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).

Keywords: Apoptosis; Histopathology; Pneumococcal meningitis; Vascular inflammation.

Fig. 1

Apoptotic cells in hippocampus dentate gyrus. a Overview of hippocampus in HE stain. The apoptotic cells are marked with red dots. b–d Three apoptotic cells are indicated by arrows and magnified in b, c and d. Arrows again indicate the apoptotic cells. e. TUNEL analysis. Arrows indicate the positive cells

Fig. 2

Flow chart patient selection

Fig. 3

Pathological findings in pneumococcal meningitis. Short illustration of histological abnormalities. The score is based on severity of each lesion and also extensiveness/multifocality of the histological abnomalities. a–c Meningeal inflammation: Little (a), moderate (b) and extensive (c) infiltration of neutrophils in the sub-arachnoid space. d–f Meningeal inflammation components: mainly neutrophils (d), mainly macrophages (e) and mix of neutrophils and macrophages (f) in a late phase case. g–i Infarction: focal small hypoxic-ischemic neuronal injury with eosinophilic neurons (g), focal large established infarct with tissue degeneration and infiltration of inflammatory cells (h) and one of multifocal large infarcts with gliosis in the late phase (i). j–l Haemorrhage: focal small perivascular haemorrhages (j), multifocal parenchymal moderate size haemorrhages (k) and multifocal large haemorrhage (l). m–o Large-medium size meningeal arterial inflammation in the early phase: mild (m, admission day 3) and severe sub-endothelial inflammation with near obstruction of vascular lumen in n (admission day 3). In o (admission day 3), vascular inflammation extends into the tunica media with destruction of elastica layer. p–r Pathological changes of large-medium size arteries in the late phase: broadened tunica intima with formation of connective tissue infiltrated by various quantities of mixed inflammatory cell composed of macrophages, lymphocytes, plasma cells and neutrophils (p, admission day 18), reactive change of artery with thickening of tunica intima with near obstruction of lumen (q, admission day 21), and reactive change of artery with tunica media degeneration and dilation (r, admission day 30). s–u Pathological changes of small brain parenchymal vessels: inflammation (s), total destruction and degeneration (t) and thrombosis (u). v–x Thrombosis and parenchymal infiltration of inflammatory cells: thrombosis of artery with total obstruction (v), parenchymal infiltration of inflammatory cells (w, neutrophils are marked with asterick) and a small abscess in basal ganglia (x)