Incidence Of Sudden Unexpected Death In Epilepsy Research Articles

Early mortality in STXBP1-related disorders.

Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13years (range: 11months-46years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.

The incidence of sudden unexpected death in epilepsy (SUDEP) in the Republic of Ireland

BackgroundThe incidence of sudden unexpected death in epilepsy (SUDEP) in Ireland has previously been studied in only a small geographical area. Our aim was to calculate an incidence rate for the whole of the Republic of Ireland in 2019. MethodsAll deaths referred to the coroner in 2019 were examined. Those with a history of possible epilepsy were noted and subjected to a more detailed assessment. Cases fulfilling the definition of definite SUDEP were identified. The incidence of SUDEP was calculated using the population of the Republic of Ireland in 2019 and the known prevalence of epilepsy in Ireland. ResultsThirty-three cases of definite SUDEP were identified in the Republic of Ireland in 2019. The estimated incidence of SUDEP in the epilepsy population as a whole was 0.7/1000(0.46 – 0.94) person years. This may be a conservative estimate. More men than women were identified, and most individuals were found dead at home. SUDEP was mentioned on the death certificate in only 52 % of cases. ConclusionThis is the first nationwide study of SUDEP incidence in Ireland and provides an incidence rate in keeping with other populations. This work demonstrates that the interrogation of coronial records is a useful way to monitor epilepsy mortality albeit with certain limitations.

Mortality of epilepsy in Chinese populations: a comprehensive review.

Premature mortality is a significant part of the epilepsy burden and may vary across populations, especially between high-income and lower- and middle-income countries. People with epilepsy in China are approximately a fifth of the global population with epilepsy. Previous studies were unlikely to represent the situation in China due to limitations in design, methods, sample size, follow-up time, and other inherent population heterogeneity. By summarising the evidence on the mortality characteristics in Chinese populations with epilepsy in the last six decades, we found a median mortality rate of 14.7 (6.8-74.4)/1000 person-years and a median standardised mortality ratio (SMR) of 4.4 (2.6-12.9) in population-based studies, and a median mortality rate of 12.3 (9.5-101.5)/1000 person-years and a median SMR of 3.0 (1.5-5.1) in hospital-based studies. Vascular diseases, complications of diabetes, and accidental injuries were the leading causes of death. Risk factors for mortality were reported as older age, male, longer duration and higher frequency of seizures. Case fatality ratios of status epilepticus (SE) in adults were higher than in children, and both increased with follow-up time. Mortality in people with symptomatic epilepsy was high and varied across different primary diseases. The highest mortality rate and sudden unexpected death in epilepsy (SUDEP) incidence were reported from the least developed areas in China. Accidental injuries were the most common causes of epilepsy-related deaths, while the incidence of SUDEP may be underestimated in Chinese populations. Further research is warranted to improve the understanding of premature mortality risk so that preventative measures can be introduced to improve the situation.

Enhancing the action of serotonin by three different mechanisms prevents spontaneous seizure-induced mortality in Dravet mice.

Sudden unexpected death in epilepsy (SUDEP) is an underestimated complication of epilepsy. Previous studies have demonstrated that enhancement of serotonergic neurotransmission suppresses seizure-induced sudden death in evoked seizure models. However, it is unclear whether elevated serotonin (5-HT) function will prevent spontaneous seizure-induced mortality (SSIM), which is characteristic of human SUDEP. We examined the effects of 5-HT-enhancing agents that act by three different pharmacological mechanisms on SSIM in Dravet mice, which exhibit a high incidence of SUDEP, modeling human Dravet syndrome. Dravet mice of both sexes were evaluated for spontaneous seizure characterization and changes in SSIM incidence induced by agents that enhance 5-HT-mediated neurotransmission. Fluoxetine (a selective 5-HT reuptake inhibitor), fenfluramine (a 5-HT releaser and agonist), SR 57227 (a specific 5-HT3 receptor agonist), or saline (vehicle) was intraperitoneally administered over an 8-day period in Dravet mice, and the effect of these treatments on SSIM was examined. Spontaneous seizures in Dravet mice generally progressed from wild running to tonic seizures with or without SSIM. Fluoxetine at 30 mg/kg, but not at 20 or 5 mg/kg, significantly reduced SSIM compared with the vehicle control. Fenfluramine at 1-10 mg/kg, but not .2 mg/kg, fully protected Dravet mice from SSIM, with all mice surviving. Compared with the vehicle control, SR 57227 at 20 mg/kg, but not at 10 or 5 mg/kg, significantly lowered SSIM. The effect of these drugs on SSIM was independent of sex. Our data demonstrate that elevating serotonergic function by fluoxetine, fenfluramine, or SR 57227 significantly reduces or eliminates SSIM in Dravet mice in a sex-independent manner. These findings suggest that deficits in serotonergic neurotransmission likely play an important role in the pathogenesis of SSIM, and fluoxetine and fenfluramine, which are US Food and Drug Administration-approved medications, may potentially prevent SUDEP in at-risk patients.

