Publications

2020

Ueno, Ryo, Takashi Nagai, Nathaniel A Bates, Timothy E Hewett, and Nathan D Schilaty. (2020) 2020. “Sex Differences in Passive and Active Stiffness of the Knee Flexor Muscles During Dynamic Perturbation Test: Principal Component Analysis.”. Somatosensory & Motor Research 37 (4): 293-99. https://doi.org/10.1080/08990220.2020.1824905.

PURPOSE: The sensorimotor system is a subcomponent of the comprehensive motor control system of the body. However, the complex nature of the sensorimotor system makes it difficult to interpret findings for clinical application. The purpose of this study was to utilize principal component analysis (PCA) to identify sex differences and relationships between sensorimotor variables during a dynamic perturbation.

MATERIALS AND METHODS: Thirty physically active individuals (15 males and 15 females) were blindfolded and positioned on an isokinetic dynamometer with their knee flexed to 70°. At random, the dynamometer moved rapidly towards knee extension. Subjects were asked to resist the dynamometer as it would randomly and rapidly move towards knee extension. Torque and position values were used to calculate stiffness values.

RESULTS: PCA revealed sex differences in two principal components (PCs): PC2 in female was comprised from higher position, torque, and time values (p = .038), PC4 in females was comprised from higher active stiffness and lower short-range stiffness values (p = .032) compared to males. Torque at the resting position was correlated to the short-range passive stiffness (ρ = 0.539, p = .002), time to peak torque (ρ = -0.375, p = .003), and reactive stiffness (ρ = 0.526, p = .041).

CONCLUSIONS: Females had later reaction time and lower short-range passive stiffness and they resisted the dynamometer by their voluntary activation compared to the males thus requiring muscle activation for meaningful response. In addition, the higher resting muscle activities may correlate to short-range passive stiffness and quicker active stiffness. Abbreviations: ACL: anterior cruciate ligament; EEG: electroencephalogram; EMG: electromyography; ICC: intraclass correlation coefficient; MDC95: minimally detectable differences at 95% confidence intervals; PC: principal component; PCA: principal component analysis; POS50: position value at 50 ms; POS100: position value at 100 ms; POSprop: position value at TIMEprop; POSpk: position value at TIMEpk; POSprop-pk: position difference between POSprop and POSpk; SEM: standard error of measurements; STIFF50: short-range-stiffness at 50 ms; STIFF100: short-range-stiffness at 100 ms; STIFFreac: reactive knee stiffness (stiffness between TIMEprop to TIMEpk); TIMEprop: threshold-to-detect passive movement as the time point; TIMEpk: time at which peak hamstrings torque occurred; TIMEprop-pk: time between TIMEprop to TIMEpk; TORQ0: torque value at time zero; TORQ50: torque value at 50 ms; TORQ100: torque value at 100 ms; TORQprop: torque value at TIMEprop; TORQpk: torque value at TIMEpk; TORQ50diff: torque difference between TORQ0 and TORQ50; TORQ100diff: torque difference between TORQ0 and TORQ100.

Bates, Nathaniel A, Gregory D Myer, Rena F Hale, Nathan D Schilaty, and Timothy E Hewett. (2020) 2020. “Prospective Frontal Plane Angles Used to Predict ACL Strain and Identify Those at High Risk for Sports-Related ACL Injury.”. Orthopaedic Journal of Sports Medicine 8 (10): 2325967120957646. https://doi.org/10.1177/2325967120957646.

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.

Mumbleau, Allison M, Nathan D Schilaty, and Timothy E Hewett. (2020) 2020. “HIP MUSCLE INHIBITION AFTER HIP ARTHROSCOPY: A ROLE FOR NEUROMUSCULAR ELECTRICAL STIMULATION.”. International Journal of Sports Physical Therapy 15 (6): 1222-28. https://doi.org/10.26603/ijspt20201222.

