Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A 20-Year Study.

BACKGROUND: Understanding the incidence, causes, and trends of sudden cardiac death (SCD) among young competitive athletes is critical to inform preventive policies. METHODS: This study included National Collegiate Athletic Association athlete deaths during a 20-year time frame (July 1, 2002, through June 30, 2022). Athlete deaths were identified through 4 separate independent databases and search strategies (National Collegiate Athletic Association resolutions list, Parent Heart Watch database and media reports, National Center for Catastrophic Sports Injury Research database, and insurance claims). Autopsy reports and medical history were reviewed by an expert panel to adjudicate causes of SCD. RESULTS: A total of 143 SCD cases in National Collegiate Athletic Association athletes were identified from 1102 total deaths. The National Collegiate Athletic Association resolutions list identified 117 of 143 (82%), the Parent Heart Watch database or media reports identified 89 of 143 (62%), the National Center for Catastrophic Sports Injury Research database identified 63 of 143 (44%), and insurance claims identified 27 of 143 (19%) SCD cases. The overall incidence of SCD was 1:63 682 athlete-years (95% CI, 1:54 065-1:75 010). Incidence was higher in male athletes than in female athletes (1:43 348 [95% CI, 1:36 228-1:51 867] versus 1:164 504 [95% CI, 1:110 552-1:244 787] athlete-years, respectively) and Black athletes compared with White athletes (1:26 704 [1:20 417-1:34 925] versus 1:74 581 [1:60 247-1:92 326] athlete-years, respectively). The highest incidence of SCD was among Division I male basketball players (1:8188 [White, 1:5848; Black, 1:7696 athlete-years]). The incidence rate for SCD decreased over the study period (5-year incidence rate ratio, 0.71 [95% CI, 0.61-0.82]), whereas the rate of noncardiovascular deaths remained stable (5-year incidence rate ratio, 0.98 [95% CI, 0.94-1.04]). Autopsy-negative sudden unexplained death (19.5%) was the most common postmortem examination finding, followed by idiopathic left ventricular hypertrophy or possible cardiomyopathy (16.9%) and hypertrophic cardiomyopathy (12.7%), in cases with enough information for adjudication (118 of 143). Eight cases of death were attributable to myocarditis over the study period (1 case from January 1, 2020, through June 30, 2022), with none attributed to COVID-19 infection. SCD events were exertional in 50% of cases. Exertional SCD was more common among those with coronary artery anomalies (100%) and arrhythmogenic cardiomyopathy (83%). CONCLUSIONS: The incidence of SCD in college athletes has decreased. Male sex, Black race, and basketball are associated with a higher incidence of SCD.

Whole blood stimulation provides preliminary evidence of altered immune function following SRC.

PURPOSE: To implement an approach combining whole blood immune stimulation and causal modelling to estimate the impact of sport-related concussion (SRC) on immune function. METHODS: A prospective, observational cohort study was conducted on athletes participating across 13 university sports at a single academic institute; blood was drawn from 52 athletes, comprised of 22 athletes (n = 11 male, n = 11 female) within seven days of a physician-diagnosed SRC, and 30 healthy athletes (n = 18 female, n = 12 male) at the beginning of their competitive season. Blood samples were stimulated for 24 h under two conditions: (1) lipopolysaccharide (lps, 100ng/mL) or (2) resiquimod (R848, 1uM) using the TruCulture® system. The concentration of 45 cytokines and chemokines were quantitated in stimulated samples by immunoassay using the highly sensitive targeted Proximity Extension Assays (PEA) on the Olink® biomarker platform. A directed acyclic graph (DAG) was used as a heuristic model to make explicit scientific assumptions regarding the effect of SRC on immune function. A latent factor analysis was used to derive two latent cytokine variables representing immune function in response to LPS and R848 stimulation, respectively. The latent variables were then modelled using student-t regressions to estimate the total causal effect of SRC on immune function. RESULTS: There was an effect of SRC on immune function in males following SRC, and it varied according to prior concussion history. In males with no history of concussion, those with an acute SRC had lower LPS reactivity compared to healthy athletes with 93% posterior probability (pprob), and lower R848 reactivity with 77% pprob. Conversely, in males with a history of SRC, those with an acute SRC had higher LPS reactivity compared to healthy athletes with 85% pprob and higher R848 reactivity with 82%. In females, irrespective of concussion history, SRC had no effect on LPS reactivity. However, in females with no concussion history, those with an acute SRC had higher R848 reactivity compared to healthy athletes with 86% pprob. CONCLUSION: Whole blood stimulation can be used within a causal framework to estimate the effect of SRC on immune function. Preliminary evidence suggests that SRC affects LPS and R848 immunoreactivity, that the effect is stronger in male athletes, and differs based on concussion history. Replication of this study in a larger cohort with a more sophisticated causal model is necessary.

