Sudden Unexpected Natural Death Research Articles

Myoglobin and C5b9 immunohistochemistry studies in heart tissue from sudden unexpected natural death cases

ABSTRACT The post-mortem diagnosis for acute myocardial infarction is one of the most challenging because acute myocardial infarction in the first 4 hours does not provide specific changes. Hence, this research evaluated the effectiveness of immunohistochemistry staining for detecting early myocardial infarction. Immunohistochemical staining for myoglobin and C5b9 were conducted on myocardial tissue from four groups with the following criteria: 1. Acute myocardial infarction cases (18 cases, positive control), 2. Severe coronary atherosclerosis cases (19 cases), 3. Natural deaths with unknown cause of death (12 cases), 4. Negative control. The results were that myoglobin staining was found positive in 17 cases of group 1 (94.4%), 13 cases of group 2 (68.4%), 3 cases of group 3 (25%), and 6 cases of group 4 (60%). C5b9 staining was found positive in 18 cases of group 1(100%), 10 cases of group 2 (52.6%), 4 cases of group 3 (33.3%), and 7 cases of group 4 (70%). The results showed that no statistical significance was found in a comparative analysis between group 4 and group 2. Hence, the results of staining for C5b9 and myoglobin conflict with the findings of prior research because the specificity in identifying acute myocardial infarction was low.

Increased Platelet-Derived Growth Factor and Cytokine Levels in the Cerebrospinal Fluid of Patients of Sudden Unexpected Death with or without Viral Infection.

To clarify the pathogenesis of sudden unexpected natural death (SUD) as well as biomarkers to differentiate the underlying diseases, by performing cytokine analysis in the acute phase of pediatric patients in whom viral infection led to SUD. An acute phase cytokine analysis of pediatric patients in whom viral infection led to SUD was performed, and the data obtained were compared with those from SUD patients not associated with viral infections. Subjects included 4 boys aged 1-16 mo who died of cardiopulmonary arrest associated with viral infections. The causative viruses were identified as enterovirus, parainfluenza virus, respiratory syncytial virus, and rotavirus. The 4 other infants/children (aged 2-12 mo) died of non-infectious episodes, i.e., 1, 2, and 1 died of drowning, falling, and a traffic accident, respectively. Cerebrospinal fluid samples (CSF) of the subjects were collected during cardiopulmonary resuscitation or within 24h of the events. The infection-induced sudden death group showed elevated CSF levels of inflammatory cytokines and chemokines. No increase was observed in interleukin-10 levels. Furthermore, in the infection-induced sudden death group, platelet-derived growth factor levels correlated with inflammatory cytokine levels. Infection-associated SUD may be differentiated from noninfectious SUD by measuring the levels of acute phase-inflammatory cytokines and chemokines at the onset of SUD.

May Measurement Month 2017: screening for hypertension in Nigeria-Sub-Saharan Africa.

Hypertension and its complications are now responsible for about a quarter of emergency medical admissions in urban hospitals in Nigeria. It is the commonest risk factor for stroke, heart failure, chronic kidney disease, and dementia. Furthermore, high blood pressure is the commonest cause of sudden unexpected natural death in the country. Regrettably, the rate of awareness, treatment, and control is abysmally low in the country and in many parts of the world. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high blood pressure (BP) and to act as a temporary solution to the lack of screening programs worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. A total of 19 904 individuals with a mean age of 40.9 years, were screened during MMM17. After multiple imputation, 6709 (36.2%) had hypertension. Of individuals not receiving anti-hypertensive medication, 4140 (25.9%) were found to have hypertension. Of individuals receiving anti-hypertensive medication, 1449 (58.8%) had uncontrolled BP. MMM17 was one of the largest BP screening campaigns undertaken in Nigeria. A significant number of the participants were identified with hypertension (but not on any treatment) and uncontrolled BP despite being treated. These results suggest that opportunistic screening can identify significant numbers with raised BP.

