Sudden cardiac death in hereditary hemochromatosis: an underestimated cause of death?

Hereditary hemochromatosis (HH) is a frequent autosomal recessive disease which causes iron-overload of various organs. Of all northern European affected individuals, 90–95% show 1 of 3 known point mutations in the HFE gene. Symptoms and organs involved can vary considerably: Only a small fraction of the 200,000–400,000 persons affected in Germany develop the classical picture of liver cirrhosis and/or pancreatic fibrosis. Nevertheless, the life expectancy of persons with moderate or even subclinical symptoms is reduced, in many cases due to myocardial damage leading to cardiomyopathy with greatly increased risk of sudden cardiac death. Although the high prevalence of HH suggests that sudden cardiac death due to cardiac HH is a relatively common cause of death, the forensic literature lacks such reports. We present the case of sudden cardiac death in a young man with histological findings of massive cardial hemochromatosis which is characterized by the fact that none of the three known mutations for HH were found. This case demonstrates that genetic screening alone might not be sufficient to identify all persons at risk to developing HH.     

“Excited delirium syndrome”: Is it a cause of death?

Excited delirium syndrome (EDS) has become a controversial and vexing forensic issue due to its association with restraint and sudden unexpected death. Although some authorities and jurisdictions recognised EDS as a cause of death there is no consensus among the medical community in this regard. The overlapping nature of the spectrum of antemortem behaviours and signs with many natural disease processes complicates this issue further. We describe two deaths which initially presented as EDS-like behaviour during restraint. In the first case, the deceased was travelling on a long distance flight when he died while in the custody of air cabin crew. The autopsy revealed the cause of death as air travel-related pulmonary thromboembolism. Acute alcoholic intoxication, nicotine withdrawal, hypoxia due to acute pulmonary thromboembolism, and hypobaric environment in the air plane cabin appeared as the potential reasons for EDS-like behaviour. In the second case, the deceased died while in the custody of immigration officials. At autopsy the cause of death turned out to be tense pericardial effusion due to fibrinous pericarditis. In this case, hypoperfusion of the brain following systemic hypotension as a result of cardiac tamponade associated with pericardial effusion likely led to the EDS-like behaviour. Clinicopathologic correlation in these two cases would strongly suggest EDS as the cause of death, had the decedents not had fatal anatomical causes of death. This alerts the forensic pathologist that not all the individuals dying with signs and symptoms of EDS during restraint are accounted for EDS as the immediate cause of death.     

Renal inflammatory myofibroblastic tumor: a rare tumor indistinguishable from renal cell carcinoma—report of two cases

Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated with nephrectomy on suspicion of malignancy.     

Intracerebral hemorrhage associated with Sneddon's syndrome: is ischemia-related angiogenesis the cause? Case report and review of the literature

Sneddon's syndrome is characterized by livedo reticularis and multiple ischemic infarcts often associated with antiphospholipid antibodies. Intracerebral hemorrhage (ICH) is unusual in Sneddon's syndrome and has not been reported as the presenting complaint. We report a 38-year-old woman with a history of two miscarriages, Raynaud's phenomenon and livedo reticularis who presented acutely with ICH. Angiography showed prominent leptomeningeal and transdural anastomoses (pseudoangiomatosis). Anticardiolipin antibodies were positive. A right frontal brain biopsy failed to reveal vasculitis and a skin biopsy was nonspecific. MRI showed residual intracerebral hemorrhage (ICH), diffuse atrophy, multiple small white matter infarcts and leptomeningeal enhancement. This is the first report of Sneddon's syndrome presenting with an ICH. It shares features with the Divry-van Bogaert syndrome. We discuss the cause of the pseudoangiomatosis pattern and its role in the genesis of the hemorrhage and suggest that cerebral angiography should be done in every patient with Sneddon's syndrome, as it could impact therapy.     

Sudden death from ischaemic heart disease in a female patient with Sjögren syndrome: a case report

Primary Sj?gren syndrome (SjS) has a comparatively good prognosis except when it is complicated by non-Hodgkin's lymphoma. We performed an autopsy on a young female patient with primary SjS who had died suddenly during a meal, and we discuss the relationship between primary SjS and the cause of death. Eosinophilic change of the cardiomyocytes and severe arteriolosclerosis were observed within the myocardium. In the conduction system, lymphocyte infiltration was detected in the bundle of His, in addition to arteriosclerosis in the sinoatrial node and atrioventricular node arteries. The cause of death was diagnosed as ischaemic heart disease induced by arteriolosclerosis: its development can probably be attributed mostly to primary SjS. It should thus be kept in mind that primary SjS can occasionally result in the development of cardiovascular complications, such as ischaemic heart disease, as well as systemic lupus erythematosus or rheumatoid arthritis.     

