S100B, Actor and Biomarker of Mild Traumatic Brain Injury.
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ABSTRACT:
SUBMITTER: Oris C
PROVIDER: S-EPMC10095287 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
Publications
S100B, Actor and Biomarker of Mild Traumatic Brain Injury.
Oris Charlotte C Kahouadji Samy S Durif Julie J Bouvier Damien D Sapin Vincent V
International journal of molecular sciences 20230401 7
Mild traumatic brain injury (mTBI) accounts for approximately 80% of all TBI cases and is a growing source of morbidity and mortality worldwide. To improve the management of children and adults with mTBI, a series of candidate biomarkers have been investigated in recent years. In this context, the measurement of blood biomarkers in the acute phase after a traumatic event helps reduce unnecessary CT scans and hospitalizations. In athletes, improved management of sports-related concussions is also ...[more]
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| S-EPMC8491985 | biostudies-literature
Project description:Mild traumatic brain injury (TBI) accounts for the vast majority of the nearly two million brain injuries suffered in the United States each year. Mild TBI is commonly classified as complicated (radiographic evidence of intracranial injury) or uncomplicated (radiographically negative). Such a distinction is important because it helps to determine the need for further neuroimaging, potential admission, or neurosurgical intervention. Unfortunately, imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are costly and not without some risk. The purpose of this study was to screen 87 serum biomarkers to identify a select panel of biomarkers that would predict the presence of intracranial injury as determined by initial brain CT. Serum was collected from 110 patients who sustained a mild TBI within 24 hours of blood draw. Two models were created. In the broad inclusive model, 72kDa type IV collagenase (MMP-2), C-reactive protein (CRP), creatine kinase B type (CKBB), fatty acid binding protein-heart (hFABP), granulocyte-macrophage colony-stimulating factor (GM-CSF) and malondialdehyde modified low density lipoprotein (MDA-LDL) significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.975 and a negative predictive value (NPV) of 98.6. In the parsimonious model, MMP-2, CRP, and CKBB type significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.964 and a negative predictive value (NPV) of 97.2. These results suggest that a serum based biomarker panel can accurately differentiate patients with complicated mild TBI from those with uncomplicated mild TBI. Such a panel could be useful to guide early triage decisions, including the need for further evaluation or admission, especially in those environments in which resources are limited.
| S-EPMC5371303 | biostudies-literature
Project description:To investigate longitudinal changes in global and regional brain volume in patients 1 year after mild traumatic brain injury (MTBI) and to correlate such changes with clinical and neurocognitive metrics.This institutional review board-approved study was HIPAA compliant. Twenty-eight patients with MTBI (with 19 followed up at 1 year) with posttraumatic symptoms after injury and 22 matched control subjects (with 12 followed up at 1 year) were enrolled. Automated segmentation of brain regions to compute regional gray matter (GM) and white matter (WM) volumes was performed by using three-dimensional T1-weighted 3.0-T magnetic resonance imaging, and results were correlated with clinical metrics. Pearson and Spearman rank correlation coefficients were computed between longitudinal brain volume and neurocognitive scores, as well as clinical metrics, over the course of the follow-up period.One year after MTBI, there was measurable global brain atrophy, larger than that in control subjects. The anterior cingulate WM bilaterally and the left cingulate gyrus isthmus WM, as well as the right precuneal GM, showed significant decreases in regional volume in patients with MTBI over the 1st year after injury (corrected P < .05); this was confirmed by means of cross-sectional comparison with data in control subjects (corrected P < .05). Left and right rostral anterior cingulum WM volume loss correlated with changes in neurocognitive measures of memory (r = 0.65, P = .005) and attention (r = 0.60, P = .01). At 1-year follow-up, WM volume in the left cingulate gyrus isthmus correlated with clinical scores of anxiety (Spearman rank correlation r = -0.68, P = .007) and postconcussive symptoms (Spearman rank correlation r = -0.65, P = .01).These observations demonstrate structural changes to the brain 1 year after injury after a single concussive episode. Regional brain atrophy is not exclusive to moderate and severe traumatic brain injury but may be seen after mild injury. In particular, the anterior part of the cingulum and the cingulate gyrus isthmus, as well as the precuneal GM, may be distinctively vulnerable 1 year after MTBI.
