Asplenia as a cause of sudden unexpected death in childhood

Sudden unexpected death in childhood is rare. The commonest causes of such deaths are a result of fulminating infections of the respiratory or nervous systems. Other causes include unsuspected congenital abnormalities of the heart, acute metabolic disorders, and rarities such as internal hemorrhages and pulmonary thrombosis. Recognition of children with congenital asplenia who are otherwise normal but have an increased susceptibility to overwhelming sepsis is extremely difficult. We reviewed 1763 autopsy files from our institution over 5 years (1990-1995), of which 293 were classified as pediatric cases. The vast majority of the cases were stillbirths and deaths within the first year of life as a result of complex congenital anomalies. Four cases of asplenia were identified in our entire series, 3 of which were of the congenital syndromal variety and 1 of which was a case of isolated sporadic congenital asplenia. All 4 cases of asplenia were analyzed in detail with respect to autopsy findings and cause of death. Severe complex cardiac malformations were present in the congenital syndromal asplenia patients; these other malformations contributed significantly to their death. In this report, we discuss in detail the autopsy findings in a previously healthy 4-year-old girl who presented with a brief 8-hour history of being unwell and died within 4 hours of admission into the hospital. She had sporadic, isolated congenital asplenia complicated by high-grade type 6B pneumococcemia and acute bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome). Previously healthy children who clinically deteriorate very rapidly should have a blood smear done as part of their clinical workup. The detection of Howell-Jolly bodies on a peripheral blood smear can be an indicator of asplenia, and this diagnosis can be confirmed by medical imaging of the abdomen. Such steps may aid in the aggressive management of isolated congenital asplenia and thereby avert untimely death.     

Sudden death as a complication of bacterial endocarditis

Three cases are reported to demonstrate the range of possible lesions and wide variation in lethal mechanisms that may be found in cases of unexpected death subsequently shown to be due to bacterial endocarditis. Case 1: A 36-year-old man was found dead on his bedroom floor surrounded by drug paraphernalia. At autopsy, acute myocardial ischemia was present caused by coronary artery ostial occlusion complicating acute bacterial endocarditis of the aortic valve. Case 2: A 54-year-old man with chronic renal failure was found dead in bed at home. At autopsy, a left middle cerebral artery territory cerebral infarct was present due to septic embolization from bacterial endocarditis involving the aortic valve. Case 3: A 23-year-old man was found collapsed in a pool of blood. At autopsy, upper airway hemorrhage from an arteriobronchial fistula was present caused by septic pulmonary infarction from previous endocarditis of a congenital ventricular septal defect. This report demonstrates that bacterial endocarditis may still be a cause of sudden and unexpected death presenting to forensic mortuaries and that the underlying mechanisms may involve complex sequences of pathological changes that compromise vascular function.     

Death due to thrombotic thrombocytopenic purpura in pregnancy: case report with review of thrombotic microangiopathies of pregnancy.

Maternal death during pregnancy, although uncommon, may result from a broad range of conditions. In this paper, a case of thrombotic thrombocytopenic purpura diagnosed by postmortem examination is presented. Thrombotic thrombocytopenic purpura is one of a subset of diseases that result in the formation of microthrombi within the vasculature, either as a primary or secondary manifestation. Other conditions included in the differential diagnosis during pregnancy are hemolytic uremic syndrome, systemic lupus erythematosus, preeclampsia-eclampsia and the HELLP syndrome, acute fatty liver of pregnancy, antiphospholipid antibody syndrome, and disseminated intravascular coagulation. The histologic manifestations of these diseases can be similar and in most cases do not provide adequate information to accurately differentiate these diseases in the postmortem period. This paper addresses the need for clinical history (i.e., symptomatology, trimester of onset) and antemortem laboratory testing in addition to a thorough autopsy to accurately differentiate among the conditions named previously. In the absence of an adequate clinical history and antemortem laboratory testing, the more general diagnosis of "thrombotic microangiopathy of pregnancy" is acceptable.     

Sudden Infant and Early Childhood Death and Sinus of Valsalva Pseudoaneurysms

Two cases of occult pseudoaneurysms of the sinus of Valsalva (SoV) are reported to demonstrate different etiologies and lethal mechanisms. A previously well 9‐month‐old boy who suffered an unexpected fatal cardiorespiratory arrest was found at autopsy to have a ruptured pseudoaneurysm of the left SoV resulting in lethal hemopericardium. A 13.5‐month‐old boy died soon after presenting with a 24‐h history of poor feeding and reduced urine output. At autopsy, destruction of the noncoronary cusp of the aortic valve by bacterial endocarditis was found with extension of the inflammation into a pseudoaneurysm of the SoV with surrounding abscess formation involving the atrioventricular node. Death was most likely due to an arrhythmia. Pseudoaneurysms of the SoV are exceedingly rare but may result in sudden/unexpected death in infancy and early childhood from rupture or involvement of the conduction system or myocardium. Detailed cardiac examination is essential in all unexpected deaths in early life.     