Functional characterization of ABCC9 variants identified in sudden unexpected natural death

BackgroundGenetic variation in ion channel genes (‘channelopathies’) are often associated with inherited arrhythmias and sudden death. Genetic testing (‘molecular autopsies’) of channelopathy genes can be used to assist in determining the likely causes of sudden unexpected death. However, different in silico approaches can yield conflicting pathogenicity predictions and assessing their impact on ion channel function can assist in this regard. Methods and resultsWe performed genetic testing of cases of sudden expected death in the New York City metropolitan area and found four rare or novel variants in ABCC9, which codes for the regulatory SUR2 subunit of KATP channels. All were missense variants, causing amino acid changes in the protein. Three of the variants (A355S, M941V, and K1379Q) were in cases of infants less than six-months old and one (H1305Y) was in an adult. The predicted pathogenicities of the variants were conflicting. We have introduced these variants into a human SUR2A cDNA, which we coexpressed with the Kir6.2 pore-forming subunit in HEK-293 cells and subjected to patch clamp and biochemical assays. Each of the four variants led to gain-of-function phenotypes. The A355S and M941V variants increased in the overall patch current. The sensitivity of the KATP channels to inhibitory ‘cytosolic’ ATP was repressed for the M941V, H1305Y and K1379Q variants. None of the variants had any effect on the unitary KATP channel current or the surface expression of KATP channels, as determined with biotinylation assays, suggesting that all of the variants led to an enhanced open state. ConclusionsAll four variants caused a gain-of-function phenotype. Given the expression of SUR2-containing KATP channels in the heart and specialized cardiac conduction, vascular smooth muscle and respiratory neurons, it is conceivable that electrical silencing of these cells may contribute to the vulnerability element, which is a component of the triple risk model of sudden explained death in infants. The gain-of-function phenotype of these ABCC9 variants should be considered when assessing their potential pathogenicity.

Sudden Natural Death in Owerri Imo State, a 10 Years (2003-2012) Retrospective Postmortem Study

Abstract: Sudden unexpected natural death (SUND) was uncommon in our environment; with the adoption of western life style and societal pressures this mode of death is becoming more common. Understanding the causes of sudden natural death is important for prevention and improving treatment outcomes. Aim: The aim of this study was to describe the demographic data, the immediate cause of death and associated risk factors in the sudden unexpected natural death (SUND) cases in Imo state. Methodology: The archived case notes, Post-mortem registers and reports in the data bases of Departments of Pathology and Medical records and Biostastics of Federal Medical Centre (FMC) Owerri were used as the sources of data for this study from January 2003 to December 2012. Full post-mortem examinations were performed by consultant pathologists in the department using laid down protocols. Results: The male to female ratio was 3.3:1 with mean age of 45.2 ± 17.0. The age range was 15 to 80 years. The peak age of incidence was in the 41-50 years age group. The leading causes of SUND were the cardiovascular system (CVS) 55.4%, followed by central nervous system (CNS) which made up 23.1%, gastrointestinal system (GIT) constituted 8.5%, the Respiratory system (4.2%), Vascular disorder (4.2%) and undetermined causes (6.4%). The associated risk factors included dietary factors 14 cases (29.8%), alcohol use 9 cases (19.15%), cigarette smoking (17.02%), Diabetes mellitus 6 cases (12.76%), family history 5 cases (10.64%), those without associated factors 3 cases (6.38%) and congenital anomalies 2 cases (4.25%). Conclusion: In Nigeria, with increased western lifestyle, changes in dietary habits and rise in socioeconomic status, cardiovascular diseases especially complications of hypertension has become the most important cause of sudden unexpected natural death in our society. This calls for immediate and effective management of hypertension through effective clinical and public health policy implementation.

Genetic testing in sudden unexpected natural death in the young: New York City Office of Chief Medical Examiner's experience and perspective.

Postmortem genetic testing is a diagnostic tool that is becoming increasingly utilized. The benefits and limitations of genetic testing in cases of sudden, unexpected death in the young (≤ 40years old) are reviewed from the perspective of the Office of Chief Medical Examiner of the City of New York, whose Molecular Genetics Laboratory, accredited by College of American Pathologists, has had 15 years of postmortem testing experience. Challenges to the interpretation and communication of testing results are highlighted, and opportunities for improving testing yield are discussed for age groups across the lifespan, from infancy to adulthood.

Functional characterization of TRPM4 variants identified in sudden unexpected natural death

