Sudden Death Due to Concurrent Arrhythmogenic Cardiomyopathy and Myocarditis: An Autopsy Case / 대한법의학회지

Arrhythmogenic cardiomyopathy (ACM) is a rare genetically determined myocardial disease characterized by fibrofatty substitution of the myocardium which predisposes the patient to sudden cardiac death (SCD). In addition to the classic pathology seen in ACM, inflammatory infiltrates have been occasionally reported, suggesting a close pathophysiological relationship between ACM and inflammation. Evidence indicates that this inflammation is related to electrical instability resulting in ventricular tachycardia and SCD. This is an autopsy case of a 52-year-old female who died suddenly of concomitant ACM and myocarditis, fulfilling both histological and immunohistochemical diagnostic criteria. With the features of fatty variant ACM, the inflammatory infiltrate was prominent in the subendocardial layer of the left ventricle and was composed of mostly CD3-positive lymphocytes as well as some neutrophils and macrophages. In forensic practice, this case highlights the necessity of collecting multiple representative portions of cardiac tissue to search for inflammation, which can easily explain the cause of death and the dying process in ACM.

Education and Training of Clinical Forensic Examination in the Management of Child Abuse in Korea: Comparison with Germany, the United Kingdom, Australia, and the United States of America / 대한법의학회지

A physician is crucial in the early recognition and reporting of suspected child abuse cases to avoid fatal outcomes. In 2021, the reported rate of suspected child abuse by healthcare providers in Korea was only 1.1%. It appeared that the low reported rate by physicians are mostly due to lack of confidence in diagnosis. Clinical forensic examination by trained physicians is essential on the first physical examination on suspected cases of child abuse, focusing on documentation of injuries and preservation of evidence for legal processing. While Germany, the United Kingdom, Australia, and the United States of America have their own education and training system of clinical forensic examination stressed on undergraduate medical students and physicians, the concept of clinical forensic medicine remains insufficiently known in Korea. To effectively implement the clinical forensic examination in the management of child abuse, it is essential to understand the current status of the curriculum for medical students and physicians. A more practical and integrated education program for medical students should be developed based on real cases incorporated by the experiences of forensic pathologists. Considering the overall shortage of forensic pathologists, pediatricians, and emergency medicine physicians concerned with child abuse, postgraduate training should be focused on securing a small number of clinicians and forensic pathologists specialized in clinical forensic examination to seize the referred cases of child abuse.

An Autopsy Confirmed Case of Amyotrophic Lateral Sclerosis with TDP Pathology

The phosphorylated 43-kDa transactive response DNA-binding protein (TDP-43) was identified as a major disease protein in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We present a case with progressive muscle weakness who was diagnosed with sporadic ALS. On postmortem examination, TDP-43 immunoreactive neuronal cytoplasmic inclusions were noted in motor cortex, hippocampus and anterior horns of spinal cord, which was compatible with ALS-TDP, stage 4. This is the first documented autopsy-confirmed ALS case with ALS-TDP pathology in Korea.

New Death Investigation System in Japan / 대한법의학회지

Since after World War II, the death investigation system in Japan has been a dual system; with or without medical examiners. In areas without medical examiners, death investigation focused on unnatural death suspiciously involved with crime and depended on external postmortem examination for noncriminal cases. As a result, the forensic autopsy rate has been low, and several cases of missed homicide have been discovered. The social impact of the missed homicide of a young sumo player has encouraged the reformation of the death investigation system in Japan. “The Act on the Investigating of Cause of Death and on Identification of Bodies Handled by the Police” and the “Basic Act on Promotion of Death Investigation” were launched in 2013 and 2020, respectively. For noncriminal cases, a new type of autopsy becomes available without the consent of the bereaved family. Moreover, the concept and purpose of death investigation are not only to detect crime involvement, but also to extend respect for life and maintain personal dignity. The responsibility of the central government on death investigation service is stressed, including the establishment of a headquarters in the Ministry of Health, Labour and Welfare. This review aims to understand the background and major changes of the reform of the death investigation system in Japan and discuss the issues affecting forensic pathologists.

Lung Pathology in Septic Shock with Leukopenia / 대한법의학회지

Sepsis-related deaths are occasionally encountered in forensic practice. However, forensic pathologists are reluctant to use the terminology “sepsis” or “septic shock” as a cause of death because of the lack of definite morphological evidence. When sepsis is considered a cause of death, pathologic assessment is essential to identify the foci of infection or consequences of sepsis, such as diffuse alveolar damage (DAD). Pneumonia is known to be a common source of sepsis and can develop into DAD with progression of sepsis. The histology of DAD varies according to the immunologic status. An autopsy of a 55-year-old man who died of septic shock with leukopenia revealed only abundant gram-negative bacilli in the alveoli without typical DAD pathology.

