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Sudden unexpected death in epilepsy (SUDEP) in New Zealand; a retrospective review.
Brennan, M, Scott, S, Bergin, P
The New Zealand medical journal. 2020;(1508):65-71
Abstract
AIM: Sudden unexpected death in epilepsy (SUDEP) is well recognised and widely reported but remains poorly understood. SUDEP in young adults is 27 times more common than sudden death in control populations. The incidence of SUDEP in New Zealand is not known but up to 40 people with epilepsy may die from SUDEP every year. A review of coroner's reports of SUDEP was undertaken to learn more about SUDEP in New Zealand. METHOD Coroner's reports of all cases of possible SUDEP in New Zealand from 2007-2016 (n=190) were obtained and post-mortem and toxicology results were reviewed. Cases were categorised using published criteria. RESULTS We obtained reports of 190 cases from the coroner's office. Of these 190 cases, we determined that 123 were definite SUDEP, 40 were definite SUDEP plus, three were probable SUDEP, seven were possible SUDEP and 17 were probably not SUDEP. The number of cases per year varied from 11-26 (2013). Cases were aged 1.5-67 years, with 63% aged 15-45 (mean 37 years). Sixty-one percent were male. Eighty-seven percent of the deaths occurred at home, with 74% found dead in their bed or bedroom. The majority were not employed, with only 33% working or retired at the time of death; 15% were children or students. Information regarding work status was not available for 11%. Toxicology results were available for 155 cases; antiepileptic drug (AED) use was detected in 67% of these cases, with a single AED detected in 44%, two AEDs in 21%, and three AEDs in 3% of samples taken at autopsy. Approximately half who took an AED were taking either sodium valproate or carbamazepine. CONCLUSION This study suggests that people with epilepsy who die from SUDEP in New Zealand are young and are often compliant with their medication. We plan to establish a nationwide SUDEP registry using the EpiNet database to determine the incidence of SUDEP in New Zealand, and to track changes in SUDEP rates. We are also planning to take part in an international case-control study of SUDEP in the hope that we might learn more about risk factors that predispose people with epilepsy to SUDEP, and factors that might reduce the risk.
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Sudden unexpected death in Parkinson's disease: why is drinking water important?
Menezes-Rodrigues, FS, Scorza, CS, Fiorini, AC, Caricati-Neto, A, Scorza, CA, Finsterer, J, Scorza, FA
Neurodegenerative disease management. 2019;(4):241-246
Abstract
Parkinson's disease (PD) is one of the most common age-related neurodegenerative disorders. Several studies over the last few years have shown that PD is accompanied by high rates of premature death compared with healthy controls. Death in PD patients is usually caused by determinant factors such as pneumonia, and cerebrovascular and cardiovascular diseases. During recent years it has emerged that dehydration may also contribute to mortality in PD. Interestingly, it has been documented that a substantial proportion of patients with PD die suddenly (known as sudden and unexpected death in PD). In this article, we focus on the magnitude of the problem of sudden and unexpected death in PD, with special reference to the daily water consumption of PD patients.
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A sudden death risk score specifically for hypertension: based on 25 648 individual patient data from six randomized controlled trials.
Le, HH, Subtil, F, Cerou, M, Marchant, I, Al-Gobari, M, Fall, M, Mimouni, Y, Kassaï, B, Lindholm, L, Thijs, L, et al
Journal of hypertension. 2017;(11):2178-2184
Abstract
OBJECTIVE To construct a sudden death risk score specifically for hypertension (HYSUD) patients with or without cardiovascular history. METHODS Data were collected from six randomized controlled trials of antihypertensive treatments with 8044 women and 17 604 men differing in age ranges and blood pressure eligibility criteria. In total, 345 sudden deaths (1.35%) occurred during a mean follow-up of 5.16 years. Risk factors of sudden death were examined using a multivariable Cox proportional hazards model adjusted on trials. The model was transformed to an integer system, with points added for each factor according to its association with sudden death risk. RESULTS Antihypertensive treatment was not associated with a reduction of the sudden death risk and had no interaction with other factors, allowing model development on both treatment and placebo groups. A risk score of sudden death in 5 years was built with seven significant risk factors: age, sex, SBP, serum total cholesterol, cigarette smoking, diabetes, and history of myocardial infarction. In terms of discrimination performance, HYSUD model was adequate with areas under the receiver operating characteristic curve of 77.74% (confidence interval 95%, 74.13-81.35) for the derivation set, of 77.46% (74.09-80.83) for the validation set, and of 79.17% (75.94-82.40) for the whole population. CONCLUSION Our work provides a simple risk-scoring system for sudden death prediction in hypertension, using individual data from six randomized controlled trials of antihypertensive treatments. HYSUD score could help assessing a hypertensive individual's risk of sudden death and optimizing preventive therapeutic strategies for these patients.
