Mechanisms of unexpected death in tuberous sclerosis

Tuberous sclerosis complex is a protean autosomal dominant disorder characterized by multifocal tissue lesions arising from defects in cellular migration, proliferation, and differentiation. It has an association with sudden death. In the current study, review of all cases of sudden death due to tuberous sclerosis was undertaken at the Forensic Science Centre in Adelaide, Australia from 1991 to 2001, in addition to an analysis of cases from the literature. There were two local cases where unexpected death had occurred in individuals with known tuberous sclerosis, involving a 31-year-old male (epilepsy), and a 24-year-old female (massive hemorrhage into a renal angiomyolipoma). Fatal mechanisms in cases of tuberous sclerosis may be associated with underlying cardiovascular, renal and cerebral abnormalities. Sudden death may be due to cardiac arrhythmia, epilepsy, and intra-tumoral hemorrhage with additional complications including cardiac outflow obstruction, obstructive hydrocephalus, aneurysm rupture, and spontaneous pneumothorax. An awareness of the highly variable tissue manifestations of tuberous sclerosis and the mechanisms that may be responsible for death is necessary to establish correctly the diagnosis in occult cases (possibly with molecular confirmation), and to chart accurately organ changes in individuals with established disease.     

Unexpected infant death attributable to cardiac tumor or cardiomyopathy. Immunohistochemical and electron microscopical findings in three cases

The pathological findings, including immunohistochemical and electron microscopical findings, in three infants who died unexpectedly of cardiac tumor or cardiomyopathy are reported. The first was a 13-month-old boy with tuberous sclerosis and multiple rhabdomyomas of the heart, who presented with a postpartal cardiac murmur and moderate cardiomegaly. The further history was unknown. The rhabdomyoma nodules were composed of spider cells containing small amounts of desmin and myosin as well as isolated myofibrils. Microscopically small glioma nodules contained high amounts of GFAP. The second case, a boy 4 months of age, died of a large benign fibrous histiocytoma of the heart after an uneventful history. Tumor cells contained alpha-1-anti-chymotrypsin and lysozyme. The third case, a girl 2 months of age, died unexpectedly of histiocytoid cardiomyopathy. The affected cells contained fat droplets, glycogen granules, many leptomer myofibrils and small amounts of myosin and desmin.     

Morphometrische Untersuchungen bei stenosierender Koronarsklerose und ihre Bedeutung für die Bewertung konkurrierender Todesursachen

Coronary sclerosis is generally supposed to be the most important factor for coronary thrombosis, myocardial infarction and coronary heart death. Stenosing coronary sclerosis may be postmortally documented by angiography and morphometry. It is possible to obtain sufficient morphological data to suggest acute cardiac insufficiency, if the maximum grade of stenoses as a functional parameter and the heart weight are regarded in addition to the quantitative results of the three main branches of the coronary arteries (lumen and intima areas).Generally the cardiac results of autopsy are used individually and subjectively for the explanation of the cause of death. The conclusiveness of these results of autopsy depends on the circumstances of death and the existence of further pathological findings. Competing causes of death may exist in the form of illnesses, injuries, alcoholic and drug effects, physical strain and emotional stress or medical provisions. The quantitative valuation of the cardiac findings with a critical limit for an acute coronary death permits a more exact interpretation of such competing causes of death. This method of examination may also reveal an unpresumed competing cause of death, for example an intoxication. This was demonstrated by four autopsy cases.     

An Analysis of Possible Mechanisms of Unexpected Death Occurring in Hydatid Disease (Echinococcosis)

Abstract:  Most cases of hydatid disease in human populations are due to Echinococcus granulosus. The hydatid life cycle involves passage between definitive hosts such as dogs and intermediate hosts such as sheep. Humans become accidental intermediate hosts following ingestion of food or water contaminated with eggs or by contact with infected dogs. Although hydatid disease may remain asymptomatic, occasional cases of sudden and unexpected death present to autopsy. Causes of rapid clinical decline involve a wide range of mechanisms including anaphylaxis (with or without cyst rupture), cardiac outflow obstruction or conduction tract disturbance, pulmonary and cerebral embolism, pericarditis, cardiac tamponade, myocardial ischemia, pulmonary hypertension, peritonitis, hollow organ perforation, intracerebral mass effect, obstructive hydrocephalus, seizures, cerebral ischemia/infarction, and pregnancy complications. The autopsy assessment of cases therefore requires careful examination of all organ systems for characteristic cystic lesions, as multiorgan involvement is common, with integration of findings so that possible mechanisms of death can be determined. Measurement of serum tryptase and specific IgE levels should be undertaken for possible anaphylaxis.     

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).     

