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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).)

Introduction: It is very important to provide epileptic patients with sufficient knowledge of SUDEP and empower them regarding its prevention. This study aimed to evaluate the effect of the educational intervention of receiving information about SUDEP on medication adherence, anxiety and depression, and the safety of epileptic patients., Patients and Methods: This study was conducted on 60 epilepsy patients referred to the specialized epilepsy clinic of Imam Hossein Hospital in Tehran, Iran, from April 2022 to February 2023. Data were collected by the Morisky medication adherence scale, hospital anxiety and depression scales, and the researcher-made checklists of bathing safety, sleep safety, and patient seizure preparation before and after the intervention. The educational intervention was conducted through the video and pamphlet regarding knowledge about SUDEP. Wilcoxon and paired t-tests were used to compare the data changes following the intervention., Results: Most patients were male, with an age range of 18 to 29 years old. The mean score of anxiety and depression before and after the educational intervention did not show a statistically significant difference (P = 0.928); however, the mean scores of medication adherence, bathing safety, sleep safety, and preparation for seizure after the educational intervention increased significantly (P < 0.05)., Conclusion: Knowledge about SUDEP would be able to encourage epileptic patients to better adhere to medication; and make them empower regarding seizure preparation, bathing safety, and sleep safety., 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although animal models have helped to elaborate meaningful hypotheses about the pathophysiology of sudden and unexpected death in epilepsy (SUDEP), specific prevention strategies are still lacking, potentially reflecting the limitations of these models and the intrinsic difficulties of investigating SUDEP. The interpretation of preclinical data and their translation to diagnostic and therapeutic developments in patients thus require a high level of confidence in their relevance to model the human situation. Preclinical models of SUDEP are heterogeneous and include rodent and nonrodent species. A critical aspect is whether the animals have isolated seizures exclusively induced by a specific trigger, such as models where seizures are elicited by electrical stimulation, pharmacological intervention, or DBA mouse strains, or whether they suffer from epilepsy with spontaneous seizures, with or without spontaneous SUDEP, either of nongenetic epilepsy etiology or from genetically based developmental and epileptic encephalopathies. All these models have advantages and potential disadvantages, but it is important to be aware of these limitations to interpret data appropriately in a translational perspective. The majority of models with spontaneous seizures are of a genetic basis, whereas SUDEP cases with a genetic basis represent only a small proportion of the total number. In almost all models, cardiorespiratory arrest occurs during the course of the seizure, contrary to that in patients observed at the time of death, potentially raising the issue of whether we are studying models of SUDEP or models of periseizure death. However, some of these limitations are impossible to avoid and can in part be dependent on specific features of SUDEP, which may be difficult to model. Several preclinical tools are available to address certain gaps in SUDEP pathophysiology, which can be used to further validate current preclinical models., (© 2023 International League Against Epilepsy.)

