (per 1-point increase: AHR 1.27, 95% CI 1.26-1.27) and Medicaid coinsurance (AHR 1.17, 95% CI 1.14-1.19). Incident epilepsy was particularly associated with higher mortality when diagnosed after another neurologic condition: Parkinson disease (AHR 1.29, 95% CI 1.21-1.38), multiple sclerosis (AHR 2.13, 95% CI 1.79-2.59), dementia (AHR 1.33, 95% CI 1.31-1.36), traumatic brain injury (AHR 1.55, 95% CI 1.45-1.66), and stroke/TIA (AHR 1.20, 95% CI 1.18-1.21)., Conclusions: Newly diagnosed epilepsy is associated with high 5-year mortality among Medicare beneficiaries. Future studies that parse the interplay of effects from underlying disease, race, sex, and poverty on mortality will be critical in the design of learning health care systems to reduce premature deaths., (© 2020 American Academy of Neurology.)

Objectives: Posterior location affects the clinical presentation and outcome of ischemic stroke, but little is known about occipital intracerebral hemorrhage (ICH). We studied non-traumatic occipital ICH phenotype, outcome, and post-ICH epilepsy., Materials and Methods: Occipital ICH patients were retrospectively identified from the Helsinki ICH Study registry of 1013 consecutive ICH patients treated in our tertiary center in 2005-2010. They were compared to non-occipital ICH patients to evaluate the effect of location on functional outcome at discharge (dichotomized modified Rankin Scale, mRS), 3- and 12-month mortality, and incidence of epilepsy., Results: We found 19 occipital ICH patients (5.3% of lobar and 1.9% of all ICH). Compared to non-occipital lobar ICHs, they were younger (median age 63 vs 71 years, P = .007) and had lower National Institutes of Health Stroke Scale on admission (1 vs 8, P < .001), smaller hematoma volume (6.3 vs 17.7 ML, P = .008), and more frequently structural etiology underlying the ICH (26% vs 7%, P = .01). Mortality at both 3 and 12 months was 6%, whereas 84% reached favorable outcome (mRS 0-2) at discharge. Occipital location was associated with favorable outcome at discharge in lobar ICH (OR 11.02, 95% CI 1.55-78.20). Incidence of post-ICH epilepsy (median follow-up 2.7 years) was 18%, equaling to that of non-occipital lobar ICH., Conclusions: Occipital ICH patients are younger, have less severe clinical presentation, smaller hematoma volume, more often structural etiology, and better outcome than other ICH patients. They exhibit a similar risk of epilepsy as non-occipital ICHs., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: We aimed to determine the regional incidence and mortality of adult epilepsy, compare mortality rates with the expected in the general population, and identify predictors of shorter survival., Materials and Methods: We included all consecutive newly diagnosed epilepsy visited at a university hospital in Spain throughout 2012. We collected all relevant clinical data up to December 2018. We analyzed the incidence of epilepsy in our catchment area, studied mortality rates, and explored factors predictive of shorter survival., Results: The annual incidence of epilepsy among adults was 37.7 cases/100,000 inhabitants. We studied 110 patients with newly diagnosed epilepsy. Mean age was 52.6 years, and 53.6% were men. Eighty-nine patients (80.9%) had focal epilepsy, 50 (45.5%) had a structural etiology, and 45 (40.9%) had an unknown cause. Nineteen patients died over a median follow-up of 5.3 years. Mortality was almost four times higher than expected in general population and was increased in patients aged 40-59 years. Mortality rates were 5.5%, 12%, and 16.8% in the first, second, and third year, after which they remained stable to the end of follow-up. Independent predictors of mortality were age (p = 0.001), tumor-related epilepsy (p = 0.003), and generalized seizures (p = 0.020)., Conclusions: There is a high incidence of epilepsy among adults in our geographic area, with a mortality rate quadrupling that expected for the general population. Age, generalized seizures, and tumor-related epilepsy are independently associated with a higher risk of death., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine the health economic burden of epilepsy for Australians of working age by using life table modeling and to model whether improved seizure control may result in substantial health economic benefits., Methods: Life table modeling was used for working age Australians aged 15-69 years with epilepsy and the cohort was followed until age 70 years. Published 2017 population and epilepsy-related data regarding epilepsy prevalence, mortality, and productivity were used. This model was then re-simulated, assuming the cohort no longer had epilepsy. Differences in outcomes between these cohorts were attributed to epilepsy. Scenarios were also simulated in which the proportion of seizure-free patients increased from baseline 70% up to 75% and 80%., Results: In 2017, Australians of working age with epilepsy followed until age 70 years were predicted to experience over 14,000 excess deaths, more than 78,000 years of life lost, and over 146,000 productivity-adjusted life years lost due to epilepsy. This resulted in lost gross domestic product (GDP) of US $22.1 billion. Increasing seizure freedom by 5% and 10% would reduce health care costs, save years of life, and translate to US $2.6 billion and US $5.3 billion GDP retained for seizure freedom rates of 75% and 80%, respectively., Conclusions: Our study highlights the considerable societal and economic burden of epilepsy. Relatively modest improvements in overall seizure control could bring substantial economic benefits., (© 2020 American Academy of Neurology.)