BACKGROUND/PURPOSE: The number of hip arthroscopies (HAs) performed in the United States is increasing exponentially. Previous authors have shown improvements in short- and mid-term functional outcomes after HA. Despite established overall improvements, functional and objective impairments may persist. In particular, preliminary work demonstrates differences in hip strength between patients who undergo HA when compared to healthy controls at 12- and 24-months post-operative. The purpose of this clinical commentary is to highlight the persistent hip muscle strength and neuromuscular deficits that occur after HA, as well as propose the utilization of neuromuscular electrical stimulation (NMES) as an adjunct to strengthening exercises in early post-operative rehabilitation to address deficits.

DESCRIPTION OF TOPIC: Arthrogenic muscle inhibition (AMI), drives neuromuscular dysfunction and has been shown to occur in peripheral joints. The knee and hip have historically benefited from NMES to aid in improved muscular function, such as in those who have undergone anterior cruciate ligament reconstruction, total hip or knee arthroplasties. Improving muscular strength is a hallmark component of rehabilitation after HA, however, current post-operative HA rehabilitation protocols do not include NMES as a standard treatment intervention. Therapeutic intervention strategies to target muscular inhibition after HA, in particular with the goal to address neural reflex inhibition, have not been thoroughly investigated. This absence of understanding of this important problem yields a critical gap in the treatment of post-operative muscular deficits in patients after HA.

DISCUSSION: The consequence of hip muscle inhibition is likely to include deficits in strength and function, similar to that seen in other muscular groups. Filling the void of current knowledge with regard to muscle inhibition and strength deficits after hip arthroscopy is critical to establish standardized post-operative rehabilitation protocols, as well as to provide targeted training to address muscular inhibition. Ultimately, these strategies could produce improved outcomes guided by robust evidence-based protocols.

LEVEL OF EVIDENCE: 5.

Hedges, David M, Jordan T Yorgason, Andrew W Perez, Nathan D Schilaty, Benjamin M Williams, Richard K Watt, and Scott C Steffensen. (2020) 2020. “Spontaneous Formation of Melanin from Dopamine in the Presence of Iron.”. Antioxidants (Basel, Switzerland) 9 (12). https://doi.org/10.3390/antiox9121285.

Parkinson's disease is associated with degeneration of neuromelanin (NM)-containing substantia nigra dopamine (DA) neurons and subsequent decreases in striatal DA transmission. Dopamine spontaneously forms a melanin through a process called melanogenesis. The present study examines conditions that promote/prevent DA melanogenesis. The kinetics, intermediates, and products of DA conversion to melanin in vitro, and DA melanogenesis under varying levels of Fe3+, pro-oxidants, and antioxidants were examined. The rate of melanogenesis for DA was substantially greater than related catecholamines norepinephrine and epinephrine and their precursor amino acids tyrosine and l-Dopa as measured by UV-IR spectrophotometry. Dopamine melanogenesis was concentration dependent on the pro-oxidant species and Fe3+. Melanogenesis was enhanced by the pro-oxidant hydrogen peroxide (EC50 = 500 μM) and decreased by the antioxidants ascorbate (IC50 = 10 μM) and glutathione (GSH; IC50 = 5 μM). Spectrophotometric results were corroborated by tuning a fast-scan cyclic voltammetry system to monitor DA melanogenesis. Evoked DA release in striatal brain slices resulted in NM formation that was prevented by GSH. These findings suggest that DA melanogenesis occurs spontaneously under physiologically-relevant conditions of oxidative stress and that NM may act as a marker of past exposure to oxidative stress.

2019

Nagai, Takashi, Nathaniel A Bates, Timothy E Hewett, and Nathan D Schilaty. (2019) 2019. “Paradoxical Relationship in Sensorimotor System: Knee Joint Position Sense Absolute Error and Joint Stiffness Measures.”. Clinical Biomechanics (Bristol, Avon) 67: 34-37. https://doi.org/10.1016/j.clinbiomech.2019.04.021.

BACKGROUND: Relationships between joint position sense and the sensorimotor characteristics such as joint stiffness, time to detect motion, and time to peak torque during a perturbation test have rarely been investigated due to methodological challenges. The purpose of this study was to compare joint position sense and the sensorimotor characteristics in healthy individuals.

