The brainstem connects the forebrain to the spinal cord. It consists of three layers, the ventral basis, the intermediate tegmentum, and the dorsal tectum. Caudo-rostrally, the brainstem is divided into the medulla oblongata or myelencephalon, the metencephalon, and the mesencephalon. The tegmentum is the most conserved part of the brainstem and contains the motor and sensory nuclei of cranial nerves (CN) III-XII. They are arranged in a mediolateral direction, and, unlike the spinal cord, their afferent and efferent fibers are not macroscopically separated. The tegmental reticular formation, the brainstem core, has a lattice structure with manifold longitudinal and transverse fibers and stacked neurons. Its architecture provides maximum convergence and divergence of intrinsic and ascending/descending information from the spinal cord and forebrain. It coordinates brainstem-based vital functions, and its integrity is essential for arousal, consciousness, and goal-directed behavior. Its small aminergic and cholinergic telencephalic projection nuclei have a profound impact on mood, motivation, and cognition. Human telencephalic evolution manifests in volume increases of the cerebral crura, pons, cerebellar hemispheres, olives, pyramidal tract, and medial lemniscus. However, the spatial constraints of the posterior fossa limited the proportional expansion of the brainstem during human telencephalic evolution, rendering this evolutionarily conserved structure increasingly vulnerable to malfunction and disease.
Aneurysmal subarachnoid hemorrhage (aSAH) is a debilitating condition with significant morbidity and mortality rates. Despite advancements in treatment, understanding the underlying pathophysiology, particularly the inflammatory response, remains crucial for improving patient outcomes. In this study, we investigated the presence of transmembrane protein 119 (TMEM119) of microglial cells in cerebrospinal fluid (CSF) as a potential marker for neuroinflammation following aSAH. CSF samples were collected from aSAH patients, pathological and healthy controls, processed, and analyzed using immunocytochemistry. TMEM119-positive microglial cells were consistently identified in the CSF of aSAH patients, exhibiting amoeboid morphology and intense staining. Importantly, microglial cells were detected as early as the first day post-bleeding, persisting throughout the acute phase in some cases. Analysis of consecutive samples revealed varying trends in microglial cell numbers, with a peak during the initial phase followed by a gradual decline. Our findings suggest that microglia may migrate into the CSF following aSAH, potentially serving as an early predictor of inflammatory-related CNS damage. This study underscores the importance of understanding neuroinflammatory processes in aSAH and opens avenues for further research on the role of microglia in CNS disorders by liquid biopsy.
There are only few reports on the neuropathologic findings of fire victims. We investigated brain tissues of a 44-year-old and a 77-year-old man for neuropathologic examination with dehydration, embedding in celloidin, sectioning at 400 μm, and staining with gallocyanin. Microscopically, neurons were less well stained than those from an 87-year-old woman who died of cancer and whose brain had been fixed in formalin for three months. Glial cells were optimally stained. We observed local, laminar and disease-related qualitative and quantitative differences in the amygdaloid complex, temporal allo- and isocortex together with hyperchromatic staining of the medullary layer in the temporal lobe of both fire cases. The vasculature was well preserved and free of blood cells or clotted blood. The heat in fire deaths apparently acts as a kind of fixation, similar to the intention of formalin use, without the confounding effects of agonal and postmortem factors. Heat is most likely a major factor in microwave fixation. Thick gallocyanin-stained sections allow intuitive visual diagnosis of local and laminar neuronal degeneration or gliosis and have the potential to enhance and refine neuropathology-related diagnoses.