Objectives: DEPDC5 is a common causative gene in familial focal epilepsy with or without malformations of cortical development. Its pathogenic variants also confer a significantly higher risk for sudden unexpected death in epilepsy (SUDEP), providing opportunities to investigate the pathophysiology intersecting neurodevelopment, epilepsy, and cardiorespiratory function. There is an urgent need to gain a mechanistic understanding of DEPDC5-related epilepsy and SUDEP, identify biomarkers for patients at high risk, and develop preventive interventions., Methods: Depdc5 was specifically deleted in excitatory or inhibitory neurons in the mouse brain to determine neuronal subtypes that drive epileptogenesis and SUDEP. Electroencephalogram (EEG), cardiac, and respiratory recordings were performed to determine cardiorespiratory phenotypes associated with SUDEP. Baseline respiratory function and the response to hypoxia challenge were also studied in these mice., Results: Depdc5 deletion in excitatory neurons in cortical layer 5 and dentate gyrus caused frequent generalized tonic-clonic seizures and SUDEP in young adult mice, but Depdc5 deletion in cortical interneurons did not. EEG suppression immediately following ictal offset was observed in fatal and non-fatal seizures, but low amplitude rhythmic theta frequency activity was lost only in fatal seizures. In addition, these mice developed baseline respiratory dysfunction prior to SUDEP, during which ictal apnea occurred long before terminal cardiac asystole., Interpretation: Depdc5 deletion in excitatory neurons is sufficient to cause DEPDC5-related epilepsy and SUDEP. Ictal apnea and respiratory dysregulation play critical roles in SUDEP. Our study also provides a novel mouse model to investigate the underlying mechanisms of DEPDC5-related epilepsy and SUDEP. ANN NEUROL 2023;94:812-824., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Patients with uncontrolled epilepsy experience repeated seizures putting them at increased risk for sudden unexpected death in epilepsy (SUDEP). Data from human patients have led to the hypothesis that SUDEP results from severe cardiorespiratory suppression after a seizure, which may involve pathological deficiencies in the brainstem serotonin (5-HT) system. Rats with a genomic Kcnj16 mutation (SS Kcnj16-/- rats) are susceptible to sound-induced generalized tonic-clonic seizures (GTCS) which, when repeated once daily for up to 10 days (10-day seizure protocol), increased mortality, particularly in male rats. Here, we test the hypothesis that repeated seizures across the 10-day protocol will cause a progressive ventilatory dysfunction due to time-dependent 5-HT deficiency. Initial severe seizures led to ictal and postictal apneas and transient decreases in breathing frequency, ventilatory drive, breath-to-breath variability, and brief hypoventilation. These seizure-induced effects on ventilation were exacerbated with increasing seizures and ventilatory chemoreflexes became further impaired after repeated seizures. Tissue analyses of key brainstem regions controlling breathing showed time-dependent 5-HT system suppression and increased immunoreactivity for IBA-1 (microglial marker) without changes in overall cell counts at 3, 7, and 10 days of seizures. Fluoxetine treatment in SS Kcnj16-/- rats prevented repeated seizure-induced progressive respiratory suppression but failed to prevent seizure-related mortality. We conclude that repeated seizures cause a progressive compromise of ventilatory control in the immediate postictal period largely mediated by serotonin system suppression in brainstem regions of respiratory control. However, other unknown factors contribute to overall survival following repeated seizures in this model. NEW & NOTEWORTHY This study demonstrated that repeated seizures in a novel rat model (SS Kcnj16-/- rats) caused a progressively greater ventilatory dysfunction in the immediate postictal period associated with brainstem serotonin (5-HT) suppression. Augmenting brain 5-HT with a selective serotonin reuptake inhibitor prevented the progressive ventilatory dysfunction induced by repeated seizures but failed to prevent seizure-related mortality, suggesting that repeated seizures may lead to cardiorespiratory suppression and failure through multiple mechanisms.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in children and adults living with epilepsy. The incidence of SUDEP is comparable in both children and adults; it is approximately 1.2 per 1000 person years. The pathophysiology of SUDEP is not well understood but may involve mechanisms such as cerebral shutdown, autonomic dysfunction, altered brainstem function, and cardiorespiratory demise. Risk factors for SUDEP include the presence of generalized tonic-clonic seizures, nocturnal seizures, possible genetic predisposition, and non-adherence to antiseizure medications. Pediatric-specific risk factors are not fully elucidated. Despite recommendations from consensus guidelines, many clinicians still do not follow the practice of counseling their patients about SUDEP. SUDEP prevention has been an area of important research focus and includes several strategies, such as obtaining seizure control, optimizing treatment regimens, nocturnal supervision, and seizure detection devices. This review discusses what is currently known about SUDEP risk factors and reviews current and future preventive strategies for SUDEP., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Epilepsy is at times a fatal disease. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in people with intractable epilepsy and is defined by exclusion; non-accidental, non-toxicologic, and non-anatomic causes of death. While SUDEP often follows a bilateral tonic-clonic seizure, the mechanisms that ultimately lead to terminal apnea and then asystole remain elusive and there is a lack of preventative treatments. Based on the observation that discrete seizures lead to local and postictal vasoconstriction, resulting in hypoperfusion, hypoxia and behavioural disturbances in the forebrain we reasoned those similar mechanisms may play a role in SUDEP when seizures invade the brainstem. Here we tested this neurovascular-based hypothesis of SUDEP in awake non-anesthetized mice by pharmacologically preventing seizure-induced vasoconstriction, with cyclooxygenase-2 or L-type calcium channel antagonists. In both acute and chronic mouse models of seizure-induced premature mortality, ibuprofen and nicardipine extended life while systemic drug levels remained high enough to be effective. We also examined the potential role of spreading depolarization in the acute model of seizure-induced premature mortality. These data provide a proof-of-principle for the neurovascular hypothesis of SUDEP rather than spreading depolarization and the use of currently available drugs to prevent it., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose of Review: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in patients with epilepsy. This review highlights the recent literature regarding epidemiology on a global scale, putative mechanisms and thoughts towards intervention and prevention., Recent Findings: Recently, numerous population-based studies have examined the incidence of SUDEP in many countries. Remarkably, incidence is quite consistent across these studies, and is commensurate with the recent estimates of about 1.2 per 1000 patient years. These studies further continue to support that incidence is similar across the ages and that comparable factors portend heightened risk for SUDEP. Fervent research in patients and animal studies continues to hone the understanding of potential mechanisms for SUDEP, especially those regarding seizure-induced respiratory dysregulation. Many of these studies and others have begun to lay out a path towards identification of improved treatment and prevention means. However, continued efforts are needed to educate medical professionals about SUDEP risk and the need to disclose this to patients., Summary: SUDEP is a devastating potential outcome of epilepsy. More is continually learned about risk and mechanisms from clinical and preclinical studies. This knowledge can hopefully be leveraged into preventive measures in the near future., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in people with epilepsy (PWE). Postictal apnea leading to cardiac arrest is the most common sequence of terminal events in witnessed cases of SUDEP, and postconvulsive central apnea has been proposed as a potential biomarker of SUDEP susceptibility. Research in SUDEP animal models has led to the serotonin and adenosine hypotheses of SUDEP. These neurotransmitters influence respiration, seizures, and lethality in animal models of SUDEP, and are implicated in human SUDEP cases. Adenosine released during seizures is proposed to be an important seizure termination mechanism. However, adenosine also depresses respiration, and this effect is mediated, in part, by inhibition of neuronal activity in subcortical structures that modulate respiration, including the periaqueductal gray (PAG). Drugs that enhance the action of adenosine increase postictal death in SUDEP models. Serotonin is also released during seizures, but enhances respiration in response to an elevated carbon dioxide level, which often occurs postictally. This effect of serotonin can potentially compensate, in part, for the adenosine-mediated respiratory depression, acting to facilitate autoresuscitation and other restorative respiratory response mechanisms. A number of drugs that enhance the action of serotonin prevent postictal death in several SUDEP models and reduce postictal respiratory depression in PWE. This effect of serotonergic drugs may be mediated, in part, by actions on brainstem sites that modulate respiration, including the PAG. Enhanced activity in the PAG increases respiration in response to hypoxia and other exigent conditions and can be activated by electrical stimulation. Thus, we propose the unifying hypothesis that seizure-induced adenosine release leads to respiratory depression. This can be reversed by serotonergic action on autoresuscitation and other restorative respiratory responses acting, in part, via the PAG. Therefore, we hypothesize that serotonergic or direct activation of this brainstem site may be a useful approach for SUDEP prevention., (© 2023 International League Against Epilepsy.)