HELLP syndrome as a cause of unexpected rapid maternal death–A case report and review of the literature

Unexpected rapid death after delivery due to HELLP syndrome (HS) may become the subject of a forensic expertise. Since this syndrome is rarely encountered in forensic pathology, our objective was to point to some specific findings which might present forensic aspects of HS. These include unexpectedness, suddenness and fulminant course of this syndrome, which may confuse physicians, and on the other hand these characteristics cast doubt on violent injury, diagnostic oversights or iatrogenic injuries. Absence of classical signs of preeclampsia and non-specific clinical symptoms cause considerable differential diagnostic problems leading to a diagnostic delay or initial wrong non-obstetric diagnosis. A definitive postmortem diagnosis of HS in questionable cases of maternal death and consecutive forensic expertise of suspected medical malpractice should be based on accepted laboratory criteria and characteristic histopathological alterations.     

Change of heart: Reverse takotsubo's cardiomyopathy – A case report

Reverse takotsubo's cardiomyopathy is a rare and relatively unknown variant of takotsubo's cardiomyopathy, also known as stress cardiomyopathy or broken heart syndrome. There are significant differences in the patient age and clinical profiles between classic and reverse takotsubo's cardiomyopathy. Classic takotsubo's cardiomyopathy has been extensively described. However, the little described literature related to reverse takotsubo's cardiomyopathy is limited to the cardiology speciality, with a relative paucity described in radiology. We describe a case report of a 73 year-old female who was diagnosed with reverse takotsubo's cardiomyopathy on the basis of Cardiac MRI. Herein, we hope to bring more awareness of this condition and describe its features on MRI.     

Prolongation of the corrected QT complex--a cause of sudden cardiac death in the mountain environment?

In the mountain environment sudden cardiac death (SCD) has been shown to be responsible for the deaths of up to 52% of downhill skiers and 30% of hikers. The majority of SCD's are precipitated by a ventricular arrhythmia. Although most are likely to result from structural abnormalities associated with conditions such as ischaemic heart disease, a small but significant number may be due to abnormalities in ion channel activity, commonly known as, "channelopathies". Channelopathies have the potential to lengthen the time between ventricular depolarisation and repolarisation that can result in prolongation of the corrected QT interval (QTc) and episodes of polymorphic ventricular tachycardia (PVT) and eventually, ventricular fibrillation. This review examines the factors that prolong the QTc interval in the mountain environment and outlines a practical framework for preventing the life threatening arrhythmias that are associated with this condition.     

The role of histology in forensic autopsies: Is histological examination always necessary to determine a cause of death?

In England and Wales there is a conflict between the law and advice from regulatory bodies in relation to the sampling of human tissue for histological examination following medico-legal post-mortem examinations. Considering the results of previous publications, we performed a specific study to investigate the role of histology in determining the cause of death in cases at a forensic unit. A retrospective study of 500 adult forensic cases was performed. Cases were categorized by the role the histological examination played in determining a cause of death and its contributory factors. Furthermore, cause of death, manner of death, organ systems involved, and discrepancies were assessed. Of the 500 cases, histology was undertaken in 287 cases (58 %). Microscopic examination provided the cause of death in 2 % of cases where histology had been undertaken, and it added to the cause of death in 8 %. In 61 % of cases microscopy confirmed the macroscopic findings, and in 30 % it did not influence the medical cause of death. Histological examination of all organs in all forensic cases for the purpose of providing a medical cause of death is not supported. Practice guidance should be adjusted to reflect that, while histological examination is essential in certain circumstances, the decision to retain material for histology should be made on a case by case basis at the pathologist’s discretion.     

Case report: metastatic adamantinoma of the Tibia—an unusual presentation

A 26-year-old female with a tibial lesion diagnosed as an adamantinoma was treated with intra-lesional curettage, bone grafting and intra-medullary nailing. Six years post-surgery, she presented with an asymptomatic primary site but with a metastatic lesion in the mid-shaft of the ipsilateral femur and lung metastases. The femoral lesion was treated with wide excision and reconstructed with an allograft and plate fixation. Pulmonary metastatectomy was carried out for the lung lesions. A follow-up CT scan of the chest at 1 year after the surgery for the metastatic lesions revealed fresh unresectable bilateral metastases. Although cases of local recurrences and pulmonary metastases in adamantinoma are reported, this case is unusual in presenting without a local recurrence but with simultaneous skeletal and pulmonary metastases.     

Is horseshoe lung a component of VACTERL spectrum? Case report and review of literature

Horseshoe lung (HL) is a rare congenital anomaly that has been classically associated with Scimitar syndrome. Very few cases have been described in the context of the VACTERL spectrum. We present a case of a newborn girl with mesocardia, tracheoesophageal fistula, and imperforated anus, who required O2 support at birth and during hospitalization. A chest CT angiography revealed a HL as an incidental finding. We suspect that HL and the VACTERL spectrum, are not separated entities but likely a further expansion of VACTERL-associated symptoms. HL might be underdiagnosed in asymptomatic patients as Chest CT angiography is not part of the routine work up for patients with VACTERL association.     