On the skull, the best known and most frequently observed autopsy findings are the heat fractures of the skull and the burn hematoma. The macromorphological changes of the brain have been described comparatively less frequently in the primary and secondary literature. We have evaluated the fire deaths of our institute over a period of 10 years with regard to the macromorphological changes of the skull and brain and described four stages (0-III) after postmortem fireexposure. In stage 0, the scalp showed up to third-degree burns, but the skull and brain were not affected. In stage I, in which the scalp showed fourth degree burns but the skull was still completely intact and unbroken, a certain hardening of the brain and a paling of the lateral parts of the temporal lobes, in particular, could already be regularly observed. In stage II, the head skin was burned away, and the skull was charred but still closed. There was a noticeable shrinkage of the dura mater, which was often torn. The brain itself appeared shrunken, pale and showed a flattening of the convolutions and a spreading of the furrows. In stage III, the skull was opened, charred to calcified and broken in clods. Tears in the dura mater led to herniation of brain tissue to the outside. The aim of this study was to classify the macromorphological changes of the skull and brain after fire exposure, both chronologically and according to their severity. The proposed staged classification (0-III) is intended to summarize the findings and to update and complement the descriptions in the older literature. It can be seen as an extension and further development of the Crow-Glassman scale, which classifies the extent of fire destruction of human bodies.
Background: E-scooters have been part of road traffic in Germany for over 4.5 years and have since then become more important in police traffic control. The present study aims to give a first description of e-scooter cases in the catchment area of the Institute of Forensic Medicine in W & uuml;rzburg. Material and methods: All driving ability reports on e-scooter riders (n = 84) between June 2019 and January 2024 were retrospectively evaluated. Performance deficits, driving errors, circumstances and the substances detected in blood were analyzed. Results: Almost all e-scooter riders in our study population were men aged between 20-30 years. Most riders were under the influence of cannabis, amphetamines or alcohol. The main reason for traffic control was missing or expired insurance license plates. The times of offenses had a tendency towards the evening through night and towards warmer seasons of the year. The offenders showed less performance impairment during the medical examination performed later than during the police examination. Discussion: Compared to previous e-scooter studies, this work also examined the influence of drugs on e-scooter riders. The retrospective data analysis revealed similar trends, e.g., in terms of age, gender and seasonal distribution but also some differences. The results show the need of further studies examining the influence of drugs on e-scooter riding.
Traumatic brain injury (TBI) is a ubiquitous, common sequela of accidents with an annual prevalence of several million cases worldwide. In forensic pathology, structural proteins of the cellular compartments of the CNS in serum and cerebrospinal fluid (CSF) have been predominantly used so far as markers of an acute trauma reaction for the biochemical assessment of neuropathological changes after TBI. The analysis of endogenous metabolites offers an innovative approach that has not yet been considered widely in the assessment of causes and circumstances of death, for example after TBI. The present study, therefore, addresses the question whether the detection of metabolites by liquid-chromatography-mass spectrometry (LC/MS) analysis in post mortem CSF is suitable to identify TBI and to distinguish it from acute cardiovascular control fatalities (CVF). Metabolite analysis of 60 CSF samples collected during autopsies was performed using high resolution (HR)-LC/MS. Subsequent statistical and graphical evaluation as well as the calculation of a TBI/CVF quotient yielded promising results: numerous metabolites were identified that showed significant concentration differences in the post mortem CSF for lethal acute TBI (survival times up to 90 min) compared to CVF. For the first time, this forensic study provides an evaluation of a new generation of biomarkers for diagnosing TBI in the differentiation to other causes of death, here CVF, as surrogate markers for the post mortem assessment of complex neuropathological processes in the CNS (“neuroforensomics”).