Sudden unexpected death in epilepsy: A critical view of the literature.

Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected, witnessed or unwitnessed, non-traumatic and non-drowning death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus in which postmortem examination does not reveal other causes of death. Lower diagnostic levels are assigned when cases met most or all of these criteria, but data suggested more than one possible cause of death. The incidence of SUDEP ranged from 0.09 to 2.4 per 1000 person-years. Differences can be attributed to the age of the study populations (with peaks in the 20-40-year age group) and the severity of the disease. Young age, disease severity (in particular, a history of generalized TCS), having symptomatic epilepsy, and the response to antiseizure medications (ASMs) are possible independent predictors of SUDEP. The pathophysiological mechanisms are not fully known due to the limited data available and because SUDEP is not always witnessed and has been electrophysiologically monitored only in a few cases with simultaneous assessment of respiratory, cardiac, and brain activity. The pathophysiological basis of SUDEP may vary according to different circumstances that make that particular seizure, in that specific moment and in that patient, a fatal event. The main hypothesized mechanisms, which could contribute to a cascade of events, are cardiac dysfunction (included potential effects of ASMs, genetically determined channelopathies, acquired heart diseases), respiratory dysfunction (included postictal arousal deficit for the respiratory mechanism, acquired respiratory diseases), neuromodulator dysfunction, postictal EEG depression and genetic factors.

Sudden unexpected death in epilepsy in children.

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.

Trend of Sudden Unexpected Death in Epilepsy Incidence Rate in Rural West China.

Objectives: To explore the trend of sudden unexpected death in epilepsy (SUDEP) incidence rate over time in rural west China.Methods: We scanned probable SUDEP patients from the epilepsy program between 2010 and 2019 in rural West China and performed a verbal autopsy for each eligible patient. We calculated the crude and sex-adjusted incidence rate of SUDEP per person-year over a calendar year and the year of follow-up. We calculated the incidence rate ratio with the Poisson model in STATA 12.0 and calculated the annual percentage change (APC) and average annual percentage change in Joinpoint Trend Analysis Software 4.8.0.1 to analyze the trend of SUDEP incidence rate.Results: In 2010–2019, 44 probable SUDEPs were identified from 10,128 patients with a total person-year of 31,347. The crude and sex-adjusted incidence rates of SUDEP were 1.40 and 1.45%0. Twenty-five (56.8%) of the 44 probable SUDEPs had no generalized tonic-clonic seizure 3 months before their death. The incidence of probable SUDEP decreased significantly in the calendar year [APC = −11.7, 95% confidence interval (CI): −21.7 to −0.3] and in time of follow-up (average annual percentage change = −21.2, 95% CI: −34.3 to −5.4). Comparing the first 5 years in follow-up with the subsequent 3 years, the incidence rate of SUDEP decreased significantly (estimated incidence rate ratio = 0.4, 95% CI: 0.2 to 0.8).Significance: SUDEP happened to 1.4 cases per thousand patient-years in convulsive epilepsy in rural west China between 2010 and 2019. The incidence rate of SUDEP presented a downward trend over the time of follow-up.

Reader Response: Temporal Trends and Autopsy Findings of SUDEP Based on Medicolegal Investigations in the United States.

I read the article by Cihan et al.1 with interest. Sudden unexpected death in epilepsy (SUDEP) is a dreadful event for families and physicians caring for patients with epilepsy. A case-control examination of SUDEP postmortems has shown no seasonal and diurnal patterns exist for SUDEP.1 A downward trend in the incidence of SUDEP over 8 years is a welcome finding. Greater awareness, access to affordable medical care, and changes in antiseizure drug prescribing may have had positive effects on the incidence of SUDEP.

The SANTÉ study at 10 years of follow-up: Effectiveness, safety, and sudden unexpected death in epilepsy.

