Journal of neurotrauma
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Journal of neurotrauma · Feb 2023
Feasibility and utility of a flexible outcome assessment battery for longitudinal traumatic brain injury research: A TRACK-TBI study.
The effects of traumatic brain injury (TBI) are difficult to measure in longitudinal cohort studies, because disparate pre-injury characteristics and injury mechanisms produce variable impairment profiles and recovery trajectories. In preparation for the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, which followed patients with injuries ranging from uncomplicated mild TBI to coma, we designed a multi-dimensional Flexible outcome Assessment Battery (FAB). The FAB relies on a decision-making algorithm that assigns participants to a Comprehensive (CAB) or Abbreviated Assessment Battery (AAB) and guides test selection across all phases of recovery. ⋯ Among participants followed at 2w (n = 2094), 3m (n = 1871), 6m (n = 1736), and 12m (n = 1607) post-injury, 95-99% received valid completion scores on the FAB, in full or in part, either in person or by telephone. Level of function assessed by the FAB-enabled approach at 2w was associated with 6m and 12m GOSE scores (proportional odds p < 0.001). These findings suggest that the participant classification methodology afforded by the FAB may enable more effective data collection to improve detection of natural history changes and TBI treatment effects.
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Journal of neurotrauma · Feb 2023
Long-term Changes in Brain Connectivity Reflected in Quantitative Electrophysiology of Symptomatic Former NFL Players.
Exposure to repetitive head impacts (RHI) has been associated with long-term disturbances in cognition, mood, and neurobehavioral dysregulation, and reflected in neuroimaging. Distinct patterns of changes in quantitative features of the brain electrical activity (quantitative electroencephalogram [qEEG]) have been demonstrated to be sensitive to brain changes seen in neurodegenerative disorders and in traumatic brain injuries (TBI). While these qEEG biomarkers are highly sensitive at time of injury, the long-term effects of exposure to RHI on brain electrical activity are relatively unexplored. ⋯ Within the NFL population, the algorithm separating AFE <12 from AFE ≥12 resulted in a sensitivity = 76%, a specificity = 52%, and an AUC = 0.72. The presence of a profile of EEG abnormalities in the NFL retirees and in those with younger AFE includes features associated with neurodegeneration and the disruption of neuronal transmission between regions. These results support the long-term consequences of RHI and the potential of EEG as a biomarker of persistent changes in brain function.
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Journal of neurotrauma · Feb 2023
Ccr2 gene ablation does not influence seizure susceptibility, tissue damage or cellular inflammation after murine pediatric traumatic brain injury.
Pediatric traumatic brain injury (TBI) is a major public health issue, and a risk factor for the development of post-traumatic epilepsy that may profoundly impact the quality of life for survivors. As the majority of neurotrauma research is focused on injury to the adult brain, our understanding of the developing brain's response to TBI remains incomplete. Neuroinflammation is an influential pathophysiological mechanism in TBI, and is thought to increase neuronal hyperexcitability, rendering the brain more susceptible to the onset of seizures and/or epileptogenesis. ⋯ Similarly, acute post-injury treatment with a CCR2 antagonist did not influence seizure susceptibility or the extent of tissue damage in wild-type (WT) mice. Together, our findings suggest that CCR2 is not a crucial driver of epileptogenesis or neuroinflammation after TBI in the developing brain. We propose that age may be an important factor differentiating our findings from previous studies in which targeting CCL2/CCR2 has been reported to be anti-inflammatory, neuroprotective or anti-seizure.
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Journal of neurotrauma · Feb 2023
Saliva cortisol as a biomarker of injury in youth sport-related concussion.
Increasing rates of sport-related concussion (SRC) in youth impose a significant burden on public health systems and the lives of young athletes. Accurate prediction for those likely to develop persistent post-concussion symptomology (PPCS) using a fluid biomarker, reflecting both acute injury and recovery processes, would provide the opportunity for early intervention. Cortisol, a stress hormone released through the hypothalamic-pituitary-adrenal (HPA) axis following injury, may provide a missing physiological link to clinical recovery. ⋯ Exploratory time-to-event analysis revealed a point estimate suggesting a potential association between low cortisol levels and days to medical clearance to return to play. Although preliminary, these findings suggest that the HPA axis may be dysregulated post-SRC. Further, our exploratory analysis and case presentation of post-injury outliers highlight the need to further research cortisol as a prognostic biomarker to inform individualized sex-specific care after SRC.