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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 2  |  Page : 417-422

Traumatic brain injury: serum S-100B protein measurement related to neuroradiological findings


1 Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Neurosurgery, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
3 Department of Critical Care, Sheben El Koum Teaching Hospital, Shebeen El-Kom, Egypt

Date of Submission15-Aug-2017
Date of Acceptance26-Dec-2017
Date of Web Publication25-Jun-2019

Correspondence Address:
Ahmed A Metwally
Saad Zaghlol Street, Tala, Menoufia 32611
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_564_17

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  Abstract 

Objective
The aim of this study was to estimate the level of S-100B protein as a biological marker and to assess its sensitivity in the detection and prediction of outcome of traumatic brain injury (TBI) patients compared with radiological and clinical scores.
Background
TBI has a tremendous impact on public health. S-100B protein increases in cases of TBI and does not increase in nonbrain injuries. S-100B has been found to correlate with the severity of head injury.
Patients and methods
The study was a prospective, randomized, controlled study. Forty critical patients were divided into two groups; group I had 20 patients with TBI and group II had 20 patients with head-free trauma. Group I had a sampling of serum S-100B at day 1, 3, 5, and at discharge, and the results were correlated with computed tomography brain findings, Glasgow Coma Scale, and outcome. Group II had a sampling of serum S-100B at day 1, and the result was correlated with the results of group I.
Results
Significant difference between the results of S-100B in group I and group II was detected (P < 0.001), with higher results of S-100B in TBI patients. Significant difference between the results of S-100B in survival and nonsurvival for patients in group I was detected (P = 0.002), with higher results of S-100B in nonsurvival patients. Significant correlation between the results of S-100B and Glasgow Coma Scale in group I was detected (P = 0.002).
Conclusion
S-100B is a prognostic marker in TBI, specific to TBI, and not correlated to the findings in computed tomography brain.

Keywords: computed tomography, outcome, S-100 calcium-binding protein B, traumatic brain injury


How to cite this article:
Doha NM, Ammar AS, El-Mashad MM, Metwally AA. Traumatic brain injury: serum S-100B protein measurement related to neuroradiological findings. Menoufia Med J 2019;32:417-22

How to cite this URL:
Doha NM, Ammar AS, El-Mashad MM, Metwally AA. Traumatic brain injury: serum S-100B protein measurement related to neuroradiological findings. Menoufia Med J [serial online] 2019 [cited 2019 Sep 16];32:417-22. Available from: http://www.mmj.eg.net/text.asp?2019/32/2/417/260898




  Introduction Top


Traumatic brain injury (TBI) has a tremendous impact on public health. In general, it is agreed that a TBI with a Glasgow Coma Scale (GCS) of 13 or above is mild; 9–12 is moderate; and 8 or below is severe[1].

Mild TBI constitutes one of the most frequent motives for emergency hospital care and the first among the neurological illnesses. In contrast, severe TBI is one of the main causes of trauma-related mortality[1].

S-100B protein is a 21 kDa calcium-binding protein (Ca2+). It is found mainly in the cytosol of astroglial cells and Schwann cells. It has extracranial origin, and is found in the skeletal muscle, skin, fat, and in melanoma tumors[2],[3].

S-100B protein has intracellular functions which are Ca2+ regulating multiple functions as protein phosphorylation and degradation, while the extracellular functions under physiological conditions are neurotrophic factor and under pathological conditions are neurotoxic[2].

S-100B protein can be detected in the serum, cerebrospinal fluid, or in the urine. It increases in cases of TBI either isolated or in cases with poly-traumatic injuries, but does not increase in nonbrain injuries[4],[5],[6].

S-100B protein serum levels have been found to correlate with the severity of head injury. It shows a high sensitivity in the screening of patients with mild head injury. It can be used as a biomarker for computed tomography (CT) brain triage, which may improve patient screening and decrease the number of CT brain scans performed[5],[7],[8].

It can also increase with higher intracranial pressure, disruption of the blood–brain–barrier, or with invasive neurosurgical procedures[5],[8]. There was a significant association between S-100B protein serum level and the course and outcome of patients with head injuries[5],[8],[9].

The aim of this study was to estimate the level of S-100B protein as a biological marker and to assess its sensitivity in the detection and prediction of outcome of traumatic brain injury patients compared with radiological and clinical scores.


  Patients and Methods Top


Our study was done as a prospective, randomized, controlled study after approval by the Ethics Committee of the Faculty of Medicine, Menoufia University and was carried out on 40 adult patients aged more than or equal to 18 years, who were admitted to the Menoufia University ICU from August 2015 to April 2016.

After fulfilling the inclusion criteria, written informed consents were taken from all patients or their guardians. The 40 patients were divided into two equal groups. Group I: patients with traumatic head injury who were subjected to estimation of serum levels of S-100B protein on the first, third, fifth day of admission, and on discharge and group II: patients with trauma rather than head trauma who were subjected to estimation of serum levels of S-100B protein on the first day.

