To study longitudinal associations between blood-based neural biomarkers (including total tau, neurofilament light NfL, glial fibrillary acidic protein GFAP, and ubiquitin C-terminal hydrolase-L1) ...and white matter neuroimaging biomarkers in collegiate athletes with sport-related concussion (SRC) from 24 hours postinjury to 1 week after return to play.
We analyzed clinical and imaging data of concussed collegiate athletes in the Concussion Assessment, Research, and Education (CARE) Consortium. The CARE participants completed same-day clinical assessments, blood draws, and diffusion tensor imaging (DTI) at 3 time points: 24-48 hours postinjury, point of becoming asymptomatic, and 7 days after return to play. DTI probabilistic tractography was performed for each participant at each time point to render 27 participant-specific major white matter tracts. The microstructural organization of these tracts was characterized by 4 DTI metrics. Mixed-effects models with random intercepts were applied to test whether white matter microstructural abnormalities are associated with the blood-based biomarkers at the same time point. An interaction model was used to test whether the association varies across time points. A lagged model was used to test whether early blood-based biomarkers predict later microstructural changes.
Data from 77 collegiate athletes were included in the following analyses. Among the 4 blood-based biomarkers, total tau had significant associations with the DTI metrics across the 3 time points. In particular, high tau level was associated with high radial diffusivity (RD) in the right corticospinal tract (β = 0.25, SE = 0.07,
= 0.016) and superior thalamic radiation (β = 0.21, SE = 0.07,
= 0.042). NfL and GFAP had time-dependent associations with the DTI metrics. NfL showed significant associations only at the asymptomatic time point (|β|s > 0.12, SEs <0.09,
s
< 0.05) and GFAP showed a significant association only at 7 days after return to play (βs > 0.14, SEs <0.06,
s
< 0.05). The
values for the associations of early tau and later RD were not significant after multiple comparison adjustment, but were less than 0.1 in 7 white matter tracts.
This prospective study using data from the CARE Consortium demonstrated that in the early phase of SRC, white matter microstructural integrity detected by DTI neuroimaging was associated with elevated levels of blood-based biomarkers of traumatic brain injury. Total tau in the blood showed the strongest association with white matter microstructural changes.
This study reports our findings from 22 patients (ages ranging from 42 to 73 yr; mean = 55.2) with recalcitrant idiopathic Parkinson's disease (PD) who received implants of fetal ventral ...mesencephalic tissue using an MRI-guided stereotactic procedure and who have been followed for at least 6 mo postoperatively, employing the guidelines established by the Core Assessment Program for Intracerebral Transplantations. Evaluations were videotaped and were performed both on and off levodopa medications. To date, we have seven patients with 24 mo, three with 18 mo, three with 12 mo, and nine with 6 mo of postsurgical assessments. Comparing surgical outcomes to levels prior to fetal transplants we found: 1) mean levodopa levels were reduced 46% at 6 mo, 12% at 12 mo, 20% at 18 mo, and 54% at 24 mo; 2) Unified Parkinson's Disease Rating Scale (UPDRS) scores with patients on levodopa were improved by an average of 38% (6 mo), 50.2% (12 mo), 69.3% (18 mo), and 73.9% (24 mo), while off medication scores showed reductions ranging from 24.7% at 6 mo to 55.1% at 24 mo. Other measures, including Hoehn-Yahr staging, Activities of Daily Living, and dyskinesia rating scales, were also significantly improved following fetal transplants. Timed motor tasks (finger dexterity, supination-pronation, foot tapping, and Stand-Walk-Sit) performance also demonstrated highly significant improvements. Patient's self-rating scores indicated that the patients typically perceived substantial improvements in their condition. However, substantial variability in the improvements following surgery still persists and range from nominal improvements in performance to significant changes that can be classified as altering the overall lifestyle of the patients. To date, 4 of the 22 subjects were considered by the physicians to be nonresponders; that is, there were no clinically relevant improvements in these patients' conditions.
A recent systematic review determined that the physiological effects of concussion may persist beyond clinical recovery. Preclinical models suggest that ongoing physiological effects are accompanied ...by increased cerebral vulnerability that is associated with risk for subsequent, more severe injury. This study examined the association between signal alterations on diffusion tensor imaging following clinical recovery of sport-related concussion in athletes with and without a subsequent second concussion.
Average mean diffusivity (MD) was calculated in a region of interest (ROI) in which concussed athletes (
= 82) showed significantly elevated MD acutely after injury (<48 h), at an asymptomatic time point, 7 days post-return to play (RTP), and 6 months relative to controls (
= 69). The relationship between MD in the identified ROI and likelihood of sustaining a subsequent concussion over a 1-year period was examined with a binary logistic regression (re-injured, yes/no).