BackgroundThe TRPM4 gene encodes the subunit of the Ca2+-activated nonselective cation channel, which is enriched in the specialized cardiac conduction system and Purkinje fibers. To date, several putative disease-causing variants in TRPM4 have been reported to be associated with cardiac arrhythmia and progressive conduction disease. Here, we report the functional effects of previously uncharacterized variants of uncertain significance (VUS) that we have found while performing a “genetic autopsy” in individuals who have suffered sudden unexpected death (SUD) in the New York City area. Methods and ResultsWe have identified thirteen uncommon missense VUS in TRPM4 by testing 95 targeted genes implicated in channelopathy and cardiomyopathy in 330 cases of SUD. In several cases there were co-existing VUS in one or more other genes that were tested. We selected four TRPM4 VUS (C20S, A380V, L595V and I1082S) for functional characterization, since these cases lacked detectable variants in other genes of our testing panel. Two of the cases were infants, one was a child and one an adult. RNA-seq data analysis showed that the longer TRPM4b splice variant is predominantly expressed in adult and fetal human heart. We therefore used site-directed mutagenesis to introduce these variants in a TRPM4b cDNA. HEK293 cells were transfected with the cDNAs and patch clamping was performed to assess the functional consequences of the TRPM4 mutants. The TRPM4 current was recorded in excised patches and was significantly reduced by each of the mutants. The total protein level of TRPM4-C20S was markedly decreased, whereas the A380V and L595V mutants exhibited decreased surface expression. The TRPM4-A380V current rapidly desensitized following patch excision. ConclusionsEach of the VUS tested caused a defect in TRPM4 channel function via distinctly different mechanisms, hence, it lays the foundation for further co-segregation family studies and animal studies of the TRPM4 variants.

Sudden unexpected deaths of young adults in a tertiary care hospital for a period of four years

Introduction Sudden unexpected natural death of a young adult is rare, but has a disproportionate impact on the community. This always requires a systematic forensic autopsy. At the completion of the autopsy it is expected to have the answers for all unanswered questions. However it is a challenge to the forensic pathologist since there are many sudden deaths without significant morphological anomalies. Objective : The aim of the study was to identify the causes and characteristics of sudden death among the young adults (less than 40 years of age) Study Design : Retrospective descriptive study was done based on the reports of post mortems performed on young adults who had died suddenly and unexpectedly due to natural reasons during past 4 years. The information was gathered on a pro-forma to fulfill the objectives. The data was analyzed using SPSS statistical package version 18. Results : Out of 54 autopsies analyzed, 78 % were males. 39% of the victims were of the age group of 36 to 40 years. 33% of the victims were brought to hospital before death. In 76% of the cases, a cause of death could be identified after macroscopic autopsy examination and the percentage increased to 89% after microscopy. Microscopy revealed or confirmed the cause of death in 52% of the cases. 44% were victims of sudden cardiac death. Cause of death was unascertained at the end of all the investigations in 11% of the cases. Conclusions Cause of death has a cardiac origin in majority of sudden unexpected deaths in young adults in the sample examined. Macroscopic autopsy examination could identify a cause of death in majority while abnormalities identified at microscopic examination accounted for death in nearly half of the sudden unnatural deaths in young adults. Medico-Legal Journal of Sri Lanka 2014; 2(1) : 15-21

Neuropathology Associated with Hypoxic-Ischemic Injury in Sudden Unexpected Natural Death in Neonates and Infants

Unexpected death in neonates and infants has no explanation in a larger percentage of cases than is true for adults. Sudden death in neonates/infants secondary to central nervous system (CNS) causes is relatively uncommon. Birth injury is typically but not always recognized. Even with a history of CNS injury, the death may still be unexpected. CNS pathology is fairly common at postmortem examination, but is often not causal. One of the most common critical neuropathologies is hypoxic-ischemic and may be hemorrhagic. In both the acute and chronic phases, the differentiation from nonaccidental trauma needs to be evaluated. Evaluation is best achieved in a well-fixed brain. Some pathology cannot be seen macroscopically and requires microscopic sections.

Forensic Considerations of Spontaneous Pneumothorax in Sudden Unexpected Natural Death

Spontaneous pneumothorax is an uncommon and potentially overlooked cause of natural death requiring a deviation from the routine autopsy approach for accurate diagnosis. In cases of suspected spontaneous pneumothorax, the postmortem examination should incorporate plain film radiography or computed tomography as well as special dissection techniques. Spontaneous pneumothoraces can be divided into two types: primary spontaneous pneumothorax, which occurs in patients without clinically evident lung disease, and secondary spontaneous pneumothorax, which occurs as a complication of underlying pleural or pulmonary pathology. Progression of either of these entities to tension pneumothorax is a life-threatening condition and should be considered a potential cause of death in the appropriate circumstances.

