Deaths related to stroke and cerebrovascular disease

Cerebrovascular disease is a common cause of death and the general histopathologist will often be responsible for the post mortem examination of stroke-related death. The pathological findings vary depending on the type of stroke, its location and aetiology. The underlying pathology is variable and includes atherosclerosis, cardiogenic embolism and small vessel disease alongside many rarer causes. The adequate post mortem examination of stroke is essential to usefully inform clinical teams, coronial services and relatives and requires proper preparation, familiarity with the range of underlying pathological processes, careful gross examination and judicious use of histology.     

Use of post-mortem computed tomography during the COVID-19 pandemic

Post mortem computed tomography (PMCT) is widely used in England and Wales to supplement or replace traditional invasive Coroner's autopsy. Using PMCT and coronary angiography, the cause of death can be determined without invasive examination in approximately 70% of cases, assuming a typical Coroner's autopsy case mix. Coroner's autopsy services continued during the COVID-19 pandemic and have identified deaths resulting from COVID-19 undiagnosed in life. In some areas of England, PMCT was used to replace traditional autopsy due to concerns over infection risk to mortuary staff associated with invasive autopsy. Health and safety concerns also resulted in changes to post mortem scanning protocols. PMCT has been used to identify potential COVID-19 deaths and assist in the selection of cases for viral studies. There is typically bilateral ground-glass opacities and consolidation within the lungs on CT; although these changes are not specific for COVID-19, the diagnosis can be confirmed with post mortem nose and throat swabs.     

Cardiac implantable electronic devices: what the pathologist needs to know

Cardiac implantable electronic devices include implantable loop recorders, pacemakers and implantable cardioverter defibrillators. The prevalence of these devices is increasing and they are therefore increasingly likely to be encountered at post mortem. This review will provide an overview of the different types of device, including their indications, their normal form and function, as well as the complications, both procedural and longer term, that are associated with them. An understanding of these devices will facilitate a greater understanding of the underlying disease processes affecting the patient, and which may have contributed to their death. Interrogation of the device itself may also provide clarity on cause of death for a large proportion of patients where post mortem examination alone has failed to do so.     

The pathology of cot deaths.

An examination of the pathological features of 12 consecutive cases of sudden death in infancy was undertaken with particular reference to the lung changes used a combined radiological and pathological study of formalin vapour-inflated lungs. Certain common features in the cases in which there are no post mortem changes to explain death (typical cot deaths) are described and compared with cases with an acceptable cause of death and with control cases. It was concluded that severe dehydration is a potentially avoidable factor underlying cot deaths and many other sudden infant deaths with no explainable causes; that petechial haemorrhages are a constant feature of cot deaths and indicate a respiratory/hypoxic mode of death; that absence of petechiae indicates some other explanation for death. It is suggested that the minor respiratory or other infections which are usually present at autopsy in cot deaths may sometimes exaggerate a preexisting state of dehydration and that the dehydration may contribute more directly to death than the infection.     

Daily application of post-mortem computed tomography digital autopsy in a public mortuary

The digital autopsy has gained increasing attention in the past decade as post mortem computed tomography has become more widely available. Whether conducted with, or without, radiographic contrast, digital autopsies have been shown to be a valuable adjunct to invasive examinations in the investigation of natural and unnatural deaths. This radiology investigation has the potential to reduce the number of full invasive autopsies performed, allowing for more targeted, or limited, invasive examinations. In certain deaths, the digital autopsy may obviate the need for an invasive examination entirely. This article considers the daily use of post mortem computed tomography in routine coronial autopsy practice in a busy public mortuary in England. The integration of the digital autopsy into the investigation of natural deaths (including decomposing and embalmed bodies) is first considered before dealing with commonly encountered unnatural deaths after surgery, industrial disease, trauma, drug overdose and suicides.     

Teaching and examining for post-mortem CT-scanned autopsies

The traditional style of autopsy teaching and training requires adaptation for the evolving practice of post mortem radiology, with the pathology trainee learning to interpret radiological diagnostic data mapped against the ante mortem information and external examination. The potential benefits of post mortem radiology require cautious evaluation in the training environment, as some pathologies are not well seen by post mortem computerized tomography (PMCT). There is also the trap of some pathology being readily found, which is not relevant to the cause of death. This article debates the standard format of the PMCT report and how one should judge if additional testing or invasive autopsy are required. The article also considers what is being sought in those facing examination with PMCT-based questions.     

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.     

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.     

