High altitude modulates concussion incidence, severity, and recovery in young athletes.

BACKGROUND: High altitude may affect concussion, but prior studies are limited . We tested whether high altitude affects sport-related concussion (SRC) incidence, severity, and recovery. METHODS: Twenty-five thousand eight hundred fifteen baseline and post-injury Immediate Post-Concussion Assessment and Cognitive Testing results were compiled from Florida and Colorado, low (27 m or 62 m) and high (1,640 m or 1,991 m) altitude locations, respectively. Incidence, severity, and recovery of injury were compared between altitudes. RESULTS: High altitude was associated with increased suspected concussion incidence (adjusted OR, 2.04 [95% CI, 1.86 to 2.24];P < .0001). However, high altitude was associated with lower concussion severity measured by Severity Index (SI) (adjusted OR, 0.42 [95% CI, 0.37 to 0.49];P < .0001). High altitude was associated with decreased recovery from post-concussive symptoms in the migraine (ß, -2.72 [95% CI, -3.31 to -2.13]; P < .0001), cognitive (ß, -1.88 [95% CI, -2.40 to -1.36]; P < .0001), and sleep symptom clusters (ß, -0.30 [95% CI, -0.52 to -0.08]; P = .007). Athletes with initial SI≥8 showed prolonged neurocognitive dysfunction at high altitude (HR, 1.38 [95% CI, 1.06 to 1.81]; P = .02). CONCLUSIONS: High altitude was associated with increased suspected concussions and prolonged recovery but less severe initial injury.

Combined Treatment of High-Flow Scalp Arteriovenous Malformations.

INTRODUCTION: Appropriate treatment of scalp arteriovenous malformations (SAVMs) remains largely unclear given the rarity of reported cases. This single-institution case series presents consecutive patients with extracranial SAVMs and long-term follow up.The primary aim of this study was to review treatment decisions, evaluate clinical outcomes, and compare our experience to available literature in order to better understand SAVMs and improve future outcomes. MATERIALS AND METHODS: A retrospective review of consecutive patients with extracranial SAVMs between January 2015 and December 2019 was performed. Treatment factors of interest included embolization method, embolic agents, and decision to proceed with surgical resection. Relevant clinical outcomes included recurrence rates, cure rates, and complications. RESULTS: Seven patients were included in the present series. Satisfactory outcomes were ultimately achieved for all 7 patients using embolization with or without combined surgical resection. Embolizations performed in combination with resection were curative in 4 of 4 cases (100%). Embolizations performed without resection were curative in 0 of 4 cases (0%), satisfactory in 2 of 4 cases (50%), and unsatisfactory in 2 of 4 cases (50%). DISCUSSION: All SAVM patients in this series were treated satisfactorily using embolization with or without operative resection. This study strongly suggests that embolization combined with surgical resection during the same admission yields the best treatment outcomes for SAVMs, specifically demonstrating lower rates of recurrence and embolization-related complications. Decisions on whether or not to proceed with resection should be made by the interventional radiologist, the plastic surgeon, and the patient together.

Mobile Interventional Stroke Teams Improve Outcomes in the Early Time Window for Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Endovascular thrombectomy for large vessel occlusion stroke is a time-sensitive intervention. The use of a Mobile Interventional Stroke Team (MIST) traveling to Thrombectomy Capable Stroke Centers to perform endovascular thrombectomy has been shown to be significantly faster with improved discharge outcomes, as compared with the drip-and-ship (DS) model. The effect of the MIST model stratified by time of presentation has yet to be studied. We hypothesize that patients who present in the early window (last known well of ≤6 hours) will have better clinical outcomes in the MIST model. METHODS: The NYC MIST Trial and a prospectively collected stroke database were assessed for patients undergoing endovascular thrombectomy from January 2017 to February 2020. Patients presenting in early and late time windows were analyzed separately. The primary end point was the proportion with a good outcome (modified Rankin Scale score of 0-2) at 90 days. Secondary end points included discharge National Institutes of Health Stroke Scale and modified Rankin Scale. RESULTS: Among 561 cases, 226 patients fit inclusion criteria and were categorized into MIST and DS cohorts. Exclusion criteria included a baseline modified Rankin Scale score of >2, inpatient status, or fluctuating exams. In the early window, 54% (40/74) had a good 90-day outcome in the MIST model, as compared with 28% (24/86) in the DS model (P<0.01). In the late window, outcomes were similar (35% versus 41%; P=0.77). The median National Institutes of Health Stroke Scale at discharge was 5.0 and 12.0 in the early window (P<0.01) and 5.0 and 11.0 in the late window (P=0.11) in the MIST and DS models, respectively. The early window discharge modified Rankin Scale was significantly better in the MIST model (P<0.01) and similar in the late window (P=0.41). CONCLUSIONS: The MIST model in the early time window results in better 90-day outcomes compared with the DS model. This may be due to the MIST capturing high-risk fast progressors at an earlier time point. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03048292.

