Sudden death in childhood and adolescence

Sudden natural deaths of individuals between the ages of 2 and 20 years which occurred during a 20-year period were identified from mortuary records. Necropsy reports and histological sections were reviewed; 169 sudden natural deaths were identified amongst 1012 deaths in that age group. Ninety-two sudden deaths occurred to children with recognized disorders; congenital heart disease, asthma, and epilepsy were the commonest problems identified. Amongst the 77 deaths of apparently healthy children, infection was the most frequently recognized disease. Only 11 deaths were unexplained, comprising 1 per cent of the necropsy population or 6.5 per cent of sudden natural deaths, a much smaller proportion than pertains in infancy. Necropsy examination of children dying suddenly yields useful information.     

A de novo BRPF1 variant in a case of Sudden Unexplained Death in Childhood

Sudden Unexplained Death in Childhood (SUDC), the death of a child that remains unexplained after a complete autopsy and investigation, is a rare and poorly understood entity. This case report describes a 3-year-old boy with history of language delay and ptosis, who died suddenly in his sleep without known cause. A pathogenic de novo frameshift mutation in BRPF1, a gene which has been associated with the syndrome of Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP), was identified during a post-mortem evaluation. The finding of a pathogenic variant in BRPF1, which has not previously been associated with sudden death, in an SUDC case has implications for this child's family and contributes to the broader field of SUDC research. This case demonstrates the utility of post-mortem genetic testing in SUDC.     

Neuropathology of epilepsy: epilepsy-related deaths and SUDEP

Most pathologists will encounter deaths in patients with epilepsy in their practice, including sudden deaths. A systematic approach to these post-mortem examinations is required, including gathering relevant clinical details and around the circumstances of death, in order to correctly categorise these cases. Macroscopic and histological examination of the brain can reveal (i) the underlying cause of the epilepsy, as cortical dysplasia or tumours, (ii) sequel of previous seizures, including hippocampal sclerosis and contusions and (iii) potentially the cause of death. Sudden and unexpected death in epilepsy (SUDEP) is still under-reported as a cause of death. Although by definition there is no structural or toxicological cause of death at post-mortem, clinical and experimental studies together with neuropathological findings are beginning to identify alterations in central autonomic regions, including the brainstem, critical for cardio-respiratory regulation. Neuropathology investigations following post-mortem examinations form an essential component in the identification of disease mechanisms in epilepsy-related deaths and their future prevention.     

Neuropathology of epilepsy: epilepsy-related deaths and SUDEP

Most pathologists will encounter deaths in patients with epilepsy in their practice, including sudden deaths. A systematic approach to these post-mortem examinations is required, including gathering relevant clinical details and around the circumstances of death, in order to correctly categorise these cases. Macroscopic and histological examination of the brain can reveal (i) the underlying cause of the epilepsy, as cortical dysplasia or tumours, (ii) sequel of previous seizures, including hippocampal sclerosis and contusions and (iii) potentially the cause of death. Sudden and unexpected death in epilepsy (SUDEP) is still under-reported as a cause of death. Although by definition there is no structural or toxicological cause of death at post-mortem, clinical and experimental studies together with neuropathological findings are beginning to identify alterations in central autonomic regions, including the brainstem, critical for cardio-respiratory regulation. Neuropathology investigations following post-mortem examinations form an essential component in the identification of disease mechanisms in epilepsy-related deaths and their future prevention.     

Sudden death in epilepsy

Since at least 1868, the literature has recorded an excess of deaths associated with epilepsy which are thought to be seizure-related but in which the exact mechanism of death is not yet established. Sudden unexpected death in epilepsy (SUDEP) was defined in 1996 and is the recommended terminology to certify these deaths. The investigation and certification of these deaths has been criticized and there are no specific published guidelines. Most post-mortem examinations in possible SUDEP deaths will be at the request of the medico-legal authority who should provide the pathologist with full medical history and circumstances surrounding the death. A detailed external examination, complete internal examination and histology, toxicology and appropriate neuropathology are all essential elements of the investigation to establish the cause of death. The ultimate aim is to provide the relatives and government with accurate information to inform healthcare provision and decrease mortality associated with epilepsy.     

