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1.
Sports Med ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773581

RESUMO

BACKGROUND: Potential links between a history of sport-related concussions and later-life neurobiological and psychological brain health have been studied in former collision-sport athletes. However, empirical studies of how former athletes perceive the future of their brain health as a result of these injuries are missing. OBJECTIVES: We aimed to (1) identify the extent to which former National Football League players currently have concerns about their long-term psychological and cognitive functioning as a result of concussions sustained while playing football; (2) examine whether current concerns are different than concerns they had while playing football; (3) examine the relationship between current brain health concerns and self-reported concussion history (SR-CHx); and (4) explore other important factors associated with these concerns. METHODS: In this cross-sectional study, former National Football League players with a SR-CHx of one or more concussions (n = 1514; aged mean [standard deviation] = 52.3 [15.7] years) completed a general health questionnaire. Participants reported their lifetime concussion history, as well as both their current concerns and concerns while playing football (i.e., retrospective concerns) regarding the long-term effects of concussions on their memory, thinking skills, and risk of developing chronic traumatic encephalopathy. Current and retrospective concerns were self-reported on a five-point Likert scale. Four concussion history categories were created based on SR-CHx: 1-2 (n = 309); 3-5 (n = 413); 6-9 (n = 356); and 10 + (n = 436) lifetime concussions. Proportions of participants reporting each level of current and retrospective concerns were examined to identify whether concerns presently exist in these former players, and whether their current concerns are different than retrospective concerns. Next, we explored associations between current concerns and SR-CHx. RESULTS: More than one-third of participants reported being currently "extremely concerned" about memory problems (36.9%), thinking skills (37.8%), and developing chronic traumatic encephalopathy (39.5%). In contrast, when asked about concerns while playing, most reported being "not at all concerned" regarding memory = 61.2%, thinking skills = 56.1%, and developing chronic traumatic encephalopathy = 71.2%. Of those who retrospectively endorsed being "not at all" or "slightly" concerned regarding memory (n = 1159/1514), thinking skills (n = 1080/1514), and developing chronic traumatic encephalopathy (n = 1219/1514), approximately half reported being currently "moderately" or "extremely" concerned about those same issues (n = 586/1159; n = 534/1080; n = 619/1219, respectively). Current concerns regarding memory (χ216 = 316.61; p < 0.001; V = 0.264), thinking skills (χ216 = 333.17; p < 0.001; V = 0.271), and developing chronic traumatic encephalopathy (χ216 = 280.85; p < 0.001; V = 0.249) were significantly related to SR-CHx, with more concussions being associated with greater current concerns. CONCLUSIONS: Former National Football League players reported significant concerns regarding the potential effects of their prior concussions on long-term brain health, and these concerns are more prevalent now than when they were playing football. Cognitive and mental health concerns are readily identifiable targets for clinical intervention. Clinicians working with former players may wish to explore the extent to which individual players experience these concerns, the nature and depth of these concerns, and the impact of these concerns on the player's functioning and well-being.

2.
Med Sci Sports Exerc ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34593716

RESUMO

PURPOSE: To estimate prevalences of MCI and dementia diagnoses in former National Football League (NFL) players ≥50 years old and examine the relationships among these diagnoses and an array of predictors of long-term brain health. METHODS: A cross-section of former NFL players (n = 922; aged [mean ± SD] 64.8 ± 8.9 years) completed a questionnaire. Prevalences of self-reported medical diagnoses of MCI and dementia were reported alongside U.S. population estimates across 5-year age intervals (e.g., 60-64 years). Prevalence ratios (PRs) were calculated for multiple predictors of long-term brain health. RESULTS: Overall, MCI and dementia prevalences were n = 219(23.8%) and n = 82(8.9%), respectively. Each diagnosis was more prevalent in former NFL players across age groups than U.S. norms, with greater disparities at relatively younger ages (e.g., 65-69) compared with older ages. Greater prevalences of MCI and dementia were associated with: self-reported concussion history (10+ vs. 0; PRadjusted[95%CI] = 1.66[1.02-2.71] and 2.61[1.01-6.71], respectively); recent pain intensity (PRadjusted[95%CI] = 1.13[1.07-1.20] and 1.15[1.03-1.28]); and diagnoses of depression (PRadjusted[95%CI] = 2.70[1.92-3.81] and 3.22[1.69-6.14]), anxiety (PRadjusted[95%CI] = 1.96[1.26-3.07] and 3.14[1.47-6.74]), or both (PRadjusted[95%CI] = 3.11[2.38-4.08] and 4.43[2.71-7.25]). Higher MCI prevalence was related to sleep apnea (PRadjusted[95%CI] = 1.30[1.06-1.60]); higher dementia prevalence was associated with age (5-year interval, PRadjusted[95%CI] = 1.42[1.26-1.60]) and race (non-White vs. White, PRadjusted[95%CI] = 1.64[1.07-2.53]). CONCLUSIONS: Self-reported MCI and dementia prevalences were higher in former NFL players than national estimates and were associated with numerous personal factors, including mood-related disorders and a high number of self-reported concussions. Predictors of higher MCI and dementia prevalence may be modifiable and warrant consideration by clinicians and researchers as potential targets to mitigate the onset of these conditions.