Associations of prior concussion severity with brain microstructure using mean apparent propagator magnetic resonance imaging.

Magnetic resonance imaging (MRI) diffusion studies have shown chronic microstructural tissue abnormalities in athletes with history of concussion, but with inconsistent findings. Concussions with post-traumatic amnesia (PTA) and/or loss of consciousness (LOC) have been connected to greater physiological injury. The novel mean apparent propagator (MAP) MRI is expected to be more sensitive to such tissue injury than the conventional diffusion tensor imaging. This study examined effects of prior concussion severity on microstructure with MAP-MRI. Collegiate-aged athletes (N = 111, 38 females; ≥6 months since most recent concussion, if present) completed semistructured interviews to determine the presence of prior concussion and associated injury characteristics, including PTA and LOC. MAP-MRI metrics (mean non-Gaussian diffusion [NG Mean], return-to-origin probability [RTOP], and mean square displacement [MSD]) were calculated from multi-shell diffusion data, then evaluated for associations with concussion severity through group comparisons in a primary model (athletes with/without prior concussion) and two secondary models (athletes with/without prior concussion with PTA and/or LOC, and athletes with/without prior concussion with LOC only). Bayesian multilevel modeling estimated models in regions of interest (ROI) in white matter and subcortical gray matter, separately. In gray matter, the primary model showed decreased NG Mean and RTOP in the bilateral pallidum and decreased NG Mean in the left putamen with prior concussion. In white matter, lower NG Mean with prior concussion was present in all ROI across all models and was further decreased with LOC. However, only prior concussion with LOC was associated with decreased RTOP and increased MSD across ROI. Exploratory analyses conducted separately in male and female athletes indicate associations in the primary model may differ by sex. Results suggest microstructural measures in gray matter are associated with a general history of concussion, while a severity-dependent association of prior concussion may exist in white matter.

Unusual combinations of neurodegenerative pathologies with chronic traumatic encephalopathy (CTE) complicates clinical prediction of CTE.

BACKGROUND AND PURPOSE: Chronic traumatic encephalopathy (CTE) has gained widespread attention due to its association with multiple concussions and contact sports. However, CTE remains a postmortem diagnosis, and the link between clinical symptoms and CTE pathology is poorly understood. This study aimed to investigate the presence of copathologies and their impact on symptoms in former contact sports athletes. METHODS: This was a retrospective case series design of 12 consecutive cases of former contact sports athletes referred for autopsy. Analyses are descriptive and include clinical history as well as the pathological findings of the autopsied brains. RESULTS: All participants had a history of multiple concussions, and all but one had documented progressive cognitive, psychiatric, and/or motor symptoms. The results showed that 11 of the 12 participants had evidence of CTE in the brain, but also other copathologies, including different combinations of tauopathies, and other rare entities. CONCLUSIONS: The heterogeneity of symptoms after repetitive head injuries and the diverse pathological combinations accompanying CTE complicate the prediction of CTE in clinical practice. It is prudent to consider the possibility of multiple copathologies when clinically assessing patients with repetitive head injuries, especially as they age, and attributing neurological or cognitive symptoms solely to presumptive CTE in elderly patients should be discouraged.

The effects of cytomegalovirus on brain structure following sport-related concussion.

