Comparison of heart mass in seizure patients dying of sudden unexplained death in epilepsy to sudden death due to some other cause

Proposed mechanisms by which sudden unexplained death syndrome in epilepsy (SUDEP) occurs include cardiac dysrhythmias. We hypothesized that individuals dying of SUDEP would have enlarged hearts compared with normal, increasing the risk of sudden cardiac death should the autonomic nervous system initiate a dysrhythmia. We performed a retrospective case-control study in a medical examiner population, comparing the mean heart mass in a group of individuals who died of SUDEP to a group of individuals with epilepsy who died suddenly due to some unrelated cause (non-SUDEP). We found no significant difference in the mean heart mass between the 2 groups when analyzing the unadjusted data. Upon stratifying the cases by age, however, we found a significant reduction in the frequency of SUDEP in individuals 40 or more years of age with an increased heart mass compared with those younger. This reduced frequency disappeared when cases where the cause of death was indeterminate between SUDEP and heart disease were reclassified from non-SUDEP to SUDEP. With increasing age, the likelihood of finding a cause of death that competes with the possibility of SUDEP increases, making SUDEP appear to be a phenomenon of the young. The inclusion of seizure deaths evaluated in a medical examiner office in studies of SUDEP would provide the benefit of a more certain diagnosis in each given case. Moreover, the inclusion of cases from the medical examiner population would stem attrition in a clinical study due to loss to follow-up.     

Sudden unexpected death in epilepsy: neuropathologic findings

Sudden unexpected death in epilepsy refers to sudden death of an individual with a clinical history of epilepsy, in whom a postmortem examination fails to uncover a gross anatomic, toxicologic, or environmental cause of death. Evidence of terminal seizure activity may not be present. One to two percent of natural deaths certified by the medicolegal death investigator are attributed to epilepsy. Detailed microscopic examination of the brain has increasingly afforded the identification of structural changes representative of epileptogenic foci. The authors present 70 cases of death attributed to sudden unexpected death in epilepsy. These cases were classified as follows: individuals who lacked a gross brain lesion, those who had a brain lesion demonstrable at autopsy, and those who lacked neuropathologic evaluation because of decomposition or because only an external examination was done. All of the subjects had a clinical history of seizures. The authors confirm that various microscopic findings, including neuronal clusters, increased perivascular oligodendroglia, gliosis, cystic gliotic lesions, decreased myelin, cerebellar Bergmann's gliosis, and folial atrophy, are present in a higher percentage of the brains of sudden unexpected death in epilepsy subjects than in the brains of age- and sex-matched control subjects.     

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。     

Tongue bite injuries--a diagnostic criterium for death in epileptic seizure?

Bite marks of the tongue are often associated with epileptic seizures, although information about the real frequency of bite marks of the tongue is hard to find. This is also true for their presence in deaths of epileptics or in deaths in general. The purpose of this investigation was to analyze the frequency of bite marks of the tongue in deaths of epileptics in comparison to a control group. Further points of interest were the spectrum of the causes of death recorded, toxicological data as well as the presence and localization of external head injuries. The study group consisted of 105 individuals with a known history of epilepsy, the control group of 107 individuals with sudden cardiac death. Autopsy reports were analyzed retrospectively. In the first group bite marks of the tongue were seen in 21% (in the subgroup "observed death during seizure" even in 64%) and were thus significantly more frequent than in the control group (2%). In 35 cases of the study material an unnatural manner of death was found (trauma, especially craniocerebral trauma, drowning, asphyxia, intoxication) and in 70 cases a natural death was assumed. However, in 41 of these the exact cause of death was not ascertainable. According to the SUDEP criteria (Ficker 2000, Nilsson 1999) 29 of these cases could be categorized as possible or probable SUDEP (sudden unexpected death in epilepsy) with 17 showing bite marks of the tongue. The fact that half of the remaining 12 cases showed bite marks of the tongue suggests at least for these cases that death occurred during the seizure. Head injuries were reported in 41% of the epilepsy group--in the subgroup "observed death during seizure" in 73%. Our investigation did not produce evidence for a higher frequency of bite marks of the tongue in cases in which resuscitation had been attempted. In our experience the presence of fresh bite marks of the tongue--according to histological findings--is a useful signs for the assignment of death to an epileptic seizure and especially for death during acute convulsion.     

