S-100B Levels in Stroke Patients
Salim Satar
Mustafa Sahan2014, Neurosurgery Quarterly
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Abstract
Background: Serum S100B is found in the glial cells and is elevated with stroke. It can be used in the diagnostic and prognostic utility. However, the use of S100B in the emergency room is controversial. In our study, we wish to determine if the National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) have utility in predicting the acute and first month poststroke mortality and morbidity in emergency room patients, as measured by serum S100B and clinical evaluations.
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The Relationship of Serum S100B Levels with Infarction Size and Clinical Outcome in Acute Ischemic Stroke Patients
Noro Psikiyatri Arsivi, 2014
Introduction: S100B protein, which helps nerve development and differentiation, is produced by astrocytes and can be detected in peripheral circulation after brain damage. In this study, we aimed to investigate the relationship between the serum S100B protein level and the infarction volume and clinical outcome and also the early prognostic role of serum S100B protein in patients with ischemic stroke. Method: Fifty patients admitted in the first 24-hour period of acute ischemic stroke were evaluated prospectively, and the findings were compared to those of the controls (n=26). S100B levels of the patients and neurological findings on days 1, 3, and 5 and their functional outcomes on the discharge day and at the first month were recorded by the same examiner. Results: S100B levels were not affected by sex, age, or concomitant systemic diseases. The maximum levels of S100B were recorded on the 3rd day, and there was a correlation between infarct size and S100B levels. No correlation b...
The role of s100b as a predictor of the functional outcome in geriatric patients with acute cerebrovascular stroke
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Correlation of Serum S-100 Protein Level with Severity of Ischaemic Stroke
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Background: Stroke is currently the second leading cause of death worldwide and the first leading cause of death in Bangladesh. The National Institute of Health Stroke Scale is the most commonly used deficit rating scale to assess stroke severity. S-100 protein is a low molecular weight calcium-binding protein expressed mostly in glial cells like astrocytes, oligodendrocytes, and microglial cells. During the ischaemic process, S-100 protein is secreted from the glial cells into the extracellular space. After secretion, S-100 protein releases initially into the cerebrospinal fluid and then eventually into the bloodstream due to disruption of the blood-brain barrier. Aim of the study: To correlate serum S-100 protein level with the severity of ischaemic stroke. Methods: This cross-sectional study was conducted at the Department of Laboratory Medicine in collaboration with the Department of Neurology, BSMMU, Dhaka, Bangladesh from September 2018 to August 2019. A total of 70 ischaemic ...
Serum S-100 Protein, Relationship to Clinical Outcome in Acute Stroke
Annals of Clinical Biochemistry: An international journal of biochemistry and laboratory medicine, 1997
The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0·27 (0·09)μg/L, n = 68] and haemorrhagic stroke [0·43 (0·23)μg/L, n=13] compared to controls [0·11 (0·03)μg/L, n = 51, P<0·0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0·40 (0·22) μg/L], and small vessel (‘lacunar’) infarcts concentrations having the lowest [0·20 (0·06)μg/L, P<0·0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disabili...
Elevated serum S100B levels indicate a higher risk of haemorrhagic transformation after thrombolytic therapy in acute stroke
Aktuelle Neurologie, 2007
Background and Purpose-Intracerebral hemorrhage constitutes an often fatal sequela of thrombolytic therapy in patients with ischemic stroke. Early blood-brain barrier disruption may play an important role, and the astroglial protein S100B is known to indicate blood-brain barrier dysfunction. We investigated whether elevated pretreatment serum S100B levels predict hemorrhagic transformation (HT) in thrombolyzed patients with stroke. Methods-We retrospectively included 275 patients with ischemic stroke (mean age of 69Ϯ13 years; 46% female) who had received thrombolytic therapy within 6 hours of symptom onset. S100B levels were determined from pretreatment blood samples. Follow-up brain scans were obtained 24 hours after admission, and HT was classified as either hemorrhagic infarction (1, 2) or parenchymal hemorrhage (1, 2). Results-HT occurred in 80 patients (29%; 45 hemorrhagic infarction, 35 parenchymal hemorrhage). Median S100B values were significantly higher in patients with HT (0.14 versus 0.11 g/L; Pϭ0.017). An S100B value in the highest quintile corresponded to an OR for any HT of 2.87 (95% CI: 1.55 to 5.32; Pϭ0.001) in univariate analysis and of 2.80 (1.40 to 5.62; Pϭ0.004) after adjustment for age, sex, symptom severity, timespan from symptom onset to hospital admission, vascular risk factors, and storage time of serum probes. A pretreatment S100B value above 0.23 g/L had only a moderate sensitivity (0.46) and specificity (0.82) for predicting severe parenchymal bleeding (parenchymal hemorrhage 2). Conclusions-Elevated S100B serum levels before thrombolytic therapy constitute an independent risk factor for HT in patients with acute stroke. Unfortunately, the diagnostic accuracy of S100B is too low for it to function in this context as a reliable biomarker in clinical practice. (Stroke. 2007;38:000-000.)
