| 1. |
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| 2. |
- Büki, Andras, 1966-, et al.
(författare)
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Minor and repetitive head injury
- 2014
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Ingår i: Advances and Technical Standards in Neurosurgery. - Cham : Springer. - 9783319090658 - 9783319090665 ; , s. 147-192
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Bokkapitel (refereegranskat)abstract
- Traumatic brain injury (TBI) is the leading cause of death and disability in the young, active population and expected to be the third leading cause of death in the whole world until 2020. The disease is frequently referred to as the silent epidemic, and many authors highlight the "unmet medical need" associated with TBI.The term traumatically evoked brain injury covers a heterogeneous group ranging from mild/minor/minimal to severe/non-salvageable damages. Severe TBI has long been recognized to be a major socioeconomical health-care issue as saving young lives and sometimes entirely restituting health with a timely intervention can indeed be extremely cost efficient.Recently it has been recognized that mild or minor TBI should be considered similarly important because of the magnitude of the patient population affected. Other reasons behind this recognition are the association of mild head injury with transient cognitive disturbances as well as long-term sequelae primarily linked to repeat (sport-related) injuries.The incidence of TBI in developed countries can be as high as 2-300/100,000 inhabitants; however, if we consider the injury pyramid, it turns out that severe and moderate TBI represents only 25-30 % of all cases, while the overwhelming majority of TBI cases consists of mild head injury. On top of that, or at the base of the pyramid, are the cases that never show up at the ER - the unreported injuries.Special attention is turned to mild TBI as in recent military conflicts it is recognized as "signature injury."This chapter aims to summarize the most important features of mild and repetitive traumatic brain injury providing definitions, stratifications, and triage options while also focusing on contemporary knowledge gathered by imaging and biomarker research.Mild traumatic brain injury is an enigmatic lesion; the classification, significance, and its consequences are all far less defined and explored than in more severe forms of brain injury.Understanding the pathobiology and pathomechanisms may aid a more targeted approach in triage as well as selection of cases with possible late complications while also identifying the target patient population where preventive measures and therapeutic tools should be applied in an attempt to avoid secondary brain injury and late complications.
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| 3. |
- Czeiter, Endre, et al.
(författare)
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Brain Injury Biomarkers May Improve the Predictive Power of the IMPACT Outcome Calculator
- 2012
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 29:9, s. 1770-1778
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Tidskriftsartikel (refereegranskat)abstract
- Outcome prediction following severe traumatic brain injury (sTBI) is a widely investigated field of research. A major breakthrough is represented by the IMPACT prognostic calculator based on admission data of more than 8500 patients. A growing body of scientific evidence has shown that clinically meaningful biomarkers, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and alpha II-spectrin breakdown product (SBDP145), could also contribute to outcome prediction. The present study was initiated to assess whether the addition of biomarkers to the IMPACT prognostic calculator could improve its predictive power. Forty-five sTBI patients (GCS score <= 8) from four different sites were investigated. We utilized the core model of the IMPACT calculator (age, GCS motor score, and reaction of pupils), and measured the level of GFAP, UCH-L1, and SBDP145 in serum and cerebrospinal fluid (CSF). The forecast and actual 6-month outcomes were compared by logistic regression analysis. The results of the core model itself, as well as serum values of GFAP and CSF levels of SBDP145, showed a significant correlation with the 6-month mortality using a univariate analysis. In the core model, the Nagelkerke R-2 value was 0.214. With multivariate analysis we were able to increase this predictive power with one additional biomarker (GFAP in CSF) to R-2 = 0.476, while the application of three biomarker levels (GFAP in CSF, GFAP in serum, and SBDP145 in CSF) increased the Nagelkerke R-2 to 0.700. Our preliminary results underline the importance of biomarkers in outcome prediction, and encourage further investigation to expand the predictive power of contemporary outcome calculators and prognostic models in TBI.
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| 4. |
- Mondello, Stefania, et al.