All patients of at least 18 years old admitted to the ICU at the time of study with traumatic head injury, either isolated head injury or poly-trauma patients, were included in the study with exclusion of patients who had neurosurgical intervention on admission; postarrest patients; patients who have skeletal muscle, skin, fat, or melanoma tumors, sedated patients; and severe hypoxemic patients.

All patients in group I on admission were subjected to detailed history taking (age, sex, weight, and comorbidities including cardiothoracic trauma, abdominal trauma, orthopedic trauma, chest disease, diabetes mellitus, hypertension, or renal disease). Each patient was scored by coded revised trauma score (RTSc), acute physiology and chronic health evaluation II, GCS, and sequential organ failure and assessment score (SOFA)[10],[11],[12],[13]. CT brain was done for each patient.

For each patient, serum sample was withdrawn for the estimation of S-100B protein level within 24 h of head injury by enzyme-linked immune-sorbent assay kit (Sunred Biological Technology, Shanghai, China) as described by the manufacturer.

All patients in group I in the ICU were scored by GCS every 12 h; RTSc at day 3, 5, and on discharge; SOFA at day 3, 5, and on discharge; had sample of serum S-100B protein level at day 3, 5, and on discharge; and had CT brain if GCS was deteriorated.

All patients in group II on admission were subjected to detailed history taking (age, sex, weight, and comorbidities including cardiothoracic trauma, abdominal trauma, orthopedic trauma, chest disease, diabetes mellitus, hypertension, or renal disease), and had a sample of serum S-100B protein level within 24 h of trauma to be estimated by enzyme-linked immune-sorbent assay.

Statistical analysis

Results were statistically analyzed by statistical package for the social sciences (SPSS), version 20 (SPSS Incorporation, Chicago, Illinois, USA). Two types of statistics were done: descriptive, for example, percentage, mean and SD, and analytical by Student's t-test which is a single test used to collectively indicate the presence of any significant difference between two means for a normally distributed quantitative variable; Mann–Whitney U-test which is a nonparametric test of Student's t-test, repeated measures analysis of variance (ANOVA) which is a single test used to collectively indicate the presence of any significant difference between several time sequences for a normally distributed quantitative variable; Friedman test which is the nonparametric version of repeated measures ANOVA; post-hoc test which is used after repeated measures ANOVA or Friedman tests and show any significant difference between the individual time sequences; Fisher's exact test which is used to compare between two groups regarding one qualitative variable in a 2 × 2 contingency table when the expected count of any of the cells is less than 5; Z-test which is used to compare between two proportions; Spearman's correlation analysis which is used to show strength and direction of association between one quantitative variable and ordinal qualitative variable; receiver operating characteristic (ROC curve) which is a graphical plot of the sensitivity versus false positive rate (1 − specificity) and is also known as ROC curve, because it is a comparison of two operating characteristics true positive rate and false positive rate; and a P value of less than 0.05 was set to be significant.


  Results Top


Our study included 40 patients, 20 patients in one group. The general demographic data and baseline characteristics of the enrolled patients in both groups showed no statistical significant difference among the studied groups [Table 1].
Table 1: Demographic data and patient characteristics

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Distribution of the studied groups regarding S-100B protein at day 1 shows that the mean of results of S-100B protein in day 1 was 1050.85 in group I, while it was 332.0 in group II with statistically highly significant difference between two means (P < 0.001) [Table 2].
Table 2: Distribution of the studied groups regarding S-100B protein at day 1

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Distribution of the survival and nonsurvival patients in the head trauma group regarding S-100B protein shows that the mean of results of S-100B protein in day 3 was 2125.75 in nonsurvival patients, while it was 753.62 in survival patients with statistically significant difference between two means (P = 0.002). The mean of the results of S-100B protein in day 5 was 2370.75 in nonsurvival patients while it was 670.75 in survival patients with statistically significant difference between two means (P = 0.002), and shows that the means of results of S-100B protein in nonsurvival patients was progressively increased from day 1 to 5; the means of the results of S-100B protein in survival was regressively decreased from day 1 to day of discharge [Table 3] and [Figure 1].
Table 3: Distribution of the survival and nonsurvival patients in head trauma group regarding S-100B protein

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Figure 1: Distribution of the survival and nonsurvival patients in the head trauma group regarding S-100B protein.