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.     

Two Fatal Cases of Hidden Pneumonia in Young People*

Abstract: Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by inflammation of the lung parenchyma leading to impaired gas exchange. This condition is often lethal, usually requiring mechanical ventilation and admission to an intensive care unit. We present two fatal cases of hidden pneumonia in young people and discuss the pathophysiological mechanism of ARDS with reference to the histological pattern. A complete forensic approach by means of autopsy and histological, immunohistochemical, and microbiological, examination was carried out. In both cases the cause of death was cardio‐respiratory failure following an acute bilateral pneumonia with diffuse alveolar damage and ARDS associated with sepsis and disseminated intravascular coagulation. Our cases suggest on one side the importance of an early diagnosis to avoid unexpected death while on the other that the diagnosis of ARDS has to be confirmed on the basis of a careful postmortem examination and a complete microscopy and microbiological study.     

Acute pancreatitis presenting as sudden, unexpected death: an autopsy-based study of 27 cases

Acute pancreatitis represents a spectrum of disease, ranging from a mild, transitory illness to a severe, rapidly progressive hemorrhagic form, with massive necrosis and mortality rates of up to 24%. The reported incidence of acute pancreatitis diagnosed first at clinicopathologic autopsy ranges between 30% and 42%. To better describe outpatient fatalities due to acute pancreatitis that present as sudden, unexpected death, we retrospectively reviewed the autopsy files at the Institute of Legal Medicine, University of Hamburg, Germany, from 2000-2004. Individual cases were analyzed for sex, age, race, circumstances of death, social background of the deceased and previous medical history, seasonal occurrence of the disease, blood alcohol concentration at the time of death, body mass index, autopsy findings, histopathology, and etiology of acute pancreatitis. Among the 6178 autopsies carried out during the 5-year period evaluated, there were 27 cases of acute pancreatitis that presented as sudden, unexpected death. In all cases, the diagnosis was first made at autopsy. The male:female ratio was 1.7:1 and the mean age was 52 years (range, 30-91 years). Etiologies of acute pancreatitis included alcohol (n=19), gall stones (n=2), other identified etiologic factors (n=3), and idiopathic (n=3). Complications of acute pancreatitis included lung edema and/or acute respiratory distress syndrome, peritonitis, disseminated intravascular coagulation, and sepsis. At least 20 subjects (74%) had lived isolated, with no social contacts. Contrary to the clinical observations of a clear seasonal variation in the onset of acute pancreatitis, we found no correlation between death due to acute pancreatitis and a specific month or season. Many prior studies have suggested that the majority of deaths in severe acute pancreatitis occur in the late phase of the disease as a result of pancreatic sepsis. Conversely, in the present study, the majority of affected individuals died during the very early phase of the disease. While gallstones represent the main etiologic factor in most larger clinical series, biliary etiology seems to play only a minor role in outpatient deaths undergoing medicolegal autopsies. Data derived from medicolegal autopsy studies should be included in future population-based studies of acute pancreatitis.     

Sudden unexpected death in infancy and childhood due to undiagnosed neoplasia: an autopsy study

Sudden unexpected death due to clinically undiagnosed neoplasia in infancy and childhood (SUDNIC) is a rare phenomenon, with only small numbers of cases reported in the literature. In the majority of instances, the tumors involve critical structures within the heart or central nervous system and include gliomas, medulloblastomas, rhabdomyomas, and neoplasms of stromal elements. A 20-year retrospective review of autopsy records from the Hospital for Sick Children, Toronto, was performed (1984-2003, n = 4926), and 7 cases of SUDNIC were identified (0.14%). In addition, 1 case was obtained from the files of the Children's and Women's Health Centre of British Columbia, Vancouver. Diagnoses included 2 cases of acute leukemia (1 myelogenous, 1 lymphoblastic), 2 cases of mediastinal lymphoblastic lymphoma (pre-T cell type), 1 papillary fibroelastoma of the mitral valve prolapsing into and totally occluding the left anterior descending coronary artery, 1 medulloblastoma, 1 Wilms tumor associated with fatal intraperitoneal hemorrhage, and 1 widely disseminated gastric carcinoma. These cases demonstrate that infants and children may have minimal or no symptoms in the presence of significant disease and highlight the need for a thorough autopsy examination in cases of sudden unexpected death in infancy and childhood.     

