Editorial

The necessity of a uniform definition of sudden coronary death: Witnessed death within 1 hour of the onset of acute symptoms☆

Primary brain tumors have the potential to present a substantial health hazard, ultimately resulting in unforeseen fatalities. Despite the enhanced comprehension of many diseases, the precise prediction of disease progression continues to pose a significant challenge. The objective of this study is to investigate cases of unexpected mortality resulting from primary brain tumors and analyze the variables that contribute to such occurrences.

This systematic review explores research on individuals diagnosed with primary brain tumors who experienced unexpected deaths. It uses PRISMA standards and searches PubMed, Google Scholar, and Scopus. Variables considered include age, gender, symptoms, tumor type, WHO grade, postmortem findings, time of death - time taken from first medical presentation or hospital admission to death, comorbidity, and risk factors.

This study examined 46 studies to analyze patient-level data from 76 individuals with unexpected deaths attributed to intracranial lesions, deliberately excluding colloid cysts. The cohort's age distribution showed an average age of 37 years, with no significant gender preference. Headache was the most common initial symptom. Astrocytomas, meningiomas, and glioblastoma were the most common lesions, while the frontal lobe, temporal lobe, and cerebellum were common locations. Meningiomas and astrocytomas showed faster deaths within the first hour of hospital admission.

The etiology of unforeseen fatalities resulting from cerebral tumors elucidates an intricate and varied phenomenon. Although unexpected deaths account for a very tiny proportion of total fatalities, it is probable that their actual occurrence is underestimated as a result of underreporting and misdiagnosis.

Sudden cardiac death is, by definition, an unexpected, untimely death caused by a cardiac condition in a person with known or unknown heart disease. This major international public health problem accounts for approximately 15-20% of all deaths. Typically more common in older adults with acquired heart disease, SCD also can occur in the young where the cause is more likely to be a genetically transmitted process. As these inherited disease processes can affect multiple family members, it is critical that these deaths are appropriately and thoroughly investigated. Across the United States, SCD cases in those less than 40 years of age will often fall under medical examiner/coroner jurisdiction resulting in scene investigation, review of available medical records and a complete autopsy including toxicological and histological studies. To date, there have not been consistent or uniform guidelines for cardiac examination in these cases. In addition, many medical examiner/coroner offices are understaffed and/or underfunded, both of which may hamper specialized examinations or studies (e.g., molecular testing). Use of such guidelines by pathologists in cases of SCD in decedents aged 1-39 years of age could result in life-saving medical intervention for other family members. These recommendations also may provide support for underfunded offices to argue for the significance of this specialized testing. As cardiac examinations in the setting of SCD in the young fall under ME/C jurisdiction, this consensus paper has been developed with members of the Society of Cardiovascular Pathology working with cardiovascular pathology-trained, practicing forensic pathologists.

Pathology of sudden death and clinicopathologic correlations are treated in this chapter. Definition, epidemiology, and pathogenetic mechanisms are first addressed. Sudden death is mostly cardiovascular and arrhythmic in origin, with ventricular fibrillation as the precipitating mechanism of cardiac arrest. The majority of cases present with a pathologic substrate at the level of coronary arteries, myocardium, valves, conduction system, and great arteries. However, there are cases without substrate (ion channel diseases) which require molecular investigations in search of transmissible, genetically determined disease. The chapter is mostly devoted to sudden death in the young, with particular reference to the athletes. Anatomy and pathology of the cardiac conduction system is also dealt with, including ECG correlations. AV block and ventricular preexcitation are taken into detailed consideration. Atrial fibrillation, its causes, substrates, potential complications, and treatment are also extensively treated. Guidelines and useful recommendations for postmortem study of sudden death appear at the end of the chapter.

Sudden unexpected death in epilepsy (SUDEP) has been identified as one of the most prevalent causes of mortality in epilepsy, and SUDEP has consequently become an important topic of research. The causes appear multifactorial, including epilepsy-induced cardiac arrest. Current understanding of autopsy negative sudden unexplained death (SUD) in general population and its relation to sudden arrhythmic death syndrome (SADS) could shed some light in SUDEP. Mutual attention to the findings of sudden death in cardiology and epilepsy are discussed here. We performed a narrative review on SUDEP, epilepsy and molecular/genetic autopsy in this population. A proposal of an extended terminology for SUDEP classification is discussed in light of recent issues related to molecular autopsy and genetics. The extended classification might be a step forward in research protocols and a tool for better understanding SUDEP.

