Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68

Background: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. Methods: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. Results: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic–ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). Conclusions: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.

OBJECTIVE:To describe the neuropathological features of N-methyl-D-aspartate receptor (NMDAR)-encephalitis in an archival autopsy cohort. METHODS:We examined four autopsies from patients with NMDAR-encephalitis; two patients were untreated, three had comorbidities: small cell lung cancer, brain post-transplant lymphoproliferative disease (PTLD), and overlapping demyelination. RESULTS:The two untreated patients had inflammatory infiltrates predominantly composed of perivascular and parenchymal CD3+ /CD8- T cells and CD79a+ B cells/plasma cells in basal ganglia, amygdala, and hippocampus with surrounding white matter. The hippocampi showed a significant decrease of NMDAR-immunoreactivity that correlated with disease severity. The patient with NMDAR-encephalitis and immunosuppression for kidney transplantation developed a brain monomorphic PTLD. Inflammatory changes were compatible with NMDAR-encephalitis. Additionally, plasma cells accumulated in the vicinity of the necrotic tumor along with macrophages and activated microglia that strongly expressed pro-inflammatory activation markers HLA-DR, CD68, and IL18. The fourth patient developed demyelinating lesions in the setting of a relapse 4 years after NMDAR-encephalitis. These lesions exhibited the hallmarks of classic multiple sclerosis with radially expanding lesions and remyelinated shadow plaques without complement or immunoglobulin deposition, compatible with a pattern I demyelination. INTERPRETATION:The topographic distribution of inflammation in patients with NMDAR-encephalitis reflects the clinical symptoms of movement disorders, abnormal behavior, and memory dysfunction with inflammation dominantly observed in basal ganglia, amygdala, and hippocampus, and loss of NMDAR-immunoreactivity correlates with disease severity. Co-occurring pathologies influence the spatial distribution, composition, and intensity of inflammation, which may modify patients' clinical presentation and outcome. ANN NEUROL 2021;90:725-737.

Aims The main intention of this retrospective study was to investigate whether chronic illicit drug abuse, especially the intravenous use of opioids (heroin), could potentially trigger the development of myocardial fibrosis in drug addicts. Design A retrospective case–control study was performed using myocardial tissue samples from both drug-related deaths (DRD) with verifiable opioid abuse and non-drug-related deaths in the same age group. Setting Department of Forensic Medicine, Medical University of Vienna, Austria (1993–94). Participants Myocardial specimens were retrieved from 76 deceased intravenous opioid users and compared to those of 23 deceased non-drug users. Measurements Drug quantification was carried out using the enzyme-multiplied immunoassay technique (EMIT), followed by [gas chromatography–mass spectrometry (GC–MS), MAT 112®], and analysed using the Integrator 3390A by Hewlett Packard® and LABCOM.1 computer (MSS-G.G.). The amount of fibrous connective tissue (FCT) in the myocardium was determined by using the morphometric software LUCIA Net version 1.16.2©, Laboratory Imaging, with NIS Elements 3.0®. Findings Drug analysis revealed that 67.11% were polydrug users and the same proportion was classified as heroin addicts (6-monoacetylmorphine, 6-MAM)—32.89% were users of pure heroin. In 76.32% of DRD cases, codeine was detected. Only 2.63% consumed cocaine. The mean morphine concentrations were 389.03 ng/g in the cerebellum and 275.52 ng/g in the medulla oblongata, respectively. Morphometric analysis exhibited a strong correlation between DRD and myocardial fibrosis. The mean proportion of FCT content in the drug group was 7.6 ± 2.9% (females: 6.30 ± 2.19%; males: 7.91 ± 3.01%) in contrast to 5.2 ± 1.7% (females: 4.45 ± 1.23%; males: 5.50 ± 1.78%) in the control group, indicating a significant difference (P = 0.0012), and a significant difference in the amount of FCT between females and males (P = 0.0383). There was no significant interaction of age and FCT (P = 0.8472). Conclusions There is a long-term risk of cardiac dysfunction following chronic illicit drug abuse with opioids as a principal component. Regular cardiological examination of patients receiving substitution treatment with morphine is strongly recommended.