Is there progress in the autopsy diagnosis of sudden unexpected death in adults?

Sudden death is now currently described as natural unexpected death occurring within 1h of new symptoms. Most studies on the subject focused on cardiac causes of death because most of the cases are related to cardiovascular disease, especially coronary artery disease. The incidence of sudden death varies largely as a function of coronary heart disease prevalence and is underestimated. Although cardiac causes are the leading cause of sudden death, the exact incidence of the other causes is not well established because in some countries, many sudden deaths are not autopsied. Many risk factors of sudden cardiac death are identified: age, gender, heredity factors such as malignant mutations, left ventricular hypertrophy and left ventricle function impairment. The role of the police surgeon in the investigation of sudden death is very important. This investigation requires the interrogation of witnesses and of the family members of the deceased. The interrogation of physicians of the rescue team who attempted resuscitation is also useful. Recent symptoms before death and past medical history must be searched. Other sudden deaths in the family must be noted. The distinction between sudden death at rest and during effort is very important because some lethal arrhythmia are triggered by catecholamines during stressful activity. The type of drugs taken by the deceased may indicate a particular disease linked with sudden death. Sudden death in the young always requires systematic forensic autopsy performed by at least one forensic pathologist. According to recent autopsy studies, coronary artery disease is still the major cause of death in people aged more than 35 years. Cardiomyopathies are more frequently encountered in people aged less than 35 years. The most frequent cardiomyopathy revealed by sudden death is now arrhythmogenic right ventricular cardiomyopathy also known simply as right ventricular cardiomyopathy (RVC). The postmortem diagnosis of cardiomyopathies is very important because the family of the deceased will need counseling and the first-degree relatives may undergo a possible screening to prevent other sudden deaths. In each case of sudden death, one important duty of the forensic pathologist is to inform the family of all autopsy results within 1 month after the autopsy. Most of the recent progress in autopsy diagnosis of sudden unexpected death in the adults comes from molecular biology, especially in case of sudden death without significant morphological anomalies. Searching mutations linked with functional cardiac pathology such as long-QT syndrome, Brugada syndrome or idiopathic ventricular fibrillation is now the best way in order to explain such sudden death. Moreover, new syndromes have been described by cardiologists, such as short-QT syndrome and revealed in some cases by a sudden death. Molecular biology is now needed when limits of morphological diagnosis have been reached.     

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.     

Changing trends in the diagnosis of sudden infant death

A study of 114 consecutive cases of unexpected infant death that occurred in South Australia over a 5-year period from January 1994 to December 1998 was undertaken. There were 45 deaths attributed to sudden infant death syndrome (SIDS), 19 to natural causes, 21 to accidents. and 5 to homicides; 24 cases were listed as "undetermined." Although there has been a genuine and continued decline in SIDS numbers in this population, there has also been an increase in the diagnosis of cases of accidental asphyxia due to unsafe sleeping environments and of cases in which the family background and autopsy findings suggested more complex mechanisms. The change in diagnostic profile has followed the introduction of more rigorous clinical history review, death scene examination, and autopsy testing. Thus, although diagnostic outcomes have altered in this population, it is more likely the result of more careful interpretation of the extensive investigations that are now undertaken rather than arbitrary reclassification.     

Sudden death in an infant resulting from torsion of the uterine adnexa

A 2-month-old infant girl died suddenly as a result of torsion of the uterine adnexa. The infant was found unresponsive in bed and was pronounced dead shortly after her arrival at a hospital. There were no antecedent signs of illness. At autopsy, the right ovary and right fallopian tube were twisted and were dark purple, swollen, and necrotic. The right ovary was enlarged by a follicle cyst 4 cm in diameter, which likely precipitated the torsion. The mechanism of death was unclear but may have resulted from the release of cytokines produced in response to necrotic adnexal tissue. Fatal uterine adnexal torsion has been reported rarely in infants; in all those cases there were antecedent symptoms. Torsion of the uterine adnexa should be included in the differential diagnosis of sudden death in infancy.     

