Consecutive Autopsies Research Articles

Prevalence of metabolic dysfunction-associated steatotic liver disease and steatohepatitis in Türkiye: A forensic autopsy study

Background and aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic in Türkiye and worldwide. The aim of this study was to evaluate the prevalence and predictors of MASLD and steatohepatitis among adults who died of unnatural causes including sudden death and non-burn trauma. MethodWe conducted a prospective review of all consecutive adult forensic autopsies for natural (sudden unexpected) and non-natural (Suicidal, homicidal and accidental) suspicious deaths carried out at the Istanbul Council of Forensic Medicine from February to May 2022. Four wedge biopsies were extracted from sagittal sectioned liver specimens. A liver pathologist with 20 years of experience examined each case for steatosis, ballooning, inflammation, and fibrosis. ResultsAmong 1797 autopsies, 62 met inclusion criteria. Overall, 43.3 % (n = 26) of autopsies showed evidence of steatotic liver disease, with a distribution of steatosis severity as: Grade I (28.3 %), Grade II (6.6 %), and Grade III (8.3 %). All these cases met at least one cardiometabolic criteria and diagnosed with MASLD. Ballooning was observed in 20.0 % of cases (5 cases grades 1 and 7 cases grade 2), and Inflammation was present in 51.7 % (9 cases with grade 0–1, 12 with 1–2, 7 with 2–3, and 3 with 5–6). Notably, 46.1 % (n = 12) of MASLD cases and 20.0 % (n = 12) of all cases were diagnosed with steatohepatitis, with three cases exhibiting delicate perisinusoidal fibrosis and one case showing portal fibrosis. ConclusionThe histopathological findings from this autopsy study confirmed the markedly high prevalence of MASLD and steatohepatitis within the general adult population, highlighting the concerning burden of steatotic liver disease in Türkiye.

Hypertrophy of the inferior olivary nucleus in corticobasal degeneration: A neuropathological study.

Corticobasal degeneration (CBD) is a rare neurodegenerative disorder. The status of the inferior olivary nucleus (ION) in CBD has been inadequately investigated. In this study, we conducted a pathological investigation of the ION in CBD. We reviewed the data of Japanese patients with pathologically confirmed CBD who underwent consecutive autopsies between 1985 and 2020 at our institute. We retrospectively examined clinical data from medical records and clinicopathological conferences and semi-quantitatively assessed the ION, central tegmental tract, superior cerebellar peduncle, and dentate nucleus. Of the 32 patients included, 14 (43.8%) had hypertrophy of the ION (HION), of whom 6 showed laterality. In the 14 HION cases, with or without laterality, except in 1 unevaluable case, atrophy/myelin pallor of the central tegmental tract was observed on the same side as the hypertrophy. Ten patients with HION, with or without laterality, had atrophy/myelin pallor of the superior cerebellar peduncle on the contralateral side to the hypertrophy. The ION presents with hypertrophic changes in CBD. The lesion is a primary degeneration in CBD and is related to the degeneration of the Guillain-Mollaret triangle. This finding contributes to the elucidation of the specific pathological characteristics of CBD.

Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains

BackgroundHypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients.MethodsBrain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups.ResultsThe COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls.ConclusionsAcute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative.

Analysis of the causes of 9 sudden deaths and 24 deaths after short-term hospitalization using 112 consecutive autopsy cases

Analysis of the causes of 9 sudden deaths and 24 deaths after short-term hospitalization using 112 consecutive autopsy cases

Characteristics of oldest‐old individuals with ‘Pure’ Limbic‐predominant age‐related TDP‐43 encephalopathy: a 90+ Study case series