| S-EPMC3662902 | biostudies-other
Project description:ObjectivesResearch suggests that the majority of mild traumatic brain injury (mTBI) patients exhibit both cognitive and emotional dysfunction within the first weeks of injury, followed by symptom resolution 3-6 months postinjury. The neuronal correlates of said dysfunction are difficult to detect with standard clinical neuroimaging, complicating differential diagnosis and early identification of patients who may not recover. This study examined whether resting state functional magnetic resonance imaging (fMRI) provides objective markers of injury and predicts cognitive, emotional, and somatic complaints in mTBI patients semiacutely (<3 weeks postinjury) and in late recovery (3-5 month) phases.MethodsTwenty-seven semiacute mTBI patients and 26 gender, age, and education-matched controls were studied. Fifteen of 27 patients returned for a follow-up visit 3-5 months postinjury. The main dependent variables were spontaneous fluctuations (temporal correlation) in the default-mode (DMN) and fronto-parietal task-related networks as measured by fMRI.ResultsSignificant differences in self-reported cognitive, emotional, and somatic complaints were observed (all P < 0.05), despite normal clinical (T1 and T2) imaging and neuropsychological testing results. Mild TBI patients demonstrated decreased functional connectivity within the DMN and hyper-connectivity between the DMN and lateral prefrontal cortex. Measures of functional connectivity exhibited high levels of sensitivity and specificity for patient classification and predicted cognitive complaints in the semi-acute injury stage. However, no changes in functional connectivity were observed across a 4-month recovery period.ConclusionsAbnormal connectivity between the DMN and frontal cortex may provide objective biomarkers of mTBI and underlie cognitive impairment.
| S-EPMC3204375 | biostudies-literature
Project description:Individuals with a history of mild traumatic brain injury (mTBI) are at an increased risk for neurodegenerative disease, suggesting that intrinsic neuroprotective mechanisms, such as the endogenous antioxidant reservoir, may be depleted long-term after mTBI. Here, we retrospectively analyzed symptoms and blood antioxidants in patients with a history of mTBI who presented to Resilience Code, a sports medicine clinic in Colorado. Significant decreases in alpha-tocopherol, selenium, linoleic acid, taurine, docosahexaenoic acid, and total omega-3 were measured in the total mTBI population versus controls. Male mTBI patients showed depletion of a larger array of antioxidants than females. Patients with a history of mTBI also reported significantly worsened emotional, energy, head, and cognitive symptoms, with males displaying more extensive symptomology. Multiple or chronic mTBI patients had worsened symptoms than single or acute/subchronic mTBI patients, respectively. Finally, male mTBI patients with the largest reductions in polyunsaturated fatty acids (PUFAs) displayed worse symptomology than male mTBI patients with less depletion of this antioxidant reservoir. These results demonstrate that antioxidant depletion persists in patients with a history of mTBI and these deficits are sex-specific and associated with worsened symptomology. Furthermore, supplementation with specific antioxidants, like PUFAs, may diminish symptom severity in patients suffering from chronic effects of mTBI.