3.
Neurology ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675105

RESUMO

BACKGROUND AND OBJECTIVES: Sport-related concussions affect millions of individuals across the United States each year and current techniques to diagnose and monitor them rely largely on subjective measures. Our goal was to discover and validate objective, quantifiable non-invasive biomarkers with the potential to be used in sport-related concussion diagnosis. METHODS: Urine samples from a convenience series of healthy control collegiate athletes who had not sustained a concussion and athletes who sustained a concussion as diagnosed by a sports medicine physician within seven days were collected prospectively and studied. Participants also completed an instrumented single-task gait analysis as a functional measure. Participants were recruited from a single collegiate athletic program, were ≥18 years old, and were excluded if they had a concomitant injury, active psychiatric conditions or pre-existing neurological disorders. Using Tandem Mass Tags (TMT) mass spectroscopy and enzyme-linked immunosorbent assays (ELISA), urinary biomarkers of concussion were identified and validated. RESULTS: Forty-eight control and 47 concussion age- and sex-matched athletes were included in the study (51.6%F, 48.4%M, average age 19.6y). Participants represented both contact and non-contact sports. All but one of the post-concussion participants reported experiencing symptoms at the time of data collection. Insulin-like growth factor 1 (IGF-1) and IGF binding protein 5 (IGFBP5) were downregulated in the urine of athletes with concussions compared to healthy controls. Multivariable risk algorithms developed to predict the probability of sport-related concussion showed that IGF-1 multiplexed with single-task gait velocity predicts concussion risk across a range of post-injury timepoints (AUC=0.786; 95% CI:0.690-0.884). When IGF-1 and IGFBP5 are multiplexed with single-task gait velocity, they accurately distinguish between healthy controls and concussion at acute timepoints (AUC=0.835, 95% CI:0.701-0·968, p<0.001). DISCUSSION: These noninvasive biomarkers, discovered in an objective and validated manner, may be useful in diagnosing and monitoring sport-related concussions in both acute phases of injury in addition to several days post-injury. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that urinary IGF-1 and IGFBP5 multiplexed with single-task gait velocity may be useful in diagnosing sport-related concussion. TRIAL REGISTRATION INFORMATION: Clinicaltrials.gov identifier NCT02354469, submitted February 2015, first patient enrolled August 2015 (https://clinicaltrials.gov/ct2/show/NCT02354469).

