Sudden Unexpected Deaths In Epilepsy Research Articles

Comparison of patient non-specific seizure detection using multi-modal signals

Epilepsy is the neurological disorder affecting around 50 million people worldwide. It is characterized by recurrent and unpredictable seizures. Correctly counting seizure occurrences is crucial for diagnosis and treatment of epilepsy, which will lower the risk of SUDEP (sudden unexpected deaths in epilepsy). Many previous researches on patient-specific seizure detection have obtained a good performance but with limited practicability in clinical setting. On the other hand, patient non-specific detection is clinically practicable but with limited performance. This study aims to improve the performance of patient non-specific seizure detection by comparing performances among one modality based models and multi-modal based model. The study was based on clinical data from the open source Siena Scalp EEG Database, which consist of simultaneous EEG (Electroenchephalography) and ECG (electrocardiography) recording from 14 patients with focal epilepsy. The seizures were annotated by an epilepsy expert after a careful review of the clinical and EEG data of each patient. First, relevant signal pre-processing were performed, followed by features extraction. Then, machine learning approach based on random forest was employed for seizure detection with leave-one-patient-out cross validation scheme. EEG detector and ECG detector were separately trained with each signal. Multi-modal detector was based on combining EEG detector and ECG detector by the late integration approach with the Boolean operation “OR” strategy. The performances were compared among those three detectors and with the state of the art. The result has shown that the multi-modal detector achieved a sensitivity of 87.62% and outperformed the ECG detector (41.55%), the EEG detector (81.43%), and the state-of-the-art non-specific detectors. Notably, the ECG detector detected some seizures which EEG detector failed to detect. This indicated that the ECG signal was beneficial for increasing sensitivity. However, due to the “OR” fusion strategy, the multi-modal detector also inherited the false detections resulted from either EEG detector or ECG detector. The findings of the study demonstrate the potential of improving performance of patient non-specific seizure detection by multimodal data. It shows that the proposed method should be further validated on large database and further development should focus on lowering false detections before clinical application.

Medication adherence, anxiety and depression, and safety of epileptic patients following receiving information about sudden unexpected deaths in epilepsy: A quasi-experimental study with before/after design

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

Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link.

Sleep disturbances, such as insomnia, obstructive sleep apnea, and daytime sleepiness, are common in people diagnosed with epilepsy. These disturbances can be attributed to nocturnal seizures, psychosocial factors, and/or the use of anti-epileptic drugs with sleep-modifying side effects. Epilepsy patients with poor sleep quality have intensified seizure frequency and disease progression compared to their well-rested counterparts. A better understanding of the complex relationship between sleep and epilepsy is needed, since approximately 20% of seizures and more than 90% of sudden unexpected deaths in epilepsy occur during sleep. Emerging studies suggest that neuroinflammation, (e.g., the CNS immune response characterized by the change in expression of inflammatory mediators and glial activation) may be a potential link between sleep deprivation and seizures. Here, we review the mechanisms by which sleep deprivation induces neuroinflammation and propose that neuroinflammation synergizes with seizure activity to worsen neurodegeneration in the epileptic brain. Additionally, we highlight the relevance of sleep interventions, often overlooked by physicians, to manage seizures, prevent epilepsy-related mortality, and improve quality of life.

CARDIOVASCULAR RISK PROFILE IN YOUNG PATIENTS WITH EPILEPSY

Abstract Objective: The risk of premature deaths in patients with epilepsy (approx. 50 mln. patients worldwide) is about 2–3 times higher as compared to general population. This phenomenon is mainly explained by cardiovascular causes as well as sudden unexpected deaths in epilepsy (SUDEP). Epilepsy is associated with sympathetic overdrive and renin-angiotensin-system abnormalities all of which may be implicated in organ damage (both directly and indirectly via high blood pressure; BP). In our study, we aimed at the evaluation of several cardiovascular risk factors and organ damage in patients with epilepsy; its’ relation to disease control and comorbid hypertension. Design and method: A total of 48 patients and matched controls were included in the study. Anthropometry, biochemical assessment, office and ambulatory blood pressure, structural and/ or functional vascular changes were recorded. One-way ANOVA and ANCOVA were employed (mean ± SE). Results: Patients were comparable in terms of age and BMI. Hypertensives were aware of high BP in 50% of cases. Study subgroups were comparable in terms of heart rate, serum uric acid, triglicerides, HDL, glucose, serum creatinine and eGFR, serum potassium (P = NS for all comparisons). Total cholesterol was the lowest in well-controlled epileptic patients which was followed by refractory disease and epilepsy with comorbid hypertension (167.6 ± 6.7 vs. 196.9 ± 7.4 vs. 223.5 ± 8.9; respectively). Patients with refractory epilepsy had comparable serum LDL and PWV to hypertensive well-controlled epileptics; both contrasted with values recorded in patients with well-controlled epilepsy who were free of hypertension (LDL: 121.7 ± 6.8 vs. 140.9 ± 8.2 vs. 99.2 ± 6.1; respectively, and PWV: 6.4 ± 0.24 vs. 6.8 ± 0.30 vs. 5.5 ± 0.22; respectively). Reported differences were valid after adjustment for age and BMI. Conclusions: Except for BP values, patients with refractory epilepsy who are free of hypertension have similar CV risk profile to patients with high BP. These findings along with underdiagnosed hypertension may explain higher CV mortality and morbidity documented in epilepsy.