The dorsal raphe nucleus (DR) and the pre-Bötzinger complex (PBC) may play an important role in regulating seizure-induced respiratory arrest (S-IRA), the main contributor to sudden unexpected death in epilepsy. Here, we describe pharmacological, optogenetic, and retrograde labeling approaches to specifically modulate the DR to PBC serotonergic pathway. We detail steps for implanting optical fibers and viral infusion into DR and PBC regions and optogenetic techniques for exploring the role of 5-hydroxytryptophan (5-HT) neural circuit of DR-PBC in S-IRA. For complete details on the use and execution of this protocol, please refer to Ma et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sudden Unexpected Death in Epilepsy (SUDEP) is a major concern for people with epilepsy, their families, their care givers, and medical professionals. There is inconsistency in the SUDEP counselling doctors provide, compared to what is recommended in clinical guidelines. Numerous national and international surveys have highlighted how epilepsy professionals, usually doctors, deliver SUDEP risk counselling, particularly, when they deliver it and to whom. These surveys help understand the unmet need, develop suitable strategies, and raise awareness among clinicians with the eventual goal to reduce SUDEPs. However, there is no standardised survey or essential set of questions identified that can be used to evaluate SUDEP counselling practice globally. This focused review analyses the content of all published SUDEP counselling surveys for medical professionals (n=16) to date covering over 4000 doctors across over 30 countries and five continents. It identifies 36 question themes across three topics. The questions are then reviewed by an expert focus group of SUDEP communication experts including three doctors, an expert statistician and SUDEP Action, an UK based charity specialising in epilepsy deaths with a pre-set criterion. The review and focus group provide ten essential questions that should be included in all future surveys inquiring on SUDEP counselling. They could be used to evaluate current practice and compare findings over time, between services, across countries and between professional groups. They are provided as a template to download and use. The review also explores if there is a continued need in future for similar surveys to justify this activity., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: A clinical risk score for sudden unexpected death in epilepsy (SUDEP) in patients with drug-resistant focal epilepsy could help improve prevention., Methods: A case-control study was conducted including (i) definite or probable SUDEP cases collected by the French National Sentinel Mortality Epilepsy Network and (ii) control patients from the French national research database of epilepsy monitoring units. Patients with drug-resistant focal epilepsy were eligible. Multiple logistic regressions were performed. After sensitivity analysis and internal validation, a simplified risk score was developed from the selected variables., Results: Sixty-two SUDEP cases and 620 controls were included. Of 21 potential predictors explored, seven were ultimately selected, including generalized seizure frequency (>1/month vs. <1/year: adjusted odds ratio [AOR] 2.6, 95% confidence interval [CI] 1.25-5.41), nocturnal or sleep-related seizures (AOR 4.49, 95% CI 2.68-7.53), current or past depression (AOR 2.0, 95% CI 1.19-3.34) or the ability to alert someone of an oncoming seizure (AOR 0.57, 95% CI 0.33-0.98). After internal validation, a clinically usable score ranging from -1 to 8 was developed, with high discrimination capabilities (area under the receiver operating curve 0.85, 95% CI 0.80-0.90). The threshold of 3 has good sensitivity (82.3%, 95% CI 72.7-91.8), whilst keeping a good specificity (82.7%, 95% CI 79.8-85.7)., Conclusions: These results outline the importance of generalized and nocturnal seizures on the occurrence of SUDEP, and show a protective role in the ability to alert someone of an oncoming seizure. The SUDEP-CARE score is promising and will need external validation. Further work, including paraclinical explorations, could improve this risk score., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Sudden unexpected death in epilepsy (SUDEP) is the major cause of premature death in epilepsy patients, particularly those with refractory epilepsy. Sudden unexpected death in epilepsy is thought to be related to peri-ictal cardiac dysfunction, respiratory depression, and autonomic dysfunction, albeit the exact etiology is unknown. Sudden unexpected death in epilepsy prevention remains a huge challenge. The sole presence and frequency of generalized tonic-clonic seizures (GTCS) are the most important risk factors for SUDEP, and nocturnal monitoring may lower the risk with the use of remote listening devices. In addition, studies in animal models of SUDEP have discovered that multiple neurotransmitters, including serotonin (5-HT) and adenosine, may be involved in the pathophysiological mechanisms of SUDEP and that these neurotransmitters could be the targets of future pharmacological intervention for SUDEP. The latest research findings on the epidemiology, clinical risk factors, and probable causes of SUDEP are presented in this review., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Persons with epilepsy (PWE) have an up to 34-fold increased risk of dying suddenly and unexpectedly compared with the general population. Despite being potentially preventable by optimal care, sudden unexpected death in epilepsy (SUDEP) is one of the most frequent causes of death in PWE, especially in children and younger adults. The incidence of SUDEP in the general epilepsy population is rather consistent at 1.2 to 1.3 per 1000 person-year across series. Several risk factors for SUDEP have been identified, but with focal-to-bilateral or generalized tonic-clonic seizures and sleeping alone as the most significant. Thereby, optimal care and nocturnal surveillance might decrease the risk of SUDEP. Finally, PWE wants information about SUDEP, and providing this information might increase adherence to the treatment and thereby good seizure control. This narrative review provides an update on SUDEP., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is a fatal event, occurring in patients with epilepsy, in which seizures may or may not precede the exitus, and no other potential causes of death are identifiable. The proposed pathophysiological mechanisms for SUDEP include cardio-respiratory dysfunctions, brainstem arousal system impairment, and dysregulation in the neurotransmitter/neuromodulator systems. This narrative review provides an overview of primary research on SUDEP in paediatric populations. Some studies report an incidence of paediatric SUDEP which is about five times lower than in adults (between 0.02 and 0,34 per 1,000 person-years) even if more recent studies suggested similar incidence rates than in adulthood (between 1.20 / 1,000 and 1.45 / 1,000 person per years). Risk factors for SUDEP in children include genetic predisposition, neurological comorbidities, epilepsy phenotype, adequacy/adherence to treatment, adequate supervision by caregivers and access to adequate health care support. The early identification of risk factors, the definition of reliable biomarkers and the building of efficacious preventive strategies, including parental/caregiver counselling, novel technological devices, and pharmacological treatments, may reduce the risk of paediatric SUDEP., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare, (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is a tragic and unexpected cause of death in patients with a known diagnosis of epilepsy. It occurs in up to 6.3 to 9.3/1,000 patients with drug-resistant epilepsy. The main three risk factors associated with SUDEP are the presence of generalized tonic-clonic seizures, the presence of a seizure in the past year, and an intellectual disability. There are several mechanisms that can result in SUDEP. The most likely sequence of events appears to be a convulsive seizure, overactivation of the autonomic nervous system, cardiorespiratory dysfunction, and death. While the risk of SUDEP is relatively high in patients with drug-resistant epilepsy, studies indicate that more than 50% of patients and caregivers are unaware of the diagnosis. Counseling about the diagnosis and preventative measures at the time of diagnosis is important. There are numerous interventions that may reduce the risk of SUDEP, including conservative measures such as nocturnal surveillance with a bed partner (where applicable) and automated devices. Optimizing seizure control with antiseizure medications and surgical interventions can result in a reduced risk of SUDEP., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Sudden Unexpected Death in Epilepsy (SUDEP) accounts for 20% of mortality in those with recurrent seizures. While risk factors, monitoring systems, and standard practices are in place, the pathophysiology of SUDEP is still not well understood. Better knowledge of SUDEP and its potential mechanisms of action is crucial to reducing risk in this patient population and developing potential treatment options. Clinical studies and animal models of SUDEP suggest that diminished post-ictal respiratory control may be the dominant mechanism contributing to mortality. Recently, it was demonstrated that the depletion of the neuropeptide galanin in the amygdala occurs in human SUDEP. The amygdala plays a key role in the central integration of respiratory signaling; the depletion of galanin may represent a critical change that predisposes individuals to SUDEP., Materials and Methods: To evaluate the impact of enhancing galaninergic signaling to potentially protect against SUDEP, we studied seizure-induced respiratory arrest (S-IRA) following central (intracerebroventricular, intra-amygdala) and systemic (intraperitoneal, subcutaneous) administration of galanin analogs. Seizure naïve and seizure experienced (fully kindled) mice were tested., Results: Central and systemically administered galanin analogs protect against S-IRA in naïve C57Bl/6J mice. Differential efficacy between receptor subtype-selective analogs varied based on the route of administration. Sub-chronic systemic administration at doses that reduced 6 Hz seizures also protected against S-IRA. Acute treatment benefits also extended to fully kindled mice experiencing tonic extension., Significance: These data demonstrate that galanin analogs may be protective against post-ictal respiratory collapse., Competing Interests: CM was a former full-time employee of NeuroAdjuvants, Inc., a biotechnology company seeking to develop galanin-based neuropeptides for CNS conditions. CM holds two patents for galanin-based therapies for CNS conditions (University of Utah). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Collard, Aziz, Rapp, Cutshall, Duyvesteyn and Metcalf.)

