Epilepsy-related Deaths Research Articles

Antiseizure Medications and Sudden Unexpected Death in Epilepsy: An Updated Review.

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.

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.

Mortality among persons with epilepsy in onchocerciasis-endemic and non-endemic areas of sub-Saharan Africa: A systematic review and meta-analysis

To document epilepsy-related mortality in sub-Saharan Africa (SSA) and investigate possible associations with onchocerciasis endemicity. Systematic review with meta-analysis. Searches were performed in PubMed and Google Scholar (search terms: 'epilepsy'; 'mortality/death'; 'sub-Saharan Africa'). Included studies were classified as high-risk or low-risk for onchocerciasis based on documented endemicity data. Pooled mortality rates and annual case fatality rates (CFR) were calculated, and risk factors for mortality among persons with epilepsy (PWE) were investigated using meta-regression analysis. The 28 eligible studies reported 30 epilepsy surveys, of which 9 (30.0%) were conducted in onchocerciasis high-risk sites. The pooled epilepsy mortality rate was 20.9 (95% CI: 5.9-74.4) per 100,000 person-years, and the pooled CFR was 36.2 (95% CI: 23.9-54.4) per 1,000 PWE per year, albeit with substantial between-study heterogeneity. Compared to onchocerciasis low-risk sites, high-risk sites had higher pooled mortality (342.9 versus 10.0 per 100,000 PY; p<0.001) and CFR (57.0 versus 26.6 per 1,000 PWE per year; p=0.001). Mortality of PWE was almost five-fold that of people without epilepsy (mortality risk ratio: 4.9; 95% CI: 3.5-6.8). Studies in onchocerciasis high-risk sites and the study which recruited only PWE with nodding syndrome were associated with higher CFR (p=0.044 and p=0.002, respectively). The leading causes of epilepsy-related death were status epilepticus (58.5%), drowning (15.7%), and sudden unexpected death in epilepsy (10.1%). Epilepsy mortality remains high in SSA. Most reported causes of death among PWE might be averted by improving seizure control. Better epilepsy prevention and care are urgently needed, particularly in onchocerciasis-endemic settings.

Epilepsy-related mortality during the COVID-19 pandemic: A nationwide study of routine Scottish data

ObjectiveTo examine whether epilepsy-related deaths increased during the COVID-19 pandemic and if the proportion with COVID-19 listed as the underlying cause is different between people experiencing epilepsy-related deaths and those experiencing deaths unrelated to epilepsy. MethodsThis was a Scotland-wide, population-based, cross-sectional study of routinely-collected mortality data pertaining to March–August of 2020 (COVID-19 pandemic peak) compared to the corresponding periods in 2015–2019. ICD-10-coded causes of death of deceased people of any age were obtained from a national mortality registry of death certificates in order to identify those experiencing epilepsy-related deaths (coded G40–41), deaths with COVID-19 listed as a cause (coded U07.1–07.2), and deaths unrelated to epilepsy (death without G40–41 coded). The number of epilepsy-related deaths in 2020 were compared to the mean observed through 2015–2019 on an autoregressive integrated moving average (ARIMA) model (overall, men, women). Proportionate mortality and odds ratios (OR) for deaths with COVID-19 listed as the underlying cause were determined for the epilepsy-related deaths compared to deaths unrelated to epilepsy, reporting 95% confidence intervals (CIs). ResultsA mean number of 164 epilepsy-related deaths occurred through March–August of 2015–2019 (of which a mean of 71 were in women and 93 in men). There were subsequently 189 epilepsy-related deaths during the pandemic March–August 2020 (89 women, 100 men). This was 25 more epilepsy-related deaths (18 women, 7 men) compared to the mean through 2015–2019. The increase in women was beyond the mean year-to-year variation seen in 2015–2019. Proportionate mortality with COVID-19 listed as the underlying cause was similar between people experiencing epilepsy-related deaths (21/189, 11.1%, CI 7.0–16.5%) and deaths unrelated to epilepsy (3,879/27,428, 14.1%, CI 13.7–14.6%), OR 0.76 (CI 0.48–1.20). Ten of 18 excess epilepsy-related deaths in women had COVID-19 listed as an additional cause. ConclusionsThere is little evidence to suggest there have been any major increases in epilepsy-related deaths in Scotland during the COVID-19 pandemic. COVID-19 is a common underlying cause of both epilepsy-related and unrelated deaths.

