Sepsis-associated encephalopathy: a magnetic resonance imaging and spectroscopy study (original) (raw)
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Imaging in sepsis-associated encephalopathy—insights and opportunities
Nature Reviews Neurology, 2013
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.
Neuroanatomy and Physiology of Brain Dysfunction in Sepsis
Clinics in chest medicine, 2016
Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels.
Shock, 2019
Sepsis-induced brain injury is associated with an acute deterioration of mental status resulting in cognitive impairment and acquisition of new functional limitations in sepsis survivors. However, the exact nature of brain injury in this setting is often subtle and remains to be fully characterized both in pre-clinical studies and at the bedside. Given the translation potential for the use of magnetic resonance imaging (MRI) 1 to define sepsis-induced brain injury, we sought to determine and correlate the cellular changes with neuroradiographic presentations in a classic murine model of sepsis induced by cecal ligation and puncture (CLP) 2. Sepsis was induced in 6-10week-old male C57/BL6 mice by CLP. We used immunohistochemistry (IHC) 3 to define neuropathology in a mouse model of sepsis along with parallel studies using MRI, focusing on cerebral edema, blood-brain barrier (BBB) 4 disruption, and microglial activation on days 1 and 4 days after CLP. We demonstrate that septic mice had evidence of early axonal injury, inflammation and robust microglial activation on day 1 followed by cytotoxic edema on day 4 in the cortex, thalamus, and hippocampus in the absence of BBB disruption. We note the superiority of the MRI to detect subtle brain injury and cytotoxic cerebral edema in comparison to the traditional gold standard assessment, i.e., percent brain water (wet-dry weight method). We conclude that inflammatory changes in the septic brain can be detected in real-time, and further studies are needed to understand axonal injury and the impact of inhibition of microglial activation on the development of cerebral edema.
Neurocritical care, 2018
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. 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. MRI of SIBD patients were normal (...
Sepsis-associated encephalopathy: not just delirium
Clinics, 2011
Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsisassociated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations.
Brain lesions in septic shock: a magnetic resonance imaging study
Intensive care …, 2007
Background: Understanding of sepsis-induced brain dysfunction remains poor, and relies mainly on data from animals or post-mortem studies in patients. The current study provided findings from magnetic resonance imaging of the brain in septic shock. Methods: Nine patients with septic shock and brain dysfunction [7 women, median age 63 years (interquartile range 61-79 years), SAPS II: 48 (44-56), SOFA: 8 (6-10)] underwent brain magnetic resonance imaging including gradient echo T1weighted, fluid-attenuated inversion recovery (FLAIR), T2-weighted and diffusion isotropic images, and mapping of apparent diffusion coefficient. Results: Brain imaging was normal in two patients, showed multiple ischaemic strokes in two patients, and in the remaining patients showed white matter lesions at the level of the centrum semiovale, predominating around Virchow-Robin spaces, ranging from small multiple areas to diffuse lesions, and characterised by hyperintensity on FLAIR images. The main lesions were also characterised by reduced signal on diffusion isotropic images and increased apparent diffusion coefficient. The lesions of the white matter worsened with increasing duration of shock and were correlated with Glasgow Outcome Score. Conclusion: This preliminary study showed that sepsis-induced brain lesions can be documented by magnetic resonance imaging. These lesions predominated in the white matter, suggesting increased blood-brain barrier permeability, and were associated with poor outcome.
Neurological Sequelae of Sepsis: I) Septic Encephalopathy
The Open Critical Care Medicine Journal, 2011
Septic encephalopathy (SE) or sepsis-associated delirium is the most common encephalopathy in ICU patients. It is defined by brain dysfunction due to systemic inflammatory response syndrome and extracranial infection. Clinically, acute impairment in level of consciousness and confusion are primarily defining symptoms. Precise clinical evaluation of brain function is crucial, although the necessary diagnostic tools are limited and require further verification in clinical studies. Therefore, SE is often underestimated and not frequently diagnosed. This review gives an overview of clinical features, epidemiological data, pathophysiological processes, imaging and neuropathological findings as well as diagnostic and therapeutic approaches in SE patients to characterize this severe neurological complication of sepsis.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, 2018
The purpose of this study was to evaluate a set of widely used nuclear medicine imaging agents as possible methods to study the early effects of systemic inflammation on the living brain in a mouse model of sepsis-associated encephalopathy (SAE). The lipopolysaccharide (LPS)-induced murine systemic inflammation model was selected as a model of SAE. C57BL/6 mice were used. A multimodal imaging protocol was carried out on each animal 4 h following the intravenous administration of LPS using the following tracers: [Tc][2,2-dimethyl-3-[(3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(3E)-3-hydroxyiminobutan-2-yl]azanide ([Tc]HMPAO) and ethyl-7-[I]iodo-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate ([I]iomazenil) to measure brain perfusion and neuronal damage, respectively; 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) to measure cerebral glucose uptake. We assessed microglia activity on another group of mice using 2-[6-chloro-2-(4-[I]iodophenyl)-imidazo[1,2-a]pyridin-3-yl]-N-et...
Critical care (London, England), 2017
Brain homeostasis deteriorates in sepsis, giving rise to a mostly reversible sepsis-associated encephalopathy (SAE). Some survivors experience chronic cognitive dysfunction thought to be caused by permanent brain injury. In this study, we investigated neuroaxonal pathology in sepsis. We conducted a longitudinal, prospective translational study involving (1) experimental sepsis in an animal model; (2) postmortem studies of brain from patients with sepsis; and (3) a prospective, longitudinal human sepsis cohort study at university laboratory and intensive care units (ICUs). Thirteen ICU patients with septic shock, five ICU patients who died as a result of sepsis, fourteen fluid-resuscitated Wistar rats with fecal peritonitis, eleven sham-operated rats, and three human and four rat control subjects were included. Immunohistologic and protein biomarker analysis were performed on rat brain tissue at baseline and 24, 48, and 72 h after sepsis induction and in sham-treated rats. Immunohist...