scholarly journals FAIR Data Reuse in Traumatic Brain Injury: Exploring Inflammation and Age as Moderators of Recovery in the TRACK-TBI Pilot

2021 ◽  
Vol 12 ◽  
Author(s):  
J. Russell Huie ◽  
Austin Chou ◽  
Abel Torres-Espin ◽  
Jessica L. Nielson ◽  
Esther L. Yuh ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Detrimental Effect ◽  
Principal Component ◽  
Data Reuse ◽  
Clinical Knowledge ◽  
Guiding Principle ◽  
Data Stewardship ◽  
Scientific Questions ◽  
Qualitative Changes

The guiding principle for data stewardship dictates that data be FAIR: findable, accessible, interoperable, and reusable. Data reuse allows researchers to probe data that may have been originally collected for other scientific purposes in order to gain novel insights. The current study reuses the Transforming Research and Clinical Knowledge for Traumatic Brain Injury (TRACK-TBI) Pilot dataset to build upon prior findings and ask new scientific questions. Specifically, we have previously used a multivariate analytics approach to multianalyte serum protein data from the TRACK-TBI Pilot dataset to show that an inflammatory ensemble of biomarkers can predict functional outcome at 3 and 6 months post-TBI. We and others have shown that there are quantitative and qualitative changes in inflammation that come with age, but little is known about how this interaction affects recovery from TBI. Here we replicate the prior proteomics findings with improved missing value analyses and non-linear principal component analysis and then expand upon this work to determine whether age moderates the effect of inflammation on recovery. We show that increased age correlates with worse functional recovery on the Glasgow Outcome Scale-Extended (GOS-E) as well as increased inflammatory signature. We then explore the interaction between age and inflammation on recovery, which suggests that inflammation has a more detrimental effect on recovery for older TBI patients.

scholarly journals Age, Sex and Cerebral Microbleed Effects On White Matter Degradation After Traumatic Brain Injury

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 886-887
Author(s):  
Andrei Irimia ◽  
Ammar Dharani ◽  
Van Ngo ◽  
David Robles ◽  
Kenneth Rostowsky
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Diffuse Axonal Injury ◽  
Principal Component ◽  
Older Age ◽  
Analysis Of Covariance ◽  
Future Research ◽  
Cerebral Microbleed

Abstract Mild traumatic brain injury (mTBI) affects white matter (WM) integrity and accelerates neurodegeneration. This study assesses the effects of age, sex, and cerebral microbleed (CMB) load as predictors of WM integrity in 70 subjects aged 18-77 imaged acutely and ~6 months after mTBI using diffusion tensor imaging (DTI). Two-tensor unscented Kalman tractography was used to segment and cluster 73 WM structures and to map changes in their mean fractional anisotropy (FA), a surrogate measure of WM integrity. Dimensionality reduction of mean FA feature vectors was implemented using principal component (PC) analysis, and two prominent PCs were used as responses in a multivariate analysis of covariance. Acutely and chronically, older age was significantly associated with lower FA (F2,65 = 8.7, p < .001, η2 = 0.2; F2,65 = 12.3, p < .001, η2 = 0.3, respectively), notably in the corpus callosum and in dorsolateral temporal structures, confirming older adults’ WM vulnerability to mTBI. Chronically, sex was associated with mean FA (F2,65 = 5.0, p = 0.01, η2 = 0.1), indicating males’ greater susceptibility to WM degradation. Acutely, a significant association was observed between CMB load and mean FA (F2,65 = 5.1, p = 0.009, η2 = 0.1), suggesting that CMBs reflect the acute severity of diffuse axonal injury. Together, these findings indicate that older age, male sex, and CMB load are risk factors for WM degeneration. Future research should examine how sex- and age-mediated WM degradation lead to cognitive decline and connectome degeneration after mTBI.

