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Prior studies suggest that concussion may lead to an increased risk of a subsequent time-loss sport-related injury, but the mechanisms responsible are unknown. We measured the symptom and dual-task gait outcomes for athletes initially post-concussion and after clinical recovery. Participants then self-reported any additional injuries incurred in the year after their concussion. Forty-two athletes (52% female, mean age = 16.8 ± 3.2 years) completed the study. They underwent a dual-task gait evaluation and symptom inventory within 21 days post-concussion, and again after they were deemed clinically recovered. Approximately one year later, participants documented if they had sustained any subsequent sport-related injuries. The repeated measures analysis of variance (ANOVA) was used to evaluate changes in dual-task gait and symptoms across time and between groups. A significant group*time interaction (p = 0.02) indicated that the group that went on to sustain a subsequent time-loss injury after returning to sports (n = 15) demonstrated significant average walking speed dual-task cost worsening across time (−17.9 ± 9.1% vs. −25.1 ± 12.5%; p = 0.007). In contrast, the group that did not sustain an additional injury walked with consistent dual-task cost values across time (−25.2 ± 9.2% vs. −24.6 ± 8.4%; p = 0.76). Symptoms improved for all participants (main effect of time, p < 0.001; Post-Concussion Symptom Scale [PCSS] = 25.0 ± 16.9 vs. 2.8 ± 7.5; p < 0.001), but did not differ between groups (p = 0.77). Significant dual-task gait cost worsening throughout concussion recovery was associated with time-loss injuries during sports in the year after a concussion. These findings indicate that worsening ability to execute a concurrent gait and cognitive task may relate to the risk of incurring an injury during sports after clinical concussion recovery.

Biomarkers can be broadly defined as qualitative or quantitative measurements that convey information on the physiopathological state of a subject at a certain time point or disease state. Biomarkers can indicate health, pathology, or response to treatment, including unwanted side effects. When used as outcomes in clinical trials, biomarkers act as surrogates or substitutes for clinically meaningful endpoints. Biomarkers of disease can be diagnostic (the identification of the nature and cause of a condition) or prognostic (predicting the likelihood of a person's survival or outcome of a disease). In addition, genetic biomarkers can be used to quantify the risk of developing a certain disease. In the specific case of traumatic brain injury, surrogate blood biomarkers of imaging can improve the standard of care and reduce the costs of diagnosis. In addition, a prognostic role for biomarkers has been suggested in the case of post-traumatic epilepsy. Given the extensive literature on clinical biomarkers, we will focus herein on biomarkers which are present in peripheral body fluids such as saliva and blood. In particular, blood biomarkers, such as glial fibrillary acidic protein and salivary/blood S100B, will be discussed together with the use of nucleic acids (eg, DNA) collected from peripheral cells.

Differential tractography and correlation tractography are new tractography modalities to study neuronal changes in brain diseases, but their performances in detecting neuronal injuries are yet to be investigated in patients with mild traumatic brain injury (mTBI). Here we investigated the white matter injury in mTBI patients using differential and correlation tractography. The diffusion MRI was acquired at 33 mTBI patients and 31 health controls. 7 of the mTBI patients had one-year follow-up scans, and differential tractography was used to evaluate injured fiber bundles on these 7 patients. All subjects were evaluated using digital symbol substitution test (DSST) and trail making test A (TMT-A), and the correlation tractography was performed to explore the exact pathways related to the cognitive performance. Our results showed that differential tractography revealed neuronal changes in the corpus callosum in all 7 follow-up mTBI patients with FDR between 0.007 and 0.17. Further, the correlation tractography showed that the splenium of the corpus callosum, combined with the right superior longitudinal fasciculus and right cingulum, were correlated with DSST (FDR=0.001669) in the acute mTBI patients. The cognitive impairment findings in the acute stage and the longitudinal findings in the corpus callosum in the chronic stage of mTBI patients suggest that differential tractography and correlation tractography are valuable tools in the diagnostic and prognostic evaluation of neuronal injuries in mTBI patients.

