Sudden death resulting from lesions of the cardiac conduction system

Sudden unexpected deaths in young persons with noncontributory histories, autopsy results, and drug screen results are a common problem in forensic pathology. As part of the evaluation of such cases, the cardiac conduction system (CCS) should be studied. To determine the type and incidence of lethal CCS lesions, the authors reviewed their files of sudden unexpected cardiac deaths with particular attention to cases with causes of death in the conduction system. Cases of sudden cardiac death in patients aged < or=40 years during a 10-year period (Michigan) and a 4 year-period (Spain) were selected from the files. From this group, cases were identified in which the cause of death was a lethal change in the CCS. The portions of the heart containing the CCS were excised, and at least one hematoxylin and eosin slide and at least one trichrome or elastic trichrome slide per block were studied. In the two centers, 381 cases of sudden cardiac death were identified. The most common causes of sudden cardiac death were arteriosclerotic narrowing of the coronary arteries, cardiomyopathy, and myocarditis. In 82 cases, there was no identifiable cause of death even after complete gross and microscopic autopsy was performed, a medical history was obtained, and a drug screen was performed. In 11 cases, the CCS contained lesions that were considered lethal: narrowing of the atrioventricular node artery by fibromuscular hyperplasia (7 cases) and atrioventricular node tumors (4 cases). The 11 cases accounted for 2.9% of the 381 cases of sudden cardiac death and 11.8% of the indeterminable cases. It was concluded that examination of the CCS in deaths in which the gross and microscopic autopsy, history, and drug screen fail to provide a cause of death can yield a cause of death in a significant percentage of cases. If heart block was not documented during life and no explanatory lesions were found during routine cardiac examination, examination of the CCS can yield valuable information.     

Sudden cardiac death in a young woman: tumor of the atrioventricular (AV) node or citalopram intoxication?

Atrioventricular (AV) node tumor is a very rare lesion of the cardiac conduction system. Clinically, it is associated with complete AV block and sudden cardiac death, often in apparently healthy young people.We report a case of a 24-year-old woman who developed ventricular fibrillation during sexual intercourse and died before admittance to the hospital. The woman had a medical history of depression and was treated with citalopram.At first, no macroscopic or microscopic pathologic changes were found. Toxicologic analysis showed a toxic level of citalopram in the blood. Further microscopic examination of the cardiac conduction system disclosed a tumor of the AV node. Immunohistochemical staining confirmed endodermal origin in accordance with the latest hypothesis of the pathogenesis of this tumor.It was concluded that this young woman died of cardiac arrhythmia due to the AV tumor and not from citalopram intoxication, as first suspected. This case emphasizes the importance of a microscopic examination of the cardiac conduction system in cases of sudden unexpected death, even in cases with a plausible cause and manner of death at first glance.     

Sudden epilepsy deaths and the forensic pathologist

Sudden unexpected deaths in epileptic persons are not rare events, most commonly encountered by the forensic pathologist rather than the clinician. Such deaths may represent 1-1.5% of all "natural" deaths certified by the medical examiner or coroner. The typical victim is a black male about 30 years of age who tends to abuse alcohol, with a history of generalized epilepsy for more than 1 year and likely for more than 10 years. There are a lack of obvious anatomic causes for the death at autopsy, but 60-70% of cases will have a lesion in the brain (most commonly old trauma) to explain the epilepsy. Most victims have no blood levels of anticonvulsant medications at the time of death. We have evolved a form for use by medical examiner/coroner's investigators at the scene to collect relevant information which will be of assistance to the pathologist in interpreting the case. Estimated prevalence of sudden epilepsy death, mechanisms, and other features of such cases are reviewed briefly.     