Accuracy of magnetic resonance imaging in determining cause of sudden death in adults: comparison with conventional autopsy

AIM: To determine the accuracy and define the limitations of post mortem magnetic resonance imaging (MRI) in determining the cause of sudden death in adults. METHODS AND RESULTS: Sudden unexpected adult deaths in the community, reported to the Coroner (n = 10), excluding suspicious, violent or potentially drug-related deaths, were submitted to whole body MRI, followed by full invasive autopsy. The MRI scans were reported independently by four radiologists, blinded to the autopsy findings; two had previous experience of post mortem MRI. An abnormality that related to the cause of death as identified at autopsy, was identified by at least one radiologist in eight cases. These were pulmonary consolidation (autopsy finding pneumonia) (n = 1), pneumoperitoneum (autopsy finding perforated peptic ulcer) (n = 2), left ventricular failure (autopsy finding ischaemic heart disease) (n = 4), and disseminated bronchial carcinoma (n = 1). However, in only one case were all radiologists able to provide a confident cause of death (disseminated bronchial carcinoma). In two cases, in which death occurred 2-6 days and 3-6 days before MRI, early decomposition prevented interpretation of the images. Severe coronary artery atheroma was detected at autopsy in 7/10, but these lesions were not detected by MRI. Previous experience in reporting post mortem MRI, without autopsy comparison, did not result in more accurate interpretation of the images. CONCLUSIONS: This pilot study suggests that post mortem MRI can identify some abnormalities relating to the common causes of sudden death in adults, but there is a need for greater experience in correlating MRI with autopsy findings before a reliable cause of death can be made by MRI alone. Inability to image coronary artery lesions, differentiating thrombus from clot and pulmonary oedema from pneumonic exudates, are specific problems that may be corrected with greater experience and higher resolution scans.     

Tissue and organ donation for research in forensic pathology: the MRC Sudden Death Brain and Tissue Bank

Novel methodological approaches to the investigation of brain and non-central nervous system disorders have led to increased demand for well-characterized, high quality human tissue samples, particularly from control cases. In the setting of the new Human Tissue legislation, we sought to determine whether relatives who have been suddenly bereaved are willing to grant authorization for research use of post mortem tissue samples and organs in sufficient numbers to support the establishment of a brain and tissue bank based in the forensic service. Research authorization was sought from families on the day prior to forensic post mortem examination followed up by written confirmation. We have to date selected individuals who have died suddenly (age range 1-89 years) and who were likely to have normal brains or who had displayed symptoms of a CNS disorder of interest to researchers, including psychiatric disorders. One hundred and eleven families have been approached during the first 2 years of this project. Research use of tissue samples was authorized by 96% of families and 17% agreed to whole brain donation. Audit of families' experience does not suggest that they are further distressed by being approached. Respondents expressed a clear view that the opportunity for research donation should be open to all bereaved families. Despite the sometimes long post mortem intervals, the quality of tissue samples is good, as assessed by a range of markers including Agilent BioAnalyzer quantification of RNA integrity (mean value 6.4). We conclude that the vast majority of families are willing to support research use of post mortem tissues even in the context of sudden bereavement and despite previous adverse publicity. The potential for acquisition of normal CNS and non-CNS tissues and of various hard-to-get CNS disorders suggests that efforts to access the forensic post mortem service for research material are eminently worthwhile.     

