Asymmetrical cortical surface area decrease in epilepsy patients with postictal generalized electroencephalography suppression.

Postictal generalized electroencephalographic suppression is a possible electroencephalographic marker for sudden unexpected death in epilepsy. We aimed to investigate the cortical surface area abnormalities in epilepsy patients with postictal generalized electroencephalographic suppression. We retrospectively included 30 epilepsy patients with postictal generalized electroencephalographic suppression (PGES+), 21 epilepsy patients without postictal generalized electroencephalographic suppression (PGES-), and 30 healthy controls. Surface-based analysis on high-resolution T1-weighted images was conducted and cortical surface areas were compared among the three groups, alongside correlation analyses with seizure-related clinical variables. Compared with PGES- group, we identified reduced surface area in the bilateral insula with more extensive distribution in the right hemisphere in PGES+ group. The reduced right insular surface area was associated with younger seizure-onset age. When compared with healthy controls, PGES- group presented reduced surface area in the left caudal middle frontal gyrus; PGES+ group presented more widespread surface area reductions in the right posterior cingulate gyrus, left postcentral gyrus, middle frontal gyrus, and middle temporal gyrus. Our results suggested cortical microstructural impairment in patients with postictal generalized electroencephalographic suppression. The significant surface area reductions in the insular cortex supported the autonomic network involvement in the pathology of postictal generalized electroencephalographic suppression, and its right-sided predominance suggested the potential shared abnormal brain network for postictal generalized electroencephalographic suppression and sudden unexpected death in epilepsy.

Altered ventilatory responses to hypercapnia-hypoxia challenges in a preclinical SUDEP model involve orexin neurons.

Failure to recover from repeated hypercapnia and hypoxemia (HH) challenges caused by severe GCS and postictal apneas may contribute to sudden unexpected death in epilepsy (SUDEP). Our previous studies found orexinergic dysfunction contributes to respiratory abnormalities in a preclinical model of SUDEP, Kcna1-/- mice. Here, we developed two gas challenges consisting of repeated HH exposures and used whole body plethysmography to determine whether Kcna1-/- mice have detrimental ventilatory responses. Kcna1-/- mice exhibited an elevated ventilatory response to a mild repeated hypercapnia-hypoxia (HH) challenge compared to WT. Moreover, 71% of Kcna1-/- mice failed to survive a severe repeated HH challenge, whereas all WT mice recovered. We next determined whether orexin was involved in these differences. Pretreating Kcna1-/- mice with a dual orexin receptor antagonist rescued the ventilatory response during the mild challenge and all subjects survived the severe challenge. In ex vivo extracellular recordings in the lateral hypothalamus of coronal brain slices, we found reducing pH either inhibits or stimulates putative orexin neurons similar to other chemosensitive neurons; however, a significantly greater percentage of putative orexin neurons from Kcna1-/-mice were stimulated and the magnitude of stimulation was increased resulting in augmentation of the calculated chemosensitivity index relative to WT. Collectively, our data suggest that increased chemosensitive activity of orexin neurons may be pathologic in the Kcna1-/- mouse model of SUDEP, and contribute to elevated ventilatory responses. Our preclinical data suggest that those at high risk for SUDEP may be more sensitive to HH challenges, whether induced by seizures or other means; and the depth and length of the HH exposure could dictate the probability of survival.

Impact of COVID-19 Pandemic Interventions on Sudden Unexpected Death in Infancy Incidence in France.

