Journal of neurotrauma
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Journal of neurotrauma · Jul 2020
The Cumulative Influence of Inflammatory Response Genetic Variation on Long-Term Neurobehavioral Outcomes following Pediatric Traumatic Brain Injury Relative to Orthopedic Injury: An Exploratory Polygenic Risk Score.
The addition of genetic factors to prognostic models of neurobehavioral recovery following pediatric traumatic brain injury (TBI) may account for unexplained heterogeneity in outcomes. The present study examined the cumulative influence of candidate genes involved in the inflammatory response on long-term neurobehavioral recovery in children with early childhood TBI relative to children with orthopedic injuries (OI). Participants were drawn from a prospective, longitudinal study evaluating outcomes of children who sustained TBI (n = 67) or OI (n = 68) between the ages of 3 and 7 years. ⋯ Higher inflammatory response PRS were associated with more executive dysfunction and behavior problems in children with TBI but not in children with OI. The cumulative influence of inflammatory response genes as measured by PRS explained additional variance in long-term neurobehavioral outcomes, over and above well-established predictors and single candidate SNPs tested individually. The results suggest that some of the unexplained heterogeneity in long-term neurobehavioral outcomes following pediatric TBI may be attributable to a child's genetic predisposition to a greater or lesser inflammatory response to TBI.
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Journal of neurotrauma · Jul 2020
Comparative StudyA Comparison of Methods for Classifying Persistent Post-concussive Symptoms in Children.
Pediatric mild traumatic brain injury (pmTBI) has received increased public scrutiny over the past decade, especially regarding children who experience persistent post-concussive symptoms (PPCS). However, several methods for defining PPCS exist in clinical and scientific literature, and even healthy children frequently exhibit non-specific, concussive-like symptoms. Inter-method agreement (six PPCS methods), observed misclassification rates, and other psychometric properties were examined in large cohorts of consecutively recruited adolescent patients with pmTBI (n = 162) 1 week and 4 months post-injury and in age/sex-matched healthy controls (HC; n = 117) at equivalent time intervals. ⋯ In conclusion, the self-reporting of symptom burden is only modestly reliable in typically developing adolescents over a 4-month period, with additional evidence for systematic bias in both adolescent and parental ratings. Significant variation existed for identifying pmTBI patients who had "recovered" (i.e., those who did not meet individual criteria for PPCS) from concussion across the six definitions, representing a considerable challenge for estimating the true incidence rate of PPCS in published literature. Although relatively straightforward to obtain, current findings question the utility of the most commonly used Simple Change scores for diagnosis of PPCS in clinical settings.
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Journal of neurotrauma · Jul 2020
Comparative StudyWhite matter integrity and its relationship to cognitive-motor integration in females with and without post-concussion syndrome.
Fifteen percent of individuals who sustain a concussion go on to develop post-concussion syndrome (PCS). These persistent symptoms are believed to be attributed to damage to white matter tracts and impaired neurotransmission. Specifically, declines in white matter integrity after concussion have been found along the long-coursing axons underlying the frontoparietal network. ⋯ However, examination of the data collapsed across participants revealed significant associations between performance on a CMI task and white matter integrity. Further investigation into additional causes of symptoms in those with PCS (including psychological and cervicogenic factors) will strengthen our understanding of this diverse group. Nonetheless, this study demonstrates that white matter integrity is related to levels of performance in tasks that require rule-based movement control.
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Journal of neurotrauma · Jul 2020
Observational StudyUsing Variance to Explore the Diagnostic Utility of Baseline Concussion Testing.
The Graded Symptom Checklist (GSC), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and King-Devick Test (KDT) are considered important components of concussion assessment. Whether baseline testing improves the diagnostic utility of these tests remains unclear. We performed an observational cohort study to investigate the within-subject and between-subjects variability of these tests over repeated assessments during two football seasons to examine whether baseline testing reduces variability in test performance. ⋯ A small, but significant, practice effect was observed for the BESS and KDT tests. When athletes are evaluated during a football season for concussion using the GSC, SAC, and BESS, comparing their scores to baseline performance is likely no more beneficial than comparing them to normative population data for identifying neurological changes associated with concussion. For the KDT, comparison to baseline testing is likely beneficial because of significantly higher between-subjects variability.
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Journal of neurotrauma · Jul 2020
Penetrating Traumatic Brain Injury Triggers Subacute Dysregulation of Cathepsin B Protein Levels Independently of Cysteine Protease Activity in Brain and Cerebral Spinal Fluid.
Cathepsin B (CatB), a lysosomal cysteine protease, is important to brain function and may have dual utility as a peripheral biomarker of moderate-severe traumatic brain injury (TBI). The present study determined levels of pro- and mature (mat) CatB protein as well as cysteine protease activity within the frontal cortex (FC; proximal injury site), hippocampus (HC; distal injury site), and cerebral spinal fluid (CSF) collected 1-7 days after craniotomy and penetrating ballistic-like brain injury (PBBI) in rats. Values were compared with naïve controls. ⋯ Notably, CatB levels were significantly higher in CSF collected within 3 days after TBI compared with non-TBI controls. Collectively, this work indicates that CatB and its cysteine protease activity may serve as collective molecular signatures of TBI progression that differentially vary within both proximal and distal brain regions. CatB and its protease activity may have utility as a surrogate, translational biomarker of acute-subacute TBI.