E‑Scooter sind seit über 4,5 Jahren Teil des Straßenverkehrs in Deutschland und haben seitdem in der polizeilichen Verkehrskontrolle zunehmend an Bedeutung gewonnen [16]. Das Ziel der vorliegenden Arbeit war es, eine Erstbeschreibung über die im Institut für Rechtsmedizin der Universität Würzburg bearbeiteten Fälle anzufertigen. Alle Fahrsicherheitsgutachten über E‑Scooter-Fahrer (n = 84) am Institut für Rechtsmedizin Würzburg aus dem Zeitraum Juni 2019 bis Januar 2024 wurden retrospektiv ausgewertet. Hierbei wurden u. a. Ausfallerscheinungen, Fahrfehler, Tatumstände und die im Blut nachgewiesenen Substanzen analysiert. Fast alle E‑Scooter-Fahrer in unserem Kollektiv waren Männer, viele im jüngeren Alter. Die häufigsten nachgewiesenen Substanzen im Blut waren Cannabinoide, Amphetamine und Alkohol, der häufigste Grund einer Verkehrskontrolle ein fehlendes bzw. abgelaufenes Versicherungskennzeichen. Die Vorfallszeitpunkte lagen eher abends bis nachts und zu wärmeren Jahreszeiten. Die Beschuldigten waren bei der späteren ärztlichen Untersuchung weniger leistungsreduziert als bei der polizeilichen. Im Vergleich zu früheren E‑Scooter-Studien untersuchte diese Arbeit auch den Einfluss von Drogen auf die Fahrsicherheit. Die retrospektive Datenanalyse ergab z. T. ähnliche Tendenzen z. B. bezüglich Alter, Geschlecht und jahreszeitlicher Verteilung, z. T auch Unterschiede. Weitere Studien zum Einfluss von Drogen auf E‑Scooter-Fahren erscheinen vor diesem Hintergrund unabdinglich.
Based on the assumption that postmortem cerebrospinal fluid (CSF) is contaminated depending on the chosen sampling technique in the forensic setting resulting in bloody or at least hemolytic CSF samples, we systematically documented a total of 183 postmortem CSF samples. These samples were all assessed for their quality and color, regardless of the cause of death or the postmortem interval. The investigations were carried out through subjective assessment of color and turbidity, as well as objective measurements of the optical density (OD) of the CSF supernatants after centrifugation of each sample, with standardized photographic documentation. The observations revealed that in 28 cases the CSF was absolutely (crystal-) clear and transparent. Most of our samples showed color changes ranging from xanthrochromic to rose. Intensive staining of the supernatants was only found in a small proportion of the examined collective. We found that postmortem CSF has no uniform appearance but rather a diverse range of color spectra, and the color, as well as the OD of the CSF, correlates significantly with the postmortem interval (p < 0.001) when sampled using the proposed standard procedure.
In Europe, 350,000 people die suddenly and unexpectedly every year. The majority of sudden deaths are caused by cardiac alterations and known as sudden cardiac death (SCD). The interpretation of medicolegal findings is especially difficult in those SCDs where there is no morphological correlate and no antemortem electrocardiograms or relevant medical history are available. The Wolff-Parkinson-White (WPW) syndrome, in which an accessory electrical conduction pathway exists between the atrium and the ventricle in addition to the physiological conduction system, is mostly a benign disease of the heart, which may lead to cardiac arrhythmia. A 16-year-old boy with a known history of WPW syndrome since the second year of life had consumed alcohol before death and was found sitting on the toilet fully dressed. The autopsy performed on the deceased 3 days postmortem showed a marked mass increase of the heart with left ventricular concentric hypertrophy and macroscopic signs of cardiomyopathy. In the microscopic examination, the right and left ventricles and the atria were found to have a regular structure with normal vessels. Hematoxylin-eosin (HE) and elastica-van-Gieson (EvG) staining disclosed a thin accessory muscle bridge connecting the left atrium with the left ventricle as a possible morphological correlate of a fatal cardiac arrhythmia.
Sepsis is one of the major threats for the survival and prognosis of patients in intensive care units. In cases where detailed clinical data and monitoring is available, the diagnosis of sepsis is reliable. But when clinical data are incomplete or missing and sepsis is only suspected based on the autopsy results, the picture is often equivocal. This report describes the gross pathological findings obtained from the autopsy of a 48-year-old woman with Crohn's disease after surgical intervention. Macroscopically, we found intestinal perforation and signs of peritonitis. Histologically, the pulmonary/bronchial arteries were lined with E-selectin (CD 62E)-positive endothelial cells, which are an established postmortem histological marker of sepsis. We extended our investigations to the cerebral cortex and subcortical medullary layer. The endothelium of the cortical vessels and those in the cerebral medullary layer were likewise immunopositive for E-selectin. Furthermore, numerous TMEM119-positive, highly ramified microglial cell profiles were found in the grey and white matter. Microglial cells were lining the vascular profiles. In addition, TMEM119-positive microglial profiles were abundant in the cerebrospinal fluid (CSF). Multiorgan E-selectin positivity of the vascular endothelia provides further evidence for the postmortem diagnosis of sepsis.