Real-World Experience with Artificial Intelligence-Based Triage in Transferred Large Vessel Occlusion Stroke Patients.

BACKGROUND AND PURPOSE: Randomized controlled trials have demonstrated the importance of time to endovascular therapy (EVT) in clinical outcomes in large vessel occlusion (LVO) acute ischemic stroke. Delays to treatment are particularly prevalent when patients require a transfer from hospitals without EVT capability onsite. A computer-aided triage system, Viz LVO, has the potential to streamline workflows. This platform includes an image viewer, a communication system, and an artificial intelligence (AI) algorithm that automatically identifies suspected LVO strokes on CTA imaging and rapidly triggers alerts. We hypothesize that the Viz application will decrease time-to-treatment, leading to improved clinical outcomes. METHODS: A retrospective analysis of a prospectively maintained database was assessed for patients who presented to a stroke center currently utilizing Viz LVO and underwent EVT following transfer for LVO stroke between July 2018 and March 2020. Time intervals and clinical outcomes were compared for 55 patients divided into pre- and post-Viz cohorts. RESULTS: The median initial door-to-neuroendovascular team (NT) notification time interval was significantly faster (25.0 min [IQR = 12.0] vs. 40.0 min [IQR = 61.0]; p = 0.01) with less variation (p < 0.05) following Viz LVO implementation. The median initial door-to-skin puncture time interval was 25 min shorter in the post-Viz cohort, although this was not statistically significant (p = 0.15). CONCLUSIONS: Preliminary results have shown that Viz LVO implementation is associated with earlier, more consistent NT notification times. This application can serve as an early warning system and a failsafe to ensure that no LVO is left behind.

Effects of Recurrent Mild Traumatic Brain Injuries on Incidence, Severity, and Recovery of Concussion in Young Student-Athletes.

OBJECTIVE: To examine the effects of recurrent concussions on the incidence, severity, and recovery of significant neurocognitive dysfunction (SND) in young athletes. SETTING: Various US youth sports organizations that utilize Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) for baseline and postinjury concussion testing. PARTICIPANTS: Data from 11 563 ImPACT baseline evaluations of US student-athletes aged 12 to 22 years were separated into 2 cohorts: subjects reporting 2 or more previous concussions (PC; n = 976 baseline evaluations) at baseline and a control group reporting zero previous concussions (CT; n = 7743 baseline evaluations). Subjects reporting 1 prior concussion were excluded. DESIGN: Retrospective cohort. MAIN MEASURES: Differences in SND incidence, severity, and recovery between the 2 cohorts were assessed using chi-squared tests, t tests, survival analyses, and multivariate regressions. RESULTS: The PC cohort had a higher incidence of head injury leading to ImPACT (436.7 per 1000 person-years vs 194.4 per 1000 person-years, P < .0001) and a higher incidence of SND (140.4 vs 71.8, P < .0001) than controls. However, the Severity Index (SI) demonstrated that SND severity was lower in the PC group (7.55 vs 8.59, P = .04). Adjusted analyses similarly demonstrated that the PC cohort had increased SND incidence (odds ratio = 1.93; 95% CI, 1.61 to 2.31; P < .0001), decreased SI (ß = -1.37; 95% CI, -2.40 to -0.34; P = .009), and equivalent recovery (hazard ratio = 0.98; 95% CI, 0.76 to 1.72; P = .90). CONCLUSION: Participants with a history of concussion have a higher incidence of SND but present with lower severity SND, which may be a result of increased concussion education or symptom awareness. Recurrent concussion has no significant impact on acute neurocognitive recovery. Together, these results provide evidence against the supposition that a history of concussion increases the severity of future SND.

Trends in Peripheral Nerve Epidemiology and Reconstruction: A State Database Study of Direct Repairs, Grafts, and Conduits.