METHODS: A total of 26 subjects were recruited and completed joint position sense and a perturbation test on isokinetic dynamometer. Joint position sense was assessed by comparison of the absolute angle difference between a reference and replicated position. During the perturbation test, the dynamometer moved the knee flexion angle from 70° to 30° (0° represents a full knee extension) at the velocity of 500° per second at random. Subjects were asked to react and pull back the leg as soon as they perceived the movement. Pearson or Spearman's correlation coefficients were used to assess these relationships (P < 0.05).

FINDINGS: Larger joint position sense absolute error values were significantly correlated with higher short-range at 50 milliseconds (r = 0.572, P = 0.002), at 100 milliseconds (ρ = 0.416, P = 0.035), and reactive joint stiffness (r = 0.395, P = 0.046).

INTERPRETATION: There was a paradoxical relationship between higher joint stiffness and worsened joint position sense. Potential reasons include sensory weighting within the sensorimotor system and thixotropic properties (after-effects of muscle eccentric contractions to increase stiffness and alter joint position sense).

Bates, Nathaniel A, Maria C Mejia Jaramillo, Manuela Vargas, April L McPherson, Nathan D Schilaty, Christopher Nagelli V, Aaron J Krych, and Timothy E Hewett. (2019) 2019. “External Loads Associated With Anterior Cruciate Ligament Injuries Increase the Correlation Between Tibial Slope and Ligament Strain During in Vitro Simulations of in Vivo Landings.”. Clinical Biomechanics (Bristol, Avon) 61: 84-94. https://doi.org/10.1016/j.clinbiomech.2018.11.010.

BACKGROUND: The aim of the present study was to evaluate the relationship between tibial slope angle and ligament strain during in vitro landing simulations that induce ACL failure through the application of variable external loading at the knee. The hypothesis tested was that steeper posterior tibial slope angle would be associated with higher ACL strain during a simulated landing task across all external loading conditions.

METHODS: Kinetics previously derived from an in vivo cohort performing drop landings were reproduced on 45 cadaveric knees via the mechanical impact simulator. MRIs were taken of each specimen and used to calculate medial compartment posterior tibial slope, lateral compartment posterior tibial slope, and coronal plane tibial slope. Linear regression analyses were performed between these angles and ACL strain to determine whether tibial slope was a predictive factor for ACL strain.

FINDINGS: Medial and lateral posterior tibial slope were predictive factors for ACL strain during some landings with higher combined loads. Medial posterior slope was more predictive of ACL strain in most landings for male specimens, while lateral posterior and coronal slope were more predictive in female specimens, but primarily when high abduction moments were applied.

INTERPRETATION: Tibial slope has the potential to influence ACL strain during landing, especially when large abduction moments are present at the knee. Deleterious external loads to the ACL increase the correlation between tibial slope and ACL strain, which indicates that tibial slope angles are an additive factor for athletes apt to generate large out-of-plane knee moments during landing tasks.

Schilaty, Nathan D, Nathaniel A Bates, Aaron J Krych, and Timothy E Hewett. (2019) 2019. “Frontal Plane Loading Characteristics of Medial Collateral Ligament Strain Concurrent With Anterior Cruciate Ligament Failure.”. The American Journal of Sports Medicine 47 (9): 2143-50. https://doi.org/10.1177/0363546519854286.

BACKGROUND: Both the anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) bear load during athletic tasks of landing, cutting, pivoting, and twisting. As dynamic knee valgus is a purported mechanism for ACL injury, the MCL should bear significant strain load with valgus force.

HYPOTHESIS: The intact MCL will demonstrate a significant increase in strain upon failure of the ACL at 25° of knee flexion.

STUDY DESIGN: Controlled laboratory study.

