Negative autopsy and sudden cardiac death

Forensic medicine defines the unexplained sudden death as a death with a non-conclusive diagnosis after autopsy. Molecular diagnosis is being progressively incorporated in forensics, mainly due to improvement in genetics. New genetic technologies may help to identify the genetic cause of death, despite clinical interpretation of genetic data remains the current challenge. The identification of an inheritable defect responsible for arrhythmogenic syndromes could help to adopt preventive measures in family members, many of them asymptomatic but at risk of sudden death. This multidisciplinary translational research requires a specialized team.     

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.     

Macrophage activation syndrome: an autopsy case of sudden death

In a context of viral gastroenteritis, we report an unusual case of sudden death in an 8-year-old child. The only macroscopic abnormality observed in the autopsy was a diffuse mesenteric adenitis. Organ samples were taken for histopathological examination and a diffuse lymphocytic infiltration was observed. A sinusoidal histiocytic hyperplasia was found in the lymph nodes. Microscopic examination of the lungs and the lymph nodes revealed haemophagocytic lesions (lymphocytes within the cytoplasm of histiocytic macrophages). Immunohistochemical studies demonstrated that the histiocytes were CD68+ PS100- CD1A-. Following this microscopic examination macrophage activation or haemophagocytic syndrome was diagnosed. The syndrome is a distinct clinical entity characterised by fever, pancytopaenia, splenomegaly, and haemophagocytosis in the bone marrow, liver and lymph nodes. It is a clinical entity that is very difficult to diagnose due to the lack of specific clinical signs. It is generally a complication of an infectious process, an aggravation of an auto-immune disease or a complication of a neoplastic process. The physiopathology involves a disregulation of T lymphocytes and particularly T helper lymphocytes. To make this diagnosis the anatomopathological examination must be performed by an experienced practitioner. The presence of a lymphocyte infiltrate of macrophagic histiocytes in myeloid organs and especially positive CD68+ immune markers are the anatomopathological proofs of diagnosis. The autopsy examination must be carefully performed and include systematic sample harvesting for anatomopathological examination. The results of all these examinations taken together allow the diagnosis of haemophagocytic syndrome to be finally made.     

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.     

Marfan syndrome and sudden death within a family - aetiologic, molecular and diagnostic issues at autopsy

Although Marfan syndrome has a range of characteristic morphological features involving the ocular, cardiovascular and musculoskeletal systems, the phenotype is variable. In addition, mutations have been identified in the gene encoding for fibrillin-1 and also in the transforming growth factor-β receptor 2 (TGF-βR2) gene. Two cases are presented of sudden and unexpected deaths in cousins who manifested morphologic features of Marfan syndrome at autopsy. Case 1: A 36-year-old male who collapsed and was found at autopsy to have arachnodactyly, a high arched palate and lethal aortic dissection with haemopericardium. Case 2: A 34-year-old male who collapsed and was found at autopsy to have arachnodactyly, a high arched palate, pes cavus and a dysplastic mitral valve. Current aetiological theories and molecular findings are discussed. While family follow-up and counselling are advised when cases come to autopsy, given the variability in phenotype and genotype, and the difficulties that exist in attempting to determine clinical prognosis from either of these, such deaths may raise more concerns for surviving family members than providing answers.     

Pulmonary arteriovenous malformation causing sudden death due to spontaneous hemothorax

A sudden death due to hemothorax caused by spontaneous rupture of a congenital pulmonary arteriovenous malformation (AVM) is reported. A 44-year-old woman died unexpectedly with chest pain and dyspnea. The post-mortem examination revealed a massive right-sided hemothorax arising from a subpleural AVM of the upper lobe. There were multiple telangiectases in the tongue and the tonsils, as typically associated with Osler–Weber–Rendu disease (hereditary hemorrhagic telangiectasia, HHT). The post-mortem molecular genetic analysis proved the presence of a disease-causing mutation in the endoglin gene constituting a predisposition for pulmonary AVMs. According to the literature, almost half of the AVMs in the lung are seen in HHT patients. Based on the presented case and the relevant literature, the article addresses the forensic aspects of fatal hemothorax and the importance of detecting the source of bleeding.     

