A high-performance core laboratory GFAP/UCH-L1 test for the prediction of intracranial injury after mild traumatic brain injury.

Background: A glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) blood biomarker panel can reliably eliminate the need to perform a head computed tomography (CT) scan in selected patients with traumatic brain injury (TBI). Currently, this FDA cleared panel can be run both on a core laboratory platform or a hand-held single-sample point of care platform. This study examined test characteristics of the panel as analyzed on a core lab-based fast high-throughput platform.

Uncovering the hidden effects of repetitive subconcussive head impact exposure: A mega-analytic approach characterizing seasonal brain microstructural changes in contact and collision sports athletes.

Repetitive subconcussive head impacts (RSHI) are believed to induce sub-clinical brain injuries, potentially resulting in cumulative, long-term brain alterations. This study explores patterns of longitudinal brain white matter changes across sports with RSHI-exposure. A systematic literature search identified 22 datasets with longitudinal diffusion magnetic resonance imaging data.

A Pilot Study Investigating the Use of Serum Glial Fibrillary Acidic Protein to Monitor Changes in Brain White Matter Integrity After Repetitive Head Hits During a Single Collegiate Football Game.

Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurological outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after nonconcussive RHHs during a single sporting contest, raising the possibility that they could be used in real time to monitor the brain's early response to repeated asymptomatic head hits. To test this hypothesis, we measured GFAP in serum immediately before (T0), immediately after (T1) and 45 min (T2) after a single collegiate football game in 30 athletes.

The Interval Between Concussions Does Not Influence Time to Asymptomatic or Return to Play: A CARE Consortium Study.

Introduction: The purpose of this study was to determine if the time interval between two concussive events influences the number of days to asymptomatic status, days to return to play, or performance on common post-concussion assessments following the second concussion.

Methods: Data from 448 collegiate athletes and service academy cadets with two concussions (time between concussions: median 295.0 days [interquartile range: 125.

Effectiveness of biomedical interventions on the chronic stage of traumatic brain injury: a systematic review of randomized controlled trials.

Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice.

Identification of Concussion Subtypes Based on Intrinsic Brain Activity.

Importance: The identification of brain activity-based concussion subtypes at time of injury has the potential to advance the understanding of concussion pathophysiology and to optimize treatment planning and outcomes.

Objective: To investigate the presence of intrinsic brain activity-based concussion subtypes, defined as distinct resting state quantitative electroencephalography (qEEG) profiles, at the time of injury.

Design, Setting, And Participants: In this retrospective, multicenter (9 US universities and high schools and 4 US clinical sites) cohort study, participants aged 13 to 70 years with mild head injuries were included in longitudinal cohort studies from 2017 to 2022.

Clinical performance of a multiparametric MRI-based post concussive syndrome index.

Introduction: Diffusion Tensor Imaging (DTI) has revealed measurable changes in the brains of patients with persistent post-concussive syndrome (PCS). Because of inconsistent results in univariate DTI metrics among patients with mild traumatic brain injury (mTBI), there is currently no single objective and reliable MRI index for clinical decision-making in patients with PCS.

Purpose: This study aimed to evaluate the performance of a newly developed PCS Index (PCSI) derived from machine learning of multiparametric magnetic resonance imaging (MRI) data to classify and differentiate subjects with mTBI and PCS history from those without a history of mTBI.

Longitudinal Associations of Clinical and Biochemical Head Injury Biomarkers With Head Impact Exposure in Adolescent Football Players.

Importance: Consequences of subconcussive head impacts have been recognized, yet most studies to date have included small samples from a single site, used a unimodal approach, and lacked repeated testing.

Objective: To examine time-course changes in clinical (near point of convergence [NPC]) and brain-injury blood biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], and neurofilament light [NF-L]) in adolescent football players and to test whether changes in the outcomes were associated with playing position, impact kinematics, and/or brain tissue strain.

Design, Setting, And Participants: This multisite, prospective cohort study included male high school football players aged 13 to 18 years at 4 high schools in the Midwest during the 2021 high school football season (preseason [July] and August 2 to November 19).

Effects of Physical Exertion on Early Changes in Blood-Based Brain Biomarkers: Implications for the Acute Point of Care Diagnosis of Concussion.

Blood-based brain biomarkers (BBM) such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have potential to aid in the diagnosis of concussion. Recently developed point-of-care test devices would enable BBMs to be measured in field settings such military and sport environments within minutes of a suspicious head hit. However, head hits in these environments typically occur in the setting of vigorous physical exertion, which can itself increase BBMs levels.

Defining an Approach to Monitoring Brain Health in Individuals Exposed to Repetitive Head Impacts: Lessons Learned from Radiation Safety.

Recently, there has been increased concern over the effect of repetitive head impacts (RHIs, both concussive and subconcussive impacts) on long-term brain health. This concern has led researchers and policy makers to consider establishing RHI thresholds in order to mitigate the potential long-term effects of RHI exposure. However, the concept of thresholding relies on twin streams of information: 1) biomedical research relevant to the short and long-term risks of exposure to RHIs, and 2) societal standards for "acceptable risk.

Titrating the Translational Relevance of a Low-Level Repetitive Head Impact Model.

Recently, there has been increased attention in the scientific community to the phenomenon of sub-concussive impacts, those hits to the head that do not cause the signs and symptoms of a concussion. Some authors suggest that sub-concussive impacts may alter behavior and cognition, if sustained repetitively, but the mechanisms underlying these changes are not well-defined. Here, we adapt our well-established weight drop model of repetitive mild traumatic brain injury (rmTBI) to attempt to produce a model of low-level repetitive head impacts (RHI).

Pairwise versus Transitive Inverse Consistent Longitudinal Rigid Registration of Magnetic Resonance Images of Athletes With Repetitive Non-Concussive Head Injuries: Effects on Regional Distributions of Diffusion Measures.

