Journal of neurotrauma
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Journal of neurotrauma · Jun 2013
Group-based trajectory analysis applications for prognostic biomarker model development in severe TBI: a practical example.
Over the last decade, biomarker research has identified potential biomarkers for the diagnosis, prognosis, and management of traumatic brain injury (TBI). Several cerebrospinal fluid (CSF) and serum biomarkers have shown promise in predicting long-term outcome after severe TBI. Despite this increased focus on identifying biomarkers for outcome prognostication after a severe TBI, several challenges still exist in effectively modeling the significant heterogeneity observed in TBI-related pathology, as well as the biomarker-outcome relationships. ⋯ Further, many biomarker studies to date have focused on the prediction power of biomarkers without controlling for potential clinical and demographic confounders that have been previously shown to affect long-term outcome. In this article, we demonstrate the application of a practical approach to delineate and describe distinct subpopulations having similar longitudinal biomarker profiles and to model the relationships between these biomarker profiles and outcomes while taking into account potential confounding factors. As an example, we demonstrate a group-based modeling technique to identify temporal S100 calcium-binding protein B (S100b) profiles, measured from CSF over the first week post-injury, in a sample of adult subjects with TBI, and we use multivariate logistic regression to show that the prediction power of S100b biomarker profiles can be superior to the prediction power of single-point estimates.
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Journal of neurotrauma · Jun 2013
S100b as a prognostic biomarker in outcome prediction for patients with severe traumatic brain injury.
As an astrocytic protein specific to the central nervous system, S100b is a potentially useful marker in outcome prediction after traumatic brain injury (TBI). Some studies have questioned the validity of S100b, citing the extracerebral origins of the protein as reducing the specificity of the marker. This study evaluated S100b as a prognostic biomarker in adult subjects with severe TBI (sTBI) by comparing outcomes with S100b temporal profiles generated from both cerebrospinal fluid (CSF) (n = 138 subjects) and serum (n = 80 subjects) samples across a 6-day time course. ⋯ Possibly as a result of extracerebral sources of S100b in serum, as represented by high ISS scores (p = 0.032), temporal serum profiles were associated with acute mortality (p = 0.015). High CSF S100b levels were observed in women (p = 0.022) and older subjects (p = 0.004). Multivariate logistic regression confirmed CSF S100b profiles in predicting GOS and DRS and showed mean and peak serum S100b as acute mortality predictors after sTBI.
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Journal of neurotrauma · Jun 2013
Variable, not always persistent, postconcussion symptoms after mild TBI in U.S. military service members: a five-year cross-sectional outcome study.
This study examined postconcussion symptom reporting within the first 5 years after mild traumatic brain injury (mTBI). Participants were 167 U. S. military service members (mean age, 27.6 years; 74.3% blast; 96.4% male) who were evaluated subsequent to injuries sustained in theater during Operations Iraqi and Enduring Freedom (92.8%) or from other combat-related operations. ⋯ A substantial minority had also improved (4.0-24.1%) or "developed" new symptoms (16.9-27.8%). Using regression analyses, baseline symptoms were somewhat predictive of PCD symptom reporting at follow-up, though this was not always reliable. Follow-up for all service members who sustain a combat-related mTBI in the context of polytrauma, regardless of the presence or absence of symptom reporting in the acute recovery stage, should be considered the rule, not the exception.
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Journal of neurotrauma · Jun 2013
Clinical TrialGrowth hormone replacement therapy in patients with traumatic brain injury.
In patients with severe traumatic brain injury (TBI), a growth hormone deficiency (GHD) is frequent and may contribute to the cognitive sequelae and reduction in quality of life (QoL). Recent studies have suggested that GH replacement therapy (GHRT) can improve processing speed and memory. The aim of the study was to analyze the efficacy of GHRT on cognition, activities of daily living (ADL), and QoL and the factors that predicted and contributed to these effects. ⋯ Greatest improvements were associated with lower performance before treatment. The magnitude of the improvements in ADL and QoL was moderately correlated with the improvement in cognition. In conclusion, replacement therapy can improve cognition and QoL in patients with TBI who have GHD, especially in those with severe disabilities.
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Journal of neurotrauma · Jun 2013
Remote brain network changes after unilateral cortical impact injury and their modulation by acetylcholinesterase inhibition.
We explored whether cerebral cortical impact injury (CCI) effects extend beyond direct lesion sites to affect remote brain networks, and whether acetylcholinesterase (AChE) inhibition elicits discrete changes in functional activation of motor circuits following CCI. Adult male rats underwent unilateral motor-sensory CCI or sham injury. Physostigmine (AChE inhibitor) or saline were administered subcutaneously continuously via implanted minipumps (1.6 micromoles/kg/day) for 3 weeks, followed by cerebral perfusion mapping during treadmill walking using [(14)C]-iodoantipyrine. ⋯ This phenomenon, augmented by physostigmine, may partially compensate motor deficits. FC decreased inter-hemispherically and in negative, but not positive, intra-hemispherical FC, and it was not affected by physostigmine. Circuit-based approaches into functional brain reorganization may inform future behavioral or molecular strategies to augment targeted neurorehabilitation.