AbstractBackgroundLimbic‐predominant age‐related TDP‐43 encephalopathy (LATE) is an important contributor to dementia at age 90+. Given the high prevalence of multiple pathologies in the oldest old, the prevalence of ‘pure’ LATE and its clinical and cognitive features are poorly understood. The aims of this report are: (1) to determine the prevalence of ‘pure’ LATE among participants of The 90+ Study and (2) to describe clinical and cognitive features of ‘pure’ LATE.MethodIndividuals for this report were identified from a total of 364 consecutive autopsies of The 90+ Study . We compared medical histories and cognition in three groups: those with ‘pure’ LATE, ‘pure’ Alzheimer’s disease neuropathologic change (ADNC), and ‘pure’ primary age‐related tauopathy (PART). ‘Pure’ LATE was defined as TDP‐43 in the hippocampus or neocortex, no moderate/severe ADNC, and no limbic/cortical Lewy bodies. ‘Pure’ ADNC group was defined as moderate/severe ADNC, no TDP‐43, and no limbic/cortical Lewy bodies. ‘Pure’ PART group was defined as limbic/cortical phosphorylated tau inclusions (Braak tau stage ≥2), no amyloid (A score = 0 and C score = 0), no TDP‐43, and no limbic/cortical Lewy bodies. All groups had <2 microvascular lesions.ResultLATE pathology was prevalent in the cohort (36%) but only 5 participants (1.4%) had ‘pure’ LATE. ‘Pure’ LATE group was on average older at death, more educated, and had lower proportion of women (Table) compared to the other two groups. Duration of cognitive impairment was longest and dementia was more prevalent in ‘pure’ LATE (6 years, 80%) compared to ‘pure’ ADNC (3 years, 43%) and ‘pure’ PART (3 years, 22%). Memory and executive function were more frequently impaired in ‘pure’ LATE compared to the other two groups (Table). Furthermore, histories of cardiovascular disease, syncope, depression, and extrapyramidal signs were more common, whereas osteoarthritis was less common, in ‘pure’ LATE compared to the other two groups (Table).ConclusionGiven the high prevalence of multiple pathologies, ‘pure’ LATE is a relatively rare finding in the oldest old. Identifying differences between ‘pure’ LATE and other dementia related neuropathologies in this case series, may provide valuable insight to inform proper ante‐mortem diagnosis of LATE.

Distribution of proteinase K-resistant anti-α-synuclein immunoreactive axons in the cardiac plexus is unbiased to the left ventricular anterior wall.

Lewy body disease (LBD) is characterized by the appearance of Lewy neurites and Lewy bodies, which are predominantly composed of α-synuclein. Notably, the cardiac plexus (CP) is one of the main targets of LBD research. Although previous studies have reported obvious differences in the frequency of Lewy body pathology (LBP) in the CP, none of them have confirmed whether LBP preferably appears in any part of the CP. Thus, we aimed to clarify the emergence and/or propagation of LBP in the CP. In this study, 263 consecutive autopsy cases of patients aged ≥50 years were included, with one region per case selected from three myocardial perfusion areas (MPAs) and subjected to proteinase K and then immunohistochemically stained with anti-α-synuclein antibodies to assess LBP. We stained all three MPAs in 17 cases with low-density LBP and observed the actual distribution of LBP. LBP were identified in the CP in 20.2% (53/263) of patients. Moreover, we found that LBP may appear in only one region of MPAs, mainly in the young-old group (35.3% (6/17) of patients). These findings suggest that it is possible to underestimate LBP in the CP, especially in the young-old group, by restricting the search to only one of the three MPAs.