The neurotrophic herpes virus cytomegalovirus is a known cause of neuropathology in utero and in immunocompromised populations. Cytomegalovirus is reactivated by stress and inflammation, possibly explaining the emerging evidence linking it to subtle brain changes in the context of more minor disturbances of immune function. Even mild forms of traumatic brain injury, including sport-related concussion, are major physiological stressors that produce neuroinflammation. In theory, concussion could predispose to the reactivation of cytomegalovirus and amplify the effects of physical injury on brain structure. However, to our knowledge this hypothesis remains untested. This study evaluated the effect of cytomegalovirus serostatus on white and grey matter structure in a prospective study of athletes with concussion and matched contact-sport controls. Athletes who sustained concussion (n = 88) completed MRI at 1, 8, 15 and 45 days post-injury; matched uninjured athletes (n = 73) completed similar visits. Cytomegalovirus serostatus was determined by measuring serum IgG antibodies (n = 30 concussed athletes and n = 21 controls were seropositive). Inverse probability of treatment weighting was used to adjust for confounding factors between athletes with and without cytomegalovirus. White matter microstructure was assessed using diffusion kurtosis imaging metrics in regions previously shown to be sensitive to concussion. T1-weighted images were used to quantify mean cortical thickness and total surface area. Concussion-related symptoms, psychological distress, and serum concentration of C-reactive protein at 1 day post-injury were included as exploratory outcomes. Planned contrasts compared the effects of cytomegalovirus seropositivity in athletes with concussion and controls, separately. There was a significant effect of cytomegalovirus on axial and radial kurtosis in athletes with concussion but not controls. Cytomegalovirus positive athletes with concussion showed greater axial (P = 0.007, d = 0.44) and radial (P = 0.010, d = 0.41) kurtosis than cytomegalovirus negative athletes with concussion. Similarly, there was a significant association of cytomegalovirus with cortical thickness in athletes with concussion but not controls. Cytomegalovirus positive athletes with concussion had reduced mean cortical thickness of the right hemisphere (P = 0.009, d = 0.42) compared with cytomegalovirus negative athletes with concussion and showed a similar trend for the left hemisphere (P = 0.036, d = 0.33). There was no significant effect of cytomegalovirus on kurtosis fractional anisotropy, surface area, symptoms and C-reactive protein. The results raise the possibility that cytomegalovirus infection contributes to structural brain abnormalities in the aftermath of concussion perhaps via an amplification of concussion-associated neuroinflammation. More work is needed to identify the biological pathways underlying this process and to clarify the clinical relevance of this putative viral effect.

Trajectories of Daily Postconcussion Symptoms in Children.

OBJECTIVES: To identify trajectories of daily postconcussion symptoms (PCS) from the acute postinjury period to symptom resolution among concussed children and examine demographic factors and acute PCS associated with the identified symptom trajectories. SETTING AND PARTICIPANTS: Seventy-nine participants with a concussion were enrolled within 72 hours of injury and completed a daily survey that assessed PCS from enrollment until symptom resolution. DESIGN: This was a prospective cohort study among concussed children aged 11-17 years. MAIN MEASURES: Children rated their concussion symptoms daily using the Post-Concussion Symptom Scale. Symptom duration was assessed using participants' date of symptom resolution and coded as a dichotomous variable: (1) PCS duration 14 days or less or (2) PCS duration longer than 14 days. RESULTS: Of the 79 participants, most were male ( n = 53, 67%), injured during a sporting activity ( n = 67, 85%), or had PCS that persisted for more than 14 days post-injury ( n = 41, 52%). Group-based trajectory modeling yielded 4 trajectory groups: (1) low acute/resolved PCS ( n = 39, 49%), (2) moderate/persistent PCS ( n = 19, 24%), (3) high acute/persistent PCS ( n = 13, 16%), and (4) high acute/resolved PCS ( n = 8, 10%). No significant associations were found between demographic factors and the trajectory group. A higher symptom burden at injury was associated with an increased odds of being in the high acute/resolved or high acute/persistent recovery groups than being in the low acute/resolved group (odds ratio [OR] 1.39, 95% CI = 1.11-1.74; OR = 1.33, 95% CI = 1.11-1.60, respectively), as was a higher symptom severity at injury (OR = 1.09, 95% CI = 1.03-1.15; OR = 1.06, 95% CI = 1.02-1.11, respectively). CONCLUSION: Our findings may help clinicians identify concussed children on slower recovery trajectories, and implement early, individualized treatment plans that foster optimal recovery for concussed children.

T1-VIBE and STIR MRI of lumbar pars interarticularis injuries in elite athletes: fracture characterisation and potential prognostic indicators.

