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Background: The most common presentation of knee osteochondritis dissecans (OCD) is a stable lesion on the lateral aspect of the medial femoral condyle (MFC) in an adolescent or pre-adolescent athlete. Standard of care for conservative treatment, include activity modification and weight bearing protection. Failed conservative management often leads arthroscopy and drilling of the lesion. Two different primary drilling techniques have been utilized, but no prospective studies have compared their relative effectiveness. Hypothesis/Purpose: The study hypothesis was that trans-articular (TAD) and retro-articular drilling (RAD) would demonstrate similar rates of healing, times to return to sports, and patient-reported outcome scores (PROs). Methods: Skeletally immature (n=113) patients presenting with radiograph indicated stable OCD of the MFC who did not demonstrate healing despite a minimum of 3 months of non-operative treatment were prospectively enrolled and randomized to TAD or RAD, for which 17 surgeon-investigators (at 14 centers, representing all major regions in the U.S.). Serial radiographs were obtained every 6 weeks to assess healing, and PROs were obtained at 6 months, 12 months, and 24 months. Twelve patients were due to lesion instability detected at the time of surgery, Results: Ninety-one study subjects were included, consisting of 51 TAD and 40 RAD patients, with the two groups being of similar age (12.6 years vs. 11.9 years), sex distribution (45% vs. 27% female, p=0.081), and 2-year PRO response rate (both 90%). No significant difference between TAD and RAD was detected in follow-up Pedi-IKDC, Lysholm, Marx knee activity score, or KOOS QOL scores (Table 1). Revision/additional OCD surgery occurred in 10% of patients in RAD and 4% in TAD. 71% of TAD patients reached a ‘healed’ status at a mean of 1.15 years, compared with 58% RAD patients at a mean of 1.06 years. Conclusion: While both primary forms of OCD drilling (TAD and RAD) showed consistent post-operative healing, achieving a completely ‘healed’ status was often a more prolonged process, taking approximately 1 year, despite clinical improvement being achieved much sooner. While PROs were similar between drilling techniques, revision surgery rates were more than twice as common with RAD compared with TAD but the overall risk was low and the Absolute Risk was only 6%. [Table: see text]

Background: Anterior cruciate ligament (ACL) injury reduction training has focused on lower body strengthening and landing stabilization. In vitro studies have shown that quadriceps forces increase ACL strain, and hamstring forces decrease ACL strain. However, the magnitude of the effect of the quadriceps and hamstrings forces on ACL loading and its timing during in vivo landings remains unclear. Purpose: To investigate the effect and timing of knee muscle forces on ACL loading during landing. Study Design: Descriptive laboratory study. Methods: A total of 13 young female athletes performed drop vertical jump trials, and their movements were recorded with 3-dimensional motion capture. Lower limb joint motion and muscle forces were estimated with OpenSim and applied to a musculoskeletal finite element (FE) model to estimate ACL loading during landings. The FE simulations were performed with 5 different conditions that included/excluded kinematics, ground-reaction force (GRF), and muscle forces. Results: Simulation of landing kinematics without GRF or muscle forces yielded an estimated median ACL strain and force of 5.1% and 282.6 N. Addition of GRF to kinematic simulations increased ACL strain and force to 6.8% and 418.4 N ( P < .05). Addition of quadriceps force to kinematics + GRF simulations nonsignificantly increased ACL strain and force to 7.2% and 478.5 N. Addition of hamstrings force to kinematics + GRF simulations decreased ACL strain and force to 2.6% and 171.4 N ( P < .001). Addition of all muscles to kinematics + GRF simulations decreased ACL strain and force to 3.3% and 195.1 N ( P < .001). With hamstrings force, ACL loading decreased from initial contact (time of peak: 1-18 milliseconds) while ACL loading without hamstrings force peaked at 47 to 98 milliseconds after initial contact ( P = .024-.001). The knee flexion angle increased from 20.9° to 73.1° within 100 milliseconds after initial contact. Conclusion: Hamstrings activation had greater effect relative to GRF and quadriceps activation on ACL loading, which significantly decreased and regulated the magnitude and timing of ACL loading during in vivo landings. Clinical Relevance: Clinical training should focus on strategies that influence increased hamstrings activation during landing to reduce ACL loads.

Background: Knee abduction moment during landing has been associated with anterior cruciate ligament (ACL) injury. However, accurately capturing this measurement is expensive and technically rigorous. Less complex variables that lend themselves to easier clinical integration are desirable. Purpose: To corroborate in vitro cadaveric simulation and in vivo knee abduction angles from landing tasks to allow for estimation of ACL strain in live participants during a landing task. Study Design: Descriptive laboratory study. Methods: A total of 205 female high school athletes previously underwent prospective 3-dimensional motion analysis and subsequent injury tracking. Differences in knee abduction angle between those who went on to develop ACL injury and healthy controls were assessed using Student t tests and receiver operating characteristic analysis. A total of 11 cadaveric specimens underwent mechanical impact simulation while instrumented to record ACL strain and knee abduction angle. Pearson correlation coefficients were calculated between these variables. The resultant linear regression model was used to estimate ACL strain in the 205 high school athletes based on their knee abduction angles. Results: Knee abduction angle was greater for athletes who went on to develop injury than for healthy controls ( P < .01). Knee abduction angle at initial contact predicted ACL injury status with 78% sensitivity and 83% specificity, with a threshold of 4.6° of knee abduction. ACL strain was significantly correlated with knee abduction angle during cadaveric simulation ( P < .01). Subsequent estimates of peak ACL strain in the high school athletes were greater for those who went on to injury (7.7-8.1% ± 1.5%) than for healthy controls (4.1-4.5% ± 3.6%) ( P < .01). Conclusion: Knee abduction angle exhibited comparable reliability with knee abduction moment for ACL injury risk identification. Cadaveric simulation data can be extrapolated to estimate in vivo ACL strain. Athletes who went on to ACL injury exhibited greater knee abduction and greater ACL strain than did healthy controls during landing. Clinical Relevance: These important associations between the in vivo and cadaveric environments allow clinicians to estimate peak ACL strain from observed knee abduction angles. Neuromuscular control of knee abduction angle during dynamic tasks is imperative for knee joint health. The present associations are an important step toward the establishment of a minimal clinically important difference value for ACL strain during landing.