Eleven of 82 concussed athletes (13.4%) sustained a second concussion within 12 months of initial injury. Mean MD at 7 days post-RTP was significantly higher in those athletes who went on to sustain a repeat concussion within 1 year of initial injury than those who did not (
= 0.048;
= 0.75). In this underpowered sample, the relationship between MD at 7 days post-RTP and likelihood of sustaining a secondary injury approached significance χ
= 4.17,
= 0.057;
= 0.03, SE = 0.017; OR = 1.03, CI = 0.99, 1.07.
These preliminary findings raise the hypothesis that persistent signal abnormalities in diffusion imaging metrics at RTP following concussion may be predictive of a repeat concussion. This may reflect a window of cerebral vulnerability or increased susceptibility following concussion, though understanding the clinical significance of these findings requires further study.
Concussion is a brain injury induced by biomechanical forces that is broadly defined as a complex pathophysiological process affecting the brain. The intricate link between biomechanical input and ...concussion injury response is poorly understood. We aimed to test the hypothesis that greater biomechanical forces would result in the presentation of more concussion-related symptoms that would take longer to resolve. The objective of this study was to investigate the relationship between an array of biomechanical parameters measured for concussive impacts and the presentation and resolution of concussion symptoms. A total of 319 collegiate football players from six universities were recruited to participate in this study. Certified athletic trainers and/or team physicians at each site diagnosed and treated concussions sustained by subjects through participation in football. The subjects' helmets were instrumented with accelerometer arrays that measured linear and rotational head accelerations for each impact experienced during games and practices. Correlations between biomechanical measurements associated with concussion symptom presentation and recovery were quantified. A total of 22 subjects collectively sustained 25 concussions, with three subjects sustaining two concussions each. Biomechanical measures associated with injury were not found to be correlated with number of symptoms, Sport Concussion Assessment Tool 3 Symptom Severity Score, or time to symptom resolution. Linear and rotational accelerations associated with injury were not correlated with symptom severity for any of the 22 individual symptoms evaluated. Further, we found no association between impact location and presence of any individual symptom when ignoring severity grade. While concussive impacts did not stand out relative to impacts that did not result in injury, concussive impacts were among the most severe for each individual player. This suggests tolerance to head acceleration might be individual-specific, meaning similar biomechanical inputs can produce different injury presentations between individuals. Future investigations should consider individual-specific analyses of tolerance to head acceleration and injury response.
To evaluate the response of cavernous sinus meningiomas to stereotactic radiosurgery, we reviewed our 54-month experience with 34 patients. All patients underwent radiosurgery with a 201-source ...cobalt-60 gamma unit. Twenty-eight patients (82%) had previous histological confirmation of a meningioma (1 to 5 cranial base craniotomies per patient); 6 (18%) were treated on the basis of neuroimaging criteria alone. The single-fraction radiation tumor margin dose (10 to 20 Gy) was designed to conform to the irregular tumor volumes in all patients. The maximum radiation dose to the optic nerve or tract was reduced to 9 Gy in 31 patients. No patient had tumor growth (100% tumor control) during the follow-up interval (median, 26 mo). Tumor regression was observed in 56% of patients imaged at an average of 18 months. Eight patients (24%) improved clinically at follow-up examinations. Four patients developed new or worsened cranial nerve deficits during the follow-up interval; two had subsequent full improvement. No patient developed an endocrinopathy or new extraocular muscle paresis. Stereotactic radiosurgery, using multiple isocenter dosimetry facilitated by the gamma unit, is an accurate, safe, and effective technique to prevent the growth of tumors involving the cavernous sinus. Despite the proximity of such tumors to adjacent cranial nerves, complications were rare. The maximum length of hospital stay was 36 hours, and all patients returned to their preoperative employment status within 3 to 5 days.
Sport-related concussion (SRC) is an important public health issue. White-matter alterations after SRC are widely studied by neuroimaging approaches, such as diffusion magnetic resonance imaging ...(MRI). Although the exact anatomical location of the alterations may differ, significant white-matter alterations are commonly observed in long fiber tracts, but are never proven. In the present study, we performed streamline tractography to characterize the association between tract length and white-matter microstructural alterations after SRC. Sixty-eight collegiate athletes diagnosed with acute concussion (24-48 h post-injury) and 64 matched contact-sport controls were included in this study. The athletes underwent diffusion tensor imaging (DTI) in 3.0 T MRI scanners across three study sites. DTI metrics were used for tract-based spatial statistics to map white-matter regions-of-interest (ROIs) with significant group differences. Whole-brain white-mater streamline tractography was performed to extract "affected" white-matter streamlines (i.e., streamlines passing through the identified ROIs). In the concussed athletes, streamline counts and DTI metrics of the affected white-matter fiber tracts were summarized and compared with unaffected white-matter tracts across tract length in the same participant. The affected white-matter tracts had a high streamline count at length of 80-100 mm and high length-adjusted affected ratio for streamline length longer than 80 mm. DTI mean diffusivity was higher in the affected streamlines longer than 100 mm with significant associations with the Brief Symptom Inventory score. Our findings suggest that long fibers in the brains of collegiate athletes are more vulnerable to acute SRC with higher mean diffusivity and a higher affected ratio compared with the whole distribution.