BACKGROUND: Peripheral nerve injuries (PNIs) are most commonly treated with direct nerve repair procedures or nerve autografts. However, recent advancements in synthetic and vein conduits have led to their increased utilization. The present study quantifies the incidence of these procedures over time and geography and identifies differences in complication rates, illustrating the current epidemiologic climate regarding conduit use for PNI repair. METHODS: A query was conducted using the State Ambulatory Surgery and Services Databases data from 2006 to 2011 in both Florida and California for patients undergoing nerve repair, nerve grafting, synthetic conduits, and vein conduits. Patient zip code data were analyzed to determine the geographic distribution of various types of repair. In addition, text-mining algorithms were used to identify trends in PNI-related publications. RESULTS: In the 6-year period investigated, direct nerve repair was the most frequently used procedure for PNIs. However, the utilization of direct repairs declined significantly from 2006 to 2011. Synthetic and vein conduits demonstrated a significant increase over the same period. There were significantly higher rates of complications for autologous grafts (3.3%), vein conduits (3.5%), and synthetic conduits (2.4%), as compared with direct nerve repairs (1.4%). There was a nonsignificant difference in infection rates between these types of nerve repair. CONCLUSIONS: From an epidemiologic perspective, both graft and synthetic conduit-based PNI repairs are increasing in prevalence both in clinical practice and in the academic literature. This will likely continue in the future with the development of advancements in biologic and synthetic nerve conduit PNI repair options.

Abnormal Scn1b and Fxyd1 gene expression in the pulled-through ganglionic colon may influence functional outcome in patients with Hirschsprung's disease.

PURPOSE: Smooth muscle cells are electrically coupled to ICC and PDGFRα+ cells, to regulate smooth muscle contraction. Recent studies have reported that the voltage-gated sodium channel type 1ß (Scn1b), and the chloride channel subunit, Fxyd1, are highly expressed by both ICC and PDGFRα+ cells in the mouse colon. We designed this study to investigate the expression of the Scn1b and Fxyd1 genes in the normal human colon and in HSCR. METHODS: HSCR tissue specimens (n = 6) were collected at the time of pull-through surgery, while control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 6). qRT-PCR analysis was undertaken to quantify Scn1b and Fxyd1 gene expression, and immunolabelling of Scn1b and Fxyd1 proteins were visualized using confocal microscopy. RESULTS: qRT-PCR analysis revealed significant downregulation of Scn1b and Fxyd1 genes in both aganglionic and ganglionic HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a reduction in Scn1b and Fxyd1 protein expression in both aganglionic and ganglionic HSCR colon compared to controls. CONCLUSION: Scn1b and Fxyd1 expression was significantly downregulated in HSCR colon. These results add to mounting evidence suggesting that the pulled-through ganglionic segment of bowel in these patients is abnormal, despite the presence of ganglion cells.

Altered expression of KCNG3 and KCNG4 in Hirschsprung's disease.

PURPOSE: Voltage-gated potassium ion channels have long been implicated in gastrointestinal motility. Recent studies have highlighted the role of voltage-gated channel subfamily G member 3 (KCNG3) and 4 (KCNG4) genes in the electrical functioning of interstitial cells of Cajal and PDGFRα+ cells of the mouse colon. We designed this study to investigate KCNG3 and KCNG4 expression in the normal human colon and in Hirschsprung's disease (HSCR). METHODS: HSCR tissue specimens (n = 6) were collected at the time of pull-through surgery, while control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 6). qRT-PCR analysis was undertaken to quantify KCNG3 and KCNG4 gene expression, and immunolabelling of KCNG3 and KCNG4 proteins was visualized using confocal microscopy. RESULTS: qRT-PCR analysis revealed significant downregulation of the KCNG3 and KCNG4 genes in both aganglionic and ganglionic HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed KCNG3 and KCNG4 expression within neurons, ICC and PDGFRα+ cells of the myenteric plexus and smooth muscle layers, with a reduction in both proteins in aganglionic and ganglionic HSCR colon compared to controls. CONCLUSION: KCNG3 and KCNG4 gene expression is significantly downregulated in HSCR colon, suggesting a role for these genes in colonic motility. KCNG3 and KCNG4 downregulation within ganglionic specimens highlights the physiologically abnormal nature of this segment in HSCR patients.

Altered expression of inflammasomes in Hirschsprung's disease.