OBJECTIVE: To study the impact of non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic on the monthly incidence of sudden unexpected death in infancy (SUDI) cases overall and those with a viral or bacterial identification. STUDY DESIGN: We conducted an interrupted time-series analysis using seasonally adjusted Poisson regression models from the French national prospective and multicenter SUDI registry, that included all SUDI cases under age one year who died from 2016 to 2021 in mainland France. RESULTS: Of 998 SUDI cases analyzed, 750 were recorded during the pre-pandemic period (January 2016 through March 2020) and 248 during the NPI period (April 2020 through December 2021). We found a significant seasonal pattern of overall monthly SUDI incidence, with a peak observed periodically from November to February. The monthly SUDI incidence decreased significantly from the pre-pandemic to NPI periods (adjusted incidence rate ratio 0.83 [95% confidence interval 0·72-0·96]). In particular, the monthly incidence of SUDI cases with a viral or bacterial identification decreased, while no significant difference was found for SUDI cases without a viral or bacterial identification. CONCLUSION: NPIs were associated with a significant change in the incidence of SUDI cases with a viral or bacterial identification. Further investigations are needed to analyze the pathophysiologic role of viruses and bacteria in the SUDI.

Mortality of Epilepsy in Chinese Populations: A Comprehensive Review.

BACKGROUND: 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. SUMMARY: By summarising the evidence on the mortality characteristics in Chinese populations with epilepsy in the last 6 decades, we found a median mortality rate of 14.7 (6.8-74.4)/1,000 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)/1,000 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 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. KEY MESSAGES: 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.

Fatal child abuse detected by systematic post-mortem fundus photograph in sudden death in infancy.

In living children, the use of a wide field fundus camera such as RetCam is the gold standard practice to document retinal haemorrhages in suspected cases of abusive head trauma (AHT). In case of sudden unexpected death in infancy (SUDI), child abuse must be considered as a possible cause of death and an eye examination is required. However, no example of post-mortem fundus photograph (PMFP) of retinal haemorrhages related to AHT is yet available for clinicians.We report a SUDI case, with no external traumatic lesions or limb fractures, for which prompt PMFP showed retinal haemorrhages typical of AHT: child abuse was subsequently confirmed by the forensic investigation. We discuss why PMFP is a relevant screening test to detect retinal haemorrhages in the case of SUDI and why the use of the RetCam should be further investigated.

Clinical exome sequencing elucidates underlying cause of death in sudden unexpected death of infants: two case reports.

Sudden unexpected death in infants (SUDI) is a traumatic event for families, and unfortunately its occurrence remains high in many parts of the world. Whilst cause of death is resolved for most cases, others remain undetermined following postmortem investigations. There has been a recognition of the role of genetic testing in unexplained cases, where previous studies have demonstrated the resolution of cases through DNA analyses. Here we present two case reports of SUDI cases admitted to Salt River Mortuary, South Africa, and show that underlying causes of death were determined for both infants using clinical exome sequencing. The first infant was heterozygous for a variant (rs148175795) in COL6A3, which suggested a bronchopulmonary dysplasia phenotype. This hypothesis led to finding of a second candidate variant in DMP1 (rs142880465), which may contribute towards a digenic/polygenic mechanism of a more severe phenotype. Histological analysis of retained tissue sections showed an asphyxial mechanism of death, where bronchiolar muscle weakness from an underlying bronchopulmonary dysplasia may have contributed to the asphyxia by affecting respiration. In the second infant, a homozygous variant (rs201340753) was identified in MASP1, which was heterozygous in each parent, highlighting the value of including parental DNA in genetic studies. Whilst mannose-binding lectin deficiency could not be assessed, it is plausible that this variant may have acted in combination with other risk factors within the triple-risk model to result in sudden death. These results may have genetic implications for family members, and represent possible new candidate variants for molecular autopsies.

The influence of risk factors, biomarkers and care settings on SUDEP counseling.

Although sudden unexpected death in epilepsy (SUDEP) is the most feared epilepsy outcome, there is a dearth of SUDEP counseling provided by neurologists. This may reflect limited time, as well as the lack of guidance on the timing and structure for counseling. We evaluated records from SUDEP cases to examine frequency of inpatient and outpatient SUDEP counseling, and whether counseling practices were influenced by risk factors and biomarkers, such as post-ictal generalized EEG suppression (PGES). We found a striking lack of SUDEP counseling despite modifiable SUDEP risk factors; counseling was limited to outpatients despite many patients having inpatient visits within a year of SUDEP. PGES was inconsistently documented and was never included in counseling. There is an opportunity to greatly improve SUDEP counseling by utilizing inpatient settings and prompting algorithms incorporating risk factors and biomarkers.