Effect of the monoaminergic stabiliser (−)-OSU6162 on mental fatigue following stroke or traumatic brain injury

2020 ◽  
Vol 32 (6) ◽  
pp. 303-312
Author(s):  
Marie K.L. Nilsson ◽  
Birgitta Johansson ◽  
Maria L. Carlsson ◽  
Robert C. Schuit ◽  
Lars Rönnbäck
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rating Scale ◽  
Activity Index ◽  
Principal Component ◽  
Mental Fatigue ◽  
Activity Level ◽  
Therapeutic Effects ◽  
Double Blind ◽  
Good Tolerability

AbstractObjective:The purpose of the present study was to evaluate the efficacy and safety of (−)-OSU6162 in doses up to 30 mg b.i.d. in patients suffering from mental fatigue following stroke or traumatic brain injury (TBI).Methods:This 4 + 4 weeks double-blind randomised cross-over study included 30 patients afflicted with mental fatigue following a stroke or head trauma occurring at least 12 months earlier. Efficacy was assessed using the Mental Fatigue Scale (MFS), the Self-rating Scale for Affective Syndromes [Comprehensive Psychopathological Rating Scale (CPRS)], the Frenchay Activity Index (FAI), and a battery of neuropsychological tests. Safety was evaluated by recording spontaneously reported adverse events (AEs).Results:There were significant differences on the patients’ total FAI scores (p = 0.0097), the subscale FAI outdoor scores (p = 0.0243), and on the trail making test (TMT-B) (p = 0.0325) in favour of (−)-OSU6162 treatment. Principal component analysis showed a clear overall positive treatment effect in 10 of 28 patients; those who responded best to treatment had their greatest improvements on the MFS. Reported AEs were mild or moderate in severity and did not differ between the (−)-OSU6162 and the placebo period.Conclusion:The most obvious beneficial effects of (−)-OSU6162 were on the patients’ activity level, illustrated by the improvement on the FAI scale. Moreover, a subgroup of patients showed substantial improvements on the MFS. Based on these observed therapeutic effects, in conjunction with the good tolerability of (−)-OSU6162, this compound may offer promise for treating at least part of the symptomatology in patients suffering from stroke- or TBI-induced mental fatigue.

scholarly journals GFAP-BDP as an Acute Diagnostic Marker in Traumatic Brain Injury: Results from the Prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

2013 ◽  
Vol 30 (17) ◽  
pp. 1490-1497 ◽  
Author(s):  
David O. Okonkwo ◽  
John K. Yue ◽  
Ava M. Puccio ◽  
David M. Panczykowski ◽  
Tomoo Inoue ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Diagnostic Marker ◽  
Clinical Knowledge

scholarly journals Principal Component Analysis of the Cytokine and Chemokine Response to Human Traumatic Brain Injury

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e39677 ◽  
Author(s):  
Adel Helmy ◽  
Chrystalina A. Antoniades ◽  
Mathew R. Guilfoyle ◽  
Keri L. H. Carpenter ◽  
Peter J. Hutchinson
Keyword(s):  
Traumatic Brain Injury ◽  
Principal Component Analysis ◽  
Brain Injury ◽  
Principal Component ◽  
Component Analysis

Placebo-controlled cross-over study of the monoaminergic stabiliser (−)-OSU6162 in mental fatigue following stroke or traumatic brain injury

2012 ◽  
Vol 24 (5) ◽  
pp. 266-274 ◽  
Author(s):  
Birgitta Johansson ◽  
Arvid Carlsson ◽  
Maria L. Carlsson ◽  
Magdalena Karlsson ◽  
Marie K.L. Nilsson ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Statistical Significance ◽  
Principal Component ◽  
Mental Fatigue ◽  
Self Assessment ◽  
Double Blind ◽  
Positive Treatment ◽  
Secondary Endpoints ◽  
Returning To Work

Objective: Mental fatigue occurring after a stroke or traumatic brain injury (TBI) often results in difficulties returning to work and pursuing social activities. No effective treatment of this condition is available today. In this study, we have tested a novel pharmacological strategy using the monoaminergic stabiliser (−)-OSU6162.Methods: (−)-OSU6162 was given orally for 4 weeks in doses increasing from 15 to 45 mg b.i.d. to 12 patients suffering from mental fatigue, following upon stroke (n=6) or TBI (n=6). (−)-OSU6162 was compared with placebo using a double-blind, randomised cross-over design. Patients included were well rehabilitated physically with no gross impairment in cognitive functions other than those related to the mental fatigue.Results: (−)-OSU6162 caused a remarkable improvement in mental stamina, as evaluated by a self-assessment scale on mental fatigue. Statistical significance was reached on the primary endpoint (Mental Fatigue Scale). There was a trend towards improvement in the secondary endpoints processing speed and attention. Principal component analysis showed an overall positive treatment effect in 7 of 12 patients. Beneficial responses were seen already during the first few days of active drug treatment. Increasing dosage caused no further improvement. Adverse reactions consisted of short-lasting mild nausea and attenuated appetite. These side effects disappeared upon dose reduction.Conclusion: The monoaminergic stabiliser (−)-OSU6162 offers promise as a candidate for treatment of mental fatigue after a stroke or TBI.