Sudden Unexpected Natural Death in the Youth; an Iranian Single Center Investigation

Background: Sudden unexpected natural death (SUND) has not been studied in Iran. Herein we investigated its main causes in our country.Methods: Records of 80 cases registered to a single referral center were investigated to determine the distribution of sex, age, and etiology of death.Results: Fifty eight (72.5%), 6 (7.5%), 6 (7.5%) and 4 (5%) of our cases have died due to various types of heart diseases, cerebral events, pulmonary emboli and gastrointestinal bleeding (GIB), respectively. Moreover, men are victims of SUND more that women (83.7% vs.16.3%, respectively).Conclusion: Policies should be planned by the governments to prevent youth mortality in societies. These attempts should especially target ischemic heart disease.

Postmortem computed tomography is an informative approach for prevention of sudden unexpected natural death in the elderly

Less than 10% of unnatural death cases have been examined by autopsy in Japan. In particular, the causes of death in the elderly have not yet been actively investigated. Here, we evaluated the possible use of postmortem computed tomography (PMCT) to investigate the causes of sudden unexpected natural death (SUND) in the elderly. Death cases confirmed within 24 hours since the onset of symptoms at the Emergency Department of Mie University Hospital were defined as sudden death cases. A total of 212 sudden death cases, including 175 SUND cases, that occurred in a 3-year period from September 2006 to August 2009 were investigated. The number of sudden death cases was highest in patients in their seventies (56 cases, 26%), followed by patients in their eighties and sixties. Sudden death occurred more in men than in women in their fifties to seventies, while it occurred more in women than in men over the age of 90. PMCT was performed in more than 80% of SUND cases regardless of age of the deceased. The causes in 26 cases (27.1%) were established by PMCT, many of which were hemorrhagic diseases. Signs of aortic aneurysm rupture were detected by PMCT in the thoracic and abdominal areas of 8 patients in their seventies and over, whereas signs were absent in the younger group. Also, more than 18% of sudden death cases in patients in their seventies and over were bathing-related sudden death (BRSD). BRSD was rarely caused by hemorrhagic diseases, suggesting that a drop in blood pressure caused by bathing is an important factor in BRSD. PMCT is a method that is relatively acceptable by bereaved families. It is useful for establishing the causes of approximately 30% of the SUND cases examined. The PMCT findings suggested that early detection and treatment of thoracic and abdominal aortic aneurysms and preventive measurements of bathing-related drop in blood pressure are important for the prevention of SUND in the elderly.

Prospective study of coroner's autopsies in Benin City, Nigeria.

A prospective study of 726 cases of coroner's autopsies carried out over a period of two years (1st January, 1996 - 31st December, 1997) was reviewed. The causes and circumstances of death are defined and classified into natural and unnatural deaths. Fifty cases (6.3%) were children while the remaining 676 cases (93.1%) were adults in a male to female ratio of 2.6 to 1. The most common indications for coroner's autopsies were sudden unnatural deaths (SUDs) accounting for 485 cases (66.8%) and also sudden unexpected natural deaths (SUNDs) (241 cases) accounting for 33.2%. In the first category, road traffic accidents accounted for 86.7% of cases with deaths involving motor vehicle drivers and their passengers (41.8%); pedestrians (37.1%); and motorcyclists and their passengers (18.6%). The commonest causes of death in all road traffic accidents were craniocerebral injuries and haemorrhagic shock. In the second category the most common causes of sudden unexpected natural death were cardiovascular diseases resulting from complications of hypertension (54.7%) occurring in apparently healthy individuals. Other causes of death were pneumonia, pulmonary tuberculosis, typhoid fever and neoplastic diseases. This study showed that in Nigeria, with an increasing acquisition of dietary and life style habits of the developed western world, there is becoming a concomitant risk of deaths from road traffic accidents and sudden unexpected natural deaths from hypertensive cardiovascular disease.

外因死の疑いで司法解剖となった内因性急死の2例

Two judicial autopsy cases of sudden unexpected natural death were reported. In both cases it was suspected that the victims had died of a traffic accident or violent injury. It became clear, however, that both the cause of death had been myocardial infarction by the forensic autopsies and that the suspects had not been criminally responsible for the death of the victims. It is expected that sudden unexpected natural death whose cause and manner are unclear at first may occur more frequently following the increase of the number of death from ischemic heart disease in the future. In these circumstances the forensic autopsy of such cases will become more important socially.

