Diagnosis Of Sepsis-associated Encephalopathy Research Articles

Application of magnetic resonance imaging-related techniques in the diagnosis of sepsis-associated encephalopathy: present status and prospect.

Sepsis-associated encephalopathy (SAE) refers to diffuse brain dysfunction secondary to systemic infection without central nervous system infection. The early diagnosis of SAE remains a major clinical problem, and its diagnosis is still exclusionary. Magnetic resonance imaging (MRI) related techniques, such as magnetic resonance spectroscopy (MRS), molecular MRI (mMRI), arterial spin-labeling (ASL), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI), currently provide new options for the early identification of SAE. This review collected clinical and basic research and case reports related to SAE and MRI-related techniques in recent years, summarized and analyzed the basic principles and applications of MRI technology in diagnosing SAE, and provided a basis for diagnosing SAE by MRI-related techniques.

Non-hepatic Hyperammonemia: A Potential Therapeutic Target for Sepsis-associated Encephalopathy.

Sepsis-Associated Encephalopathy (SAE) is a common complication in the acute phase of sepsis, and patients who develop SAE have a higher mortality rate, longer hospital stay, and worse quality of life than other sepsis patients. Although the incidence of SAE is as high as 70% in sepsis patients, no effective treatment is available for this condition. To develop an effective treatment for SAE, it is vital to explore its pathogenesis. It is known that hyperammonemia is a possible factor in the pathogenesis of hepatic encephalopathy as ammonia is a potent neurotoxin. Furthermore, our previous studies indicate that non-hepatic hyperammonemia seems to occur more often in sepsis patients; it was also found that >50% of sepsis patients with non-hepatic hyperammonemia exhibited encephalopathy and delirium. Substatistical analyses indicate that non-hepatic hyperammonemia is an independent risk factor for SAE. This study updates the definition, clinical manifestations, and diagnosis of SAE; it also investigates the possible treatment options available for non-hepatic hyperammonemia in patients with sepsis and the mechanisms by which non-hepatic hyperammonemia causes encephalopathy.

Research Progress in Clinical Electrophysiological Assessment of Patients with Sepsis-Associated Encephalopathy

Sepsis-associated encephalopathy(SAE) caused by infections outside the central nervous system always presents extensive brain damage.It is common in clinical practice and associated with a poor prognosis.There are problems in the assessing and diagnosing of SAE.Many factors,such as sedation and mechanical ventilation,make it difficult to assess SAE,while electrophysiological examination may play a role in the assessment.We reviewed the studies of electrophysiological techniques such as electroencephalography and somatosensory evoked potentials for monitoring SAE,hoping to provide certain evidence for the clinical evaluation and diagnosis of SAE.

Clinical features, electroencephalogram, and biomarkers in pediatric sepsis-associated encephalopathy

To date, no specific diagnostic criteria for sepsis-associated encephalopathy (SAE) have been established. We studied 33 pediatric patients with sepsis prospectively and evaluated the level of consciousness, the presence of delirium, electroencephalographic (EEG) findings, and plasma levels of neuron-specific enolase and S100-calcium-binding protein-B. A presumptive diagnosis of SAE was primarily considered in the presence of a decreased level of consciousness and/or delirium (clinical criteria), but specific EEG abnormalities were also considered (EEG criteria). The time course of the biomarkers was compared between groups with and without clinical or EEG criteria. The Functional Status Scale (FSS) was assessed at admission, discharge, and 3–6 months post-discharge. Clinical criteria were identified in 75.8% of patients, EEG criteria in 26.9%, both in 23.1%, and none in 23.1%. Biomarkers did not differ between groups. Three patients had an abnormal FSS at discharge, but no one on follow-up. A definitive diagnostic pattern for SAE remained unclear. Clinical criteria should be the basis for diagnosis, but sedation may be a significant confounder, also affecting EEG interpretation. The role of biomarkers requires a better definition. The diagnosis of SAE in pediatric patients remains a major challenge. New consensual diagnostic definitions and mainly prognostic studies are needed.

Plasma miR-370-3P as a Biomarker of Sepsis-Associated Encephalopathy, the Transcriptomic Profiling Analysis of Microrna-Arrays From Mouse Brains.