Abstract BACKGROUND A complicated mild traumatic brain injury (C-mTBI) is an mTBI with some form of intracranial abnormality identified radiographically. The lack of knowledge in recovery patterns and no clear guidelines on return to activity in children with C-mTBI provide unique challenges to physicians. OBJECTIVE To examine recovery patterns among three cohorts: mTBI, mTBI with skull fracture only (mTBI-SF), and C-mTBI via a cross-sectional survey. METHODS Caregivers of children with mTBI (from hospital database queries 2010–2013) were mailed a questionnaire on preinjury health, postinjury recovery, and activity patterns before and after injury. We examined degree (0-10 with 10 being complete recovery) and length (in months) of recovery in children with mTBI, and associations of potential risk factors to these variables. RESULTS Of the 1777 surveyed, a total of 285 complete responses were analyzed for this study. Data included 175 (61.4%) children with mTBI, 33 (11.6%) children with mTBI-SF, and 77 (27.0%) children with C-mTBI. Older age and C-mTBI (vs mTBI) were significantly associated with a lower degree and longer period of recovery (P < .05). Predicted probabilities of complete recovery for children with mTBI, those with mTBI-SF, and those with C-mTBI were 65.5%, 52.7%, and 40.0%, respectively. Predicted probabilities of not yet completely recovered after more than a year since injury for these groups were 11.3%, 24.4%, and 37.6%, respectively. CONCLUSION These results demonstrate significant differences in children with different forms of mTBI, and argue for further investigation of treatment plans individualized for each form of mTBI.

Introduction Mild traumatic brain injury (mTBI) represents a major public health concern and affects millions of people worldwide every year. Diagnosis mainly relies on clinical criteria and computed tomography (CT) scans. GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin carboxyl-terminal hydrolase-L1) have been recently studied as potential biomarkers of mTBI. This study retrospectively evaluated the possible use of these combined biomarkers as negative predictors for excluding brain injuries in patients with suspected mTBI in the emergency department. Methods Adult patients ( n  = 130) enrolled at Tor Vergata University Hospital (Rome, Italy), consecutively registered at the triage of the emergency department between October 2022 and January 2023, with non-penetrating TBI and Glasgow Coma Scale (GCS) score of 13–15, were considered. All eligible patients underwent intracranial CT scans and blood tests, within 12 h after trauma, for GFAP and UCH-L1 serum concentrations. Results Intracranial CT detected injuries in only seven patients (5%); GFAP and UCH-L1 tested positive in 96 patients and negative in 34 patients (74% vs. 26%). Combined biomarkers had a sensitivity equal to 1.00 (95% CI 0.64-1.00) and a negative predictive value (NPV) of 1.00 (0.99-1.00) in mTBI diagnosis with a negative CT. Conclusions Combined laboratory tests for GFAP and UCH-L1 biomarkers might play a potential clinical role in avoiding unnecessary head CT scans after mTBI in emergency departments.

Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable insight into the neuropathological state. This study used liquid chromatography-mass spectrometry (LC-MS) to examine plasma lipid concentrations at 11 days following sham (no injury), one (1×) or two (2×) mTBI in rats. Eighteen lipid species were identified that distinguished between sham, 1× and 2× mTBI. Three distinct patterns were found: (1) lipids that were altered significantly in concentration after either 1× or 2× F mTBI: cholesterol ester CE (14:0) (increased), phosphoserine PS (14:0/18:2) and hexosylceramide HCER (d18:0/26:0) (decreased), phosphoinositol PI(16:0/18:2) (increased with 1×, decreased with 2× mTBI); (2) lipids that were altered in response to 1× mTBI only: free fatty acid FFA (18:3 and 20:3) (increased); (3) lipids that were altered in response to 2× mTBI only: HCER (22:0), phosphoethanolamine PE (P-18:1/20:4 and P-18:0/20:1) (increased), lysophosphatidylethanolamine LPE (20:1), phosphocholine PC (20:0/22:4), PI (18:1/18:2 and 20:0/18:2) (decreased). These findings suggest that increasing numbers of mTBI induce a range of changes dependent upon the lipid species, which likely reflect a balance of damage and reparative responses.