Early mortality in STXBP1-related disorders.

INTRODUCTION: 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. METHODS: Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. RESULTS: 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 13 years (range: 11 months-46 years). 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). CONCLUSION: 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.

Trends in Sudden Unexpected Deaths in an Australian Population: Impact of the COVID-19 Pandemic.

BACKGROUND AND AIM: SARS-CoV-2 infection is associated with increased cardiovascular (CV) morbidity and mortality, manifesting as increased adverse outcomes in the first 30 days, extending to 12 months. This study aimed to investigate trends in sudden unexpected deaths between 2018 and 2022, with a focus on CV deaths. METHOD: A retrospective analysis was performed on autopsy reports (n=9,330) obtained from New South Wales Coroners Court, Australia, specifically targeting cases of unexplained deaths that occurred between 2018 and 2022. Statistical analysis was conducted using chi-square tests and a post hoc analysis with Bonferroni correction, as well as analysis of variance with multiple comparisons. RESULTS: There were 349 (18.3%) CV deaths in 2018, 346 (18.0%) in 2019, 338 (17.5%) in 2020, 395 (21.9%) in 2021, and (23.4%) 413 in 2022 (p=0.0002). Among CV deaths, the number of deaths from sudden arrhythmic death syndrome were 25 (7.2%) in 2018, 26 (7.5%) in 2019, 18 (5.3%) in 2020, 52 (13.2%) in 2021, and 80 (19.4%) in 2022 (p=0.0001). Atherosclerosis was the most common cause of death among all CV categories; there were 196 (56.2%) atherosclerosis deaths in 2018, 207 (59.8%) in 2019, 192 (56.8%) in 2020, 221 (56.0%) in 2021, and 197 (47.7%) in 2022 (p=0.43). The average age of death from sudden arrhythmic death syndrome (42.8±19.1 years) across 2018-2022 was younger than atherosclerosis (56.2±12.4 years) and total groups (53.1±15.1 years) (p<0.001). Males comprised 76% of all CV deaths from 2018 to 2022 (p<0.0001). CONCLUSIONS: Compared with pre-pandemic data, a noteworthy increase in CV deaths was observed in occurrence with the escalation in COVID-19 cases in Australia. This may be attributed to direct or indirect factors, such as lifestyle modifications, disrupted access to routine cardiac care, or COVID-19 infection-triggered CV deaths.

[Incidence of sudden death in epilepsy (SUDEP): update and limitations]. / Inzidenz des plötzlichen Epilepsietodes (SUDEP): Update und Limitationen.

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

Sudden unexpected death from subvalvular hemorrhagic cyst complicated with coronary heart disease in an adult.

Cardiac blood cysts are rare benign tumors. It is commonly found in the heart valve and left ventricle of newborns by autopsy and is rarely seen in adults [1, 2]. The typical histopathology of cardiac blood cysts is a closed, round, blood-containing cystic mass attached to the heart valve or endocardium. This article reports a rare case of sudden death due to a giant subaortic cardiac blood cyst with coronary heart disease in an adult patient and summarizes the pathological features, aiming to provide a reference for the forensic pathological identification of cardiac blood cysts.

Death in a bathtub of an adolescent with neurofibromatosis type 2 exhibiting meningioangiomatosis with white matter involvement.