Elevated Serum S100B Levels Indicate a Higher Risk of Hemorrhagic Transformation After Thrombolytic Therapy in Acute Stroke
2000
Background and Purpose-Intracerebral hemorrhage constitutes an often fatal sequela of thrombolytic therapy in patients with ischemic stroke. Early blood-brain barrier disruption may play an important role, and the astroglial protein S100B is known to indicate blood-brain barrier dysfunction. We investigated whether elevated pretreatment serum S100B levels predict hemorrhagic transformation (HT) in thrombolyzed patients with stroke. Methods-We retrospectively included 275 patients with ischemic stroke (mean age of 69Ϯ13 years; 46% female) who had received thrombolytic therapy within 6 hours of symptom onset. S100B levels were determined from pretreatment blood samples. Follow-up brain scans were obtained 24 hours after admission, and HT was classified as either hemorrhagic infarction (1, 2) or parenchymal hemorrhage (1, 2). Results-HT occurred in 80 patients (29%; 45 hemorrhagic infarction, 35 parenchymal hemorrhage). Median S100B values were significantly higher in patients with HT (0.14 versus 0.11 g/L; Pϭ0.017). An S100B value in the highest quintile corresponded to an OR for any HT of 2.87 (95% CI: 1.55 to 5.32; Pϭ0.001) in univariate analysis and of 2.80 (1.40 to 5.62; Pϭ0.004) after adjustment for age, sex, symptom severity, timespan from symptom onset to hospital admission, vascular risk factors, and storage time of serum probes. A pretreatment S100B value above 0.23 g/L had only a moderate sensitivity (0.46) and specificity (0.82) for predicting severe parenchymal bleeding (parenchymal hemorrhage 2). Conclusions-Elevated S100B serum levels before thrombolytic therapy constitute an independent risk factor for HT in patients with acute stroke. Unfortunately, the diagnostic accuracy of S100B is too low for it to function in this context as a reliable biomarker in clinical practice. (Stroke. 2007;38:2491-2495.)
S-100&#946; protein as a biomarker in acute hemorrhagic stroke
International Journal of Research in Medical Sciences, 2014
S-100β is a member of S-100 super family of proteins. This family of proteins is called so because they are 100% soluble in ammonium sulfate. S-100 is an acidic protein and has a molecular weight of 21 kilodalton. It consists of two subunit α chain and β chain. It is known that combination of these subunits is different from the location in human body. S-100β is located in glial cell and schwann cell, S-100αβ in glial cell, and S-100αα in ABSTRACT Acute hemorrhagic stroke, a subtype of acute stroke is one of the leading causes of death and disability throughout the world. At present, the diagnosis of acute hemorrhagic stroke is mainly based on Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) but till now no biomarkers are routinely used in acute hemorrhagic stroke management. This article is a critical and descriptive review on the role of S100β protein as a biomarker in acute hemorrhagic stroke. Plasma S-100β level increases significantly in acute hemorrhagic stroke patients when compared to the normal subjects. Beside, the plasma S-100β can be correlated to the volume of hemorrhage in brain measured by plane CT scan. Plasma S-100β is an useful biomarker in acute hemorrhagic stroke and can be used for estimation of volume of hemorrhage in brain in acute hemorrhagic stroke patients. Thus, S-100β can be useful as an alternative to CT scan/MRI in diagnosis and in taking therapeutic decision in acute hemorrhagic stroke management.
Conclusions:
The NIHSS scale is a much more reliable method to determine mortality and morbidity and also adds no extra cost. Therefore, it is not recommended to measure S100B in the emergency room, but if it is measured, then the time between measurement and onset of stroke symptoms should be determined.
Key Words: acute ischemic stroke, S100B, GCS, NIHSS (Neurosurg Q 2014;24:87-90) C erebrovascular accidents are currently the second most common cause of mortality in the world. It is important to recognize the symptoms and diagnose this disease as early as possible. Serum S100B is found primarily in the glial cells of the central and peripheral nervous system and is elevated with stroke, cerebral hemorrhage, hypoxic brain damage, traumatic brain injury, or neurodegenerative disorders. [1][2][3][4][5][6][7] The glial-derived protein S100B is used in the diagnosis of several diseases and as a predictive marker for improving clinical management, outcome, and survival of patients. 8,9 However, it is controversial whether S100B has diagnostic and prognostic utility in the emergency room setting.