4.
Lancet Child Adolesc Health ; 5(11): 792-799, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34600629

RESUMO

BACKGROUND: Sport-related concussion is a public health problem, particularly in adolescents. Quality of life is reduced in adolescents with persistent post-concussive symptoms (symptoms >28 days). We replicated a previous randomised controlled trial to validate the safety, efficacy, and generalisability of, and objective adherence to, prescribed early targeted heart rate subsymptom threshold aerobic exercise compared with placebo-like stretching exercise for adolescent recovery from sport-related concussion and for reducing the risk of persistent post-concussive symptoms. METHODS: This randomised controlled trial was done at three community and hospital-affiliated sports medicine concussion centres in the USA. Male and female adolescent athletes (aged 13-18 years) presenting within 10 days of sport-related concussion were randomly assigned to individualised subsymptom threshold aerobic or stretching exercise at least 20 min daily, for up to 4 weeks after injury. Exercise adherence and intensity were measured by heart rate monitors. The primary outcome was clinical recovery (ie, return to baseline symptoms, normal exercise tolerance, and a normal physical examination) within the 4-week intervention period, and development of persistent post-concussive symptoms beyond 28 days after injury. This study is registered with ClinicalTrials.gov, NCT02959216. FINDINGS: Between Aug 1, 2018, and March 31, 2020, 118 adolescents were recruited (61 were randomly assigned to the aerobic exercise group and 57 to the stretching exercise group) and included in the intention-to-treat analysis. On survival analysis, controlling for sex, site, and mean daily exercise time, patients assigned to aerobic exercise were more likely to recover within 4 weeks after injury compared with those assigned to stretching exercise, with a 48% reduced risk of persistent post-concussive symptoms (hazard ratio for stretching vs aerobic exercise of 0·52 [95% CI 0·28-0·97], p=0·039). No adverse events were reported. INTERPRETATION: This multicentre study found that early treatment with subsymptom threshold aerobic exercise safely speeds recovery from sport-related concussion and reduces the risk for persistent post-concussive symptoms, an important result given the impact of delayed recovery on adolescent quality of life. Adherence was good and there were no adverse events from this non-pharmacological treatment. These results suggest that physicians should not only permit, but consider prescribing, early subsymptom threshold physical activity to adolescents as treatment for sport-related concussion and to reduce the risk of persistent post-concussive symptoms. FUNDING: American Medical Society for Sports Medicine.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34663623

RESUMO

OBJECTIVE: This study investigated the longitudinal course of depressive symptom severity over 19 years in former American football players and the influence of concussion history, contact sport participation and physical function on observed trajectories. METHODS: Former American football players completed a general health questionnaire involving demographic information, medical/psychiatric history, concussion/football history and validated measures of depression and physical function at three time points (2001, 2010 and 2019). Parallel process latent growth curve modelling tested associations between concussion history, years of football participation, and overall and change in physical function on the overall level and trajectory of depressive symptoms. RESULTS: Among the 333 participants (mean(SD) age, 48.95 (9.37) at enrolment), there was a statistically significant, but small increase in depressive symptom severity from 2001 (48.34 (7.75)) to 2019 (49.77 (9.52)), slope=0.079 (SE=0.11), p=0.007. Those with greater concussion history endorsed greater overall depressive symptom severity, B=1.38 (SE=0.33), p<0.001. Concussion history, B<0.001 (SE=0.02), p=0.997 and years of participation, B<0.001 (SE=0.01), p=0.980, were not associated with rate of change (slope factor) over 19 years. Greater decline in physical function, B=-0.71 (SE=0.16), p<0.001, was predictive of a faster growth rate (ie, steeper increase) of depression symptom endorsement over time. CONCLUSIONS: Concussion history, not years of participation, was associated with greater depressive symptom severity. Neither factor was predictive of changes over a 19-year period. Decline in physical function was a significant predictor of a steeper trajectory of increased depressive symptoms, independent of concussion effects. This represents one viable target for preventative intervention to mitigate long-term neuropsychiatric difficulties associated with concussion across subsequent decades of life.