(författare)
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Glial Neuronal Ratio : A Novel Index for Differentiating Injury Type in Patients with Severe Traumatic Brain Injury
- 2012
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 29:6, s. 1096-1104
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Tidskriftsartikel (refereegranskat)abstract
- Neurobiochemical marker levels in blood after traumatic brain injury (TBI) may reflect structural changes detected by neuroimaging. This study evaluates whether correlations between neuronal (ubiquitin carboxyterminal hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarkers may be used as an indicator for differing intracranial pathologies after brain trauma. In 59 patients with severe TBI (Glasgow Coma Scale [GCS] score <= 8) serum samples were obtained at the time of hospital admission and analyzed for UCH-L1 and GFAP. Glial neuronal ratio (GNR) was evaluated as the ratio between GFAP and UCH-L1 concentrations. A logistic regression analysis was used to identify variables associated with type of injury. GNR had a median of 0.85 and was positively correlated with age (R = 0.45, p = 0.003). Twenty-nine patients presented with diffuse injury and 30 with focal mass lesions as assessed by CT scan at admission and classified according to the Marshall Classification. GNR was significantly higher in the focal mass lesion group compared with the diffuse injury group (1.77 versus 0.48, respectively; p = 0.003). Receiver operating characteristic curve analysis showed that GNR discriminated between types of injury (area under the curve [AUC] = 0.72; p = 0.003). GNR was more accurate earlier (<= 12 h after injury) than later (AUC = 0.80; p = 0.002). Increased GNR was independently associated with type of injury, but not age, gender, GCS score, or mechanism of injury. GNR was significantly higher in patients who died, but was not an independent predictor of death. The data from the present study indicate that GNR provides valuable information about different injury pathways, which may be of diagnostic significance. In addition, GNR may help to identify different pathophysiological mechanisms following different types of brain trauma, with implications for therapeutic interventions.
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| 5. |
- Mondello, Stefania, et al.
(författare)
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The Challenge of Mild Traumatic Brain Injury : Role of Biochemical Markers in Diagnosis of Brain Damage
- 2013
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Ingår i: Medicinal research reviews (Print). - : John Wiley & Sons. - 0198-6325 .- 1098-1128. ; 34:3, s. 503-531
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Forskningsöversikt (refereegranskat)abstract
- During the past decade there has been an increasing recognition of the incidence of mildtraumatic brain injury (mTBI) and a better understanding of the subtle neurological and cognitive deficitsthat may result from it. A substantial, albeit suboptimal, effort has been made to define diagnostic criteriafor mTBI and improve diagnostic accuracy. Thus, biomarkers that can accurately and objectively detectbrain injury after mTBI and, ideally, aid in clinical management are needed. In this review, we discuss thecurrent research on serum biomarkers for mTBI including their rationale and diagnostic performances.Sensitive and specific biomarkers reflecting brain injury can provide important information regardingTBI pathophysiology and serve as candidate markers for predicting abnormal computed tomographyfindings and/or the development of residual deficits in patients who sustain an mTBI. We also outline theroles of biomarkers in settings of specific interest including pediatric TBI, sports concussions and militaryinjuries, and provide perspectives on the validation of such markers for use in the clinic. Finally, emergingproteomics-based strategies for identifying novel markers will be discussed.
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| 6. |
- Welch, Robert D, et al.
(författare)
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Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B to Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury.
- 2016
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 33:2, s. 203-214
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Tidskriftsartikel (refereegranskat)abstract
- Head Computed Tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multi-center observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (Glial Fibrillary Acidic Protein [GFAP], Ubiquitin C-Terminal Hydrolase-L1 [UCH-L1] and S100B measured within 6-hours of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury), was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value > 40 pg/ml. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/ml) and S100B had a specificity of only 2% (cutoff value 30 pg/ml). All three biomarkers had similar values for areas under the receiver operator characteristic curve; 0.79 (95% CI; 0.70 to 0.88) for GFAP, 0.80 (0.71 to 0.89) for UCH-L1, and 0.75 (0.65 to 0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p=0.21 and p=0.77 respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values < 40 pg/ml could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
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| 7. |
- Welch, Robert D., et al.
(författare)
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Ability of serum glial fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B to differentiate normal and abnormal head computed tomography findings in patients with suspected mild or moderate traumatic brain injury
- 2016
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 33:2, s. 203-214
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Tidskriftsartikel (refereegranskat)abstract
- Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
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| 8. |
- Zhang, Zhiqun, et al.
(författare)
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Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products
- 2014
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.
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| 9. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 10. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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