Mortality in children with epilepsy: Cohort study using the clinical practice research datalink

To estimate Mortality Rate (MR) in UK children with epilepsy (CWE) compared to children without epilepsy (CWOE), describe causes of death, determine Mortality Rate Ratios (MRRs) for cause-specific mortality, and to analyse the contribution of co-morbidities (respiratory disease, neoplasm, and congenital disorders) to mortality rate. Retrospective cohort study of children born between 1998 and 2017, using linked data from the Clinical Practice Research Datalink Gold (Set 18). Epilepsy diagnoses were identified using previously validated codes. Causes of death were defined as natural or non-natural. Epilepsy-related deaths in CWE were those where underlying or contributing cause of death was epilepsy, status epilepticus, seizures, ill-defined/unknown cause or sudden death. We used Cox proportional hazard analysis to investigate associations of epilepsy and mortality. There were 1,191,304 children followed for 13,994,916 person-years (median: 12) if which 9665 (0.8%) had epilepsy. Amongst CWE, 3.4% died. MR of CWE was 4.1 (95%CI 3.7-4.6)/1,000 person-years. CWE had an increased adjusted all-cause mortality (MRR 50.9,95%CI 44.8-57.7) compared to CWOE. Amongst the 330 deaths in CWE, 323 (98%) were natural, 7 (2%) non-natural, 80 (24%) epilepsy-related. MRR of non-natural deaths was 2.09 (95%CI 0.92,4.74, p=0.08). Amongst CWE, 3.4% died during the study period. All-cause mortality rate in CWE was 4/1,000 person-years representing a fifty-fold increased mortality risk, after taking into account sex and socioeconomic status, compared to similarly aged children who did not have epilepsy. Causes of death mostly were not seizure-related. Non-natural death in CWE was uncommon.

SUDEP counseling: Where do we stand?

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in children and adults living with epilepsy. Several recent clinical practice guidelines have recommended that all individuals living with epilepsy and their caregivers be informed about SUDEP as a part of routine epilepsy counseling. Furthermore, several studies over the last two decades have explored the state of SUDEP counseling. Patients with epilepsy and their families want to be informed about the risk of SUDEP at or near the time of diagnosis, and preferably in person. Despite guideline recommendations, many pediatric and adult neurologists do not routinely inform individuals with epilepsy and their families about SUDEP. Some neurologists discuss SUDEP with only a subset of patients with epilepsy, such as those with risk factors like frequent generalized or focal to bilateral tonic-clonic seizures, nocturnal seizures, noncompliance, or medically refractory epilepsy. Proponents of routine SUDEP counseling argue that patients with epilepsy and their families have a "right to know" and that counseling may positively impact epilepsy self-management (i.e., behavioral modification and risk reduction). Some neurologists still believe that SUDEP counseling may cause unnecessary stress and anxiety for patients and their families (although this is erroneous) and that they also have a "right not to know." This narrative review explores the current gaps in SUDEP counseling, patients' and caregivers' perspectives of SUDEP counseling, and SUDEP prevention.

Mortality risk in adults with intellectual disabilities and epilepsy: an England and Wales case-control study.