6.
JAMA Pediatr ; 175(11): 1124-1131, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34491285

RESUMO

Importance: There are limited data to guide screen time recommendations after concussion. Objective: To determine whether screen time in the first 48 hours after concussion has an effect on the duration of concussive symptoms. Design, Setting, and Participants: This randomized clinical trial was conducted in the pediatric and adult emergency departments of a tertiary medical center between June 2018 and February 2020. Participants included a convenience sample of patients aged 12 to 25 years presenting to the emergency department within 24 hours of sustaining a concussion. A total of 162 patients were approached, 22 patients met exclusion criteria, and 15 patients declined participation; 125 participants were enrolled and randomized. Interventions: Patients were either permitted to engage in screen time (screen time permitted group) or asked to abstain from screen time (screen time abstinent group) for 48 hours after injury. Main Outcomes and Measures: The primary outcome was days to resolution of symptoms, defined as a total Post-Concussive Symptom Scale (PCSS) score of 3 points or lower. Patients completed the PCSS, a 22-symptom scale that grades each symptom from 0 (not present) to 6 (severe), each day for 10 days. Kaplan-Meier curves and Cox regression modeling were used to compare the 2 groups. A Wilcoxon rank sum test was also performed among participants who completed the PCSS each day through recovery or conclusion of the study period. Results: Among 125 patients with concussion, the mean (SD) age was 17.0 (3.4) years; 64 participants (51.2%) were male. A total of 66 patients were randomized to the screen time permitted group, and 59 patients were randomized to the screen time abstinent group. The Cox regression model including the intervention group and the patient's self-identified sex demonstrated a significant effect of screen time (hazard ratio [HR], 0.51; 95% CI, 0.29-0.90), indicating that participants who engaged in screen time were less likely to recover during the study period. In total, 91 patients were included in the Wilcoxon rank sum test (47 patients from the screen time permitted group, and 44 patients from the screen time abstinent group). The screen time permitted group had a significantly longer median recovery time of 8.0 days (interquartile range [IQR], 3.0 to >10.0 days) compared with 3.5 days (IQR, 2.0 to >10.0 days; P = .03) in the screen time abstinent group. The screen time permitted group reported a median screen time of 630 minutes (IQR, 415-995 minutes) during the intervention period compared with 130 minutes (IQR, 61-275 minutes) in the screen time abstinent group. Conclusions and Relevance: The findings of this study indicated that avoiding screen time during acute concussion recovery may shorten the duration of symptoms. A multicenter study would help to further assess the effect of screen time exposure. Trial Registration: ClinicalTrials.gov Identifier: NCT03564210.

7.
J Neurotrauma ; 38(20): 2881-2895, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34375128

RESUMO

Mild traumatic brain injury (mTBI) is a major cause of morbidity and mortality with a poorly understood pathophysiology. Animal models have been increasingly utilized to better understand mTBI and recent research has identified visual deficits in these models that correspond to human literature. While visual impairment is being further characterized within TBI, the implications of impaired vision on behavioral tasks commonly utilized in animal models has not been well described thus far. Visual deficits may well confound behavioral tests that are believed to be isolated to cognitive functioning such as learning and memory. We utilized a mouse model of repetitive mTBI (rmTBI) to further characterize visual deficits using an optomotor task, electroretinogram, and visually evoked potential, and located likely areas of damage to the visual pathway. Mice were tested on multiple behavioral metrics, including a touchscreen conditional learning task to better identify the contribution of visual dysfunction to behavioral alterations. We found that rmTBI caused visual dysfunction resulting from damage distal to the retina that likely involves pathology within the optic nerve. Moreover, loss of vision led to poorer performance of rmTBI animals on classic behavioral tests such as the Morris water maze that would otherwise be attributed solely to learning and memory deficits. The touchscreen conditional learning task was able to differentiate rmTBI induced learning and memory dysfunction from visual impairment and is a valuable tool for elucidating subtle changes resulting from TBI.

10.
J Cereb Blood Flow Metab ; : 271678X211021771, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229511

RESUMO

Cerebrovascular reactivity (CVR) deficits in adolescents with concussion may persist after resolution of neurological symptoms. Whether or not CVR deficits predict long term neurological function is unknown. We used adolescent mice closed head injury (CHI) models (54 g, 107 cm or 117 cm drop height), followed by blood oxygenation level dependent (BOLD)-functional MRI with CO2 challenge to assess CVR and brain connectivity. At one week, 3HD 107 cm mice showed delayed BOLD responses (p = 0.0074), normal striatal connectivity, and an impaired respiratory rate response to CO2 challenge (p = 0.0061 in ΔRmax). The 107 cm group developed rotarod deficits at 6 months (p = 0.02) and altered post-CO2 brain connectivity (3-fold increase in striatum to motor cortex correlation coefficient) by one year, but resolved their CVR and respiratory rate impairments, and did not develop cognitive or circadian activity deficits. In contrast, the 117 cm group had persistent CVR (delay time: p = 0.016; washout time: p = 0.039) and circadian activity deficits (free-running period: 23.7 hr in sham vs 23.9 hr in 3HD; amplitude: 0.15 in sham vs 0.2 in 3HD; peak activity: 18 in sham vs 21 in 3HD) at one year. Persistent CVR deficits after concussion may portend long-term neurological dysfunction. Further studies are warranted to determine the utility of CVR to predict chronic neurological outcome after mild traumatic brain injury.

