Medico legal investigations into sudden sniffing deaths linked with trichloroethylene

Sudden deaths attributed to sniffing trichloroethylene are caused by the abuse of this solvent which produces pleasant inebriating effects with rapid dissipation. In the event of repeated cycles of inhalation, a dangerous and uncontrolled systemic accumulation of trichloroethylene may occur, followed by central nervous system depression, coma and lethal cardiorespiratory arrest.Sometimes death occurs outside the hospital environment, without medical intervention or witnesses and without specific necroscopic signs.Medico legal investigations into sudden sniffing deaths associated with trichloroethylene demand careful analysis of the death scene and related circumstances, a detailed understanding of the deceased's medical history and background of substance abuse and an accurate evaluation of all autopsy and laboratory data, with close cooperation between the judiciary, coroners and toxicologists.     

Unnatural causes of sudden unexpected deaths initially thought to be sudden infant death syndrome

The aim of this clinicopathological study was to determine the frequency of infant deaths due to unnatural causes among cases of sudden and unexpected infant death. Nine institutes of legal medicine in Germany that took part in the German study on Sudden Infant Death Syndrome (GeSID), representing 35% of the German territory, investigated in a 3-year period (from 1998 to 2001) 339 cases of infant death that were not expected to be due to unnatural causes from the first external examination. All cases were investigated by complete, standardised, post-mortem examination including death scene investigation, autopsy, histology, toxicology and neuropathology. The frequency of unnatural deaths was 5.0% (n=17). The causes of death were head injury (n=7), suffocation (n=5), poisoning (n=2), neglect (n=2) and septicaemia due to aspiration of a foreign body (n=1). Two deaths were unsuspected accidents and 12 were due to infanticide. In 3 cases, it was not possible to differentiate between accidental death and infanticide. A complete postmortem examination including an analysis of the clinical history, death scene investigation, autopsy, histology, toxicology, and neuropathology is mandatory to differentiate sudden and unexpected deaths due to natural causes (e.g. SIDS) and cases of unnatural death.Contributors at Institutes of Legal Medicine: U. Deml, Friedrich-Alexander-University, Erlangen; A. Freislederer, University Duisburg-Essen, Essen; S. Heide, Martin-Luther-University, Halle; H.-J. Kaatsch, S. Ritz-Timme, Christian-Albrechts-University, Kiel; K.-P. Larsch, A. Fiegut, Medizinische Hochschule Hannover, Hannover; H.W. Leukel, Johann-Wolfgang-Goethe-University, Frankfurt am Main; C. Ortmann, Friedrich-Schiller-University, Jena; R. Penning, Ludwig-Maximilians-University, Munich.     

Cardiac MRI and CT features of inheritable and congenital conditions associated with sudden cardiac death

Cardiac MRI (CMR) and electrocardiogram (ECG)-gated multi-detector computed tomography (MDCT) are increasingly important tools in the identification and assessment of cardiac-related disease processes, including those associated with sudden cardiac death (SCD). While the commonest cause of SCD is coronary artery disease (CAD), in patients under 35 years inheritable cardiomyopathies such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are important aetiologies. CMR in particular offers both accurate delineation of the morphological abnormalities associated with these and other conditions and the possibility for risk stratification for development of ventricular arrhythmias with demonstration of macroscopic scar by delayed enhancement imaging with intravenous gadolinium.     

A sudden death due to cardiac conduction system injury from a blunt chest impact

We report a case of sudden death due to cardiac conduction system injury from a blunt chest impact. A 20 year old male, kicked in the precordial region, lost consciousness, and was confirmed dead on arrival at a hospital emergency care unit. According to his friends, they played a golf competition accompanied with a physical punishment. The victim, losing the game, allowed the winner to give him several kicks in the chest. Although well prepared against each kick, he fell down instantaneously after the final impact, and death was confirmed at a hospital. There was no apparent sign of injury on the body surface. At autopsy, there was no evident subcutaneous or intramuscular hemorrhages, rib or sternum fracture. Subendocardial hemorrhage in the region of the atrioventricular node and a contusion extending from the posterior wall of the left ventricle to the upper ventricular septum were observed. Histological examination revealed injury of atrioventricular node and His' bundle. Although the cardiac injury including contusion of the myocardium itself was not so extensive, it was considered that arrhythmia was induced by the cardiac conduction system failure, which was considered to be the cause of death.     