The diagnosis of sepsis-associated encephalopathy (SAE), an alteration of conscious from sepsis, is difficult due to the similarity to altered states of conscious that occur from other causes. Transcriptomic analyses between mouse brains at 24 h after cecal ligation and puncture (CLP) (SAE brain as evaluated by SHIRPA score) and at 120 h post-CLP (survivor) were performed to discover the SAE biomarker. Then, candidate microRNAs were validated in mouse and patient samples.As such, increased miR-370-3p in SAE mouse-brains (compared with recovery phase) was demonstrated by transcriptomic miR-profiling and was highly expressed in brain (but not other organs) of 24 h post-CLP mice. Plasma miR-370-3p also increased in CLP but was non-detectable in bilateral-nephrectomy (BiNx, a representative model of acute uremic encephalopathy) despite blood brain barrier permeability defect (determined by plasma s100β and Evan blue dye assay) in both conditions. In parallel, high plasma miR-370-3p was demonstrated in patients with SAE (but not sepsis alone or uremia) suggesting the specificity toward SAE. The association among TNF-α, miR-370-3p and brain apoptosis was demonstrated by high serum TNF-α and increased brain apoptosis in SAE mice, TNF-α (but not other cytokines) activated miR-370-3p expression in PC-12 neuron cell, and increased cell apoptosis in miR-370-3p transfected PC-12 after incubation with TNF-α.In conclusion, miR-370-3p increased in brain and plasma of SAE mice but not uremic encephalopathy. Perhaps, TNF-α enhances cell susceptibility toward brain apoptosis in SAE, in part, through miR-370-3p induction in neuron. Our pilot results in patients with SAE supported the possibility that plasma miR-370-3p is an interesting SAE biomarker candidate. Further studies are warranted.

202 Neural Biomarker Panel for Sepsis-Associated Encephalopathy and Sepsis Outcomes

Sepsis-associated encephalopathy (SAE), the state of altered mentation (AMS) as a result of infection is a poorly understood yet common ED presentation that may have long-term implications. To date, there have been no contemporary serum biomarker available for the diagnosis, management, or prognosis of AMS in SAE. We investigated the diagnostic and prognostic utility of six neural biomarkers (glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL1), S100 calcium-binding protein B (S100B), Tau protein, Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH)) to assess their role in predicting cognitive performance and outcomes in ED sepsis. A single center, prospective, longitudinal study of ED patients > 18 years with suspected or confirmed infection and systemic inflammatory response syndrome criteria was performed. Those with a history of neurologic, chronic liver or kidney disease were excluded. AMS was defined a priori by the clinician and serial serum collection for biomarker analysis was performed 0, 6, 12, 18, 24, 48, and 72 hours after enrollment. Subjects were enrolled within 6 hours of ED arrival. Outcomes included cerebral performance category (CPC) and mortality at 6-months. Associations between sepsis patients with and without AMS and outcomes were tested by Fisher’s exact test and Mann-Whitney U-test. Receiver operator characteristics curves were created to evaluate the utility of biomarker concentrations or change in biomarkers concentrations in the diagnosis of SAE and prognosis of outcomes. Potential cutoff points were defined by the Youden’s J statistic. Of the 23 sepsis patients recruited, 11 (47.8%) and 12 (52.2%) presented with and without AMS, respectively. The mean age of the AMS cohort was 70.3 years (95% CI 58-82), versus the non-AMS 51.7 years (95% CI 40-63) (p=0.023). There was no difference in sex, race, ethnicity, or APACHE II score at baseline observed. Of the biomarker concentrations or change in concentrations analyzed at the defined study collection time points, 19, 17, and 16 unique measures demonstrated discriminatory utility in the diagnosis of SAE and the identification of outcomes. The concentration ratio between GFAP/UCHL1 at baseline demonstrates the best utility in diagnosing SAE with an AUC of 0.93 (95% CI .83-.99). The concentration ratio between GFAP/S100b, UCHL1/pNFH, Tau/S100b, and S100b/pNFH at 72 hours demonstrated complete discriminatory utility in prognosticating neurological performance at hospital discharge and mortality at 6 months. In this pilot, S100B, pNFH, GFAP, UCHL1, Tau, and NFL were able to discriminate between subjects demonstrating diagnosed acute SAE, and therefore can be useful to determine the prognosis for persistent cognitive dysfunction and long-term survival among sepsis patients. Biomarker cut points have been further identified to inform clinicians as to whether the subject’s biomarker levels are abnormal.