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Spearman's correlation between S-100B protein and GCS, SOFA, and RTSc at different time sequences in the head trauma group shows that there is a statistically significant difference in Spearman's correlation between S-100B protein and GCS at day 1 (P = 0.005), day 3 (P = 0.012), and day 5 (P = 0.002) and no statistically significant difference at discharge, statistically significant difference in Spearman's correlation between S-100B protein and SOFA at day 3 (P = 0.045) and day 5 (P = 0.002) and no statistically significant difference at day 1 and discharge, and statistically significant difference in Spearman's correlation between S-100B protein and RTSc at day 3 (P = 0.014) and day 5 (P = 0.028) and no statistically significant difference at day 1 and at discharge [Table 4].
Table 4: Spearman's correlation between S-100B protein and Glasgow Coma Scale, sequential organ failure and assessment score and coded revised trauma score at different time sequences

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Distribution of S-100B protein among the head trauma patient group regarding CT brain findings shows that there is no statistically significant difference in any findings of CT brain [Table 5].
Table 5: Distribution of S-100B protein among the head trauma patient group regarding computed tomography brain results

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  Discussion Top


We found that the mean S-100B protein in day 1 was 1050.85 in group I, while it was 332.0 in group II with statistically highly significant difference between two means. Results in the head trauma group were higher.

This agreed with Sharma et al.[9], who found that the mean S-100B in day 1 in the head trauma group was 67 and the mean in day 1 in the control group was 45 with statistically significant difference between two means, and Pham et al.[14] who found that the main species of S-100B released from the brain was the B–B homodimer, and his results show that the extracranial sources of S-100B do not affect the serum levels.

This disagreed with Pfortmualler et al.[15] who found that S-100B concentrations are essentially the same with and without head injury in patients with major trauma, and Routsi et al.[16] found that patients who suffer from trauma, presenting multiple injuries to the thorax, extremities and abdominal organs without any identified damages to the central nervous system, have been shown to exhibit elevated S-100B concentrations in serum.

We found that the mean S-100B protein in survival at day 1 was 973, at day 3 was 753, and at day 5 was 670. The mean S-100B protein in nonsurvival at day 1 was 1360, at day 3 was 2125, and at day 5 was 2370. Results were higher in nonsurvival patients and poor outcome patients with statistically significant difference at days 3 and 5.

This agreed with Thelin et al.[17] who found that the S-100B levels in serum are a useful marker in predicting the outcome and validating the treatment effect and Kellermann et al.[18] who found that the mean S-100B in poor outcome patients was 0.26, and in good outcome patients was 0.13, and found that high initial S-100B levels of more than 0.7 μg/dl in serum are associated with 100% mortality, which might help to guide therapy strategies in severe neurotrauma, Fan et al.[19] who found that the mean S-100B in severe TBI patients was 82, and in moderate TBI patients was 42, so his conclusion was that S-100B increased in the plasma of TBI patients, especially in patients with diffuse axonal injury (DAI) and the initial plasma S-100B is associated with neurological outcomes, Sharma et al.[9] who found that the mean S-100B in nonsurvival was 216, and in survival was 57, and found that there was a significant association between S-100B protein level and the outcome and course of patients with head injuries, Thelin et al.[20] who found that the S-100B levels promoting S-100B as a marker for brain death diagnostics (0.372 μg/l the first 24 h) are the levels in patients that we repeatedly have seen return to a favorable outcome 12 months after injury, and Vos et al.[21] who found that S-100B was the strongest single predictor of unfavorable outcome with 100% discrimination, and S-100B levels in serum are adjuncts to the assessment of brain damage after TBI and may enhance prognostication when combined with clinical variables.

This disagreed with Kleindienst et al.[22] who found that high S-100B levels in the cerebrospinal fluid (CSF) and serum were inconsistently associated with the outcome. The passage of S-100B from CSF to blood (100 × serumS-100B/CSFS-100B) was significantly decreased although the albumin quotient suggested an 'open' blood–CSF barrier, events possibly interfering with the blood–brain–barrier did not affect the S-100B passage, so his conclusion was that S-100B measurements do not reliably predict the outcome, and a compromised blood–CSF barrier did not affect the passage of S-100B from CSF to serum.

We found that there is correlation between S-100B protein and GCS in day 1, 3, and 5.

This agreed with the result of Fan et al.[19] the ROC curve of whom was based on the initial plasma S-100B and GCS to correlate them with the long-term neurological outcome assessment and ROC analysis indicated that both S-100B and GCS status are the prediction of patients' neurological outcome and there is correlation between them.

We found that there is no statistically significant difference in the distribution of S-100B protein among the head trauma patient group regarding CT brain results.

This disagreed with the result of Thelin et al.[23], who found that there is a significant correlation between S-100B protein and Rotterdam CT score and Stockholm CT score, Thelin et al.[24] found that there is secondary increases in serum levels of S-100B, even as low as more than or equal to 0.05 μg/l, beyond 48 h after TBI are strongly correlated to the development of clinically significant secondary radiological findings of Korfias et al.[25] who found that S-100B has been shown to increase in the focal, more severe, lesions compared with more diffuse injuries.


  Conclusion Top


S-100B is a prognostic marker in TBI and corresponds to the severity of injury and outcome of patients. S-100B is specific to TBI. S-100B is not correlated to the findings in CT brain and their severity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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