Pathophysiology of septic encephalopathy - an unsolved puzzle

The clinical study by van der Boogaard and colleagues recently published in Critical Care [1] was designed to unravel some of the open questions regarding the pathophysiology of septic encephalopathy. The authors mimicked inflammation-associated encephalopathy by induction of experimental endotoxemia using Escheria coli-derived lipopolysaccharides (LPSs) in 15 healthy young volunteers. Outcome parameters were serum levels of cytokines, cortisol, neuron specific enolase, S100-β, as well as electroencephalographic changes and cognitive function in comparison to a healthy cohort of ten control volunteers. Interestingly, van der Boogaard and colleagues described that the endotoxin-induced 'cytokine storm' and cortisol release failed to provoke any signs of septic encephalopathy [1]. No clinically relevant electroencephalographic changes occurred, and markers of neuronal damage (neuron specific enolase, S100-β) were found to be slightly reduced following LPS challenge. Endotoxemia even resulted in a higher state of alertness and improved cognitive function in comparison to the healthy cohort. The authors concluded that temporary systemic inflammation caused by endotoxemia cannot provoke the development of septic encephalopathy. Nonetheless, their present study shed some further light towards our understanding of the immunological pathophysiology of septic encephalopathy, as it appears unlikely that bacterial LPS is a driving force in the development of septic encephalopathy. Note worthy, the spectrum of responsible microorganisms has shifted from predominantly Gram-negative bacteria in the late 1970s and 1980s to predominantly Gram-positive bacteria and fungal infections at present [2].The authors' findings underscore the complexity and ambiguity of septic encephalopathy, which continues to be a puzzling complication of the sepsis syndrome. This is of particular concern, as up to 70% of all septic patients develop signs of such brain damage [3]. Traditionally, septic enc