People with epilepsy (PWE) may die suddenly and unexpectedly and without a clear under-lying pathological etiology; this is called SUDEP (sudden unexpected death in epilepsy). The pooled estimated incidence rate for SUDEP is 23 times the incidence rate of sudden death in the general population with the same age. Empowering healthcare professionals, PWE, and their care-givers with the appropriate knowledge about SUDEP is very important to enable efficient preventive measures in PWE. In the current narrative review, following a brief discussion on the definition, epidemiology, and risk factors for SUDEP, the authors discuss the importance of appropriately educating healthcare professionals, PWE, and their caregivers about SUDEP., Competing Interests: Conflict of interest Boulenouar Mesraoua: Grant for Qatar National Research Fund. Ali A. Asadi-Pooya: Honoraria from Cobel Daruo, Tekaje, Sanofi, Actoverco, and RaymandRad; Royalty: Oxford University Press (Book publication); Grant from the National Institute for Medical Research Development. TorbjörnTomson reports advisory board and speaker’s honoraria from Arvelle, Eisai, GW Pharma, Sanofi, Sun Pharmaceutical Industries Ltd, and UCB, and research support from Arvelle, Bial, Eisai, GlaxoSmithKline, Teva, GW Pharma, Arvelle, and UCB., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sudden and unexpected death is defined as sudden death without any obvious cause and where the person was seen in habitual conditions within the last 24 hours before death. Persons with epilepsy have a 34-fold increased risk of dying suddenly and unexpectedly compared with the background population. In persons with epilepsy these deaths are referred to as sudden unexpected death in epilepsy (SUDEP). This review finds that the risk is highest in younger adults, and SUDEP is the second leading cause of death in persons with epilepsy aged 1-49 years. Good seizure control is important in the prevention of SUDEP.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among epilepsy patients, occurring even more frequently in cases with anti-epileptic drug resistance. Despite some advancements in characterizing SUDEP, the underlying mechanism remains incompletely understood. This review summarizes the latest advances in our understanding of the pathogenic mechanisms of SUDEP, in order to identify possible targets for the development of new strategies to prevent SUDEP. Based on our previous research along with the current literature, we focus on the role of sleep-disordered breathing (SDB) and its related neural mechanisms to consider the possible roles of monoaminergic neurons in the modulation of respiration during sleep and the occurrence of SUDEP. Overall, this review suggests that targeting the monoaminergic neurons is a promising approach to preventing SUDEP. The proposed roles of SDB and related monoaminergic neural mechanisms in SUDEP provide new insights for explaining the pathogenesis of SUDEP., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is a devastating yet overlooked complication of epilepsy. The rare and complex nature of SUDEP makes it challenging to study. No prediction or prevention of SUDEP is currently available in a clinical setting. In the past decade, significant advances have been made in our knowledge of the pathophysiologic cascades that lead to SUDEP. In particular, studies of brain, heart, and respiratory functions in both human patients at the epilepsy monitoring unit and animal models during fatal seizures provide critical information to integrate computational tools for SUDEP prediction. The rapid advances in automated seizure detection and prediction algorithms provide a fundamental framework for their adaption in predicting SUDEP. If a SUDEP can be predicted, then there will be a potential for medical intervention to be administered, either by their caregivers or via an implanted device automatically delivering electrical stimulation or medication, and finally save lives from fatal seizures. This article presents recent developments of SUDEP studies focusing on the pathophysiologic basis of SUDEP and computational implications of machine learning techniques that can be adapted and extended for SUDEP prediction. This article also discusses some novel ideas for SUDEP prediction and rescue including principal component analysis and closed-loop intervention., (© 2022 Bin Gu and Hojjat Adeli, published by De Gruyter, Berlin/Boston.)

Sudden Unexpected Death in Epilepsy (SUDEP) remains a leading cause of death in people with epilepsy. Despite the constant risk for patients and bereavement to family members, to date the physiological mechanisms of SUDEP remain unknown. Here we explore the potential to identify putative predictive signals of SUDEP from online digital behavioral data using text and sentiment analysis tools. Specifically, we analyze Facebook timelines of six patients with epilepsy deceased due to SUDEP, donated by surviving family members. We find preliminary evidence for behavioral changes detectable by text and sentiment analysis tools. Namely, in the months preceding their SUDEP event patient social media timelines show: i) increase in verbosity; ii) increased use of functional words; and iii) sentiment shifts as measured by different sentiment analysis tools. Combined, these results suggest that social media engagement, as well as its sentiment, may serve as possible early-warning signals for SUDEP in people with epilepsy. While the small sample of patient timelines analyzed in this study prevents generalization, our preliminary investigation demonstrates the potential of social media data as complementary data in larger studies of SUDEP and epilepsy., 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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Seizure-related injuries and sudden unexpected death in epilepsy (SUDEP) are severe complications of epilepsy. Risk factors include pharmacoresistant epilepsy, high frequency of tonic-clonic seizures, and absence of nocturnal supervision. Seizure detection devices are medical devices that rely on movement and other biological parameters to detect seizures, and are increasingly used to alert care givers. There is no high-grade evidence that seizure detection devices prevent SUDEP or seizure-related injuries, but international guidelines for their prescription were recently published. A degree project at Gothenburg University recently performed a survey among epilepsy teams for children and adults at all six tertiary epilepsy centres and all regional technical aid centres. The surveys showed marked regional variation in the prescription and dispensation of seizure detection devices. National guidelines and a national register would promote equal access and facilitate follow-up.

Epileptic networks are intimately connected with the autonomic nervous system, as exemplified by a plethora of ictal (during a seizure) autonomic manifestations, including epigastric sensations, palpitations, goosebumps and syncope (fainting). Ictal autonomic changes might serve as diagnostic clues, provide targets for seizure detection and help us to understand the mechanisms that underlie sudden unexpected death in epilepsy (SUDEP). Autonomic alterations are generally more prominent in focal seizures originating from the temporal lobe, demonstrating the importance of limbic structures to the autonomic nervous system, and are particularly pronounced in focal-to-bilateral and generalized tonic-clonic seizures. The presence, type and severity of autonomic features are determined by the seizure onset zone, propagation pathways, lateralization and timing of the seizures, and the presence of interictal autonomic dysfunction. Evidence is mounting that not all autonomic manifestations are linked to SUDEP. In addition, experimental and clinical data emphasize the heterogeneity of SUDEP and its infrequent overlap with sudden cardiac death. Here, we review the spectrum and diagnostic value of the mostly benign and self-limiting autonomic manifestations of epilepsy. In particular, we focus on presentations that are likely to contribute to SUDEP and discuss how wearable devices might help to prevent SUDEP., (© 2021. Springer Nature Limited.)

Out-of-hospital cardiac arrest (OHCA) remains a major threat to public health worldwide. OHCA patients presenting initial shockable ventricular tachycardia/ventricular fibrillation (VT/VF) rhythm have a better survival rate. We sought to develop a simple SACAF score to discriminate VT/VF from non-VT/VF OHCAs based on the Taiwan multicenter hospital-based registry database. We analyzed the in- and pre-hospital data, including demographics, baseline comorbidities, response times, automated external defibrillator information, and the 12-lead ECG recording closest to the OHCA event in bystander-witnessed OHCA patients. Among the 461 study patients, male sex (OR 2.54, 95% CI = 1.32-4.88, P = 0.005), age ≤ 65 years (OR 2.78, 95% CI = 1.64-4.70, P < 0.001), cardiovascular diseases (OR 2.97, 95% CI = 1.73-5.11, P < 0.001), and atrial fibrillation (AF) (OR 2.36, 95% CI = 1.17-4.76, P = 0.017) were independent risk factors for VT/VF OHCA (n = 81) compared with non-VT/VF OHCA (n = 380). A composite SACAF score was developed (male Sex, Age ≤ 65 years, Cardiovascular diseases, and AF) and compared with the performance of a modified CHA 2 DS 2 -VASc score (Cardiovascular diseases, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke, Vascular disease, Age 65-74 years, female Sex category). The area under the receiver operating characteristic curve (AUC) of the SACAF was 0.739 (95% CI = 0.681-0.797, P < 0.001), whereas the AUC of the modified CHA 2 DS 2 -VASc was 0.474 (95% CI = 0.408-0.541, P = 0.464). A SACAF score of ≥ 2 was useful in discriminating VT/VF from non-VT/VF OHCAs with a sensitivity of 0.75 and a specificity of 0.60. In conclusion, the simple SACAF score appears to be useful in discriminating VT/VF from non-VT/VF bystander-witnessed OHCAs and the findings may also shed light on future mechanistic evaluation., (© 2021. The Author(s).)