Metabolomics investigation of post-mortem human pericardial fluid

IntroductionDue to its peculiar anatomy and physiology, the pericardial fluid is a biological matrix of particular interest in the forensic field. Despite this, the available literature has mainly focused on post-mortem biochemistry and forensic toxicology, while to the best of authors’ knowledge post-mortem metabolomics has never been applied. Similarly, estimation of the time since death or post-mortem interval based on pericardial fluids has still rarely been attempted.ObjectivesWe applied a metabolomic approach based on 1H nuclear magnetic resonance spectroscopy to ascertain the feasibility of monitoring post-mortem metabolite changes on human pericardial fluids with the aim of building a multivariate regression model for post-mortem interval estimation.MethodsPericardial fluid samples were collected in 24 consecutive judicial autopsies, in a time frame ranging from 16 to 170 h after death. The only exclusion criterion was the quantitative and/or qualitative alteration of the sample. Two different extraction protocols were applied for low molecular weight metabolites selection, namely ultrafiltration and liquid-liquid extraction. Our metabolomic approach was based on the use of 1H nuclear magnetic resonance and multivariate statistical data analysis.ResultsThe pericardial fluid samples treated with the two experimental protocols did not show significant differences in the distribution of the metabolites detected. A post-mortem interval estimation model based on 18 pericardial fluid samples was validated with an independent set of 6 samples, giving a prediction error of 33–34 h depending on the experimental protocol used. By narrowing the window to post-mortem intervals below 100 h, the prediction power of the model was significantly improved with an error of 13–15 h depending on the extraction protocol. Choline, glycine, ethanolamine, and hypoxanthine were the most relevant metabolites in the prediction model.ConclusionThe present study, although preliminary, shows that PF samples collected from a real forensic scenario represent a biofluid of interest for post-mortem metabolomics, with particular regard to the estimation of the time since death.

Comparative pathological study of Carbon‐11 labeled Pittsburgh compound‐B PET Centiloid Scale and amyloid beta deposition in postmortem brains

AbstractBackgroundCentiloid Scale (CL) was developed to standardize the quantitative results of amyloid beta (Aβ) positron emission tomography (PET). CL can allow not only categorization of the binary results of amyloid PET as positive or negative, but also parametric weighting within each category. To date, several neuropathological studies evaluated the performance of CL, but further validation studies of the Asian population, elderly cohorts, and relatively short intervals between PET scanning and autopsy may be required.MethodTwenty‐two consecutive autopsy cases registered to the Brain Bank for Aging Research, who received Carbon‐11 labeled Pittsburgh compound‐B PET were included. Amyloid PET results of CL were compared with the final neuropathological diagnosis and the grading of Aβ deposition.ResultThe mean age of the 22 patients at death was 81.0 (SD: 8.4) years, seven of whom fulfilled pathological diagnosis of Alzheimer’s disease (AD). The mean interval from PET to autopsy was 17.5 (SD: 15.3) months. The mean CL was higher in the AD group (88.5 [SD: 30.9]) than in the non‐AD group (9.7 [SD: 25.6], p <0.001). Cutoff value of 50 could segregated seven AD and two non‐AD patients above and 13 non‐AD patients below. CL correlated with CERAD plaque score, Thal phase, and Braak amyloid stage with polyserial correlation coefficient of 0.93, 0.87, and 0.87, respectively. The lower limit of the CL value corresponding to moderate to frequent CERAD plaque score or equal to or more than Thal phase 4 was 17.31.ConclusionThe CL value is in good agreement with the extent of Aβ accumulation. The cutoff value for predicting moderate or greater accumulation of Aβ was 15‐20, and the cutoff value for predicting AD pathology was 50‐60. Further accumulation and integration of data will allow us to establish more appropriate cutoff value.

Bystander CD8 + T cells may be involved in the acute phase of diffuse alveolar damage.

Acute respiratory distress syndrome (ARDS) is a serious complication of systemic inflammatory response syndrome, and diffuse alveolar damage (DAD) is a histological manifestation of ARDS. Endothelial cell injury is mainly responsible for ARDS. Many neutrophils and macrophages/monocytes, which are inflammatory cells that play a role in innate immunity, infiltrate the lung tissue in DAD. In recent years, it has become clear that CD8 plays an important role not only in the acquired immune system, but also in the innate immune system. Non-antigen-activated bystander CD8 + T cells express the unique granzyme B (GrB) + /CD25-/programmed cell death-1 (PD-1)-phenotype. The involvement of bystander CD8 + T cells in lung tissue in DAD is an unexplored field. This study aimed to determine whether bystander CD8 is involved in DAD. Twenty-three consecutive autopsy specimens were retrieved from patients with DAD, and the phenotypes of infiltrating lymphocytes in the DAD lesions were evaluated using immunohistochemistry. In most cases, the number of CD8 + T cells was higher than that of CD4 + T cells, and many GrB + cells were also observed. However, the number of CD25 + and PD-1 + cells was low. We conclude that bystander CD8 + T cells may be involved in cell injury during the development of DAD.