| S-EPMC10976465 | biostudies-literature
Project description:ImportanceTraumatic brain injury (TBI) affects millions of people in the US each year. Most patients with TBI seen in emergency departments (EDs) have a Glasgow Coma Scale (GCS) score of 15 and a head computed tomography (CT) scan showing no acute intracranial traumatic injury (negative head CT scan), yet the short-term and long-term functional outcomes of this subset of patients remain unclear.ObjectiveTo describe the 2-week and 6-month recovery outcomes in a cohort of patients with mild TBI with a GCS score of 15 and a negative head CT scan.Design, setting, and participantsThis cohort study analyzed participants who were enrolled from January 1, 2014, to December 31, 2018, in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective, observational cohort study of patients with TBI that was conducted in EDs of 18 level I trauma centers in urban areas. Of the total 2697 participants in the TRACK-TBI study, 991 had a GCS score of 15 and negative head CT scan and were eligible for inclusion in this analysis. Data were analyzed from September 1, 2021, to May 30, 2022.Main outcomes and measuresThe primary outcome was the Glasgow Outcome Scale-Extended (GOS-E) score, which was stratified according to functional recovery (GOS-E score, 8) vs incomplete recovery (GOS-E score, <8), at 2 weeks and 6 months after the injury. The secondary outcome was severity of mild TBI-related symptoms assessed by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score.ResultsA total of 991 participants (mean [SD] age, 38.5 [15.8] years; 631 male individuals [64%]) were included. Of these participants, 751 (76%) were followed up at 2 weeks after the injury: 204 (27%) had a GOS-E score of 8 (functional recovery), and 547 (73%) had a GOS-E scores less than 8 (incomplete recovery). Of 659 participants (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery. Most participants with incomplete recovery reported that they had not returned to baseline or preinjury life (88% [479 of 546]; 95% CI, 85%-90%). Mean RPQ score was 16 (95% CI, 14-18; P < .001) points lower at 2 weeks (7 vs 23) and 18 (95% CI, 16-20; P < .001) points lower at 6 months (4 vs 22) in participants with a GOS-E score of 8 compared with those with a GOS-E score less than 8.Conclusions and relevanceThis study found that most participants with a GCS score of 15 and negative head CT scan reported incomplete recovery at 2 weeks and 6 months after their injury. The findings suggest that emergency department clinicians should recommend 2-week follow-up visits for these patients to identify those with incomplete recovery and to facilitate their rehabilitation.
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Project description:BackgroundSerum biomarker S100B has been explored for its potential benefit to improve clinical decision-making in the management of patients suffering from traumatic brain injury (TBI), especially as a pre-head computed-tomography screening test for patients with mild TBI. Although being already included into some guidelines, its implementation into standard care is still lacking. This might be explained by a turnaround time (TAT) too long for serum S100B to be used in clinical decision-making in emergency settings.MethodsS100B concentrations were determined in 136 matching pairs of serum and lithium heparin blood samples. The concordance of the test results was assessed by linear regression, Passing Pablok regression and Bland-Altman analysis. Bias and within- and between-run imprecision were determined by a 5 × 4 model using pooled patient samples. CT scans were performed as clinically indicated.ResultsOverall, S100B levels between both blood constituents correlated very well. The suitability of S100B testing from plasma was verified according to ISO15189 requirements. Using a cut-off of 0.105 ng/ml, a sensitivity and negative predictive value of 100% were obtained for identifying patients with pathologic CT scans. Importantly, plasma-based testing reduced the TAT to 26 min allowing for quicker clinical decision-making. The clinical utility of integrating S100B in TBI management is highlighted by two case reports.ConclusionsPlasma-based S100B testing compares favorably with serum-based testing, substantially reducing processing times as the prerequisite for integrating S100B level into management of TBI patients. The proposed new clinical decision algorithm for TBI management needs to be validated in further prospective large-scale studies.