Neurofibromatosis type 2 (NF2) is a neurocutaneous syndrome characterized by the development of multiple benign tumors, including vestibular schwannomas and meningiomas, in the nervous system. Seizures are rarely associated with NF2, and the lethality of this condition typically stems from tumor growth and related complications, leaving the incidence of sudden death largely unreported. This report discribes a 16-year-old girl with a history of NF2 and occasional seizures who died unexpectedly in a bathtub. Postmortem examination revealed multiple tumors in the cranial nerves (schwannoma), under the dura mater (meningioma), and in the upper cervical cord (neurofibroma). Typical signs of drowning, such as foam in the airways, were not present. Upon histological examination, meningioangiomatosis (MA) was observed in the cerebellum and the cerebral cortex, specifically in the frontal lobe, temporal lobe, and insula. The MA extended into the white matter, exhibiting severe perivascular fibrosis and cystic dilatation of perivascular spaces in the frontal lobe and cerebellum. Additionally, glial microhamartomas were detected both around and separate from the MA. These autopsy findings suggest that sudden unexpected death in epilepsy (SUDEP) was the cause of death rather than drowning. Moreover, while NF2-associated MA is typically asymptomatic, unlike sporadic MA, which commonly presents with seizures, the spread of MA into the white matter is unusual in an NF2 patient. Therefore, MA with the white matter involvement could have been a factor causing the seizures and the occurrence of SUDEP in this NF2 patient.

Screening for viral pathogens in the gastrointestinal tract from cases of sudden unexpected death in infancy at the Tygerberg Medico-legal Mortuary.

Sudden and unexpected death in infancy (SUDI) may be triggered by an external risk or exposure. Intestinal infections with enteric viruses may disrupt the gut and enhance bacterial toxins present in SUDI cases. While diarrhoeal disease deaths have decreased worldwide, approximately half a million deaths still occur in children in Sub- Saharan Africa and South Asia. Furthermore, the role of viral enteropathogens in SUDI cases have not been investigated. The aim of this study was to describe specific viral pathogens in stool samples collected from SUDI cases and age-matched, apparently healthy infants in Cape Town, South Africa. Stool samples were collected from 176 SUDI cases between June 2017 and May 2018. In addition, stool samples were collected from the nappies of 30 age-matched, apparently healthy infants as a control group. Real-time polymerase chain reaction was performed on the stool samples for viral detection. A total of 111 SUDI cases were positive for viruses, with rotavirus (38.6%; 68/176) and norovirus GI and GII (30.0%; 53/176) were prevalent in SUDI cases. Adenovirus Type F was present in only 15.9% (28/176), astrovirus in 9.7% (17/176), and sapovirus in 0.6% (1/176) of cases. In the control samples, norovirus GII was detected most frequently (36.7%; 11/30), followed by rotavirus (33.3%; 10/30), and sapovirus in 6.7% (2/30). While there was no significant association between SUDI cases and enteric viruses, the majority of viruses were significantly associated with the seasons. The study confirms the importance of rotavirus vaccination and describes the significance of norovirus infection in children, post rotavirus vaccine introduction.

A unified hypothesis of SUDEP: Seizure-induced respiratory depression induced by adenosine may lead to SUDEP but can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray.

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.

Sudden unexpected death in epilepsy during cenobamate clinical development.

OBJECTIVE: We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program. METHODS: We retrospectively analyzed deaths among all adults with uncontrolled focal (focal to bilateral tonic-clonic [FBTC], focal impaired awareness, focal aware) or primary generalized tonic-clonic (PGTC) seizures who received ≥1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.8 to 11 seizures per 28 days and median epilepsy duration ranged from 20 to 24 years. Total person-years included all days that a patient received cenobamate during completed studies or up to June 1, 2022, for ongoing studies. All deaths were evaluated by two epileptologists. All-cause mortality and SUDEP rates were expressed per 1000 person-years. RESULTS: A total of 2132 patients (n = 2018 focal epilepsy; n = 114 idiopathic generalized epilepsy) were exposed to cenobamate for 5693 person-years. Approximately 60% of patients with focal seizures and all patients in the PGTC study had tonic-clonic seizures. A total of 23 deaths occurred (all in patients with focal epilepsy), for an all-cause mortality rate of 4.0 per 1000 person-years. Five cases of definite or probable SUDEP were identified, for a rate of .88 per 1000 person-years. Of the 23 overall deaths, 22 patients (96%) had FBTC seizures, and all 5 of the SUDEP patients had a history of FBTC seizures. The duration of exposure to cenobamate for patients with SUDEP ranged from 130 to 620 days. The SMR among cenobamate-treated patients in completed studies (5515 person-years of follow-up) was 1.32 (95% confidence interval [CI] .84-2.0), which was not significantly different from the general population. SIGNIFICANCE: These data suggest that effective long-term medical treatment with cenobamate may reduce excess mortality associated with epilepsy.