Subgemmal neurogenous plaques of the tongue: a systematic autopsy study.

Subgemmal neurogenous plaque (SNP) is a subepithelial nerve plexus associated with taste buds, occasionally observed in tongue biopsies. There is no evaluation of the prevalence of this structure in the general population. We present a systematic study of samples obtained at random from the dorsal portion of the oral tongue in 205 consecutive complete autopsies. Each sample was about 15 mm long and 10 mm thick. Four hundred fifty-eight samples were routinely obtained and an average of 2.23±0.88 samples per case (range 1-7) was collected. The total number of SNPs observed was 556, with a mean of 2.71±2.68 per case (range 0-16). This means that for every 15 linear mm of the oral tongue, approximately 2.7 SNPs can be present. SNPs display several ages, and they do not show sex differences. The mean size of these structures was 2.1±0.94 mm (range 0.6-3.6 mm). SNP is characterized by its unique neural, zonal pattern with a superficial neurofibroma-like area and a deeper neuroma-like area. Special features of the SNPs include the presence of taste buds (49.1%), ganglion cells (26.3%), dilated thin-walled vessels (11.3%), salivary gland excretory ducts emptying on the surface of the papillae (6.1%), moderate-severe inflammatory infiltrate (6.8%), presence of lymphoid tissue in the vicinity (7.0%), and hyperplasia of the epithelial cover with pseudoepitheliomatous appearance (7.0%). The differential diagnoses include schwannoma, neurofibroma, ganglioneuroma, traumatic neuroma, mucosal neuroma, and squamous cell carcinoma. SNPs are small, normal structures that may undergo hyperplasia and are usually seen incidentally.

Prevalence of Imaging-Detected Silent Female Breast Cancer in Autopsy Specimens: A Study Using Image-Guided Biopsies.

Background This study was conducted to evaluate the prevalence of imaging-detected silent breast cancer in females, with the hypothesis that the incidence of imaging-detected silent breast cancer in females is greater than the true disease incidence. The main purpose of this study is the attempt to prove whether breast imaging can identify silent breast cancers that apparently are common inserial histology analysis. Methodology A series of 217 consecutive medicolegal autopsies on fresh Portuguese cadavers were performed from July 2016 to December 2019 at the National Institute of Legal Medicine and Forensic Science, Lisbon, Portugal. The criteria for exclusion were age younger than 40 years, the autopsy performed in less than 48 hours after death, any major injury to one or both breasts, and known or clinically evident breast cancer. Once the eligibility criteria were met, and the sample collection authorization was obtained, a bilateral subcutaneous modi-fied radical mastectomy was performed in each fresh cadaver at the National Institute of Legal Medicine and Forensic Science. Mammography, ecography, and excisionalbiopsies of suspect areas were conducted on the collected samples. Results The indication for excisional biopsy by imaging was assigned in eight cases, and no breast cancer was discovered in the excised specimens. Conclusions In light of the findings, it cannot be concluded that the imaging-detected silent breast cancer prevalence is higher than the actual incidence of the disease, so the author's initial hypothesis was rejected. Mammography does not overdiagnose breast cancer.Benign breast alterations are common, accounting for 43.6% of the corpses collected, while low-suspicion alterations were discovered in 1.84% of breast samples.The objective examination, which included inspection and palpation, missed 37.5% of the biopsied breast changes. This finding indicated that an objective examination leads to a significant number of false-negative results which cannot be used as a screening method.