OBJECTIVES: To assess how pars interarticularis fracture characteristics on T1-VIBE and STIR MRI relate to healing and identify anatomical parameters that may impact healing. MATERIALS AND METHODS: A retrospective review of an MRI series of lumbar pars interarticularis injuries in elite athletes over a 3-year period. Fracture configurations, signal intensities and anatomical parameters were recorded by two radiologists. Statistical analysis employed multilevel mixed-effects linear regressions, adjusted for repeated measures and baseline covariates. RESULTS: Forty-seven lumbar pars interarticularis injuries among 31 athletes were assessed. On final scans for each athlete, 15% (7/47) injuries had worsened, 23% (11/47) remained stable, 43% (20/47) partially healed and 19% (9/47) healed completely. Healing times varied, quickest was 49 days for a chronic fracture in a footballer. Bone marrow oedema signal was highest in worsened fractures, followed by improved, and lowest in stable fractures. As healing progressed, T1-VIBE signal at the fracture line decreased. Bone marrow oedema and fracture line signal peaked at 90-120 days before decreasing until 210-240 days. Fractures with smaller dimensions, more vertical orientation and a longer superior articular facet beneath were significantly associated with better healing (p < 0.05). CONCLUSION: Most diagnosed athletic pars interarticularis injuries improve. Normalising T1-VIBE signal at the fracture line is a novel measurable indicator of bony healing. Contrastingly, bone marrow oedema signal is higher in active fractures irrespective of healing or deterioration. Injuries initially perceived as worsening may be exhibiting the normal osteoclastic phase of healing. Better outcomes favour smaller, vertical fractures with a longer superior articular facet beneath.

Symptom resolution following a repeat concussion within the same athlete.

INTRODUCTION: Repeat sport-related concussion (SRC) is anecdotally associated with prolonged recovery. Few studies have examined repeat concussion within the same athlete. We sought to explore differences in symptom burden and recovery outcomes in an individual athlete's initial and repeat SRC. METHODS: A retrospective within-subject cohort study of athletes aged 12-23 years diagnosed with two separate SRCs from 11/2017-10/2020 was conducted. Primary outcomes were initial symptom severity and time-to-symptom-resolution. Secondary outcomes included return-to-learn (RTL) and return-to-play (RTP) duration. RESULTS: Of 868 athletes seen, 47 athletes presented with repeat concussions. Median time between concussions was 244 days (IQR 136-395). Comparing initial to repeat concussion, no differences were observed in time-to-clinic (4.3 ± 7.3vs.3.7 ± 4.6 days, p = 0.56) or initial PCSS (26.2 ± 25.3 vs. 30.5 ± 24.1, p = 0.32). While a difference was observed in time-to-symptom resolution between initial/repeat concussion (21.2 ± 16.3 vs. 41.7 ± 86.0 days, p = 0.30), this did not reach statistical significance. No significant differences were observed in time-to-RTL (17.8 ± 60.6 vs. 6.0 ± 8.3 days, p = 0.26) and RTP (33.2 ± 44.1 vs. 29.4 ± 39.1 days, p = 0.75). Repeat concussion was not associated with symptom resolution on univariate (HR 1.64, 95% CI 0.96-2.78, p = 0.07) and multivariable (HR 0.85, 95% CI 0.49-1.46, p = 0.55) Cox regression. CONCLUSION: No significant differences in symptom duration and RTP/RTL were seen between initial/repeat concussion.

Concussion symptom presentation and clinical recovery among pediatric athletes: comparing concussions sustained during school and summer months.

OBJECTIVE: We examined post-concussion symptom presentation, exercise, and sleep among pediatric athletes who sustained concussion during the school year vs. summer months. METHODS: We evaluated athletes 6-18 years old within 21-days of concussion. They reported symptoms (Health and Behavior Inventory), with cognitive/somatic domain sub-scores calculated, and indicated if they had exercised or experienced sleep problems since injury. We grouped patients by injury season: summer months (June-August) vs. school year (September-May). RESULTS: 350 patients (14.4 ± 2.4 years old; 37% female; initial visit 8.8 ± 5.3 days post-concussion) were seen for care: 24% sustained a concussion during summer months, 76% during the school year. Lower cognitive (median = 7 [IQR = 1, 15] vs. 9.5 [4, 17]; p = 0.01), but not somatic (7 [2.5, 11] vs. 8 [4, 13]; p = 0.06), HBI scores were observed for patients injured during the summer. Groups were similar in proportion exercising (16% vs 17%) and endorsing sleep problems (29% vs 31%). After adjustments, sustaining a concussion during the summer predicted total (ß=-3.43; 95%CI = -6.50, -0.36; p = 0.029) and cognitive (ß = -2.29; 95%CI = -4.22, -0.36; p = 0.02), but not somatic (ß=-1.46; 95%CI = -2.84, -0.08; p = 0.04), symptom severity. CONCLUSION: Pediatric patients with concussion may present with greater cognitive symptoms during the school year, compared to summer months.

Subclinical, long-term psychological symptoms following sport-related concussion: are athletes more depressed than we think?