AIM OF THE STUDY: The pathogenesis of Hirschsprung's disease-associated enterocolitis (HAEC) is poorly understood. Inflammasomes are a large family of multiprotein complexes that act to mediate host immune responses to microbial infection and have a regulatory or conditioning influence on the composition of the microbiota. Inflammasomes and the apoptosis-associated speck-like protein (ASC) lead to caspase-1 activation. The activated caspase-1 promotes secretion of pro-inflammatory cytokines (IL-1ß and IL-18) from their precursors (pro-IL-1ß and pro-IL-18). Inflammasomes have been implicated in a host of inflammatory disorders. Among the inflammasomes, NLRP3, NLRP12 and NLRC4 are the most widely investigated. Knock-out mice models of inflammasomes NLRP3, NLRP12, NLRC4, caspase-1 and ASC are reported to have higher susceptibility to experimental colitis. The purpose of this study was to investigate the expression of NLRP3, NLRP12, NLRC4, caspase-1, ASC, pro-IL-1ß and pro-IL-18 in the bowel specimens from patients with HSCR and controls. METHODS: Pulled-through colonic specimens were collected from HSCR patients (n = 6) and healthy controls from the proximal colostomy of children with anorectal malformations (n = 6). The gene expression of NLRP3, NLRP12, NLRC4, caspase-1, ASC, pro-IL-1ß and pro-IL-18 was assessed using qPCR. The protein distribution was assessed using immunofluorescence and confocal microscopy. MAIN RESULTS: qRT-PCR analysis revealed that NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß gene expressions was significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR compared to controls. Confocal microscopy revealed a markedly decreased expression of NLRP3, NLRP12, NLRC4 and ASC protein in the colonic epithelium of aganglionic and ganglionic bowel of patients with HSCR compared to controls. CONCLUSIONS: To our knowledge, this is the first study analyzing NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß gene expressions in patients with HSCR. Decreased expression of NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß in the aganglionic and ganglionic bowel may increase susceptibility of HSCR patients to develop HAEC.

AI software detection of large vessel occlusion stroke on CT angiography: a real-world prospective diagnostic test accuracy study.

BACKGROUND: Artificial intelligence (AI) software is increasingly applied in stroke diagnostics. However, the actual performance of AI tools for identifying large vessel occlusion (LVO) stroke in real time in a real-world setting has not been fully studied. OBJECTIVE: To determine the accuracy of AI software in a real-world, three-tiered multihospital stroke network. METHODS: All consecutive head and neck CT angiography (CTA) scans performed during stroke codes and run through an AI software engine (Viz LVO) between May 2019 and October 2020 were prospectively collected. CTA readings by radiologists served as the clinical reference standard test and Viz LVO output served as the index test. Accuracy metrics were calculated. RESULTS: Of a total of 1822 CTAs performed, 190 occlusions were identified; 142 of which were internal carotid artery terminus (ICA-T), middle cerebral artery M1, or M2 locations. Accuracy metrics were analyzed for two different groups: ICA-T and M1 ±M2. For the ICA-T/M1 versus the ICA-T/M1/M2 group, sensitivity was 93.8% vs 74.6%, specificity was 91.1% vs 91.1%, negative predictive value was 99.7% vs 97.6%, accuracy was 91.2% vs 89.8%, and area under the curve was 0.95 vs 0.86, respectively. Detection rates for ICA-T, M1, and M2 occlusions were 100%, 93%, and 49%, respectively. As expected, the algorithm offered better detection rates for proximal occlusions than for mid/distal M2 occlusions (58% vs 28%, p=0.03). CONCLUSIONS: These accuracy metrics support Viz LVO as a useful adjunct tool in stroke diagnostics. Fast and accurate diagnosis with high negative predictive value mitigates missing potentially salvageable patients.

Novel Grading Scales for Static and Flexion-Extension Magnetic Resonance Imaging in Patients with Cervical Spondylotic Myelopathy.

BACKGROUND: Flexion-extension magnetic resonance imaging (MRI) has potential to identify cervical pathology not detectable on conventional static MRI. Our study evaluated standard quantitative and novel subjective grading scales for assessing the severity of cervical spondylotic myelopathy in dynamic sagittal MRI as well as in static axial and sagittal images. METHODS: Forty-five patients underwent both conventional and flexion-extension MRI prior to anterior cervical discectomy and fusion from C4 through C7. In addition to measuring Cobb angles and cervical canal diameter, grading scales were developed for assessment of vertebral body translation, loss of disc height, change in disc contour, deformation of cord contour, and cord edema. Data were collected at all levels from C2-C3 through C7-T1. Variations in measurements between cervical levels and from flexion through neutral to extension were assessed using Mann-Whitney, Kruskal-Wallis, and two-way ANOVA tests. RESULTS: Cervical canal diameter, vertebral translation, and posterior disc opening changed significantly from flexion to neutral to extension positions (P < 0.01). When comparing operative versus nonoperative cervical levels, significant differences were found when measuring sagittal cervical canal dimensions, vertebral translation, and posterior disc opening (P < 0.01). Degenerative loss of disc height, disc dehydration, deformation of ventral cord contour, and cord edema were all significantly increased at operative levels versus nonoperative levels (P < 0.01). CONCLUSIONS: Flexion-extension MRI demonstrated significant changes not available from conventional MRI. Subjective scales for assessing degenerative changes were significantly more severe at levels with operative cervical spondylotic myelopathy. The utility of these scales for planning surgical intervention at specific and adjacent levels is currently under investigation.

Time from image acquisition to endovascular team notification: a new target for enhancing acute stroke workflow.