Convulsive seizures are the most consistently reported risk factor for SUDEP. However, the precise mechanisms by which convulsive seizures trigger fatal cardiopulmonary changes are still unclear. Additionally, it is not clear why some seizures cause death when most do not. This article reviews the physiologic changes that occur during and after convulsive seizures and how these may contribute to SUDEP. Seizures activate specific cortical and subcortical regions that can cause potentially lethal cardiorespiratory changes. Clinical factors, including sleep state, medication treatment and withdrawal, positioning and posturing during seizures, and underlying structural or genetic conditions may also affect specific aspects of seizures that may contribute to SUDEP. While seizure control, either through medication or surgical treatment, is the primary intervention that reduces SUDEP risk, unfortunately, seizures cannot be fully controlled despite maximal treatment in a significant proportion of people with epilepsy. Thus specific interventions to prevent adverse seizure-related cardiopulmonary consequences are needed. The potential roles of repositioning/stimulation after seizures, oxygen supplementation, cardiopulmonary resuscitation and clinical treatment options in reducing SUDEP risk are explored. Ultimately, understanding of these factors may lead to interventions that could reduce or prevent SUDEP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rationale: Our previous study showed that the recently approved anticonvulsant drug, fenfluramine, which enhances the release of serotonin (5-hydroxytryptamine, 5-HT) in the brain, prevents seizure-induced respiratory arrest (S-IRA) in the DBA/1 mouse model of sudden unexpected death in epilepsy (SUDEP). The present study examined the role of 5-HT receptor subtypes in mediating the effect of this agent by combined administration of fenfluramine with selective 5-HT receptor antagonists prior to seizure in DBA/1 mice., Methods: Fenfluramine (15 mg/kg, i.p.) was administered to primed DBA/1 mice, and audiogenic seizure (Sz) was induced 16 h later. Thirty min prior to Sz induction a selective antagonist acting on 5-HT 1A , 5-HT 2 , 5-HT 3 5-HT 4 , 5-HT 5A , 5-HT 6 or 5-HT 7 receptors at a sub-toxic dose was administered, and changes in seizure-induced behaviors were evaluated. Follow-up studies examined the effect of administration of a 5-HT 4 receptor agonist, BIMU 8, as well as the effect of co-administration of ineffective doses of fenfluramine and BIMU-8 on Sz behaviors., Results: The 5-HT 4 antagonist (GR125487) was the only 5-HT receptor antagonist that was able to reverse the action of fenfluramine to block Sz and S-IRA. Treatment with the 5-HT 4 receptor agonist (BIMU-8), or co-administration of ineffective doses of BIMU-8 and fenfluramine significantly reduced the incidence of S-IRA and tonic Sz in DBA/1 mice. The antagonists for 5-HT 3 , 5-HT 5A 5-HT 6 , and 5-HT 7 receptors did not significantly affect the action of fenfluramine. However, the 5-HT 1A and the 5-HT 2 antagonists enhanced the anticonvulsant effects of fenfluramine., Conclusions: These findings suggest that the action of fenfluramine to prevent seizure-induced sudden death in DBA/1 mice is mediated primarily by activation of 5-HT 4 receptors. These studies are the first to indicate the therapeutic potential of 5-HT 4 receptor agonists either alone or in combination with fenfluramine for preventing SUDEP. Enhancement of the anticonvulsant effect of fenfluramine by 5-HT 1A and 5-HT 2 antagonists may involve presynaptic actions of these antagonists. Thus, the Sz and S-IRA blocking actions of fenfluramine involve complex interactions with several 5-HT receptor subtypes. These data also provide further support for the serotonin hypothesis of SUDEP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is the sudden and unexpected death of an epilepsy patient, which occurs under benign circumstances without evidence of typical causes of death. SUDEP concerns all epilepsy patients. The individual risk depends on the characteristics of the epilepsy and seizures as well as on living conditions. Focal to bilateral and generalized tonic-clonic seizures (TCS), nocturnal seizures and lack of nocturnal supervision increase the risk. Most SUDEP cases are due to a fatal cascade of apnea, hypoxemia and asystole in the aftermath of a TCS. Two thirds of SUDEP cases in unsupervised epilepsy patients with TCS could probably be prevented. Wearables can detect TCS and alert caregivers. SUDEP information is desired by most patients and relatives, has a favorable impact on treatment adherence and behavior and has no negative effects on mood and quality of life.Recommendations of the committee on patient safety of the German Society of Epileptology: the ultimate treatment goal is seizure freedom. If this cannot be achieved, control of TCS should be sought. All epilepsy patients and their relatives should be informed about SUDEP and risk factors. Patients and relatives should be informed about measures to counteract the elevated risk and imminent SUDEP. The counselling should be performed during a face-to-face discussion, at the time of first diagnosis or during follow-up visits. The counselling should be documented. Wearables for TCS detection can be recommended. If TCS persist, therapeutic efforts should be continued. The bereaved should be contacted after a SUDEP., (© 2021. The Author(s).)

We evaluated baseline sudden unexpected death in epilepsy (SUDEP) knowledge and counseling practices among national and international adult neurology trainees with a 12-question online survey. The survey was emailed to all 169 U.S. neurology residency program directors and select international neurology/epilepsy program leaders. Program leaders were asked to distribute the survey link to adult neurology trainees. There were 161 respondents in the U.S. and 171 respondents outside the U.S. The latter were from 25 Latin American, European, Asian, and African countries. More than 90% of all trainees reported familiarity with SUDEP definition. Familiarity with SUDEP risk factors and mitigation measures ranged from 56% to 67% across these groups, with international trainees slightly more familiar with risk factors (67% vs. 61% in U.S.) but less familiar with mitigation measures (56% vs. 63% in U.S.). Approximately half of national (49%) and international (54%) trainees rarely or never counseled patients on SUDEP. Less than half of national (44%) and international (41%) trainees were educated about SUDEP. Many U.S. and adult neurology trainees remain unfamiliar with SUDEP risk factors and mitigation measures. Sudden unexpected death in epilepsy counseling falls below recommended standards. We suggest that worldwide neurology training programs' leaderships consider improving SUDEP education targeted at adult neurology trainees., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) remains an important cause of epilepsy-related mortality, especially in patients with refractory epilepsy. The exact cause is not known, but postictal cardiac, respiratory, and brainstem dysfunctions are implicated. SUDEP prevention remains a big challenge. Except for low-quality evidence of preventive effect of nocturnal supervision for SUDEP, no other evidence-based preventive modality is available. Other potential preventive strategies for SUDEP include reducing the occurrence of generalized tonic-clonic seizures using seizure detection devices, detecting cardiorespiratory distress through respiratory and heart rate monitoring devices, preventing airway obstruction (safety pillows), and reducing central hypoventilation using selective serotonin reuptake inhibitors and adenosine and opiate antagonists. However, none of the above-mentioned modalities has been proven to prevent SUDEP. The present review intends to provide insight into the available SUDEP prevention modalities.