Background: Cumulative exposure to repetitive sub-concussive head impacts in contact sports may have deleterious effects on brain function, even in the absence of acute symptoms. Moreover, anatomical and biomechanical factors may predispose female athletes to higher risk compared to males. At present, there is no effective injury prevention strategy to protect female athletes from sports-related head impact. Hypothesis/Purpose: (1). We aimed to use resting-state fMRI to investigate the effect of a full season of competitive soccer on brain functional network integrity in female high school athletes. (2). We also aimed to evaluate the efficacy of a jugular vein compression neck collar device, designed to mitigate potential injury by reducing the brain slosh effect. Methods: A total of 125 high school female soccer athletes were included in this study. These athletes were assigned randomly to a non-collar (n=55, age=16.06±1.06 yrs) or collar group (n=70, 15.81±0.95 yrs) before the season started. High resolution 3D T1-weighted images and resting-state fMRI data were collected prospectively at pre-season and again at post-season. Data processing and analysis were conducted in the MATLAB-based programs Statistical Parametric Mapping (SPM12) and Connectivity Toolbox (Conn). Functional connectivity was computed between each pair of 105 anatomically delineated regions of interest (ROI). Network Based Statistics were applied to detect coherent patterns of altered connectivity from pre- to post-season. Results: The non-collar group showed a significant pattern of altered connectivity (p-FWE = 0.047) spanning 60% of ROIs (63/105) and 1.7% of ROI-ROI connections (94/5,460). 65 of the 94 altered connections were weakened from pre-to-post season and tended to occur in the right hemisphere. 29 of the 94 altered connections were strengthened from pre-to-post season and tended to involve regions in the occipital lobe. The collar group did not show any statistically significant change (p-FWE = 0.223). Conclusion: The results of this study indicate that exposure to repetitive sub-concussive head impacts during a single season of competitive female soccer induces changes in brain functional connectivity. The observed increases and decreases of functional connectivity strength comprising the pattern of altered connectivity are congruent with a heterogeneous response to insult wherein some connections are reduced in strength due to neuronal damage and other “detour” connections are strengthened to preserve network function. Comparatively, the absence of alterations in the collar group suggest that the jugular vein compression collar may have generated a potentially protective effect to preserve brain functional network integrity during exposure to head impacts. [Figure: see text]

Background: Patellofemoral pain (PFP) is a chronic knee condition that affects over 1 in 4 physically-active girls. PFP symptomology contributes to dysfunctional motor control and heightened kinesiophobia (i.e., fear of pain/movement). Both chronic pain and kinesiophobia induce substantial changes throughout the central nervous system (CNS) in many populations who experience pain (e.g., low back pain), but such relationships have not been explored in pediatric patients with PFP. As current treatment approaches for PFP generally fail to provide complete symptom mitigation, identifying the mechanisms by which kinesiophobia exacerbate PFP and disrupt the CNS could provide mechanistic neural pathways to guide novel, brain-based treatments for pain relief. Hypothesis/Purpose: The purpose of this study was to determine the relationship between kinesiophobia and brain functional activation during a knee motor control task in pediatric patients with PFP. Methods: Girls clinically diagnosed with PFP ( n = 15; 14.3 ± 3.2 yrs) were positioned supine in a 3 Tesla magnetic resonance imaging (MRI) scanner and completed a series of unilateral 45° knee extension/flexion movements during functional MRI (fMRI). Patients completed this open kinetic chain movement at a frequency of 1.2 Hz (Figure 1.1). Patients also completed the Tampa Scale of Kinesiophobia (TSK; scores range from 0 – 68, with scores greater than 37 indicating high kinesiophobia). Correlation analyses were performed to determine whether kinesiophobia was associated with brain activity during the motor task. Statistical corrections were made to account for multiple, voxel-wise comparisons. Results: Study patients exhibited high kinesiophobia, with a mean TSK score of 38.27 (SD = 5.79). Neuroimaging analyses revealed that greater kinesiophobia was directly associated with increased brain activity in a cluster located within the occipital pole/cuneus, supracalcarine cortex, and intracalcarine cortex (p < .001, z-max = 4.30; Figure 1). Conclusion: The results revealed that the degree of kinesiophobia was related to the magnitude of visual-related brain activity for knee motor control. As perceived fear of movement increases, patients with PFP may recruit additional visual resources to compensate for pain-disrupted somatosensory processing. Future interventions that promote sensorimotor engagement and reduce visual feedback for motor control (i.e., dynamic movements with occluded vision) may be beneficial to reorganize neural processes, decrease kinesiophobia, and restore an active lifestyle in young girls with PFP. Tables/Figures: [Figure: see text]

Background: Anterior cruciate ligament (ACL) injuries are debilitating for athletes. While numerous motor and biomechanical deficits contribute to the inciting ACL injury mechanism, the limited knowledge about the underlying neural drivers of these deficits has impeded intervention development to reduce ACL injury rates. A prospective investigation using functional magnetic resonance imaging (fMRI) in female soccer players revealed decreased connectivity between the primary somatosensory cortex and cerebellum for athletes that went on to ACL injury athletes compared to their healthy teammates. Although information about inter-region connectivity patterns is informative, this finding does elucidate the individual, intra-region brain activity that may be further underlie ACL injury mechanisms. Hypothesis/Purpose: The purpose of this study was to prospectively investigate the intra-region regularity of the blood oxygen-level dependent (BOLD) signal activity in 25 knee-related regions of interests (ROI) between athletes who sustained an ACL injury and matched controls. Methods: Adolescent female soccer athletes were evaluated using fMRI to capture resting-state brain connectivity prior to their competitive season. Two of these athletes (16.0±0yrs, 169.0±2.8cm, 60.1±8.3kg) later experienced an ACL injury and were matched to eight uninjured teammates (15.9±0.8yrs, 164.0±4.9cm, 58.3±7.6kg). Standard fMRI data processing was used to determine resting-state BOLD signal activity in 25 knee-related ROIs. Sample entropy (SampEn) was then used to quantify the regularity of each individual ROI. A lower SampEn value indicates a ROI’s BOLD signal activity was more regular (predictable) and a higher value indicates a signal’s activity was more irregular (unpredictable). T-tests—with a Bonferroni correction for the familywise error rate ( p < .002)—were used to compare SampEn values between both groups for all 25 ROIs. Results: ACL injured athletes ( M = 0.35±0.01) exhibited higher SampEn values in the left primary motor cortex than matched, uninjured athletes ( M = 0.29±0.02; t(8)=4.62, p=.0017, d=3.65). Conclusion: Athletes who sustained an ACL injury exhibited less regularity in BOLD signal activity of the left primary motor cortex. As the primary motor cortex serves as the final destination in the brain before efferent information is sent to the spinal cord to initiate movement, decreased BOLD signal regularity in this region may alter such cortical-spinal transmission. Considering ACL injuries often occur during unpredictable environments, irregular activity of motor cortex activity may dampen an athlete’s ability to sustain a safe knee position. These findings may help to guide development of brain-driven biofeedback training to promote adaptive neuroplasticity that ‘pushes’ the motor cortex towards more regular activity. [Figure: see text]