We evaluated the efficacy and safety of deep brain anterior thalamus stimulation after 7 and 10years, and report the incidence of sudden unexpected death in epilepsy (SUDEP) and overall mortality in adults in the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTÉ) study. After the 3-month blinded and 9-month unblinded phases, subjects continued to be assessed during long-term follow-up (LTFU) and later a continued therapy access phase (CAP), to further characterize adverse events and the incidence of SUDEP. Stimulus parameter and medication changes were allowed. One hundred ten implanted subjects accumulated a total of 938 device-years of experience (69 subjects during the LTFU phase and 61 subjects in the CAP phase). Prior to study closure, 57 active subjects continued therapy at 14 study centers, with follow-up of at least 10 (maximum 14) years. At 7years, median seizure frequency percent reduction from baseline was 75% (p<.001), with no outcome differences related to prior vagus nerve stimulation or resective surgery. The most severe seizure type, focal to bilateral tonic-clonic, was reduced by 71%. Adding new antiseizure medications did not impact the pattern of seizure reduction over time. There were no unanticipated serious adverse events in the study. The definite-plus-probable SUDEP rate, based on SANTÉ study experience (two deaths in 938years) and previous pilot studies (0 deaths in 76years), indicated a rate of 2.0 deaths for 1000 person-years. Overall mortality was 6.9 deaths per 1000 person-years. The long-term efficacy and safety profiles of the deep brain stimulation (DBS) system for epilepsy are favorable and demonstrate stable outcomes. Improvement in frequency of the most severe seizure type may reduce SUDEP risk. The SUDEP rate with DBS (2.0) is comparable to other neuromodulation treatments (i.e., vagus nerve stimulation, responsive neurostimulation) for drug-resistant focal epilepsy.

Treatments for the prevention of Sudden Unexpected Death in Epilepsy (SUDEP).

Treatments for the prevention of Sudden Unexpected Death in Epilepsy (SUDEP).

Editors' note: Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP)

In “Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP)”, Vilella et al. found that in a cohort of patients with intractable generalized or focal epilepsy, 22% of seizures were followed by postconvulsive central apnea (PCCA), defined as ≥1 missed breath without any other explanation; one of these patients died of probable SUDEP, suggesting that the incidence of SUDEP is 5.1 per 1,000 patient-years. They concluded that PCCA may be a clinical biomarker for SUDEP. Pursuant to these findings, Rose et al. report a case of SUDEP in a patient with PCCA; however, they comment that although PCCA may be associated with SUDEP, they suspect that it is not a requirement for SUDEP, given that there is a known relationship between SUDEP and prone positioning (which can lead to obstructive apnea). They also question the proposed incidence rate of SUDEP, as it was based on only 1 death. Dasheiff notes that (1) it is not possible to distinguish between PCCA and central sleep apnea without advanced instrumentation, and (2) a threshold higher than 1 missed breath should be used to define PCCA. Vilella et al. respond that (1) the true incidence of PCCA and SUDEP, both individually and separately, is, indeed, unknown; (2) there may be a multitude of risk factors for SUDEP, including both prone positioning and PCCA; and (3) using a higher bar to define PCCA would, actually, better illustrate the relationship between PCCA and SUDEP in this series. Further research on the risk factors and incidence of SUDEP is needed. In “Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP)”, Vilella et al. found that in a cohort of patients with intractable generalized or focal epilepsy, 22% of seizures were followed by postconvulsive central apnea (PCCA), defined as ≥1 missed breath without any other explanation; one of these patients died of probable SUDEP, suggesting that the incidence of SUDEP is 5.1 per 1,000 patient-years. They concluded that PCCA may be a clinical biomarker for SUDEP. Pursuant to these findings, Rose et al. report a case of SUDEP in a patient with PCCA; however, they comment that although PCCA may be associated with SUDEP, they suspect that it is not a requirement for SUDEP, given that there is a known relationship between SUDEP and prone positioning (which can lead to obstructive apnea). They also question the proposed incidence rate of SUDEP, as it was based on only 1 death. Dasheiff notes that (1) it is not possible to distinguish between PCCA and central sleep apnea without advanced instrumentation, and (2) a threshold higher than 1 missed breath should be used to define PCCA. Vilella et al. respond that (1) the true incidence of PCCA and SUDEP, both individually and separately, is, indeed, unknown; (2) there may be a multitude of risk factors for SUDEP, including both prone positioning and PCCA; and (3) using a higher bar to define PCCA would, actually, better illustrate the relationship between PCCA and SUDEP in this series. Further research on the risk factors and incidence of SUDEP is needed.

