Biomarcadores na encefalopatia séptica: revisão sistemática dos estudos clínicos

Zenaide, P; Gusmao-Flores, Dimitri

doi:10.1590/s0103-507x2013000100011

Cited by 24 publications

(5 citation statements)

References 37 publications

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“…Preexisting studies on SAE analyzed non-specific biomarkers like interleukin-6, neuron-specific enolase (NSE) or S100B protein [19, 21–23,47,48,49]. The results were found to be controversial [19,48,49]. Our group is first to analyze the prognostic value of CSF and plasma NfH and NfL levels in SAE patients which might have importance for the prediction of long-term neurological sequelae and survival in sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the need for prolonged registration of EEG to detect abnormalities over time is not practicable in the ICU setting and previous studies showed no association between EEG and brain dysfunction detected by CAM-ICU [18]. In this context body fluid biomarkers may be of diagnostic value [6,19,20]. A common limitation to previous studies on SAE was that biomarkers investigated are not specific for the neuro-axonal compartment and results have been contradictory [21–26].…”

Section: Introductionmentioning

confidence: 99%

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The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy – A prospective, pilot observational study

Ehler¹,

Petzold²,

Wittstock³

et al. 2019

PLoS ONE

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Sepsis-associated encephalopathy (SAE) contributes to mortality and neurocognitive impairment of sepsis patients. Neurofilament (Nf) light (NfL) and heavy (NfH) chain levels as biomarkers for neuroaxonal injury were not evaluated in cerebrospinal fluid (CSF) and plasma of patients with sepsis-associated encephalopathy (SAE) before. We conducted a prospective, pilot observational study including 20 patients with septic shock and five patients without sepsis serving as controls. The assessment of SAE comprised a neuropsychiatric examination, electroencephalography (EEG), magnetic resonance imaging (MRI) and delirium screening methods including the confusion assessment method for the ICU (CAM-ICU) and the intensive care delirium screening checklist (ICDSC). CSF Nf measurements in sepsis patients and longitudinal plasma Nf measurements in all participants were performed on days 1, 3 and 7 after study inclusion. Plasma NfL levels increased in sepsis patients over time (p = 0.0063) and remained stable in patients without sepsis. Plasma NfL values were significantly higher in patients with SAE (p = 0.011), significantly correlated with the severity of SAE represented by ICDSC values (R = 0.534, p = 0.022) and correlated with a poorer functional outcome after 100 days (R = -0.535, p = 0.0003). High levels of CSF Nf were measured in SAE patients. CSF NfL levels were higher in non-survivors (p = 0.012) compared with survivors and correlated with days until death (R = -0.932, p<0.0001) and functional outcome after 100 days (R = -0.749, p<0.0001). The present study showed for the first time that Nf levels provide complementary prognostic information in SAE patients indicating a higher chance of death and poorer functional/cognitive outcome in survivors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy – A prospective, pilot observational study

Ehler¹,

Petzold²,

Wittstock³

et al. 2019

PLoS ONE

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“…Specific biomarkers for neuroaxonal injury could be helpful in diagnosing DAI or SAE in vivo [ 49 ]. Previous clinical studies have been focused on neuron-specific enolase and S100B to diagnose brain injury in sepsis, with heterogeneous results [ 23 ]. Elevated Nf levels as markers of axonal injury were detected in various neurological conditions and may be of future use in SAE [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…Beside advances in histology, in vivo diagnostics can detect axonal injury in SAE [ 19 , 20 ]. Imaging and biomarker studies have been used to detect brain injury and predict neurologic outcome [ 21 – 23 ]. Nevertheless, both the primary mechanisms underlying SAE and the temporal development of SAE over the course of sepsis remain elusive [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Translational evidence for two distinct patterns of neuroaxonal injury in sepsis: a longitudinal, prospective translational study

