Journal of neurotrauma
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Traumatic brain injury (TBI) results in disparate outcomes ranging from persistent disorders of consciousness to symptom resolution. Despite the breadth and complexity of TBI recovery, most clinical trials dichotomize outcome by establishing an arbitrary cut-point, above and below which recovery is described as "favorable" and "unfavorable," respectively. For example, the widely used eight-level Glasgow Outcome Scale-Extended (GOSE) is typically collapsed into these two categories. ⋯ We illustrate the lack of standardization in defining "unfavorable" and "favorable" TBI outcome on the GOSE by identifying the broad range of cut-points, from a score of 3 (part-time supervision in the home required) to 7 (presence of some residual of symptoms), that have been used to dichotomize the GOSE. We also highlight the ethical concerns related to characterizing TBI outcomes solely from the perspective of investigators and clinicians, rather than patients and caregivers. Finally, we suggest that a pragmatic, immediate solution to GOSE dichotomization is to report the likelihood of achieving each of the eight GOSE outcome levels and propose a study design for a new patient- and caregiver-centered TBI outcome metric.
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Journal of neurotrauma · Jul 2022
DREADD-mediated activation of the locus coeruleus restores descending nociceptive inhibition after traumatic brain injury in rats.
Disruption of endogenous pain control mechanisms including descending pain inhibition has been linked to several forms of pain including chronic pain after traumatic brain injury (TBI). The locus coeruleus (LC) is the principal noradrenergic (NA) nucleus participating in descending pain inhibition. We therefore hypothesized that selectively stimulating LC neurons would reduce nociception after TBI. ⋯ Unexpectedly, the effects of LC activation in the DREADD-expressing rats were blocked by the α-1 adrenergic receptor antagonist prazosin, but not the α-2 adrenergic receptor antagonist atipamezole. These results suggest that directly stimulating the LC after TBI can reduce both early and late manifestations of dysfunctional endogenous pain regulation. Clinical approaches to activating descending pain circuits may reduce suffering in those with pain after TBI.
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Journal of neurotrauma · Jul 2022
Multicenter StudyDefining biologic phenotypes of mild traumatic brain injury using saliva microRNA profiles.
Concussion is a heterogeneous injury that relies predominantly on subjective symptom reports for patient assessment and treatment. Developing an objective, biological test could aid phenotypic categorization of concussion patients, leading to advances in personalized treatment. This prospective multi-center study employed saliva micro-ribonucleic acid (miRNA) levels to stratify 251 individuals with concussion into biological subgroups. ⋯ The miRNAs that defined concussion clusters regulate 16 physiological pathways, including adrenergic signaling, estrogen signaling, fatty acid metabolism, GABAergic signaling, synaptic vesicle cycling, and transforming growth factor (TGF)-β signaling. These results show that saliva miRNA levels may stratify individuals with concussion based on underlying biological perturbations that are relevant to both symptomology and pharmacological targets. If validated in a larger cohort, miRNA assessment could aid individualized, biology-driven concussion treatment.
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Journal of neurotrauma · Jul 2022
Multicenter StudyFunctional short-term outcomes and mortality in children with severe traumatic brain injury - comparing decompressive craniectomy and medical management.
The effect of decompressive craniectomy (DC) on functional outcomes and mortality in children after severe head trauma is strongly debated. The lack of high-quality evidence poses a serious challenge to neurosurgeons' and pediatric intensive care physicians' decision making in critically ill children after head trauma. This study was conducted to compare DC and medical management in severely head-injured children with respect to short-term outcomes and mortality. ⋯ After risk adjustment by logistic regression modeling, the odds ratio was 1.56 (95% confidence interval 1.01-2.40) for poor outcome at intensive care unit discharge and 1.20 (0.74-1.95) for mortality after DC. In summary, DC was associated with increased odds for poor short-term outcomes in children with severe head trauma. This finding should temper enthusiasm for DC in children until a large randomized controlled trial has answered more precisely if DC in children is beneficial or increases rates of vegetative state.
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Journal of neurotrauma · Jul 2022
ReviewTau pathology, metal dyshomeostasis and repetitive mild traumatic brain injury: an unexplored link paving the way for neurodegeneration.
Repetitive mild traumatic brain injury (r-mTBI), commonly experienced by athletes and military personnel, causes changes in multiple intracellular pathways, one of which involves the tau protein. Tau phosphorylation plays a role in several neurodegenerative conditions including chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disorder linked to repeated head trauma. There is now mounting evidence suggesting that tau phosphorylation may be regulated by metal ions (such as iron, zinc and copper), which themselves are implicated in aging and neurodegenerative disorders such as Alzheimer's disease (AD). ⋯ The authors highlight that metal dyshomeostasis has yet to be investigated in the context of repeat head trauma or CTE. Given the evidence that metal dyshomeostasis contributes to the onset and/or progression of neurodegeneration, and that CTE itself is a neurodegenerative condition, this brings to light an uncharted link that should be explored. The development of adequate models of r-mTBI and/or CTE will be crucial in deepening our understanding of the pathological mechanisms that drive the clinical manifestations in these conditions and also in the development of effective therapeutics targeted toward slowing progressive neurodegenerative disorders.