OBJECTIVE: To quantify the time between initial image acquisition (CT angiography (CTA)) and notification of the neuroendovascular surgery (NES) team, a potentially high yield time window to target for optimization of endovascular thrombectomy (ET) treatment times. METHODS: We reviewed our multihospital database for all patients with a stroke with emergent large vessel occlusion treated with ET between January 1, 2017 and August 5, 2020. We dichotomized patients into rapid (≤20 min) and delayed (>20 min) notification times and analyzed treatment characteristics and outcomes. RESULTS: Of 367 patients with ELVO undergoing ET for whom notification data were available, the median time from CTA to NES team notification was 24 min (IQR 12-47). The median total treatment time was 180 min (IQR 129-252). The median times from CTA to NES team notification for rapid (n=163) and delayed (n=204) cohorts were 11 (IQR 6-15) and 43 (IQR 30-80) min, respectively (p<0.001). The median overall times to reperfusion were 134 min (IQR 103-179) and 213 min (IQR 172-291), respectively (p<0.001). The delayed patients had a significantly lower National Institutes of Health Stroke Scale (NIHSS) score on presentation (15 (IQR 9-20) vs 16 (IQR 11-22), p=0.03), were younger (70 (IQR 60-79) vs 77 (IQR 64-85), p<0.001), and more often presented with posterior circulation occlusion (16.7% vs 7.4%, p<0.01). The group with rapid notification time had a statistically larger median improvement in NIHSS score from admission to discharge (6 (IQR 0.5-14) vs 5 (IQR 0.5-10), p=0.04). CONCLUSIONS: Time delays from initial CTA acquisition to NES team notification can prevent expedient treatment with ET. Process improvements and automated stroke detection on imaging with automated notification of the NES team may ultimately improve time to reperfusion.

Sport Contact Level Affects Post-Concussion Neurocognitive Performance in Young Athletes.

OBJECTIVE: Contact level affects the incidence of sports-related concussion. However, the effects of contact level on injury severity and recovery are less clear and are the focus of this study. METHOD: Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) for athletes aged 12-22 was performed at baseline (n = 10,907 for 7,058 athletes), after suspected concussion determined by physicians or athletic trainers (n = 5,062 for 4,419 athletes), and during follow-up visits (n = 3,264 for 2,098 athletes). Athletes played contact/collision (CC), limited contact (LC), and noncontact (NC) sports. Injury incidence, severity, and recovery were measured using raw and change from baseline neurocognitive test scores. Comparisons between groups used univariate analysis and multivariable regression controlling for demographic variables. RESULTS: Compared to CC athletes, LC and NC athletes showed decreased suspected concussion incidence. At initial post-injury testing, all neurocognitive test scores were similar between groups except changes from baseline for processing speed were improved for LC compared to CC athletes. Upon follow-up testing, raw neurocognitive scores were better for NC compared to the contact collision athletes in verbal memory, processing speed, total symptom score, migraine cluster, cognitive cluster, and neuropsychiatric cluster scores. For change from baseline scores, LC athletes exhibited better performance on verbal memory, processing speed, and reaction time but also showed higher neuropsychiatric scores than CC athletes. CONCLUSION: Neurocognitive scores between contact levels were similar at the first post-injury test. However, follow up showed many improved scores and symptoms for limited and NC sports compared to CC sports, which may indicate faster recovery.

Impact of Psychiatric Illnesses and Selective Serotonin Reuptake Inhibitor Medications on Baseline Neurocognitive Testing.

INTRODUCTION: Neurocognitive tests are an integral component of sport-related concussion (SRC) workup. A history of psychiatric illness (HPI) is common among young athletes. Investigations of factors that influence athletes' baseline neurocognitive function are crucial for an accurate assessment of SRC. OBJECTIVE: In this study, we aim to elucidate the effect of HPI and selective-serotonin reuptake inhibitor (SSRI) medication use on baseline neurocognitive performance in young athletes. METHODS: We conducted a retrospective cross-sectional study of Immediate Post-Concussion Assessment and Cognitive Testing assessments. A total of 268 athletes with HPI and a control group of 6,364 athletes were included. The outcomes were total symptom score based on post-concussion symptom scale, verbal memory, visual memory, visual motor, reaction time, and impulse control scores with self-reported HPI status and SSRI use. RESULTS: Athletes with HPI had an elevated symptom score in both univariate analysis (p < .0001) and multivariate analysis (p < .0001). HPI influence on visual memory score was not robust to multivariate analysis (p = .24). Athletes with HPI who reported SSRI medication use had the same baseline neurocognitive performance as other athletes with HPI. HPI influences athletes' baseline neurocognitive performance by elevating symptom scores. HPI does not alter any of the objective neurocognitive composite scores in contrast to previous work. CONCLUSIONS: Clinicians should consider the impact of HPI on baseline neurocognitive performance during the assessment of a suspected SRC. Additional research is required to bolster our findings on SSRI use and ascertain the effects of other drug classes on baseline neurocognitive performance.