Objective: We conducted a nationwide case-control study in Sweden to test the hypothesis that antiepileptic drugs (AEDs) mono- or polytherapy, adherence, antidepressants, neuroleptics, β-blockers, and statins are associated with sudden unexpected death in epilepsy (SUDEP) risk., Methods: Included were 255 SUDEP cases and 1,148 matched controls. Information on clinical factors and medications came from medical records and the National Patient and Prescription Registers. The association between SUDEP and medications was assessed by odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for potential risk factors including type of epilepsy, living conditions, comorbidity, and frequency of generalized tonic-clonic seizures (GTCS)., Results: Polytherapy, especially taking 3 or more AEDs, was associated with a substantially reduced risk of SUDEP (OR 0.31, 95% CI 0.14-0.67). Combinations including lamotrigine (OR 0.55, 95% CI 0.31-0.97), valproic acid (OR 0.53, 95% CI 0.29-0.98), and levetiracetam (OR 0.49, 95% CI 0.27-0.90) were associated with reduced risk. No specific AED was associated with increased risk. Regarding monotherapy, although numbers were limited, the lowest SUDEP risk was seen in users of levetiracetam (0.10, 95% CI 0.02-0.61). Having nonadherence mentioned in the medical record was associated with an OR of 2.75 (95% CI 1.58-4.78). Statin use was associated with a reduced SUDEP risk (OR 0.34, 95% CI 0.11-0.99) but selective serotonin reuptake inhibitor use was not., Conclusion: These results provide support for the importance of medication adherence and intensified AED treatment for patients with poorly controlled GTCS in the effort to reduce SUDEP risk and suggest that comedication with statins may reduce risk., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Non-trauma fracture (NTFx), an indicator of skeletal fragility, is a risk factor for mortality among adults with epilepsy. NTFx may elicit its effect on mortality through development of respiratory disease (RD) and cardiovascular disease (CVD). Therefore, the objective was to determine if NTFx increases risk for RD and CVD, and if incident RD and CVD mediates the association between NTFx and mortality for adults with epilepsy., Methods: Data were gathered from Optum Clinformatics® Data Mart years 2011-2016 for this retrospective cohort study. Diagnosis codes identified adults (≥18 years) with epilepsy, NTFx, RD (pneumonia, chronic obstructive pulmonary disease, interstitial/pleura disease), CVD (ischemic heart disease, heart failure, cerebrovascular disease), and baseline comorbidities. Crude incidence rate (IR) and crude IR ratio (IRR and 95 % confidence intervals [CI]) was estimated for mortality and incidence of RD and CVD for up to 2 years of follow up. Cox regression estimated hazard ratios (HR and 95 % CI) for each outcome, comparing adults with vs. without NTFx after adjusting for sociodemographics and baseline comorbidities. Separate mediation analyses estimated the extent that incident RD and CVD mediated the association between NTFx and mortality., Results: Adults with epilepsy with vs. without NTFx had a higher crude incidence of mortality (IRR = 2.42; 95 %CI = 2.24-2.60) and each RD and CVD measure (IRR = 1.60-2.02). After adjustments, the HR remained elevated for mortality (HR = 1.66; 95 %CI = 1.54-1.79) and each RD and CVD measure (HR = 1.18-1.61). Incident pneumonia and interstitial/pleura disease mediated 9.82 % and 7.51 %, respectively, of the association between NTFx and mortality., Conclusions: In a relatively short follow up of 2 years, NTFx was a robust risk factor for mortality, RD, and CVD among adults with epilepsy, and post-NTFx incidence of RD mediated a portion of the association between NTFx and mortality., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Sudden unexpected death in epilepsy (SUDEP) is the second leading neurological cause of potential years of lifelost after stroke. Despite growing numbers of studies on social aspects of epilepsy, there is a paucity of research on the awareness of SUDEP among the parents of children with epilepsy (CWE), especially in Turkey. In this study, we aimed to evaluate the knowledge of parents of the CWE regarding SUDEP in the tertiary setting., Material and Methods: A total of 146 parents (108 female) aged 19 to 55 years (median age:34) of CWE were included at Marmara University, School of Medicine, Department of Pediatric Neurology outpatient clinic between May 2018 and September 2018. A total of 30 multiple-choice questions and a written survey were administered, which consisted of three sections. In the first section, the sociodemographics of parents and CWE were questioned. In the second section, the severity of epilepsy was evaluated. In the third section, the knowledge level and awareness of parents of CWE were assessed., Results: Of 146 parents, only 16.6% previously heard about SUDEP, while 45% of them heard from their relatives. The presence of prior knowledge of SUDEP was associated with the presence of prolonged postictal confusion and longer duration of epilepsy (p < 0.05). Ninety-seven (66%) parents desired to be informed about SUDEP, while 76 (54.7%) of them agreed that this information should be given at the time of diagnosis. The degree of anxiety in parents regarding death of epilepsy-related causes was significantly related with prolonged postictal confusion (p < 0.001) and using three or more antiepileptic drugs (p = 0.005)., Conclusion: Our data suggest that knowledge about SUDEP among parents with CWE found inadequate in Turkey. There should be much effort to inform parents and caregivers in epilepsy clinics on SUDEP, which may help to reduce the associated risk factors., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In this narrative review, we will discuss some of the significant risks and dramatic consequences that are associated with epilepsy: depression, suicide, seizure-related injuries, and mortality, both in adults and in children. Considering the high prevalence of depression among people with epilepsy (PWE), routine and periodic screening of all PWE for early detection and appropriate management of depression is recommended. PWE should be screened for suicidal ideation regularly and when needed, patients should be referred for a psychiatric evaluation and treatment. When starting an antiepileptic drug (AED) or switching from one to another AED, patients should be advised to report to their treating physician any change in their mood and existence of suicidal ideation. The risk of injuries for the general epilepsy population is increased only moderately. The risk is higher in selected populations attending epilepsy clinics and referral centers. This being said, there are PWE that may suffer frequent, severe, and sometimes even life-threatening seizure-related injuries. The most obvious way to reduce risk is to strive for improved seizure control. Finally, PWE have a 2-3 times higher mortality rate than the general population. Deaths in PWE may relate to the underlying cause of epilepsy, to seizures (including sudden unexpected death in epilepsy [SUDEP] and seizure related injuries) and to status epilepticus, as well as to other conditions that do not appear directly related to epilepsy. Improving seizure control and patient education may be the most important measures to reduce epilepsy related mortality in general and SUDEP in particular.