Accurate alignment of longitudinal diffusion weighted imaging (DWI) scans of a subject is necessary to investigate longitudinal changes in DWI-derived diffusion measures such as fractional anisotropy (FA), mean diffusivity (MD), and quantitative anisotropy (QA). Currently, studies investigating these changes in the context of repetitive non-concussive head injuries (RHIs) perform pairwise rigid registration of all scans of a subject to the first scan or any other reference scan or template. Prajapati .

Neutrophil Gene Expression Patterns in Multiple Trauma Patients Indicate Distinct Clinical Outcomes.

Introduction: Patients after polytrauma suffer from posttraumatic immune system dysregulation and multiple organ dysfunction. Genome-wide microarray profiling in monocytes revealed a regulatory network of inflammatory markers around the transcription factor AP-1 in severely injured patients. Recent research focuses on the role of neutrophils in posttraumatic inflammation.

Short-Term Neurologic Manifestations of Repetitive Head Impacts Among Athletes: A Scoping Review.

Objective: To summarize the evidence linking contact sports-related repetitive head impacts (RHIs) and short-term declines in neurologic function.

Methods: A scoping review following the guidelines in the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and searching 3 databases (PubMed, EMBASE, and Web of Science) was performed. Peer-reviewed research articles were eligible for inclusion if they were full-length English language articles published between 1999 and 2019 examining athletes between the ages of 14 and 40 years exposed to RHIs, and reporting cognitive, vestibular, and/or oculomotor outcomes within 4 weeks of last head hit exposure.

A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality.

Research suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolites mediated the statistical relationship between miRNAs and VR-based motor control ( 0.

Transitive Inverse Consistent Rigid Longitudinal Registration of Diffusion Weighted Magnetic Resonance Imaging: A Case Study in Athletes With Repetitive Non-Concussive Head Injuries.

Significant longitudinal changes in metrics derived from diffusion weighted magnetic resonance (MR) images of the brain have been observed in athletes subject to repetitive non-concussive head injuries (RHIs). Accurate alignment of longitudinal scans of a subject is an important step in detecting and quantifying these changes. Currently, tools such as DSI Studio [1], FreeSurfer [2], and FSL [3] perform pairwise rigid registration of all scans in a longitudinal sequence to the first time-point scan (or to another reference scan or template).

The biological significance and clinical utility of emerging blood biomarkers for traumatic brain injury.

HUIBREGTSE, M.E, Bazarian, J.J.

Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl-terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury.

Objective: The objective was to determine the accuracy of a new, rapid blood test combining measurements of both glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) for predicting acute traumatic intracranial injury (TII) on head CT scan after mild traumatic brain injury (mTBI).

Methods: Analysis of banked venous plasma samples from subjects completing the Prospective Clinical Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) trial, enrolled 2012-2014 at 22 investigational sites in the United States and Europe. All subjects were ≥18 years old, presented to an emergency department (ED) with a nonpenetrating head injury and Glasgow Coma Scale score (GCS) 9-15 (mild to moderate TBI), underwent head CT scanning as part of their clinical care, and had blood sampling within 12 h of injury.

Classification of Comprehensive Neuro-Ophthalmologic Measures of Postacute Concussion.

Importance: Symptom-based methods of concussion diagnosis in contact sports result in underdiagnosis and repeated head injury exposure, increasing the risk of long-term disability. Measures of neuro-ophthalmologic (NO) function have the potential to serve as objective aids, but their diagnostic utility is unknown.

Objective: To identify NO measures that accurately differentiate athletes with and without concussion.

Validation of a Machine Learning Brain Electrical Activity-Based Index to Aid in Diagnosing Concussion Among Athletes.

Importance: An objective, reliable indicator of the presence and severity of concussive brain injury and of the readiness for the return to activity has the potential to reduce concussion-related disability.

Objective: To validate the classification accuracy of a previously derived, machine learning, multimodal, brain electrical activity-based Concussion Index in an independent cohort of athletes with concussion.

Design, Setting, And Participants: This prospective diagnostic cohort study was conducted at 10 clinical sites (ie, US universities and high schools) between February 4, 2017, and March 20, 2019.

Understanding Traumatic Brain Injury in Females: A State-of-the-Art Summary and Future Directions.

In this report, we identify existing issues and challenges related to research on traumatic brain injury (TBI) in females and provide future directions for research. In 2017, the National Institutes of Health, in partnership with the Center for Neuroscience and Regenerative Medicine and the Defense and Veterans Brain Injury Center, hosted a workshop that focused on the unique challenges facing researchers, clinicians, patients, and other stakeholders regarding TBI in women. The goal of this "Understanding TBI in Women" workshop was to bring together researchers and clinicians to identify knowledge gaps, best practices, and target populations in research on females and/or sex differences within the field of TBI.

Progesterone Treatment Does Not Decrease Serum Levels of Biomarkers of Glial and Neuronal Cell Injury in Moderate and Severe Traumatic Brain Injury Subjects: A Secondary Analysis of the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECT) III Trial.

Early treatment of moderate/severe traumatic brain injury (TBI) with progesterone does not improve clinical outcomes. This is in contrast with findings from pre-clinical studies of progesterone in TBI. To understand the reasons for the negative clinical trial, we investigated whether progesterone treatment has the desired biological effect of decreasing brain cell death.

ADHD May Associate With Reduced Tolerance to Acute Subconcussive Head Impacts: A Pilot Case-Control Intervention Study.

Objective: To test our hypothesis that individuals with ADHD would exhibit reduced resiliency to subconcussive head impacts induced by ten soccer headings.

Method: We conducted a case-control intervention study in 51 adults (20.6 ± 1.