11.
West J Emerg Med ; 22(3): 782-791, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-34125061

RESUMO

INTRODUCTION: We sought to validate a handheld, near-infrared spectroscopy (NIRS) device for detecting intracranial hematomas in children with head injury. METHODS: Eligible patients were those <18 years old who were admitted to the emergency department at three academic children's hospitals with head trauma and who received a clinically indicated head computed tomography (HCT). Measurements were obtained by a blinded operator in bilateral frontal, temporal, parietal, and occipital regions. Qualifying hematomas were a priori determined to be within the brain scanner's detection limits of >3.5 milliliters in volume and <2.5 centimeters from the surface of the brain. The device's measurements were positive if the difference in optical density between hemispheres was >0.2 on three successive scans. We calculated diagnostic performance measures with corresponding exact two-sided 95% Clopper-Pearson confidence intervals (CI). Hypothesis test evaluated whether predictive performance exceeded chance agreement (predictive Youden's index > 0). RESULTS: A total of 464 patients were enrolled and 344 met inclusion for primary data analysis: 10.5% (36/344) had evidence of a hematoma on HCT, and 4.7% (16/344) had qualifying hematomas. The handheld brain scanner demonstrated a sensitivity of 58.3% (21/36) and specificity of 67.9% (209/308) for hematomas of any size. For qualifying hematomas the scanner was designed to detect, sensitivity was 81% (13/16) and specificity was 67.4% (221/328). Predictive performance exceeded chance agreement with a predictive Youden's index of 0.11 (95% CI, 0.10 - 0.15; P < 0.001) for all hematomas, and 0.09 (95% CI, 0.08 - 0.12; P < 0.001) for qualifying hematomas. CONCLUSION: The handheld brain scanner can non-invasively detect a subset of intracranial hematomas in children and may serve an adjunctive role to head-injury neuroimaging decision rules that predict the risk of clinically significant intracranial pathology after head trauma.


Assuntos
Encéfalo/diagnóstico por imagem , Traumatismos Craniocerebrais/diagnóstico , Hemorragia Intracraniana Traumática/diagnóstico por imagem , Testes Imediatos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Criança , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Neuroimagem/métodos , Prognóstico , Tomografia Computadorizada por Raios X/métodos
12.
J Neurol ; 268(11): 4349-4361, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34028616

RESUMO

OBJECTIVE: The goals of this study were to assess the ability of salivary non-coding RNA (ncRNA) levels to predict post-concussion symptoms lasting ≥ 21 days, and to examine the ability of ncRNAs to identify recovery compared to cognition and balance. METHODS: RNA sequencing was performed on 505 saliva samples obtained longitudinally from 112 individuals (8-24-years-old) with mild traumatic brain injury (mTBI). Initial samples were obtained ≤ 14 days post-injury, and follow-up samples were obtained ≥ 21 days post-injury. Computerized balance and cognitive test performance were assessed at initial and follow-up time-points. Machine learning was used to define: (1) a model employing initial ncRNA levels to predict persistent post-concussion symptoms (PPCS) ≥ 21 days post-injury; and (2) a model employing follow-up ncRNA levels to identify symptom recovery. Performance of the models was compared against a validated clinical prediction rule, and balance/cognitive test performance, respectively. RESULTS: An algorithm using age and 16 ncRNAs predicted PPCS with greater accuracy than the validated clinical tool and demonstrated additive combined utility (area under the curve (AUC) 0.86; 95% CI 0.84-0.88). Initial balance and cognitive test performance did not differ between PPCS and non-PPCS groups (p > 0.05). Follow-up balance and cognitive test performance identified symptom recovery with similar accuracy to a model using 11 ncRNAs and age. A combined model (ncRNAs, balance, cognition) most accurately identified recovery (AUC 0.86; 95% CI 0.83-0.89). CONCLUSIONS: ncRNA biomarkers show promise for tracking recovery from mTBI, and for predicting who will have prolonged symptoms. They could provide accurate expectations for recovery, stratify need for intervention, and guide safe return-to-activities.