People with epilepsy (PWE) and people with intellectual disabilities (ID) both live shorter lives than the general population and both conditions increase the risk of death further. We aimed to measure associations between certain risk factors for death in PWE and ID. A retrospective case-control study was conducted in ten regions in England and Wales. Data were collected on PWE registered with secondary care ID and neurology services between 2017 and 2021. Prevalence rates of neurodevelopmental, psychiatric and medical diagnoses, seizure frequency, psychotropic and antiseizure medications (ASM) prescribed, and health activity (epilepsy reviews/risk assessments/care plans/compliance etc.) recorded were compared between the two groups. 190 PWE and ID who died were compared with 910 living controls. People who died were less likely to have had an epilepsy risk assessment but had a greater prevalence of genetic conditions, older age, poor physical health, generalized tonic-clonic seizures, polypharmacy (not ASMs) and antipsychotic use. The multivariable logistic regression for risk of epilepsy-related death identified that age over 50, medical condition prevalence, antipsychotic medication use and the lack of an epilepsy review in the last 12months as associated with increased risk of death. Reviews by psychiatrists in ID services was associated with a 72% reduction in the odds of death compared neurology services. Polypharmacy and use of antipsychotics may be associated with death but not ASMs. Greater and closer monitoring by creating capable health communities may reduce the risk of death. ID services maybe more likely to provide this holistic approach.

Mortality, and life expectancy in Epilepsy and Status epilepticus-current trends and future aspects.

Patients with epilepsy carry a risk of premature death which is on average two to three times higher than in the general population. The risk of death is not homogenously distributed over all ages, etiologies, and epilepsy syndromes. People with drug resistant seizures carry the highest risk of death compared to those who are seizure free, whose risk is similar as in the general population. Most of the increased risk is directly related to the cause of epilepsy itself. Sudden unexplained death in epilepsy patients (SUDEP) is the most important cause of epilepsy-related deaths especially in the young and middle-aged groups. Population based studies with long-term follow up demonstrated that the first years after diagnosis carry the highest risk of death, while in the later years the mortality decreases. Improved seizure control and being exposed to a specialized comprehensive care centre may help to reduce the risk of death in patients with epilepsy. The mortality of status epilepticus is substantially increased with case fatality rates between 4.6% and 39%, depending on its cause and duration, and the age of the population studied. The epidemiological data on overall and cause specific mortality as well as their determinants and risk factors are critically reviewed and methodological issues pertinent to the studies on mortality of epilepsy and Status epilepticus are discussed.

Sudden unexpected death in epilepsy: Investigation of autopsy-based studies.

Epilepsy is a common neurological disorder that is associated with increased morbidity and mortality. Sudden unexpected death in epilepsy (SUDEP) is one of the most common causes for epilepsy-related deaths and its characteristics remain largely unknown, particularly from a forensic autopsy perspective. The present study aimed to investigate the neurological, cardiac, and pulmonary findings for a total of 388 SUDEP decedents, encompassing three cases from our forensic center during 2011-2020 and 385 literature-reported autopsy cases. In the cases mentioned in this study, two of them presented with only mild cardiac abnormalities, such as focal myocarditis and mild coronary atherosclerosis of the left anterior coronary artery. The third one was negative of any pathological findings. After pooling together these SUDEP cases, we found that neurological changes (n = 218 cases, 56.2%) were the most common postmortem findings associated with SUDEP, with cerebral edema/congestion (n = 60 cases, 15.5%) and old traumatic brain injury (n = 58 cases, 14.9%) being the major findings. Interstitial fibrosis, myocyte disarray/hypertrophy, and mild coronary artery atherosclerosis were the most common findings related to primary cardiac pathology, documented in 49 (12.6%), 18 (4.6%), and 15 (3.9%) cases, respectively. Non-specific pulmonary edema was the major finding in the lungs. This is an autopsy-based study that reports the scenario of postmortem findings for SUDEP cases. Our study paves the way for understanding the pathogenesis of SUDEP and the interpretation of death.