The management of blunt carotid artery dissections caused by hanging remains controversial, especially with regard to diagnostic work-up and treatment options. We present 2 men, 49 and 41 years of age, who were treated for bilateral common carotid artery dissection caused by strangulation. In the first patient, additional cricotracheal separation and blunt thyroid gland trauma was observed. Bilateral saphenous vein graft interposition was accomplished in both patients. In the first patient, tracheal repair and suture of the thyroid gland completed the procedure. At 1 year of follow-up, both patients were capable of managing their lives independently. A systematic review of the literature on managing near-hanging and nonfatal strangulation victims is included in this report to allow this case series to be put into perspective.

Aim: A central respiratory regulation disturbance-triggered by impaired oxygen supply to the brainstem-is being discussed as an aetiological factor in sudden infant death syndrome. In this experimental study, further insight was sought into how far cervical spine movements may induce critical narrowing of the vertebral arteries. Methods: In 10 infant bodies, the vertebral arteries were cannulated close to their origin and perfused with a fluid bolus of 5 ml in 2 s. The intravascular peak pressure created was memorized. Individual resistance indices were computed for every vertebral artery by relating the average pressure maximum from 10 measurements each with maximal rotation of the neck to either side alone and then with additional hyperextension of the cervical spine to the average peak pressure in neutral head position. Results: Alterations of position-induced pressure changes occurred in the vertebral arteries of all children. Considering exclusively the combined movements of rotation plus extension, resistance increased ipsi- and contralaterally-no matter which side the head was turned-in three infants. A further three reacted with resistance surges only contralateral to the direction of rotation, and one only ipsilateral. Double contralateral associated with only one-directional ipsilateral rise was observed twice, and vice versa once.Conclusion: The presented method enables crude quantification of postmortem dynamic resistance alterations in the vertebral arteries. How far such measurements reflect authentic circulatory conditions during life remains to be assessed.

Mass media reports attribute the occurrence of decomposed or mummified corpses in a domestic setting mainly to an increasing social isolation of elderly people. Not much is known about the demographic and medical conditions under which individuals are found months or even years after death in their homes. For this study, autopsy reports of individuals found dead and mummified or decomposed between 1993 and 1997 with those from 1963 to 1967 were retrospectively analyzed. Between 1993 and 1997, a total number of 320 individuals were found decomposed at home compared to 412 such cases between 1963 and 1967. The proportion of individuals older than 64 years was significantly higher during the 1990s study period. Furthermore, the proportion of deaths attributable to natural causes was significantly lower during the 1990s, whereas the rate of suicides was nearly three times higher.

Sudden infant death (SID) is the most common cause of death among infants aged 2 to 12 months in Austria. The complete autopsy required in order to diagnose SID, including the additional investigations, and the comprehensive autopsies needed for epidemiological studies are not common practice because of the different statutory regulations in the provinces and the absence of a uniform federal law in this regard. According to statistics, in the last four years only 83% (1997) to 70% (1999) of the reported SID cases in Austria were autopsied. Our survey in the forensic medicine and pathological institutes of Austria also revealed markedly different practices in regard of the manner in which autopsies are performed and parents are interviewed and followed up. For this reason, the SIDS Consensus Work Group of Austrian centers for the prevention of sudden infant death recommends the following: a) a comprehensive autopsy by a trained specialist to be established as a prerequisite for diagnosing "SIDS"; b) performing autopsies on a centralized basis in those forensic or pathological institutes that have agreed to adhere to protocol-based autopsy standards; c) the introduction of quality control in terms of a regional clinical-pathological conference; and d) standardizing the elements of the interview with parents of SID victims.Implementing these measures and entering the collected information into a data base in which the master data are encoded by the individual institutions, will help to evaluate the role of major epidemiological risk factors that information campaigns are focused upon, namely sleeping in prone position, the role of nicotine, etc. In addition, it will be necessary to formulate federal laws that standardize the divergent provincial regulations.

