scholarly journals Towards the Development of an Integrative, Evidence-Based Suite of Indicators for the Prediction of Outcome Following Mild Traumatic Brain Injury: Results from a Pilot Study

2020 ◽  
Vol 10 (1) ◽  
pp. 23 ◽  
Author(s):  
Aleksandra Gozt ◽  
Melissa Licari ◽  
Alison Halstrom ◽  
Hannah Milbourn ◽  
Stephen Lydiard ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Fibrillary Acidic Protein ◽  
Mild Traumatic Brain Injury ◽  
Diffusion Tensor ◽  
Neuron Specific Enolase ◽  
Mean Diffusivity ◽  
Small Sample ◽  
Acidic Protein ◽  
Healthy Controls

Background: Persisting post-concussion symptoms (PPCS) is a complex, multifaceted condition in which individuals continue to experience the symptoms of mild traumatic brain injury (mTBI; concussion) beyond the timeframe that it typically takes to recover. Currently, there is no way of knowing which individuals may develop this condition. Method: Patients presenting to a hospital emergency department (ED) within 48 h of sustaining a mTBI underwent neuropsychological assessment and demographic, injury-related information and blood samples were collected. Concentrations of blood-based biomarkers neuron specific enolase, neurofilament protein-light, and glial fibrillary acidic protein were assessed, and a subset of patients also underwent diffusion tensor–magnetic resonance imaging; both relative to healthy controls. Individuals were classified as having PPCS if they reported a score of 25 or higher on the Rivermead Postconcussion Symptoms Questionnaire at ~28 days post-injury. Univariate exact logistic regression was performed to identify measures that may be predictive of PPCS. Neuroimaging data were examined for differences in fractional anisotropy (FA) and mean diffusivity in regions of interest. Results: Of n = 36 individuals, three (8.33%) were classified as having PPCS. Increased performance on the Repeatable Battery for the Assessment of Neuropsychological Status Update Total Score (OR = 0.81, 95% CI: 0.61–0.95, p = 0.004), Immediate Memory (OR = 0.79, 95% CI: 0.56–0.94, p = 0.001), and Attention (OR = 0.86, 95% CI: 0.71–0.97, p = 0.007) indices, as well as faster completion of the Trails Making Test B (OR = 1.06, 95% CI: 1.00–1.12, p = 0.032) at ED presentation were associated with a statistically significant decreased odds of an individual being classified as having PPCS. There was no significant association between blood-based biomarkers and PPCS in this small sample, although glial fibrillary acidic protein (GFAP) was significantly increased in individuals with mTBI relative to healthy controls. Furthermore, relative to healthy age and sex-matched controls (n = 8), individuals with mTBI (n = 14) had higher levels of FA within the left inferior frontal occipital fasciculus (t (18.06) = −3.01, p = 0.008). Conclusion: Performance on neuropsychological measures may be useful for predicting PPCS, but further investigation is required to elucidate the utility of this and other potential predictors.

scholarly journals Early Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein in Predicting the Outcome of Mild Traumatic Brain Injury

2019 ◽  
Vol 36 (10) ◽  
pp. 1551-1560 ◽  
Author(s):  
Iftakher Hossain ◽  
Mehrbod Mohammadian ◽  
Riikka S.K. Takala ◽  
Olli Tenovuo ◽  
Linnéa Lagerstedt ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Fibrillary Acidic Protein ◽  
Mild Traumatic Brain Injury ◽  
Acidic Protein ◽  
Neurofilament Light

scholarly journals Diffusion Tensor Imaging of the Evolving Response to Mild Traumatic Brain Injury in Rats

2019 ◽  
Vol 13 ◽  
pp. 117906951985862 ◽  
Author(s):  
Wouter S Hoogenboom ◽  
Todd G Rubin ◽  
Kenny Ye ◽  
Min-Hui Cui ◽  
Kelsey C Branch ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Diffusion Tensor Imaging ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Diffusion Tensor ◽  
Axonal Injury ◽  
Mean Diffusivity ◽  
Multiple Time ◽  
Post Injury

Mild traumatic brain injury (mTBI), also known as concussion, is a serious public health challenge. Although most patients recover, a substantial minority suffers chronic disability. The mechanisms underlying mTBI-related detrimental effects remain poorly understood. Although animal models contribute valuable preclinical information and improve our understanding of the underlying mechanisms following mTBI, only few studies have used diffusion tensor imaging (DTI) to study the evolution of axonal injury following mTBI in rodents. It is known that DTI shows changes after human concussion and the role of delineating imaging findings in animals is therefore to facilitate understanding of related mechanisms. In this work, we used a rodent model of mTBI to investigate longitudinal indices of axonal injury. We present the results of 45 animals that received magnetic resonance imaging (MRI) at multiple time points over a 2-week period following concussive or sham injury yielding 109 serial observations. Overall, the evolution of DTI metrics following concussive or sham injury differed by group. Diffusion tensor imaging changes within the white matter were most noticeable 1 week following injury and returned to baseline values after 2 weeks. More specifically, we observed increased fractional anisotropy in combination with decreased radial diffusivity and mean diffusivity, in the absence of changes in axial diffusivity, within the white matter of the genu corpus callosum at 1 week post-injury. Our study shows that DTI can detect microstructural white matter changes in the absence of gross abnormalities as indicated by visual screening of anatomical MRI and hematoxylin and eosin (H&E)-stained sections in a clinically relevant animal model of mTBI. Whereas additional histopathologic characterization is required to better understand the neurobiological correlates of DTI measures, our findings highlight the evolving nature of the brain’s response to injury following concussion.