et al. 2017

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BackgroundBrain 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.MethodsWe 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. Immunohistochemistry was performed on human brain tissue from sepsis nonsurvivors and in control patients without sepsis. The clinical diagnostics of SAE comprised longitudinal clinical data collection and magnetic resonance imaging (MRI) and electroencephalographic assessments. Statistical analyses were performed using SAS software (version 9.4; SAS Institute, Inc., Cary, NC, USA). Because of non-Gaussian distribution, the nonparametric Wilcoxon test general linear models and the Spearman correlation coefficient were used.ResultsIn postmortem rat and human brain samples, neurofilament phosphoform, β-amyloid precursor protein, β-tubulin, and H&E stains distinguished scattered ischemic lesions from diffuse neuroaxonal injury in septic animals, which were absent in controls. These two patterns of neuroaxonal damage were consistently found in septic but not control human postmortem brains. In experimental sepsis, the time from sepsis onset correlated with tissue neurofilament levels (R = 0.53, p = 0.045) but not glial fibrillary acidic protein. Of 13 patients with sepsis who had clinical features of SAE, MRI detected diffuse axonal injury in 9 and ischemia in 3 patients.ConclusionsIschemic and diffuse neuroaxonal injury to the brain in experimental sepsis, human postmortem brains, and in vivo MRI suggest these two distinct lesion types to be relevant. Future studies should be focused on body fluid biomarkers to detect and monitor brain injury in sepsis. The relationship of neurofilament levels with time from sepsis onset may be of prognostic value.Trial registrationClinicalTrials.gov, NCT02442986. Registered on May 13, 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1850-7) contains supplementary material, which is available to authorized users.

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“…Neuron-specific enolase (NSE) is a gamma-enolase isomer of the cytoplasmic glycolytic enzyme found in neurons and neuroendocrine cells (Zenaide and Gusmao-Flores 2013) Severe disability one and a half years later GFAP in paediatric septic patients; their results showed higher levels of serum NSE, S100 β and GFAP than that of controls and that NSE and S100 β were the highest in children who did not survive sepsis .…”

Section: Nsementioning

confidence: 99%

Paediatric sepsis-associated encephalopathy (SAE): a comprehensive review

Dumbuya

Liang

et al. 2023

Mol Med

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Sepsis-associated encephalopathy (SAE) is one of the most common types of organ dysfunction without overt central nervous system (CNS) infection. It is associated with higher mortality, low quality of life, and long-term neurological sequelae, its mortality in patients diagnosed with sepsis, progressing to SAE, is 9% to 76%. The pathophysiology of SAE is still unknown, but its mechanisms are well elaborated, including oxidative stress, increased cytokines and proinflammatory factors levels, disturbances in the cerebral circulation, changes in blood–brain barrier permeability, injury to the brain’s vascular endothelium, altered levels of neurotransmitters, changes in amino acid levels, dysfunction of cerebral microvascular cells, mitochondria dysfunction, activation of microglia and astrocytes, and neuronal death. The diagnosis of SAE involves excluding direct CNS infection or other types of encephalopathies, which might hinder its early detection and appropriate implementation of management protocols, especially in paediatric patients where only a few cases have been reported in the literature. The most commonly applied diagnostic tools include electroencephalography, neurological imaging, and biomarker detection. SAE treatment mainly focuses on managing underlying conditions and using antibiotics and supportive therapy. In contrast, sedative medication is used judiciously to treat those showing features such as agitation. The most widely used medication is dexmedetomidine which is neuroprotective by inhibiting neuronal apoptosis and reducing a sepsis-associated inflammatory response, resulting in improved short-term mortality and shorter time on a ventilator. Other agents, such as dexamethasone, melatonin, and magnesium, are also being explored in vivo and ex vivo with encouraging results. Managing modifiable factors associated with SAE is crucial in improving generalised neurological outcomes. From those mentioned above, there are still only a few experimentation models of paediatric SAE and its treatment strategies. Extrapolation of adult SAE models is challenging because of the evolving brain and technical complexity of the model being investigated. Here, we reviewed the current understanding of paediatric SAE, its pathophysiological mechanisms, diagnostic methods, therapeutic interventions, and potential emerging neuroprotective agents.

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Biomarcadores na encefalopatia séptica: revisão sistemática dos estudos clínicos

Cited by 24 publications

References 37 publications

The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy – A prospective, pilot observational study

The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy – A prospective, pilot observational study

Translational evidence for two distinct patterns of neuroaxonal injury in sepsis: a longitudinal, prospective translational study

Paediatric sepsis-associated encephalopathy (SAE): a comprehensive review

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