INTRODUCTION: In adolescent and collegiate athletes with sport-related concussion (SRC), we sought to evaluate the prevalence and predictors of long-term psychological symptoms. METHODS: A cohort study was conducted of athletes 12-24-year-old diagnosed with SRC between November 2017 and April 2022. Athletes/proxies were interviewed on psychological symptoms (i.e. anger, anxiety, depression, and stress). Participants who scored ≥75th percentile on one or more PROMIS (Patient-Reported Outcomes Measurement System) measures were operationalized to have subclinical, long-term psychological symptoms. Uni/multivariable regressions were used. RESULTS: Of 96 participants (60.4% male), the average age was 16.6 ± 2.6 years. The median time from concussion to interview was 286 days (IQR: 247-420). A total of 36.5% athletes demonstrated subclinical, long-term psychological symptoms. Univariate logistic regression revealed significant predictors of these symptoms: history of psychiatric disorder (OR = 7.42 95% CI 1.37,40.09), substance use (OR = 4.65 95% CI 1.15,18.81), new medical diagnosis since concussion (OR = 3.43 95% CI 1.27,9.26), amnesia (OR = 3.42 95% CI 1.02,11.41), other orthopedic injuries since concussion (OR = 3.11 95% CI 1.18,8.21), age (OR = 1.24 95% CI 1.03,1.48), days to return-to-play (OR = 1.02 95% CI 1.00,1.03), and psychiatric medication use (OR = 0.19 95% CI 0.05,0.74). Multivariable model revealed significant predictors: orthopedic injuries (OR = 5.17 95% CI 1.12,24.00) and return-to-play (OR = 1.02 95% CI 1.00,1.04). CONCLUSIONS: Approximately one in three athletes endorsed long-term psychological symptoms. Predictors of these symptoms included orthopedic injuries and delayed RTP.

Exploring the association between cognitive activity and symptom resolution following concussion in adolescents aged 11-17 years.

OBJECTIVE: As opposed to postconcussion physical activity, the potential influence of cognitive activity on concussion recovery is not well characterised. This study evaluated the intensity and duration of daily cognitive activity reported by adolescents following concussion and examined the associations between these daily cognitive activities and postconcussion symptom duration. METHODS: This study prospectively enrolled adolescents aged 11-17 years with a physician-confirmed concussion diagnosis within 72 hours of injury from the emergency department and affiliated concussion clinics. Participants were followed daily until symptom resolution or a maximum of 45 days postinjury to record their daily cognitive activity (intensity and duration) and postconcussion symptom scores. RESULTS: Participants (n=83) sustained their concussion mostly during sports (84%), had a mean age of 14.2 years, and were primarily male (65%) and white (72%). Participants reported an average of 191 (SD=148), 166 (SD=151) and 38 (SD=61) minutes of low-intensity, moderate-intensity and high-intensity daily cognitive activity postconcussion while still being symptomatic. Every 10 standardised minutes per hour increase in moderate-intensity or high-intensity cognitive activities postconcussion was associated with a 22% greater rate of symptom resolution (adjusted hazard ratio (aHR) 1.22, 95% CI 1.01 to 1.47). Additionally, each extra day's delay in returning to school postconcussion was associated with an 8% lower rate of symptom resolution (aHR 0.92, 95% CI 0.85 to 0.99). CONCLUSION: In adolescents with concussion, more moderate-high intensity cognitive activity is associated with faster symptom resolution, and a delayed return to school is associated with slower symptom resolution. However, these relationships may be bidirectional and do not necessarily imply causality. Randomised controlled trials are needed to determine if exposure to early cognitive activity can promote concussion recovery in adolescents.

Early Identification and Management of Cervical Impairments in Pediatric Patients With Concussion May Reduce Risk of Delayed Recovery.

