Blood-CSF-barrier permeability in tuberculous meningitis and its association with clinical, MRI and inflammatory cytokines

Abstract

Blood -cerebrospinal fluid-barrier (BCB) disruption in tuberculous meningitis (TBM) may be mediated by inflammatory cytokines, and may determine clinico-radiological severity and outcome. We report BCB permeability in TBM and its relationship with inflammatory cytokines (TNF-α, IL-1β and IL-6), clinical severity, MRI changes and outcome. 55 TBM patients with a median age of 26 years were included. Their clinical, cerebrospinal fluid (CSF) and MRI findings were noted. The severity of meningitis was graded into stages I to III. Cranial MRI was done, and the presence of exudates, granuloma, hydrocephalus and infarctions was noted. BCB permeability was assessed by a ratio of CSF albumin to serum albumin (Q_alb). The concentration of TNF-α, IL-1β and IL-6 in CSF were measured by cytokine bead array. The Q_alb in the patients was more than the mean + 2.5 SD of controls. In TBM, Q_alb correlated with TNF- α (r = 0.47; p = 0.01), CSF cells (r = 0.29; p = 0.02) and exudate on MRI (0.18 ± 0.009 Vs 0.13 ± 0.008; p = 0.04). There was however no association of Q_alb with demographic variables, stage, tuberculoma, infarction and hydrocephalus. At 6 months, 11(20%) died, 10(18.2%) had poor and 34(61.8%) had a good recovery. BCB permeability in TBM correlated with TNF-α, CSF pleocytosis and exudates but not with severity of meningitis and outcome.