Anesthetic management of a pediatric patient with Dravet syndrome: A case report

Dravet syndrome (DS) is a rare and severe myoclonic epilepsy, with onset commonly occurring in infancy. Seizures are triggered by various causes, including fever, bathing, and light stimulus. DS is refractory to drug treatment. Moreover, status epilepticus (SE) can cause serious encephalopathy and epilepsy-related deaths. There are very few reports of general anesthesia in DS patients. Herein, we report our experience with the anesthetic management of a pediatric patient with DS. A 5-year-old boy (height, 112 cm; weight, 19 kg) was diagnosed with DS through SCN1A genetic testing, which revealed a de novo novel missense mutation. His medical history included drug-resistant epilepsy, developmental delay, and hypotonia. His seizures tended to be triggered daily by a rise in body temperature (BT), bathing, and light stimulus. He could not receive adequate dental treatment due to DS, although he had previously undergone dental treatment under restraint at the pediatric dentistry department of our hospital. The patient was scheduled for intensive dental treatment under general anesthesia due to noncooperation, and DS-related limitations. By considering the risk posed by elevated BT, seizure-inducing drugs were avoided, and general anesthesia was completed as planned, uneventfully. Although fluctuation of BT occurred during the procedure, it was finally controlled at the end of anesthesia at about the same level as at anesthesia induction. However, small seizures and a single generalized convulsion were observed accompanied by fever on postoperative day 1. The patient was discharged from the hospital without major problems on postoperative day 3, because of detailed planning and close preoperative cooperation with the attending pediatrician. It is essential to pay attention to managing BT and to avoid drugs that induce seizures during anesthesia for patients with DS. Cautious preoperative planning for anesthesia based on evaluation of the patient and rapid postoperative response in collaboration with the attending pediatrician is necessary in case an epileptic seizure occurs.

Quality of life in dogs with idiopathic epilepsy and their owners with an emphasis on breed-A pilot study.

Epilepsy in dogs is a common chronic and serious disorder and may have an impact on the quality of life of the owners as well as the dogs themselves. The aim of this pilot study was to investigate the QoL score of dogs suffering from idiopathic epilepsy and their owners and if possible, investigate whether a breed specific difference exists. Owners, either Dutch or Belgium, were asked to participate in a web based SurveyMonkey questionnaire. A total of 402 questionnaires representing 402 dogs with epilepsy were suitable for further analysis. Of the 402 dogs, 253 were males and 149 were females. Ninety-nine different breeds were represented. Fourteen breeds (177 dogs in total) were used to calculate breed specific scores; Australian Shepherd (n = 8), Beagle (n = 7), Belgian Tervuren dog (n = 9), Belgian Groenendaeler dog (n = 8), Border Collie (n = 38), Chihuahua (n = 9), Dachshund (n = 13), Drentsche Patrijshond (a Dutch partridge dog) (n = 14), French Bulldog (n = 12), Golden Retriever (n = 17), Labrador Retriever (n = 18), and Rottweiler (n = 12). For the Border Collie, there was a statistically significant correlation between "epilepsy related death," the severity of the seizures (p < 0.001) and cluster seizures (p < 0.001). The quality of life of the Border Collie was scored lower compared to all other dogs (p = 0.02). There were three breeds that had a minimal decrease in the overall quality of life score compared to all other dogs: the Chihuahua (p = 0.03), Dachshund (p = 0.001), and Golden retriever (p = 0.01). The score for "caring for my epileptic dog decreases my own QoL" was high for the Border Collie, Boxer, French Bulldog, and Rottweiler, but was only found to be statistically significantly higher in the Border Collie (p = 0.01). Scores for the Golden Retriever (p = 0.04) and Labrador (p = 0.006) were lower. In conclusion, this study reports breed specific quality of life scores of dogs with epilepsy and their owners, and underlines that breed by itself, is also an important factor when managing epilepsy in dogs.

“Untold Distress” – How did the COVID-19 pandemic affect those who had previously experienced an epilepsy-related bereavement?