Mechanisms of unexpected and/or sudden death in Lafora disease

A 23-year-old male was found dead wedged between two chairs at his home address. His past history included a diagnosis of Lafora disease (a type of heritable progressive myoclonic epilepsy) at the age of 16 years. This had been characterised by the development of epilepsy and progressive motor impairment and mental deterioration. Diagnosis had been confirmed by demonstration of mutation in the EPM2A gene on chromosome 6q24. At autopsy, petechial haemorrhages were noted of the face and conjunctivae bilaterally. There were no other significant findings apart from gastric contents within the airways. Death was attributed to positional asphyxia complicated by aspiration of gastric contents. Although death in Lafora disease is usually predictable and often protracted, sudden and/or unexpected death may occur and involve status epilepticus, sudden unexpected epileptic death, choking, aspiration of gastric contents, and cardiac arrhythmias. In addition, the possibility exists of unnatural causes of death, such as accidents, provoked by epilepsy or physical inability of the victims to extricate themselves from dangerous situations, or homicides, provoked by difficulties in caring for individuals with significant and progressive disabilities.     

Subependymoma and unexpected death

A previously healthy 53-year-old man died suddenly and unexpected. The main finding at the post mortem examination was a large 4th ventricle subependymoma, a rare brain tumour related to the ventricles of the brain. The salient features of subependymoma are described with emphasis on the microscopic picture and distinction from subependymal giant cell astrocytoma, as the tumour harboured large, bizarre astrocytes. Coronary atherosclerosis and mild cardiac hypertrophy were present as the only pathologic changes outside the central nervous system. The cause of death is discussed in light of earlier reports on brain tumours and sudden fatal incidents.     

癫痫的神经病理学研究进展

癫是一种常见的脑疾病,可引起猝死,以往人们侧重于对癫脑电活动的研究,而近年来癫的神经病理学研究已成为临床和法医工作者的一个研究热点。本文依据一系列文献资料分别从癫的发育障碍、瘤性异常增殖、海马硬化、双重病理改变、苔藓纤维发芽等神经病理学变化方面进行综述,进而探讨其法医学意义,希望对癫猝死的法医病理学诊断提供一定的帮助。     

Inferior Vena Cava Tumor Thrombosis Secondary to Metastatic Uterine Cancer: A Rare Cause of Sudden Unexpected Death

Pulmonary tumor thromboembolus (PTTE) secondary to uterine cancer is a rare cause of sudden unexpected deaths in the elderly population. Additionally, tumor extension to the inferior vena cava (IVC) makes it rarer. No such cases have been previously reported in the forensic literature. We report this phenomenon in a previously healthy 70‐year‐old woman with no other known risk factors for the development of deep vein thrombosis. The deceased was found dead while watching television with her relatives. Autopsy examination revealed that her death was attributed to a saddle embolus lodged in the main pulmonary arteries. A uterine tumor was discovered, and microscopic examination revealed low‐grade endometrial stromal sarcoma with angiolymphatic invasion. The tumor cells were also found in the embolus and the remnant thrombosis attached to the inner wall of the IVC. This case demonstrates a sudden unexpected death caused by acute PTTE following seeding of uterine cancer into the IVC and raises awareness of such events.     

Cerebrovascular malformation causing sudden death. Analysis of three cases and review of the literature

Three unusual cases of sudden death resulting from cerebrovascular malformation (CVM) are presented. CVMs are highly variable in location and morphology, and may be difficult to detect. Two of the patients discussed here had CVMs that involved the circle of Willis directly, and produced rapidly fatal subarachnoid hemorrhage at the base of the brain; both of these subjects were in their late 30s. One had a history of epilepsy; the other had been completely asymptomatic prior to the catastrophic event. The third was an asymptomatic 6 year old with a cerebellar CVM, who survived long enough for inconclusive neurosurgical intervention. In all three cases, the diagnosis was not made prior to autopsy; in one case, the circumstances of death were initially misleading. The relevant literature is reviewed and discussed, with emphasis on differential diagnosis, anatomic examination, and background investigation.     