An autopsy case of sudden death in a patient with idiopathic scoliosis

A 38-year-old woman with idiopathic scoliosis (right convex thoracic scoliosis, 78 degrees; left convex lumbar curvature, 75 degrees) died suddenly. Forensic autopsy and histopathologic examination revealed chronic congestive oedema, numerous cavities and atrophic changes of heart. These changes, including both respiratory changes and biventricular failure caused by hypoplastic cardiac changes, were due to a deformed thoracic cage. This case illustrates that not only abnormalities of respiratory function and cor pulmonare, but also hypoplastic cardiac changes, may cause sudden death in a patient with untreated scoliosis.     

Acute epiglottitis as cause of sudden death

Summary Acute epiglottitis as a cause of sudden death in 2 adults and 2 children within a period of 2 months is reported. The cases illustrate the characteristic course of the disease and its morbid anatomy. Culture of necropsy specimens gave abundant growth ofHaemophilus influenzae in 3 cases, including 2 in which blood, CSF, lung and splenic tissue yielded heavy growth of this organism.

---

Zusammenfassung Es werden 4 plötzliche Todesfälle (2 Erwachsene, 2 Kinder) als Folge einer akuten Epiglottitis beschrieben, die innerhalb von 2 Monaten zu Sektion kamen. Die Fälle illustrieren den charakteristischen Krankheitsverlauf und die patologisch-anatomischen Befunde. Bei der bakteriologischen Untersuchung wurde bei 3 Fällen Haemophilus influenzae nachgewiesen (Kultur), davon bei 2 in Blut, Liquor, Lunge und Milz.

     

Diagnosis of sudden coronary death in the autopsy room: guidelines for forensic pathologists

The pathological techniques employed in examining cases of sudden coronary death can vary widely. Visual assessment of coronary narrowing can lead to over-estimation of the true stenosis and may result in overdiagnosis of sudden coronary death. On the other hand, inappropriate examination of the whole epicardial coronary tree while searching for acute coronary lesions may lead to underdiagnosis. The approach recommended in this paper should minimize the possibility of such errors in the diagnosis of sudden coronary death.     

致猝死的冠状动脉起源异常及其临床意义

目的 了解起自对侧冠状动脉窦并可能引发青少年运动员猝死的冠状动脉畸形在国人中的发病率,结合文献资料比较其影像学特点和临床意义.方法 应用PACS系统顺序回顾14 343例不伴有其他心脏大血管畸形的国人CT冠状动脉成像所见,选取左、右冠状动脉起自对侧冠状动脉窦及左、右单冠状动脉的病例,对冠状动脉开口位置、走行路径、非粥样硬化狭窄截面形态、径线、狭窄程度及冠状动脉近段与主动脉壁夹角进行分析统计.结果 检出冠状动脉发自对侧冠状动脉窦(包括单冠状动脉)74例,其近段走行于主、肺动脉之间者59例.右冠状动脉起自左冠状动脉窦且走行于主、肺动脉之间55例,左冠状动脉起自右冠状动脉窦且走行于主、肺动脉间2例,左、右单冠状动脉且走行于大动脉间者各1例.国人此类冠状动脉近段走行于两大动脉之间的起源异常发病率为4.1‰(59/14 343).右冠状动脉起自左冠状动脉窦,起始段常伴非粥样硬化性狭窄,狭窄面积≥50%者29例(52.7%),≥70%者3例(5.4%).近段走行于主、肺动脉之间的右冠状动脉起自左窦是左冠状动脉起自右窦的18.7倍(56/3).结论 CT冠状动脉成像是诊断冠状动脉起源异常的最佳影像学手段.国人中该畸形的解剖类型分布有其特点,这一特点对引发我国青少年运动性猝死的影响值得探讨.     

Pulmonary vascular occlusive disease presenting as sudden death

We report a case of pulmonary vascular occlusive disease (also termed pulmonary veno occlusive disease) which caused the sudden death of an eleven-year-old girl. The post-mortem findings are described and the current theories of aetiology and pathogenesis of this unusual condition are reviewed. The clinical picture is characterized by pulmonary hypertension with marked increase of pulmonary arterial pressure but often normal or only slightly elevated wedge pressure. The pulmonary vasculature, especially the veins, show progressive fibrotic occlusion. The aetiology is unknown but an infective cause is considered most likely. Definitive diagnosis usually depends on an open lung biopsy or, more commonly, autopsy examination.     