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The Interplay Between Diabetes and Pancreatitis: Two Case Reports of Sudden, Natural Deaths and a Review of the Literature.
Butler, DC, Emanuel, AJ, Self, SE, Batalis, NI
Journal of forensic sciences. 2017;(2):519-524
Abstract
Diabetes mellitus (DM) is a common disease involving insulin resistance or deficit that, when left unchecked, may cause severe hyperglycemia and subsequent end-organ damage. Acute pancreatitis (AP) is inflammation of the pancreas that can lead to significant morbidity and mortality. AP and DM both account for a significant amount of sudden deaths, and rarely both disease processes may be present in the same decedent, causing some difficulty in wording the cause of death statement. Although much research has been directed at studying the causes and risk factors for AP and DM, there is a complex interplay between these diseases that is not fully understood. This study presents two autopsy cases of sudden, natural deaths that illustrate this interplay, along with a review of the literature. An algorithm for differentiating AP and DM is then discussed in the context of the presented cases as a proposed aid for forensic pathologists in the certification of such deaths.
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Sudden death due to aortic pathology.
Papagiannis, J
Cardiology in the young. 2017;(S1):S36-S42
Abstract
Sudden death from aortic dissection of an ascending aortic aneurysm is an uncommon but important finding in all series of sudden death in young, apparently healthy athletes. Individuals at risk include those having any of a variety of conditions in which structural weakness of the ascending aorta predisposes to pathological dilation under prolonged periods of increased wall stress. These conditions include Marfan syndrome, Loeys-Dietz syndrome, bicuspid aortic valve, and the vascular form of Ehlers-Danlos syndrome. Diagnostic criteria, surveillance strategies, medical management, and surgical indications are discussed. Finally, the current recommendations for sports participation are provided.
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[The Brugada Syndrome as a Cause of Sudden Death. Diagnostics and Clinical Manifestations in Children].
Miklashevich, IM, Shkolnikova, MA
Kardiologiia. 2016;(10):63-71
Abstract
The Brugada syndrome is a hereditary potentially arrhythmogenic disease related to the category of channelopathies. It is manifested as syncopal states and sudden death in young people in the absence of structural cardiac disease. The basis of the disease is genetically determined abnormality of function of ionic channels of cardiomyocytes (sodium, potassium, calcium) phenotypically manifesting as sustained or transitory segment-ST elevation and high risk of polymorphic ventricular tachycardia, fibrillation, and sudden death. The only proven method of prevention of fatal arrhythmia and sudden death is cardioverter defibrillator implantation.
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The biophysical characterization of the first SCN5A mutation R1512W identified in Chinese sudden unexplained nocturnal death syndrome.