Time-to-event clinical trial designs: Existing evidence and remaining concerns.

Well-designed placebo-controlled clinical trials are critical to the development of novel treatments for epilepsy, but their design has not changed for decades. Patients, clinicians, regulators, and innovators all have concerns that recruiting for trials is challenging, in part, due to the static design of maintaining participants for long periods on add-on placebo when there are an increasing number of options for therapy. A traditional trial maintains participants on blinded treatment for a static period (e.g., 12 weeks of maintenance), during which participants on placebo have an elevated risk of sudden unexpected death in epilepsy compared to patients on an active treatment. Time-to-event trials observe participants on blinded treatment until a key event occurs (e.g., post-randomization seizure count matches pre-randomization monthly seizure count). In this article, we review the evidence for these designs based on re-analysis of prior trials, one published trial that used a time-to-second seizure design, and experience from an ongoing blinded trial. We also discuss remaining concerns regarding time-to-event trials. We conclude that, despite potential limitations, time-to-event trials are a potential promising mechanism to make trials more patient friendly and reduce placebo exposure, which are urgent needs to improve safety and increase recruitment to trials.

Assessing retinal hemorrhages with non-invasive post-mortem fundus photographs in sudden unexpected death in infancy.

INTRODUCTION: In the case of sudden unexpected death in infancy (SUDI), eye examination is systematic to detect retinal hemorrhages (RH) that are a crucial hallmark for abusive head trauma (AHT). The aim of this study is to assess the ability of non-invasive post-mortem fundus photographs (PMFP) to detect RH in case of SUDI. METHODS: Bicentric retrospective analysis of consecutive cases of SUDI under 2 years of age were managed by two French SUDI referral centers with PMFP by RetCam (Clarity Medical Systems USA). PMFP were reviewed randomly, twice, by three independent ophthalmologists blinded for clinical data. RESULTS: Thirty cases (60 eyes) were included. Median age was 3.5 months (interquartile [1.6; 6.0]). No child died of AHT. Image quality was sufficient to assert presence or absence of RH in 50 eyes (83%). Sufficient quality rate was significantly higher when the post-mortem interval was inferior to 18 h (91%, 42/46) as opposed to over 18 h (57%, 8/14, p=0.0096). RH were found in six eyes (10%), four children (13%), with excellent inter and intra-raters' concordance (Cohen's Kappa from 0.81 [0.56-1.00] to 1.00 [1.00-1.00]). CONCLUSION: PMFP can detect RH in case of SUDI and is a relevant systematic screening test to be carried out as soon as the deceased child arrives in the hospital. It can decrease the need of eye removal for pathological examination, but further studies are needed to define the best decision algorithm.

Life after SUDEP: Experiences of traumatic loss and growth.

PURPOSE: To understand the experiences of bereaved relatives of individuals who passed due to sudden unexpected death in epilepsy (SUDEP) and to explore the impacts of death in their lives. METHODS: The principles of fundamental qualitative description informed all design decisions. Stratified purposeful sampling included 21 bereaved relatives (parent, sibling, or spouse/partner), aged at least 18 years, of persons who passed away because of SUDEP. In-depth one-to-one interviews were conducted. Directed content analysis was used to code, categorize, and synthesize the interview data. RESULTS: There was some criticism of emergency response and medical professionals involved in providing insensitive or poor care immediately after SUDEP occurred. Personal hardships described by participants following SUDEP included loss of personal identity, feeling depressed, experiencing guilt, having panic attacks, requiring therapy, as well as having difficulty with anniversaries, dates, and cleaning up a child's room. Bereaved spouses and parents in particular spoke of experiencing challenges in maintaining other relationships following the death. Some participants spoke of experiencing increased financial hardships. Ways of coping included keeping oneself busy, honoring the memory of the loved one, relying on friends and families, and engaging in advocacy/community work, including raising awareness on epilepsy and SUDEP. CONCLUSIONS: Sudden unexpected death in epilepsy affected several aspects of the day-to-day lives of bereaved relatives. Though methods of coping were similar to the usual strategies adopted by all bereaved relatives, advocacy work related to raising awareness about epilepsy and SUDEP was unique to this group. Guidelines on SUDEP should ideally include recommendations for trauma-informed support and assessment for depression and anxiety to the bereaved relatives as well.