Seventy-six pituitary adenomas of akromegalic patients were investigated to find out the prognostic relevance of the intracytoplasmic distribution of cytokeratins (CK), immunohistochemically defined hormone production profile, proliferative activity and clinical presentation. CK distribution, growth fraction (MIB1 index) and hormone production profile were analyzed by means of immunohistochemistry. Apoptotic activity was investigated by the TUNEL method. Two different CK distribution patterns were seen: a dot-like pattern in 29 cases (type 1 adenomas), and a perinuclear fibrillary pattern in 47 cases (type 2 adenomas). Type 2 adenomas showed more prominent coexpression of prolactin (p < 0.0001), luteotrophic hormone (p < 0.002), follicle-stimulating hormone (p < 0.005), thyroid-stimulating hormone (p < 0.0001), and alpha-subunit (p < 0.005), as compared to type 1 adenomas. The mean MIB1 index was significantly higher in type 1 vs. type 2 tumors (4.23%, range: 1.93% - 9.83% vs. 2.07%, range: 0.67% - 4.87%, p < 0.0001). Apoptotic activity was too low in both examined groups to be used for balancing of tumor cell turnover. Clinical analysis of patients with type 1 adenomas revealed female predominance, younger age, larger tumor size, and more frequently aggressive growth with higher incidence of suprasellar extension (p < 0.0001) and cavernous sinus infiltration (p < 0.0001), as well as larger proportions of re-operations and incomplete resections (34.5% vs. 8.51%). Additionally, the interval until re-operation was shorter in type 1 adenomas (mean: 16 months, range: 9 - 21 months vs. mean: 57 months, range: 18- 158 months). We conclude that classification of adenomas of akromegalic patients based on intracytoplasmic CK distribution, combined with examination of proliferative activity, and immunohistochemically defined hormone production profile, provides important prognostic information for the management of akromegalic patients.

The Shwachman-Diamond syndrome (SDS) is a rare congenital disorder for which inheritance by an autosomal recessive trait has been suggested. Shwachman-Diamond syndrome is defined by exocrine pancreatic insufficiency combined with severe neutropenia. Moreover, SDS patients are at risk to develop neoplastic hematologic diseases. We describe 2 SDS-affected daughters of consanguine parents who were born 1 year apart, at 35 and 36 weeks of gestation, and who died at the age of 4 and 3.5 months, respectively, due to respiratory infections. Histologic bone marrow evaluation of the second-born child revealed a diffuse proliferation of immature B cells, which comprised 40% of the total cellularity. These cells were identified as precursor B cells by immunophenotyping studies (CD79a(+)/CD10(+)/CD20(-)/CD22(-)/CD34(-)/ terminal deoxynucleotidyl transferase(-)). Molecular determination of the immunoglobulin heavy-chain gene status did not reveal clonality. The emergence of this peculiar B-cell population was interpreted as a marked increase of hematogones. Although the clinical significance and the exact function of hematogones is still obscure, they may play a critical regenerative role in the regulation of hemopoiesis, but without malignant potential in SDS. Immunophenotyping and molecular studies, therefore, have potential value in the differential diagnosis of primary bone marrow failures. This report adds SDS to the spectrum of conditions in which a prominent number of hematogones may be observed.

The substance methadone is used for substitution therapy since the 1960s in the U.S. Mainly because of the endemic spread of HIV-1 infections among intravenous drug abusers methadone was made legally available through medical prescription in Austria in 1987. Legal authorities today also allow the patient to take home the necessary daily consumption for weekends or public holidays. The drug is distributed as a watery solution in tiny bottles, which are fitted with an ordinary screw cap. This kind of distribution may, however, have fatal consequences. This is demonstrated in the following case of accidental poisoning of an infant: A two-year-old girl whose parents were both participating in the substitution scheme was found dead in her bed in Vienna in 1997. Forensic autopsy revealed a methadone concentration in the liver tissue of 640 ng/g. The criminal investigation determined that the girl had opened a bottle of methadone solution and subsequently had taken the drug. Considering the circumstances of this accident, from the medical point of view safety devices for the screw caps of the methadone bottles should be required by law, in order to avoid future accidental poisoning.

