Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.

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.

Neuropathological Variability within a Spectrum of NMDAR-Encephalitis.

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.

Successful repair of bilateral common carotid artery dissections from hanging.

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.

Micromorphological changes in cardiac tissue of drug-related deaths with emphasis on chronic illicit opioid abuse.

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.

[Sudden infant death in Austria--status quo and recommendations of the SIDS Consensus Working Group for Improved Registration]. / Der plötzliche Säuglingstod in Osterreich--Status quo und Empfehlungen der SIDS-Konsensusarbeitsgruppe zur verbesserten Erfassung.

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.

Discovery of decomposed and mummified corpses in the domestic setting--a marker of social isolation?

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.