Mechanisms of Lethal Cerebrovascular Accidents in Turner Syndrome

A case of intracerebral hemorrhage in Turner syndrome is reported with an analysis of possible causes of cerebrovascular accidents in this condition. A 42‐year‐old woman with known Turner syndrome died soon after hospital admission having been found unconscious at her home address. At autopsy, she showed typical features of Turner syndrome with short stature, webbing of the neck, underdeveloped breasts, and an increased carrying angle of the arm. Death was due to a large left‐sided intracerebral hemorrhage extending from the left basal ganglia into the white matter of the frontal lobe and lateral ventricle. Cases of unexpected death in Turner syndrome may arise from occult cerebrovascular accidents which may be hemorrhagic or nonhemorrhagic. Associated features include hypertension, vascular malformations, accelerated atherogenesis, cystic medial necrosis, and moyamoya syndrome. The possibility of Turner syndrome should be considered in cases where there has been a lethal cerebrovascular event in a younger woman.     

Particularities Regarding the Etiology of Sepsis in Forensic Services

If in clinical practice definitive diagnostic criteria had been established, after death sepsis is often difficult to diagnose, especially if a site of origin is not found or if no clinical data are available. This article will analyze the etiology of sepsis in a medical‐legal service with emphasis on the differences in diagnosing it in clinical and forensic environments. A total of 78 cases of sepsis cases diagnosed or confirmed at the autopsy were selected. The etiological agent was determined either during the hospitalization or by postmortem bacteriology. A high prevalence of Gram‐negative sepsis was found, especially multidrug‐resistant micro‐organisms. Most frequent etiological agents were Acinetobacter baumannii, Escherichia coli, Enterobacter, Enterococcus, Pseudomonas, and Klebsiella. Polymicrobial sepsis is much more frequent than in nonforensic cases. In legal medicine, the prevalence of Gram‐negative sepsis is much higher than in nonforensic autopsies, and the point of origin is shifted toward the skin and the gastrointestinal system.     

Sudden infant death, large intestinal volvulus, and a duplication cyst of the terminal ileum

A previously well 7-week-old boy was found unresponsive and cyanotic in his cot in the morning. Resuscitative attempts achieved only partial response with subsequent terminal cardiac arrest occurring later in the day. At autopsy a large intestinal volvulus was found associated with disseminated Clostridium perfringens sepsis. In addition, a duplication cyst of the terminal ileum was present. Although rare, right-sided colonic volvulus may be a cause of unexpected death in infancy. While predisposing factors to volvulus may include intestinal duplication cysts, the anatomic relation of the duplication to the volvulus must be carefully determined before a causal relation can be accepted; the cyst in this case was most likely incidental to the terminal event.     

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.     

Brain amino acid abnormalities in kidney disease and diabetes mellitus

The present postmortem study examines whether specific amino acid abnormalities associated with renal diseases or diabetes mellitus in animal experiments and on clinical examination may also be found in human brain samples obtained at clinical autopsies. The material includes 12 deceased with renal insufficiency, 23 deceased with diabetes mellitus and 26 control cases with lethal cardiovascular diseases (without a history of hepatic, renal or metabolic disturbances). The autopsy and clinical records were retrospectively analyzed for age, sex, postmortem delay, cause of death, substantial preexisting diseases and histological findings. The analysis of free amino acid concentrations in human brain specimens was performed applying a Beckman amino acid analyzer. The results were evaluated using the U-test according to Mann, Willcox and Whitney. A P-value less than 0.05 was considered to be significantly different. Differences of amino acid concentrations attributable to sex, age and postmortem delay were not significant. The comparison of postmortem amino acid concentrations in the brains of patients with diabetes mellitus and controls did not reveal relevant changes. However, the patients with renal diseases, as compared to controls, showed a significant cerebral increase of urea, phenylethanolamine and gamma-aminobutyric acid. Thus, the postmortem amino acid analysis may contribute to the understanding of pathophysiological mechanisms of uremic encephalopathy and may supplement the conventional postmortem morphological diagnosis in kidney diseases by indication of functional impairment.     

Homicide as a cause of the sudden infant death syndrome

The homicidal asphyxiation of a 10 1/2-month-old male infant and the attempted asphyxiation of his 4-month-old sibling, documented by parental confession, is presented as evidence that murder may sometimes be mistaken as sudden infant death syndrome (SIDS). A review of the literature of the relationship between murder and SIDS deaths reveals the suspicions of some physicians but few published cases; this reflects not only the difficulties of making a determination of murder by suffocation, since no injuries may be present, but also a lack of awareness among physicians who must evaluate infant deaths. It is recommended that murder should be considered in the differential diagnosis of sudden, unexpected death in infants and that the autopsy should include full-body x-rays and at least an initial look at the social history of the child.