Sudden, Unexpected, Natural Death in Childhood

One thousand nine hundred and fifty four autopsies performed at British Columbia's Children's Hospital during a 7-year period were reviewed to determine the causes of sudden unexpected natural death in the age group from birth to 17 years. Of the 126 cases found, the largest group, 86 cases, was sudden infant death syndrome (SIDS). Nine deaths were the result of infection: 4 cases of H. influenza meningitis, 2 cases of meningococcemia, 2 cases of acute epiglottitis, and 1 case of necrotizing tracheobronchitis. Epilepsy, ruptured AV malformations, and brain tumors combined to make up an equally large group of 9 cases. Cardiac lesions were the third largest group, 6 cases. The three groups that posed the most difficulty in assigning a cause of death were (a) the group that were like SIDS yet had other confounding features, (b) the group in which metabolic death was suspected but not proven, and (c) death in epilepsy.

Child Abuse by Drowning

Drowning as a form of subtle fatal child abuse is difficult to distinguish from accidental immersion or from sudden unexpected natural death when the circumstances of immersion are concealed. Homicidal drownings are unwitnessed, usually occurring in the home, and the victims are young, either infants or toddlers. Accidental drownings are more likely to involve toddlers or older children in public areas such as swimming pools, drainage ditches, lakes, and rivers. This is especially true in rural areas. In cities, bathtubs remain a major site of accidental childhood drownings. Perpetrators of deliberate drownings often fit the sociopathologic profile of a child abuser. Because there is often a survival interval between immersion and death, pathologic findings consistent with postimmersion syndrome suggest the cause of death. Foreign material in the lungs, if immersion was other than in clear tap water, and injuries of the face are other positive correlating factors. A thorough investigation of the circumstances and cooperation between the investigating agency and the pathologist are essential to determine the correct manner of death in these cases.

Sudden unexpected natural death in young persons

In a series of 1920 medico-legal autopsies, 78 cases fulfilled the criteria of sudden unexpected natural death in the age group 2–30 years. In 39 (50%) of these cases a health hazardous condition was known. A large group included epileptics, alcoholics, obstetric/gynecologic conditions, and drug addicts. For prophylactic reasons the medical intervention should focus on earlier detection, if possible, of acute myocarditis, better instruction to epileptics as to thorough medication and information of parents. Physicians should be reminded about the danger of inflammatory processes in the upper respiratory tract, especially acute tracheobronchitis and acute epiglottitis.

Fatty liver in sudden childhood death. Implications for Reye's syndrome?

We studied the livers of 21 children dying a traumatic death or sudden unexpected natural death and found that fatty metamorphosis of the liver appears to be ubiquitous. Therefore, the finding of microvesicular panlobular fatty liver alone does not justify the diagnosis of Reye's syndrome. In fact, because fatty change appears to be so prevalent, previous reports that relied on fatty changes as diagnostic of Reye's syndrome cannot be validated.

Cardiovascular Abnormalities in Children: A Ten-Year Forensic Pathologic Study

In order to obtain information on types, incidence, and significance of cardiovascular abnormalities in children, a total of 104 consecutive medicolegal autopsies of children aged 8 days to 16 years during a 10-year period from May 1974 to April 1984 were studied. Extensive histological examination of the hearts was performed in 92 out of 104 cases and complemented with chemical and microbiological analyses. In the natural death group consisting of 53 children, 26 (49%) showed abnormalities: 7 (13%) malformations, 11 (21%) cardiomyopathies, 5 (9%) idiopathic subaortic hypertrophy, and 3 (7%) a heart weight only 50% of the expected weight. In the violent death ("control") group, abnormalities were found in 8 of 39 cases (21%), all of which were cardiomyopathy. Only 5 of 34 cardiovascular abnormalities (every 7th case), all complex malformations, were clinically recognized. In 14 (15%) of the total 92 examined cases the cardiovascular abnormality was the only apparent cause of death, and in 12 (13%) a contributing cause of sudden unexpected natural death, while in 3 (3%) it was related to a fatal accidental injury. In 5 (13%) of the 39 cases of violent death, cardiomyopathy was an incidental finding without any connection to the circumstances or cause of death. The causes of cardiovascular abnormalities were associated with bacterial and viral infections, respiratory disorders, phenytoin sensitivity, or were unknown. Because of the differences in diagnostic criteria employed by previous investigators, it cannot be determined whether the incidence of the cardiovascular abnormalities and sudden cardiac death in children found in this material was higher than in other studies.

SUDDEN OR UNEXPECTED NATURAL DEATH DUE TO RUPTURED INTRACRANIAL ANEURYSM: SURVEY OF 250 FORENSIC CASES

SUDDEN OR UNEXPECTED NATURAL DEATH DUE TO RUPTURED INTRACRANIAL ANEURYSM: SURVEY OF 250 FORENSIC CASES