OBJECTIVE: Previous research, including high-quality systematic reviews, has found that cervical injury, which often accompanies concussive head injury, can delay recovery from concussion. One pilot randomized controlled trial found that focused cervical assessment and appropriate intervention in children and young adults with persisting postconcussive symptoms (PPCS) improved recovery outcomes. Our sports medicine clinics adopted this approach early (within 2 weeks) in children (aged 10-18 years) after concussion. This study describes our clinical management protocol and compares the recovery trajectories in children after concussion with and without a concomitant cervical injury. DESIGN: Prospective cohort study. SETTING: Three university-affiliated outpatient sports medicine clinics from September 2016 to December 2019. PATIENTS: One-hundred thirty-four concussed children with cervical impairment (mean age 14.9 years, 65% male, and 6.2 days since concussion) were compared with 130 concussed children without cervical impairment (mean age 14.9 years, 57% male, and 6.0 days since concussion). INDEPENDENT VARIABLES: Examination findings related to the cervical spine (range of motion, cervical spasm, and cervical tenderness). MAIN OUTCOME MEASURES: Recovery time (measured in days), concussion symptom burden (Postconcussion Symptom Scale), and incidence of PPCS. RESULTS: Children with cervical impairment reported a higher initial symptom burden; however, there were no differences in recovery time (33.65 [28.20-39.09] days vs 35.98 [27.50-44.45] days, P = 0.651) or incidence of PPCS (40.0% vs 34.3%, P = 0.340). CONCLUSIONS: We conclude that within this pediatric population, early identification and management of cervical injuries concomitant with concussion may reduce the risk of delayed recovery.

Menstrual Cycle Patterns After Concussion in Adolescent Patients.

OBJECTIVE: To describe menstrual cycle patterns in adolescents with concussion and investigate whether menstrual cycle phase at injury influenced postconcussion cycle pattern changes or concussion symptoms. STUDY DESIGN: Data were collected prospectively from patients aged 13-18 years presenting to a specialty care concussion clinic for an initial visit (≤28 days postconcussion) and, if clinically indicated, at a follow-up visit 3-4 months postinjury. Primary outcomes included menstrual cycle pattern change since injury (change/no change), menstrual cycle phase at time of injury (calculated using date of last period before injury), and symptom endorsement and severity, measured by Post-Concussion Symptom Inventory (PCSI). Fisher exact tests were used to determine the association between menstrual phase at injury and change in cycle pattern. Multiple linear regression was used to determine whether menstrual phase at injury was associated with PCSI endorsement and symptom severity, adjusting for age. RESULTS: Five hundred twelve postmenarchal adolescents were enrolled (age 15.2 ± 1.4 years), with 111 (21.7%) returning for follow-up at 3-4 months. Menstrual pattern change was reported by 4% of patients at initial visit and 10.8% of patients at follow-up. At 3-4 months, menstrual phase at injury was not associated with menstrual cycle changes (P = .40) but was associated with endorsement of concussion symptoms on the PCSI (P = .01). CONCLUSIONS: At 3-4 months' postconcussion, 1 in 10 adolescents experienced a change in menses. Menstrual cycle phase at injury was associated with postconcussion symptom endorsement. Leveraging a large sample of postconcussion menstrual patterns, this study represents foundational data regarding potential menstrual cycle effects of concussion in female adolescents.

Diffusion Imaging of Sport-related Repetitive Head Impacts-A Systematic Review.

Repetitive head impacts (RHI) are commonly observed in athletes participating in contact sports such as American football, ice hockey, and soccer. RHI usually do not result in acute symptoms and are therefore often referred to as subclinical or "subconcussive" head impacts. Epidemiological studies report an association between exposure to RHI and an increased risk for the development of neurodegenerative diseases. Diffusion magnetic resonance imaging (dMRI) has emerged as particularly promising for the detection of subtle alterations in brain microstructure following exposure to sport-related RHI. The purpose of this study was to perform a systematic review of studies investigating the effects of exposure to RHI on brain microstructure using dMRI. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to determine studies that met inclusion and exclusion criteria across three databases. Seventeen studies were identified and critically evaluated. Results from these studies suggest an association between white matter alterations and RHI exposure in youth and young adult athletes. The most consistent finding across studies was lower or decreased fractional anisotropy (FA), a measure of the directionality of the diffusion of water molecules, associated with greater exposure to sport-related RHI. Whether decreased FA is associated with functional outcome (e.g., cognition) in those exposed to RHI is yet to be determined. This review further identified areas of importance for future research to increase the diagnostic and prognostic value of dMRI in RHI and to improve our understanding of the effects of RHI on brain physiology and microstructure.

Lower systemic nitric oxide bioactivity, cerebral hypoperfusion and accelerated cognitive decline in formerly concussed retired rugby union players.