Zheng, J, Zhou, F, Su, T, Huang, L, Wu, Y, Yin, K, Wu, Q, Tang, S, Makielski, JC, Cheng, J
Medicine. 2016;(23):e3836
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Abstract
Increasing evidence observed in clinical phenotypes show that abrupt breathing disorders during sleep may play an important role in the pathogenesis of sudden unexplained nocturnal death syndrome (SUNDS). The reported Brugada syndrome causing mutation R1512W in cardiac sodium channel α subunit encoded gene SCN5A, without obvious loss of function of cardiac sodium channel in previous in vitro study, was identified as the first genetic cause of Chinese SUNDS by us. The R1512W carrier was a 38-year-old male SUNDS victim who died suddenly after tachypnea in nocturnal sleep without any structural heart disease. To test our hypothesis that slight acidosis conditions may contribute to the significant loss of function of mutant cardiac sodium channels underlying SUNDS, the biophysical characterization of SCN5A mutation R1512W was performed under both extracellular and intracellular slight acidosis at pH 7.0. The cDNA of R1512W was created using site-directed mutagenesis methods in the pcDNA3 plasmid vector. The wild type (WT) or mutant cardiac sodium channel R1512W was transiently transfected into HEK293 cells. Macroscopic voltage-gated sodium current (INa) was measured 24 hours after transfection with the whole-cell patch clamp method at room temperature in the HEK293 cells. Under the baseline conditions at pH 7.4, R1512W (-175 ± 15 pA/pF) showed about 30% of reduction in peak INa compared to WT (-254 ± 23 pA/pF, P < 0.05). Under the acidosis condition at pH 7.0, R1512W (-130 ± 17 pA/pF) significantly decreased the peak INa by nearly 50% compared to WT (-243 ± 23 pA/pF, P < 0.005). Compared to baseline condition at pH 7.4, the acidosis at pH 7.0 did not affect the peak INa in WT (P > 0.05) but decreased peak INa in R1512W (P < 0.05). This initial functional study for SCN5A mutation in the Chinese SUNDS victim revealed that the acidosis aggravated the loss of function of mutant channel R1512W and suggested that nocturnal sleep disorders-associated slight acidosis may trigger the lethal arrhythmia underlying the sudden death of SUNDS cases in the setting of genetic defect.
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Serum Magnesium and Sudden Death in European Hemodialysis Patients.
de Roij van Zuijdewijn, CL, Grooteman, MP, Bots, ML, Blankestijn, PJ, Steppan, S, Büchel, J, Groenwold, RH, Brandenburg, V, van den Dorpel, MA, Ter Wee, PM, et al
PloS one. 2015;(11):e0143104
Abstract
Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77-94), the HR for cardiovascular mortality 0.73 (95% CI 0.62-0.85) and for sudden death 0.76 (95% CI 0.62-0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time.
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Is sudden unexplained nocturnal death syndrome in Southern China a cardiac sodium channel dysfunction disorder?
Liu, C, Tester, DJ, Hou, Y, Wang, W, Lv, G, Ackerman, MJ, Makielski, JC, Cheng, J
Forensic science international. 2014;:38-45
Abstract
Sudden unexplained nocturnal death syndrome (SUNDS) remains an enigma to both forensic pathologists and physicians. Previous epidemiological, clinical, and pilot genetic studies have implicated that SUNDS is most likely a disease allelic to Brugada syndrome (BrS). We have performed postmortem genetic testing to address the spectrum and role of genetic abnormalities in the SCN5A-encoded cardiac sodium channel and its several associated proteins in SUNDS victims from Southern China. Genomic DNA extracted from the blood samples of 123 medico-legal autopsy-negative SUNDS cases and 104 sex-, age- and ethnic-matched controls from Southern China underwent comprehensive amino acid coding region mutational analysis for the BrS associated genes SCN5A, SCN1B, SCN2B, SCN3B, SCN4B, MOG1, and GPD1-L using PCR and direct sequencing. We identified a total of 7 unique (4 novel) putative pathogenic mutations (all in SCN5A; V95I, R121Q [2 cases], R367H, R513H, D870H, V1764D, and S1937F) in 8/123 (6.5%) SUNDS cases. Three SCN5A mutations (V95I, R121Q, and R367H) have been previously implicated in BrS. An additional 8 cases hosted rare variants of uncertain clinical significance (SCN5A: V1098L, V1202M, R1512W; SCN1B: V138I [3 cases], T189M [2 cases]; SCN3B: A195T). There were no non-synonymous mutations found in SCN2B, SCN4B, MOG1, or GPD1-L. This first comprehensive genotyping for SCN5A and related genes in the Chinese Han population with SUNDS discovered 13 mutations, 4 of them novel, in 16 cases, which suggests cardiac sodium channel dysfunction might account for the pathogenesis of 7-13% of SUNDS in Southern China.
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Sudden unexpected death in Dravet syndrome: respiratory and other physiological dysfunctions.
Kalume, F
Respiratory physiology & neurobiology. 2013;(2):324-8
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Abstract
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.