Littre hernia--a rare cause of unexpected death in the elderly

A rare case of sudden and unexpected death is reported in an 87-year-old woman who was found dead at her home. At autopsy, the most striking finding was of a right-sided direct inguinal hernia containing a 20 mm infarcted Meckel diverticulum, with proximal small intestinal obstruction. Significant stenosing atherosclerosis was present in all three major epicardial coronary arteries, but with no histological evidence of acute or chronic ischemic myocardial damage. Death was attributed to small intestinal obstruction due to direct inguinal herniation (and infarction) of a Meckel diverticulum (a Littre hernia), complicating ischemic heart disease. Although Littre hernias are not a reported cause of sudden death in the elderly, congenital gastrointestinal anomalies may rarely play a significant role in terminal episodes well beyond childhood years. The autopsy assessment of sudden death at any age involves detailed examination of the entire length of the intestinal tract.     

Desquamative interstitial pneumonia in an infant. Mimicry of sudden infant death syndrome

A 15-week-old infant girl, without a prior history of overt illness, was found dead while sleeping between her two parents. The gross examination at autopsy showed only congested lungs, and the initial diagnosis was sudden infant death (SID). On microscopic examination, a desquamative interstitial pneumonia (DIP) was observed. The widespread, patchy intraalveolar histiocytic desquamation was associated with lymphocytic infiltration of bronchiolar and aveolar walls, which together provided convincing evidence that an interstitial pneumonitis was the cause of death. A viral etiology seems most likely in view of the accompanying chronic inflammation of bronchial submucosal glands.     

Fatal neurotoxic response to neuroleptic medications: case report and review of the literature

Neuroleptic malignant syndrome (NMS) is a diagnosis of exclusion difficult to make due to a lack of pathognomonic features. Diagnosing NMS by postmortem examination becomes increasingly challenging when possible underlying brain pathology is obscured. The diagnosis is based on clinical history and laboratory findings. Autopsy and histologic findings, if any, usually are reflective of hyperthermia or complications (eg, aspiration pneumonia) of NMS. The authors describe a case of a 36-year-old Hispanic woman with a presumptive diagnosis of pseudoseizures, treated with various combinations of neuroleptic medications over a 6-week period prior to her sudden, unexpected, in-hospital death. Neuroleptic malignant syndrome is likely to have contributed to this patient's death. Confounding factors and medicolegal issues of a postmortem diagnosis of NMS are discussed.     

Sudden death in right ventricular dysplasia with minimal gross abnormalities

Arrhythmogenic right ventricular cardiomyopathy is emerging as a relatively common cause of exercise-induced sudden death in the young. The diagnostic criteria at autopsy are, however, not fully established, leading to both over- and underdiagnosis. We report a young man and a young woman dying suddenly of right ventricular dysplasia during exercise, in whom the gross autopsy findings in the right ventricle were minimal or even absent. However, the histologic features in both right and left ventricles were typical of the disease, and consisted of fibrofatty infiltrates with typical myocyte degeneration of the right ventricle and subepicardial regions of the left ventricle. These cases illustrate that microscopic findings are diagnostic and may be present in the absence of gross findings. Marked fat replacement is not essential for the diagnosis of right ventricular dysplasia, and the right ventricle should be extensively sampled histologically in all cases of sudden unexpected death, especially those that are exercise related.     

Evaluation of diagnostic tools applied in the examination of sudden unexpected deaths in infancy and early childhood

During the period between 1984 and 1999, 309 cases of sudden unexpected death in infancy and early childhood (0-3 years) were investigated at the Institute of Forensic Medicine in Oslo. In 73 cases, an explainable cause of death was found. In this non-sudden infant death syndrome (SIDS) group, 42 cases were due to disease, 14 to accidents, 7 to neglect/abuse and 10 cases were due to homicide. In 43 cases, there were pathological findings at the autopsy or suspect features in the history and/or circumstances, which were, however, insufficient to explain death ("borderline" SIDS). In the remaining 193 cases, nothing of significance was detected ("pure" SIDS).The purpose of the present study was to evaluate the importance of the different diagnostic tools used in diagnosing non-SIDS and borderline SIDS cases. The definition of SIDS requires a negative history as well as a negative autopsy result. Thus, the following variables were analysed: circumstances, medical history and autopsy, which included a gross pathological investigation, histology, neuropathology, microbiology, radiology and toxicology. In diagnosing deaths due to disease, histology, neuropathology and microbiology were the most important diagnostic tools. In contrast, information about the circumstances of death and the gross pathological findings at autopsy most often revealed the cause of death in accidents and cases of neglect/abuse and homicide.Following the drop in SIDS rate in Norway after 1989, the share of pure SIDS in proportion to the total population of sudden unexpected deaths in infancy and early childhood has decreased. The increasing proportion of non-SIDS and borderline SIDS cases presents a challenge to improve the quality of the investigation in cases of sudden death in infancy and early childhood.     