Unclassified sudden infant death associated with pulmonary intra-alveolar hemosiderosis and hemorrhage

The significance of severe pulmonary intra-alveolar hemosiderosis in sudden infant death is controversial in forensic pathology. We report a previously healthy 9-month-old female infant who died suddenly and unexpectedly after being placed and then found prone in her crib. Her gestation and delivery were uncomplicated, and she had no history of anemia, hemoptysis, chest trauma, or chronic lung disease. Autopsy revealed diffuse severe pulmonary congestion and severe multifocal intra-alvedar hemorrhage. Metabolic and toxicological screening, microbiologic cultures, and vitreous chemistry were noncontributory. A diagnosis of SIDS had been made by the medical examiner. Subsequent semiquantitative assessment of the severity of pulmonary intra-alveolar hemosiderosis prompted consideration of other disorders, including a heretofore undescribed lethal infantile variant of idiopathic pulmonary hemosiderosis, but none could be confirmed. Therefore, we assigned a study diagnosis of unclassified sudden infant death. We recommend that a diagnosis of SIDS not be made in cases with unexplained large numbers of intra-alveolar PS. We also recommend that quantitative assessment of lung sections stained for iron be undertaken in cases with numerous intra-alveolar macrophages in order to accumulate data that might allow diagnostic correlations with the circumstances of death and autopsy findings.     

Reaction patterns in selected lymphatic tissues associated with sudden infant death (SID)

In 50 cases of sudden infant death cervical, paratracheal and lung hilar lymph nodes, the thymus and the spleen were investigated by histology and immunohistochemistry (CD 20, 21, 45RO). The cases were divided into 3 groups based on autopsy findings including extensive histology: A – without pathological changes (N = 12), B – with minimal to intermediate inflammation (N = 23) and C – with severe inflammation (N = 15). In accordance with previous results the frequency of “pathological” lymph node changes, such as paracortical lymphoid hyperplasia and variegated hyperplasia of the pulp increased from group A to group C. The B-cell antigens reacted accordingly. A pronounced lymphodepletation of the thymus as a sign of a long lasting stimulation of the T-cell system was also observed increasingly from group A to C. In summary, in none of the cases results obtained were indicative of a defect of the T- or B-cell system. The results in group A seem to indicate that changes in the reaction pattern of the lymphoid tissues could be a more sensitive method of detection of early stages of inflammation than local histology. Received: 14 October 1996 / Received in revised form: 23 December 1996     

Association between sudden unexpected deaths in bathtubs and ambient temperature among elderly Japanese adults: A time-series regression study

BackgroundSudden unexpected deaths in bathtubs among elderly Japanese adults occur predominantly during the cold season. This study investigated the relationship between these deaths and bathing day temperature among elderly adults in Tokyo.MethodsData for 1408 cases of bath-related deaths from January 1 to December 31, 2015 were obtained from the Tokyo Medical Examiner’s Office. We excluded 409 cases for the following reasons: criminal death, injury-related death, suicide, intoxication, non-sudden death, not bathtub-related death, out-of-bathroom death, subject aged under 65 years, undetermined bathing date, institutional housing, and bathing not at subject’s home. Ultimately, 999 cases were analyzed. Daily mean temperature data were collected. A time-series regression study was performed to estimate the influence of sex, age, and bathing day temperature. Monthly changes in the population bathing in a bathtub were considered in the model.ResultsThe relative risk (RR) of sudden unexpected death in a bathtub was 1.381 for males (95% confidence interval [CI]: 1.218–1.564) compared to females. The RRs were 4.182 (95% CI: 3.523–4.986) and 9.382 (95% CI: 7.836–11.273) among those aged 75–84 years and ≥85 years, respectively, compared to among those aged 65–74 years. The RR increased to 1.092 (95% CI: 1.082–1.102) as the daily mean temperature decreased by 1 °C.ConclusionSudden unexpected death in a bathtub correlated with bathing day temperature among elderly Japanese adults, and extremely low temperature, male sex, and older age increased the risk of such death. Our findings provide insight into preventing sudden unexpected deaths in bathtubs.     