PurposeThis study explores the impact of the COVID-19 pandemic and lockdown on people with lived experience of sudden bereavement as a consequence of an epilepsy-related death. MethodWe developed an online survey with fixed choice and open-ended response formats to collect data on grief symptoms and well-being during the pandemic. A total of 275 people bereaved by epilepsy-related deaths between 1980–2020 participated in this study: with 79 participants providing free-text responses for inductive thematic analysis. ResultsIn total, 84% of participants reported a bereavement following a sudden death of a person aged under 40, with 22% aged 19 and under. The majority (77% of participants) reported they had been thinking more about the person who died compared to before the COVID-19 outbreak and 54% had experienced more distressing flashbacks to the time of death. Additionally, 61% reported more difficulties falling asleep and staying asleep and 88% of participants reported that the outbreak and response measures had negatively impacted upon their mental health. Medication was being taken for a diagnosed mental health condition by 33% of participants at the time of the study. We categorized these negative experiences during COVID in to four main-themes - ‘Family’, ‘Lifestyle’, ‘Personal Well-being’ and ‘Health Services and Shielding Populations’. The ‘Personal Well-being’ theme was inextricably linked to grief symptoms including ‘reflection on the death’, ‘re-exposure to feeling’, ‘grief’, ‘salience of sudden deaths in the media’ and ‘inability to commemorate anniversaries and rituals’. These findings were consistent for bereaved people irrespective of the recency of the death. ConclusionThis study highlights the impact of the disruption caused by the pandemic on the grief-management of those bereaved by epilepsy-related death. Grief is not static and its management is connected to the psychosocial and formal support structures that were disrupted during the pandemic. The removal of these supports had an adverse effect upon the mental health and well-being of many bereaved. There is an urgent need for a system-wide transformation of epilepsy and mental health services to be inclusive of the needs and experiences of people impacted by sudden deaths in epilepsy and the contribution of the specialist service developed by families and clinicians to meet this gap.

Trends of Epilepsy-Related Mortality in South Korea.

Epilepsy increases the risk of death in affected individuals of any age. We aimed to determine the mortality caused by epilepsy and its time trends in Korea. We obtained population and cause of death data between 1993 and 2019 from Statistics Korea. We identified death caused by epilepsy or status epilepticus. We calculated the crude mortality rate (CMR), age-specific mortality rate, age-standardized mortality rate (ASMR, corresponding to epilepsy-related deaths per 100,000 persons in the general population), and the proportional mortality (PM, corresponding to the proportion of epilepsy-related deaths among all-cause deaths). In 2019, 471 deaths were caused by epilepsy (CMR=0.92), accounting for 0.16% of all deaths in that year. The age-specific mortality rate increased with age, up to 7.01% among individuals aged 80 years and older, while the PM was the highest (3.80%) among individuals aged 5-14 years, which decreased with age. Between 1993 and 2019, the CMR, ASMR, and PM peaked in 2002, and the CMR then rebounded after the trough in this trend in 2011 while the ASMR continued to decrease, and the PM became relatively stable from 2011. Starting in 2005, the age-specific mortality rate for epilepsy had an increasing tendency over time among those aged 75 years or older, and a decreasing tendency in the younger age groups. A declining tendency of mortality from epilepsy was found in the overall population of Korea over recent decades. However, epilepsy is a notable cause of death in children, and epilepsy-related mortality is increasing in the elderly population.

Case-control study developing Scottish Epilepsy Deaths Study Score to predict epilepsy-related death.