Sudden arrhythmic death and cardiomyopathies in the young: a molecular and pathology overview

Cardiovascular disease is a significant cause of sudden death (SD) requiring autopsy investigation. Non-ischaemic causes of SD are more prevalent in young people (<35 years of age) and conditions such as cardiomyopathies and channelopathies account for about one half of cases.The pathologist's task is to provide the correct diagnosis and, when dealing with a genetic disease, to initiate pre-symptomatic cardiologic and genetic cascade screening of first-degree family members. Early identification is important because SD can be the first and last clinical presentation of the underlying disease and the only medical examination undertaken is the autopsy. A standardized and detailed post-mortem procedure on the SD victims, in combination with molecular testing (“molecular autopsy”), will provide vital information for the family in preventing a further tragedy. Therefore proper sampling to allow post-mortem DNA analysis as well as accurate morphological evaluation, are mandatory, as recommended in the guidelines for autopsy investigation of SD from the Association for European Cardiovascular Pathology.     

Vascular causes of sudden death in infancy, childhood, and adolescence

Vascular causes of sudden death in infancy, childhood, and adolescence range from primary disorders of the vasculature involving structural compromise, as in anomalous coronary arteries, to vascular problems that may arise as secondary phenomena, such as the infectious arteritides. The etiology of the underlying condition may be understood, as in fatal pulmonary thromboembolism, or it may be shrouded in mystery, as in idiopathic arterial calcinosis. The absence of a clinical history indicating an underlying vascular problem in a number of disorders that may cause sudden childhood death underlines the importance of a meticulous autopsy examination in such cases.     

Mathematical model of death and reproduction of mitochondria in the irradiated organism

Institute for Physicotechnical Problems, Moscow. N. É. Bauman Moscow Higher Technical School. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 3, pp. 257–259, March, 1990.     

Neurotransmitter receptors in the life and death of oligodendrocytes

Oligodendrocytes are crucial to the function of the mammalian brain: they increase the action potential conduction speed for a given axon diameter and thus facilitate the rapid flow of information between different brain areas. The proliferation and differentiation of developing oligodendrocytes, and their myelination of axons, are partly controlled by neurotransmitters. In addition, in models of conditions like stroke, periventricular leukomalacia leading to cerebral palsy, spinal cord injury and multiple sclerosis, oligodendrocytes are damaged by glutamate and, contrary to dogma, it has recently been discovered that this damage is mediated in part by N-methyl-D-aspartate receptors. Mutations in oligodendrocyte neurotransmitter receptors or their interacting proteins may cause defects in CNS function. Here we review the roles of neurotransmitter receptors in the normal function, and malfunction in pathological conditions, of oligodendrocytes.     

Impact of gender on asthma in childhood and adolescence: a GA2LEN review

A number of studies have shown gender differences in the prevalence of wheeze and asthma. The aim of this review was to examine published results on gender differences in childhood and adolescent asthma incidence and prevalence, define current concepts and to identify new research needs.
A Medline search was performed with the search words (gender OR sex) AND (child OR childhood OR adolescence) AND (asthma). Articles that reported on abscence or prescence of gender differences in asthma were included and reviewed, and cross-references were checked. Boys are consistently reported to have more prevalent wheeze and asthma than girls. In adolescence, the pattern changes and onset of wheeze is more prevalent in females than males. Asthma, after childhood, is more severe in females than in males, and is underdiagnosed and undertreated in female adolescents. Possible explanations for this switch around puberty in the gender susceptibility to develop asthma include hormonal changes and gender-specific differences in environmental exposures. This aspect needs consideration of the doctors and allergists who diagnose and treat asthmatic individuals.
In conclusion, sex hormones are likely to play an important role in the development and outcome of the allergic immune response and asthma in particular. By obtaining functional data from appropriate models, the exact underlying mechanisms can be unravelled. To examine the effect of gender-specific differences in environmental exposures and changes of asthma prevalence and severity in puberty, larger populations may need to be investigated.     