Serum levels of digoxin in sudden cardiac deaths

Summary Digoxin was determined in postmortem serum samples from 100 patients who died suddenly of cardiac disease. Twenty patients had digoxin levels below the therapeutic range. Twenty-one patients had normal values within the therapeutic range (1.2–2.5nmol/l). In ten cases there was probably an overdosage. Another 15 patients had markedly elevated levels. No digoxin concentration was found (below 0.5nmol/l) in 34 patients. The importance of determination of digoxin levels both by the clinician and the pathologist is stressed as well as the necessity of using a correct sampling technique at autopsy.     

Volatile lipophilic substances management in case of fatal sniffing

Death due to inhalation of aliphatic hydrocarbons such as butane and propane is a particularly serious problem worldwide, resulting in several fatal cases of sniffing these volatile substances in order to “get high”. Despite the number of cases published, there is not a unique approach to case management of fatal sniffing. In this paper we illustrate the volatile lipophilic substances management in a case of a prisoner died after sniffing a butane-propane gas mixture from prefilled camping stove gas canisters, discussing the comprehensive approach of the crime scene, the autopsy, histology and toxicology.A large set of accurate values of both butane and propane was obtained by gas chromatography–mass spectrometry analyzing the following post-mortem biological samples: peripheral blood, heart blood, vitreous humor, liver, lung, heart, brain/cerebral cortex, fat tissue, kidney, and allowed an in depth discussion about the cause of death. A key role is played by following the proper sampling approach during autopsy.     

An unusual case of sudden death in an alcohol addict

Summary The sudden and unexpected death of a 40-year-old female alcohol addict is described. At the autopsy recent rib fractures were found. The extremity of one fractured rib had caused a massive haemorrhage by erosion of a coronary artery.

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Zusammenfassung Beschrieben wird der plötzliche und unerwartete Tod einer 40-jährigen Alkoholikerin. Anläßlich der gerichtlichen Leichenöffnung, wurden frischere Rippenfrakturen festgestellt. Der Reibeeffekt der gebrochenen Rippen verletzte ein Herzkranzgefäß und führte zu einer massiven intrathorakalen Blutung, die als Todesursache gewertet werden muß.

     

Cardiac Magnetic Resonance Scar Imaging for Sudden Cardiac Death Risk Stratification in Patients with Non-Ischemic Cardiomyopathy

In patients with non-ischemic cardiomyopathy (NICM), risk stratification for sudden cardiac death (SCD) and selection of patients who would benefit from prophylactic implantable cardioverter-defibrillators remains challenging. We aim to discuss the evidence of cardiac magnetic resonance (CMR)-derived myocardial scar for the prediction of adverse cardiovascular outcomes in NICM. From the 15 studies analyzed, with a total of 2747 patients, the average prevalence of myocardial scar was 41%. In patients with myocardial scar, the risk for adverse cardiac events was more than 3-fold higher, and risk for arrhythmic events 5-fold higher, as compared to patients without scar. Based on the available observational, single center studies, CMR scar assessment may be a promising new tool for SCD risk stratification, which merits further investigation.     

Cardiac sudden death in a young cannabis user

We report a case of sudden death due to acute coronary syndrome (ACS) in a young cannabis user. A man in his late thirties died at home, and marijuana was found. The autopsy revealed severe occlusion by an atherosclerotic plaque in the left anterior descending artery. The histopathological examination revealed ischemic changes, likely caused by cannabis-induced sympathetic β-adrenergic stimulation. Both cannabinoid receptors (CB1 and CB2) were expressed in the atherosclerotic lesions. The CB2 expression was higher than CB1 expression in the atherosclerotic plaque, corresponding to macrophage infiltration. Since cannabis is regarded as a casual drug due to its lower levels of dependency, some individuals have supported legalized marijuana use. However, this case report will provide cautions on the casual use of cannabis.     