Context: Lightning-related injuries are among the top 10 causes of sport-related death at all levels of sport, including the nearly 8 million athletes participating in US secondary school sports., Objective: To investigate the adoption of lightning safety policies and the factors that influence the development of comprehensive lightning safety policies in United States secondary schools., Design: Cross-sectional study., Setting: Secondary school., Patients or Other Participants: Athletic trainers (ATs)., Main Outcome Measure(s): An online questionnaire was developed based on the "National Athletic Trainers' Association Position Statement: Lightning Safety for Athletics and Recreation" using a health behavior model, the precaution adoption process model, along with facilitators of and barriers to the current adoption of lightning-related policies and factors that influence the adoption of lightning policies. Precaution adoption process model stage (unaware for need, unaware if have, unengaged, undecided, decided not to act, decided to act, acting, maintaining) responses are presented as frequencies. Chi-square tests of associations and prevalence ratios with 95% CIs were calculated to compare respondents in higher and lower vulnerability states, based on data regarding lightning-related deaths., Results: The response rate for this questionnaire was 13.43% (n = 365), with additional questionnaires completed via social media (n = 56). A majority of ATs reported maintaining (69%, n = 287) and acting (6.5%, n = 27) a comprehensive lightning safety policy. Approximately 1 in 4 ATs (25.1%, n = 106) described using flash to bang as an evacuation criterion. Athletic trainers practicing in more vulnerable states were more likely to adopt a lightning policy than those in less vulnerable states (57.4% versus 42.6%, prevalence ratio [95% CI] = 1.16 [1.03, 1.30]; P = .009). The most commonly cited facilitator and barrier were a requirement from a state high school athletics association and financial limitations, respectively., Conclusions: A majority of ATs related adopting (eg, maintaining and acting) the best practices for lightning safety. However, many ATs also indicated continued use of outdated methods (eg, flash to bang)., (© by the National Athletic Trainers' Association, Inc.)

Objective: First, we will update recommendations for the prehospital management and care of patients with exertional heat stroke (EHS) in the secondary school setting. Second, we provide action items to aid clinicians in developing best-practice documents and policies for EHS. Third, we supply practical strategies clinicians can use to implement best practice for EHS in the secondary school setting., Data Sources: An interdisciplinary working group of scientists, physicians, and athletic trainers evaluated the current literature regarding the prehospital care of EHS patients in secondary schools and developed this narrative review. When published research was nonexistent, expert opinion and experience guided the development of recommendations for implementing life-saving strategies. The group evaluated and further refined the action-oriented recommendations using the Delphi method., Conclusions: Exertional heat stroke continues to be a leading cause of sudden death in young athletes and the physically active. This may be partly due to the numerous barriers and misconceptions about the best practice for diagnosing and treating patients with EHS. Exertional heat stroke is survivable if it is recognized early and appropriate measures are taken before patients are transported to hospitals for advanced medical care. Specifically, best practice for EHS evaluation and treatment includes early recognition of athletes with potential EHS, a rectal temperature measurement to confirm EHS, and cold-water immersion before transport to a hospital. With planning, communication, and persistence, clinicians can adopt these best-practice recommendations to aid in the recognition and treatment of patients with EHS in the secondary school setting., (© by the National Athletic Trainers' Association, Inc.)

Objective: We aimed to describe how often and why clinicians counsel people with epilepsy about sudden unexpected death in epilepsy (SUDEP). Understanding counseling gaps can help design interventions., Methods: We searched clinical notes of 77,924 patients from 2010 to 2014 from six hospitals to find examples of SUDEP counseling and seizure safety counseling. Visits were coded for patient, clinician, and visit factors, and documented reasons for counseling. We evaluated factors associated with SUDEP vs. seizure safety counseling, and reasons for counseling using bivariate and multivariable statistics. Reasons for counseling included: poor medication adherence, lifestyle factors (e.g., poor sleep, drinking alcohol), patient/family reluctance to make recommended medication adjustment, epilepsy surgery considerations, and patient education only., Results: Analysis was restricted to two of six hospitals where 91% of counseling occurred. Documentation of SUDEP counseling was rare (332 of 33,821 patients, 1.0%), almost exclusively by epileptologists (98.5% of counseling), and stable over time, X 2 (4, n = 996) = 3.81, p = 0.43. Adult neurologists were more likely to document SUDEP counseling than pediatric (OR = 1.65, 95% CI = 1.12-2.44). Most SUDEP counseling was documented with a goal of seizure reduction (214 of 332, 64.5%), though some was for patient education only (118 of 332, 35.5%). By the time SUDEP counseling was documented, the majority of patients had refractory epilepsy (187 of 332, 56.3%) and/or a potentially modifiable risk factor (214 of 332, 64.5%). Neurologists with more years of clinical experience (OR = 2.18, 95% CI = 1.12-4.25) and more senior academic titles (OR = 2.25, 95% CI = 1.27-3.99) were more likely to document SUDEP counseling for patient education only. People with ≥2 anti-seizure medications (ASM) were more likely to receive counseling for patient education (OR = 2.72, 95% CI = 1.49-4.97)., Conclusions: Documentation of SUDEP is rare, and varies by clinician, hospital, and patient factors. Efforts to increase SUDEP counseling should focus on junior clinicians, and emphasize starting the conversation soon after onset of epilepsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: We assessed patterns of health care utilization to further characterize chronic comorbidities prior to sudden death., Method: From March 1, 2013, through February 28, 2015, all out-of-hospital deaths aged 18-64 reported by emergency medical services in Wake County, North Carolina, were screened to adjudicate 399 sudden death victims. Retrospective analysis of clinical records on victims determined health care utilization. Health care utilization frequency was assessed by latent growth curve analysis., Results: Medical records were available for 264 victims (aged 53.5 ± 9.2) who were predominantly male (65%) and white (64%). Of these, 210 (80%) victims had at least one visit within two years of death and 73 (28%) had a visit within one month of death. Over the two years prior to death, there was an increasing frequency of doctor visits ( P < .001). Victims averaged 3.7 ± 4.6 yearly visits and were categorized into low (0.4 visits/year), medium (3.3 visits/year), and high (11.4 visits/year) tiers of visit frequency. The high visit tier had a greater prevalence of coronary artery disease (38%), hypertension (80%), diabetes (58%), depression (74%), anxiety (64%), and substance misuse (46%) ( P < .001)., Limitations: Those who were non-free-living, minors, without formal medical records, and adults aged 65 and older were excluded from the analysis., Conclusions: A majority of sudden death victims utilized health care within two years prior to death and had comorbidities that may have contributed to their unexpected death. The increasing frequency of visits prior to death provided an opportunity for health care providers to address potential victims' chronic medical conditions to potentially prevent death., (©2021 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Abstract: Although largely benign, sickle cell trait (SCT) has been associated with exertion-related events, to include sudden death. In 2011, a summit on SCT introduced the term exercise collapse associated with SCT (ECAST). A series of ECAST deaths in military personnel in 2019 prompted reevaluation of current efforts and led to a second summit in October 2019 hosted by the Consortium for Health and Military Performance of the Uniformed Services University in Bethesda, MD. The goals were to (1) review current service policies on SCT screening, (2) develop draft procedural instructions for executing current policy on SCT within the Department of Defense, (3) develop draft clinical practice guidelines for management of ECAST, (4) establish a framework for education on SCT and ECAST, and (5) prepare a research agenda to address identified gaps., (Copyright © 2021 by the American College of Sports Medicine.)