It has been established that the current measures used to clinically evaluate patients in the emergency room are for the most part useful to determine the prognosis of patients. In particular, the Glasgow Coma Scale (GCS) is used to evaluate patients with head trauma or lesions in the primary central nervous system. It can also be used during initial evaluations of emergency room patients with conscious disorder. 10 In addition, the National Institutes of Health Stroke Scale (NIHSS) is used to measure neurological deficits in acute stroke incidents. 11 The current scales used to measure cerebrovascular accidents have advantages either in cost or manufacturing time, but the goal for the new diagnostic and prognostic criteria is that they would better categorize progression of the early and late stages of the disease.
In this study, we wish to determine whether the NIHSS and GCS have utility in predicting the acute and first month poststroke mortality and morbidity in emergency room patients, as measured by serum S100B and clinical evaluations.
MATERIALS AND METHODS
The study group was composed of 62 consecutive patients who were admitted to the emergency room with acute ischemic stroke and were hospitalized within the intensive care unit of the Neurology Department. All of the patients were examined thoroughly and the diagnoses were confirmed using applied cerebral computed tomography and a consultation from the Neurology Department. Serum samples were drawn to measure S100B on admission and before discharged. After a detailed neurological examination, GCS and NIHSS were used to determine the consciousness of the patients. Patients with a score between 0 and 6 on the NIHSS scale were classified as having a mild stroke, between 7 and 15 a moderate stroke and between 16 and 38 a serious stroke. 12,13 After initial medical care in the emergency room, patients were transferred to the Neurology intensive care unit and received standard, universally accepted medical therapy. The mortality rate of the study group was measured and serum samples were obtained at the time of discharge to measure S100B.
One month after stroke onset, the functional status of each patient was determined using the modified Rankin Disability Scale (mRDS) as part of a program monitoring the quality of inpatient stroke care. The mRDS score ranges from 0 to 6, with higher scores indicating greater impairment (6 indicates death). Before analysis, the mRDS score was categorized into "good outcome" (0 to 2; patient is independent) versus "poor outcome" (3 to 6; patient is dependent or dead). 14,15 This study complies with the Principles of Ethical Publishing as described in the International Journal of Cardiology. 16
Estimation of the Total Infarction Volume
The total volume of the infarction areas that were present in the computed tomography scans were estimated by multiplying these areas by the thickness (2 mm) and adding them together. The results are expressed as mean ± SD. GCS indicates Glasgow Coma Scale; NIHSS, National Institutes of Health Stroke Scale; S100B-1, on admission; S100B-2, before discharged. Laboratory Parameters S100B levels were determined using the electrochemiluminescence method on the Elecsys-2010 analyzer.
Statistical Analysis
Statistics were performed using SPSS 11.0. The parametric data are presented as mean and SD values, whereas the nonparametric data are presented as frequencies. The parametric demographic parameters were evaluated using the Student t test and the nonparametric parameters were evaluated using the w 2 test. When correlation analysis was used to determine the relationship between variables, multiple regression analysis was performed in order to estimate independent risk factors.
RESULTS
The average age of the study group patients (28 males and 34 females) was 68.3 ± 11.9 (26 to 88) years. GCS scores ranged from 8 to 15 (average = 12.8 ± 2.5) and NIHSS scores from 1 to 30 (average = 11.1 ± 8.2).
The average hospital stay was 11.7 ± 6.2 (1 to 38) days. Nine patients (14.5%) died while in the hospital. When comparing the patients who died to those who did not, it was found that the average age was similar but the S100B level and NIHSS score was significantly higher and the GCS score was significantly lower in the patient who died ( Table 1). The stepwise logistic regression analysis showed that NIHSS was an independent predictor of mortality in hospital (odds ratio = 1.48; 95% confidence interval, 1.01-2.18; P < 0.05).
Table 1
Comparison of Characteristics Data Between Alive and Dead Subjects in Hospital
It was found that the S100B level immediately after the stroke was significantly related to the NIHSS and GCS scores (r = 0.543, P < 0.001 and r = À 0.459, P < 0.001). In addition, the clinical state and S100B levels of patients varied with the length of time between the stroke onset and emergency room treatment (Figs. 1-3).
Figure 1
Serum S100B levels compared with the National Institutes of Health Stroke Scale (NIHSS).