METHODS: In vivo kinetics/kinematics of 44 healthy athletic participants were measured to determine stratification of injury risk (ie, low, medium, and high) in 3 degrees of knee forces/moments (knee abduction moment, anterior tibial shear, and internal tibial rotation). These stratified kinetic values were input into a cadaveric impact simulator to assess ligamentous strain during a simulated landing task. Uniaxial and multiaxial load cells and differential variable reluctance transducer strain sensors were utilized to collect mechanical data for analysis. Conditions of external loads applied to the cadaveric limbs were varied and randomized.

RESULTS: ACL strain increased with increased dynamic knee abduction moment (χ2[5] = 14.123, P = .0148). The most extreme dynamic knee abduction moment condition demonstrated significantly higher ACL strain compared with lower loaded trials (P≤ .0203). Similarly, MCL strain increased with dynamic knee abduction moment (χ2[5] = 36.578, P < .0001). Matched-pairs analysis compared ACL strain with MCL strain (maximum ACL strain - maximum MCL strain) and demonstrated high strain for the ACL versus the MCL (S177 = 6223.5, P < .0001).

CONCLUSION: Although significant, MCL strain had minimal increase with increased dynamic knee abduction moment, and the event of ACL failure did not significantly increase MCL strain when compared with high dynamic knee abduction moment conditions in the cadaveric model. The ACL bears more strain than the MCL at increasing amounts of dynamic knee abduction moment at 25° of knee flexion, which may explain the limited concomitant MCL injury rate that can occur during a dynamic valgus collapse of the knee.

CLINICAL RELEVANCE: These characteristics of ACL and MCL strain are important to understand the mechanisms that drive these injuries at the knee and will improve rehabilitation and injury prevention techniques.

Bates, Nathaniel A, Nathan D Schilaty, Christopher Nagelli V, Aaron J Krych, and Timothy E Hewett. (2019) 2019. “Multiplanar Loading of the Knee and Its Influence on Anterior Cruciate Ligament and Medial Collateral Ligament Strain During Simulated Landings and Noncontact Tears.”. The American Journal of Sports Medicine 47 (8): 1844-53. https://doi.org/10.1177/0363546519850165.

BACKGROUND: Anterior cruciate ligament (ACL) tears and concomitant medial collateral ligament (MCL) injuries are known to occur during dynamic athletic tasks that place combinatorial frontal and transverse plane loads on the knee. A mechanical impact simulator that produces clinical presentation of ACL injury allows for the quantification of individual loading contributors leading to ACL failure.

PURPOSE/HYPOTHESIS: The objective was to delineate the relationship between knee abduction moment, anterior tibial shear, and internal tibial rotation applied at the knee and ACL strain during physiologically defined simulations of impact at a knee flexion angle representative of initial contact landing from a jump. The hypothesis tested was that before ACL failure, abduction moment would induce greater change in ACL strain during landing than either anterior shear or internal rotation.

STUDY DESIGN: Controlled laboratory study.

METHODS: Nineteen cadaveric specimens were subjected to simulated landings in the mechanical impact simulator. During simulations, external knee abduction moment, internal tibial rotation moment, and anterior tibial shear loads were derived from a previously analyzed in vivo cohort and applied to the knee in varying magnitudes with respect to injury risk classification. Implanted strain gauges were used to track knee ligament displacement throughout simulation. Kruskal-Wallis tests were used to assess strain differences among loading factors, with Wilcoxon each pair post hoc tests used to assess differences of magnitude within each loading.

RESULTS: Each loading factor significantly increased ACL strain (P < .005). Within factors, the high-risk magnitude of each factor significantly increased ACL strain relative to the baseline condition (P≤ .002). However, relative to knee abduction moment specifically, ACL strain increased with each increased risk magnitude (P≤ .015).

CONCLUSION: Increased risk levels of each load factor contributed to increased levels of ACL strain during a simulated jump landing. The behavior of increased strain between levels of increased risk loading was most prevalent for changes in knee abduction moment. This behavior was observed in the ACL and MCL.

CLINICAL RELEVANCE: Knee abduction moment may be the predominant precursor to ACL injury and concomitant MCL injury. As knee abduction occurs within the frontal plane, primary preventative focus should incorporate reduction of frontal plane knee loading in landing and cutting tasks, but secondary reduction of transverse plane loading could further increase intervention efficacy. Constraint of motion in these planes should restrict peak ACL strain magnitudes during athletic performance.