NEW FINDINGS: What is the central question of this study? What are the molecular, cerebrovascular and cognitive biomarkers of retired rugby union players with concussion history? What is the main finding and its importance? Retired rugby players compared with matched controls exhibited lower systemic nitric oxide bioavailability accompanied by lower middle cerebral artery velocity and mild cognitive impairment. Retired rugby players are more susceptible to accelerated cognitive decline. ABSTRACT: Following retirement from sport, the chronic consequences of prior-recurrent contact are evident and retired rugby union players may be especially prone to accelerated cognitive decline. The present study sought to integrate molecular, cerebrovascular and cognitive biomarkers in retired rugby players with concussion history. Twenty retired rugby players aged 64 ± 5 years with three (interquartile range (IQR), 3) concussions incurred over 22 (IQR, 6) years were compared to 21 sex-, age-, cardiorespiratory fitness- and education-matched controls with no prior concussion history. Concussion symptoms and severity were assessed using the Sport Concussion Assessment Tool. Plasma/serum nitric oxide (NO) metabolites (reductive ozone-based chemiluminescence), neuron specific enolase, glial fibrillary acidic protein and neurofilament light-chain (ELISA and single molecule array) were assessed. Middle cerebral artery blood velocity (MCAv, doppler ultrasound) and reactivity to hyper/hypocapnia ( CVR CO 2 hyper ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hyper}}}$ / CVR CO 2 hypo ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hypo}}}$ ) were assessed. Cognition was determined using the Grooved Pegboard Test and Montreal Cognitive Assessment. Players exhibited persistent neurological symptoms of concussion (U = 109(41) , P = 0.007), with increased severity compared to controls (U = 77(41) , P < 0.001). Lower total NO bioactivity (U = 135(41) , P = 0.049) and lower basal MCAv were apparent in players (F2,39  = 9.344, P = 0.004). This was accompanied by mild cognitive impairment (P = 0.020, 95% CI, -3.95 to -0.34), including impaired fine-motor coordination (U = 141(41) , P = 0.021). Retired rugby union players with history of multiple concussions may be characterised by impaired molecular, cerebral haemodynamic and cognitive function compared to non-concussed, non-contact controls.

Can motor proficiency testing predict sports injuries and sports-induced bleeds in people with haemophilia?

INTRODUCTION: Predicting the risk of sports injuries and sports-induced bleeds (SIBs) in people with haemophilia (PWH) may support clinical counselling. AIM: To assess the association between motor proficiency testing and sports injuries and SIBs and to identify a specific set of tests for predicting injury risk in PWH. METHODS: In a single centre, prospective study male PWH aged 6-49 playing sports ≥1x/week were tested for running speed and agility, balance, strength and endurance. Test results below -2Z were considered poor. Sports injuries and SIBs were collected for 12 months while 7 days of physical activity (PA) for each season was registered with accelerometers. Injury risk was analysed according to test results and type of physical activity (%time walking, cycling, running). Predictive values for sports injuries and SIBs were determined. RESULTS: Data from 125 PWH (mean [± SD] age: 25 [± 12], 90% haemophilia A; 48% severe, 95% on prophylaxis, median factor level: 2.5 [IQR 0-15]IU/dl) were included. Few participants (n = 19, 15%) had poor scores. Eighty-seven sports injuries and 26 SIBs were reported. Poor scoring participants reported 11/87 sports injuries and 5/26 SIBs. The current tests were poor predictors of sports injuries (Range PPV: 0%-40%), or SIBs (PPV: 0%-20%). PA type was not associated with season (activity seasonal p values > .20) and type of PA was not associated with sports injuries or SIBs (Spearman's rho < .15). CONCLUSION: These motor proficiency- and endurance tests were unable to predict sports injuries or SIBs in PWH, potentially due to few PWH with poor results and low numbers of sports injuries and SIBs.

Clotting factor activity levels and bleeding risk in people with haemophilia playing sports.

BACKGROUND: Improved treatment options for people with haemophilia (PWH) have increased the possibilities for sports participation, but the risk of sports-induced bleeding (SIB) is still considered considerable by many. AIM: To assess sports associated injury- and bleeding risk in PWH and to assess clotting levels associated with safe sports participation. METHODS: Sports injuries and SIBs were prospectively collected for 12 months in PWH aged 6-49 without inhibitors playing sports at least once weekly. Injuries were compared according to factor levels, severity, joint health, sports risk category and sports intensity. Factor activity at the time of injury was estimated using a pharmacokinetic model. RESULTS: 125 participants aged 6-49 (41 children, 90% haemophilia A; 48% severe, 95% severe on prophylaxis) were included. Sports injuries were reported by 51 participants (41%). Most participants (62%) reported no bleeds at all and only 16% reported SIBs. SIBs were associated with factor levels at time of injury (OR: 0.93/%factor level (CI 0.88-0.99); p = .02), but not with haemophilia severity (OR: 0.62 (CI 0.20-1.89); p = .40), joint health, sports risk category or sports intensity. PWH with factor levels <10% during sports injury had a bleeding risk of 41% versus 20% in those with higher (>10%) factor levels. CONCLUSION: The results of this study emphasize the importance of clotting factor levels in prevention of bleeds. This information is vital for patient counselling and tailoring prophylactic treatment with clotting factors and non-replacement therapy.