Lung Pathology in Septic Shock with Leukopenia / 대한법의학회지

Sepsis-related deaths are occasionally encountered in forensic practice. However, forensic pathologists are reluctant to use the terminology “sepsis” or “septic shock” as a cause of death because of the lack of definite morphological evidence. When sepsis is considered a cause of death, pathologic assessment is essential to identify the foci of infection or consequences of sepsis, such as diffuse alveolar damage (DAD). Pneumonia is known to be a common source of sepsis and can develop into DAD with progression of sepsis. The histology of DAD varies according to the immunologic status. An autopsy of a 55-year-old man who died of septic shock with leukopenia revealed only abundant gram-negative bacilli in the alveoli without typical DAD pathology.

Comparison of Neuropathological Characteristics between Multiple System Atrophy Cerebellar Type and Parkinsonian Type

Background@#Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by various combinations of parkinsonism, cerebellar ataxia, autonomic dysfunction and pyramidal signs. Two clinical subtypes are recognized: MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P). The aim of this study was to compare pathological features between MSA-C and MSA-P. @*Methods@#Two autopsy confirmed cases with MSA were included from the Pusan National University Hospital Brain Bank. Case 1 had been clinically diagnosed as MSA-C and case 2 as MSA-P. The severity of neuronal loss and gliosis as well as the glial and neuronal cytoplasmic inclusions were semiquantitatively assessed in both striatonigral and olivopontocerebellar regions. Based on the grading system, pathological phenotypes of MSA were classified as striatonigral degeneration (SND) predominant (SND type), olivopontocerebellar degeneration (OPC) predominant (OPC type), or equivalent SND and OPC pathology (SND=OPC type). @*Results@#Both cases showed widespread and abundant α-synuclein positive glial cytoplasmic inclusions in association with neurodegenerative changes in striatonigral or olivopontocerebellar structures, leading to the primary pathological diagnosis of MSA. Primary age-related tauopathy was incidentally found but Lewy bodies were not in both cases. The pathological phenotypes of MSA were MSA-OPC type in case 1 and MSA-SND=OPC type in case 2. @*Conclusions@#Our data suggest that clinical phenotypes of MSA reflect the pathological characteristics.

Progress in Method and Reliability of Diatom Test in Drowning / 대한법의학회지

The forensic significance of the diatom test in diagnosing death due to drowning has been controversial for a long time as diatoms are detected in the non-drowning cases as well. This false positivity may originate from the antemortem as well as postmortem penetration of the diatoms into the bodies.Another problem with the diatom test is the lack of standardization among the different kinds of diatom extraction and identification methods. The author first reviewed the progress in the methods used in the diatom test and then studied the historical arguments in the diagnosis of drowning. Lastly, the research trend in the diatom test since 2000 was evaluated by classifying the manuscripts searched using the keyword “drowning and diatom” on PubMed. Recent studies tend to support the reliability of the diatom test in the diagnosis of drowning when quantitative and qualitative analyses are performed properly with maximum possible reduction in contamination during the preparation of the test samples.

Lung Pathology in Septic Shock with Leukopenia / 대한법의학회지

Sepsis-related deaths are occasionally encountered in forensic practice. However, forensic pathologists are reluctant to use the terminology “sepsis” or “septic shock” as a cause of death because of the lack of definite morphological evidence. When sepsis is considered a cause of death, pathologic assessment is essential to identify the foci of infection or consequences of sepsis, such as diffuse alveolar damage (DAD). Pneumonia is known to be a common source of sepsis and can develop into DAD with progression of sepsis. The histology of DAD varies according to the immunologic status. An autopsy of a 55-year-old man who died of septic shock with leukopenia revealed only abundant gram-negative bacilli in the alveoli without typical DAD pathology.

