Journal of neurotrauma
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Journal of neurotrauma · Oct 2017
Focal electroencephalographic changes index post-traumatic confusion and outcome.
While the duration and severity of post-traumatic confusional state (PTCS) after traumatic brain injury have well-established implications for long-term outcomes, little is known about the underlying pathophysiology and their role in functional outcomes. Here, we analyzed the delta-to-alpha frequency band power ratios (DAR) from localized scalp areas derived from standard resting electroencephalographic (EEG) data recorded during eyes closed state in 49 patients diagnosed with PTCS. Higher global, occipital, parietal, and temporal DARs were significantly associated with the severity of PTCS, as assessed by the Confusion Assessment Protocol (CAP) observed on the same day, after controlling for injury severity. ⋯ Our finding that posterior DAR is a marker of PTCS and functional recovery post-injury, likely reflects functional de-afferentation of the posterior medial complex (PMC) in PTCS. Altered function of the PMC is proposed as a unifying physiological mechanism underlying both acute and chronic confusional states. We discuss the relationship of these findings to electrophysiological markers associated with disorders of consciousness.
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Journal of neurotrauma · Oct 2017
The Relationship between Cerebral Vasoreactivity and Post-Concussive Symptom Severity.
While pathophysiology underlying post-concussion symptom burden is unknown, data suggest that cerebrovascular dysfunction may be among the culprits. We sought to determine whether the degree of impairment in the ability of cerebrovasculature to buffer against changes in arterial gases (vasoreactivity) is associated with concussion symptoms. In 15 participants (19 ± 5 years, 1 week to 1 year post-injury) diagnosed with concussion, we assessed vasoreactivity from the slope of the linear relationship of beat-by-beat middle cerebral artery blood flow velocity (transcranial Doppler ultrasound) to end-tidal CO2 during progressive increases in end-tidal CO2 (air rebreathing). ⋯ Higher vasoreactivity was strongly associated with more severe headaches (R2 = 0.57; p < 0.01) and worse cognitive symptoms (R2 = 0.71; p < 0.01). Thus, cerebral vasoreactivity relates strongly to post-concussive headache and cognitive symptom burden. This has significant implications for understanding the pathophysiology underlying post-concussive symptom burden and for devising effective treatment options.
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Journal of neurotrauma · Oct 2017
Concussion mechanisms and activities in youth, high school, and college football.
Our purpose was to determine concussion mechanism and activity differences among three cohorts of football players: youth, high school, and college. Participants in this prospective cohort study were youth (ages 5-14 years, 118 teams, 310 team-seasons), high school (96 teams, 184 team-seasons), and college (34 teams, 71 team-seasons) football players. Athletic trainers collected athlete-exposure (AE) and concussion data during the 2012-2014 seasons. ⋯ Findings were similar during practices. Compared with college football game concussions (15.8%), a smaller proportion of youth (6.3%, IPR = 0.40, 95% CI: 0.17-0.93) and high school (9.5%, IPR = 0.60, 95% CI: 0.38-0.95) football game concussions occurred while an individual was being blocked. Concussion mechanism and activity differences should be considered when developing concussion prevention and sport-safety methods specific to different age levels, in order to maximize effectiveness.
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Journal of neurotrauma · Oct 2017
The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration to Accelerate Diagnosis and Treatment of Traumatic Brain Injury.
The Traumatic Brain Injury Endpoints Development (TED) Initiative is a 5-year, Department of Defense-funded project that is working toward the ultimate goal of developing better designed clinical trials, leading to more precise diagnosis, and effective treatments for traumatic brain injury (TBI). TED is comprised of leading academic clinician-scientists, along with innovative industry leaders in biotechnology and imaging technology, patient advocacy organizations, and philanthropists, working collaboratively with regulatory authorities, specifically the U. S. ⋯ This article summarizes the Initiative's Stage I progress over the first 18 months, including intensive engagement with a number of FDA divisions responsible for review and validation of biomarkers and clinical outcome assessments, progression into the prequalification phase of the FDA's Medical Device Development Tool program for a candidate set of neuroimaging biomarkers, and receipt of the FDA's Recognition of Research Importance Letter and a Letter of Support regarding TBI. Other signal achievements relate to the creation of the TED Metadataset, harmonizing study measures across eight major TBI studies, and the leadership role played by TED investigators in the conversion of the NINDS TBI Common Data Elements to Clinical Data Interchange Standards Consortium standards. This article frames both the near-term expectations and the Initiative's long-term vision to accelerate approval of treatments for patients affected by TBI in urgent need of effective therapies.
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Journal of neurotrauma · Oct 2017
Frontal TBI increases impulsive decision making in rats: A potential role for the inflammatory cytokine interleukin-12.
Traumatic brain injury (TBI) is associated with the development of numerous psychiatric diseases. Of particular concern for TBI patients is the impact of chronic impulsivity on daily functioning. Despite the scope of the human problem, little has been done to address impulsivity in animal models of brain injury. ⋯ Whereas a significant lesion was only evident in severely injured rats, analysis of cytokine levels within the frontal cortex revealed a selective increase in interleukin (IL)-12 that was associated with the magnitude of the change in impulsive choice caused by both milder and severe TBI. These findings suggest that tissue loss alone cannot explain the increased impulsivity observed, and that inflammatory pathways mediated by IL-12 may be a contributing factor. The findings from this study highlight the sensitivity of sophisticated behavioral measures designed to assess neuropsychiatric dysfunction in the detection of TBI-induced cognitive impairments and their utility in identifying potential mechanistic pathways and therapeutic targets.