This study aimed to develop a risk prediction model for epilepsy-related death in adults. In this age- and sex-matched case-control study, we compared adults (aged ≥16 years) who had epilepsy-related death between 2009 and 2016 to living adults with epilepsy in Scotland. Cases were identified from validated administrative national datasets linked to mortality records. ICD-10 cause-of-death coding was used to define epilepsy-related death. Controls were recruited from a research database and epilepsy clinics. Clinical data from medical records were abstracted and used to undertake univariable and multivariable conditional logistic regression to develop a risk prediction model consisting of four variables chosen a priori. A weighted sum of the factors present was taken to create a risk index-the Scottish Epilepsy Deaths Study Score. Odds ratios were estimated with 95% confidence intervals (CIs). Here, 224 deceased cases (mean age 48 years, 114 male) and 224 matched living controls were compared. In univariable analysis, predictors of epilepsy-related death were recent epilepsy-related accident and emergency attendance (odds ratio 5.1, 95% CI 3.2-8.3), living in deprived areas (odds ratio 2.5, 95% CI 1.6-4.0), developmental epilepsy (odds ratio 3.1, 95% CI 1.7-5.7), raised Charlson Comorbidity Index score (odds ratio 2.5, 95% CI 1.2-5.2), alcohol abuse (odds ratio 4.4, 95% CI 2.2-9.2), absent recent neurology review (odds ratio 3.8, 95% CI 2.4-6.1) and generalized epilepsy (odds ratio 1.9, 95% CI 1.2-3.0). Scottish Epilepsy Deaths Study Score model variables were derived from the first four listed before, with Charlson Comorbidity Index ≥2 given 1 point, living in the two most deprived areas given 2 points, having an inherited or congenital aetiology or risk factor for developing epilepsy given 2 points and recent epilepsy-related accident and emergency attendance given 3 points. Compared to having a Scottish Epilepsy Deaths Study Score of 0, those with a Scottish Epilepsy Deaths Study Score of 1 remained low risk, with odds ratio 1.6 (95% CI 0.5-4.8). Those with a Scottish Epilepsy Deaths Study Score of 2-3 had moderate risk, with odds ratio 2.8 (95% CI 1.3-6.2). Those with a Scottish Epilepsy Deaths Study Score of 4-5 and 6-8 were high risk, with odds ratio 14.4 (95% CI 5.9-35.2) and 24.0 (95% CI 8.1-71.2), respectively. The Scottish Epilepsy Deaths Study Score may be a helpful tool for identifying adults at high risk of epilepsy-related death and requires external validation.

Epilepsy-associated death in the Southwestern Ontario: A clinicopathological correlation study.

Patients with epilepsy are at elevated risk for premature mortality, of which sudden unexpected death in epilepsy (SUDEP) is one of the leading causes. SUDEP incidence varies significantly depending on the population and the methods used to document the cause of death. We performed retrospective case review at the London Health Sciences Centre for the period of 2000 to 2018. Clinical information, scene investigations, general pathology findings, toxicology, and neuropathology findings were obtained, examined, and confirmed by two neuropathologists and one epileptologist. The characteristics were compared and summarized. We also evaluated the impact of 2010 revision of Ontario Coroner Act Regulation, which significantly limited whole brain examination. Among the 12,206 cases reviewed, we identified 152 cases with a known history of epilepsy. Ninety-seven cases (64%) were classified as SUDEP. There were significantly more SUDEP decedents found dead unwitnessed at night in prone position, than non-SUDEP. Generalized seizures were strongly associated with SUDEP. A male predominance was observed in SUDEP group between 15 and 35 years old. Near half of the brains examined were "unremarkable." There was no difference in neuropathology findings between SUDEP and non-SUDEP groups. After implementation of the 2010 revision of Ontario Coroner Act Regulation, fixed whole brain examination was reduced from 88% to 7% of the epilepsy-related death investigation. Except a lower diagnosis rate of "inflammatory/infectious changes," there were no significant differences in neuropathology findings. This is the first detailed clinical-pathological study on epilepsy-related death based on a Canadian cohort. This study reinforces the previously reported findings in SUDEP and highlights the importance of clinicopathological correlation for accurate classification of epilepsy-related death.