scholarly journals Comparing Glial Fibrillary Acidic Protein (GFAP) in Serum and Plasma Following Mild Traumatic Brain Injury in Older Adults

2020 ◽  
Vol 11 ◽  
Author(s):  
Nathan A. Huebschmann ◽  
Teemu M. Luoto ◽  
Justin E. Karr ◽  
Ksenia Berghem ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Older Adults ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Fibrillary Acidic Protein ◽  
Mild Traumatic Brain Injury ◽  
Acidic Protein

scholarly journals Imaging biomarkers of vascular and axonal injury are spatially distinct in chronic traumatic brain injury

2021 ◽  
pp. 0271678X2098515
Author(s):  
Margalit Haber ◽  
Franck Amyot ◽  
Cillian E Lynch ◽  
Danielle K Sandsmark ◽  
Kimbra Kenney ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Diffusion Tensor ◽  
Axonal Injury ◽  
Diffuse Axonal Injury ◽  
Mean Diffusivity ◽  
Cerebrovascular Reactivity ◽  
Imaging Biomarkers ◽  
Healthy Controls ◽  
Mean Values

Traumatic Brain Injury (TBI) is associated with both diffuse axonal injury (DAI) and diffuse vascular injury (DVI), which result from inertial shearing forces. These terms are often used interchangeably, but the spatial relationships between DAI and DVI have not been carefully studied. Multimodal magnetic resonance imaging (MRI) can help distinguish these injury mechanisms: diffusion tensor imaging (DTI) provides information about axonal integrity, while arterial spin labeling (ASL) can be used to measure cerebral blood flow (CBF), and the reactivity of the Blood Oxygen Level Dependent (BOLD) signal to a hypercapnia challenge reflects cerebrovascular reactivity (CVR). Subjects with chronic TBI (n = 27) and healthy controls (n = 14) were studied with multimodal MRI. Mean values of mean diffusivity (MD), fractional anisotropy (FA), CBF, and CVR were extracted for pre-determined regions of interest (ROIs). Normalized z-score maps were generated from the pool of healthy controls. Abnormal ROIs in one modality were not predictive of abnormalities in another. Approximately 9-10% of abnormal voxels for CVR and CBF also showed an abnormal voxel value for MD, while only 1% of abnormal CVR and CBF voxels show a concomitant abnormal FA value. These data indicate that DAI and DVI represent two distinct TBI endophenotypes that are spatially independent.

scholarly journals One-Year Prospective Study of Plasma Biomarkers From CNS in Patients With Mild Traumatic Brain Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Gerard Janez Brett Clarke ◽  
Toril Skandsen ◽  
Henrik Zetterberg ◽  
Cathrine Elisabeth Einarsen ◽  
Casper Feyling ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Fibrillary Acidic Protein ◽  
Mild Traumatic Brain Injury ◽  
Time Window ◽  
Brain Mri ◽  
Demographic Variables ◽  
Acidic Protein ◽  
Observation Study ◽  
Diagnostic Time

Objective: To investigate the longitudinal evolution of three blood biomarkers: neurofilament light (NFL), glial fibrillary acidic protein (GFAP) and tau, in out-patients and hospitalized patients with mild traumatic brain injury (mTBI) compared to controls, along with their associations—in patients—with clinical injury characteristics and demographic variables, and ability to discriminate patients with mTBI from controls.Methods: A longitudinal observation study including 207 patients with mTBI, 84 age and sex-matched community controls (CCs) and 52 trauma controls (TCs). Blood samples were collected at 5 timepoints: acute (<24 h), 72 h (24–72 h post-injury), 2 weeks, 3 and 12 months. Injury-related, clinical and demographic variables were obtained at inclusion and brain MRI within 72 h.Results: Plasma GFAP and tau were most elevated acutely and NFL at 2 weeks and 3 months. The group of patients with mTBI and concurrent other somatic injuries (mTBI+) had the highest elevation in all biomarkers across time points, and were more likely to be victims of traffic accidents and violence. All biomarkers were positively associated with traumatic intracranial findings on MRI obtained within 72 h. Glial fibrillary acidic protein and NFL levels were associated with Glasgow Coma Scale (GCS) score and presence of other somatic injuries. Acute GFAP concentrations showed the highest discriminability between patients and controls with an Area Under the Curve (AUC) of 0.92. Acute tau and 2-week NFL concentrations showed moderate discriminability (AUC = 0.70 and AUC = 0.75, respectively). Tau showed high discriminability between mTBI+ and TCs (AUC = 0.80).Conclusions: The association of plasma NFL with traumatic intracranial MRI findings, together with its later peak, could reflect ongoing secondary injury or repair mechanisms, allowing for a protracted diagnostic time window. Patients experiencing both mTBI and other injuries appear to be a subgroup with greater neural injury, differing from both the mTBI without other injuries and from both control groups. Acute GFAP concentrations showed the highest discriminability between patients and controls, were highly associated with intracranial traumatic injury, and showed the largest elevations compared to controls at the acute timepoint, suggesting it to be the most clinically useful plasma biomarker of primary CNS injury in mTBI.