Inborn errors of metabolism can cause epileptic encephalopathies. Biallelic loss-of-function variants in the ITPA gene, encoding inosine triphosphate pyrophosphatase (ITPase), have been reported in epileptic encephalopathies with lack of myelination of the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices (MIM:616647). ITPase plays an important role in purine metabolism. In this study, we identified two novel homozygous ITPA variants, c.264-1 G > A and c.489-1 G > A, in two unrelated consanguineous families. The probands had epilepsy, microcephaly with characteristic magnetic resonance imaging findings (T2 hyperintensity signals in the pyramidal tracts of the internal capsule, delayed myelination, and thin corpus callosum), hypotonia, and developmental delay; both died in early infancy. Our report expands the knowledge of clinical consequences of biallelic ITPA variants.

Objective: To investigate the hypothesis that patients diagnosed with psychogenic nonepileptic seizures (PNES) on video-EEG monitoring (VEM) have increased mortality by comparison to the general population., Methods: This retrospective cohort study included patients evaluated in VEM units of 3 tertiary hospitals in Melbourne, Australia, between January 1, 1995, and December 31, 2015. Diagnosis was based on consensus opinion of experienced epileptologists and neuropsychiatrists at each hospital. Mortality was determined in patients diagnosed with PNES, epilepsy, or both conditions by linkage to the Australian National Death Index. Lifetime history of psychiatric disorders in PNES was determined from formal neuropsychiatric reports., Results: A total of 5,508 patients underwent VEM. A total of 674 (12.2%) were diagnosed with PNES, 3064 (55.6%) with epilepsy, 175 (3.2%) with both conditions, and 1,595 (29.0%) received other diagnoses or had no diagnosis made. The standardized mortality ratio (SMR) of patients diagnosed with PNES was 2.5 (95% confidence interval [CI] 2.0-3.3). Those younger than 30 had an 8-fold higher risk of death (95% CI 3.4-19.8). Direct comparison revealed no significant difference in mortality rate between diagnostic groups. Among deaths in patients diagnosed with PNES (n = 55), external causes contributed 18%, with 20% of deaths in those younger than 50 years attributed to suicide, and "epilepsy" was recorded as the cause of death in 24%., Conclusions: Patients diagnosed with PNES have a SMR 2.5 times above the general population, dying at a rate comparable to those with drug-resistant epilepsy. This emphasizes the importance of prompt diagnosis, identification of risk factors, and implementation of appropriate strategies to prevent potential avoidable deaths., (© 2020 American Academy of Neurology.)