En France, la mort subite cardiaque (MSC) représente environ 30 000 à 50 000 décès par an. La MSC, tous âges et sexes confondus, est due à une maladie coronaire athéroscléreuse dans plus de 80 % des cas. En revanche, chez le sujet jeune (< 35 ans), les causes de MSC sont variées : génétiques, malformatives, infectieuses, toxiques, immunologiques… Dans cette population, il est donc important d’établir précisément la cause du décès afin de prévenir d’autres MSC chez les apparentés. La détermination de la cause du décès chez le cas index doit reposer sur une approche pluridisciplinaire. Cet article examine les différents aspects des autopsies et des investigations complémentaires : histologie, toxicologie, génétique, virologie, biochimie. Six observations illustrent l’importance de cette démarche pluridisciplinaire. Il existe deux catégories d’autopsies : judiciaire et médicale. Leur point commun est la recherche de la cause du décès. En revanche, plusieurs aspects les distinguent. Une autopsie judiciaire est ordonnée par un magistrat dans le cadre d’une enquête judiciaire à la suite d’un « obstacle médico-légal » mentionné dans le certificat de décès. Au cours des autopsies, des prélèvements sont effectués et placés sous scellés, mais c’est le magistrat qui décide si des analyses complémentaires doivent être ordonnées. Le médecin légiste intervient en tant qu’auxiliaire de la justice, mais il est donc confronté à la difficulté de faire valoir son rôle en matière de santé publique, pourtant essentiel. Les autopsies médicales, pratiquées par des pathologistes, sont demandées par des médecins cliniciens. Ces autopsies doivent respecter les exigences de recherche du consentement. Toutes les analyses utiles sont effectuées, ce qui permet un diagnostic précis par une approche pluridisciplinaire. L’histologie est indispensable, complétée parfois par immunohistochimie pour préciser des infiltrats inflammatoires (CD3, CD68). Les myocardites virales sont parmi les causes les plus fréquentes de MSC chez le sujet jeune. Des analyses virologiques sont pratiquées à partir de prélèvements congelés, par biologie moléculaire. Des analyses toxicologiques et biochimiques peuvent s’avérer utiles. Le concept d’« autopsie moléculaire » souligne l’importance des analyses génétiques chez le cas index jeune. La cardiomyopathie hypertrophique et la cardiomyopathie ventriculaire droite arythmogène sont les causes génétiques les plus fréquentes chez le sujet jeune. Cette approche pluridisciplinaire est donc indispensable pour une meilleure connaissance et la prévention des MSC.

In France, the incidence of sudden cardiac deaths (SCD) is approximately 30,000–50,000 per year. In the whole population, their cause is an atherosclerotic coronary disease in more than 80 % of cases, but in the young (< 35 years old), causes are various, including genetic, infectious, toxic, congenital anomalies, immune…Therefore a multidisciplinary approach is required for a better knowledge and prevention of SCD. In this article, we examine different aspects of autopsies and complementary investigations: histopathology, toxicology, biochemistry, genetics and virology. Six cases illustrate the importance of a multidisciplinary approach. There are two categories of autopsies: medicolegal or medical. Medicolegal autopsies are requested by a judicial authority when a death is considered suspicious. These autopsies are performed by forensic doctors. Most of them are not pathologists. During the autopsies, blood and tissue samples are taken, but analyses are done only at the request of the judicial authority if the analyses are useful for the truth. Consequently, the cause of death can remain uncertain. Medical autopsies are performed by a pathologist at the request of a clinician. The family consent is required. Useful analyses are performed, which is essential for the determination of a precise cause of death. In the young, “molecular autopsy”, in addition to histology and other analyses, is essential in preventing genetic causes of SCD.

Sudden cardiac death in young adults is rarely related to ischaemic or hypertensive heart disease but has increasingly been associated with a number of inheritable conditions including cardiomyopathies, channelopathies and storage disorders. Once other potential causes of death have been excluded, a careful consideration must be given to inheritable cardiac conditions through careful macroscopic and microscopic examination of the heart and where necessary supported by investigation of the potential underlying genetic abnormality. A pragmatic approach to the examination of the heart is given together with the potential inheritable causes to be considered. When appropriate, support should be sought from a special interest cardiac pathologist through the UK Cardiac Pathology Network (UKCPN).