Evaluation of differences across age groups in the incidence, severity, and recovery of concussion in adolescent student-athletes from 2009 to 2019.

OBJECTIVE: Concussion incidence is known to be highest in children and adolescents; however, there is conflicting evidence about the effect of age on concussion risk and recovery within the adolescent age range. The heterogeneity of results may be partially due to the use of age groupings based on convenience, making comparisons across studies difficult. This study evaluated the independent effect of age on concussion incidence, severity, and recovery in student-athletes aged 12-18 years using cluster analysis to define groupings. METHODS: Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores of 11,403 baseline tests and 4922 postinjury tests were used to calculate the incidence rates for adolescent student-athletes grouped into 3 age bands (12-13, 14-15, and 16-18 years of age) on the basis of clustering analysis. The recently created Severity Index was used to compare concussion severity between groups. Follow-up tests for subjects who sustained a concussion were used to evaluate recovery time. The chi-square test and 1-way ANOVA were used to compare differences in demographic characteristics and concussion incidence, severity, and recovery. Multivariable logistic and linear regressions were used to evaluate the independent effects of age on concussion incidence and severity, respectively. Multivariable Cox hazard regression was used to evaluate differences in recovery time. Further analyses were conducted to directly compare findings across studies on the basis of the age groupings used in prior studies. RESULTS: Multivariable regression analyses demonstrated that the 14- to 15-year-old age group had a significantly higher concussion incidence than both the 12- to 13-year-old (14- to 15-year-old group vs 12- to 13-year-old group, OR 1.57, 95% CI 1.16-2.17, p = 0.005) and 16- to 18-year-old (16- to 18-year-old group vs 14- to 15-year-old group, OR 0.79, 95% CI 0.69-0.91, p = 0.0008) age groups. There was no difference in incidence between the 12- to 13-year-old and 16- to 18-year-old groups (16- to 18-year group vs 12- to 13-year group, OR 1.26, 95% CI 0.93-1.72, p = 0.15). There were also no differences in concussion severity or recovery between any groups. CONCLUSIONS: This study found that concussion incidence was higher during mid-adolescence than early and late adolescence, suggesting a U-shaped relationship between age and concussion risk over the course of adolescence. Age had no independent effect on concussion severity or recovery in the 12- to 13-, 14- to 15-, and 16- to 18-year-old groups. Further analysis of the various age groups revealed that results may vary significantly with minor changes to groupings, which may explain the divergent results in the current literature on this topic. Thus, caution should be taken when interpreting the results of this and all similar studies, especially when groupings are based on convenience.

Incidence and Severity of Concussions Among Young Soccer Players Based on Age, Sex, and Player Position.

BACKGROUND: Previously studied risk factors for sports-related concussion in soccer players include sex, age, and player position. However, prior studies were limited in number, they reported conflicting results, and most did not assess initial concussion severity. PURPOSE/HYPOTHESIS: The purpose of this study was to conduct an in-depth analysis of soccer players across key demographic groups (sex, age, position) for both concussion incidence and severity. It was hypothesized that concussion incidence and severity would be higher among male players, players aged ≥17 years, and goalkeepers. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The authors analyzed baseline and postinjury ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing) scores for athletes aged 12 to 22 years between July 2009 and June 2019. Players were assigned to an age group based on when they had their most recent baseline test. Concussion incidence and concussion severity index were compared using t tests and multivariate logistic regression. RESULTS: For 1189 individuals who reported soccer as their primary sport, 1032 contributed 1754 baseline ImPACT tests (some individuals had multiple baseline tests), whereas 445 individuals were suspected of sustaining a concussion and then referred for a postinjury 1 test. Of these players, 254 (24.6%) had both a baseline and a postinjury test and were analyzed for concussion severity. Linear regression showed that forwards had a lower incidence of ImPACT-proxied concussions than goalkeepers had (P = .008). Female players had a significantly higher incidence of ImPACT concussions compared with male players (mean, 0.07 [female] vs 0.04 [male] concussions per person-year; P = .05). Players in the ≥17-year age group had a higher incidence of ImPACT concussions than players in the 15- to 16-year age group (P = .04), although the 15- to 16-year age group had more severe concussions than the ≥17-year age group (mean severity index, 2.91 [age 15-16 years] vs 1.73 [age ≥17 years]; P = .001). CONCLUSION: Female soccer players experienced a higher incidence of concussion than did male players, and goalkeepers experienced a greater incidence of ImPACT concussions than did forwards. Players of both sexes and all positions in the 15- to 16-year age group showed increased initial concussion severity compared with the ≥17-year age group, despite a lower comparative incidence of ImPACT concussions. Further study is needed to understand whether sex and player position affect concussion severity.