Objectives: At any point in time, a person's lifetime health is the number of healthy life years they are expected to experience during their lifetime. In this article we propose an equity-relevant health metric, Health Adjusted Age at Death (HAAD), that facilitates comparison of lifetime health for individuals at the onset of different medical conditions, and allows for the assessment of which patient groups are worse off. A method for estimating HAAD is presented, and we use this method to rank four conditions in six countries according to several criteria of "worse off" as a proof of concept., Methods: For individuals with specific conditions HAAD consists of two components: past health (before disease onset) and future expected health (after disease onset). Four conditions (acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), schizophrenia, and epilepsy) are analysed in six countries (Ethiopia, Haiti, China, Mexico, United States and Japan). Data from 2017 for all countries and for all diseases were obtained from the Global Burden of Disease Study database. In order to assess who are the worse off, we focus on four measures: the proportion of affected individuals who are expected to have HAAD<20 (T20), the 25th and 75th percentiles of HAAD for affected individuals (Q1 and Q3, respectively), and the average HAAD (aHAAD) across all affected individuals., Results: Even in settings where aHAAD is similar for two conditions, other measures may vary. One example is AML (aHAAD = 59.3, T20 = 2.0%, Q3-Q1 = 14.8) and ALL (58.4, T20 = 4.6%, Q3-Q1 = 21.8) in the US. Many illnesses, such as epilepsy, are associated with more lifetime health in high-income settings (Q1 in Japan = 59.2) than in low-income settings (Q1 in Ethiopia = 26.3)., Conclusion: Using HAAD we may estimate the distribution of lifetime health of all individuals in a population, and this distribution can be incorporated as an equity consideration in setting priorities for health interventions., Competing Interests: The authors have declared that no competing interests exist.

This case series aimed to characterize the clinical features, management, and outcomes of apnea in infants with trisomy 18. Participants in this study were infants with trisomy 18 who were born alive and admitted to the neonatal intensive care unit in Kyushu University Hospital from 2000 to 2018. Retrospective analysis was performed on clinical data recorded in our department. Twenty-seven infants with trisomy 18 were admitted to our hospital during the study period, of which 25 (nine males, 16 females) were enrolled as eligible participants in this study. Among them, 14 started presenting with apnea from median 3.5 days of age (range 0-47d). In these infants with apnea, eight received respiratory support of positive pressure ventilation (PPV). The 1-year survival rate of infants in the PPV group was higher than that of non-PPV-supported infants (5 out of 8 vs 0 out of 6 infants). Five PPV-supported infants received a diagnosis of epilepsy, which was controlled by antiepileptic drugs. Postnatal respiratory intervention provides better prognosis in infants with trisomy 18. Improved survival leads to accurate diagnosis and treatment of apneic events in association with epilepsy. WHAT THIS PAPER ADDS: Respiratory support is effective against apnea in infants with trisomy 18. Intervention with ventilation provides a higher chance of prolonged survival. Improved survival leads to the accurate diagnosis and treatment of epilepsy-associated apnea., (© 2019 Mac Keith Press.)

With the exponential development of mobile health technologies over the past ten years, there has been a growing interest in the potential applications in the field of epilepsy, and specifically for seizure detection. Better detection of seizures is probably one of the best ways to improve patient safety. Overall, we are observing an exponential increase in the number of non-EEG based seizure detection systems and a progressive homogenization of their evaluation procedures. Most importantly, the properties of these devices for detection of tonic-clonic seizures are now very interesting, both in terms of sensitivity and in terms of false-alarm rates. Accordingly, we might expect that these be used in clinical practice in the near future, especially in patients at high risk of seizure-related injuries or sudden unexpected death in epilepsy (SUDEP)., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)