Blunt Traumatic Brain Injury and Alzheimer Pathology

Introduction: Traumatic brain injury (TBI) has been associated with a greater risk of late-life dementia, including Alzheimer’s disease (AD), but only a few studies examined the relationship between residuals of blunt TBI and autopsy-proven AD. The objective of the present study was to examine the incidence of fully developed AD pathology after documented blunt TBI, and the frequency of residuals of blunt TBI in a series of cases with definite AD. Methods: Among a sample of 1,750 consecutive autopsy cases of elderly demented patients, those cases with residuals of blunt (closed) TBI and definite AD pathology were assessed, and among 933 individuals with autopsy-proven AD, those with residuals of blunt TBI were selected. Results: Among 190 autopsy cases with residuals of blunt TBI, 28 (14.7%; mean age 77.2 ± 10.6 years) revealed the pathological features of definite AD (Braak stage V or VI; ABC 3/3/3), while among 1,150 elderly controls (Braak stage < IV, mean age 77.3 ± 9.5 years), 160 (13.6%) showed residuals of blunt TBI. The second part of the study included 933 consecutive cases with definite AD (Braak stage V or VI; ABC 3/3/3, mean age 82.3 ± 8.4 years), in which 30 cases (3.3%; mean age 77.8 ± 10.7 years) showed morphological residuals of blunt TBI. Conclusion: The results of this retrospective study, on the one hand, did not support the idea that blunt TBI and its morphological residuals are responsible for the development of definite AD, whereas the second part of the study, showing morphological residuals of blunt TBI among 3.3% of definite AD cases were similar to the results in a clinical series who sustained moderate to severe TBI. Considering these conflicting results, further studies on the relationship between the severity and location of morphological residuals of blunt TBI and the development of AD pathology are warranted.

Clinicopathological features of progressive supranuclear palsy with asymmetrical atrophy of the superior cerebellar peduncle.

Progressive supranuclear palsy (PSP) can be diagnosed despite the presence of asymmetrical parkinsonism depending on the clinical diagnostic criteria. Some studies have reported that atrophy of the superior cerebellar peduncle (SCP) is more frequent in PSP than in Parkinson's disease. There have also been reports of PSP cases with an asymmetrically atrophic SCP. Therefore, we analyzed 48 specimens from consecutive autopsy cases that were neuropathologically diagnosed as PSP to investigate the laterality of brain lesions, including the SCP. We measured the width of the SCP and evaluated the laterality of atrophy. We semi-quantitatively evaluated neuronal loss, atrophy/myelin pallor, and tau pathology in three steps. Asymmetrical atrophy of the SCP was present in seven (14.6%) of 48 cases. The atrophic side of the SCP corresponded to the dominant side of the tau pathology in the cerebellar dentate nucleus. It was opposite to the dominant side of the myelin pallor and tau pathology in the red nucleus and of the tau pathology in the central tegmental tract and inferior olivary nucleus, coinciding with the neurologically systematic anatomy of the Guillain-Mollaret triangle. Neurodegeneration of PSP can progress asymmetrically from one side to the initially intact side in PSP with an initial predominance of Richardson's syndrome, progressive gait freezing, ocular motor dysfunction, parkinsonism, or corticobasal syndrome. To our knowledge, no previous study has reported asymmetrical PSP neuropathology; this is the first study to report the presence of PSP cases with asymmetrical SCP atrophy and systematically asymmetrical degeneration of the Guillain-Mollaret triangle.