Diaphragmatic pacing for the prevention of sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy is the leading cause of epilepsy related death. Currently, there are no reliable methods for preventing sudden unexpected death in epilepsy. The precise pathophysiology of sudden unexpected death in epilepsy is unclear; however, convergent lines of evidence suggest that seizure-induced respiratory arrest plays a central role. It is generally agreed that sudden unexpected death in epilepsy could be averted if the patient could be rapidly ventilated following the seizure. The diaphragm is a muscle in the chest which contracts to draw air into the lungs. Diaphragmatic pacing is a surgical intervention which facilitates normal ventilation in situations, such as spinal cord injury and sleep apnoea, in which endogenous respiration would be inadequate or non-existent. In diaphragmatic pacing, electrodes are implanted directly onto diaphragm or adjacent to the phrenic nerves which innervate the diaphragm. These electrodes are then rhythmically stimulated, thereby eliciting contractions of the diaphragm which emulate endogenous breathing. The goal of this study was to test the hypothesis that seizure-induced respiratory arrest and death can be prevented with diaphragmatic pacing. Our approach was to induce respiratory arrest using maximal electroshock seizures in adult, male, C57BL6 mice outfitted with EEG and diaphragmatic electrodes (n = 8 mice). In the experimental group, the diaphragm was stimulated to exogenously induce breathing. In the control group, no stimulation was applied. Breathing and cortical electrographic activity were monitored using whole body plethysmography and EEG, respectively. A majority of the animals that did not receive the diaphragmatic pacing intervention died of seizure-induced respiratory arrest. Conversely, none of the animals that received the diaphragmatic pacing intervention died. Diaphragmatic pacing improved postictal respiratory outcomes (two-way ANOVA, P < 0.001) and reduced the likelyhood of seizure-induced death (Fisher’s exact test, P = 0.026). Unexpectedly, diaphragmatic pacing did not instantly restore breathing during the postictal period, potentially indicating peripheral airway occlusion by laryngospasm. All diaphragmatically paced animals breathed at some point during the pacing stimulation. Two animals took their first breath prior to the onset of pacing and some animals had significant apnoeas after the pacing stimulation. Sudden unexpected death in epilepsy results in more years of potential life lost than any other neurological condition with the exception of stroke. By demonstrating that seizure-induced respiratory arrest can be prevented by transient diaphragmatic pacing in animal models we hope to inform the development of closed-loop systems capable of detecting and preventing sudden unexpected death in epilepsy.

Sudden Unexpected Death in Epilepsy.

Epilepsy is a complex neurological condition with numerous etiologies and treatment options. In a subset of these patients, sudden unexpected death can occur, and to date, there are numerous explanations as to the pathophysiological mechanisms and how to mitigate these catastrophic outcomes. Approximately 2.3 million Americans have epilepsy, and nearly 150,000 people develop the condition each year. Sudden unexpected death in epilepsy (SUDEP) accounts for 2–18% of all epilepsy-related deaths and this is equivalent to one death in 1000 person-years of diagnosed epilepsy. It is more common in young adults aged 20–45. Seizures in the past year; the absence of terminal remission in the last five years; increased seizure frequency, particularly GTCS; and nocturnal seizures are the most potent modifiable risk factors for SUDEP. Patients not receiving any antiepileptic drug therapy are at higher risk of SUDEP. Patient education on medication compliance; care plans for seizure clusters (rescue medicines); epilepsy self-management programs; and lifestyle changes to avoid seizure-triggering factors, including avoiding excessive alcohol use and sleep deprivation, should be provided by health care providers. Continued research into SUDEP will hopefully lead to effective interventions to minimize occurrences. At present, aggressive control of epilepsy and enhanced education for individuals and the public are the most effective weapons for combating SUDEP. This narrative review focuses on updated information related to SUDEP epidemiology; pathophysiology; risk factor treatment options; and finally, a discussion of important clinical studies. We seek to encourage clinicians who care for patients with epilepsy to be aggressive in controlling seizure activity and diligent in their review of risk factors and education of patients and their families about SUDEP.

P.106 Impact of comorbid sleep disorders in patients with epilepsy on mortality risk