The Effects of Attention-Deficit/Hyperactivity Disorder Symptoms on the Association between Head Impacts and Post-Season Neurocognitive and Behavioral Outcomes.

OBJECTIVE: Having attention-deficit/hyperactivity disorder (ADHD) is a risk factor for concussion that impacts concussion diagnosis and recovery. The relationship between ADHD and repetitive subconcussive head impacts on neurocognitive and behavioral outcomes is less well known. This study evaluated the role of ADHD as a moderator of the association between repetitive head impacts on neurocognitive test performance and behavioral concussion symptoms over the course of an athletic season. METHOD: Study participants included 284 male athletes aged 13-18 years who participated in high school football. Parents completed the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN) ratings about their teen athlete before the season began. Head impacts were measured using an accelerometer worn during all practices and games. Athletes and parents completed behavioral ratings of concussion symptoms and the Attention Network Task (ANT), Digital Trail Making Task (dTMT), and Cued Task Switching Task at pre- and post-season. RESULTS: Mixed model analyses indicated that neither head impacts nor ADHD symptoms were associated with post-season athlete- or parent-reported concussion symptom ratings or neurocognitive task performance. Moreover, no relationships between head impact exposure and neurocognitive or behavioral outcomes emerged when severity of pre-season ADHD symptoms was included as a moderator. CONCLUSION: Athletes' pre-season ADHD symptoms do not appear to influence behavioral or neurocognitive outcomes following a single season of competitive football competition. Results are interpreted in light of several study limitations (e.g., single season, assessment of constructs) that may have impacted this study's pattern of largely null results.

Back from the sideline, but back to baseline? A pediatric case study examining neuropsychological functioning after sustaining multiple sport-related concussions.

Most individuals recover quickly from a concussion; however, youth who sustain multiple concussions may be at risk for long-term cognitive impairments. This case study examines the neuropsychological performance of a 13-year-old malewith five head injuries. After his first concussion during study participation (fourth injury overall), several improvements were observed, likely due to practice effects, yet after sustaining another concussion <2 years later,declines were observed in visuoconstruction, verbal memory, and intellectual functioning. Across serial re-evaluation, his vocabulary knowledge declined, and fewer improvements were observed than anticipated when accounting for serial practice effects, highlighting the possible cumulative impact of multiple concussions.

Persisting Concussion Symptoms from Bodychecking: Unrecognized Toll in Boys' Ice Hockey.

OBJECTIVES: Youth hockey is a high-impact sport and can cause concussions with lasting effects. We hypothesized that important injury prevention information would accrue from longitudinal tracking of concussed players with persisting concussion symptoms (PCS). METHODS: This case series comprised 87 consecutive concussed ice hockey players aged 10-18 including 66 males and 21 females referred to our Concussion Clinic from 1997 to 2017 and followed longitudinally by clinic visits and questionnaires. RESULTS: PCS occurred in 70 (80.4%) of 87 concussed players and lasted 1-168 months in males and 3-26 months in females. Bodychecking was the most common concussion mechanism in 34 (39.1%) players and caused PCS in 24 (70.6%) with symptom duration 4.00 [2.75, 14.50] months (median [IQR]). The remaining 53 players had other concussion mechanisms with PCS in 86.8% (p = 0.113) with similar duration (p = 0.848). CONCLUSIONS: This is the first longitudinal study of concussion with PCS in youth hockey and showed that symptoms can last for several years. Bodychecking was the commonest mechanism of prolonged disability from concussion in boys and girls' hockey with average PCS duration of 12.3 months but several years in some players. The injury prevention message is to raise the age of permitted bodychecking to 18 in boys' hockey from age 13 to 14 where it is currently. In this case series, this change could have prevented the majority of the bodycheck concussions and several years of suffering from PCS and is strong evidence for raising the permitted age for bodychecking in boys' ice hockey to age 18.