Hemoperitoneum due to rupture of a subserosal vein overlying a uterine leiomyoma

Uterine leiomyoma is the most common tumor in women of reproductive age, but rarely does it lead to fatal hemoperitoneum. We present an autopsy case in which the cause of death was massive hemoperitoneum due to rupture of a subserosal vein overlying a uterine leiomyoma. We report the case of a 28-year-old Japanese woman who had tuberous sclerosis and was gravida 0, para 0. She had a uterine leiomyoma leading to dysmenorrhea. Autopsy revealed a pinhole-sized rupture of a subserosal vein superficial to the leiomyoma that resulted in fatal hemoperitoneum. Rupture of a subserosal vein overlying a uterine leiomyoma may cause sudden and unexpected death.     

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 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.     

Unsuspected hereditary hemochromatosis at forensic autopsy: its presentation, confirmation, and implications

Hereditary hemochromatosis (HH) is one of the most common genetic disorders and may present clinically in a variety of ways. The most common presentation is micronodular cirrhosis with possible associated diabetes. However, HH may also present with cardiac dysfunction and sudden death. The confirmation of unsuspected HH at autopsy is complicated by the growing number of genetic abnormalities, which are not detected by current commercial genetic testing for C282Y and H63D mutations. Consequently, quantitative liver iron studies on fresh or paraffin embedded liver is recommended in confirming HH. The importance of detection and confirmation of HH cannot be overemphasized given the need to screen surviving family members in preventing organ damage of asymptomatic individuals. We present a case of a 38-year-old white woman with micronodular cirrhosis secondary to unsuspected HH that was confirmed by a quantitative liver iron study. The possible presentation of cardiac sudden death from HH, confirmation issues and implications of a HH diagnosis for surviving family members are also discussed.     

实验性心脏震荡的法医病理学研究

本研究应用可产生稳定打击速度并可同时测定瞬间冲击速度及冲击力大小的机械式弹性拉力打击器，分别以６．７ｍ／ｓ及８．０ｍ／ｓ速度冲击大胸骨部心前区建立了心脏震荡动物模型，在左右心室压力及心电图监测下冲击后６０分钟进行尸体剖验检查，并应用多种组织化学染色、透射电镜技术、免疫组织化学染色以及硝酸镧示踪电镜技术对心肌组织学行系统性研究。结果表明：１．心前区受冲击瞬间左右心室内压力急骤升高，随即可恢复至正常水平。心电图在冲击后即刻表现为持续短暂的异常心律，逐渐恢复至正常心律。２．心脏血管麻痹性扩张，但宏观及微观均无损伤性所见。３．心肌超微结构有一定程度损害，心肝细胞膜破裂或通透性增高。本研究提示：心脏震荡者心脏宏观、微观无特殊改变，但超结构及心肌细胞膜轻度损害。     

Fatal hyperthermia in hot baths in individuals with multiple sclerosis

The authors report the case of a 47-year-old black man with a history of multiple sclerosis who was found dead in a bathtub, head above water, with a body temperature of 105.7 F. Results of a complete autopsy and toxicologic screen were negative. Individuals with multiple sclerosis, if immersed in hot water, develop motor weakness, which may be so severe as to prevent them from getting out of the water, whether they be in a bathtub or whirlpool bath. In this case, the individual was trapped in a bathtub in which there was a continuous flow of hot water. This overwhelmed an already impaired thermoregulatory mechanism, causing hyperthermia and death.     

A rapid postmortem cardiac troponin T assay: laboratory evidence of sudden cardiac death

Postmortem examination may be useful in establishing the cause of sudden unexpected death. In many instances, however, limitations of staffing, budget, and time may force the pathologist to triage cases to external examination rather than autopsy. A rapid assay for cardiac troponin T (cTnT) to document suspected cardiac-related deaths may optimize the use of the time and resources of the autopsy pathologist. Peripheral blood was sampled percutaneously before each of 40 autopsies and placed in the well of the Cardiac T Rapid Assay unit in accordance with the included instructions, and the results were read after 15 minutes. The assay result, decedent age, postmortem interval, and evidence of cardiopulmonary resuscitation were tabulated and subsequently correlated with the cause of death. On final sign-out of each of the autopsies, the cause of death was determined to be cardiac-related (n = 20) versus the cause in non-cardiac control subjects (n = 20). This determination was made while the investigators were blinded to the cTnT assay result. Of the 20 cardiac deaths, 17 (85%) showed positive results for cTnT compared with 6 (30%) false-positive results among the 20 control cases; this result was statistically significant according to the chi-square test. In the over-50 age group, the sensitivity of this assay in detecting cardiac-related death was 91%, with a specificity of 86%. Perimortem cardiopulmonary resuscitation did not appear to result in false-positive results. In the appropriate setting, this rapid assay for cTnT can provide valuable data supportive of a cardiac-related death. This inexpensive test may best be used in triaging sudden deaths in persons over 50 to external examination versus complete autopsy.     