Athletic trainers surveyed in 1999 demonstrated little consensus on the use of concussion grading scales and return-to-play criteria. Most relied on clinical examination or symptom checklists to evaluate athletes with concussion. To investigate the current trends of certified athletic trainers in concussion assessment and management. Subjects were invited to participate in a 32-question Internet survey. An Internet link to the survey was e-mailed to the subjects. A total of 2750 certified athletic trainers and members of the National Athletic Trainers' Association were randomly e-mailed and invited to participate. Survey questions addressed topics including years of certification, number of concussions evaluated each year, methods of assessing concussion, and guidelines used for return to play. Compliance with the recent position statement of the National Athletic Trainers' Association on sport-related concussion was also evaluated. Certified athletic trainers averaged 9.9 +/- 7.3 years of certification and evaluated an average of 8.2 +/- 6.5 concussions per year. To assess concussion, 95% reported using the clinical examination, 85% used symptom checklists, 48% used the Standardized Assessment of Concussion, 18% used neuropsychological testing, and 16% used the Balance Error Scoring System. The most frequently used concussion grading scale and return-to-play guideline belonged to the American Academy of Neurology (30%). When deciding whether to return an athlete to play, certified athletic trainers most often used the clinical examination (95%), return-to-play guidelines (88%), symptom checklists (80%), and player self-report (62%). The most important tools for making a return-to-play decision were the clinical examination (59%), symptom checklists (13%), and return-to-play guidelines (12%). Only 3% of certified athletic trainers surveyed complied with the recent position statement, which advocated using symptom checklists, neuropsychological testing, and balance testing for managing sport-related concussion. Our findings suggest that only a small percentage of certified athletic trainers currently follow the guidelines proposed by the National Athletic Trainers' Association. Various assessment methods and tools are currently being used, but clinicians must continue to implement a combination of methods and tools in order to comply with the position statement.

The cingulum, connecting the orbitofrontal cortex to the medial temporal lobe, involves in diverse cognition functions including attention, memory, and motivation. To investigate the relationship between the cingulum injury and cognitive impairment in patients with chronic mild traumatic brain injury, we evaluated the integrity between the anterior cingulum and the basal forebrain using diffusion tensor tractography in 73 patients with chronic mild traumatic brain injury (39 males, 34 females, age 43.29 ± 11.42 years) and 40 healthy controls (22 males, 18 females, age 40.11 ± 16.81 years). The patients were divided into three subgroups based on the integrity between the anterior cingulum and the basal forebrain on diffusion tensor tractography: subgroup A (n = 19 patients) - both sides of the anterior cingulum were intact; subgroup B (n = 36 patients) - either side of the anterior cingulum was intact; and subgroup C (18 patients) - both sides of the anterior cingulum were discontinued. There were significant differences in total Memory Assessment Scale score between subgroups A and B and between subgroups A and C. There were no significant differences in diffusion tensor tractography parameters (fractional anisotropy, apparent diffusion coefficient, and fiber volume) between patients and controls. These findings suggest that the integrity between the anterior cingulum and the basal forebrain, but not diffusion tensor tractography parameter, can be used to predict the cognitive function of patients with chronic mild traumatic brain injury. This study was approved by Yeungnam University Hospital Institutional Review Board (approval No. YUMC-2014-01-425-010) on August 16, 2017.

Background： The ability to predict posttraumatic stress disorder （PTSD） is a critical issue in the management of patients with mild traumatic brain injury （mTBI）, as early medical and rehabilitative interventions may reduce the risks of long-term cognitive changes. The aim of the present study was to investigate how diffusion tensor imaging （DTI） metrics changed in the transition from acute to chronic phases in patients with mTBI and whether the alteration relates to the development of PTSD. Methods： Forty-three patients with mTBI and 22 healthy volunteers were investigated. The patients were divided into two groups： successful recovery （SR, n = 22） and poor recovery （PR, n = 21）, based on neurocognitive evaluation at 1 or 6 months after injury. All patients underwent magnetic resonance imaging investigation at acute （within 3 days）, subacute （10-20 days）, and chronic （1-6 months） phases after injury. Group differences of fractional anisotropy （FA） and mean diffusivity （MD） were analyzed using tract-based spatial statistics （TBSS）. The accuracy of DTI metrics for classifying PTSD was estimated using Bayesian discrimination analysis. Results： TBSS showed white matter （WM） abnormalities in various brain regions. In the acute phase, FA values were higher for PR and SR patients than controls （all P 〈 0.05）. In subacute phase, PR patients have higher mean MD than SR and controls （all P 〈 0.05）. In the chronic phase, lower FA and higher MD were observed in PR compared with both SR and control groups （all P 〈 0.05）. PR and SR groups could be discriminated with a sensitivity of 73%, specificity of 78%, and accuracy of 75.56%, in terms of MD value in subacute phase. Conclusions： Patients with mTBI have multiple abnormalities in various WM regions. DTI metrics change over time and provide a potential indicator at subacute stage for PTSD following mTBI.