The anaphylaxis hypothesis of sudden infant death syndrome (SIDS): mast cell degranulation in cot death revealed by elevated concentrations of tryptase in serum

A series of cases of sudden unexpected post-neonatal deaths from two centres in the UK have been investigated for evidence of mast cell activation using the biochemical markers tryptase and 9α,11β-PGF₂. Tryptase was selected as a possible marker because it is a component of mast cell secretory granules and, unlike histamine, it is not released from basophils. The prostaglandin 9α,11β-PGF₂ is an initial and pharmacologically active metabolite of PGD₂, the major mast cell-derived cyclo-oxygenase product. This prostaglandin was chosen to serve as a marker of newly generated mediator release. In the study, unexplained infant deaths were associated with a higher concentration of tryptase in serum compared with cases of unexpected, but subsequently explained death. However, 9α,11β-PGF₂ was found to be an unsuitable post mortem marker in this situation. These results provide direct evidence that mast cell degranulation, possibly as a result of anaphylaxis, may be occurring around the time of death in some cases of cot death.     

Pulmonary tuberculosis

We present a case of previously undiagnosed and unsuspected pulmonary tuberculosis (TB) identified on post mortem histology. The presentation of TB in the mortuary is reviewed and we present the key learning points regarding dealing with this infection in the post mortem patient.Trainees should appreciate that although a rare occurrence, pulmonary TB may go undiagnosed until after death, and given its ability to survive in the post mortem patient, the use of personal protective equipment is paramount.     

Frequency of glove puncture in the post mortem room.

The post mortem room is a potential source of danger from contamination caused by glove punctures. The objective of this study was to assess the incidence of hand injury and hand contamination during post mortem examinations. A prospective study of injury and glove puncture rate was conducted during post mortem examinations performed in 1990 on adults in Northwick Park Hospital mortuary. Four pathologists and two assistants performed a total of 44 post mortem examinations on adults. All participants completed a questionnaire after each examination, recording the total number of gloves used and the number of hand injuries and glove perforations sustained. Just over 8.3% of gloves were punctured; 31.8% of these punctures went unnoticed. Evisceration was the procedure most likely to result in hand contamination. The study highlights a significant risk which could be reduced by more care, frequent glove changes, and hand washing during post mortem examinations. In particular, gloves should be changed and hand washed when evisceration has been completed.     

Unrecognized viral infections and chromosome abnormalities as a cause of fetal death – examination with fluorescence in situ hybridization,immunohistochemistry and polymerase chain reaction

Fifteen to 50% of fetal deaths remain unexplained after post‐mortem examination depending on inclusion criteria and classification systems. Our aim was to examine a selection of unexplained fetal deaths in order to investigate whether any common chromosome aberrations or viral infections were present. Reports from 351 fetal autopsies performed at the Department of Pathology and Medical Genetics at St. Olavs University Hospital from 2001 through 2010 were reviewed. Of these, 105 fetal deaths were classified as unexplained. Tissue samples from 30 cases were further examined with fluorescence in situ hybridization (FISH) to detect abnormalities in chromosomes 13, 18, and 21. The samples were also examined with immunohistochemistry (IHC) and polymerase chain reaction (PCR) to detect infections with cytomegalovirus, parvovirus B19, herpes simplex virus 1 and 2, enterovirus, and parechovirus. In two cases, a possible trisomy 13 mosaicism was found. No viruses were detected. In our selection of 30 unexplained cases, possible trisomy 13 mosaicism was found in two cases, and no viruses were detected. High degree of maceration and missing placental examination often complicate the investigation of fetal death, and extensive ancillary examinations do not necessarily contribute to a more specific diagnosis.     

Pathologic detection of early myocardial infarction: a critical review of the evolution and usefulness of modern techniques.

The limitations of post mortem detection of early myocardial infarction by hematoxylin and eosin staining stimulated a search for the development of improved diagnostic methods based on biochemical and morphologic changes. Methods used and/or investigated included electron microscopic examination, gross and microscopic histochemical stains (tetrazolium salts, phosphotungstic acid-hematoxylin, trichrome, periodic acid-Schiff, hematoxylin-basic fuchsin-picric acid), fluorescence, immunohistochemical techniques, and chemical analysis of pericardial fluid. This practical review, designed for both forensic and hospital-based autopsy pathologists, examines the methods available for post mortem diagnosis of myocardial infarction for cases in which death might have occurred before the evolution of changes detectable by hematoxylin and eosin staining. The status and potential usefulness of each adjunct to classical morphologic examination is summarized. Recent developments are highlighted, including the possibility of using apoptosis as a marker for acute ischemic injury.     