Assuntos
Concussão Encefálica , Adolescente , Adulto , Biomarcadores , Concussão Encefálica/diagnóstico , Criança , Humanos , Testes Neuropsicológicos , RNA , Saliva , Adulto Jovem
14.
J Pediatr ; 235: 178-183.e1, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33894265

RESUMO

OBJECTIVE: To examine whether the presence of clinical guidelines and clinical decision support (CDS) for mild traumatic brain injury (mTBI) are associated with lower use of head computed tomography (CT). STUDY DESIGN: We conducted a cross-sectional study of 45 pediatric emergency departments (EDs) in the Pediatric Hospital Information System from 2015 through 2019. We included children discharged with mTBI and surveyed ED clinical directors to ascertain the presence and implementation year of clinical guidelines and CDS. The association of clinical guidelines and CDS with CT use was assessed, adjusting for relevant confounders. As secondary outcomes, we evaluated ED length of stay and rates of 3-day ED revisits and admissions after revisits. RESULTS: There were 216 789 children discharged with mTBI, and CT was performed during 20.3% (44 114/216 789) of ED visits. Adjusted hospital-specific CT rates ranged from 11.8% to 34.7% (median 20.5%, IQR 17.3%, 24.3%). Of the 45 EDs, 17 (37.8%) had a clinical guideline, 9 (20.0%) had CDS, and 19 (42.2%) had neither. Compared with EDs with neither a clinical guideline nor CDS, visits to EDs with CDS (aOR 0.52 [0.47, 0.58]) or a clinical guideline (aOR 0.83 [0.78, 0.89]) had lower odds of including a CT for mTBI. ED length of stay and revisit rates did not differ based on the presence of a clinical guideline or CDS. CONCLUSIONS: Clinical guidelines for mTBI, and particularly CDS, were associated with lower rates of head CT use without adverse clinical outcomes.


Assuntos
Concussão Encefálica/diagnóstico por imagem , Sistemas de Apoio a Decisões Clínicas , Guias de Prática Clínica como Assunto , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adolescente , Concussão Encefálica/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Bases de Dados Factuais , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Inquéritos e Questionários
15.
JAMA Netw Open ; 4(3): e210599, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33656530

RESUMO

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. Design, Setting, and Participants: This cohort study was conducted among athletes with and without concussion who were aged 17 to 22 years between 2016 and 2017. Eye movements and cognitive function were measured a median of 19 days after injury among patients who had an injury meeting the study definition of concussion while playing a sport (retrospectively selected from a concussion clinic), then compared with a control group of participants without concussion (enrolled from 104 noncontact collegiate athlete volunteers without prior head injury). Data analysis was conducted from November 2019 through May 2020. Exposure: Concussion. Main Outcomes and Measures: Classification accuracy of clinically important discriminator eye-tracking (ET) metrics. Participants' eye movements were evaluated with a 12-minute ET procedure, yielding 42 metrics related to smooth pursuit eye movement (SPEM), saccades, dynamic visual acuity, and reaction time. Clinically important discriminator metrics were defined as those with significantly different group differences and area under the receiver operator characteristic curves (AUROCs) of at least 0.70. Results: A total of 34 participants with concussions (mean [SD] age, 19.7 [2.4] years; 20 [63%] men) and 54 participants without concussions (mean [SD] age, 20.8 [2.2] years; 31 [57%] men) completed the study. Six ET metrics (ie, simple reaction time, discriminate reaction time, discriminate visual reaction speed, choice visual reaction speed, and reaction time on 2 measures of dynamic visual acuity 2) were found to be clinically important; all were measures of reaction time, and none were related to SPEM. Combined, these 6 metrics had an AUROC of 0.90 (95% CI, 0.80-0.99), a sensitivity of 77.8%, and a specificity of 92.6%. The 6 metrics remained significant on sensitivity testing. Conclusions and Relevance: In this study, ET measures of slowed visual reaction time had high classification accuracy for concussion. Accurate, objective measures of NO function have the potential to improve concussion recognition and reduce the disability associated with underdiagnosis.