ПАТОЛОГІЯ ЛЕГЕНЬ ПРИ COVID-19: БАГАТОІНСТИТУЦІЙНА КОГОРТА РОЗТИНІВ ЛЬВОВА ТА ЛЬВІВСЬКОЇ ОБЛАСТІ

Introduction. In Ukraine 2,2 million coronavirus disease-19 (COVID-19) cases are reported now with 51,8 thousand deaths. Methods. A retrospective analysis of 1036 consecutive autopsies at COVID-19 in 2020 was conducted on the basis of the Lviv Regional Office for Autopsy and Lviv Railway Clinical Hospital. The diagnosis of COVID-19 was confirmed by clinical signs of viral pneumonia, nasopharyngeal smear analysis, and radiological changes. Statistical study was performed with IBM SPSS Statistics 24.0. Results. The majority (72.4%) were elderly (after 60 y.o., fig.2) males (54.1%) and females (45.9%), with age range from 19 to 93 years (mean age 66.9 ± 0.4 years). All examined patients had pneumonia, which was detected during a clinical examination with CT diagnosis and confirmed at autopsy. Acute phase of pneumonia was diagnosed in 18.5% of cases, proliferative phase – in 18.6%, fibrotic phase – in 5.9%. And in 53.5% of cases prevailed signs of progressive fibrosis associated with exudative lesions. COVID-19 was single original cause of death in 88.7% cases. In the lungs were identified: the typical virus-induced changes in epithelial cells of the trachea, bronchi, bronchioles and alveoli (100%, n=1036); different phases of diffuse alveolar damage in majority of cases (96.5%); manifestations of innate/adaptive immunity were described; pathological changes in microvasculature (large vessel thrombi were detected in 37.9%). Conclusion. Our study results prove the importance of pathological examination of tissues during autopsies to determine the pathophysiological mechanisms and underlying causes of death of patients with COVID-19. &nbsp;

Morphological study of the phrenic nerve to determine a reference value for the myelinated fiber density in elderly individuals.

Phrenic nerves (PNs) play an important role in respiration; however, very few morphological studies have assessed them. This study aimed to provide control reference values, including the density of large and small myelinated PN fibers, for future pathological studies. We assessed a total of nine nerves from eight cases among consecutive autopsy cases registered to the Brain Bank for Aging Research between 2018 and 2019 (five men and three women, mean age 77.0 ± 7.0 years). The nerves were sampled distally, and their structures were analyzed using semi-thin sections stained with toluidine blue. The mean and standard deviation of the density of each myelinated fiber of the PN was 6908 ± 1132 fibers/mm2 (total myelinated fiber), 4095 ± 586 fibers/mm2 (large diameter myelinated fiber; diameter ≥7 μm), and 2813 ± 629 fibers/mm2 (small diameter myelinated fiber; diameter <7 μm). There was no correlation between myelinated fiber density and age. This study provides the density measurement of the human PN myelinated fiber, and these findings can be used as reference values for the PN in elderly individuals.

Postmortem investigation of more than 100 consecutive autopsy cases in femoral blood, cardiac blood, brain tissue and muscle tissue

Drug concentrations in peripheral blood are most often used in interpretation of toxicological results in postmortem cases. However, peripheral blood is not always available or suitable for analysis, especially in advanced stages of decomposition. Therefore, other matrices than peripheral blood need to be investigated in order to reveal the cause of death. However, there is no obvious second choice. In this study, we analyzed postmortem femoral blood, cardiac blood, brain tissue and muscle tissue in order to investigate if drug concentrations in these alternative matrices were comparable to femoral blood and thereby useful for toxicological interpretation. A total of 104 consecutive autopsies where toxicological investigation was included were performed in a four-month period. Femoral blood ( n = 89), cardiac blood ( n = 85), brain tissue ( n = 91) and muscle tissue ( n = 104) were analyzed in all cases when available. Quantification of 69 common drugs and metabolites of toxicological interest was performed with four different multi-analyte methods all employing automated sample preparation and UHPLC MS/MS in MRM mode. In 104 autopsy cases, we were able to detect a total of 53 drugs and metabolites. Alternative matrix to femoral blood concentration ratios were calculated for 47 analytes for cardiac blood, 49 analytes for brain tissue and 50 analytes for muscle tissue, respectively. However, about half of the analytes were only detected in < 5 cases. Median ratios of analytes detected in ≥ 5 cases were determined to 0.59–1.9 (median = 1.1) for cardiac blood to femoral blood, 0.57–2.5 (median = 1.5) for brain tissue to femoral blood and 0.67–7.0 (median = 1.4) for muscle tissue to femoral blood. The largest deviation in ratios was observed for THC in muscle tissue. Here muscle tissue to femoral blood ratios varied from 2.3 to 20 with a median of 7.0 ( n = 10). It is, however, a well-known fact that quantitative analysis of THC in muscle tissue is challenging, which our data also support. We therefore recommend that THC in muscle tissue should be reported as “detected” instead of a concentration. Analysis of postmortem cardiac blood, brain tissue and muscle tissue revealed that concentrations were not directly comparable to those of femoral blood. However, 85% of the median ratios of alternative matrix to femoral blood of analytes detected in ≥ 5 cases, where in the range 0.5–2.0, and were therefore not markedly different. This demonstrates that interpretation of postmortem concentration in other matrices than femoral blood can be challenging and must be performed with caution.