AIMS:To investigate the quality of heroin seized in Vienna between 1987 and 1995 and to examine whether there was a relationship between the quality of heroin and the rate of drug-related deaths.DESIGN:Reports of heroin seizure analysis and post-mortem reports of heroin-related deaths in Vienna from 1987 to 1995 were analysed.RESULTS:There were 386 seizures of heroin comprising a total weight of 25 640.12 g heroin. All the seizures were in the base form. All seizures also contained a diluent, mainly lactose. Additionally, in 95 seizures caffeine, in four seizures paracetamol and in three seizures metaqualon were detected. Of a total of 764 drug-related deaths 506 cases were classified as heroin-related deaths. In 336 cases other central nervous system-depressant drugs and/or alcohol could be detected in the blood in addition to morphine (polydrug heroin-related deaths). There was evidence of a trend towards greater polydrug involvement during the study period. The age of victims of polydrug heroin-related deaths remained unchanged over time while the age of victims of pure heroin-related deaths decreased significantly. The morphine concentration in the medulla oblongata in heroin-related deaths decreased significantly. Finally, there was no statistically significant relationship between the rate of heroin-related deaths per year and the diacetylmorphine concentration of heroin seizures in that year.CONCLUSION:The results did not substantiate the widely held belief that increases in heroin-related deaths could be explained by an increase in the quality of heroin.

The smuggling of illicit drugs by means of body packing has become a common problem at European airports. Europe is considered to be the fastest growing market for cocaine worldwide, and the air route is the most frequently used method of trafficking cocaine. Smuggling illicit drugs by use of body packing is considered to be a high toxicological hazard because of the risk of leakage or a package bursting. We report about the first case of suicide of a body packer by re-ingesting the content of excreted cocaine packages. The consequence of this case is that the death scene investigation and autopsy assessments in case of a body packer's death should always consider the possibility of re-ingested packages. Detention personnel should be instructed by forensic and criminalistic experts to take preventive measures.

Drugs that affect the central nervous system are generally assumed to have the potential to impair driving ability. In a retrospective survey, police files and the results of toxicological urine analysis from drivers suspected of driving under the influence of drugs in Vienna from 1993 to 1996 were investigated. Decisive for police intervention was "unsafe driving" (swerving, hesitating, going too slowly, etc.), driving at high speed within the city limits, driving through red lights or stop signs, and driving at night without lights. In one-fifth of the cases drivers caused a traffic accident. Casting suspicion on driving under influence of drugs was mainly caused by impaired coordination of movements, bloodshot eyes, slurred speech, drowsiness, conspicuous behavior, and changed pupils. In the majority of the study population more than two symptoms were recorded by police. In 94% of the cases police suspicions could be confirmed by toxicological urine analysis.

In Austria every death is subject to an examination by a medical doctor authorized by the local health authority. If death is suspected to be natural and/or perpetrated by another person, this doctor has to report it to the police. Depending on the investigation results, the examining magistrate in charge demands a judicial autopsy at the Institute of Forensic Medicine. In 1989, 41 murders of old patients by nursing assistants in a Viennese public hospital were disclosed. The main aim of this retrospective study was to determine any change in the demand for forensic autopsies by the Viennese health authority, as well as by the criminal court, after 1989. Furthermore, it was of interest to analyze the reporting practices of medical doctors examining corpses, as well as thr reaction of the criminal court during the study period. After 1989, there was a significant increase of non-judicial and judicial autopsies, performed by Viennese forensic pathologists. In addition, there was a significant increase of reports to the police by coroners as well as by forensic pathologists, paralleled by a higher rate of forensic autopsies demanded by the examining magistrate. This increase of forensic autopsies took place even though the overall rate of deaths in Vienna significantly decreased during the 10-year study period. Thus, the disclosure of 41 murders in the Viennese hospital in 1989 can be assumed as a turning point in the reporting practices of Viennese coroners, as well as the autopsy rate handled by Viennese forensic pathologists.