Reforming the coroner and death certification service

The intention of the Home Office is to introduce a new system that combines an independent check on all deaths and a professional oversight of death patterns, with, for the majority of cases, the minimum of bureaucracy. No public consultation is intended, so that reforms are not delayed. However as the proposals are developed in the coming months, the details, practicalities and costs will be discussed “with relevant professionals (not defined) and those with experience of the existing arrangements”. The imperfections of the present system are outlined. It is hoped the medical profession will have an input, since statements such as “ ‘hospital post mortems’, which are for medical research and public health protection purposes” need amendment. There should be a change in perception of the audit value of this procedure to BOTH the family and the treating doctor. Unfortunately it is proposed the new system in total should cost no more than at present. “Professionals” (not defined) will be involved in the financial detail.All deaths, after verification and certification of the medical cause of death (if known) would then be referred to the ‘medical examiner’ based in the coroner's office. He/she would be a qualified doctor employed by the new coroner service and independent of the Health Service. The medical examiner could provide supplementary advice on medical matters required by the coroner. “Retention of tissue should only take place where absolutely necessary and the coroner and his or her other staff should take account of the needs of families and friends carefully throughout the process.” “Coroners could take advice from their medical examiner to ascertain and prescribe the minimum level of invasiveness to establish the cause of death.” This issue is far from resolved, as signified by a recent call from the DoH giving a grant to study the value of MRI versus a full post mortem. No thought is given to systemic diseases, which may present in one organ system or another disease process, other than that causing death. Medical examiners will have to keep abreast of current developments in medicine BUT will be outside the NHS, which could cause problems. Medical examiners will be appointed (with an input from Regional Directors of Public Health) and managed from within the coroner service. They would work closely with the registrar of births and deaths.Deaths from unnatural causes or when the medical cause of death is unknown will result in judicial inquests. The medical examiner will have an input into causes of death and relevant investigations.Details of the proposed structure of the system are given, as well as the investigative and other roles of Coroner's officers.The establishment of medico-legal centres, as “examples of good practice” is advocated. The drawbacks of this system are stressed in this paper. There is at present an on-going review of forensic pathology services and it is hoped thought will be given to the increasing trend for sub-specialisation in medicine.     

Can arcuate artery morphology predict mortality from ischaemic heart disease?

OBJECTIVES: The degree of atherosclerosis in the uterine and cardiac vasculature are closely related. Examination of the uterine vessels at the time of hysterectomy might therefore indicate that individual's risk of death from ischaemic heart disease (IHD). A pilot study was performed to see if women with severe coronary artery atherosclerosis (CAA) at post mortem had more arcuate artery intimal damage at the time of their hysterectomy than controls. METHODS: Post mortem reports from women who had died in 1993-1997 were studied to identify women who had previously undergone hysterectomy in the same hospital. Cases (those with severe CAA) and controls (without CAA) were matched for age of death and hysterectomy. Stored myometrial sections were re-cut and stained with elastic van Gieson. The medial thickness and intimal changes of the arcuate arteries were analysed using computerised morphology and compared using the paired t-test. RESULTS: From all the post mortem reports studied, only six pairs fitted the strict criteria for analysis. The cases showed a trend towards smaller medial area than controls (-11.3%, 95% CI -27.1 to +4.5, P = 0.1), but there was no difference in the degree of intimal damage or lumen occlusion. The two cases who had premenopausal hysterectomies (and deaths at under 60 years old) both had severe intimal damage and marked lumen occlusion whilst their controls had neither. CONCLUSIONS: Arcuate artery morphology at the time of hysterectomy may be predictive of death from IHD. A larger case-control study is both feasible and promising.     

Asthma deaths; persistent and preventable mortality

Bronchial asthma remains a significant cause of mortality at all ages, despite the increased understanding of its pathogenesis and the range of drugs available for its treatment. Changes in therapeutic management can influence death rates and constant surveillance, combined with high-quality post mortem investigations, is essential. Disease severity, poor disease management and adverse psychosocial circumstances are all risk factors for asthma mortality. Bronchial asthma causes characteristic histological changes in the mucosa of the airways which are present even before the clinical diagnosis of asthma can be made. These include fibrous thickening of the lamina reticularis of the epithelial basement membrane, smooth muscle hypertrophy and hyperplasia, increased mucosal vascularity and an eosinophil-rich inflammatory cell infiltrate. In addition, mucoid plugging of the airway lumen is frequently associated with fatal asthma. The recognition of these changes can allow the diagnosis of asthma to be made for the first time at autopsy, in those cases where asthma goes undiagnosed in life. Acute severe asthma may be accompanied by pneumothorax and surgical emphysema of the mediastinum. Disorders which may mimic asthma include pulmonary embolism, chronic obstructive pulmonary disease and anaphylaxis, but careful post mortem examination and appropriate investigations should reveal the true cause of death.     