Disseminated Neonatal Herpes Simplex Virus Infection with Escherichia Coli Coinfection

Neonatal herpes simplex virus (HSV) infection is an uncommon disease that rarely presents as sudden unexpected death of a previously healthy newborn. Clinical manifestations are variable; signs and symptoms may be subtle and nonspecific. Neonatal infection may present with mucocutaneous (skin, eye, and/or mouth), disseminated, or central nervous system disease. Morbidity and mortality are dependent upon disease presentation and treatment. The infection is most frequently transmitted during the peripartum period, although the majority of mothers have no known history of HSV infection at the time of delivery. Findings at autopsy include gastrointestinal or mucocutaneous ulcers, diffuse hepatic necrosis, adrenal necrosis, pneumonitis, and splenic necrosis. Characteristic intranuclear viral inclusions are identified on microscopic examination. Coinfection with bacterial organisms may contribute to death. Autopsy examination with appropriate ancillary studies, including cultures, is critical given that many infants lack cutaneous manifestations of disease and remain undiagnosed prior to death.     

Cardiac rhabdomyoma presenting as sudden infant death syndrome

A case of cardiac rhabdomyoma presenting as sudden infant death in a four-and-one-half month-old infant is reported. The child was the product of an essentially uncomplicated pregnancy and enjoyed good health before his unexpected, sudden death. Autopsy examination revealed the presence of multiple cardiac lesions which histologically were diagnosed as rhabdomyomas. Death was attributed to fatal cardiac arrhythmia caused by the tumor. To the authors' knowledge this represents the first reported case in the forensic science literature of death as a result of cardiac rhabdomyoma presenting as sudden infant death syndrome (SIDS).     

Lethal manifestations of systemic lupus erythematosus in a forensic context

Systemic lupus erythematosus is an autoimmune connective tissue disorder that affects multiple organs. While the clinical manifestations may vary in intensity over time and be associated with chronic disease, occasional cases occur where sudden and unexpected death has occurred. Cardiovascular disease is common, with accelerated atherosclerosis, intravascular thrombosis associated with antiphospholipid syndrome, and hypertensive cardiomegaly. Vasculitis with superimposed thrombosis may result in critical reduction in blood to vital organs, such as the heart and brain with infarction. Mesenteric ischemia may be caused by vasculitis, thrombosis, and accelerated atherosclerosis and may result in lethal intestinal infarction. Other diverse causes of sudden death include myocarditis, epilepsy, pulmonary hypertension, pulmonary thromboembolism, and sepsis. The autopsy evaluation of such cases requires careful examination of all organs with extensive histological sampling to include blood vessels, and microbiological sampling for bacteria, viruses, and fungi.     

Stressful events as a trigger of sudden death: a study of 43 medico-legal autopsy cases

