scholarly journals Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury

2021 ◽  
Vol 16 ◽  
pp. 117727192110534
Author(s):  
Ker Rui Wong ◽  
William T O’Brien ◽  
Mujun Sun ◽  
Glenn Yamakawa ◽  
Terence J O’Brien ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Elevated Serum ◽  
Serum Levels ◽  
Long Bone ◽  
Post Injury ◽  
Neurofilament Light ◽  
Peripheral Injury ◽  
Long Bone Fracture ◽  
Severe Tbi

Introduction: Serum neurofilament light (NfL) is an emerging biomarker of traumatic brain injury (TBI). However, the effect of peripheral injuries such as long bone fracture and skeletal muscle injury on serum NfL levels is unknown. Therefore, the aim of this study was to determine whether serum NfL levels can be used as a biomarker of TBI in the presence of concomitant peripheral injuries. Methods: Rats were randomly assigned to one of four injury groups: polytrauma (muscle crush + fracture + TBI; n = 11); peripheral injuries (muscle crush + fracture + sham-TBI; n = 12); TBI-only (sham-muscle crush + sham-fracture + TBI; n = 13); and triple-sham (n = 7). At 2-days post-injury, serum levels of NfL were quantified using a Simoa HD-X Analyzer. Results: Compared to triple-sham rats, serum NfL concentrations were higher in rats with peripheral injuries-only, TBI-only, and polytrauma. When compared to peripheral injury-only rats, serum NfL levels were higher in TBI-only and polytrauma rats. No differences were found between TBI-only and polytrauma rats. Conclusion: Serum NfL levels did not differ between TBI-only and polytrauma rats, indicating that significant peripheral injuries did not affect the sensitivity and specificity of serum NfL as a biomarker of moderate TBI. However, the finding of elevated serum NfL levels in rats with peripheral injuries in the absence of a TBI suggests that the presence of such injuries may limit the utility of NfL as a biomarker of less severe TBI (eg, concussion).

Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans

2020 ◽  
pp. 1-7
Author(s):  
Sara M. Lippa ◽  
Jessica Gill ◽  
Tracey A. Brickell ◽  
Louis M. French ◽  
Rael T. Lange
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Outcome ◽  
Service Members ◽  
Neurocognitive Performance ◽  
Blood Biomarkers ◽  
Post Injury ◽  
Blood Draw ◽  
Neurofilament Light ◽  
History Of

Abstract Objective: This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). Method: Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. Results: Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065–.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052–.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029). Conclusions: Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.

scholarly journals Systemic and local cardiac inflammation after experimental long bone fracture, traumatic brain injury and combined trauma in mice

2021 ◽  
Vol 28 ◽  
pp. 39-46
Author(s):  
Ina Lackner ◽  
Birte Weber ◽  
Melanie Haffner-Luntzer ◽  
Simona Hristova ◽  
Florian Gebhard ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Bone Fracture ◽  
Long Bone ◽  
Cardiac Inflammation ◽  
Long Bone Fracture

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric Moderate to Severe Traumatic Brain Injury

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012222
Author(s):  
Emily L Dennis ◽  
Karen Caeyenberghs ◽  
Kristen R Hoskinson ◽  
Tricia L Merkley ◽  
Stacy J Suskauer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Behavioral Problems ◽  
Child Behavior Checklist ◽  
Injury Severity ◽  
Meta Analysis ◽  
Post Injury ◽  
Severe Tbi ◽  
Future Work

Objective:Our study addressed aims: (1) test the hypothesis that moderate-severe TBI in pediatric patients is associated with widespread white matter (WM) disruption; (2) test the hypothesis that age and sex impact WM organization after injury; and (3) examine associations between WM organization and neurobehavioral outcomes.Methods:Data from ten previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric msTBI working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline.Results:Five hundred and seven children and adolescents (244 with complicated mild to severe TBI [msTBI] and 263 controls) were included. Patients were clustered into three post-injury intervals: acute/subacute - <2 months, post-acute - 2-6 months, chronic - 6+ months. Outcomes were dMRI metrics and post-injury behavioral problems as indexed by the Child Behavior Checklist (CBCL). Our analyses revealed altered WM diffusion metrics across multiple tracts and all post-injury intervals (effect sizes ranging between d=-0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time post-injury. We observed a sex-by-group interaction: females with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (𝞫=0.043), which coincided with more parent-reported behavioral problems (𝞫=-0.0027).Conclusions:WM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically-meaningful patient subtypes.