Possible role of SCN4A skeletal muscle mutation in apnea during seizure.

SCN4A gene mutations cause a number of neuromuscular phenotypes including myotonia. A subset of infants with myotonia‐causing mutations experience severe life‐threatening episodic laryngospasm with apnea. We have recently identified similar SCN4A mutations in association with sudden infant death syndrome. Laryngospasm has also been proposed as a contributory mechanism to some cases of sudden unexpected death in epilepsy (SUDEP). We report an infant with EEG‐confirmed seizures and recurrent apneas. Whole‐exome sequencing identified a known pathogenic mutation in the SCN4A gene that has been reported in several unrelated families with myotonic disorder. We propose that the SCN4A mutation contributed to the apneas in our case, irrespective of the underlying cause of the epilepsy. We suggest this supports the notion that laryngospasm may contribute to some cases of SUDEP, and implicates a possible shared mechanism between a proportion of sudden infant deaths and sudden unexpected deaths in epilepsy.

Under-reporting of sudden unexpected death in epilepsy.

The identification and characterization of sudden unexpected deaths in epilepsy (SUDEP) may be improved, helping to optimize prevention and intervention. We set out to assess the frequency and demographic and clinical characteristics of SUDEP cases in a sudden death cohort. All out-of-hospital deaths were investigated from March 1, 2013 to February 28, 2015 in Wake County, NC, attended by the Emergency Medical Services. Cases were screened and adjudicated by three physicians to identify sudden death cases from any cause among free-living adults, aged 18-64. In total, 399 sudden death victims were identified during this two-year period. Seizure history, demographic and clinical characteristics, and healthcare utilization patterns were assessed from death records, emergency response scene reports, and medical records. Sudden death cases with a history of seizures were summarized by an experienced chart abstractor (SC) and adjudicated by an experienced neurologist (OD). We then compared demographic and clinical characteristics and healthcare utilization patterns of neurologist-identified SUDEP cases to other sudden death victims in our population-based registry of sudden death from any cause. SUDEP accounted for 5.3% of sudden deaths. However, seizures or complications of seizures were only considered the primary cause of death on death certificates in 1.5% of sudden deaths. SUDEP cases were more likely to have a history of alcohol abuse. Mental health disorders and a low level of medication compliance and healthcare utilization were common among SUDEP victims. SUDEP accounts for approximately 5.3% of sudden deaths from any cause in individuals aged between 18 and 64. Death certificates underestimate the burden of sudden death in epilepsy, attributing only 1.5% of sudden deaths to seizures or complications of seizures. Accurate documentation of epileptic disorders on death certificates is essential for the surveillance of SUDEP. Further, interventions that promote better use of medical services and patient engagement with healthy living practices may reduce sudden deaths in epilepsy.

Underestimation of sudden deaths among patients with seizures and epilepsy.

To determine the definite and potential frequency of seizures and epilepsy as a cause of death (COD) and how often this goes unrecognized. Prospective determination of seizures or epilepsy and final COD for individuals aged 18-90 years with out-of-hospital sudden cardiac deaths (SCDs) from the population-based San Francisco POST SCD Study. We compared prospective seizure or epilepsy diagnosis and final COD as adjudicated by a multidisciplinary committee (pathologists, electrophysiologists, and a vascular neurologist) vs retrospective adjudication by 2 epileptologists with expertise in seizure-related mortality. Of 541 SCDs identified during the 37-month study period (mean age 62.8 years, 69% men), 525 (97%) were autopsied; 39/525 (7.4%) had seizures or epilepsy (mean age: 58 years, range: 27-92; 67% men), comprising 17% of 231 nonarrhythmic sudden deaths. The multidisciplinary team identified 15 cases of epilepsy, 6 sudden unexpected deaths in epilepsy (SUDEPs), and no deaths related to acute symptomatic seizures. The epileptologists identified 25 cases of epilepsy and 8 definite SUDEPs, 10 possible SUDEPs, and 5 potential cases of acute symptomatic seizures as a COD. Among the 25 patients identified with epilepsy by the epileptologists, they found definite or possible SUDEP in 72% (18/25) vs 24% (6/25) by the multidisciplinary group (6/15 cases they identified with epilepsy). The epileptologists identified acute symptomatic seizures as a potential COD in 5/14 patients with alcohol-related seizures. Epilepsy is underdiagnosed among decedents. Among patients with seizures and epilepsy who die suddenly, seizures and SUDEP often go unrecognized as a potential or definite COD.

Sudden unexpected death in epilepsy.

