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. Glial fibrillary acidic protein (GFAP) changes were correlated with three measures of head impact exposure (number of hits, total linear acceleration, and total rotational acceleration captured by helmet impact sensors) and to changes in brain white matter (WM) integrity, estimated by regional changes in fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging from 24 h before (T1) to 48 h after (T3) the game. To account for the potentially confounding effects of physical exertion on GFAP, correlations were adjusted for kilocalories of energy expended during the game measured by wearable body sensors. All 30 participants were male with a mean age of 19.5 ± 1.2 years. No participant had a concussion during the index game. We observed a significant increase in GFAP from T0 to T1 (mean 79.69 vs. 91.95 pg/mL, p = 0.008) and from T0 to T2 (mean 79.69 vs. 99.21 pg/mL, p < 0.001). WM integrity decreased in multiple WM regions but was statistically significant in the right fornix (mean % FA change -1.43, 95% confidence interval [CI]: -2.20, -0.66). T0 to T2 increases in GFAP correlated with reduced FA in the left fornix, right fornix, and right medical meniscus and with increased MD in the right fornix (r-values ranged from 0.59 to 0.61). Adjustment for exertion had minimal effect on these correlations. GFAP changes did not correlate to head hit exposure, but after adjustment for exertion, T0 to T2 increases correlated with all three hit metrics (r-values ranged from 0.69 to 0.74). Thus, acute elevations in GFAP after a single collegiate football game of RHHs correlated with in-game head hit exposure and with reduced WM integrity 2 days later. These results suggest that GFAP may be a biologically relevant indicator of the brain's early response to RHHs during a single sporting event. Developing tools to measure the neurological response to RHHs on an individual level has the potential to provide insight into the heterogeneity in adverse outcomes after RHH exposure and for developing effective and personalized countermeasures. Owing to the small sample size, these findings should be considered preliminary; validation in a larger, independent cohort is necessary.

Improving Employee Safety Through a Comprehensive Patient Behavioral Program.

BACKGROUND: Health care workers in the United States are facing increasing rates of exposure to aggressive behavior, resulting in an increase in employee injuries related specifically to patient behavioral events. By leveraging interprofessional collaboration and system-level innovation, we aimed to reduce the rate of employee injuries related to patient behavioral events at a children's hospital by 50% over a 3-year period. METHODS: An interdisciplinary quality improvement team comprising physicians, behavior analysts, nursing, and other key stakeholders developed a comprehensive behavior program in our children's hospital. The team developed 5 key pillars: aggression mitigation tools, clinical resources, advanced training, screening and management, and behavior emergency response. The outcome measure was rate of reported employee safety events related to patient behavioral events. This was tracked via prospective time series analysis statistical process control chart using established rules to detect special cause variation. RESULTS: The average rate of employee injuries resulting from patient behavioral events decreased from 0.96 to 0.39 per 1000 adjusted patient-days, with special cause variation observed on a statistical process control U-chart. This improvement has been sustained for 16 months. Staff members who experienced injuries included nurses and patient technicians, with common antecedents to injuries including medical interventions or patient requests that could not be safely met. CONCLUSIONS: A unified and multimodal system aimed to address pediatric patient behavioral events can reduce employee injuries and foster a culture of employee safety in the pediatric inpatient setting.

7T MRI Versus 3T MRI of the Brain in Professional Fighters and Patients With Head Trauma.

Many studies have investigated the imaging sequelae of repetitive head trauma with mixed results, particularly with regard to the detection of intracranial white matter changes (WMCs) and cerebral microhemorrhages (CMHs) on ≤3 Tesla (T) field magnetic resonance imaging (MRI). 7T MRI, which has recently been approved for clinical use, is more sensitive at detecting lesions associated with multiple neurological diagnoses. In this study, we sought to determine whether 7T MRI would detect more WMCs and CMHs than 3T MRI in 19 professional fighters, 16 patients with single TBI, versus 82 normal healthy controls (NHCs). Fighters and patients with TBI underwent both 3T and 7T MRI; NHCs underwent either 3T (n = 61) or 7T (n = 21) MRI. Readers agreed on the presence/absence of WMCs in 88% (84 of 95) of 3T MRI studies (Cohen's kappa, 0.76) and in 93% (51 of 55) of 7T MRI studies (Cohen's kappa, 0.79). Readers agreed on the presence/absence of CMHs in 96% (91 of 95) of 3T MRI studies (Cohen's kappa, 0.76) and in 96% (54 of 56) of 7T MRI studies (Cohen's kappa, 0.88). The number of WMCs detected was greater in fighters and patients with TBI than NHCs at both 3T and 7T. Moreover, the number of WMCs was greater at 7T than at 3T for fighters, patients with TBI, and NHCs. There was no difference in the number of CMHs detected with 7T MRI versus 3T MRI or in the number of CMHs observed in fighters/patients with TBI versus NHCs. These initial findings suggest that fighters and patients with TBI may have more WMCs than NHCs and that the improved voxel size and signal-to-noise ratio at 7T may help to detect these changes. As 7T MRI becomes more prevalent clinically, larger patient populations should be studied to determine the cause of these WMCs.