Assuntos
Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/fisiopatologia , Concussão Encefálica/diagnóstico , Concussão Encefálica/fisiopatologia , Cognição , Movimentos Oculares , Adolescente , Traumatismos em Atletas/classificação , Traumatismos em Atletas/complicações , Concussão Encefálica/classificação , Concussão Encefálica/complicações , Estudos de Coortes , Feminino , Humanos , Masculino , Tempo de Reação , Adulto Jovem
16.
Brain Inj ; 35(6): 734-741, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33760683

RESUMO

BACKGROUND: Cellular prion protein (PrPC) is a lipid raft protein abundant within CNS. It is regulated by a disintegrin and metalloproteinase domain containing protein 10 (ADAM10). PrPC has previously been implicated as a biomarker for TBI. ADAM10 has not been investigated as a TBI biomarker. OBJECTIVE: We evaluated PrPC and ADAM10 as candidate biomarkers for TBI. METHODS: We performed ELISA for ADAM10 and PrPC on plasma samples of patients with TBI admitted to Brigham and Women's Hospital. Plasma samples from 20 patients admitted for isolated TBI were acquired from a biobank with clinical information. Control plasma (37 samples) was acquired from a commercial source. GraphPad was used to conduct statistical analysis. RESULTS: 37 controls and 20 TBI samples were collected. Of the patients with TBI, eight were mild, three were moderate, and nine were severe. Both PrPC and ADAM10 were elevated in patients with TBI compared with control (p < .001). ADAM10 exhibited greater expression in patients with worse clinical grade. There was no significant association of either PrPC or ADAM10 with time after injury. CONCLUSIONS: Our results indicate that PrPC and ADAM10 appear to be useful potential tools for screening of TBI. ADAM10 is closely associated with clinical grade.


Assuntos
Lesões Encefálicas Traumáticas , Príons , Proteína ADAM10 , Secretases da Proteína Precursora do Amiloide , Biomarcadores , Feminino , Humanos , Proteínas de Membrana , Projetos Piloto , Proteínas Priônicas
17.
J Pediatr ; 233: 249-254.e1, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33524386

RESUMO

OBJECTIVE: To determine if racial/ethnic differences exist in the diagnosis and mechanism of injury among children and adolescents visiting the emergency department (ED) for concussion and minor head trauma (MHT). STUDY DESIGN: A retrospective, cross-sectional study of patient (age ≤19 years) visits to the ED for concussion between 2010-2015, using the National Hospital Ambulatory Medical Care Survey, was completed. The primary study exposure was race/ethnicity. Outcome measures included ED visits that resulted in a concussion/MHT diagnosis and mechanism of injury. Mechanism categories included sport, motor vehicle collision, fall, assault, and other mechanism. A multivariable logistic regression and multinomial logistic regression were conducted to assess relationships between race/ethnicity and outcomes. Findings were weighted to reflect population estimates. RESULTS: In total, 1263 child/adolescent visits for concussion/MHT were identified, representing an estimated 6.6 million child/adolescent visits nationwide. Compared with non-Hispanic White pediatric patients, non-Hispanic Black patients were least likely to have an ED visit for a concussion/MHT (P < .001; OR, 0.66; 95% CI, 0.52-0.83) The odds of non-Hispanic Black children/adolescents (OR, 3.80; 95% CI, 1.68-8.55) and children/adolescents of other race/ethnicity (OR, 4.93; 95% CI, 1.09-22.23) sustaining a concussion/MHT resulting from assault vs sport was higher. CONCLUSIONS: Amid the emerging focus on sport-related concussion, these ethnic/racial differences in ED diagnosis of concussion/MHT demonstrate sociodemographic differences that warrant further attention. Assault may be a more common mechanism of concussion among children/adolescents of a racial minority.


Assuntos
Concussão Encefálica/diagnóstico , Grupos de Populações Continentais , Traumatismos Craniocerebrais/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Grupos Étnicos , Disparidades em Assistência à Saúde , Admissão do Paciente/estatística & dados numéricos , Adolescente , Concussão Encefálica/etnologia , Criança , Traumatismos Craniocerebrais/etnologia , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índices de Gravidade do Trauma , Estados Unidos/epidemiologia
18.
Sci Adv ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33523853

RESUMO

Small interfering RNA (siRNA)-based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We report a nanoparticle platform for BBB pathophysiology-independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing. Together, our data suggest that this nanoparticle platform is a promising next-generation drug delivery approach for the treatment of TBI.