Sudden unexpected death in epilepsy (SUDEP) is a devastating complication in children with epilepsy. Children with generalized tonic-clonic convulsions, nocturnal seizures, and co-morbid developmental delay/intellectual disability are at higher risk of SUDEP. The pathogenic mechanisms are incompletely understood and involve cardiac, respiratory, autonomic and cerebral dysfunction. Prone positioning is also significantly associated with SUDEP and may be a target for SUDEP prevention. Good epilepsy control also attenuates the risk; hence, it is important to provide adequate antiepileptic drug therapy with stress on drug compliance as well as early surgical referral for seizure control, wherever necessary. It is recommended that parents of children with epilepsy be counseled about the risk factors for SUDEP and potential measures of SUDEP prevention. We herein provide a pediatric perspective of the problem and guidance about parental counselling for its prevention.

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.)

Genetic or idiopathic generalized epilepsies (IGEs) account for 15-20% of all epilepsies. These syndromes have always been considered as good prognosis forms of epilepsy over time; however, for some patients, there is a need to maintain antiseizure drugs (ASD) for a long-time. Drug resistance is not uncommon (7-15%). Lifestyle remains essential and is an integral part of the treatment. Comorbidities such as obstructive sleep apnea syndrome must be considered and treated. A highly underestimated condition is the risk of sudden unexpected death in epilepsy (SUDEP). Very few data are available about the prevalence of SUDEP in IGE, but patients with generalized tonic-clonic seizures (GTCS) are exposed to this risk. IGEs are also characterized by a specific pharmalogical sensisitivity but may be aggravated by ASDs. Historically, the treatment of IGEs has relied mostly on valproate but this drug should be avoided in women of childbearing potential. Women with IGE not treated with valproate are more likely to have unsatisfactory seizure control. Female gender appears now as a new risk factor for drug-resistance. Finally, aside from the typical forms, there are epilepsies that fulfill most of the criteria of IGE, but that have an unusual history with GTCS, absences, falls, and drug resistance. Patients do not have psychomotor regression, brain magnetic resonance imaging is normal. EEG shows generalized fast rhythms during NREM sleep. These patients with refractory generalized epilepsy with sleep-related fast activities do not belong to a well-established syndromic category. These cases are considered "intermediary" between IGE and epileptic encephalopathies., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Sickle cell trait (SCT) has been associated with an increased risk of sudden death in athletes during strenuous exercise. In August 2010, the National Collegiate Athletic Association (NCAA) began requiring athletes to be screened for SCT, provide proof of SCT status, or sign a waiver and launched an educational campaign for athletes, coaches, and medical staff. The impact of this program is unknown. The purpose of this study was to determine the incidence of death associated with sickle cell trait (daSCT) in NCAA athletes before and after legislation., Hypothesis: NCAA SCT legislation will decrease the incidence of daSCT., Study Design: Observational study., Level of Evidence: Level 2., Methods: A database of NCAA athlete deaths from 2000 to 2019 was reviewed for daSCT. A total of 8,309,050 athlete-years (AY) were included. Incidence of death was calculated before and after legislation., Results: The incidence of daSCT in Division I (DI) football athletes before legislation (n = 9) was 1:28,145 AY and after legislation (n = 1) was 1:250,468 AY (relative risk [RR], 0.112; 95% CI, 0.003-0.811; P = 0.022), an 89% reduction in risk after legislation was enacted. The incidence of daSCT in African American DI football athletes before legislation (n = 9) was 1:12,519 AY and after legislation (n = 1) was 1:118,464 AY (RR, 0.106; 95% CI, 0.002-0.763; P = 0.017), also an 89% risk reduction after legislation was enacted. For all NCAA athletes, the incidence of daSCT was 1:489,749 AY before legislation (n = 10) and 1:1,705,780 AY after legislation (n = 2) (RR, 0.288; 95% CI, 0.031-1.347; P = 0.146)., Conclusion: The incidence of daSCT in DI football athletes has decreased significantly since legislation was enacted. Cases of daSCT outside of football are rare. It is unclear whether the decrease is related to screening for SCT, education, or both., Clinical Relevance: This is the first evidence that NCAA SCT legislation may save lives.