Sudden unexpected death in epilepsy. A nationwide population‐based study

The incidence of sudden unexpected death in epilepsy (SUDEP) varies between studies. We determined the incidence of SUDEP in the entire Icelandic population during a 20-year period. All individuals in Iceland with epilepsy who died unexpectedly from January 1, 1991 through December 31, 2010 were included. Case ascertainment was based on autopsies, reimbursement for antiepileptic drugs, death certificates, information from neurologists, and medical records. The incidence of SUDEP was calculated according to the total number of residents in Iceland during the study period and an estimated epilepsy population of Iceland. We identified 37 individuals (26 men, 11 women) with definite SUDEP (n=29), definite SUDEP plus (n=4), and probable SUDEP (n=4). Incidence of SUDEP was 0.6 per 100000 person-years for the general population, and higher among men. The estimated incidence of SUDEP in the epilepsy population was 1.3 per 1000 person-years. SUDEP accounted for 0.1% of all deaths in Iceland during the study period. SUDEP is an important cause of death in working-age people. This study provides the incidence of SUDEP in an unselected population of an entire country. The SUDEP incidence in the epilepsy population is comparable to that of previous studies.

Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a R1407X/+ Mice.

Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in patients with drug-resistant epilepsy. Most SUDEP cases occur in bed at night and are preceded by a generalized tonic-clonic seizure (GTCS). Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly caused by mutations in the SCN1A gene. Affected individuals suffer from refractory seizures and an increased risk of SUDEP. Here, we demonstrate that mice with the Scn1aR1407X/+ loss-of-function mutation (DS) experience more spontaneous seizures and SUDEP during the early night. We also evaluate effects of long-term ketogenic diet (KD) treatment on mortality and seizure frequency. DS mice showed high premature mortality (44% survival by P60) that was associated with increased spontaneous GTCSs 1–2 days prior to SUDEP. KD treated mice had a significant reduction in mortality (86% survival by P60) compared to mice fed a control diet. Interestingly, increased survival was not associated with a decrease in seizure frequency. Further studies are needed to determine how KD confers protection from SUDEP. Moreover, our findings implicate time of day as a factor influencing the occurrence of seizures and SUDEP. DS mice, though nocturnal, are more likely to have SUDEP at night, suggesting that the increased incidence of SUDEP at night in may not be solely due to sleep.

Fenfluramine, a serotonin-releasing drug, prevents seizure-induced respiratory arrest and is anticonvulsant in the DBA/1 mouse model of SUDEP.

Prevention of sudden unexpected death in epilepsy (SUDEP) is a critical goal for epilepsy therapy. The DBA/1 mouse model of SUDEP exhibits an elevated susceptibility to seizure-induced death in response to electroconvulsive shock, hyperthermia, convulsant drug, and acoustic stimulation. The serotonin hypothesis of SUDEP is based on findings that treatments which modify serotonergic function significantly alter susceptibility to seizure-induced sudden death in several epilepsy models, including DBA/1 mice. Serotonergic abnormalities have also recently been observed in human SUDEP. Fenfluramine is a drug that enhances serotonin release in the brain. Recent studies have found that the addition of fenfluramine improved seizure control in patients with Dravet syndrome, which has a high incidence of SUDEP. Therefore, we investigated the effects of fenfluramine on seizures and seizure-induced respiratory arrest (S-IRA) in DBA/1 mice. The dose and time course of the effects of fenfluramine (i.p.) on audiogenic seizures (Sz) induced by an electric bell in DBA/1 mice were determined. Videos of Sz-induced behaviors were recorded for analysis. Statistical significance (P<0.05) was evaluated using the chi-square test. Sixteen hours after administration of 15mg/kg of fenfluramine, a high incidence of selective block of S-IRA susceptibility (P<0.001) occurred in DBA/1 mice without blocking any convulsive behavior. Thirty minutes after 20-40mg/kg of fenfluramine, significant reductions of seizure incidence and severity, as well as S-IRA susceptibility occurred, which were long-lasting (≥48hours). The median effective dose (ED50 ) of fenfluramine for significantly reducing Sz at 30minutes was 21mg/kg. This study presents the first evidence for the effectiveness of fenfluramine in reducing seizure incidence, severity, and S-IRA susceptibility in a mammalian SUDEP model. The ability of fenfluramine to block S-IRA selectively suggests the potential usefulness of fenfluramine in prophylaxis of SUDEP. These results further confirm and extend the serotonin hypothesis of SUDEP.