Genetic analysis of sudden cardiac death victims: a survey of current forensic autopsy practices

Autopsy-negative sudden cardiac deaths (SCD) seen in forensic practice are most often thought to be the result of sudden arrhythmic death syndrome. Postmortem genetic analysis is recommended in such cases, but is currently performed in only a few academic centers. In order to determine actual current practice, an on-line questionnaire was sent by e-mail to members of various forensic medical associations. The questions addressed routine procedures employed in cases of sudden cardiac death (autopsy ordering, macroscopic and microscopic cardiac examination, conduction tissue examination, immunohistochemistry and electron microscopy, biochemical markers, sampling and storage of material for genetic analyses, toxicological analyses, and molecular autopsy). Some questions concerned the legal and ethical aspects of genetic analyses in postmortem examinations, as well as any existing multidisciplinary collaborations in SCD cases. There were 97 respondents, mostly from European countries. Genetic testing in cases of sudden cardiac death is rarely practiced in routine forensic investigation. Approximately 60% of respondents reported not having the means to perform genetic postmortem testing and 40% do not collect adequate material to perform these investigations at a later date, despite working at university hospitals. The survey demonstrated that many of the problems involved in the adequate investigation of SCD cases are often financial in origin, due to the fact that activities in forensic medicine are often paid by and dependent on the judicial authorities. Problems also exist concerning the contact with family members and/or the family doctor, as well as the often-nonexistent collaboration with others clinicians with special expertise beneficial in the investigation of SCD cases, such as cardiologists and geneticists. This study highlights the importance in establishing guidelines for molecular autopsies in forensic medicine.     

Cardiac arrhythmias and sudden death in infancy: implication for the medicolegal investigation

Genetically transmitted diseases are an important cause of juvenile sudden cardiac death (SCD). In a considerable proportion of individuals in which a medicolegal investigation is performed, structural heart disease is absent, and the medical examiner fails to discover an adequate cause of death. In such cases, an inherited arrhythmogenic disease should be considered, which manifests with life-threatening ventricular tachycardia or SCD. Molecular diagnosis is progressively becoming an important tool for these questions. Therefore, postmortem genetic testing (“molecular autopsy”) should be considered as a part of the comprehensive medicolegal investigation in SCD cases without apparent structural heart disease. It will have implications not only for the deceased individual but also for living family members in preventing (further) cardiac events by expert counseling, appropriate lifestyle adjustment, and adequate treatment, if available.     

An autopsy case of sudden death in a boy with primary pulmonary hypertension: a case report

We report a rare autopsy case of sudden death due to primary pulmonary hypertension. A seven-year-old boy, who had been diagnosed with primary pulmonary hypertension at the age of four years, died suddenly. Forensic autopsy and histopathologic examination revealed extensive obstruction of small muscular pulmonary arteries by plexiform lesions and concentric intimal thickenings, compatible with primary pulmonary hypertension. We concluded that plexiform lesions of pulmonary arteries produced right ventricular hypertrophy and dilatation, decreased the preload of the left ventricle and subsequently led to biventricular failure. This autopsy and histopathologic examination suggested a possible pathophysiologic mechanism of sudden death due to primary pulmonary hypertension in a child.     

Post-mortem computed tomography in sudden death by asthma

Ground glass attenuation (GGA) of the lungs is a common finding of post-mortem computed tomography (PMCT) that is associated with pulmonary congestion and edema due to cardiac failure during the agonal period, or due to post-mortem hypostasis. However, hypo-attenuation of the lung is an atypical finding of PMCT, and is usually a consequence of hypovolemic states before death or postmortem body posture after death. Previous studies have shown a few differential diagnoses, such as hypothermia, massive hemorrhage, asphyxiation by hanging, and dehydration, for hypo-attenuation of the lung. This report presents the case of a woman who died suddenly because of an asthma attack. Our PMCT analysis demonstrated hypoattenuation of the lung in this case. We suggest fatal asthma as a differential diagnosis for the appearance of hypo-attenuation of lungs on PMCT.