Günseli Orhun1, Figen Esen2, Perihan Ergin Özcan2, Serra Sencer3, Başar Bilgiç4, Canan Ulusoy5, Handan Noyan5, Melike Küçükerden5, Achmet Ali2, Mehmet Barburoğlu3, Erdem Tüzün5. 1. Department of Anesthesiology and Intensive Care, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. gunseli_orhun@hotmail.com. 2. Department of Anesthesiology and Intensive Care, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 3. Department of Neuroradiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 4. Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 5. Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Abstract
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.
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.
Entities:
Keywords:
Brain dysfunction; C5a; IL-12; Neuroimaging; Sepsis; Tau
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