Of all tuberculosis (TB) cases, 1% affects the central nervous system (CNS), with a mortality rate of up to 60%. Our aim is to fill the 'key gap' in TBM research by analyzing brain specimens in a unique historical cohort of 84 patients, focusing on granuloma formation. We describe three different types: non-necrotizing, necrotizing gummatous, and necrotizing abscess type granuloma. Our hypothesis is that these different types of granuloma are developmental stages of the same pathological process. All types were present in each patient and were mainly localized in the leptomeninges. Intra-parenchymal granulomas were less abundant than the leptomeningeal ones and mainly located close to the cerebrospinal fluid (subpial and subependymal). We found that most of the intraparenchymal granulomas are an extension of leptomeningeal lesions which is the opposite of the classical Rich focus theory. We present a 3D-model to facilitate further understanding of the topographic relation of granulomas with leptomeninges, brain parenchyma and blood vessels. We describe innate and adaptive immune responses during granuloma formation including the cytokine profiles. We emphasize the presence of leptomeningeal B-cell aggregates as tertiary lymphoid structures. Our study forms a basis for further research in neuroinflammation and infectious diseases of the CNS, especially TB.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has revealed diverse neurological manifestations of coronavirus disease 2019 (COVID-19). This case report begins with a background review of the neurological effects of COVID-19, focusing on stroke, neuroinflammation, and coagulopathy. It then describes the clinical course and autopsy findings of a young patient presenting with COVID-19–associated stroke. The formal neuropathological examination is presented, along with the systemic and brain histological features. Interesting aspects include multiterritory hemorrhagic infarctions, microinfarcts throughout the cortex and white matter, and prominent mixed inflammatory cell cuffing of intracerebral blood vessels distant from the infarcts.

Background: Tuberculous meningitis (TBM), caused by Mycobacterium tuberculosis, is the most severe form of extrapulmonary tuberculosis and isassociated with high morbidity and mortality, particularly when diagnosis is delayed. Improved understanding of the metabolic alterations associated withTBM may support the development of novel diagnostic biomarkers and provide insights into disease pathophysiology. Method: In this study, we applied anuntargeted two-dimensional gas chromatography–time-of-flight mass spectrometry (GC×GC-TOFMS) metabolomics approach to formalin-fixed, paraffin-embedded (FFPE) postmortem human brain tissue from 41 TBM cases and 36 tissue sections from 6 non-TBM control cases. Metabolomics data wereprocessed, normalized, and analyzed using multivariate and univariate statistical approaches, including principal component analysis (PCA) and partialleast squares–discriminant analysis (PLS-DA), with variable importance in projection (VIP) scores. These results were further correlated with patient clinical data. Results: Distinct metabolic profiles were observed between TBM and control tissues. Several metabolites were significantly reduced in TBM samples, particularly within the alkane and alkene classes, with additional decreases observed in metabolites associated with alcohols, fatty acids, lipids, carbohydrates, and amino acids. These metabolic alterations suggest substantial perturbations, primarily in the host lysine degradation pathway (linked to the kynurenine pathway), in TBM-affected brain tissue. Conclusion: Collectively, these findings provide insight into the metabolic landscape of terminalTBM and suggest potential metabolic pathways that may contribute to disease pathophysiology. Further investigation of these metabolic signatures in accessible patient tissue and biofluids may support the development of biomarkers and inform future therapeutic strategies for TBM.

Background/Objectives Parvovirus B19 (PVB19) is the most frequently detected virus in endomyocardial biopsy (EMB) specimens of patients with acute myocarditis in both the developed world and South Africa. Its pathogenic role, however, remains debated as it is also commonly detected in hearts of patients with idiopathic dilated cardiomyopathy and cohorts of patients undergoing cardiac surgery and post-mortem cohorts without histological evidence of myocarditis. We sought to investigate the incremental diagnostic role of PVB19 viral load on EMB in a local cohort of patients with confirmed myocarditis. Methods This is a retrospective cross-sectional study. Consecutive adults presenting to a single tertiary centre in South Africa between August 2017 and January 2022 with clinically suspected acute myocarditis who had undergone both cardiac magnetic resonance imaging (CMR) and EMB, and had PVB19 detected by polymerase chain reaction (PCR) in EMB specimens, were included. Results Forty-nine patients with clinically suspected myocarditis had PVB19 detected on EMB specimens. Acute myocarditis was confirmed by CMR and/or EMB in 39 patients. The median high sensitivity troponin T (295.0ng/L vs 57.5ng/L, p = 0.035) and PVB19 viral load (483copies/ml vs 226copies/ml, p = 0.02) were significantly higher in patients with confirmed acute myocarditis compared to those without. The optimal PVB19 viral load threshold to determine clinical significance in the local population was 316copies/ml. Conclusions The mere presence of PVB19 in EMB specimens of patients with clinically suspected myocarditis appears to be insufficient for proving its causal role in acute myocarditis in South Africa. However, the presence of high viral copies may be used to inform the clinical relevance of a positive PVB19 EMB result.