Decreasing SUDEP incidence in a tertiary epilepsy center between 1981 and 2016: Effects of better patient supervision

ObjectiveThe objective of this study was to investigate the incidence of sudden unexpected death in epilepsy (SUDEP) in a tertiary epilepsy center in the years 1981–2016 with an emphasis on patient supervision and nursing intervention in different departments. MethodsWe identified 14 SUDEP cases (probable, definite, definite plus). Patient-years (PY) and incidence were calculated for the periods of six years for the general epileptology wards (adults and children) and, in addition, for the epilepsy monitoring unit (EMU) since 1990. ResultsThe incidence of SUDEP showed a decreasing trend over time (r = −0.81; p = 0.053, two-sided; Pearson correlation coefficient). This is especially true in children (no SUDEP occurred in pediatric general epileptology since 1992). Additionally, in the EMU (314 PY since the start of 1990), no SUDEP occurred. Sudden unexpected death in epilepsy incidence was highest (6.8/1000 PY) in the early time periods (1981–1992) and lowest (1.7/1000 PY) in the later time periods (1999–2010). In the general epileptology wards (3579 PY), the overall incidence was 3.9 per 1000 PY (95% confidence interval (CI): 2.1–6.6). ConclusionsWe assume that the decreased SUDEP incidence is an effect of better supervision by the use of technical means (e.g., video cameras, pulse oximeters, seizure detection systems) and rooming-in of parents or family.

Sudden unexpected death in epilepsy: Risk factors, biomarkers, and prevention.

Sudden unexpected death in epilepsy (SUDEP) is one of the most important direct epilepsy-related causes of death, with an incidence in adults of 1.2 per 1000 person-years. Generalized tonic-clonic seizures have consistently emerged as the leading risk factor for SUDEP, particularly when such seizures are uncontrolled. High seizure burden, lack of antiepileptic drug (AED) treatment, polytherapy, intellectual disability, and prone position at the time of death are other key risk factors. Unfortunately, despite advances in treatment, overall mortality rates in epilepsy are rising. It is imperative that we learn more about SUDEP so that effective prevention strategies can be implemented. To help identify persons at greater risk of SUDEP and in need of closer monitoring, biomarkers are needed. Candidate biomarkers include electrocardiographic, electroencephalographic, and imaging abnormalities observed more frequently in those who have died suddenly and unexpectedly. As our knowledge of the pathophysiologic mechanisms behind SUDEP has increased, various preventative measures have been proposed. These include lattice pillows, postictal oxygen therapy, selective serotonin reuptake inhibitors, and inhibitors of opiate and adenosine receptors. Unfortunately, no randomized clinical trials are available to definitively conclude these measures are effective. Rather, gaining the best control of seizures possible (with AEDs, devices, and resective surgery) still remains the intervention with the best evidence to reduce the risk of SUDEP. In this evidence-based review, we explore the incidence of SUDEP and review the risk factors, biomarkers, and latest prevention strategies.

Evolution over time of SUDEP incidence: A nationwide population-based cohort study.

Prompted by a recent report on declining incidence of sudden unexpected death in epilepsy (SUDEP) following implantation of a vagus nerve stimulator (VNS), we analyzed SUDEP risk over 6 years in a population-based cohort of 60 952 epilepsy patients in Sweden. All deaths from July 1, 2006 through December 31, 2011, were identified. Those with epilepsy mentioned on the death certificate were adjudicated for SUDEP using medical records and autopsy reports. In all, 292 SUDEP cases were identified. Comparing the first years (2006-2007) with the subsequent 4 years (2008-2011), the crude and standardized (to the US 2000 population) incidence of SUDEP (whether or not possible SUDEP was included) was significantly lower during the second time period; Incidence rate ratios based on standardized rates was estimated at 0.76 (95% confidence interval [CI] 0.60-0.97, P = .027) for SUDEP. The incidence of SUDEP decreased by 7% per year during the 6-year follow-up. Our data thus suggest that, for unknown reasons, incidence of SUDEP decreases with duration of follow-up. This has implications for patient counseling as well as for the design of studies attempting to assess the effectiveness of an intervention against SUDEP, which clearly needs to include a control group.

Incidence of sudden unexpected death in epilepsy in children is similar to adults.