Background: Anterior cruciate ligament (ACL) injuries predominantly occur via non-contact mechanisms, secondary to motor coordination errors resulting in aberrant frontal plane knee loads that exceed the thresholds of ligament integrity. However, central nervous system processing underlying high injury-risk motor coordination errors remain unknown, limiting the optimization of current injury reduction strategies. Purpose: To evaluate the relationships between brain activity during motor tasks with injury-risk loading during a drop vertical jump. Methods: Thirty female high school soccer players (16.10 ± 0.87 years, 165.10 ± 4.64 cm, 63.43 ± 8.80 kg) were evaluated with 3D biomechanics during a standardized drop vertical jump from a 30 cm box and peak knee abduction moment was extracted as the injury-risk variable of interest. A neuroimaging session to capture neural activity (via blood-oxygen-level-dependent signal) was then completed which consisted of 4 blocks of 30 seconds of repeated bilateral leg press action paced to a metronome beat of 1.2 Hz with 30 seconds rest between blocks. Knee abduction moment was evaluated relative to neural activity to identify potential neural contributors to injury-risk. Results: There was a direct relationship between increased landing knee abduction moment and increased neural activation within regions corresponding to the lingual gyrus, intracalcarine cortex, posterior cingulate cortex, and precuneus (r2= 0.68, p corrected < .05, z max > 3.1; Table 1 & Figure 1). Conclusion: Elevated activity in regions that integrate sensory, spatial, and attentional information may contribute to elevated frontal plane knee loads during landing. Interestingly, a similar activation pattern related to high-risk landing mechanics has been found in those following injury, indicating that predisposing factors to injury may be accentuated by injury or that modern rehabilitation does not recover prospective neural control deficits. These data uncover a potentially novel brain marker that could guide the discovery of neural-therapeutic targets that reduce injury risk beyond current prevention methods. [Table: see text][Figure: see text]

Background: Aberrant frontal and sagittal plane knee motor control biomechanics contribute to increased anterior cruciate ligament (ACL) injury risk. Emergent data further indicates alterations in brain function may underlie ACL injury high risk biomechanics and primary injury. However, technical limitations have limited our ability to assess direct linkages between maladaptive biomechanics and brain function. Hypothesis/Purpose: (1) Increased frontal plane knee range of motion would associate with altered brain activity in regions important for sensorimotor control and (2) increased sagittal plane knee motor control timing error would associate with altered activity in sensorimotor control brain regions. Methods: Eighteen female high-school basketball and volleyball players (14.7 ± 1.4 years, 169.5 ± 7 cm, 65.8 ± 20.5 kg) underwent brain functional magnetic resonance imaging (fMRI) while performing a bilateral, combined hip, knee, and ankle flexion/extension movements against resistance (i.e., leg press) Figure 1(a). The participants completed this task to a reference beat of 1.2 Hz during four movement blocks of 30 seconds each interleaved in between 5 rest blocks of 30 seconds each. Concurrent frontal and sagittal plane range of motion (ROM) kinematics were measured using an MRI-compatible single camera motion capture system. Results: Increased frontal plane ROM was associated with increased brain activity in one cluster extending over the occipital fusiform gyrus and lingual gyrus ( p = .003, z > 3.1). Increased sagittal plane motor control timing error was associated with increased brain activity in multiple clusters extending over the occipital cortex (lingual gyrus), frontal cortex, and anterior cingulate cortex ( p < .001, z > 3.1); see Figure 1 (b). Conclusion: The associations of increased knee frontal plane ROM and sagittal plane timing error with increased activity in regions that integrate visuospatial information may be indicative of an increased propensity for knee injury biomechanics that are, in part, driven by reduced spatial awareness and an inability to adequately control knee abduction motion. Increased activation in these regions during movement tasks may underlie an impaired ability to control movements (i.e., less neural efficiency), leading to compromised knee positions during more complex sports scenarios. Increased activity in regions important for cognition/attention associating with motor control timing error further indicates a neurologically inefficient motor control strategy. [Figure: see text]

Background: Anterior cruciate ligament (ACL) injury is secondary to a multifactorial etiology encompassing anatomical, biological, mechanical, and neurological factors. The nature of the injury being primarily due to non-contact mechanics further implicates neural control as a key injury-risk factor, though it has received considerably less study. Purpose: To determine the contribution of neural activity to injury-risk mechanics in ecological sport-specific VR landing scenarios. Methods: Ten female high-school soccer players (15.5±0.85 years; 165.0±6.09 cm; 59.1±11.84 kg) completed a neuroimaging session to capture neural activity during a bilateral leg press and a 3D biomechanics session performing a header within a VR soccer scenario. The bilateral leg press involved four 30 s blocks of repeated bilateral leg presses paced to a metronome beat of 1.2 Hz with 30 s rest between blocks. The VR soccer scenario simulated a corner-kick, requiring the participant to jump and head a virtual soccer ball into a virtual goal (Figure 1A-E). Initial contact and peak knee flexion and abduction angles were extracted during the landing from the header as injury-risk variables of interest and were correlated with neural activity. Results: Evidenced in Table 1 and Figure 1 (bottom row), increased initial contact abduction, increased peak abduction, and decreased peak flexion were associated with increased sensory, visual-spatial, and cerebellar activity (r2= 0.42-0.57, p corrected < .05, z max > 3.1, table & figure 1). Decreased initial contact flexion was associated with increased frontal cortex activity (r2= 0.68, p corrected < .05, z max > 3.1). Conclusion: Reduced neural efficiency (increased activation) of key regions that integrate proprioceptive, visual-spatial, and neurocognitive activity for motor control may influence injury-risk mechanics in sport. The regions found to increase in activity in relation to higher injury-risk mechanics are typically activated to assist with spatial navigation, environmental interaction, and precise motor control. The requirement for athletes to increase their activity for more basic knee motor control may result in fewer neural resources available to maintain knee joint alignment, allocate environmental attention, and handle increased motor coordination demands. These data indicate that strategies to enhance efficiency of visual-spatial and cognitive-motor control during high demand sporting activities is warranted to improve ACL injury-risk reduction. [Figure: see text][Table: see text]

Background: Patellofemoral pain (PFP) is a chronic knee condition that inhibits movement quality and can cascade into kinesiophobia (i.e., fear of pain/movement). Despite its high prevalence in adolescent girls, PFP etiology has remained elusive, potentially due to an incomplete understanding of how pain, motor control, and kinesiophobia interact with central nervous system (CNS) functioning. Discovering linkages between motor control, kinesiophobia, and the CNS for patients with PFP could provide novel opportunities to refine neural therapeutic strategies for enhanced, personalized treatment approaches. Hypothesis/Purpose: To identify neural markers of kinesiophobia in pediatric patients with PFP. Methods: Adolescent girls clinically diagnosed with PFP ( n = 14; 14.3 ± 3.2 yrs) were positioned supine in a magnetic resonance imaging (MRI) scanner. A modified Clarke’s test (patellofemoral grind test) was administered to the left knee of patients during brain functional MRI (fMRI) acquisition. The experimenter placed a hand at the superior patellar border applying intermittent distal pressure while the patient contracted her quadriceps. Patients also completed a quadriceps contraction test without application of external pressure (control). Kinesiophobia was measured using the Tampa Scale of Kinesiophobia. fMRI analyses compared brain activation between the two tasks, and correlation analyses were performed to assess relationships between task-induced brain activity and kinesiophobia. Statistical corrections were made to account for multiple, voxel-wise comparisons. Results: Evidenced in Table 1 and Figure 1A, neuroimaging analyses revealed distinct bidirectional activation during the Clarke’s test compared to the control (all p corrected < .05, all z max > 3.1). Table 1 and Figure 1B further highlight that greater kinesiophobia was associated with increased brain activity during the Clarke’s test in two clusters (both p corrected < .05, both z max > 3.1), but no relationships between kinesiophobia and brain activity during the control test were observed (all p corrected > .05, all z max < 3.1). Conclusion: The current results indicate that the Clarke’s test induced differential pain-related brain activity relative to the control (e.g., paracingulate gyrus). The patients’ degree of kinesiophobia was also related to brain activity in regions important for sensorimotor control, attention, and pain. Collectively, these data indicate that PFP may be due to alterations in nociceptive processing throughout the CNS, providing novel complementary pathways for targeted restoration of patellofemoral joint dysfunction. Future research should consider combined mechanistic pain profiling, sensorimotor, psychometric, and CNS assessments to identify patients most susceptible to kinesiophobia to refine treatment approaches that work towards a goal of disease prevention. Tables/Figures: [Figure: see text][Table: see text]