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. Thus, efforts to develop BBMs as acute concussion aids in field settings need to account for the effects of physical exertion. To determine the acute effects of physical exertion on the BBMs, we measured GFAP, UCH-L1, tau, and neurofilament light chain (NF-L) immediately before, immediately after, and 45 min after a single workout session consisting of aerobic and resistance exercises in 30 collegiate football players. Subjects wore body sensors measuring several aspects of exertion and underwent diffusion tensor imaging 24 h before and 48 h after exertion. All subjects were male with a mean age of 19.5 ± 1.2 years. The mean duration of activity during the workout session was 94 ± 31 min. There was a significant decrease in serum GFAP immediately after (median decrease of 27.76%, p < 0.0001) and a significant increase in serum UCH-L1 45 min after (median increase of 37.11%, p = 0.016) exertion, compared with pre-exertion baseline. No significant changes in tau or NF-L were identified. The duration of exertion had a significant independent linear correlation to the increase in serum UCHL1 from pre-exertion to 45 min after exertion (r = 0.68, p = 0.004). There were no significant pre- to post-exertional changes in any of the 39 examined brain white matter regions, and biomarker changes did not correlate to variation in white matter integrity in any of these regions. Thus, exertion appeared to be associated with immediate decreases in serum GFAP and very acute (45 min) increases in UCH-L1. These changes were related to the duration of exertion, but not to changes in brain white matter integrity. Our results have important implications for how these BBMs might be used to aid in the on-scene diagnosis of concussion occurring in the setting of physical exertion.

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. RESULTS: Fifty-two articles met criteria for review: 14 reported oculomotor outcomes, 23 reported vestibular outcomes, and 36 reported cognitive function. Short-term RHI-related declines in neurologic function were reported in 42.9% of oculomotor studies, in 20.8% of vestibular studies, and in 33.3% of cognitive studies. Most of the 52 studies involved American football, soccer, or ice hockey athletes at the collegiate ( n = 23) or high school ( n = 14) level. Twenty-four (46%) studies involved only male athletes. Wearable sensors were used to measure RHIs in 24 studies (46%), while RHIs were not measured in 26 studies (50%). In addition, many studies failed to control for attention-deficit/hyperactivity disorder/learning disability and/or concussion history. CONCLUSION: The results of this scoping review suggest that the evidence linking RHIs to short-term declines in neurologic function is relatively sparse and lacking in methodological rigor. Although most studies failed to find a link, those that did were more likely to use objective measures of RHIs and to control for confounders. More careful trial design may be needed to definitively establish a causal link between RHIs and short-term neurologic dysfunction.

Sex Moderates the Relationship That Number of Professional Fights Has With Cognition and Brain Volumes.

Objective: Incidence of concussions and report of symptoms are greater among women across sports. While structural brain changes and cognitive declines are associated with repetitive head impact (RHI), the role of sex is not well-understood. This study aimed to determine if there is a moderating effect of sex on the relationship the number of professional fights has with cognitive functioning and regional brain volumes in a cohort of boxers, mixed martial artists, and martial artists. Methods: A total of 55 women were matched with 55 men based on age, years of education, ethnicity, and fighting style. Cognition was assessed via the CNS Vital Signs computerized cognitive battery and supplemental measures. Structural brain scans, demographic data, and number of professional fights (NoPF) were also considered. The matched pairs were compared via analysis of covariance, accounting for total brain volume. Within-subject moderation models were utilized to assess the moderating effect of sex on the relationship between NoPF and brain volumes and cognitive performance. Results: Men were observed to have poorer performance on measures of psychomotor speed when compared to women. On a series of analyses assessing the role of sex as a moderator of the relationship between NoPF and regional brain volumes/cognitive performance, a significant moderation effect was observed across multiple measures of cognitive functioning, such that men had poorer performance. Differences in numerous regional brain volumes were also observed, such that the relationship between NoPF and brain volumes was steeper among men. Conclusion: Sex was observed to be an important moderator in the relationship between NoPF, aspects of cognitive functioning, and volumes of numerous brain regions, suggesting that sex differences in neuroanatomic and cognitive response to RHI deserve further attention.

The Relationship Between Fighting Style, Cognition, and Regional Brain Volume in Professional Combatants: A Preliminary Examination Using Brief Neurocognitive Measures.

OBJECTIVE: Repetitive head impacts (RHIs) in combat sports are associated with cognitive decline and brain volume reduction. While fighting style differences between boxers, mixed martial artists (MMAs), and martial artists (MAs) have resulted in a broader spectrum of injury, the effects of RHIs on MAs relative to other fighters have not yet been explored. This study aimed to determine a differential effect of fighting style on cognition and brain. SETTING: A large outpatient medical center specializing in neurological care. PARTICIPANTS, DESIGN, AND MAIN MEASURES: In total, 40 MAs, 188 boxers, and 279 MMAs were compared on baseline measures of subcortical regional brain volumes, after controlling for total brain volumes, and cognitive performance. RESULTS: Significant differences between MAs, MMAs, and boxers were observed in subcortical brain structure volumes and cognitive measures. MMAs and MAs consistently had larger volumes and higher scores than boxers. Fighting style significantly moderated the relationship between the number of professional fights and the volumes of various subcortical brain structures and performance on a measure of processing speed at baseline. CONCLUSIONS: Differences in RHIs across fighting styles may be of clinical significance. Exploring changes over time within the MA, boxer, and MMA cohorts may provide insight into longer-term discrepancies in subcortical regional brain volumes and cognitive functioning across fighting styles.