Background: This is an updated version of the original Cochrane Review, published in 2016, Issue 7. Sudden Unexpected Death in Epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic or non-drowning death of people with epilepsy, with or without evidence of a seizure, excluding documented status epilepticus and in whom postmortem examination does not reveal a structural or toxicological cause for death. SUDEP has a reported incidence of 1 to 2 per 1000 patient-years and represents the most common epilepsy-related cause of death. The presence and frequency of generalised tonic-clonic seizures (GTCS), male sex, early age of seizure onset, duration of epilepsy, and polytherapy are all predictors of risk of SUDEP. The exact pathophysiology of SUDEP is currently unknown, although GTCS-induced cardiac, respiratory, and brainstem dysfunction appears likely. Appropriately chosen antiepileptic drug treatment can render around 70% of patients free of all seizures. However, around one-third will remain drug-resistant despite polytherapy. Continuing seizures place patients at risk of SUDEP, depression, and reduced quality of life. Preventative strategies for SUDEP include reducing the occurrence of GTCS by timely referral for presurgical evaluation in people with lesional epilepsy and advice on lifestyle measures; detecting cardiorespiratory distress through clinical observation and seizure, respiratory, and heart rate monitoring devices; preventing airway obstruction through nocturnal supervision and safety pillows; reducing central hypoventilation through physical stimulation and enhancing serotonergic mechanisms of respiratory regulation using selective serotonin reuptake inhibitors (SSRIs); and reducing adenosine and endogenous opioid-induced brain and brainstem depression., Objectives: To assess the effectiveness of interventions in preventing SUDEP in people with epilepsy by synthesising evidence from randomised controlled trials of interventions and cohort and case-control non-randomised studies., Search Methods: For the latest update we searched the following databases without language restrictions: Cochrane Register of Studies (CRS Web, 4 February 2019); MEDLINE (Ovid, 1946 to 1 February 2019); SCOPUS (1823 to 4 February 2019); PsycINFO (EBSCOhost, 1887 to 4 January 2019); CINAHL Plus (EBSCOhost, 1937 to 4 February 2019); ClinicalTrials.gov (5 February 2019); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP, 5 February 2019). We checked the reference lists of retrieved studies for additional reports of relevant studies and contacted lead study authors for any relevant unpublished material. We identified any grey literature studies published in the last five years by searching: Zetoc database; ISI Proceedings; International Bureau for Epilepsy (IBE) congress proceedings database; International League Against Epilepsy (ILAE) congress proceedings database; abstract books of symposia and congresses, meeting abstracts, and research reports., Selection Criteria: We aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs; prospective non-randomised cohort controlled and uncontrolled studies; and case-control studies of adults and children with epilepsy receiving an intervention for the prevention of SUDEP. Types of interventions included: early versus delayed pre-surgical evaluation for lesional epilepsy; educational programmes; seizure-monitoring devices; safety pillows; nocturnal supervision; selective serotonin reuptake inhibitors (SSRIs); opiate antagonists; and adenosine antagonists., Data Collection and Analysis: We aimed to collect data on study design factors and participant demographics for included studies. The primary outcome of interest was the number of deaths from SUDEP. Secondary outcomes included: number of other deaths (unrelated to SUDEP); change in mean depression and anxiety scores (as defined within the study); clinically important change in quality of life, that is any change in quality of life score (average and endpoint) according to validated quality of life scales; and number of hospital attendances for seizures., Main Results: We identified 1277 records from the databases and search strategies. We found 10 further records by searching other resources (handsearching). We removed 469 duplicate records and screened 818 records (title and abstract) for inclusion in the review. We excluded 785 records based on the title and abstract and assessed 33 full-text articles. We excluded 29 studies: eight studies did not assess interventions to prevent SUDEP; eight studies were review articles, not clinical studies; five studies measured sensitivity of devices to detect GTCS but did not directly measure SUDEP; six studies assessed risk factors for SUDEP but not interventions for preventing SUDEP; and two studies did not have a control group. We included one cohort study and three case-control studies of serious to critical risk of bias. The 6-month prospective cohort study observed no significant effect of providing patients with SUDEP information on drug compliance and quality of life, anxiety and depression levels. The study was too short and with no deaths observed in either group to determine a protective effect. Two case control studies reported a protective effect for nocturnal supervision against SUDEP. However due to significant heterogeneity, the results could not be combined in meta-analysis. One study of 154 SUDEP cases and 616 controls reported an unadjusted odds ratio (OR) of 0.34 (95% CI 0.22 to 0.53; P < 0.0001). The same study demonstrated the protective effect was independent of seizure control, suggesting that nocturnal supervision is not just a surrogate marker of seizure control. The second case-control study of 48 SUDEP cases and 220 controls reported an unadjusted OR of 0.08 (95% CI 0.02 to 0.27; P < 0.0001). The third case-control study of residential care centre patients who were already receiving physical checks more than 15 minutes apart throughout the night did not report any protective effect for additional nocturnal supervision (physical checks < 15 minutes apart; use of listening devices; dormitory setting; and use of bed sensors). However the same study did ascertain a difference between centres: the residential centre with the lowest level of supervision had the highest incidence of SUDEP. The case-control studies did not report on quality of life or depression and anxiety scores., Authors' Conclusions: We found limited, very low-certainty evidence that supervision at night reduces the incidence of SUDEP. Further research is required to identify the effectiveness of other current interventions - for example seizure detection devices, safety pillows, SSRIs, early surgical evaluation, educational programmes, and opiate and adenosine antagonists - in preventing SUDEP in people with epilepsy., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Sudden unexpected death in epilepsy (SUDEP) is generally considered to result from a seizure, typically convulsive and usually but not always occurring during sleep, followed by a sequence of events in the postictal period starting with respiratory distress and progressing to eventual cardiac asystole and death. Yet, recent community-based studies indicate a 3-fold greater incidence of sudden cardiac death in patients with chronic epilepsy than in the general population, and that in 66% of cases, the cardiac arrest occurred during routine daily activity and without a temporal relationship with a typical seizure. To distinguish a primarily cardiac cause of death in patients with epilepsy from the above description of SUDEP, we propose the concept of the "Epileptic Heart" as "a heart and coronary vasculature damaged by chronic epilepsy as a result of repeated surges in catecholamines and hypoxemia leading to electrical and mechanical dysfunction." This review starts with an overview of the pathophysiological and other lines of evidence supporting the biological plausibility of the Epileptic Heart, followed by a description of tools that have been used to generate new electrocardiogram (EKG)-derived data in patients with epilepsy that strongly support the Epileptic Heart concept and its propensity to cause sudden cardiac death in patients with epilepsy independent of an immediately preceding seizure., Competing Interests: Declaration of competing interest No funding was received for the preparation of this review. LivaNova PLC (London UK) funded Beth Israel Deaconess Medical Center for cited clinical studies by the authors, RL Verrier, Principal Investigator, Drs. Pang, Nearing, and Schachter, coinvestigators. Dr. Schachter is Editor-in-Chief of Epilepsy & Behavior. Otherwise, none of the authors has a competing interest to report., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To identify predictors of left ventricular ejection fraction (LVEF) improvement in patients with newly detected cardiomyopathy using wearable cardioverter defibrillators (WCDs)., Background: WCDs are useful in preventing sudden cardiac death in patients with reduced LVEF <35% while awaiting implantable cardioverter defibrillator (ICD) placement. In many patients, LVEF improves and an ICD is not indicated., Methods: Patients who received WCDs from November 2013 to November 2015 were identified and followed over a period of 2 years. Clinical variables were examined. The primary outcome was improvement in LVEF ≥35%. Predictors of outcome were determined using a multivariate logistic regression model., Results: A total of 179 patients were followed. Median age was 65 (interquartile range [IQR]: 56, 73) years, 69.3% were men. Median baseline LVEF was 20% (IQR: 15, 30). LVEF improved ≥35% in 47.5% patients, with patients being younger (62 vs 68.5 years, P = .006), having lower blood urea nitrogen (BUN) (19 vs 24 mg/dL, P = .002), fewer left bundle branch block (LBBB 9.5% vs 25.8%, P = .004), shorter QRS duration (98 vs 112 ms, P < .001), and higher use of angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) (92.9% vs 74.4%, P = .001) compared to those without LVEF improvement. Absence of LBBB (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.11-0.70), lower BUN (OR 0.13, 95% CI 0.02-0.76), and ACEI/ARB use (OR 3.53, 95% CI 1.28-9.69) were identified as independent predictors. Ventricular tachycardia/ventricular fibrillation was observed in three patients, all of whom received successful WCD shocks., Conclusion: Absence of LBBB, lower BUN, and ACEI/ARB use predicts LVEF improvement. WCDs help treat arrhythmic events., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)