Background: Frontal plane trunk lean with a side-to-side difference in lower extremity kinematics during landing increases unilateral knee abduction moment and consequently anterior cruciate ligament (ACL) injury risk. However, the biomechanical features of landing with higher ACL loading are still unknown. Validated musculoskeletal modeling offers the potential to quantify ACL strain and force during a landing task. Purpose: To investigate ACL loading during a landing and assess the association between ACL loading and biomechanical factors of individual landing strategies. Study Design: Descriptive laboratory study. Methods: Thirteen young female athletes performed drop vertical jump trials, and their movements were recorded with 3-dimensional motion capture. Electromyography-informed optimization was performed to estimate lower limb muscle forces with an OpenSim musculoskeletal model. A whole-body musculoskeletal finite element model was developed. The joint motion and muscle forces obtained from the OpenSim simulations were applied to the musculoskeletal finite element model to estimate ACL loading during participants’ simulated landings with physiologic knee mechanics. Kinematic, muscle force, and ground-reaction force waveforms associated with high ACL strain trials were reconstructed via principal component analysis and logistic regression analysis, which were used to predict trials with high ACL strain. Results: The median (interquartile range) values of peak ACL strain and force during the drop vertical jump were 3.3% (–1.9% to 5.1%) and 195.1 N (53.9 to 336.9 N), respectively. Four principal components significantly predicted high ACL strain trials, with 100% sensitivity, 78% specificity, and an area of 0.91 under the receiver operating characteristic curve ( P < .001). High ACL strain trials were associated with (1) knee motions that included larger knee abduction, internal tibial rotation, and anterior tibial translation and (2) motion that included greater vertical and lateral ground-reaction forces, lower gluteus medius force, larger lateral pelvic tilt, and increased hip adduction. Conclusion: ACL loads were higher with a pivot-shift mechanism during a simulated landing with asymmetry in the frontal plane. Specifically, knee abduction can create compression on the posterior slope of the lateral tibial plateau, which induces anterior tibial translation and internal tibial rotation. Clinical Relevance: Athletes are encouraged to perform interventional and preventive training to improve symmetry during landing.

Background: Sports-related concussion is a significant public health problem which may result in exacerbated or prolonged neurologic deficits. A neck collar device has been developed to apply mild jugular vein compression, increasing intracranial blood volume, with the intent of reducing brain slosh and preventing damage to brain microstructure from head impact exposure. Hypothesis/Purpose: We aimed to quantify the alterations in white matter (WM) diffusion properties and network structural connectivity in high school athletes after sports-related concussion and to test the effect of a jugular vein compression collar device worn during the concussive event. Methods: 379 athletes (male American football and female Soccer) were included in this report. Of the 16693 total athlete exposures, 40 resulted in a diagnosed concussion and were included in these analyses. Prospective longitudinal MRI data were collected at pre-season and post-concussion: 20 athletes were in the non-collar group (12M, age =15.93±1.27yrs) and 20 athletes were in the non-collar group (16M, age=16.37±1.06yrs). DTI parameters, including fractional anisotropy (FA), and mean, axial and radial diffusivity (MD/AD/RD), were calculated to determine post-concussion alterations in WM diffusion properties. Graph analysis was utilized to quantify post-concussion changes in WM structural connectivity. Results: Diffusion property results revealed significant pre-season to post-concussion increases in MD, AD and RD within the non-collar group (p0.05). The pre-season to post-concussion MD, AD, or RD increase was significantly greater (pDiscussion & Conclusion: Results indicate that sports related concussion is associated with alterations in WM diffusion properties. The mean local efficiency of the network, a structural connectivity index reflecting network wiring redundancy and tolerance to brain injury, was also found to decrease after the concussion. Results indicate that wearing a neck collar device has the potential to limit these WM changes following a concussive event. Further studies are warranted to investigate the temporal progression of these changes for preventing long-term, neurologic squeala. [Figure: see text][Figure: see text]

Background: The safest and most effective technique for anterior cruciate ligament (ACL) reconstruction in skeletally immature patients is currently unknown. Purpose: To evaluate the functional and patient-reported outcomes of a specific all-epiphyseal ACL reconstruction technique in which the graft, bone tunnels, and fixation do not cross the knee growth plates. Study Design: Case series; Level of evidence, 4. Methods: Twenty-seven patients (23 boys, 4 girls; mean age, 11 years; range, 8-15 years) underwent an all-epiphyseal ACL reconstruction with a single femoral transverse epiphyseal tunnel and primarily split tibial epiphyseal tunnels. Outcomes were evaluated in terms of the manual Lachman test, range of motion, pain, return to activity, angular or leg-length deformity on imaging, and International Knee Documentation Committee (IKDC) or Pedi-IKDC score an average of 3.8 years postoperatively, with a minimum 2-year follow-up. Results: The mean IKDC score was 94 ± 11. There were no growth arrests, but 3 patients had knee overgrowth, and 2 required a subsequent guided growth procedure. The ACL graft failed in 4 patients (15%), and 2 patients had contralateral ACL tears (7%). There were 5 subsequent ipsilateral meniscal tears, 4 of which were retears of a repaired meniscus. Ipsilateral knee reinjury significantly correlated with the number of associated injuries at the time of index surgery ( P = .040) and the number of sports played ( P = .029). Conclusion: All-epiphyseal ACL reconstruction resulted in excellent long-term functional outcomes, despite a high rate of complications (48%) and secondary procedures (37%) in this highly active cohort. The incidence of graft failure was similar to other standard ACL reconstruction techniques for patients younger than 20 years.