Forensic Review of Hot Bath-Related Death in the Elderly: Focused on Japanese Studies / 대한법의학회지

Hot bath-related deaths occur occasionally in Korea, particularly in the winter season among elderly people. The postmortem determination of the cause and manner of death is often difficult because the investigation depends predominantly on postmortem external examination. Moreover, the pathogenesis of sudden death during immersion in a hot bath tub is not easily explained. Confusion regarding the manner of death, whether accidental or natural, causes some conflicts in the compensation of life insurance. This study reviewed the literature, particularly Japanese studies about epidemiology, pathophysiology, and the disputes regarding determination of the manner of death. We concluded that the cause and manner of death are not as simple as only natural disease or drowning; there are complicated cases mixed with accidental and natural causes. Extensive epidemiological studies and thorough investigation, including full autopsy and toxicologic studies, are essential for comprehensive understanding of hot bath-related deaths in Korea.

The Brain Donation Program in South Korea

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.

Forensic Review of Hot Bath-Related Death in the Elderly: Focused on Japanese Studies / 대한법의학회지

Hot bath-related deaths occur occasionally in Korea, particularly in the winter season among elderly people. The postmortem determination of the cause and manner of death is often difficult because the investigation depends predominantly on postmortem external examination. Moreover, the pathogenesis of sudden death during immersion in a hot bath tub is not easily explained. Confusion regarding the manner of death, whether accidental or natural, causes some conflicts in the compensation of life insurance. This study reviewed the literature, particularly Japanese studies about epidemiology, pathophysiology, and the disputes regarding determination of the manner of death. We concluded that the cause and manner of death are not as simple as only natural disease or drowning; there are complicated cases mixed with accidental and natural causes. Extensive epidemiological studies and thorough investigation, including full autopsy and toxicologic studies, are essential for comprehensive understanding of hot bath-related deaths in Korea.

An Autopsy Confirmed Case of Semantic Variant Primary Progressive Aphasia with Frontotemporal Lobar Degeneration-TDP type C

A 62-year-old man presented with a one-year history of word finding difficulty, impaired single word comprehension and personality changes including aggression, apathy and eating change. Brain MRIs showed severe atrophy in the left anterior temporal lobe. The clinical syndromic diagnosis was semantic variant primary progressive aphasia. He died at age 70 of pneumonia. At autopsy, transactive response DNA-binding protein (TDP) immunoreactive long dystrophic neurites were predominantly found in the cerebral cortices, which were compatible with frontotemporal lobar degeneration-TDP type C pathology.

Proposal Guidelines for Standardized Operating Procedures of Brain Autopsy: Brain Bank in South Korea

To obtain an in-depth understanding of brain diseases, including neurodegenerative diseases, psychiatric illnesses, and neoplasms, scientific approach and verification using postmortem human brain tissue with or without disease are essential. Compared to other countries that have run brain banks for decades, South Korea has limited experience with brain banking; nationwide brain banks started only recently. The goal of this study is to provide provisional guidelines for brain autopsy for hospitals and institutes that have not accumulated sufficient expertise. We hope that these provisional guidelines will serve as a useful reference for pathologists and clinicians who are involved and interested in the brain bank system. Also, we anticipate updating the provisional guidelines in the future based on collected data and further experience with the practice of brain autopsy in South Korea.

Expression of Connexin 43 in the Myocardium in Sudden Unexplained Nocturnal Death Syndrome / 대한법의학회지

Sudden unexplained nocturnal death syndrome (SUNDS) occurs predominantly in Southeast Asian people including Koreans. SUNDS is problematic for forensic pathologists because the diagnosis depends on the "exclusion of diagnosis." Moreover, the pathogenesis of SUNDS is still unclear although some cases are known to be intimately related to the Brugada syndrome. Connexin 43 (Cx43) is a principal protein of gap junction in adult cardiac myocytes, being distributed to the intercalated discs and phosphorylated in normal condition. Ischemia and hypoxia alter the expression of total Cx43 (tCx43) resulting in redistribution of non-phosphorylated Cx43 (npCx43) to the sarcoplasm or lateral cell borders of cardiac myocytes by continuing dephosphorylation. This study aimed to compare the immunoexpression pattern of Cx43 in the cardiac myocytes of SUNDS and ischemic heart disease (IHD). The study group was 26 cases of SUNDS and the control group of 24 cases of IHD with severe coronary atherosclerosis, showing no myocardial ischemic change. There was a significantly different expression of both tCx43 and npCX43 between the SUNDS and IHD group. A greater reduction in both tCx43 and npCx43 and a more delayed redistribution pattern was seen in the myocardium of SUNDS when compared with IHD. In conclusion, these results suggest that the reduced Cx43 expression in SUNDS may be inherent and indicate a risk of arrhythmia.

