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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.

Unruptured intracranial aneurysms are usually not managed on an emergency basis, although for patients, uncertainty and waiting can be stressful. We assessed the incidence of aneurysms rupturing during the initial period of awareness of having an aneurysm. We studied all patients visiting our service with an unruptured intracranial aneurysm between January 2000 and March 2013. For the exposure time (time between diagnosis and discussion of treatment plan, together with time on waiting list for treatment), we calculated incidence of aneurysmal rupture with corresponding 95 % confidence intervals. We compared this incidence with expected incidence (based on size and site for each aneurysm). 398 patients were included; five had aneurysmal rupture during the exposure time. The observed incidence of aneurysmal rupture during exposure time was 47/1,000 patient-years (95 % confidence interval 15-111); the expected incidence was 0.7/1,000. Our data suggest that the risk of aneurysmal rupture early after detection of unruptured aneurysms is higher than expected based on aneurysm characteristics.