The reports relating emotional stress to sudden death are largely anecdotal. In addition to experimental and electrophysiological studies, an opportunity for a better understanding of possible stress-related sudden death (SSD) may be provided by medico-legal autopsies. The goal of our autopsy study was to analyze cardiovascular pathologic findings in cases of SSD and if possible identify mechanisms by which the stressful event (SE) could be the cause. Forty three cases were studied (29 males and 14 females). In all cases, the SE and the death were witnessed. The age range was 22 to 90 years in males (mean, 52) and 30 to 92 years in females (mean, 64). Death occurred in all cases without premonitory symptoms. In 20 cases, death occurred during the SE and in the other 23 cases occurred within 2 h of the event. SE included fear, 15 cases; altercation, 21 cases; sexual activity, 3 cases; police questioning or arrest, 4 cases. According to police reports, in 40 cases (90%), the victims had no previous clinical history of cardiovascular disease. At autopsy, the heart weight in males ranged from 255 to 1000 g with a mean of 517 g and in females the range was 250–700 g with a mean of 417 g. In only 3 cases, gross and microscopic examination of the heart was normal. In 2 of the remaining 40 cases the subjects died of subarachnoid hemorrhage. In 38 cases, a cardiac cause of death was found as follows: coronary heart disease, 27 cases; cardiomyopathy, 6 cases; aortic valvular stenosis, 2 cases and right ventricular dysplasia, 3 cases. A coronary artery thrombosis was found in 8 cases of sudden coronary death. Post myocardial infarction fibrosis was present in 25 cases (92%) of sudden coronary death. In conclusion, it appears from our autopsy study that SSD occurs primarily in those individuals with severe heart disease, especially coronary heart disease.     

Association of right coronary artery hypoplasia with sudden death in an eleven-year-old child

Congenital coronary artery abnormalities are a rare but well-documented cause of sudden and unexpected death in the pediatric age group. Most reported cases involve both an aberrant origin and course of the abnormal vessel. A case of unexpected death occurring in an otherwise healthy eleven-year-old boy, who had been previously investigated for sudden collapse, is described. The major finding at autopsy was marked disparity in diameter between the coronary arteries due to diffuse hypoplasia of the right coronary artery. This case demonstrates the importance of meticulous examination of the coronary artery system in cases of sudden death in childhood so that significant reduction in luminal cross section will be adequately documented. The possible role played by this finding in the etiology of sudden death is discussed.     

Sudden unexpected death in epilepsy: a retrospective study

Patients with epilepsy have a mortality rate higher than that of the general population; sudden unexpected death represents a significant category of mortality in these patients. The precise frequency of occurrence of sudden unexpected death in epilepsy (SUDEP) is not well defined, with a range of 1 in 370 to 1100 in the general epileptic population. A major difficulty with incidence studies is the continued reluctance in using the term SUDEP as a cause of death, making reliance solely on death certificates inconsistent and incomplete. Knowledge about SUDEP remains limited, as no single common risk factor has yet been identified, although predisposing conditions have been suggested. The purpose of this study is to review the association between several clinical variables and SUDEP to elucidate risk factors. The characteristics of the 67 cases in this series correlate with published findings in previous studies. Attributes that may be used to define an at-risk group of epileptics include age less than 40 years, male gender, long history of seizure disorder, undermedication or poorly controlled seizure activity, and mental or physical stress. Education of physicians as to the existence of SUDEP and risk factors is imperative in improving patient education and reduction in mortality.     

Ascending Aortic Rupture through a Penetrating Atherosclerotic Ulcer: A Rare Cause of Sudden Unexpected Death

Spontaneous rupture of the aorta through an atherosclerotic lesion without preexisting aortic aneurysm, dissection, or history of trauma is very rare. Without prompt aortic repair, all cases result in sudden death with a definitive diagnosis made only intraoperatively or during autopsy. The phenomenon has been uniformly found in individuals with hypertension. The author reports a sudden unexpected death caused by spontaneous rupture of the ascending aorta in a 57‐year‐old man with a history of hypertension. The ascending aortic wall showed a longitudinal intimal tear measuring approximately 1 cm in length and rupture of the ascending aorta through an atherosclerotic ulcer, leading to massive hemopericardium and eventual death. Chronic hypertension and a penetrating atherosclerotic ulcer of the ascending aorta were the apparent underlying etiologies of the aortic rupture in the present case. This case illustrates not only the association between a rupture and a penetrating atherosclerotic ulcer with a silent death, but also raises awareness of possible such deaths.