According to the Federal Statistical Office 178,425 cases of poisoning were treated in German hospitals in 2016. Immediate clinical interventions include procedures to prevent further toxin absorption. The use of activated charcoal is considered the decontamination method of first choice after peroral poisoning. A 14-year-old girl had taken several tablets of amitriptyline with questionable suicidal intent. At the hospital where she was treated first, she had been given an unknown amount of activated charcoal via a stomach tube; however, due to the endotracheal malpositioning of the gastric tube, the activated charcoal was applied endotracheally. After this had happened, the patient was transferred to a maximum care hospital. Despite intensive care medical treatment, the girl died after 18 days of acute respiratory failure following massive aspiration of activated charcoal. The court-ordered autopsy and the subsequent microscopic examination revealed both a heterogeneous distribution of variably dense accumulations of activated charcoal in the intra-alveolar spaces of all pulmonary lobes as well as acute and chronic inflammatory changes in the lung parenchyma. Furthermore, activated charcoal was detected within the liver sinusoids and also in the tubules of the renal parenchyma.
Zusammenfassung Laut Statistischem Bundesamt wurden 2016 in Deutschland 178.425 Vergiftungsfälle im Krankenhaus behandelt. Zu den klinischen Sofortmaßnahmen gehören Verfahren zur Verhinderung weiterer Giftresorption. Die Anwendung von Aktivkohle wird dabei als Dekontaminationsverfahren der ersten Wahl nach peroralen Vergiftungen angesehen. Ein 14 Jahre alt gewordenes Mädchen habe in fraglich suizidaler Absicht mehrere Tabletten Amitriptylin eingenommen. Im erstbehandelnden Krankenhaus sei ihr eine unbekannte Menge an Aktivkohle über eine Magensonde verabreicht worden. Aufgrund der Fehllage der Magensonde wurde die Aktivkohle jedoch endotracheal appliziert. Danach erfolgte die Verlegung an ein Krankenhaus der Maximalversorgung. Trotz intensivmedizinischer Therapie sei das Mädchen nach 18 Tagen an einem akutem Lungenversagen nach massiver Aspiration von Aktivkohle verstorben. Bei der gerichtlichen Obduktion und der anschließenden mikroskopischen Untersuchung fielen sowohl eine heterogene Verteilung der intraalveolär gelegenen, variabel dichten Ansammlungen der Aktivkohle in allen Lungenlappen als auch mehrzeitige, akute sowie chronische entzündliche Veränderungen im Lungenparenchym auf. Darüber hinaus konnte Aktivkohle innerhalb der Lebersinusoide sowie in den Tubuli des Nierenparenchyms nachgewiesen werden.
Black esophagus, also known as acute esophageal necrosis, is a rare disease characterized by a circumferential black discoloration of the esophageal mucosa with an abrupt stop at the gastroesophageal junction. The exact pathogenesis is unknown, but multifactorial influences, such as acid reflux, ischemia and reduced protective mechanisms of the mucosa are discussed as possible causes. Two autopsy cases are presented with typical signs of a black esophagus. The first case showed an infection with Candida albicans, the second one died of appendicitis, so in both cases an infectious genesis might have played a role.
Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.
Traumatic brain injury (TBI) is a major cause of death and its accurate diagnosis is an important concern of daily forensic practice. However, it can be challenging to diagnose TBI in cases where macroscopic signs of the traumatic head impact are lacking and little is known about the circumstances of death. In recent years, several post-mortem studies investigated the possible use of biomarkers for providing objective evidence for TBIs as the cause of death or to estimate the survival time and time since death of the deceased. This work systematically reviewed the available scientific literature on TBI-related biomarkers to be used for forensic purposes. Post-mortem TBI-related biomarkers are an emerging and promising resource to provide objective evidence for cause of death determinations as well as survival time and potentially even time since death estimations. This literature review of forensically used TBI-biomarkers revealed that current markers have low specificity for TBIs and only provide limited information with regards to survival time estimations and time since death estimations. Overall, TBI fatality-related biomarkers are largely unexplored in compartments that are easily accessible during autopsies such as urine and vitreous humor. Future research on forensic biomarkers requires a strict distinction of TBI fatalities from control groups, sufficient sample sizes, combinations of currently established biomarkers, and novel approaches such as metabolomics and mi-RNAs.