The Efficacy of Connexin 43 Expression in the Myocardium as an Early Ischemic Marker in Forensic Autopsy / 대한법의학회지

The postmortem diagnosis of ischemic heart disease is sometimes difficult for forensic pathologists especially when microscopic ischemic change in the myocardium is not detected at the early stages of ischemic injury by conventional staining techniques. Connexin 43 (Cx43) is a gap junction protein in human myocardium, which is phosphorylated and localized to the intercalated discs in the normal cardiac muscles. However, during ischemia and hypoxia, total Cx43 (tCx43) undergoes progressive dephosphorylation and concomitant accumulation of non-phosphorylated Cx43 (npCx43) at the lateral cell borders. This study was aimed to evaluate the efficacy of the immunohistochemical expression of Cx43 in the myocardium as an early ischemic marker in forensic autopsy. The study group consisted of 24 cases listing patients who died of ischemic heart disease (IHD) with severe coronary atherosclerosis that showed no myocardial pathology. Cases of sudden death of individuals from non-IHD (n=16) were used as controls. The survival times in both IHD and non-IHD groups were within 24 hours of the onset of angina symptoms, related injury, or the event for the cause of death. There was a statistically significant difference in tCx43 and npCX43 immunopositivity in the IHD group due to their expression patterns. In the IHD group, the redistribution of Cx43 expression from the intercalated discs to the lateral cell borders occurred more frequently than in the non-IHD group. In conclusion, the different expression patterns of tCx43 and npCx43 in the myocardium in IHD could be used as adjunctive ischemic markers.

Vibrio vulnificus Sepsis: An Autopsy Case / 대한법의학회지

Vibrio vulnificus infection can lead to the rapid expansion of cellulitis or sepsis and can be lethal. Vibrio vulnificus is transmitted through seawater or ingestion of raw or undercooked shellfish. We experienced an uncommon case of death due to Vibrio sepsis, which was confirmed by autopsy. A 56-year-old man who was a sailor was found dead in a fishing boat. Autopsy was performed 3 days later. External examination revealed a few blisters and erythematous lesions on both legs. Internal examination revealed a fatty liver and edema of the legs. The skin lesions on the legs showed blisters that extended from the epidermis to the dermis, accompanied by massive acute inflammation in the dermis and subcutaneous tissue with multinuclear giant cells, as noted on the histologic examination. Vibrio vulnificus was isolated from postmortem blood and subcutaneous tissue of the leg. To the best of our knowledge, this is the first autopsy case in Korea in which Vibrio vulnificus was isolated from postmortem blood. Herein, we present a case of sepsis due to Vibrio vulnificus which was confirmed by autopsy, pathological findings, and postmortem microbiological culture.

An Autopsy Case of Frontotemporal Dementia with Motor Neuron Disease

Approximately 15% of patients with frontotemporal dementia (FTD) have co-occurring motor neuron disease (MND). FTD-MND cases have frontotemporal lobar degeneration (FTLD)-transactive response DNA-binding protein (TDP) pathology, which is divided into four subtypes (types A, B, C, and D) based on the morphological appearance, cellular location, and distribution of the abnormal TDP inclusions and dystrophic neurites. We report a patient with FTD-MND whose pathological diagnosis was FTLD-TDP type B. This is the first documented autopsy-confirmed case of FTD-MND in Korea.

An Autopsy Case of Frontotemporal Dementia with Motor Neuron Disease

Approximately 15% of patients with frontotemporal dementia (FTD) have co-occurring motor neuron disease (MND). FTD-MND cases have frontotemporal lobar degeneration (FTLD)-transactive response DNA-binding protein (TDP) pathology, which is divided into four subtypes (types A, B, C, and D) based on the morphological appearance, cellular location, and distribution of the abnormal TDP inclusions and dystrophic neurites. We report a patient with FTD-MND whose pathological diagnosis was FTLD-TDP type B. This is the first documented autopsy-confirmed case of FTD-MND in Korea.

An Autopsy Confirmed Case of Behavioral Variant Frontotemporal Dementia with Corticobasal Degeneration Pathology

A 63-year-old man presented with a 1.5-year history of progressive personality changes. Clinical evaluations revealed severe frontal dysfunction and bilateral frontal atrophy/glucose hypometabolism. He was diagnosed as probable behavioral variant frontotemporal dementia. He continued to decline, and died at the age of 66. At autopsy, numerous tau-positive gilial threads and coiled bodies were observed in the white matter. Tau-positive astrocytic plaques and neuronal cytoplasmic inclusions were also seen in cerebral cortices, which were compatible with corticobasal degeneration.