The NCAA-DoD Concussion Assessment, Research, and Education (CARE) consortium is performing a large-scale, comprehensive study of sport related concussions in college student-athletes and military ...service academy cadets. The CARE “Advanced Research Core” (ARC), is focused on executing a cutting-edge investigative protocol on a subset of the overall CARE athlete population. Here, we present the details of the CARE ARC MRI acquisition and processing protocol along with preliminary analyzes of within-subject, between-site, and between-subject stability across a variety of MRI biomarkers. Two experimental datasets were utilized for this analysis. First, two “human phantom” subjects were imaged multiple times at each of the four CARE ARC imaging sites, which utilize equipment from two imaging vendors. Additionally, a control cohort of healthy athletes participating in non-contact sports were enrolled in the study at each CARE ARC site and imaged at four time points. Multiple morphological image contrasts were acquired in each MRI exam; along with quantitative diffusion, functional, perfusion, and relaxometry imaging metrics. As expected, the imaging markers were found to have varying levels of stability throughout the brain. Importantly, between-subject variance was generally found to be greater than within-subject and between-site variance. These results lend support to the expectation that cross-site and cross-vendor advanced quantitative MRI metrics can be utilized to improve analytic power in assessing sensitive neurological variations; such as those effects hypothesized to occur in sports-related-concussion. This stability analysis provides a crucial foundation for further work utilizing this expansive dataset, which will ultimately be freely available through the Federal Interagency Traumatic Brain Injury Research Informatics System.
Researchers have been collecting head impact data from instrumented football players to characterize the biomechanics of concussion for the past 15 years, yet the link between biomechanical input and ...clinical outcome is still not well understood. We have previously shown that even though concussive biomechanics might be unremarkable in large datasets of head impacts, the impacts causing injury are of high magnitude for the concussed individuals relative to their impact history. This finding suggests a need to account for differences in tolerance at the individual level. In this study, we identified control subjects for our concussed subjects who demonstrated traits we believed were correlated to factors thought to affect injury tolerance, including height, mass, age, race, and concussion history. A total of 502 college football players were instrumented with helmet-mounted accelerometer arrays and provided complete baseline assessment data, 44 of which sustained a total of 49 concussion. Biomechanical measures quantifying impact frequency and acceleration magnitude were compared between groups. On average, we found that concussed subjects experienced 93.8 more head impacts (
p
= 0.0031), 10.2 more high magnitude impacts (
p
= 0.0157), and 1.9 × greater risk-weighted exposure (
p
= 0.0175) than their physically matched controls. This finding provides further evidence that head impact data need to be considered at the individual level and that cohort wide assessments may be of little value in the context of concussion.
In a professional setting, the introduction of female speakers without their professional title may have an impact on the public's perception of the female speaker. We examined how professional ...titles were used during speakers' introductions at the ASCO Annual Meeting.
We conducted a retrospective, observational study of video-archived speaker introductions at the 2017 and 2018 ASCO Annual Meetings. A "professional address" was defined as the professional title followed by the speaker's full name or last name. Multivariable logistic regressions were used to identify factors associated with the form of address.
Of 2,511 videos reviewed, 781 met inclusion criteria. Female speakers were addressed less often by their professional title compared with male speakers (62%
81%;
< .001). Males were less likely to use a professional address when introducing female speakers compared with females when introducing male speakers (53%
80%;
< .01). When women performed speaker introductions, no gender differences in professional address were observed (75%
82%;
= .13). Female speakers were more likely to be introduced by first name only (17%
3%;
< .001). Male introducers were more likely to address female speakers by first name only compared with female introducers (24%
7%;
< .01). In a multivariable regression including gender, degree, academic rank, and geographic location of the speaker's institution, male speakers were more likely to receive a professional address compared with female speakers (odds ratio, 2.43; 95% CI, 1.71 to 3.47;
< .01).
When introduced by men, female speakers were less likely to receive a professional address and more likely to be introduced by first name only compared with their male peers.
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