The role of environmental factors in the causation of sudden death in infants: two cases of sudden unexpected death in two unrelated infants who were cared for by the same babysitter

We report two cases of sudden unexpected death in two unrelated African American female infants, 2 months and 4 months old. Both infants were attended to by the same babysitter in the same apartment and died 39 days apart in the same bed and in the same bedroom. The autopsy of the first infant revealed sudden unexplained death in an infant. Toxicologic analysis for carbon monoxide (CO) was not performed because it was not suspected. When the second infant died, investigation into the ambient air quality within the apartment revealed high levels of CO emanating from a poorly ventilated and defective hot water heater, which was located across a hallway from the bedroom where the two babies died. CO saturation levels in the postmortem blood samples of the two babies were elevated and were similar (13% and 14%). Nicotine and cotinine were not detected in the blood sample of the two infants. Cherry-red livor mortis was absent. Acute CO intoxication was determined to be the underlying cause of these two unexpected deaths. These two cases underscore the need to integrate ambient air analysis and postmortem CO analysis as routine components of the comprehensive death investigation of infants who die suddenly and unexpectedly.     

免疫正常人和过敏性猝死者类胰蛋白酶含量测定

目的观察免疫正常人和过敏性猝死者血清类胰蛋白酶、IgE含量及类胰蛋白酶在咽喉、肺和小肠组织的表达,探讨过敏性猝死的诊断方法。方法采用荧光酶联免疫法（FEIA）测定115例正常人和6例过敏性猝死者血清类胰蛋白酶;采用酶联免疫吸附试验（ELISA）测定7例过敏性猝死者血清IgE含量;采用免疫组织化学方法观察15例过敏性猝死者咽喉、肺、小肠组织中类胰蛋白酶的表达,并采用BL-2000病理图像分析系统进行定量分析。结果①115例免疫正常人血清中类胰蛋白酶含量在0.80μg/L～8.86μg/L之间,性别之间无明显差异（P〉0.05）。20岁以下、21～40岁和41～60岁组之间血清中类胰蛋白酶含量无明显差别（P〉0.05）,而60岁以上组含量高于其他年龄组（P〈0.05）;②6例过敏性猝死者血清类胰蛋白酶含量均高于免疫正常人;③7例过敏性猝死者中有6例血清IgE水平高于正常值（〉333U/mL）;④过敏性猝死者咽喉、肺和小肠组织中类胰蛋白酶表达升高,与对照组之间有显著性差异（P〈0.01）。结论过敏性猝死者血清IgE、类胰蛋白酶含量及咽喉、肺和小肠组织类胰蛋白酶表达升高,可对敏性猝死的诊断有一定参考价值。     

Sudden Death Due to Undiagnosed Rheumatic Heart Disease in a Child

We report the case of a 5‐year‐old boy who died from complications of rheumatic heart disease with atypical presentation. He was hospitalized for recent inflammatory and neurological symptoms. He was diagnosed with viral encephalitis. He died the day after he was discharged. The macroscopic autopsy findings were unremarkable. Histology revealed typical rheumatic heart disease. Neuropathology showed cerebral infarction due to an embolic event linked with the rheumatic valvulitis. The cause of death was determined as heart failure due to rheumatic heart disease secondary to an undiagnosed acute rheumatic fever. It is related to an autoimmune response to infection with group A streptococcus. It mainly affects children in developing countries. In our case, viral encephalitis was consistent with the medical history and the proper diagnosis was made on histological analysis. Forensic pathologists should consider this diagnosis facing a sudden unexpected death in childhood, even in industrialized countries.     

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.     