Chronic Traumatic Encephalopathy in a Routine Neuropathology Service in Australia.

Chronic traumatic encephalopathy (CTE) is a neuropathological diagnosis defined by a unique pattern of hyperphosphorylated tau (p-tau) accumulation that begins in neocortical regions of the brain. It is associated with a range of neuropsychological symptoms, but a definitive diagnosis can only be made by postmortem brain examination. In 2018, we instituted CTE screening for all autopsy brains as part of our routine departmental protocol by performing p-tau immunohistochemistry on a restricted set of 3 neocortical blocks (frontal, temporal, and parietal). This strategy allowed us to identify 4 cases of low-stage CTE from 180 consecutive autopsies. Two of the 4 cases had a documented history of brain injury; for the remaining 2 cases, there was a long history of treatment-resistant tonic/clonic epilepsy suggesting that undocumented brain injuries may have occurred. Our experience indicates that 3-block CTE screening is useful in identifying CTE in routine practice. The results of this study further support the association between prior head injuries and CTE and demonstrate that, albeit uncommon, CTE does occur in the general population. Our findings suggest that p-tau screening should be routinely pursued in brain autopsy, particularly where there is a documented or likely history of traumatic brain injury.

A comparative autopsy study of the injury distribution and severity between suicidal and accidental high falls.

Falls are the second cause of accidental deaths worldwide. Falls from height are also a common method of suicide. The aim of this study is to compare the characteristics of the victims, the circumstances of the fall and the severity and distribution of the injuries reported in an autopsy case series of falls from height. This study is a retrospective analysis of consecutive autopsy cases of suicidal and accidental falls from height which were investigated in the Department of Forensic Medicine and Toxicology of the National and Kapodistrian University of Athens during the period 2011-2019. The recorded variables included demographic data of the victim, height of fall, length of hospital stay, toxicological results, the existence and location of injuries and Injury Severity Score (ISS). Victims of suicidal falls were younger (55.53 vs. 62.98, p = 0.001), they fell from higher heights (12.35 vs. 5.18m, p < 0.001), and they sustained more severe injuries compared with victims of accidental falls (ISS 51.01 vs. 40.88, p < 0.001). Injuries in the thorax, abdomen, pelvis, upper and lower extremities were more frequently observed after a suicidal fall (93.6% vs. 67.3%, 72.1% vs. 21.4%, 72.1% vs. 27.6%, 42.9% vs. 15.3%, 45.7% vs. 13.3%, respectively-p < 0.001), probably due to the higher height of fall. Our study outlines the differences in the profile of the victims and in the severity of injuries caused by falls from height depending on the intention of the victim to fall. However, a distinctive injury pattern in victims of suicidal falls was not demonstrated.

