title: Pneumococcal meningitis: clinical-pathological correlations (MeninGene-Path).
abstract: Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been treated with adjunctive dexamethasone therapy. Observed pathological processes were inflammation of medium-large arteries in 30 brains (97 %), cerebral haemorrhage in 24 (77 %), cerebritis in 24 (77 %), thrombosis in 21 (68 %), infarction in 19 (61 %) and ventriculitis in 19 (of 28 cases, 68 %). Inflammation of medium-large arteries led to obstruction of the vascular lumen in 14 (of 31 cases, 45 %). Vascular inflammation was associated with infarction and thrombosis of brain parenchymal vessels. Hippocampal dentate gyrus apoptosis between patients treated with and without dexamethasone was similar (p = 0.66); however, dexamethasone treated patients had higher total pathology score than non-dexamethasone treated patients (p = 0.003). Our study shows that vascular damage is key in the process of brain damage in pneumococcal meningitis. Data and material of this study will be made open-access for translational research in pneumococcal meningitis (MeninGene-Path).
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam (CINIMA), PO Box 22660, 1100DD, Amsterdam, The Netherlands.
authors.forename: Joo-Yeon
authors.initials: JY
authors.lastname: Engelen-Lee
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam (CINIMA), PO Box 22660, 1100DD, Amsterdam, The Netherlands.
authors.forename: Matthijs C
authors.initials: MC
authors.lastname: Brouwer
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Center of Infection and Immunity Amsterdam (CINIMA), PO Box 22660, 1100DD, Amsterdam, The Netherlands. D.vandeBeek@amc.uva.nl.
authors.forename: Diederik
authors.initials: D
authors.lastname: van de Beek
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis; D001921:Brain / Q000473:pathology*; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000473:pathology; D008297:Male; D008586:Meningitis, Pneumococcal / Q000150:complications* / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology / Q000382:microbiology; D009474:Neurons / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013927:Thrombosis / Q000209:etiology / Q000382:microbiology; D014657:Vasculitis / Q000209:etiology*
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone
keywords: Apoptosis; Histopathology; Pneumococcal meningitis; Vascular inflammation