Fatal diving: could it be an immersion pulmonary edema? Case report

International Journal of Legal Medicine - Immersion pulmonary edema is a rare, underrecognized, and potentially lethal pathology developing during scuba diving and other immersion-related...     

Epstein–Barr virus myocarditis as a cause of sudden death: two autopsy cases

Although the Epstein–Barr virus (EBV) causes acute infection accompanied by a high fever in young people, there appears to be few reports of a fatal outcome involving myocarditis. We report two cases of unexpected sudden death due to acute myocarditis possibly caused by the EBV. They each visited a hospital due to common cold-like symptoms and unexpectedly died several days later. In both cases, autopsy revealed myocardial necrosis with marked lymphocytic infiltration. Polymerase chain reaction (PCR) screening was positive for the EBV, whereas immunohistochemistry and in situ hybridization for the EBV were negative. Serological investigations showed a mild elevation in antiviral capsid antigen IgG and anti-EBV nuclear antigen IgG in both cases. Immunohistochemical study of lymphocytic infiltrates showed strong positivity for a T-cell marker (CD45R₀) in the myocardium and pharyngeal mucosa. These cases suggest the potential risk of mortality from acute EBV infection in young people, even without severe clinical manifestations, and the importance of microbiological investigations, including PCR procedures, in postmortem diagnosis of infectious diseases.     

Fentanyl: cause of death or incidental finding? Postmortem peripheral blood concentrations with and without documented transdermal patch use

We reviewed postmortem fentanyl cases to compare peripheral blood (PB) concentrations between deaths caused by fentanyl and deaths in which fentanyl was incidental. Furthermore, we describe PB concentrations in fentanyl-caused deaths with and without transdermal (TD) fentanyl use. Our review produced 20 cases with PB fentanyl. Of these, 13 were determined to be fentanyl-caused deaths. Eight of the 13 involved TD fentanyl. The remaining 7 cases were decedents undergoing therapy with fentanyl (TD, n = 3; intravenous, n = 4). In the 13 fentanyl-caused deaths, the mean PB fentanyl level was 30.1 ng/ml. In the deaths involving TD fentanyl use, the mean fentanyl level was 41.7 ng/ml. Deaths without TD fentanyl use had a mean fentanyl level of 21.3 ng/ml. There were 7 other cases with incidental fentanyl. In 3 of these, therapeutic TD fentanyl was used and the mean PB concentration was 16.6 ng/ml. In the remaining 4 deaths in which therapeutic intravenous fentanyl was employed, the mean PB fentanyl level was 8.1 ng/ml. Our review suggests that a PB fentanyl concentration equal to or greater than 25 ng/ml indicates that fentanyl should be considered as being contributory to or the cause of death. However, ranges of measured PB concentrations are once again shown to overlap between subjects who overdose and those who use fentanyl as prescribed. In addition, fentanyl-caused deaths involving TD fentanyl exposure have higher PB fentanyl concentrations than those who did not use transdermal patches. Although enlightening, our study suggests that further evaluation of fentanyl concentration variability among different postmortem blood specimens is needed.     

Pilots with vasovagal syncope: fit to fly?

Two pilots who had experienced vasovagal syncope were grounded by the aeromedical service. Pilot A had experienced three episodes of syncope in medical settings, none during flight. Pilot B had experienced four episodes of syncope in emotional/medical settings, one during flight. Whether a pilot who experienced one or more episodes of vasovagal syncope is declared fit to fly now depends on the number of episodes experienced. We propose that pilots should be assessed individually. Certainty of the diagnosis of vasovagal syncope, the chance and predictability of recurrences during flight, and the possibility of effective therapy should be assessed. Chance of recurrence during flight is low when the triggering factor is known and avoidable. Pilots with syncopal episodes in predictable (e.g., medical) situations, with clear prodromal symptoms and/or effective therapy, should be declared fit to fly. A symptom-free period and/or restriction to fly 'as or with a co-pilot' can be considered.     

Malignant transformation of a Hürthle cell tumor: case report and survey of the literature

Hürthle cell carcinoma is a relatively uncommon type of well-differentiated thyroid carcinoma. Its diagnosis has been controversial due to the difficulty in separating Hürthle cell adenoma from Hürthle cell carcinoma, thus the term Hürthle cell tumor is often used to describe both lesions. The present case of anaplastic giant-cell carcinoma in an 81-yr-old woman arose in a Hürthle cell tumor. This case illustrates the propensity of Hürthle cell tumor to undergo "malignant transformation" and argues for a more aggressive approach to such tumors.