Background: Pooled mortality has been observed to be almost threefold among people with epilepsy (PWE). Among PWE, epilepsy related deaths (including sudden death in epilepsy (SUDEP)), are commoner than other causes. Among these, around 16-36% are SUDEP, of which 80% events occur during sleep. SUDEP risk is most measured using the SUDEP Risk Inventory. To prevent SUDEP and reduce epilepsy related mortality, we need a better understanding, not only of the components of this screening inventory, but also additional clinical and neurophysiologic parameters that might be commoner among PWE and potentially associated with higher mortality risk. Methods: Patients diagnosed with active epilepsy over the last 3 years will form the study population, categorized into two groups: PWE with a comorbid sleep disorder, and PWE without diagnosis of a sleep disorder. Descriptive statistics will be used to report clinic and neurophysiologic characteristics of subjects enrolled. Results: We hypothesize that there is a significantly increased prevalence of sleep comorbidity among people with epilepsy compared to the general population. Poorer sleep quality could potentially have an association with higher mortality risk among epilepsy patients, Conclusions: We hope to identify and to add sleep factors such as primary sleep disorders and sleep disturbances to already established SUDEP-7 parameters.

Cause-specific mortality and life years lost in people with epilepsy: a Danish cohort study.

Mortality rates are two to three times higher in people with epilepsy than in the general population. This study aimed to quantify how this increased mortality translates into reduced life expectancy and to identify the underlying causes of deaths, thereby offering suggestions for how to reduce mortality associated with epilepsy. In this population-based cohort study, we included all individuals aged 0-94 years who were living in Denmark between 2000 and 2015. Using the nationwide registers, we identified people diagnosed with epilepsy and estimated the excess of life years lost due to 13 overall and nine specific causes of death. Among 6 022 160 people, we identified 129 598 with epilepsy (52.6% males), with a mean age of epilepsy onset of 36.5 years (standard deviation = 26.3 years). During the 16 years of follow-up, 851 087 individuals died, and of these 36 923 had been diagnosed with epilepsy. The average reduction in life expectancy in people with epilepsy was 11.84 years in males (95% confidence interval: 11.66-12.00) and 10.91 years in females (95% confidence interval: 10.70-11.11) compared to the general population. Life expectancy was reduced irrespective of epilepsy aetiology (symptomatic ∼14 years; idiopathic ∼8-10 years), and in particular in people with epilepsy and psychiatric comorbidity (∼13-16 years). Excess mortality was evident across all causes of death including cardiovascular disorders, accidents, and suicide. People with epilepsy experience a substantial reduction in lifespan that can only partly be explained by underlying conditions. Prevention of epilepsy-related deaths should focus on the consequences of psychiatric comorbidity and on modifiable risk factors associated with preventable causes of death such as accidents and neurological and cardiovascular disorders.

Cause of mortality among people with epilepsy in Malaysia: A hospital-based study

BackgroundThis is a follow-up study on mortality in adult patients in Malaysia. This study aimed to determine the cause of death and the factors associated with epilepsy-related death in PWE in Malaysia. MethodDeceased PWE from 2005 to 2020 were identified from the National Registry Department of Malaysia. The details of the cause of death and predictors for epilepsy-related deaths was ascertained from medical records and phone interviews. ResultThere were a total of 227 deaths, 144 (63.4%) were male, two (0.9%) underwent autopsy and 46.3% passed away in the community. The majority of deaths (55.5%) were due to causes unrelated to epilepsy. Forty-five (19.8%) death were related to epilepsy, of which, 22 (9.7%) were due to death directly related to epilepsy including probable SUDEP (5.3%) and status epilepticus (4.4%). The cause of death was unknown in 56 (24.7%) cases. Binary logistic regression analysis identified 3 predictors for epilepsy-related deaths, i.e., structural causes (OR 3.09, 95% CI 1.100–8.691, p = 0.032), younger age of death (OR 2.35, 95% CI 1.039–5.333, p = 0.040) and history of brain surgery (OR 8.09, 95% CI 2.014–32.510, p = 0.003). Twelve (5.3%) had probable SUDEP. The incidence rate of probable SUDEP was 0.42 per 1000 person-years. The majority of them had intellectual disability (9/12), generalized tonic-clonic seizures (9/12), and 2 or more ASMs (9/12). ConclusionEpilepsy-related deaths accounted for 20% of the deaths in PWE, associated with structural cause, younger age of death, and previous brain surgery. Probable SUDEP is not uncommon in Malaysia and could be under-diagnosed.