scholarly journals The evolution of white matter microstructural changes after mild traumatic brain injury: A longitudinal DTI and NODDI study

2020 ◽  
Vol 6 (32) ◽  
pp. eaaz6892 ◽  
Author(s):  
E. M. Palacios ◽  
J. P. Owen ◽  
E. L. Yuh ◽  
M. B. Wang ◽  
M. J. Vassar ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Diffusion Tensor ◽  
Diffuse Axonal Injury ◽  
Mean Diffusivity ◽  
Free Water ◽  
Long Term Outcome ◽  
Microstructural Changes

Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Cross-sectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.

Neuron-Specific Enolase, S100B, and Glial Fibrillary Acidic Protein Levels as Outcome Predictors in Patients With Severe Traumatic Brain Injury

Neurosurgery ◽  
2011 ◽  
Vol 68 (6) ◽  
pp. 1624-1631 ◽  
Author(s):  
Ana Elisa Böhmer ◽  
Jean Pierre Oses ◽  
André Prato Schmidt ◽  
Cleiton Schweister Perón ◽  
Claudio Liss Krebs ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Fibrillary Acidic Protein ◽  
Severe Traumatic Brain Injury ◽  
Neuron Specific Enolase ◽  
Acidic Protein ◽  
Outcome Predictors ◽  
Protein Levels

scholarly journals Plasma glial fibrillary acidic protein and neurofilament light chain, but not tau, are biomarkers of sports-related mild traumatic brain injury

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Etienne Laverse ◽  
Tong Guo ◽  
Karl Zimmerman ◽  
Martha S Foiani ◽  
Bharat Velani ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Glial Fibrillary Acidic Protein ◽  
Mild Traumatic Brain Injury ◽  
Light Chain ◽  
Acidic Protein ◽  
Post Injury ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Abstract Mild traumatic brain injury is a relatively common event in contact sports and there is increasing interest in the long-term neurocognitive effects. The diagnosis largely relies on symptom reporting and there is a need for objective tools to aid diagnosis and prognosis. There are recent reports that blood biomarkers could potentially help triage patients with suspected injury and normal CT findings. We have measured plasma concentrations of glial and neuronal proteins and explored their potential in the assessment of mild traumatic brain injury in contact sport. We recruited a prospective cohort of active male rugby players, who had pre-season baseline plasma sampling. From this prospective cohort, we recruited 25 players diagnosed with mild traumatic brain injury. We sampled post-match rugby players without head injuries as post-match controls. We measured plasma neurofilament light chain, tau and glial fibrillary acidic protein levels using ultrasensitive single molecule array technology. The data were analysed at the group and individual player level. Plasma glial fibrillary acidic protein concentration was significantly increased 1-h post-injury in mild traumatic brain injury cases compared to the non-injured group (P = 0.017). Pairwise comparison also showed that glial fibrillary acidic protein levels were higher in players after a head injury in comparison to their pre-season levels at both 1-h and 3- to 10-day post-injury time points (P = 0.039 and 0.040, respectively). There was also an increase in neurofilament light chain concentration in brain injury cases compared to the pre-season levels within the same individual at both time points (P = 0.023 and 0.002, respectively). Tau was elevated in both the non-injured control group and the 1-h post-injury group compared to pre-season levels (P = 0.007 and 0.015, respectively). Furthermore, receiver operating characteristic analysis showed that glial fibrillary acidic protein and neurofilament light chain can separate head injury cases from control players. The highest diagnostic power was detected when biomarkers were combined in differentiating 1-h post-match control players from 1-h post-head injury players (area under curve 0.90, 95% confidence interval 0.79–1.00, P < 0.0002). The brain astrocytic marker glial fibrillary acidic protein is elevated in blood 1 h after mild traumatic brain injury and in combination with neurofilament light chain displayed the potential as a reliable biomarker for brain injury evaluation. Plasma total tau is elevated following competitive rugby with and without a head injury, perhaps related to peripheral nerve trauma and therefore total tau does not appear to be suitable as a blood biomarker.

Sign in / Sign up

Export Citation Format

Share Document