Sudden death caused by chronic Chagas disease in a non‐endemic country: Autopsy report

Chagas disease is a tropical disease that is prevalent in Latin America. Described herein is an autopsy case of the sudden death of a 48‐year‐old Brazilian man who had stayed in Japan for 7 years. The man, who had a history of Chagas disease, collapsed unexpectedly at work. Because the cause of death was unknown, forensic autopsy examination was performed. As gross findings, the heart was dilated and rounded with an increase in size and weight. The esophagus and large intestine were dilated moderately, with extensive interstitial inflammatory infiltration in the cardiac muscle, but no apparent parasite nest was observed in various tissues. On post‐mortem laboratory examinations, indirect immunofluorescence antibody test indicated the presence of IgG antibody specific to Trypanosoma cruzi in the serum. Subsequent polymerase chain reaction amplification using DNA extracted from blood yielded the specific product derived from T. cruzi genomic DNA. These examinations indicate that the infection had resulted from the Tripanosoma parasite. The cause of death was judged to be chronic cardiomyopathy caused by Chagas disease. It is important for pathologists to know the possible involvement of chronic Chagas disease in sudden unexpected deaths in the current globalized society of Japan.     

Leucocyte antigens in human post mortem tissues: their preservation and loss as demonstrated by monoclonal antibody immunohistological staining

The development of monoclonal antibodies and of techniques for demonstrating antigens in situ in frozen tissue sections has been responsible for remarkable progress in diagnostic histopathology. We explored the potential of these techniques when applied to post mortem tissues that were frozen at various intervals after death and stained by monoclonal antibodies using immunoperoxidase technique. The monoclonal antibodies were selected according to their reactivity with essential markers of the lymphatic system and also to their availability. Lymph nodes and splenic tissue from 30 autopsy cases were stained in addition to thymic tissue from eight deceased infants. The antigens proved to be surprisingly well preserved. Staining could be precisely evaluated with UCHT1, OKT6 and anti-Leu-7 antibodies at least 72 h after death; staining with DAKO-pan-B, DAKO-LC and anti-Leu-3a was also very reliable. Antigens expressed by T-suppressor lymphocytes and dendritic reticulum cells were less well preserved. The T8-antigen of suppressor lymphocytes was usually demonstrable in the lymph nodes but less frequently in the splenic tissues. It is concluded that most leucocyte antigens are very resistant to post mortem disintegration, and that they can be reliably interpreted by immunohistological staining using monoclonal antibodies. We therefore recommend this in autopsy specimens in cases where in-vivo examination was not feasible.     

Postmorten changes in the chemistry and histology of normal and edematous brains.

The brains of 18 patients were examined post mortem for histologic criteria of edema, and samples of white and gray matter were analyzed for water, sodium, and potassium content. In a parallel experimental study, brains of cats with unilateral freezing lesions and resulting cerebral edema were similarly examined immediately after death and up to 18 hours post mortem. In both types of material, in gray matter there was a relatively rapid (within less than 4 hours) increase in water and sodium content and fall in potassium content. In normal and edematous white matter, little change was observed post mortem. No correlation could be demonstrated in any of the material studied between water content and histologic grading for cerebral edema. It is concluded that determination of water content in the white matter postmortem could be a useful tool for the neuropathologist. Histologic assessment of cerebral edema is of little value.     

Death in CHARGE syndrome after the neonatal period

Bergman JEH, Blake KD, Bakker MK, du Marchie Sarvaas GJ, Free RH, van Ravenswaaij‐Arts CMA. Death in CHARGE syndrome after the neonatal period. CHARGE syndrome is a multiple congenital anomaly syndrome that can be life‐threatening in the neonatal period. Complex heart defects, bilateral choanal atresia, esophageal atresia, severe T‐cell deficiency, and brain anomalies can cause neonatal death. As little is known about the causes of death in childhood and adolescence, we studied post‐neonatal death in patients with CHARGE syndrome. We collected medical data on three deceased children from a follow‐up cohort of 48 CHARGE patients and retrospectively on an additional four deceased patients (age at death 11 months to 22 years). We analyzed the factors that had contributed to their death. In five patients respiratory aspiration had most likely contributed to premature death, one died of post‐operative complications, and another choked during eating. From our findings and a literature review, we suggest that swallowing problems, gastro‐esophageal reflux disease, respiratory aspiration and post‐operative airway events are important contributors to post‐neonatal death in CHARGE syndrome. Cranial nerve dysfunction is proposed as the underlying pathogenic mechanism. We recommend every CHARGE patient with feeding difficulties to be assessed by a multidisciplinary team to evaluate cranial nerve function and swallowing. Timely treatment of swallowing problems and gastro‐esophageal reflux disease is important. Surgical procedures on these patients should be combined whenever possible because of their increased risk of post‐operative complications and intubation problems. Finally, we recommend performing autopsy in deceased CHARGE patients in order to gain more insight into causes of death.