Histomorphometric characteristic of human brain in acute alcoholic intoxication

Different brain sections were studied in 20 subjects, who died of ethanol intoxication and in 14 subjects who died of injuries of the heart and main vessels, in order to detect histological changes in the brain and for the purpose of defining spatial and quantitative ratios between cerebral tissue structures in alcoholic intoxication. Different histological, stereometric and morphometric tools were made use of. It was demonstrated that, in alcoholic intoxication, there occur severe disorders of the circulation with affection of vessels in the brain; there are also dystrophic and necrotic changes in neurocytes, glial cells and white substance. The square of neurons shrinks due to death of some of them in the cortex of hemispheres, thalamus and cerebellum. As for the medulla, they are more resistant, there, to ethanol. The diameter of capillaries in the studied brain sections diminishes due to a reduced tonus of cerebral arteries; the quantity of such vessels increases within a standard area, which is conditioned by the compensatory opening of reserve capillaries. All this can be important in dealing with issues of thanatogenesis and of forensic medical diagnosis in death of alcoholic intoxication.     

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.     

Traumatic venous aneurysm of the popliteal vein with outcome: a case report and review of the literature.

A case of sudden death due to recurrent pulmonary thromboembolism is described. The fatality took place three and a half weeks following blunt trauma to the left popliteal region. The patient died unexpectedly. Autopsy revealed the source of the emboli as a sacciform venous aneurysm of the popliteal vein, an entity seldom described, but important to consider in cases of soft tissue popliteal masses or unexplained pulmonary embolism, especially in otherwise healthy individuals.     

Barrett esophagus and unexpected death

Barrett esophagus is characterized by the presence of columnar mucosa in the lower esophagus in continuity with gastric mucosa. Complications include ulceration and adenocarcinoma. Although sudden and unexpected death is not a usual outcome, the case of a 63-year-old man is presented who died unexpectedly following perforation of an ulcerated Barrett esophagus, with development of an esophagopleural fistula. Sudden and/or unexpected death in individuals with Barrett esophagus may result from hemorrhage due to erosion into mural vessels, the aorta or heart, or from penetration into the pleural space, trachea, bronchi, and pericardial sac, with the development of tension pyopneumothorax, bronchial fistula, and mediastinitis. Ulceration of the lower esophagus at autopsy should prompt consideration of the possibility of a Barrett esophagus and initiate careful dissection/examination of the surrounding mediastinal tissues and vessels.     

An autopsy case of intraoperative death due to pulmonary fat embolism—possibly caused by release of tourniquet after multiple muscle-release and tenotomy of the bilateral lower limbs

We report a case of a juvenile male with muscle rigidity caused by cerebral palsy who experienced intraoperative sudden death due to pulmonary fat embolism after multiple muscle-release and tenotomy of the bilateral lower limbs. Data were obtained through review of the surgical and anesthesia records, as well as from autopsy and histopathological examination. All surgical procedures were performed within the same operation, beginning with the right lower limb and then proceeding with the left lower limb, with application of a pneumatic tourniquet to avoid intraoperative hemorrhage. Slight changes in the hemodynamics were noticed after release of the right tourniquet. Further, sudden onset of hypotension, severe bradycardia, and a marked decrease in percutaneously monitored oxygen saturation occurred just after release of the left tourniquet when the left limb was raised for casting. The patient died despite immediate and vigorous cardiopulmonary resuscitation. At autopsy performed 20 h after death, examination of the lungs revealed a pale surface, slight edema, and obvious fat droplets in the vessels at the cut surfaces. Histopathological examination with fat staining was notable for the presence of pulmonary fat embolism. These results suggest that restoration of venous return after removal of the tourniquet combined with massive fat embolism from dead spaces was the likely cause of death.     

Failure to detect elevated levels of carboxyhemoglobin in infants dying from SIDS

Carboxyhemoglobin (COHb) levels were determined in stored blood samples from 91 infants diagnosed to have died from the sudden infant death syndrome (SIDS) (0.59+/-0.41%, excluding one outlying value of 10.83%); 48 age-matched controls (0.53+/-0.38%); and three individuals who died from fire related causes (41+/-20%). No statistical differences in COHb levels were detected between blood from SIDS and control infants (p = 0.43).     