Background: Patellofemoral pain (PFP) is a common knee pain condition that affects up to 30% of adolescents and is disproportionately distributed between sexes, affecting females 2-10 times more frequently than male counterparts (Fulkerson, 2002). PFP, characterized by retro- or peripatellar pain, can be debilitating, leading to cessation of physical activity in 74% of adolescents (Fairbank, Pynsent, van Poortvliet, & Phillips, 1984). Aberrant lower-extremity biomechanics for those with PFP has been identified (Souza & Powers, 2009; Willson & Davis, 2008), but the underlying brain activation patterns contributing to pain-disrupted knee motor control is unknown. Patients with knee ligament deficiency demonstrate decreased sensorimotor activity and increased prelimbic activity in response to knee pain, compared with matched controls (Kadowaki, Tadenuma, Kumahashi, & Uchio, 2017), and those with knee ligament reconstruction demonstrate a disrupted sensory-motor brain activation strategy to control the knee (Grooms et al., 2017; Grooms, Page, & Onate, 2015). As PFP has been identified as a contributing factor to knee osteoarthritis later in life (Utting, Davies, & Newman, 2005), identifying the neural mechanisms driving pain-disrupted motor control could guide innovative neural-targeted interventions to treat and reduce knee pain. We hypothesized that patients with PFP, like those with knee ligament deficiencies and reconstruction, would demonstrate decreased sensorimotor brain activation and increased medial pain network brain activation to control the knee. We used our previously established knee motor control neuroimaging paradigm that simulates knee flexion and extension movements (Grooms et al., 2015) to identify altered neural activation patterns for those with PFP and compared those with matched controls. Methods: Four adolescent girls with patellofemoral pain (PFP: n = 4, 15.4 ± 2.2yrs, 158.5 ± 5.4 cm, 61.5 ± 15.6 kg) were matched with four adolescent girls with no history of knee pain (controls) based on age, height, and weight (Con: n =4, 16.4 ± 1.8yrs, 161.8 ± 5.1 cm, 54.9 ± 6.9 kg). Participants were positioned supine in a magnetic resonance imaging (MRI) scanner and completed a series of unilateral 45° knee extension/flexion movements at a velocity of 1.2 Hz (Figure 1; Left Panel). Various torso straps and head packing procedures were utilized to restrict excessive head motion. A second level mixed-effects (FLAME 1+2) independent samples t-test contrasted brain activation between the PFP and controls using a significance level set a priori at p < .05; Gaussian random field cluster corrected and z threshold set at z > 1.5. Results: Results revealed significantly depressed brain activation in the right parietal operculum cortex (z = 5.99, p < .001) and left Heschl’s gyrus (z = 3.83, p < .001) for the PFP compared to the controls (Figure 1; Right Panel). Discussion: The present study revealed significant differences in the neural activation patterns to control the knee between adolescent girls with PFP and those with no knee pain. Patients with PFP demonstrated less activation in sensorimotor cortices, seen in the parietal operculum, and sensory integration, seen in Heschl’s gyrus, when compared to healthy controls (Grooms et al., 2017; Kadowaki et al., 2017). These results indicate that pain may be suppressing sensory integration to control the knee for those with PFP. Congruent with previous neuroimaging investigations assessing those with knee injury (Grooms et al., 2017; Kadowaki et al., 2017), PFP appears to also induce neuroplastic effects identifiable using fMRI. These results provide a potential neural target for interventions that aim to restore sensorimotor integration in those with PFP, reduce pain, and restore an active lifestyle in young females. [Figure: see text]

Background: Anterior cruciate ligament (ACL) injury is associated with alterations in the central nervous system and resultant sensorimotor control (Courtney et al., 2005; Grooms et al., 2017). Our prospective data indicates that altered knee-motor functional brain connectivity is associated with increased risk for ACL injury (Diekfuss et al., revisions invited), revealing novel neural targets for neuromuscular training interventions. Specifically, interventions that integrate concomitant sensorimotor feedback with injury prevention techniques have the potential to enhance brain functional connectivity to optimize ACL injury risk reduction strategies. To deliver concomitant sensorimotor feedback, we have developed an augmented neuromuscular training (aNMT) system that utilizes interactive, real-time biofeedback to simultaneously target multiple biomechanical variables associated with ACL injury risk (Bonnette et al., in press; Figure 1A). aNMT calculates and maps key biomechanical parameters to an interactive graphical shape that responds in real time as a function of participants’ movements. Participants are instructed to perform exercises to achieve a goal shape, which equates to producing biomechanical parameters associated with ACL injury risk reduction, while deviations toward injury risk factors result in specific shape distortions. We hypothesized that aNMT would significantly improve biomechanics associated with ACL injury risk and also increase knee-motor functional connectivity. We further predicted that the identified connectivity changes would be associated with the hypothesized changes in biomechanics. Methods: Over six weeks of training, participants (n = 25) performed a series of aNMT-based progressive exercises (e.g., squat, overhead squat, squat jump, tuck jump, single-leg Romanian dead lift, pistol squat) and completed a drop vertical jump (DVJ) task while fully instrumented for 3D motion analysis pre- and post-training. Peak knee abduction moment (pKAM; bilateral average) from the DVJ was used as the biomechanical outcome variable. Resting-state functional magnetic resonance imaging (fMRI) scans were also collected pre- and post-training on a subset of the cohort (n = 17). Thirteen additional participants were recruited to serve as untrained controls and completed the DVJ and resting-state fMRI on two testing sessions separated by approximately 6 weeks. Twenty-five knee-motor regions of interest (ROIs) were created based on the areas of brain activation derived from previously published data (Grooms et al., 2015; Kapreli et al., 2007). Paired-samples t tests with a false discovery rate correction for multiple comparisons determined differences in functional connectivity among these 25 ROIs (post > pre). Fisher-transformed Pearson correlation coefficients between the average residual blood oxygen level dependent (BOLD) signal time series extracted from ROIs that demonstrated significant group level changes were associated with pKAM in DVJ task at pre- and post-training. The pre- and post-training Pearson correlation coefficients were subsequently compared using the cocor package (Diedenhofen & Musch, 2015) to determine if the two relationships were significantly different. Results: Results showed that pKAM in the aNMT group was significantly lower following aNMT (p < .05), while no significant changes were found between the two time points for controls (p > .05). Results also revealed significantly greater functional connectivity between the right supplementary motor area (SMA) and the left thalamus at post-training relative to pre-training for the aNMT group, t(16) = 3.37, p = .04 (Figure 1B). No significant differences between the two time points were observed for the controls (all p > .05). The association between pKAM and the right SMA and left thalamus at pre-training (r = -.22; Figure 1C) was significantly different compared to that at post-training (r = .26; Figure 1D), p < .05, with a positive relationship between pKAM and SMA and thalamus activation following aNMT biofeedback. No similar changes in pKAM and right SMA and left thalamus connectivity were observed for the untrained controls, p > .05. Conclusions/Significance: The right SMA is involved in the planning and coordination of movement, and the left thalamus is associated with neuromotor control. The increased functional connectivity between these regions, combined with the reduction in pKAM, which is associated with reduced risk of ACL injury, indicate a possible neural mechanism for improved motor adaption associated with aNMT biofeedback. These findings have distinct implications for ACL injury prevention strategies. Biofeedback tools such as aNMT can be designed to target specifically the neural drivers of aberrant movement biomechanics underlying increased ACL injury risk. [Figure: see text]