Association between Elevated Serum Tau Protein Level and Sepsis-Associated Encephalopathy in Patients with Severe Sepsis.

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis. It is imperative to recognize, diagnose, and effectively manage SAE at the early stages. The aim of this study was to evaluate the potential of using the serum tau protein level in the diagnosis of SAE and the prediction of SAE outcomes. This was a retrospective and observational study. The patients included in this study were diagnosed with severe sepsis or septic shock. The serum tau protein level was measured using a commercial enzyme-linked immunosorbent assay. The association between the level of serum tau protein and SAE was assessed by multiple logistic regression analysis. One hundred nine patients with severe sepsis were enrolled during a period of two years. Of the 109 enrolled patients, 27 developed SAE. The serum tau protein level was significantly higher in the patients with SAE than that of the non-SAE group. The serum tau protein level and the sequential organ failure assessment (SOFA) score were independent factors that were associated with SAE. The combined use of the serum tau protein level with the SOFA score improved the accuracy in distinguishing SAE from non-SAE patients. A cutoff value serum tau protein level of 75.92 pg/mL had 81.1% sensitivity and 86.1% specificity in predicting the 28-day mortality in patients with severe sepsis. We identified a close association between the serum tau protein level with the appearance of SAE in patients with severe sepsis. The serum tau protein level can be useful in the prediction of poor outcomes in patients with sepsis.

Diagnosis of sepsis associated encephalopathy: a retrospective analysis of 6 patients

Objective To investigate whether the presence of infection in a case series with coma would predict sepsis associated encephalopathy(SAE). Methods From Jan 2013 to Oct 2014, we used the criteria of systemic inflammatory response syndrome (SIRS) positive sepsis with encephalopathy and retrospective diagnosed a comatose case series with infection and from a tertiary teaching hospital intensive care unit (ICU). Results Among 6 comatose patients with evidence of infection, 3 cases were secondary infection after hemorrhagic stroke, 1 case was secondary infection after trauma, and the other 2 cases were primary infection.All patients met the diagnosis of SIRS-positive sepsis with encephalopathy.Among them, the presence of SIRS 3 criteria was in 2 cases, four criteria in 4 cases.All patients with severe brain failure (100%), in addition to 5 cases with acute respiratory failure caused by lung injury, one case with acute liver failure.Brain imaging confirmed that the delayed vasogenic edema was in two cases(33.3%), the cerebral ischemic lesions in four cases(66.7%). The ischemic lesion included 1 patient with minor infarcts and 1 case with mild white matter lesions, and with a good prognosis.The other two ischemic cases included multifocal leukoencephalopathy with central pontine myelinolysis in 1 case and extensive white matter lesions in 1 case, eventually with a poor prognosis. Conclusion SAE is a common critically illness, the use of the new classification criteria of sepsis is helpful in the diagnosis of sepsis associated encephalopathy. Key words: Sepsis; Sepsis associated encephalopathy; Coma; Systemic inflammatory response syndrome; Organ failure; Imaging

The changes of S100β in serum and brain of rats with sepsis-associated encephalopathy

Objective To study the changes of S100βin serum and brain tissue of rats with sepsisassociated encephalopathy (SAE).Methods After placement of pole plates of electroencephalogram (EEG) on the brain cortex,thirty SD rats were randomly (random number) divided into three groups post hoc:sepsis group in which rats were made to be sepsis models by cecal ligation and puncture (n =18),normal group (n =6) and sham operation group (n =6).The sepsis-associated encephalopathy was diagnosed with electroencephalogram taken by RM6240 physiological signal recorder.Meanwhile,heart rate and blood pressure were recorded.Eight hours later,serum and brain tissue of sacrificed rats were taken for measuring S100β.The results ware analyzed with one-way ANOVA.Results Of 18 sepsis rats,3 were dead,8 without SAE and 7 with SAE.The levels of S100βin serum and brain tissue of rats with SAE group were significantly higher than those in normal group and sham operation proup (P ＜ 0.05).The Ratio of brain/serum S100βin rats with SAE group was higher than that in rats without SAE (1.74 vs 1.51,P ＜ 0.05).Conclusions Significantly high level of serum S100βwas a reliable bio-marker for diagnosis of SAE in rats. Key words: S100β; Electroencephalogram; Blood-brain barrier; Sepsis-associated encephalopathy ; Sepsis ; Neurological scorings ; Bio-marker; Cecal ligation and puncture model