Derivation and validation of a new prediction model for sudden unexpected death in epilepsy based on a longitudinal prospective population-based cohort.

OBJECTIVE: We conducted a population-based, prospective cohort study with a large sample size in Ningxia Province of the Northwest, a rural area in China, by developing a model to specifically assess risk factors of sudden unexpected death in epilepsy (SUDEP) in people with convulsive epilepsy by clinical variables. METHODS: Participants with convulsive epilepsy were recruited from January 1, 2008, to April 28, 2022, in rural Northwest China. They received regular assessments and management of epilepsy at the primary healthcare level and were followed up monthly. Information on the cause of death and relevant clinical details was obtained from death certificates or neurologist-conducted verbal autopsies. Survival analysis was employed to identify potential risk factors associated with SUDEP. RESULTS: Five variables were independently associated with SUDEP: generalized tonic-clonic seizures (GTCS) with ≥1 attack during the preceding month, GTCS with >3 attacks during the preceding year, body mass index (BMI) ≥24, age of onset ≤14 years, and duration >20 years. The area under receiver operator characteristic (ROC) curve (AUC) value (95% CI) of the model was 0.789 (0.735-0.843) in the derivation dataset and 0.830 (0.758-0.902) in the validation dataset. There was agreement between the observed and predicted probabilities of SUDEP. CONCLUSIONS: This study establishes that high GTCS frequency, early age of onset, long duration of epilepsy, and being overweight are associated with an increased risk of SUDEP in individuals with convulsive epilepsy. The study also developed and validated a personalized prediction model to accurately assess the risk of SUDEP.

Distinction between epileptic and non-epileptic arousal by heart rate change.

OBJECTIVE: We investigated the difference in heart rate (HR) change between epileptic and non-epileptic arousals in adult patients with epilepsy (PWE). METHODS: This is a case-control study conducted at the University Hospitals of Cleveland Medical Center. Inclusion criteria are (1) adult (≥18 years old) PWE who had arousal related to a focal aware or impaired awareness automatism seizure with or without focal to bilateral tonic-clonic seizure during an Epilepsy Monitoring Unit (EMU) admission between January 2009 and January 2021 or (2) adult PWE who had a non-epileptic arousal during an EMU admission between July 2020 and January 2021. Outcomes are (1) a percent change in baseline HR within 60 s after arousal and (2) the highest percent change in baseline HR within a 10-s sliding time window within 60 s after arousal. RESULTS: We included 20 non-epileptic arousals from 20 adult PWE and 29 epileptic arousals with seizures from 29 adult PWE. Within 60 s after arousal, HR increased by a median of 86.7% (interquartile range (IQR), 52.7%-121.3%) in the epileptic arousal group compared to a median of 26.1% (12.9%-43.3%) in the non-epileptic arousal group (p < 0.001). The cut-off value was 48.7%. The area under the curve (AUC), sensitivity, and specificity were 0.85, 0.79, and 0.80, respectively. More than 70.1% was only in the epileptic arousals, with 100% specificity. Within 10 s of the greatest change, HR increased by 36.5 (18.7%-48.4%) in the epileptic arousal group compared to 17.7 (10.9%-23.7%) in the non-epileptic arousal group (p < 0.001). The cut-off value was 36.5%. The AUC, sensitivity, and specificity were 0.79, 0.52, and 0.95, respectively. More than 48.1% was only in the epileptic arousals, with 100% specificity. SIGNIFICANCE: Tachycardia during epileptic arousals was significantly higher and more robust compared to tachycardia during non-epileptic arousals.