Background: Previous studies have acknowledged the medial patellofemoral ligament (MPFL) as the primary stabilizer of the patella, preventing lateral displacement. MPFL reconstruction (MPFL-R) restores stability and functionality to the patellofemoral joint and has emerged as a preferred treatment option for recurrent lateral patellar instability. Purpose: To objectively measure biomechanical characteristics of athletes cleared for return to sport after MPFL-R compared with healthy controls. Study Design: Cohort study; Level of evidence, 3. Methods: A prospective case-control study design was employed on 31 total athletes. Sixteen athletes (6 male, 10 female; mean age, 16.1 ± 2.74 years; 385 ± 189 days after surgery and 235 ± 157 days after return to sport) underwent MPFL-R and were medically cleared to return to sport. This group was matched by age, sex, and activity level to 15 healthy athletes with no history of lower extremity injuries. Athletes and controls completed validated questionnaires as well as hopping, jumping, and cutting tests with 3-dimensional motion analysis and underwent strength, flexibility, laxity, and balance assessments. Results: Participants in the MPFL-R group scored significantly lower (worse) on the International Knee Documentation Committee (IKDC) (89.2 ± 7.6 vs 98.1 ± 2.0, respectively; P = .0005) and significantly higher (worse) on the Tampa Scale for Kinesiophobia (TSK) (32.4 ± 5.0 vs 25.4 ± 6.5, respectively; P = .006) than those in the control group, but there was no difference in the Kujala score (95.6 ± 5.3 vs 98.8 ± 3.0, respectively; P = .06). Participants in the MPFL-R group demonstrated reduced hip and ankle flexion relative to those in the control group ( P < .05). Participants in the MPFL-R group also took significantly longer to complete the 6-m timed hop test relative to those in the control group ( P < .05). No statistically significant differences were found in anthropometrics, knee extension or flexion strength, hamstring flexibility, hip abduction strength, or joint laxity between the MPFL-R and control groups. Conclusion: The current data indicate that MPFL-R generally restores functional symmetry, while subtle deficits in global power may remain after being released to full activity. Clinicians should ensure that athletes are fully rehabilitated before returning to sport after MPFL-R by emphasizing functional multijoint exercises.

Background:Although anterior cruciate ligament (ACL) reconstruction is generally regarded as a successful procedure, only 65% of patients return to their preinjury sport. While return-to-sport rates are likely higher in younger patients, there is a paucity of data that focus on the younger patient and their return-to-sport experience after ACL reconstruction.Purpose:To investigate a range of return-to-sport outcomes in younger athletes who had undergone ACL reconstruction surgery.Study Design:Case series; Level of evidence, 4.Methods:A group of 140 young patients (Results:Overall, 76% (95% CI, 69%-83%) of the young patient group returned to the same preinjury sport. Return rates were higher for males than females (81% vs 71%, respectively; P > .05). Of those who returned to their sport, 65% reported that they could perform as well as before the ACL injury and 66% were still currently participating in their respective sport. Young athletes who never returned to sport cited fear of a new injury (37%) or study/work commitments (30%) as the primary reasons for dropout. For those who had successfully returned to their preinjury sport but subsequently stopped participating, the most common reason cited for stopping was study/work commitments (53%). At a mean 5-year follow-up, 48% of female patients were still participating in level I (jumping, hard pivoting) sports, as were 54% of males.Conclusion:A high percentage of younger patients return to their preinjury sport after ACL reconstruction surgery. For patients in this cohort who had not sustained a second ACL injury, the majority continue to participate and are satisfied with their performance.

Background: Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach. Purpose: To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions. Study Design: Controlled laboratory study. Methods: Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 weeks. Coefficients of multiple correlation were calculated to assess the reliability of kinematic and kinetic measures during the landing phase of the movement. Results: Between-centers reliability for kinematic waveforms in the frontal and sagittal planes was good, but moderate in the transverse plane. Between-centers reliability for kinetic waveforms was good in the sagittal, frontal, and transverse planes. Conclusion: Based on these findings, the single-leg cross drop task has moderate to good reliability of kinematic and kinetic measures across institutions after implementation of a standardized testing protocol. Clinical Relevance: Multicenter collaborations can increase study numbers and generalize results, which is beneficial for studies of relatively rare phenomena, such as ACL injury. An important step is to determine the reliability of risk assessments across institutions before a multicenter collaboration can be initiated.

Objectives: Over 125,000 anterior cruciate ligament (ACL) injuries occur each year in the United States. External loads on the knee in the frontal plane, specifically the knee abduction moment (KAM), predict future ACL injury with high sensitivity and specificity. The purpose of this randomized controlled trial (RCT) was to determine if biomechanical and neuromuscular factors could be used to characterize athletes by distinct factor profiles, to examine if neuromuscular training (NMT) would decrease the potential risk factors, and if NMT would preferentially benefit athletes that exhibited specific risk profiles. The hypotheses tested were: 1) a priori chosen biomechanical and neuromuscular factors would characterize subjects into distinct at-risk profiles, 2) NMT would decrease biomechanical and neuromuscular factors related to increased injury risk and 3) the decrease in these biomechanical and neuromuscular factors would be greater in those athletes characterized by the overall higher risk profiles. Methods: A total of 624 female athletes from 52 basketball, soccer and volleyball teams participated and were screened prior to their competitive season. During the pre-season testing, the athletes performed 3 different types of tasks for which biomechanical measures were taken: 1) drop vertical jump (DVJ), 2) single leg drop (SLD), and 3) single leg cross drop (SCD) landings. Using data from these tasks a latent profile analysis (LPA) was conducted to identify distinct profiles based on pre-intervention biomechanical and neuromuscular measures. As a validation, we examined whether the profile membership was significant predictor of KAM. Analysis of Co-Variance (ANCOVA) was used to examine treatment effects of NMT on biomechanical and neuromuscular measures in the 375 athletes who completed both pre- and post-intervention tasks. Differences were considered statistically significant at pResults: LPA using six pre-intervention biomechanical measures selected a priori resulted in three distinct profiles. Athletes in profiles II and III had significant higher KAM, compared to Profile I. The Core/Trunk-based NMT significantly increased hip external rotation moments and moment impulse and increased peak trunk flexion and decreased extension. In addition, the treatment effect of NMT varied by pre-intervention risk profile. Athletes with pre-intervention risk Profile II and III (higher risk) had a more significant treatment effect of NMT than Profile I. Conclusion: This is the first study to use LPA analysis of biomechanical landing data to create KAM and potentially ACL injury risk profiles. The LPA of multiple biomechanical and neuromuscular measures identified three distinct risk groups; associated with differences in peak KAM Analysis of the RCT showed that NMT significantly increased hip external rotation moments and moment impulse and increased peak trunk flexion and decreased extension, and that alterations in risk factors are different across risk profile group, with higher risk groups showing an overall significant improvement in KAM. These findings show the existence of discernable groups of athletes that are more appropriate for NMT intervention; further study is needed in even larger cohorts to investigate ACL injury as our primary outcome variable.