To determine the incidence of sudden unexpected death in epilepsy (SUDEP) in children in Ontario, Canada. Cases of suspected pediatric SUDEP occurring between January 1, 2014, and December 31, 2015, in Ontario, Canada, were eligible for inclusion. Potential cases were identified through 3 sources: a national pediatrician surveillance program, child neurologist report, and screening of provincial forensic autopsies. Cases were classified as definite, definite plus, probable, possible, and near/near plus according to criteria described by Nashef et al. (Epilepsia 2012). Overall crude pediatric SUDEP incidence and the incidence of definite or probable pediatric SUDEP were calculated using estimates of the prevalence of pediatric epilepsy in Canada drawn from government survey data and the number of children living in Ontario. Capture-recapture analysis was used to estimate the number of missing cases and determine an adjusted definite/probable SUDEP incidence. Seventeen cases of pediatric SUDEP resulted in an overall incidence of 1.17 (95% confidence interval 0.68-1.88) per 1,000 pediatric epilepsy person-years. The definite/probable incidence, including definite (n = 11), definite plus (n = 2), or probable (n = 3) SUDEP cases, was 1.11 (0.63-1.79). Capture-recapture analysis indicated an estimated 21 (16-39) definite/probable SUDEP cases occurred during the study period, giving an adjusted incidence of definite/probable SUDEP of 1.45 (0.90-2.22) per 1,000 pediatric epilepsy person-years. SUDEP may be more common in children than widely reported, with the incidence rate of definite/probable SUDEP in children being similar to rates reported in adults.

Ranking the Leading Risk Factors for Sudden Unexpected Death in Epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is rare in well-controlled epilepsy. However, SUDEP is a common cause of death in drug-resistant epilepsy. Over the last 30 years, multiple cohort and population studies have identified clinical risk factors associated with an increased risk for SUDEP. To identify and rank the leading SUDEP risk factors from major cohort and population-based studies. The incidence of SUDEP is also evaluated in special clinical situations, including antiepileptic drug treatment, epilepsy surgery, devices, and assignment to placebo in clinical trials. A PubMed search for English language human cohort studies for the terms Sudden, Death, and Epilepsy was performed for the years 1987-2017. Risk factors for SUDEP were identified and ranked by the weighted log adjusted odds ratio (OR)/relative risk ratio (RR). The top 10 leading risk factors ranked from highest to lowest log adjusted OR/RR are the following: ≥3 GTC seizures per year; ≥13 seizures in the last year; No Antiepileptic Drug (AED) treatment; ≥3 AEDs; ≥3 GTCs in the past year; 11-20 GTC seizures in the last 3 months; age of onset 0-15 years old; IQ < 70; 3-5 AED changes in the last year; ≥3 AEDs. Two risk factors from separate sources (≥3 GTC seizures and ≥3 AEDs) occur twice in the top 10 risk factors. The top 10 risk factors for SUDEP are identified and ranked. A ranking of the top risk factors could help clinicians identify patients at highest risk for SUDEP.

The incidence of SUDEP: A nationwide population-based cohort study.

To identify all cases of sudden unexpected death in epilepsy (SUDEP) among people in Sweden during 1 year and to determine the SUDEP incidence in relation to age, sex, and psychiatric comorbidity. We included all individuals with a hospital-based ambulatory care or hospital discharge diagnosis of epilepsy in the Swedish National Patient Registry during 1998-2005 who were alive on January 1, 2008. Deaths during 2008 were identified by linkage to the National Cause of Death Registry. Death certificates, medical charts, and police and autopsy reports were extensively reviewed to identify SUDEP cases. Of 57,775 epilepsy patients alive on January 1, 2008, 1,890 died (3.3%) during 2008. Of these, 99 met the Annegers SUDEP criteria (49 definite, 19 probable, and 31 possible). SUDEP accounted for 5.2% of all deaths and 36% of deaths in the 0-15 years age group. The incidence of definite/probable SUDEP was 1.20/1,000 person-years, and higher in men (1.41) than in women (0.96). All SUDEP cases <16 years were in boys. SUDEP incidence at ages <16, 16-50, and >50 years was 1.11, 1.13, and 1.29, respectively, per 1,000 person-years. The incidence was 5-fold increased among female patients with psychiatric comorbidities compared to those without. Epilepsy was mentioned on the death certificate in only 62 of the 99 (63%) SUDEP cases. Methods relying on death certificates underestimate SUDEP incidence. SUDEP risk has been underestimated especially in boys and in older people regardless of sex. Patients with psychiatric comorbidities, women in particular, are at increased SUDEP risk.