Concussion Incidence and Recovery Among Youth Athletes With ADHD Taking Stimulant-Based Therapy.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) may affect concussion risk and recovery in youth athletes. PURPOSE: To evaluate the association between incidence of concussion and postinjury recovery of symptoms and neurocognitive dysfunction among youth athletes with ADHD and differential stimulant use. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: From 2009 to 2019, the authors administered the Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) to youth athletes at the beginning of each season. Throughout the season, athletes with concussions were examined and readministered the ImPACT both postinjury and again 7 days after the postinjury administration. These athletes (N = 7453) were divided into those with ADHD on stimulant-based therapy (ADHD+meds; n = 167), those with ADHD not on stimulant-based therapy (ADHD-only; n = 354), and those with no ADHD (non-ADHD; n = 6932). Recovery of neurocognitive dysfunction at postinjury and follow-up was calculated using the ImPACT symptom score, verbal memory, visual memory, visual motor skills, and reaction time (calculated as standardized deviations from baseline). Univariate results were confirmed with multivariate analysis. RESULTS: The ADHD+meds cohort had a lower incidence of concussion (37.3 concussions per 100 patient-years) compared with the ADHD-only group (57.0 concussions per 100 patient-years) (odds ratio [OR], 0.51 [95% CI, 0.37-0.71]; P < .0001) and non-ADHD group (52.8 concussions per 100 patient-years) (OR, 0.50 [95% CI, 0.37-0.67]; P < .0001). At postinjury, ImPACT scores were elevated from baseline to a similar extent in the ADHD+meds cohort compared with the other 2 groups. By follow-up, however, deviations from baseline were lower among the ADHD+meds group compared with the non-ADHD group in verbal memory (OR, 0.46 [95% CI, 0.28-0.76]; P = .002), visual memory (OR, 0.27 [95% CI, 0.10-0.66]; P = .005), and visual motor skills (OR, 0.58 [95% CI, 0.33-0.99]; P = .048). The deviation at follow-up was also lower among the ADHD+meds group compared with the ADHD-only group in visual memory (OR, 0.56 [95% CI, 0.33-0.96]; P = .04) and visual motor skills (OR, 0.42 [95% CI, 0.22-0.81]; P = .01). CONCLUSION: Stimulant use among youth athletes with ADHD was independently associated with reduced incidence for concussion and lower deviation from baseline in verbal memory, visual memory, and visual motor skills at 7 days postconcussion, suggesting lower neurocognitive impairment at follow-up in this group versus their peers.

Nonsteroidal anti-inflammatory drug use and concussions in adolescent athletes: incidence, severity, and recovery.

OBJECTIVE: Given concerns about the potential long-term effects of concussion in young athletes, concussion prevention has become a major focus for amateur sports leagues. Athletes have been known to frequently use anti-inflammatory medications to manage injuries, expedite return to play, and treat concussion symptoms. However, the effects of baseline nonsteroidal anti-inflammatory drug (NSAID) use on the susceptibility to head injury and concussion remain unclear. This study aims to assess the effects of preinjury NSAID use on concussion incidence, severity, and recovery in young athletes. METHODS: Data from 25,815 ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing) tests were obtained through a research agreement with ImPACT Applications Inc. Subjects ranged in age from 12 to 22 years old. Those who reported NSAID use at baseline were assigned to one (anti-inflammatory [AI]) cohort, whereas all others were assigned to the control (CT) cohort. Differences in head trauma and concussion incidence, severity, and recovery were assessed using chi-square tests, unpaired t-tests, and Kaplan-Meier plots. RESULTS: The CT cohort comprised a higher percentage (p < 0.0001) of males (66.30%) than the AI cohort (44.16%) and had a significantly greater portion of athletes who played football (p = 0.004). However, no statistically significant differences were found between the two cohorts in terms of the incidence of head trauma (CT = 0.489, AI = 0.500, p = 0.9219), concussion incidence (CT = 0.175, AI = 0.169, p = 0.7201), injury severity, or median concussion recovery time (CT = 8, AI = 8, p = 0.6416). In a multivariable analysis controlling for baseline differences between the cohorts, no association was found between NSAID use and concussion incidence or severity. CONCLUSIONS: In this analysis, the authors found no evidence that preinjury use of NSAIDs affects concussion risk in adolescent athletes. They also found no indication that preinjury NSAID use affects the severity of initial injury presentation or concussion recovery.

