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      Sepsis-Associated Encephalopathy: From Delirium to Dementia?

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          Abstract

          Sepsis is a major cause of death in intensive care units worldwide. The acute phase of sepsis is often accompanied by sepsis-associated encephalopathy, which is highly associated with increased mortality. Moreover, in the chronic phase, more than 50% of surviving patients suffer from severe and long-term cognitive deficits compromising their daily quality of life and placing an immense burden on primary caregivers. Due to a growing number of sepsis survivors, these long-lasting deficits are increasingly relevant. Despite the high incidence and clinical relevance, the pathomechanisms of acute and chronic stages in sepsis-associated encephalopathy are only incompletely understood, and no specific therapeutic options are yet available. Here, we review the emergence of sepsis-associated encephalopathy from initial clinical presentation to long-term cognitive impairment in sepsis survivors and summarize pathomechanisms potentially contributing to the development of sepsis-associated encephalopathy.

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          Most cited references63

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          Microglia and macrophages in brain homeostasis and disease

          Microglia and non-parenchymal macrophages in the brain are mononuclear phagocytes that are increasingly recognized to be essential players in the development, homeostasis and diseases of the central nervous system. With the availability of new genetic, molecular and pharmacological tools, considerable advances have been made towards our understanding of the embryonic origins, developmental programmes and functions of these cells. These exciting discoveries, some of which are still controversial, also raise many new questions, which makes brain macrophage biology a fast-growing field at the intersection of neuroscience and immunology. Here, we review the current knowledge of how and where brain macrophages are generated, with a focus on parenchymal microglia. We also discuss their normal functions during development and homeostasis, the disturbance of which may lead to various neurodegenerative and neuropsychiatric diseases.
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            Physiology of Astroglia.

            Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense of the central nervous system (CNS). Astrocytes are highly heterogeneous in morphological appearance; they express a multitude of receptors, channels, and membrane transporters. This complement underlies their remarkable adaptive plasticity that defines the functional maintenance of the CNS in development and aging. Astrocytes are tightly integrated into neural networks and act within the context of neural tissue; astrocytes control homeostasis of the CNS at all levels of organization from molecular to the whole organ.
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              Sepsis and septic shock.

              For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                05 March 2020
                March 2020
                : 9
                : 3
                : 703
                Affiliations
                [1 ]Section Translational Neuroimmunology, Department of Neurology, Jena University Hospital, 07747 Jena, Germany; ha-yeun.chung@ 123456med.uni-jena.de (H.-Y.C.); jonathan.wickel@ 123456med.uni-jena.de (J.W.)
                [2 ]Center for Sepsis Control and Care, Jena University Hospital, Jena 07747, Germany; frank.brunkhorst@ 123456med.uni-jena.de
                [3 ]Center for Clinical Studies and Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747 Jena, Germany
                Author notes
                [* ]Correspondence: christian.geis@ 123456med.uni-jena.de ; Tel.: +49-3641-9323410
                [†]

                These authors contributed equally.

                Author information
                https://orcid.org/0000-0002-9859-581X
                Article
                jcm-09-00703
                10.3390/jcm9030703
                7141293
                32150970
                88eea396-f71b-4352-8ada-dc650c6bab61
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 January 2020
                : 03 March 2020
                Categories
                Review

                sepsis,encephalopathy,brain dysfunction,sae,delirium,dementia,cognitive deficits,pathophysiology,long-term sequelae

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