Septic Encephalopathy: Relationship to Serum and Cerebrospinal Fluid Levels of Adhesion Molecules, Lipid Peroxides and S-100B Protein

Severe septic illness is often associated with cerebral manifestations such was disturbed consciousness and delirium. Little was known about its effect on the CNS. This is the first study in children that has assessed the direct mediators of brain inflammation and injury with sepsis. The serum and CSF concentrations of soluble intracellular adhesion molecule-1 (sICAM-1) (marker of endothelium-leukocyte interaction), nitric oxide (NO) and lipid peroxide (LPO) (markers for lipid peroxiclation) and S-100B protein (marker of astrocytes activation and injury), were measured in 40 children with sepsis of whom 40% had moderate to severe septic encephalopathy. Serum from 25 normal children was used for comparison. Serum values of sICAM-1, NO, LPO and S100B were elevated in patients compared to controls. The greater elevation of the CSF:serum albumin ratio suggests loss of blood-brain barrier integrity. After normalising for CSF:serum albumin ratio, we demonstrated a significant intrathecal synthesis of NO, LPO and S100B. Patients with encephalopathy had elevated serum and CSF levels of sICAM-1, NO, LPO and S100B compared to sepsis only. This study indicates that the brain is vulnerable in children with sepsis. It also suggests that coordinated interactions between immune system, vascular endothelial cells, CNS barriers, astrocytes and brain lipid peroxides, may contribute to septic encephalopathy.