Routine coronal paraffin-sections through the dorsal frontal and parieto-occipital cortex of a total of sixty cases with divergent causes of death were immunohistochemically (IHC) stained with an antibody against TMEM119. Samples of cerebrospinal fluid (CSF) of the same cases were collected by suboccipital needle-puncture, subjected to centrifugation and processed as cytospin preparations stained with TMEM119. Both, cytospin preparations and sections were subjected to computer-assisted density measurements. The density of microglial TMEM119-positive cortical profiles correlated with that of cytospin results and with the density of TMEM119-positive microglial profiles in the medullary layer. There was no statistically significant correlation between the density of medullary TMEM119-positive profiles and the cytospin data. Cortical microglial cells were primarily encountered in supragranular layers I, II, and IIIa and in infragranular layers V and VI, the region of U-fibers and in circumscribed foci or spread in a diffuse manner and high density over the white matter. We have evidence that cortical microglia directly migrate into CSF without using the glympathic pathway. Microglia in the medullary layer shows a strong affinity to the adventitia of deep vessels in the myelin layer. Selected rapidly fatal cases including myocardial infarcts and drowning let us conclude that microglia in cortex and myelin layer can react rapidly and its reaction and migration is subject to pre-existing external and internal factors. Cytospin preparations proved to be a simple tool to analyze and assess complex changes in the CNS after rapid fatal damage. There is no statistically significant correlation between cytospin and postmortem interval. Therefore, the quantitative analyses of postmortem cytospins obviously reflect the neuropathology of the complete central nervous system. Cytospins provide forensic pathologists a rather simple and easy to perform method for the global assessment of CNS affliction.
Zusammenfassung „Black esophagus“ oder „akute Ösophagusnekrose“ (AÖN) ist eine seltene Erkrankung, die sich makroskopisch durch eine zirkumferente Schwarzverfärbung der Ösophagusmukosa mit abruptem Ende am gastroösophagealen Übergang auszeichnet. Die genaue Pathogenese ist unbekannt; es werden multifaktorielle Einflüsse wie z. B. Säurereflux, Ischämie und verringerte Schutzmechanismen der Mukosa als mögliche Ursachen diskutiert. Vorgestellt werden 2 Obduktionsfälle, die typische Befunde einer AÖN aufwiesen. Zusätzlich hatten Fall 1 eine Candida -Infektion und Fall 2 eine Appendizitis, sodass eine infektiöse Genese in beiden Fällen eine Rolle gespielt haben könnte.
The aim of this pilot study was to investigate the diagnostic potential of TMEM119 as a useful microglia-specific marker in combination with immunostainings for phagocytic function and infiltrating capacity of monocytes in cases of lethal monosubstance intoxications by morphine (MOR), methamphetamine (METH), and of ethanol-associated death (ETH) respectively. Human brain tissue samples were obtained from forensic autopsies of cases with single substance abuse (MOR, n = 8; ETH, n = 10; METH, n = 9) and then compared to a cohort of cardiovascular fatalities as controls (n = 9). Brain tissue samples of cortex, white matter, and hippocampus were collected and stained immunohistochemically with antibodies against TMEM119, CD68KiM1P, and CCR2. We could document the lowest density of TMEM119-positive cells in MOR deaths with highly significant differences to the control densities in all three regions investigated. In ETH and METH deaths, the expression of TMEM119 was comparable to cell densities in controls. The results indicate that the immunoreaction in brain tissue is different in these groups depending on the drug type used for abuse.