scholarly journals Reduction of Cognitive and Motor Deficits after Traumatic Brain Injury in Mice Deficient in Poly(ADP-Ribose) Polymerase

1999 ◽  
Vol 19 (8) ◽  
pp. 835-842 ◽  
Author(s):  
Michael J. Whalen ◽  
Robert S. B. Clark ◽  
C. Edward Dixon ◽  
Paul Robichaud ◽  
Donald W. Marion ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Detrimental Effect ◽  
Memory Performance ◽  
Memory Function ◽  
Motor Deficits ◽  
Immunohistochemical Detection ◽  
Memory Acquisition ◽  
Cci Model

Poly(ADP-ribose) polymerase (PARP), or poly-(ADP-ribose) synthetase, is a nuclear enzyme that consumes NAD when activated by DNA damage. The role of PARP in the pathogenesis of traumatic brain injury (TBI) is unknown. Using a controlled cortical impact (CCI) model of TBI and mice deficient in PARP, the authors studied the effect of PARP on functional and histologic outcome after CCI using two protocols. In protocol 1, naïve mice (n = 7 +/+, n = 6 –/–) were evaluated for motor and memory acquisition before CCI. Mice were then subjected to severe CCI and killed at 24 hours for immunohistochemical detection of nitrated tyrosine, an indicator of peroxynitrite formation. Motor and memory performance did not differ between naïve PARP +/+ and –/– mice. Both groups showed nitrotyrosine staining in the contusion, suggesting that peroxynitrite is produced in contused brain. In protocol 2, mice (PARP +/+, n = 8; PARP –/–, n = 10) subjected to CCI were tested for motor and memory function, and contusion volume was determined by image analysis. PARP –/– mice demonstrated improved motor and memory function after CCI versus PARP +/+ mice ( P < 0.05). However, contusion volume was not different between groups. The results suggest a detrimental effect of PARP on functional outcome after TBI.

scholarly journals Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot: Multicenter Implementation of the Common Data Elements for Traumatic Brain Injury

2013 ◽  
Vol 30 (22) ◽  
pp. 1831-1844 ◽  
Author(s):  
John K. Yue ◽  
Mary J. Vassar ◽  
Hester F. Lingsma ◽  
Shelly R. Cooper ◽  
David O. Okonkwo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Knowledge ◽  
Common Data Elements ◽  
The Common ◽  
Data Elements

Invariance of the Bifactor Structure of Mild Traumatic Brain Injury (mTBI) Symptoms on the Rivermead Postconcussion Symptoms Questionnaire Across Time, Demographic Characteristics, and Clinical Groups: A TRACK-TBI Study

Assessment ◽  
2020 ◽  
pp. 107319112091394
Author(s):  
Stephanie Agtarap ◽  
Mark D. Kramer ◽  
Laura Campbell-Sills ◽  
Esther Yuh ◽  
Pratik Mukherjee ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Expression Patterns ◽  
Bifactor Model ◽  
General Factor ◽  
Symptom Expression ◽  
Clinical Knowledge ◽  
Visual Symptom ◽  
Postconcussion Symptoms

This study aimed to elucidate the structure of the Rivermead Postconcussion Symptoms Questionnaire (RPQ) and evaluate its longitudinal and group variance. Factor structures were developed and compared in 1,011 patients with mild traumatic brain injury (mTBI; i.e., Glasgow Coma Scale score 13-15) from the Transforming Research and Clinical Knowledge in TBI study, using RPQ data collected at 2 weeks, and 3, 6, and 12 months postinjury. A bifactor model specifying a general factor and emotional, cognitive, and visual symptom factors best represented the latent structure of the RPQ. The model evinced strict measurement invariance over time and across sex, age, race, psychiatric history, and mTBI severity groups, indicating that differences in symptom endorsement were completely accounted for by these latent dimensions. While highly unidimensional, the RPQ has multidimensional features observable through a bifactor model, which may help differentiate symptom expression patterns in the future.

Sign in / Sign up

Export Citation Format

Share Document