Thirty days after stroke, the mRDS levels significantly correlated with S100B levels on admission and before discharged and GCS and NIHSS scores. In addition, the time between stroke onset and admission to the emergency room was related to the S100B levels ( Table 2, Fig. 3). The linear logistic regression analysis indicated that NIHSS score and age were independent risk factors of mRDS (odds ratio = 1.48; 95% confidence interval, 1.01-2.18; P < 0.05) in our study population.
Table 2
Functional Outcome Modified Rankin Disability Scale (mRDS Score) at 1 Month
Figure 3
Serum S100B levels compared with the modified Rankin Disability Scale (mRDS) at 1 month.
At the 30-day follow-up, 4 patients (14.5%) died (Tables 2, 3). The NIHSS level of this dead patients were higher than alive patients; however, because of low number of patients, there was not found statistical significance (15.8 ± 9.5 and 8.4 ± 5.9, P = 0.218). DISCUSSION S100B is a low molecular weight calcium-binding protein and is found especially in glial cells of the central and peripheral nervous system. 17,18 The serum S100B level is elevated after destruction of cerebral structures, as occurs during stroke, hypoxic brain damage, traumatic brain injury, or neurodegenerative disorders. [1][2][3][4][5][6][7] The S100B levels reach a maximum 3 days after acute ischemic stroke and there is a gradual increase in levels starting 8 to 10 hours after symptom onset. 1,19 In addition, serum S100B levels are strongly correlated with brain infarct volume. 4,8 In the study by Abraha et al, 9 it was determined that there is a correlation between serum S100B levels and clinical outcome as evaluated by the modified Barthel index, Rankin scale, and Lindley score. It was concluded that the S100B protein is a prognostic factor predicting clinical outcome after acute stroke and that further studies should The results are expressed as mean ± SD. GCS indicates Glasgow Coma Scale; NIHSS, National Institutes of Health Stroke Scale; S100B-1, on admission; S100B-2, before discharged. be performed to determine how treatment affects S100B levels. In addition, Foerch et al 5 demonstrated that S100B protein levels decrease after successful thrombolysis in acute stroke; S100B serum levels were significantly reduced in acute stroke patients who had early recanalization after intravenous administration of t-PA.
Past studies have shown that serum S100B levels are elevated within the first 3 days after ischemic stroke onset. Meta-analysis suggested that S100B is not a valuable biomarker for diagnosing acute ischemic stroke because of its low specificity and delayed kinetics and the results of this study agree with this conclusion. 19 Similar results were also found in our study. In this study, patients who died from stroke while in the emergency room had high S100B levels; however, the NIHSS score was a better predictor of mortality. The S100B levels were evaluated along with the NIHSS and GCS scores and it was found that patients who came to the hospital longer after their initial stroke symptoms had high S100B levels, whereas patients who came sooner after the onset of their symptoms had lower S100B levels (Figs. 2, 3). One potential explanation for these results in that S100B serum levels reach a maximum at 3 days after stroke. Thus, it may not be useful to measure S100B levels in the early poststroke period after admission to the emergency room, and if S100B levels are measured in this context, they should be evaluated in light of the time stroke symptoms started.
Figure 2
Serum S100B levels compared with the Glasgow Coma Scale (GCS).
Studies show that S100B can help predict long-term prognosis. One study showed that patients with acute stroke and S100B levels higher that 0.2 g/L measured 48 hours after stroke had a much worse functional status. 6 Another study showed that patients who had faster changes in S100B levels in the first 24 hours after stroke had worse outcomes at the 3-month follow-up visit. 20 Fassbender et al 7 reported that there was a relationship between neurological outcomes as determined by the Scandinavian Stroke Scale and serum S100B levels.
In our study, we found that initial S100B levels measured while the patients were in the emergency room were better predictors of 1-month outcomes than later S100B levels but that the most useful prognostic measure was the NIHSS score. It was determined by regression analysis that NIHSS and age were independent predictors of long-term mRDS values. It was concluded that 1 reason that S100B was not determined to be clinically valuable as a prognostic indicator was because it was measured in the early poststroke period.
In addition, increased S100B levels were seen in 2 patients during follow-up and their mRDS levels were high in 1 month after stroke. It is hypothesized that increased S100B levels during follow-up are related to continuing cell death and that it may be useful to measure S100B levels to predict long-term prognosis.
CONCLUSIONS
For patients who come to the emergency room with a stroke prediagnosis, the S100B levels may be a useful prognostic measure initially and during follow-up. How-ever, it has been observed that the NIHSS scale is a much more reliable method to determine mortality and mobility and also adds no extra cost. Therefore, on the basis of the results of this study, it is not recommended to measure S100B in the emergency room, but if it is measured, then the time between measurement and onset of stroke symptoms should be determined.