19.
Brain Inj ; 35(2): 226-232, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459038

RESUMO

Objective: Concussion is associated with dysautonomia, altered blood pressure (BP) control, and may cause Orthostatic Hypotension (OH). We measured prevalence of OH using the 1-minute supine-to-standing OH Test in adolescents with concussion and controls.Participants: Adolescents within 10 days of injury (Concussion Group, n = 297, 15.0 ± 1.7 years, 59% male) were compared with controls (Control Group, n = 214, 15.0 ± 1.5 years, 58% male).Methods: BP, heart rate (HR), and complaints of lightheadedness/dizziness were measured after 2-minute supine and 1-minute standing. Control Group was assessed once. Concussion Group was assessed twice; (1) initial visit (mean 6.0 ± 3 days-since-injury) and (2) after clinical recovery (mean 46.3 ± 42 days-since-injury).Results: Initial visit; Concussion Group reported feeling lightheaded/dizzy on postural change more often than the Control Group (37% vs 4%, p < .001) but did not differ in meeting standard OH criteria (3% vs 5%, p = .32). Experiencing symptoms did not correlate with meeting OH criteria, but correlated with abnormal vestibulo-ocular reflex. After clinical recovery; Concussion Group did not differ in experiencing lightheaded/dizziness on postural change than controls (4%, p = .65).Conclusion: Adolescents commonly experience orthostatic intolerance after concussion without meeting the standard criteria for OH.


Assuntos
Concussão Encefálica , Hipotensão Ortostática , Adolescente , Pressão Sanguínea , Concussão Encefálica/complicações , Tontura/etiologia , Feminino , Frequência Cardíaca , Humanos , Hipotensão Ortostática/etiologia , Masculino
20.
JAMA Neurol ; 78(5): 596-608, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33464290

RESUMO

Importance: Mild traumatic brain injury (TBI) is experienced by 55.9 million people globally each year. The symptoms of mild TBI are diverse and sometimes long-lasting, requiring frequent use of pharmacological interventions to mitigate them. A thorough understanding of the data supporting pharmacological interventions is important for decision-making among clinicians treating this common injury. Objective: To systematically review studies of pharmacological interventions and their associations with symptom burden reduction among patients with mild TBI and to use an evidence-based model to identify potential directions for future research that may aid in clinical decision-making. Evidence Review: A systematic review was performed in PubMed, Scopus, and Web of Science. Search strings modified for the advanced search interfaces of each search engine were developed in consultation with a librarian and included combinations of search terms, such as brain concussion, post-concussion syndrome, mild traumatic brain injury, and pharmacological treatment. Articles published between January 1, 2000, and July 1, 2020, were analyzed. Studies were included if (1) they were clinical studies with discrete analyses of participants with mild TBI or complicated mild TBI, (2) they were assessments of a pharmacological intervention, (3) they included human participants, and (4) they were published in a peer-reviewed journal in the English language. Studies were excluded if the severity of TBI among participants could not be ascertained (ie, inadequate definition of mild TBI) and the inclusion criteria for the study required intracranial hemorrhage. A total of 23 studies examining 20 pharmacological interventions met the inclusion criteria. Risk of bias was assessed using the Cochrane Risk of Bias for Randomized Trials (for randomized clinical trials) and the Cochrane Risk of Bias in Non-Randomized Studies of Interventions (for all other studies). Data were analyzed from June to September 2020. Findings: A total of 1495 articles were identified; of those, 131 articles were excluded as duplicates. Titles and abstracts were screened for inclusion and exclusion criteria among the remaining 1364 articles, and 134 of those articles received a full-text review. After exclusions, 23 studies (11 randomized clinical trials, 7 prospective observational studies, 3 retrospective observational studies, and 2 case studies) examining 20 pharmacological interventions were identified for inclusion in the systematic review. Studies included 22 distinct participant populations comprising 8277 participants with mild TBI and 45 participants without TBI. Among 23 total studies, 8 studies specifically addressed the pediatric population, 9 studies had a low risk of bias, and 16 studies reported symptom burden reduction. Of the 20 pharmacological interventions examined in the studies, methylphenidate, sertraline hydrochloride, ondansetron, amitriptyline, and melatonin were the only medications included in multiple studies. Conclusions and Relevance: This systematic review found a limited number of high-quality, clinically meaningful studies, particularly among children and individuals in the acute stage of injury; therefore, performing an evidence-based analysis that would inform clinical decision-making was not possible. Future studies are needed to focus on standardizing measures and increasing sample sizes (including large multicenter clinical trials) to generate a body of research that may provide additional options for the treatment of patients with mild TBI.

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