Objectives: Approximately 30-50% of skeletally immature patients with stable osteochondritis dissecans (OCD) lesions of the knee fail to heal with non-operative treatment, and about 30% of patients who undergo surgery fail to heal radiographically. Unfortunately it is nearly impossible to predict which patients will heal with non-surgical or surgical treatment. We identified multiple OCD features on standard radiographs that may help to predict healing rates. In this study, we test the inter- and intra- rater reliability of orthopaedic surgeons from multiple institutions on classifying these specific OCD radiographic features. Methods: Pre-treatment anteroposterior, lateral, and notch radiographs (Figure) of 45 pediatric knees containing OCD lesions of the medial or lateral femoral condyle were reviewed by 7 physician raters at different medical institutions at two time points. Images were viewed over a secure internet portal. Classifications included lesion location (medial/lateral), growth plate maturity (open/closing/closed), visibility of the progeny bone including fragmentation (yes/no), fragment displacement (none/partial/total), boundary (distinct/indistinct), shape (convex/linear/concave), and comparative radiodensity of the center and rim (more/same/less). Condylar width and lesion size were measured on all views. Inter-observer reliability was measured using free-marginal kappa (kf) and intraclass correlations. Intra-observer reliability was measured using Cohen’s kappa (kc), linear-weighted kappa (klw), and intraclass correlations depending on measurement type. Results: Inter- and intra-observer reliability were excellent for classification of lesion location (kf=0.96, kc=0.97, respectively) and skeletal maturity (ICC=0.86, klw=0.84, respectively) and for measuring knee and lesion size on all views (ICC=0.92-0.98, ICC=0.84-0.95, respectively). The visibility, fragmentation, and displacement of the progeny bone were classified with substantial reliability over time (kc=0.67, kc=0.64, klw=0.80, respectively) and moderate reliability between raters (kf=0.45, kf=0.54, ICC=0.52, respectively). The progeny bone boundary demonstrated substantial reliability between raters (kf=0.62) and moderate reliability over time (kc=0.55). Fair to moderate inter- and intra-observer reliability was obtained for classifying the shape (ICC=0.33, klw=0.53, respectively) and comparative radiodensity of parent and progeny bone (ICC=0.11-0.52, klw=0.32-0.57, respectively). Conclusion: Most of the specific OCD radiographic features tested showed good to excellent reliability. Lesion shape and density had only fair to moderate reliability. The results of the current study support the use of OCD radiographic feature classification in multi-center investigations. Each reliable feature may be correlated with healing in future studies and help to predict OCD outcome at the start of treatment.

Objectives: Hip and knee strength abnormalities have been implicated in patellofemoral pain (PFP) in multiple studies in the recent literature. However, many authors have noted that hip muscle weakness has not yet been defined as having a causal relationship to PFP due to the fact that many studies used subjects already diagnosed with PFP. The purpose of this study was to compare prospective hip and knee isokinetic strength measures in young females who subsequently went on to develop PFP relative to their uninjured healthy peers. Methods: Middle and high school female athletes (n=255) were evaluated by a physician for PFP prevalence. Isokinetic strength measurements of the knee (flexion and extension at 300°/sec) and hip (abduction at 120°/sec) were obtained prior to the start of their basketball and soccer seasons. Isokinetic torque measures (newton*meters) were normalized to leg length by mass and are described as a normalized torque (NT). Those diagnosed with PFP at pre-season were excluded and the remaining athletes were monitored by certified athletic trainers for PFP incidence during their competitive seasons. A one-way ANOVA was used to determine significant differences in knee and hip strength measures between the incident PFP and the control groups. Results: Young females who developed PFP were not different in age 12.6 ± 0.9 yrs., mass 51.4 ± 13.2 kg, height 158.8 ± 7.3 cm, or leg length 83.8 ± 4.2 cm compared to the referent control group (P>0.05). Females who developed PFP demonstrated increased normalized hip strength 0.013 ± 0.003 NT relative to the referent control group 0.011 ± 0.003 NT (P0.05). Conclusion: The findings in this study indicate that young females with greater hip abduction strength may be at an increased risk for the development of PFP. Previous studies that have looked at landing biomechanics indicated that those with PFP have increased knee abduction and increased hip adduction during landing. Combining our current data and previous literature, we theorize that greater hip abduction strength may be a resultant symptom of increased eccentric loading of the hip abductors associated with increased dynamic valgus biomechanics demonstrated to underlie increased PFP incidence. Future research is warranted to dissect the relative contributions of hip strength and recruitment and dynamic valgus alignments during landing to the pathomechanics of PFP.

Objectives: Athletes who return to sport after ACL reconstruction (ACLR) are at increased risk of future ACL injury. Proprioceptive deficits at the knee, known to be present at thetime of ACL injury, may persist for up to 2 years after ACLR. Coordinated movements of the hip and ankle are critical in the absence of normal knee proprioception during dynamic athletic movements. Failure to optimally position the knee may make the passive structures susceptible to pathologic stresses that increase the risk of subsequent ligament or graft failure. The purpose of this work was to prospectively determine if altered lower extremity coordination patterns exist in female athletes, who go on to suffer a second ACL injury to either limb, after ACLR and return to sport (RTS). The study tested the hypothesis that female athletes who sustained a second ACL injury would demonstrate altered lower extremity coordination patterns indicative of persistent neuromuscular deficits at the time of return to sport compared to female athletes who would not subsequently sustain a second ACL injury. Methods: Sixty-one female athletes, who sustained an ACL injury, underwent ACLR, completed rehabilitation and were medically cleared for RTS were enrolled in this study. Hip-ankle coordination was assessed on all athletes prior to RTS as they performed a dynamic postural coordination task. The task required participants to stand on a single leg and track the anterior-posterior (AP) movement of an oscillating 3-D square target displayed on a computer monitor. Participants tracked the target with the head so as to maintain a constant perceived distance between their head and the target by matching the amplitude and frequency of the target oscillations. Fourteen patients sustained a second ACL injury within 12 months of RTS (ACLR2). Fourteen matched subjects after ACLR, who did not suffer a second ACL injury (ACLR1), were selected for comparative analysis. Cross-recurrence quantification analysis (Figure 1) was used to characterize hip-ankle coordination patterns through the variable cross-maxline (CML). A group (ACLR1 vs. ACLR2) X target speed (slow vs. fast) X leg (affected vs. unaffected) mixed-model analysis of variance was used to identify coordination differences. Results: A significant main effect of group was observed ( p = 0.02), and indicated that the ACLR1 group exhibited more stable hip-ankle coordination overall (M = 166.2 ± 18.9) compared to the ACLR2 group (M = 108.4 ± 10.1), irrespective of target speed or tested leg. A leg x group interaction was also observed ( p = .04). A Mann-Whitney test was employed due to unequal variances between groups, and indicated that the affected leg of the ACLR1 group exhibited more stable coordination (M = 187.1 ± 23.3)compared to the affected leg of the ACLR2 group (M = 110.13 ± 9.8), p = 0.03. Conclusion: Hip-ankle coordination was altered in female athletes who subsequently sustain a second ACL injury after initial ACLR and RTS. Failure to appropriately coordinate lower extremity movement between the adjoining proximal and distal hip and ankle in the absence of normal knee proprioception, may place the knee in a high-risk position and increase the likelihood of a second ACL injury in this population.