Sudden unexpected death in patients with malignancy: a clinicopathologic study of 28 autopsy cases

Sudden unexpected death (SUD) in patients with malignancy has not been comprehensively studied. We defined SUD as intrinsic natural death within 24h after initial clinical presentation of the disease responsible for the death. Intra- and postoperative death and cases associated with a myelosuppressive state were excluded. Of 2,216 autopsy cases with malignancy registered at Saitama Cancer Center, Japan, 28 SUD cases (1.3%) were studied clinicopathologically. Fifteen cases (53.6%) died of non-neoplastic cardiovascular events (CVEs), with acute myocardial infarction (AMI) being the most common death (n=13). Ten cases (35.7%) died of neoplasm-related complications (NRCs), and a miscellaneous pathophysiology was apparent, including cardiac involvement by tumor cells (n=3), fistula formation between great vessels and the alimentary canal (n=3), hepatic rupture (n=2), cardiac tamponade (n=1), and neoplastic pulmonary emboli (n=1). An anaphylaxis reaction (AR) was the cause of SUD in three cases (10.7%). Our results imply that the main route for prevention of SUD in patients with malignancy is incorporation of measure against ischemic heart disease. In addition, a variety of mechanisms causing SUD as a complication of malignant neoplasms should be recognized, including AR. Accumulation of SUD cases is necessary to better understand the causes of SUD in patients with malignancy.     

Sudden unexpected death as a consequence of indinavir-induced nephropathy. A case report

A 60-year-old male had tested in 1986, at age 46, positive for human immunodeficiency virus (HIV). In mid-1996 he was started on a protease inhibitor regimen, which included indinavir, lamivudine and stavudine, and remained on this therapy until his death. In April 1999 he was hospitalized after a fainting episode. Although examination focusing on cardiac disease did not disclose any remarkable findings, he died suddenly one week after being discharged from hospital. At autopsy the kidneys were enlarged, with a total weight of 500 g, patchy pale gray and pinkish. Microscopy showed leukocytic cell casts in many of the tubules and collecting ducts. In many of these casts there were clefts left by crystals. In the interstitium, both in the cortex and the medulla, there was focal inflammation and fibrosis. Death was attributed to sudden cardiac dysfunction, probably ventricular fibrillation as a consequence of severe nephropathy with electrolyte disturbances. It is likely that kidney damage developed secondary to the indinavir treatment as indinavir can cause not only nephrolithiasis but also crystal-induced acute renal failure.     

Sudden cardiac death in younger adults: autopsy diagnosis as a tool for preventive medicine

Sudden death in children and younger adults can be caused by potentially heritable cardiovascular disorders, and the fatal outcome is often the first symptom in apparently healthy subjects. In these cases, a careful autopsy becomes the sole diagnostic tool to guide the clinical screening of the families. The aims of the present study were (1) to assess the pathological substrate of sudden cardiac death in children and younger adults (age, 1-40 years) in a large prospective series using strict morphological criteria; and (2) to perform cardiological assessment of the relatives of the deceased subjects with cardiomyopathies or structurally normal hearts, potentially consistent with a heritable cardiac disease. We studied 100 consecutive cases. Autopsy findings included coronary artery disease (30%, atherosclerotic in the majority of cases), cardiomyopathies (22%), and various cardiac abnormalities (28%). In the remaining 20% of cases, the presence of significant morphological abnormalities of the heart was ruled out. Twenty of 42 families in which the heart of the proband was either affected by a cardiomyopathy or failed to show significant structural abnormalities could be contacted and provided informed consent to cardiological assessment. A potentially inherited cardiac disease was diagnosed in 4 (20%). Molecular genetic analysis was restricted to 3 of these families and revealed a mutation in the ryanodine receptor type 2 gene (RyR2) in 1. Our results underline the implication of autopsy findings for relatives and the importance of cardiological screening of family members to uncover familial cardiomyopathies or genetic arrhythmias and to adopt the proper therapeutic and preventive strategies. Genetic testing is still time consuming and costly: accordingly, it should be restricted only to selected cases.     