Methodological Issues in Longitudinal Research on Cognitive Recovery after Traumatic Brain Injury: Evidence from a Systematic Review

2013 ◽  
Vol 14 (3) ◽  
pp. 450-474 ◽  
Author(s):  
Regina Schultz ◽  
Robyn L. Tate
Keyword(s):  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Longitudinal Research ◽  
Effect Sizes ◽  
Methodological Issues ◽  
Post Injury ◽  
Cognitive Recovery ◽  
Cognitive Domains ◽  
Severe Tbi

Background: Previous research addressing cognitive recovery after traumatic brain injury (TBI) in adults has predominately used cross-sectional methods. This systematic review examines longitudinal research into cognitive recovery in the first 2 years following moderate-to-severe TBI in adults and aims to identify apparent methodological issues with the existing literature.Design: Systematic review of the first 2 years post-trauma.Setting: Data were extracted from three electronic databases and manual searches of published articles until October 2012.Participants: Two hundred and forty-two participants with severe TBI and 281 comparison participants were used to calculate effect sizes.Results: Twenty papers met the selection criteria, with effect sizes computed from four studies. Moderate-to-large effect sizes were initially observed between the TBI and comparison groups on most measures (range: d = 0.2–2.8). Recovery continued in all five cognitive domains over the 2 years post-injury.Conclusions: Results demonstrated that cognitive recovery was continuous throughout the first 2 years following moderate-to-severe TBI. Findings also indicated different rates of recovery for the specific cognitive domains, highlighting the heterogeneous nature of cognitive recovery after TBI. The review highlighted several methodological issues within the limited existing literature; recommendations were developed to improve the evidence base.

scholarly journals Leptin Mediated Pathways Stabilize Posttraumatic Insulin and Osteocalcin Patterns after Long Bone Fracture and Concomitant Traumatic Brain Injury and Thus Influence Fracture Healing in a Combined Murine Trauma Model

2020 ◽  
Vol 21 (23) ◽  
pp. 9144
Author(s):  
Anja Garbe ◽  
Frank Graef ◽  
Jessika Appelt ◽  
Katharina Schmidt-Bleek ◽  
Denise Jahn ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Fracture Healing ◽  
Bone Fracture ◽  
Long Bone ◽  
Mouse Strains ◽  
Leptin Deficiency ◽  
Long Bone Fracture ◽  
Trauma Model ◽  
Deficient Mice

Recent studies on insulin, leptin, osteocalcin (OCN), and bone remodeling have evoked interest in the interdependence of bone formation and energy household. Accordingly, this study attempts to investigate trauma specific hormone changes in a murine trauma model and its influence on fracture healing. Thereunto 120 female wild type (WT) and leptin-deficient mice underwent either long bone fracture (Fx), traumatic brain injury (TBI), combined trauma (Combined), or neither of it and therefore served as controls (C). Blood samples were taken weekly after trauma and analyzed for insulin and OCN concentrations. Here, WT-mice with Fx and, moreover, with combined trauma showed a greater change in posttraumatic insulin and OCN levels than mice with TBI alone. In the case of leptin-deficiency, insulin changes were still increased after bony lesion, but the posttraumatic OCN was no longer trauma specific. Four weeks after trauma, hormone levels recovered to normal/basal line level in both mouse strains. Thus, WT- and leptin-deficient mice show a trauma specific hyperinsulinaemic stress reaction leading to a reduction in OCN synthesis and release. In WT-mice, this causes a disinhibition and acceleration of fracture healing after combined trauma. In leptin-deficiency, posttraumatic OCN changes are no longer specific and fracture healing is impaired regardless of the preceding trauma.

scholarly journals Cognitive development after traumatic brain injury in young children

2009 ◽  
Vol 16 (1) ◽  
pp. 157-168 ◽  
Author(s):  
AIMEE GERRARD-MORRIS ◽  
H. GERRY TAYLOR ◽  
KEITH OWEN YEATES ◽  
NICOLAY CHERTKOFF WALZ ◽  
TERRY STANCIN ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Development ◽  
Young Children ◽  
Family Environment ◽  
Cognitive Skills ◽  
Visual Memory ◽  
Cognitive Outcomes ◽  
Post Injury ◽  
Severe Tbi

AbstractThe primary aims of this study were to examine post-injury cognitive development in young children with traumatic brain injury (TBI) and to investigate the role of the proximal family environment in predicting cognitive outcomes. Age at injury was 3–6 years, and TBI was classified as severe (n = 23), moderate (n = 21), and complicated mild (n = 43). A comparison group of children who sustained orthopedic injuries (OI, n = 117) was also recruited. Child cognitive assessments were administered at a post-acute baseline evaluation and repeated at 6, 12, and 18 months post-injury. Assessment of the family environment consisted of baseline measures of learning support and stimulation in the home and of parenting characteristics observed during videotaped parent–child interactions. Relative to the OI group, children with severe TBI group had generalized cognitive deficiencies and those with less severe TBI had weaknesses in visual memory and executive function. Although deficits persisted or emerged across follow-up, more optimal family environments were associated with higher scores for all injury groups. The findings confirm other reports of poor recovery of cognitive skills following early childhood TBI and suggest environmental influences on outcomes. (JINS, 2010,16, 157–168.)