Authors’ Response: Thank you for allowing us to respond to the Letter to the Editor regarding our recently published study titled “Altitude Modulates Concussion Incidence Implications for Optimizing Brain Compliance to Prevent Brain Injury in Athletes.”3 We agree with the author of the letter that this published study presents important findings that have the potential to influence the science related to concussion prevention strategies. We also thank him for his interest in this study, and we are encouraged that it is stimulating ongoing discussions in the field of concussion prevention. The Letter to the Editor makes 3 major points. We will respond to each in a point-by-point fashion. We agree with the author that it is important to clarify the clinical relevance of our findings. As the authors of this article included basic scientists, public health researchers, and clinicians, we were very sensitive to the criteria required to demonstrate clinical significance and subsequently were very clear in this article that this was the first epidemiologic study to evaluate the novel hypothesis that a raised topographical altitude would be related to a reduction in concussion rates. Clinical significance must be demonstrated via a thorough line of research resulting in a progression of evidence, ideally culminating in clinical trials. Thus, we believe studies such as ours, which is in the very early stages of novel lines of research, should be used to generate hypotheses and drive additional research rather than to determine clinical significance. In addition, making determinations of clinical significance based on one statistic is inappropriate. Clinical significance should be determined only after a detailed examination of a potential clinical/public health problem, which requires an understanding of a wide range of factors: for example, the size of the population at risk; the prevalence, incidence, and/or rate of the negative health outcome in the population at risk; the seriousness/severity of the negative health outcome; and the effectiveness, availability, cost, and possible negative side effects of potential prevention and/or treatment options. When a large population is at risk for a negative health outcome (especially with potentially severe short- and/or long-term effects), even a modest rate decrease may eventually be determined to be clinically significant. The author’s claim of this study having “no clinical meaningfulness” likely reflects a lack of understanding of the current evidence and the challenge that science has had in making any strides in preventing concussion in sport to date. Nevertheless, we sincerely hope that the author and clinician readers of this journal would not make clinical decisions based solely on the results of our single study. While we made no claim of clinical significance from our study, having the author of the letter suggest that a 30% decrease in the rate of concussion among football players at higher altitude would be insignificant is simply irresponsible. In fact, our findings support the need for further research in this area specifically because the population at risk is large (1,116,739 US high school students played football in the 2012-2013 academic year), because the rate of concussion in this population has increased significantly over the past decade,1 and given the concerns regarding the potential severity of both short- and long-term outcomes for young athletes sustaining concussion. Contrary to the suggestions of the author, calculations of absolute risk are most appropriately reserved for studies much farther along in lines of research than pilot studies such as this. Again, studies of novel hypotheses, such as ours, are intended to drive discussion, generate more questions/hypotheses, and lead to additional research as we indicated in our original report—they are not intended to be used to determine clinical significance. The authors also agree with the author of the Letter to the Editor that there should be a strong methodological rational for dichotomization of comparison groups. As clearly stated in our article, the 497 study schools were dichotomized by altitude using 600-ft elevation as the cut-off point because that was the median elevation for schools in our study sample. Researchers dichotomizing study samples traditionally utilize sample medians or means as cut-off points if a clear rationale for a physiologically driven cut-off point is not available (and frequently even when one is available). Utilizing a sample median as a cut-off point for dichotomization is a standard practice, not an arbitrary decision, and the author’s categorization of it as such is inaccurate. Furthermore, the mean altitude of the schools in the lower half of our dichotomized altitude variable was 244 ft while the mean altitude of schools in the upper half was 1689 ft (data not presented in the published article), which, coupled with the overall range of the study sample from 7 to 6903 ft in elevation, demonstrates this sample’s broad representation across the altitude continuum. Finally, the High School RIO surveillance system has, for the past 8 years, captured data from a large national sample of US high schools and the aggregate data set represents the largest database of high school sports–related injuries collected to date. We feel confident that our findings from the analyses of this large national sample are generalizable to the broader population of US high school athletes, and thus the author’s description of the findings being an “artifact” of the data set is another inaccurate categorization. We acknowledge that the hydrodynamics of the intracranial space were not measured and therefore cannot confirm the mechanism by which reduction in concussion occurred. But, as speculated in the article, the physiological adaptation to higher altitude is one potential explanation for reduced concussion incidence at increased altitude. Cerebral blood flow rises in response to even mild hypoxemia (low oxygen levels), including hypoxic changes associated with increased elevations.5 Increased cerebral blood flow would also result in cerebral venous engorgement and a subsequent rise in intracranial pressure when the limits of cerebral compliance are reached.4 However, the relationship between increased altitude adaptation and mitigating concussive symptoms is unclear. While at extreme elevations, hypoxemia of the brain can have serious negative health effects (mountain sickness, high-altitude headache, and high-altitude cerebral edema), at lower altitudes, we still expect alterations of physical and physiological parameters as minor changes in air density, humidity, temperature, and oxygen levels occur, especially up to the maximum elevation of 7000 feet used in this study. However, the authors acknowledge that this relationship may be because of reasons other than the proposed physiological response to elevation, and further verification is needed. In conclusion, while we welcome the discussion generated by our publication and appreciate the viewpoints raised in the Letter to the Editor, we respectfully disagree with the author’s critiques. We are confident in our work and our realistic valuation of it as the important first step in a novel line of research. Of interest, a recent investigation reported very similar results of a 32% reduction in risk of concussion in National Football League games played at higher altitudes.2 Regardless, it is clear that more work is needed to fully understand the potential reasons or mechanism(s) underlying the results of our published investigation.

Background: Recent research indicates that the volume and/or pressure of intracranial fluid, a physiology affected by one’s altitude (ie, elevation above sea level), may be associated with the likelihood and/or severity of a concussion. The objective was to employ an epidemiological field investigation to evaluate the relationship between altitude and concussion rate in high school sports. Hypothesis: Because of the physiologies that occur during acclimatization, including a decline in intracranial compliance (a “tighter fit”), increased altitude may be related to a reduction in concussion rates in high school athletes. Study Design: Cohort study; Level of evidence, 3. Methods: Data on concussions and athlete exposures (AEs) between 2005-2006 and 2011-2012 were obtained from a large national sample of high schools (National High School Sports-Related Injury Surveillance System [High School RIO]) and were used to calculate total, competition, and practice concussion rates for aggregated sports and for football only. Results: Altitude of participating schools ranged from 7 to 6903 ft (median, 600 ft), and a total of 5936 concussions occurred in 20,618,915 exposures (2.88 per 10,000 AEs). When concussion rates were dichotomized by altitude using the median, elevated altitude was associated with a reduction in concussion rates overall (rate ratio [RR], 1.31; P < .001), in competition (RR, 1.31; P < .001), and in practice (RR, 1.29; P < .001). Specifically, high school sports played at higher altitude demonstrated a 31% reduction (95% confidence interval [CI], 25%-38%) in the incidence of total reported concussions. Likewise, concussion rates at increased altitude were reduced 30% for overall exposures, 27% for competition exposures, and 28% for practice exposures in football players ( P < .001). Conclusion: The results of this epidemiological investigation indicate increased physiological responses to altitude may be associated with a reduction in sports-related concussion rates, especially in collision sports. Future research that focuses on the potential prophylactic effect of optimizing outflow impedance and thus reduction of intracranial compliance (a “tighter fit”) in humans is warranted to determine the most effective approaches to mitigate sport-related concussion, especially in football players.