People with epilepsy have increased risk of premature death, and their life expectancy may reduce by 2-10 yr. Population- and hospital-based studies have shown that the excess mortality in epilepsy is not entirely explained by deaths directly attributable to epilepsy such as accidents and drowning during a seizure. It is also significantly contributed by deaths from other causes such as cardiac deaths, deaths due to malignancies and other causes. It had recently been recognized that sudden unexpected deaths in epilepsy (SUDEP) contributed to a small yet important proportion of mortality in epilepsy. SUDEPs are deaths (witnessed or unwitnessed) unrelated to trauma, drowning or status epilepticus and not attributable to any specific medical conditions. Several factors related to epilepsy and drug therapy have been found to be associated with higher risk of SUDEP.

B.06: Two definite sudden unexpected deaths in epilepsy in a family with a DEPDC5 mutation

Background:DEPDC5 gene, mapped to 22q12.2-q12.3, has been associated with a variety of familial epilepsies, including FFEVF, autosomal dominant nocturnal frontal lobe epilepsy, and familial TLE. Notably, DEPDC5 has never been linked to increased risk of sudden unexpected death in epilepsy (SUDEP). Methods: Cases review. Results: We studied a three-generation, non-consanguineous, French-Canadian family with nine clinically affected individuals. The index case is a 39-year-old man who started having seizures (as 2rily GTCS) at the age of 13 years. EEGs showed interictal discharges over the right anterior-temporal region. Brain MRI was unremarkable. Two individuals in this family suffered definite autopsy-confirmed SUDEP, at the ages of 58 and 50 years, respectively. Overall, seizure-history in this family can be summarized by an onset before reaching adulthood followed by subsequent progressive decrease in seizure frequency. Seizures were predominantly nocturnal 2rily GTC. Genetic analysis revealed a pathogenic heterozygous variant in the DEDPC5 gene (p.Gln216, c.646C&gt;T), which results in a premature stop codon, in all affected family members plus on heatlhy relative. Importantly, all the subjects were cognitively intact, and there was no history of cardiac symptomatology/cardiovascular risk factor. Conclusions: The finding in this family suggests that DEPDC5 mutations may be a risk factor for SUDEP.

Two Definite Sudden Unexpected Deaths in Epilepsy in a Family with a DEPDC5 Mutation (P6.365)

Two Definite Sudden Unexpected Deaths in Epilepsy in a Family with a DEPDC5 Mutation (P6.365)

Deaths in children with epilepsies: A UK-wide study

PurposeThis UK-wide review of deaths in children with epilepsies was undertaken to ascertain any demographic, clinical, organisational, or management factors associated with the deaths, and to determine the extent to which any of these may have deviated from nationally agreed best practice. MethodPaediatricians across the UK were asked to notify any deaths in children with epilepsies over a 10-month period. Hospital and community case notes were reviewed by pairs of case assessors using a structured assessment tool combining holistic and criterion-based approaches. ResultsOf 46 deaths notified, case notes were obtained on 33. The majority of children had associated developmental impairments. The majority (24), died of an associated co-morbidity rather than of epilepsy. Seven died of convulsive status epilepticus and seven as sudden unexpected deaths in epilepsy. Twenty four percent of deaths were judged to be preventable; potentially modifiable factors included fragmentation of care, support for families, and recognition of and response to acute illness in the child, including the appropriate management of prolonged seizures. ConclusionsAlthough this audit has demonstrated significant improvements in quality of care when compared with the last national audit of epilepsy deaths in 2002, further improvement is still required.

Sudden unexpected death in Dravet syndrome: Respiratory and other physiological dysfunctions

Sudden unexpected deaths in epilepsy (SUDEP) occur at an alarming higher rate in patients with Dravet syndrome (DS) than in patients with most other forms of epilepsy. DS is a severe infantile-onset epilepsy caused by a heterozygote loss-of-function mutation in SCN1A, which encodes the voltage-gated-sodium channel NaV 1.1. The mechanisms leading to SUDEP in DS or other epilepsies are not completely understood. Understanding the pathophysiological mechanisms of SUDEP, common to most epilepsies and those specific to DS, may pave the way toward the discovery of effective preventive strategies for these epilepsy-related tragic events.

Sudden unexpected death in epilepsy

Sudden unexpected death in epilepsy

Circumstances of death in sudden death in epilepsy: interviews of bereaved relatives

OBJECTIVESTo study the circumstances of death in sudden death in epilepsy.METHODSSelf referred bereaved relatives of patients with epilepsy who had died suddenly were interviewed with information obtained substantiated through other...

Sudden unexpected deaths in epilepsy—where are we now?

In people with uncontrolled chronic epilepsy there is an excess mortality directly attributable to the epilepsy itself. This is largely due to accidental and non-accidental deaths occurring during or immediately after seizures. Most sudden unexpected deaths in epilepsy fall within the latter category. To acknowledge rather than conceal these deaths is essential before prevention strategies can be addressed.