Subaortic Pseudoaneurysm of the Left Ventricle Complicating Staphyloccal Endocarditis*

Abstract: Subaortic pseudoaneurysms are rare but can be a cause of sudden death in young individuals. This case report involves a 20‐year‐old Vietnamese male who died suddenly from rupture of a subaortic pseudoaneurysm with resultant hemopericardium with tamponade. He had a history of bicuspid aortic valve with recent but healed Staphylococcal endocarditis. A review of the literature reveals few similar cases and enlightens the association between aortic bicuspid valve, endocarditis, and subvalvular aortic aneurysm. The pathogenesis as well as recent studies that identified aneurysm predisposing genes in patients with bicuspid aortic valve will be discussed.     

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.     

Brain arteriovenous malformation and its implication in forensic pathology

Despite the fact that brain arteriovenous malformations (BAVMs) are a possible cause of sudden and unexplained death, very few papers have discussed their importance in the forensic context. BAVMs consist of tangled masses of tortuous arteries and veins devoid of intervening capillaries that frequently extend from brain parenchyma into the subarachnoid space. Apart from BAVMs, three major groups of vascular malformations of the brain are known: cavernous hemangioma, venous angioma, and capillary telangiectasia. BAVMs and cavernous hemangioma often cause hemorrhages, while venous angioma and capillary telangiectasia are typically asymptomatic. Presented here is the case of a 14-year-old girl who died from a ruptured BAVM. The present case is a reminder that the forensic pathologist should be able to recognize BAVMs and to differentiate it from other types of vascular malformations. Although rare, it is a cause of sudden death not to be overlooked, especially in children.     

Evaluation of sudden death in epilepsy

Records of the Office of the Chief Medical Examiner of the State of Maryland were reviewed for all cases of natural deaths due to epilepsy occurring in 1981 and 1982. Cases involving unclear seizure history, alcoholism, or other superimposed disorders were excluded. Twenty-nine cases were accepted and analyzed with respect to age, race, sex, circumstances of death, neuropathology, and anticonvulsant therapy. Most cases involved black males, the median age at death was 26 years, and the vast majority died in bed or in the bedroom. Less than half of these individuals had neuropathological lesions. Most had detectable levels of anticonvulsants in post-mortem blood; more than half the decedents with detectable levels of phenobarbital showed therapeutic levels of this drug.     

急性心肌缺血猝死心肌中血红素加氧酶-1的表达

目的观察血红素加氧酶-1（HO-1）在急性心肌缺血猝死心肌细胞胞浆中的表达情况。方法应用免疫组织化学技术（SP法）,对27例可疑早期心肌缺血猝死（早期梗死组）、10例心肌梗死猝死（心肌梗死组）、11例冠心病非心性猝死（对照组1）以及10例正常心肌（对照组2）中HO-1的表达进行观察分析。结果早期梗死组与心肌梗死组在心肌细胞胞浆中HO-1均呈强阳性表达,对照组1和对照组2心肌细胞胞浆中HO-1弱阳性表达或无表达。早期梗死组和心肌梗死组与对照组1和对照组2之间心肌细胞内HO-1表达的差异有显著性意义（P（0.01）;镜下各组心肌细胞胞浆内HO-1表达的阳性面积率及平均光密度差别明显。结论 HO-1可以作为急性心肌缺血所致心性猝死的一个诊断指标。     

Three unusual neuropathologic-related causes of sudden death

We discuss the autopsy findings of three medico-legal cases of sudden death associated with uncommon neuropathologic findings of which the general forensic pathologist may not be familiar. Case 1 was a 43-year-old man who died of a seizure due to malignant melanoma of the temporal lobe associated with neurocutaneous melanosis (NCM). Case 2 was a 57-year-old woman with a history of mental retardation and incoordination because of chronic lead poisoning, who died of a pulmonary thromboembolism due to deep venous thrombosis status post left leg fracture after a fall down a staircase. Autopsy revealed atrophy and gliosis of her cerebellum as a result of childhood lead poisoning. The third patient was a 75-year-old woman who died as a result of acute bacterial leptomeningitis at the cervico-medullary junction with acute inflammation of the connective tissue of her upper cervical spinal column associated with subluxation of her atlantoaxial (AA) joint, also known as Grisel's syndrome.