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Imaging in sepsis-associated encephalopathy—insights and opportunities

Nature Reviews Neurology volume 9, pages 551–561 (2013)Cite this article

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Abstract

Sepsis-associated encephalopathy (SAE) refers to a clinical spectrum of acute neurological dysfunction that arises in the context of sepsis. Although the pathophysiology of SAE is incompletely understood, it is thought to involve endothelial activation, blood–brain barrier leakage, inflammatory cell migration, and neuronal loss with neurotransmitter imbalance. SAE is associated with a high risk of mortality. Imaging studies using MRI and CT have demonstrated changes in the brains of patients with SAE that are also seen in disorders such as stroke. Next-generation imaging techniques such as magnetic resonance spectroscopy, diffusion tensor imaging and PET, as well as experimental imaging modalities, provide options for early identification of patients with SAE, and could aid in identification of pathophysiological processes that represent possible therapeutic targets. In this Review, we explore the recent literature on imaging in SAE, relating the findings of these studies to pathological data and experimental studies to obtain insights into the pathophysiology of sepsis-associated neurological dysfunction. Furthermore, we suggest how novel imaging technologies can be used for early-stage proof-of-concept and proof-of-mechanism translational studies, which may help to improve diagnosis in SAE.

Key Points

  • Sepsis-associated encephalopathy (SAE) is a complication of extracranial sepsis that leads to profound neurological dysfunction, and is associated with increased mortality and cognitive impairment

  • The pathophysiology of SAE is incompletely understood but is thought to involve endothelial activation, blood–brain barrier leakage, inflammatory cell migration, and neuronal loss with neurotransmitter imbalance

  • The clinical syndrome of SAE includes features representing not only the direct effects of sepsis and host response, but also the consequences of extracranial physiological abnormalities that result from sepsis

  • Imaging studies using MRI and CT have demonstrated changes in SAE similar to those that are observed in other neurological disorders such as stroke

  • Next-generation imaging techniques—such as magnetic resonance spectroscopy, diffusion-tensor MRI and PET—could reveal pathophysiological processes of SAE to aid diagnosis, identify therapeutic targets and eliminate confounding causes

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Figure 1: Principles of diffusion-weighted imaging.
Figure 2: Pathophysiological mechanisms in SAE.
Figure 3: MRI findings in patients with sepsis.
Figure 4: Potential role of imaging in diagnosis of SAE.

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Acknowledgements

D. K. Menon is supported by a Senior Investigator Award from the National Institute for Health Research (NIHR), UK; and by the Neurosciences Theme of the NIHR Cambridge Biomedical Research Centre.

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  1. Division of Anaesthesia, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    Daniel J. Stubbs & David K. Menon

  2. Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    Adam K. Yamamoto

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D. J. Stubbs researched data for the article. A. K. Yamamoto provided radiological expertise. D. J. Stubbs and D. K. Menon provided substantial contribution to discussion of content, and wrote the article. All authors contributed to review and/or editing of the manuscript before submission.

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Stubbs, D., Yamamoto, A. & Menon, D. Imaging in sepsis-associated encephalopathy—insights and opportunities. Nat Rev Neurol 9, 551–561 (2013). https://doi.org/10.1038/nrneurol.2013.177

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