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Developments in the management of critically ill patients suffering organ dysfunctions have demonstrated that brain is the prominent organ to be effected during critical illness. Acute brain dysfunction due to pathologic neuroinflammatory processes associated with sepsis is commonly seen and related to morbidity and mortality in the ICU treatment. Studies reported that survivors of sepsis may suffer long-term cognitive dysfunction that affects quality of life. However, there are no specific approaches to diagnose acute brain dysfunction in the early phase to target protective measures. In recent years, imaging methods and biomarkers are the most important issues of studies. This review will address the current diagnostic approaches to acute brain dysfunction related to sepsis.

Background: Incidence and patterns of brain lesions of sepsis-induced brain dysfunction (SIBD) have been well defined. Our objective was to investigate the associations between neuroimaging features of SIBD patients and well-known neuroinflammation and neurodegeneration factors., Methods: In this prospective observational study, 93 SIBD patients (45 men, 48 women; 50.6 ± 12.7 years old) were enrolled. Patients underwent a neurological examination and brain magnetic resonance imaging (MRI). Severity-of-disease scoring systems (APACHE II, SOFA, and SAPS II) and neurological outcome scoring system (GOSE) were used. Also, serum levels of a panel of mediators [IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-γ, TNF-α, complement factor Bb, C4d, C5a, iC3b, amyloid-β peptides, total tau, phosphorylated tau (p-tau), S100b, neuron-specific enolase] were measured by ELISA. Voxel-based morphometry (VBM) was employed to available patients for assessment of neuronal loss pattern in SIBD., Results: MRI of SIBD patients were normal (n = 27, 29%) or showed brain lesions (n = 51, 54.9%) or brain atrophy (n = 15, 16.1%). VBM analysis showed neuronal loss in the insula, cingulate cortex, frontal lobe, precuneus, and thalamus. Patients with abnormal MRI findings had worse APACHE II, SOFA, GOSE scores, increased prevalence of delirium and mortality. Presence of MRI lesions was associated with reduced C5a and iC3b levels and brain atrophy was associated with increased p-tau levels. Regression analysis identified an association between C5a levels and presence of lesion on MRI and p-tau levels and the presence of atrophy on MRI., Conclusions: Neuronal loss predominantly occurs in limbic and visceral pain perception regions of SIBD patients. Complement breakdown products and p-tau stand out as adverse neuroimaging outcome markers for SIBD.

Introduction: Sepsis-induced brain dysfunction (SIBD) has been neglected until recently due to the absence of specific clinical or biological markers. There is increasing evidence that sepsis may pose substantial risks for long term cognitive impairment. Methods: To find out clinical and inflammatory factors associated with acute SIBD serum levels of cytokines, complement breakdown products and neurodegeneration markers were measured by ELISA in sera of 86 SIBD patients and 33 healthy controls. Association between these biological markers and cognitive test results was investigated. Results: SIBD patients showed significantly increased IL-6, IL-8, IL-10 and C4 d levels and decreased TNF-α, IL-12, C5a and iC3b levels than healthy controls. No significant alteration was observed in neuronal loss and neurodegeneration marker [neuron specific enolase (NSE), amyloid β, tau] levels. Increased IL-1β, IL-6, IL-8, IL-10, TNF-α and decreased C4 d, C5a and iC3b levels were associated with septic shock, coma and mortality. Transient mild cognitive impairment was observed in 7 of 21 patients who underwent neuropsychological assessment. Cognitive dysfunction and neuronal loss were associated with increased duration of septic shock and delirium but not baseline serum levels of inflammation and neurodegeneration markers. Conclusion: Increased cytokine levels, decreased complement activity and increased neuronal loss are indicators of poor prognosis and adverse events in SIBD. Cognitive dysfunction and neuronal destruction in SIBD do not seem to be associated with systemic inflammation factors and Alzheimer disease-type neurodegeneration but rather with increased duration of neuronal dysfunction and enhanced exposure of the brain to sepsis-inducing pathogens. [ABSTRACT FROM AUTHOR]

Objective: Incidence and patterns of brain lesions of sepsisinduced brain dysfunction (SIBD) have been well-defined. Our objective was to provide findings from brain magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) of the brain in patients showing neurological alterations due to sepsis and relate it to the inflammatory and disease severity markers of SIBD. Methods: In this prospective observational study, 93 SIBD patients (45 men, 48 women; 50.6±12.7 year-old) were enrolled. Patients underwent a neurological examination and brain MRI. Several severity-of-disease scoring systems were used for evaluation of patient outcome. Serum levels of a panel of mediators [IL-1 β, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-γ, TNF-α, complement factor Bb, C4d, C5a, iC3b, amyloid-b peptides, total tau, phosphorylated tau (p-tau), S100b, neuron-specific enolase] were measured by ELISA. Voxel-based morphometry (VBM) was employed to available patients for assessment of neuronal loss pattern in SIBD. Results: MRI of SIBD patients were normal (n=27, 29%) or showed brain lesions (n=51, 54.9%) or brain atrophy (n=15, 16.1%). VBM analysis showed neuronal loss in the insula, cingulate cortex, frontal lobe, precuneus, and thalamus. Patients with abnormal MRI findings had worse APACHE II, SOFA, GOSE scores, increased prevalence of delirium and mortality. Presence of MRI lesions was associated with reduced C5a and iC3b levels and brain atrophy was associated with increased p-tau levels. Multivariate regression analysis identified an association between reduced IL-12 level and occurrence of coma. Conclusion: Neuronal loss predominantly occurs in limbic and visceral pain perception regions of SIBD patients. Complement breakdown products, IL-12, and p-tau stand out as adverse neuroimaging and neurological outcome markers for SIBD. This work was supported by Scientific Research Projects Coordination Unit of Istanbul University. Project number 35165 and 46960. [ABSTRACT FROM AUTHOR]