| S-EPMC8141926 | biostudies-literature
Project description:Innate immune activation has been attributed a key role in traumatic brain injury (TBI) and successive morbidity. In mild TBI (mTBI), however, the extent and persistence of innate immune activation are unknown. We determined plasma cytokine level changes over 12 months after an mTBI in hospitalized and non-hospitalized patients compared with community controls; and examined their associations to injury-related and demographic variables at admission. Prospectively, 207 patients presenting to the emergency department (ED) or general practitioner with clinically confirmed mTBI and 82 matched community controls were included. Plasma samples were obtained at admission, after 2 weeks, 3 months, and 12 months. Cytokine levels were analysed with a 27-plex beads-based immunoassay. Brain magnetic resonance imaging (MRI) was performed on all participants. Twelve cytokines were reliably detected. Plasma levels of interferon gamma (IFN-γ), interleukin 8 (IL-8), eotaxin, macrophage inflammatory protein-1-beta (MIP-1β), monocyte chemoattractant protein 1 (MCP-1), IL-17A, IL-9, tumor necrosis factor (TNF), and basic fibroblast growth factor (FGF-basic) were significantly increased at all time-points in patients compared with controls, whereas IFN-γ-inducing protein 10 (IP-10), platelet-derived growth factor (PDGF), and IL-1ra were not. IL-17A and FGF-basic showed significant increases in patients from admission to follow-up at 3 months, and remained increased at 12 months compared with admission. Interestingly, MRI findings were negatively associated with four cytokines: eotaxin, MIP-1β, IL-9, and IP-10, whereas age was positively associated with nine cytokines: IL-8, eotaxin, MIP-1β, MCP-1, IL-17A, IL-9, TNF, FGF-basic, and IL-1ra. TNF was also increased in those with presence of other injuries. In conclusion, mTBI activated the innate immune system consistently and this is the first study to show that several inflammatory cytokines remain increased for up to 1 year post-injury.
| S-EPMC7502683 | biostudies-literature
Project description:Common neuroimaging findings in mild traumatic brain injury (mTBI), including sport-related concussion (SRC), are reviewed based on computed tomography and magnetic resonance imaging (MRI). Common abnormalities radiologically identified on the day of injury, typically a computed tomographic scan, are in the form of contusions, small subarachnoid or intraparenchymal hemorrhages as well as subdural and epidural collections, edema, and skull fractures. Common follow-up neuroimaging findings with MRI include white matter hyperintensities, hypointense signal abnormalities that reflect prior hemorrhage, focal encephalomalacia, presence of atrophy and/or dilated Virchow-Robins perivascular space. The MRI findings from a large pediatric mTBI study show low frequency of positive MRI findings at 6 months postinjury. The review concludes with an examination of some of the advanced MRI-based image analysis methods that can be performed in the patient who has sustained an mTBI.
| S-EPMC6581215 | biostudies-literature
Project description:Mild traumatic brain injury (mTBI) is an important public health problem. Although conventional medical imaging techniques can detect moderate-to-severe injuries, they are relatively insensitive to mTBI. In this study, we used hybrid diffusion imaging (HYDI) to detect white matter alterations in 19 patients with mTBI and 23 other trauma control patients. Within 15 days (standard deviation?=?10) of brain injury, all subjects underwent magnetic resonance HYDI and were assessed with a battery of neuropsychological tests of sustained attention, memory, and executive function. Tract-based spatial statistics (TBSS) was used for voxel-wise statistical analyses within the white matter skeleton to study between-group differences in diffusion metrics, within-group correlations between diffusion metrics and clinical outcomes, and between-group interaction effects. The advanced diffusion imaging techniques, including neurite orientation dispersion and density imaging (NODDI) and q-space analyses, appeared to be more sensitive then classic diffusion tensor imaging. Only NODDI-derived intra-axonal volume fraction (Vic) demonstrated significant group differences (i.e., 5-9% lower in the injured brain). Within the mTBI group, Vic and a q-space measure, P0, correlated with 6 of 10 neuropsychological tests, including measures of attention, memory, and executive function. In addition, the direction of correlations differed significantly between groups (R2?>?0.71 and pinteration < 0.03). Specifically, in the control group, higher Vic and P0 were associated with better performances on clinical assessments, whereas in the mTBI group, higher Vic and P0 were associated with worse performances with correlation coefficients >0.83. In summary, the NODDI-derived axonal density index and q-space measure for tissue restriction demonstrated superior sensitivity to white matter changes shortly after mTBI. These techniques hold promise as a neuroimaging biomarker for mTBI.
| S-EPMC6196746 | biostudies-literature