Cardiac pathology in 470 consecutive forensic autopsies

Cardiovascular disease continues to be the single most common generic cause of sudden and unexpected deaths. Atherosclerotic coronary heart disease and acute myocardial infarction are the most prevalent forms of fatal cardiac disease observed at autopsy. Other cardiac lesions are frequently listed as causes of death, but the prevalence of such lesions as incidental findings in the general population is unknown. In this study, 470 consecutive forensic autopsies were evaluated for minor and major anomalies. The most frequently observed major congenital finding was floppy mitral valve (5%). Tunneled coronary arteries, considered minor congenital findings, were seen in 29%. Atherosclerotic coronary heart disease was the most common major acquired finding, observed in 16% of cases. Of the 470 hearts, only 8% were considered normal.     

Sudden unexpected death from cardiac concussion (commotio cordis) with unusual legal complications

Sudden and unexpected death may result from cardiac concussion following blunt force trauma to the thorax. Undiagnosed pathologic disease must be carefully evaluated as a possible contributory element. Legal complications may arise from any autopsy. It is recommended that a photograph be taken upon completion of the autopsy. This photograph and adequate records can be used to refute any charges against the pathologist or assistants for the poor condition of a body after its release.     

Forensic dermatopathology and internal disease

The gross and microscopic analysis of skin lesions at autopsy can help the pathologist understand diseases and injuries inflicted premortem, perimortem, or postmortem. From January 2003 to January 2004, skin findings at autopsy were closely examined by a dermatologist and sampled for microscopic analysis at the Southwestern Institute of Forensic Sciences. Dermatologic abnormalities in some of these cases led to the discovery of internal disease and allowed for a more complete understanding of the pathologic disease processes affecting the individual. We present four autopsy cases with skin manifestations of internal disease, including pseudoxanthoma elasticum, calciphylaxis, the sign of Leser Trelat, and papular mucinosis, and demonstrate the usefulness of the dermatological assessment at autopsy. In all cases, discovery of these skin lesions and internal disease manifestations allowed contributing factors to the death of the individual to be uncovered.     

Forensic usefulness of the silicone rubber cast of the cardiac vessels

Adequate examination of the coronary arteries at forensic autopsy is often difficult. No matter whether the arteries are opened longitudinally or transversely, each method has its disadvantages. A technique making silicone rubber casts of the cardiac vessels providing simultaneous angiography is described. The method allows the three-dimensional precise assessment of stenotic lesions of the coronary arteries. It is concluded that the method examined could be useful for the forensic problems.     

Complete Cardiac Rupture Associated with Closed Chest Cardiac Massage: Case Report and Review of the Literature

Chest skeletal injuries are the most frequent complications of external chest massage (ECM) during cardiopulmonary resuscitation, but heart and great vessels lacerations that are indeed very rare. We report the case of a 35‐year‐old workman who collapsed and underwent ECM by his co‐workers for almost 30 min. At autopsy, no external injuries, fractures or bruises of the ribs or sternum, were observed. A hemopericardium with a rupture of the heart was found, with no signs of pre‐existent cardiac disease. Bruises of thoracic aortic wall, lung petechiae, a contusion of the liver, and bruises of lumbar muscles were found. The cause of death was due to sudden cardiac death with an extensive cardiac rupture. This is an unusual report of massive heart damage without any skeletal or muscle chest injuries, secondary to cardiopulmonary resuscitation. This kind of cardiac lesions may be considered when thoracic–abdominal trauma, or medical history, is unclear.     

Heart valve tissue donation does not preclude the diagnosis of clinically significant pediatric cardiac abnormalities

Medical examiners/coroners often have the responsibility of deciding whether to allow organ and tissue donation to proceed in cases under their jurisdiction. A 10-year retrospective study was conducted of autopsy cases in children younger than 6 years to determine whether the donation of cardiac valve tissue would preclude the diagnosis of clinically significant pediatric cardiac abnormalities. Only 1 case (0.1%) was found in the entire 10-year period in which valve tissue donation might have prevented the correct diagnosis. According to the results of the study, (1) most cardiac findings in forensic pediatric autopsies are not clinically significant; (2) clinically significant findings will be diagnosed in properly examined hearts, even those processed for valve tissue donation, and special studies will remain possible in nearly all hearts except those with suspicion of conduction defects; and (3) as long as there is good communication between forensic pathologists and organ and tissue procurement organizations, the concern of failing to diagnose significant cardiac findings should not inhibit medical examiners/coroners from allowing the donation of pediatric cardiac valve tissue.     

Fatal hyperthermia secondary to sunbathing in a patient with multiple sclerosis

A 27-year-old white woman with a history of multiple sclerosis was found dead lying on a lounger, clad in a bathing suit. She had been sunbathing for 4 hours. Significant autopsy findings consisted of numerous variably sized demyelinated plaques involving the periventricular cerebral white matter and cerebellum. Elevation of core temperature in patients with multiple sclerosis leading to transient or permanent adverse neurologic signs and symptoms has been documented for more than 60 years. This case illustrates that a modestly increased core body temperature, even from a usually innocuous activity such as sunbathing, may be fatal in patients with multiple sclerosis.