Sex-Related Differences in the Incidence, Severity, and Recovery of Concussion in Adolescent Student-Athletes Between 2009 and 2019.

BACKGROUND: The sex of an athlete is thought to modulate concussion incidence; however, the effects of sex on concussion severity and recovery are less clear. PURPOSE: To evaluate sex differences in concussion severity and recovery using a large, heterogeneous sample of young student-athletes with the goal of understanding how sex affects concussion outcomes in young athletes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The Immediate Post-Concussion Assessment and Cognitive Testing results of 11,563 baseline and 5216 postinjury tests were used to calculate the incidence of concussion of adolescent male and female student-athletes ages 12 to 22 years (median, 15 years). The postinjury tests of 3465 male and 1751 female student-athletes evaluated for concussion or head trauma were used to assess differences in the Severity Index (SI) and recovery. Chi-square tests and t tests were used to compare differences in demographic characteristics, incidence, and SI between the 2 cohorts. Multivariable linear, logistic, and Cox proportional hazards regressions were used to control for differences between cohorts in analyses of incidence, SI, and recovery. RESULTS: When we controlled for demographic differences, female participants had higher odds of concussion (odds ratio, 1.62; 95% CI, 1.40-1.86; P < .0001) and higher SI after concussion (ß = 0.67; 95% CI, 0.02-1.32; P = .04). This discrepancy in SI was a result of differences in Symptom (2.40 vs 2.94; P < .0001) and Processing Speed (0.91 vs 1.06; P = .01) composite scores between male and female participants, respectively. We found no effect of sex on time to recovery when controlling for initial concussion SI (hazard ratio, 0.94; 95% CI, 0.78-1.12; P = .48). CONCLUSION: Using large, multisport cohorts, this study provides evidence that female athletes are at higher risk for more concussions and these concussions are more severe, but male and female athletes have similar recovery times when the analysis controls for initial concussion SI.

Incidence of concussion and recovery of neurocognitive dysfunction on ImPACT assessment among youth athletes with premorbid depression or anxiety taking antidepressants.

OBJECTIVE: Concussions in youth sports comprise an estimated 1.6-3.8 million annual injuries in the US. Sex, age, and attention-deficit hyperactivity disorder (ADHD) have been identified as salient risk factors for concussion. This study seeks to evaluate the role of premorbid depression or anxiety (DA), with or without antidepressant use, on the incidence of concussion and the recovery of symptoms and neurocognitive dysfunction after concussion. METHODS: Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) was administered to 7453 youth athletes at baseline. Throughout the season, concussions were examined by physicians and athletic trainers, followed by readministration of ImPACT postinjury (PI) and again at follow-up, a median of 7 days PI. Individuals were divided into three categories: 1) unmedicated athletes with DA (DA-only, n = 315), athletes taking antidepressants (DA-meds, n = 81), and those without DA or antidepressant use (non-DA, n = 7039). Concussion incidence was calculated as the total number of concussions per total number of patient-years. The recovery of neurocognitive measures PI was calculated as standardized deviations from baseline to PI and then follow-up in the 5 composite ImPACT scores: symptom score, verbal memory, visual memory, visual motor skills, and reaction time. Univariate results were confirmed with multivariate analysis. RESULTS: There was no difference in concussion incidence between the DA-only cohort and the non-DA group. However, the DA-meds group had a significantly greater incidence of concussion than both the DA-only group (OR 2.67, 95% CI 1.88-7.18, p = 0.0001) and the non-DA group (OR 2.19, 95% CI 1.16-4.12, p = 0.02). Deviation from baseline in PI symptom scores was greater among the DA-meds group as compared to the non-DA group (OR 1.14, 95% CI 1.01-1.28, p = 0.03). At follow-up, the deviation from baseline in symptom scores remained elevated among the DA-meds group as compared to the non-DA group (OR 1.62, 95% CI 1.20-2.20, p = 0.002) and the DA-only group (OR 1.87, 95% CI 1.12-3.10, p = 0.02). Deviation from baseline in follow-up verbal memory was also greater among the DA-meds group as compared to both the non-DA group (OR 1.57, 95% CI 1.08-2.27, p = 0.02) and the DA-only group (OR 1.66, 95% CI 1.03-2.69, p = 0.04). CONCLUSIONS: Premorbid DA itself does not seem to affect the incidence of concussion or the recovery of symptoms and neurocognitive dysfunction PI. However, antidepressant use for DA is associated with 1) increased concussion incidence and 2) elevated symptom scores and verbal memory scores up to 7 days after concussion, suggesting impaired symptomatic and neurocognitive recovery on ImPACT.