Sudden and unexpected death in infancy and childhood due to pulmonary thromboembolism. An autopsy study

Because massive pulmonary thromboembolism is a rarely described cause of sudden and unexpected death in the pediatric age group, a 50-year retrospective review of autopsy cases at the Hospital for Sick Children, Toronto, Canada, was conducted to determine the local incidence and clinicopathologic features of such patients. Only 8 cases (0.05%) from a total of approximately 17,500 autopsies were found. The ages ranged from 1 month to 13 years and predisposing factors included recent surgery, congenital heart disease, in-dwelling venous catheters, sepsis, an arteriovenous malformation, occult malignancy, and prolonged immobility. This study confirms that pulmonary thromboembolism is a diagnosis that must be considered in cases of sudden and unexpected death in the pediatric age group. Its incidence, however, appears to be extremely low even in a relatively high-risk population.     

Mothers' representations of relationships with their children: relations with mother characteristics and feeding sensitivity

OBJECTIVE: To examine parenting representations and feeding interactions of mothers and their children with cerebral palsy (CP) and the extent to which mothers' representations predict their feeding behavior beyond other mother and child characteristics. METHODS: Fifty-eight mothers of children with mild to severe CP ages 16 to 52 months were interviewed with an adapted form of the Parent Development Interview (PDI). Correlation and regression analyses examined relations between representations (compliance with parental requests, achievement, secure base, enmeshment, worry about the child's future, and emotional pain), demographic characteristics, diagnostic severity, and developmental status. RESULTS: Mothers with more compliance-related concerns showed less sensitivity, acceptance, and delight during feeding. Mothers experiencing more emotional pain displayed more hostility. Mothers reporting worries about the child displayed sensitivity and delight. Representations of compliance-related experiences and worry about the child's future accounted for significant increments in explained variance in mothers' feeding behavior, after we controlled for children's skills and abilities. CONCLUSIONS: Findings suggest maternal representations of relationships are associated with caregiving behavior for mothers of children with CP apart from other child and maternal characteristics and may be a useful focus for research and practice related to parenting children with special needs.     

Sudden death of a young woman due to aortic dissection caused by Turner's syndrome

A 24-year-old woman was found dead in her bed. There had been an episode of fainting with cervicodynia 1 day before death but no significant past medical history, except for menstrual irregularities. Post-mortem examination revealed that death was due to hemopericardium caused by rupture of the ascending aorta by thoracic aortic dissection (Stanford type A). Microscopically, weakness of the aorta was due to cystic medial necrosis. On external examination, short stature, a short neck and multiple pigmented nevi were observed, while internal examination revealed coarctation of the aorta and funicular ovaries. Examination of the X chromatin showed a decrease in numbers of Barr bodies in the tissues, and a 45,X/46,XX mosaicism was suspected. It is concluded that the cause of death was aortic dissection due to Turner's syndrome.     

高血压性脑出血70例术后死亡原因分析

目的总结高血压脑出血（HCH）术后死亡的原因，探讨手术指征，选择合适的手术病例，降低死亡率。方法对70例HCH手术后死亡患者的临床资料进行回顾性分析，找出与死亡相关的主要因素。结果术前脑疝形成使中枢衰竭在1周内死亡者43例，其中双侧瞳孔散大30例，单侧瞳孔散大13例；各种并发症在2-3周内死亡者27例：肺部感染11例，上消化道出血6例，急性肾功能衰竭5例，多脏器功能衰竭3例，心功能衰竭1例，体液代谢紊乱1例。结论脑出血后脑疝形成及术后多脏器并发症是术后死亡的主要原因。脑血肿残腔再出血，恶性脑肿胀，营养衰竭是术后死亡的危险因素。及时手术减少术前脑疝形成，术后严格监测生命体征，稳定血压，早期对并发症预防性治疗及合理的营养支持是降低死亡率的关键。