Savoldi, Filippo, Zahra Nasr, Wei Hu, Nathan D Schilaty, Adriana M Delgado, Jay Mandrekar, Kenton R Kaufman, Lawrence Berglund, and Brian G Weinshenker. (2019) 2019. “McArdle Sign: A Specific Sign of Multiple Sclerosis.”. Mayo Clinic Proceedings 94 (8): 1427-35. https://doi.org/10.1016/j.mayocp.2019.01.047.

OBJECTIVE: To measure McArdle sign (rapidly reversible weakness induced by neck flexion) both qualitatively and quantitatively and to evaluate its specificity and clinical utility for diagnosis of multiple sclerosis (MS).

PATIENTS AND METHODS: In this prospective study, McArdle sign was evaluated by a technician blinded to diagnosis by measuring changes in finger extensor strength in successive trials of neck extension and flexion, first clinically and then with a torque measurement device. We studied 25 healthy controls and 81 patients with finger extensor weakness. Patients were not selected for having McArdle sign. Fifty-two patients had MS, 24 had other myelopathies, and 5 had peripheral nerve lesions accounting for their weakness. The study was conducted between February 1, 2016, and June 30, 2017.

RESULTS: The median clinical McArdle sign and the 2 quantitative measures of neck flexion-induced strength reduction were greater in patients with MS than in the other groups (P<.001). Baseline strength did not confound the difference. The area under the receiver operating characteristic curve was 0.84 (95% CI, 0.75-0.93) comparing patients with MS vs healthy controls and 0.84 (95% CI, 0.75-0.93) comparing MS vs patients with other myelopathies. The 2 quantitative and 1 clinical measurement of McArdle sign by the technician who performed the quantitative testing were correlated (r=.57 and r=.58; P<.001), and in turn, the technician's and unblinded referring physician's clinical assessments were correlated (r=.58; P<.001). McArdle sign was evident in some patients who had minor disability and who were in early phases of MS.

CONCLUSION: McArdle sign, when defined as greater than 10% neck flexion-induced reduction in strength, is entirely specific and 65% sensitive for a diagnosis of MS when compared with other conditions that mimic MS-associated myelopathy. It may facilitate diagnosis in certain clinical situations.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03122873.

Navacchia, Alessandro, Nathaniel A Bates, Nathan D Schilaty, Aaron J Krych, and Timothy E Hewett. (2019) 2019. “Knee Abduction and Internal Rotation Moments Increase ACL Force During Landing Through the Posterior Slope of the Tibia.”. Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society 37 (8): 1730-42. https://doi.org/10.1002/jor.24313.

The mechanism underlying non-contact anterior cruciate ligament (ACL) injury is multi-factorial and still an object of debate. Computational models, in combination with in vivo and cadaveric studies, can provide valuable insight into the contribution of the different factors involved. The goal of this study was to validate four knee finite element models (two males and two females) to kinematic and strain data collected in vitro with an impact-driven simulator and use them to assess how secondary external knee loads (knee abduction moment [KAM], anterior shear force, and internal rotation torque [ITR]) affect tibiofemoral contact forces and ACL force during impact. Four subject-specific knee models were developed from specimen computed tomography and magnetic resonance imaging. Patellofemoral and tibiofemoral ligament properties were calibrated to match experimentally measured kinematics and ligament strain. Average root mean square errors and correlations between experimental and model-predicted knee kinematics were below 1.5 mm and 2°, and above 0.75, respectively. Similar errors and correlations were obtained for ACL strain (< 2% and > 0.9). Model-predicted ACL forces were highly correlated with the anterior component of the tibiofemoral contact force on the lateral plateau occurring during impact (r = 0.99), which was increased by larger KAM and ITR through the posterior tibial slope and a larger contact force on the lateral side. This study provides a better understanding of the mechanism through which secondary external knee loads increase ACL injury risk during landing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1730-1742, 2019.