The role of eustachian valve and patent foramen ovale in sudden death

Sudden unexpected cardiac death is the leading cause of death in industrialized countries. Patent foramen ovale and eustachian valve are two of cardiac diseases and they may be associated with clinical disorders as embolism, stroke, plathypnea-orthodeoxia syndrome, carcinoid heart disease, atrial flutter and endocarditis. The literature for the roles of patent foramen ovale and eustachian valve in the causes of sudden deaths are reviewed.     

TUNEL: a useful screening method in sudden cardiac death

The primary objective of this study was to investigate if detection of apoptosis in the heart can be used to diagnose early myocardial ischaemia. The material consisted of myocardial tissue from autopsy cases: 10 cases with occlusive, thrombotic coronary artery disease and acute myocardial infarction, 10 cases of sudden cardiac death without coronary artery disease (CAD) and 8 controls without cardiovascular disease and with known causes of death. Necrotic changes in the myocardium were detected with hematoxylin-erythrosin-saffron, Mallory’s PTAH stain and with antibodies against complement 9. Apoptotic nuclei were visualised with two different kits using the terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end-labeling (TUNEL) method on histological sections. In the patients with CAD, early myocardial infarction was found in one defined area of the ventricular wall; apoptotic myocyte nuclei were observed not in the necrotic lesions, but evenly spread usually without a gradient, all over the myocardium with a mean number per high power field of 29% (range 3–56%) of the total number of myocyte nuclei. In the sudden cardiac deaths without CAD, necrosis was scarce and distributed both focally and irregularly in both the left and right ventricular walls. With few exceptions, the percentage of apoptotic myocyte nuclei exceeded 20% in all sections (mean 24%, range 0–68%). No difference was seen between patients with CAD and those without CAD (p > 0.05). With the TUNEL method, positively stained nuclei were seen very early and extensively all over the myocardium. It is not certain that they represent true apoptosis induced by ischemia, but TUNEL appears to be a useful screening method in cases where sudden cardiac death is suspected. Received: 20 March 2001 / Accepted: 26 June 2001     

Post-mortem toxicology analysis in a young sudden cardiac death cohort

Risk of sudden cardiac death (SCD) increases with age, and several studies have examined the impact of different drugs on cardiovascular function. However, few studies have integrated epidemiological drug consumption data and genetic background in the context of cardiac death. We performed a retrospective population-based study in forensic sudden death cases from a 9-year period in Catalonia. The young cohort included 924 cases 18–50 years old, 566 of which had a cardiac cause of death. Complete autopsy, toxicological, and histopathological studies were performed. Molecular autopsy using next-generation sequencing was performed in nearly 400 cardiac cases. Cases related with fatal acute intoxication were excluded. Drug consumption prevalence was similar between forensic cases of cardiac and non-cardiac origin (62.5% versus 69.5%), with the exception of alcohol, which was more prevalent in the cardiac group than in the non-cardiac group (23.3% versus 17.1%). Individuals in the toxicology-positive group were carriers of more rare genetic variants and were significantly younger than the toxicology-negative group. Psychopharmacological drugs were identified in 22.3% of cardiac cases, and molecular autopsy identified an association between antiepileptic drugs or caffeine and pathogenic or likely pathogenic variants in arrhythmogenic genes. Specific substances could therefore play an essential role as triggers of SCD in genetically predisposed young people.     

Giant coronary aneurysm associated with aortic mucoid medionecrosis

Summary A case of sudden death due to rupture of a dissecting aneurysm of the ascending aorta in a 38-year-old man is presented. The patient had a clinical history of severe hypertension. The autopsy also revealed the presence of a voluminous aneurysm of the right coronary artery and a solitary multilocular cyst of the right kidney. It is thought that a prodromal influenza-like syndrome and the renal lesion could have played a role in causing the vascular pathology.     

Genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying drug-induced arrhythmia and sudden unexplained deaths

Drug-induced arrhythmia is an adverse drug reaction that can be potentially fatal since it is mostly related to drug-induced QT prolongation, a known risk factor for Torsade de Pointes and sudden cardiac death (SCD). Several risk factors have been described in association to these drug-induced events, such as preexistent cardiac disease and genetic variation. Our objective was to study the genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying suspected drug-induced arrhythmias and sudden unexplained deaths in 32 patients. The genetic component in the pharmacodynamic pathway was studied by analysing 96 genes associated with higher risk of SCD through massive parallel sequencing. Pharmacokinetic-mediated genetic susceptibility was investigated by studying the genes encoding cytochrome P450 enzymes using medium-throughput genotyping. Pharmacodynamic analysis showed three probably pathogenic variants and 45 variants of uncertain significance in 28 patients, several of them previously described in relation to mild or late onset cardiomyopathies. These results suggest that genetic variants in cardiomyopathy genes, in addition to those related with channelopathies, could be relevant to drug-induced cardiotoxicity and contribute to the arrhythmogenic phenotype. Pharmacokinetic analysis showed three patients that could have an altered metabolism of the drugs they received involving CYP2C19 and/or CYP2D6, probably contributing to the arrhythmogenic phenotype. The study of genetic variants in both pharmacodynamic and pharmacokinetic pathways may be a useful strategy to understand the multifactorial mechanism of drug-induced events in both clinical practice and forensic field. However, it is necessary to comprehensively study and evaluate the contribution of the genetic susceptibility to drug-induced cardiotoxicity.     

Sudden death associated with myxomatous transformation of the mitral valve in an 8-year-old boy

An 8-year-old boy suffered a cardiac arrest while playing soccer. In contrast to a similar event at the age of 5 years, resuscitation was not successful. At autopsy, the cardiac findings were of a myxomatous transformation of the mitral valve with lacerations of the posterior cusp and the left vestibular endocardium and left ventricular hypertrophy. Sudden death due to arrhythmias in association with a myxomatous mitral valve is a rare event with only about 100 cases published world-wide. To our knowledge, the present case probably reports the youngest affected individual who died of this pathological condition. Received: 5 November 1997 / Received in revised form: 5 January 1998     

Massive parallel sequencing applied to the molecular autopsy in sudden cardiac death in the young

Sudden cardiac death in the young is a very traumatic event that occurs often in apparently healthy individuals without an explainable cause of death after a comprehensive medico-legal investigation. Knowledge about the pathologies with a risk of sudden death is increasingly showing a greater underlying genetic heterogeneity, which provides one of the main handicaps for molecular autopsy. On the other hand the enormous technological advances in sequencing technologies, allow us to analyse as many genes as we want at a cost increasingly reduced. The sum of these two factors (increased knowledge of genetics and available technologies) allow us to make an individualized study of the causes of sudden cardiac death in young adults, through massive sequencing of all potential genes involved in the process. We define this approach as massive genomic autopsy, and with this review we will try to explain the possible scenarios and methods available for its implementation.     

Histiocytoid cardiomyopathy and ventricular non-compaction in a case of sudden death in a female infant

A case of sudden infant death with histiocytoid cardiomyopathy and ventricular non-compaction was investigated with immunohistochemical methods. Histiocytoid cardiomyopathy is thought to be a developmental defect of the cardiomyocytes of the conduction system. In contrast to mature cardiomyocytes, the histiocytoid cells showed only weak reactions to desmin and myosin antibodies. They lacked cross-striation but reacted strongly to enolase and myoglobin antibodies. The protein Pax-7, seen only in cells undergoing differentiation, and the proliferation marker Ki-67 were not expressed in the histiocytoid cells. In areas of altered myocardium, clusters of CD4-, CD8-, and CD68-positive inflammatory cells were seen as well an abundance of mast cells. With the TUNEL method, it was found that many of the histiocytoid cells were undergoing apoptosis. Our results confirm that the histiocytoid cells are defective cardiomyocytes. The apoptotic and inflammatory changes point to a degenerative process rather than defective maturation of cardiomyocytes as has been suggested in some earlier studies. Ventricular non-compaction is a developmental defect of the subendocardial tissue with hypertrabeculation and weak development of the papillary muscles. Only one case combined with histiocytoid cardiomyopathy has been described previously. A causal connection between the two conditions cannot be established until more cases have been analyzed.