Systemic inflammation is associated with increased cerebrospinal fluid CRP and may affect meningitis diagnostics

Abstract

C-reactive protein (CRP) in cerebrospinal fluid (CSF) has been proposed as a highly specific diagnostic marker for bacterial meningitis. We investigated whether systemic inflammation, in the absence of CNS infection, can lead to detectable CSF CRP and examined the roles of plasma CRP and blood-brain barrier (BBB) permeability. We measured CRP in the CSF (CRP CSF ) and plasma (CRP plasma ) of patients undergoing elective aortic aneurysm surgery. Serial paired CSF and plasma samples were obtained from baseline to 72 h postoperatively. The CSF/plasma albumin quotient (Q-alb) was used as a measure of BBB permeability. In this prospective observational cohort study, 71 patients were included. CRP plasma increased significantly after surgery. CRP CSF remained undetectable (< 0.20 mg/L) until 24 h, and became detectable (> 0.20 mg/L) in 74% of patients by 72 h. Detectable CRP CSF required a minimum CRP plasma threshold (79.1 mg/L), however, not all patients exceeding this threshold exhibited detectable CRP CSF . Higher and sustained Q-alb (BBB permeability) was identified as the predominant discriminatory factor between patients with- and without detectable CRP CSF . In patients with systemic inflammation, in absence of CNS infection, systemic inflammation leading to BBB permeability can result in detectable CRP CSF . Systemic inflammation induced BBB permeability was the dominant determinant of CRP entering the CSF. These findings underscore the need for careful interpretation once CRP is detected in CSF, particularly in patients with some degree of systemic inflammation who present with symptoms suggestive of CNS infection.