Examining the Prospective Relationship between Family Affective Responsiveness and Theory of Mind in Chronic Paediatric Traumatic Brain Injury

2016 ◽  
Vol 18 (1) ◽  
pp. 88-101 ◽  
Author(s):  
Nicholas P. Ryan ◽  
Kim Mihaljevic ◽  
Miriam H. Beauchamp ◽  
Cathy Catroppa ◽  
Louise Crossley ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Theory Of Mind ◽  
Childhood And Adolescence ◽  
Post Injury ◽  
Related Factors ◽  
Lesion Location ◽  
Severe Tbi ◽  
The Impact ◽  
Affective Responsiveness

Childhood and adolescence coincide with rapid structural and functional maturation of brain networks implicated in Theory of Mind (ToM); however, the impact of paediatric traumatic brain injury (TBI) on the development of these higher order skills is not well understood. ToM can be partitioned intoconative ToM, defined as the ability to understand how indirect speech acts involving irony and empathy are used to influence the mental or affective state of the listener; andaffective ToM, concerned with understanding that facial expressions are often used for social purposes to convey emotions that we want people to think we feel. In a sample of 84 children with mild-severe TBI and 40 typically developing controls, this study examined the effect of paediatric TBI on affective and conative ToM; and evaluated the respective contributions of injury-related factors (injury severity/lesion location) and non-injury-related environmental variables (socio-economic status (SES)/family functioning) to long-term ToM outcomes. Results showed that the poorest ToM outcomes were documented in association with mild-complicated and moderate TBI, rather than severe TBI. Lesion location and SES did not significantly contribute to conative or affective ToM. Post-injury family affective responsiveness was the strongest and most significant predictor of conative ToM. Results suggest that clinicians should exercise caution when prognosticating based on early clinical indicators, and that group and individual-level outcome prediction should incorporate assessment of a range of injury- and non-injury-related factors. Moreover, the affective quality of post-injury family interactions represents a potentially modifiable risk factor, and might be a useful target for family-centred interventions designed to optimise social cognitive outcomes after paediatric TBI.

scholarly journals Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0132177 ◽  
Author(s):  
Faiez Al Nimer ◽  
Eric Thelin ◽  
Harriet Nyström ◽  
Ann M. Dring ◽  
Anders Svenningsson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Prognostic Value ◽  
Serum Levels ◽  
Comparative Assessment ◽  
Neurofilament Light

Feedback learning and behavior problems after pediatric traumatic brain injury

2016 ◽  
Vol 46 (7) ◽  
pp. 1473-1484 ◽  
Author(s):  
M. Königs ◽  
L. W. E. van Heurn ◽  
R. J. Vermeulen ◽  
J. C. Goslings ◽  
J. S. K. Luitse ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Behavior Problems ◽  
Externalizing Problems ◽  
Parent Ratings ◽  
Pediatric Traumatic Brain Injury ◽  
Learning Context ◽  
Post Injury ◽  
Feedback Learning ◽  
Severe Tbi

BackgroundFeedback learning is essential for behavioral development. We investigated feedback learning in relation to behavior problems after pediatric traumatic brain injury (TBI).MethodChildren aged 6–13 years diagnosed with TBI (n= 112; 1.7 years post-injury) were compared with children with traumatic control (TC) injury (n= 52). TBI severity was defined as mild TBI without risk factors for complicated TBI (mildRF−TBI,n= 24), mild TBI with ⩾1 risk factor for complicated TBI (mildRF+TBI,n= 51) and moderate/severe TBI (n= 37). The Probabilistic Learning Test was used to measure feedback learning, assessing the effects of inconsistent feedback on learning and generalization of learning from the learning context to novel contexts. The relation between feedback learning and behavioral functioning rated by parents and teachers was explored.ResultsNo evidence was found for an effect of TBI on learning from inconsistent feedback, while the moderate/severe TBI group showed impaired generalization of learning from the learning context to novel contexts (p= 0.03,d= −0.51). Furthermore, the mildRF+TBI and moderate/severe TBI groups had higher parent and teacher ratings of internalizing problems (p's⩽ 0.04,d's ⩾ 0.47) than the TC group, while the moderate/severe TBI group also had higher parent ratings of externalizing problems (p= 0.006,d= 0.58). Importantly, poorer generalization of learning predicted higher parent ratings of externalizing problems in children with TBI (p= 0.03,β= −0.21) and had diagnostic utility for the identification of children with TBI and clinically significant externalizing behavior problems (area under the curve = 0.77,p= 0.001).ConclusionsModerate/severe pediatric TBI has a negative impact on generalization of learning, which may contribute to post-injury externalizing problems.

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