Rupture pressure values of cerebral arteries in the presence of unruptured intracranial aneurysm

Cerebral arteries (CAs) are prone to the saccular aneurysm formation. Since aneurysms may be considered as balloon-like dilations of the locally weakened arterial wall, it should be determined whether the presence of intracranial aneurysm is related to the generalized weakening of CAs. Among 184 consecutive forensic autopsies, eight brains with a single unruptured saccular aneurysm were identified. Aneurysms with adjacent CAs and specific CA segments were excised, namely: the anterior communicating artery complex, and bifurcations of the basilar artery, internal carotid arteries, and middle cerebral arteries. Then, aneurysm and CA specimens were subjected to pressure-inflation tests until rupture occurred at the arterial bifurcation or at the wall of the CA or aneurysm. The same protocol was applied to the control group composed of CAs excised from eight brains without aneurysm. No significant differences were noted between the experimental and control groups, depending on the mean rupture pressure (1054 vs. 1048 mmHg) and rupture site (bifurcation vs. wall) of the analyzed specimens. These findings indicate that the presence of unruptured saccular aneurysm is not related to generalized weakening of CAs among autopsy subjects. Moreover, the CA bifurcations do not represent regions of decreased wall strength.

Neuropathological fingerprints of survival, atrophy and language in primary progressive aphasia.

Primary progressive aphasia is a neurodegenerative disease that selectively impairs language without equivalent impairment of speech, memory or comportment. In 118 consecutive autopsies on patients with primary progressive aphasia, primary diagnosis was Alzheimer's disease neuropathological changes (ADNC) in 42%, corticobasal degeneration or progressive supranuclear palsy neuropathology in 24%, Pick's disease neuropathology in 10%, transactive response DNA binding proteinopathy type A [TDP(A)] in 10%, TDP(C) in 11% and infrequent entities in 3%. Survival was longest in TDP(C) (13.2 ± 2.6 years) and shortest in TDP(A) (7.1 ± 2.4 years). A subset of 68 right-handed participants entered longitudinal investigations. They were classified as logopenic, agrammatic/non-fluent or semantic by quantitative algorithms. Each variant had a preferred but not invariant neuropathological correlate. Seventy-seven per cent of logopenics had ADNC, 56% of agrammatics had corticobasal degeneration/progressive supranuclear palsy or Pick's disease and 89% of semantics had TDP(C). Word comprehension impairments had strong predictive power for determining underlying neuropathology positively for TDP(C) and negatively for ADNC. Cortical atrophy was smallest in corticobasal degeneration/progressive supranuclear palsy and largest in TDP(A). Atrophy encompassed posterior frontal but not temporoparietal cortex in corticobasal degeneration/progressive supranuclear palsy, anterior temporal but not frontoparietal cortex in TDP(C), temporofrontal but not parietal cortex in Pick's disease and all three lobes with ADNC or TDP(A). There were individual deviations from these group patterns, accounting for less frequent clinicopathologic associations. The one common denominator was progressive asymmetric atrophy overwhelmingly favouring the left hemisphere language network. Comparisons of ADNC in typical amnestic versus atypical aphasic dementia and of TDP in type A versus type C revealed fundamental biological and clinical differences, suggesting that members of each pair may constitute distinct clinicopathologic entities despite identical downstream proteinopathies. Individual TDP(C) participants with unilateral left temporal atrophy displayed word comprehension impairments without additional object recognition deficits, helping to dissociate semantic primary progressive aphasia from semantic dementia. When common and uncommon associations were considered in the set of 68 participants, one neuropathology was found to cause multiple clinical subtypes, and one subtype of primary progressive aphasia to be caused by multiple neuropathologies, but with different probabilities. Occasionally, expected clinical manifestations of atrophy sites were absent, probably reflecting individual peculiarities of language organization. The hemispheric asymmetry of neurodegeneration and resultant language impairment in primary progressive aphasia reflect complex interactions among the cellular affinities of the degenerative disease, the constitutive biology of language cortex, familial or developmental vulnerabilities of this network and potential idiosyncrasies of functional anatomy in the affected individual.