Abstract
Anterior cruciate ligament (ACL) ruptures result in lasting quadriceps dysfunction that contributes to secondary injury risk and development of osteoarthritis. There is evidence of persistent reduced nervous system drive (corticospinal excitability, CSE) to the quadriceps and sex differences in both quadriceps performance and CSE post-ACL reconstruction (ACLR). The purposes of this study were to investigate the differences in CSE and quadriceps dysfunction after ACLR between sexes and relative to controls. Twenty subjects 4-9 months post ACLR and 20 age, sex, and activity matched controls participated in this study. Quadriceps performance (peak torque, PT; rate of torque development from onset to 100ms, RTD100; and RTD from 100-200ms, RTD200) and CSE (active motor threshold, AMT; slope of the stimulus response curve, SR curve slope) were measured using an isokinetic dynamometer (HUMAC NORM) and transcranial magnetic stimulation respectively. Significant group differences were found for SR curve slope, PT, RTD100, and RTD200 on the surgical limb. Males after ACLR had higher slopes (higher CSE) than females. Females after ACLR had worse surgical limb quadriceps PT than control males and slower RTD100 and RTD200 than control males and control females. Higher CSE in males after ACLR may point to a potentially adaptive neurological change in males post-ACLR and indicate greater need for novel interventions to address cortical drive in females after ACLR.
Introduction
Incidence of anterior cruciate ligament (ACL) injuries is widely known to be greater in female than male athletes.1-4 Previously, the higher risk in females was attributed to anatomical, neuromuscular, biomechanical, and hormonal risk factors with a consensus that injury risk in females is multifactorial.1,4,5 More recently, studies are beginning to investigate sex differences in recovery from ACL reconstruction (ACLR), with findings suggesting worse long-term patient reported outcomes in pain and function in females.6,7
Evidence also highlights sex differences in quadriceps function with lower normalized peak torque and slower rate of torque development (RTD) in females than males after ACLR.8-12 The relationship between quadriceps strength and self-reported function, knee biomechanics, risk of secondary injury and development of osteoarthritis is well established.13-18 Quadriceps deficits persist well beyond the standard course of care and return to sport with lasting quadriceps weakness relative to the opposite limb and to healthy controls years after ACLR.19,20 The implications of quadriceps dysfunction after ACLR and evidence of exaggerated post-ACLR quadriceps dysfunction in females warrants further investigation of quadriceps performance based on sex.
Mechanisms underlying quadriceps weakness after ACLR include altered descending neural drive from the motor cortex to the peripheral musculature.19,21,22 Specifically, corticospinal excitability (CSE) to the quadriceps differs after ACLR compared to controls and does not change during the course of post-operative rehabiliation.22-25 There is evidence of a negative relationship between motor threshold (a measure of CSE that captures the magnitude of stimulus at the motor cortex required to elicit a consistent response at the quadriceps) and quadriceps function after ACLR, meaning those with higher thresholds (lower CSE) exhibited worse quadriceps performance.23,25,26 To our knowledge only two studies have examined sex difference in CSE after ACLR. Zarzycki et al. found females exhibit higher CSE compared to males after ACLR,22 while Lepley et al. found no difference in CSE between males and females.24 Therefore, the purposes of this study were 1) to determine differences in CSE and quadriceps muscle performance between males and females after ACLR and 2) to identify relationships between CSE and quadriceps performance after ACLR. We hypothesized 1) females after ACLR would demonstrate lower CSE and poorer quadriceps performance compared to males after ACLR and healthy controls based on existing knowledge of sex differences in quadriceps performance after ACLR and 2) there would be a positive relationship between CSE and quadriceps performance measures after ACLR indicating greater excitability would be associated with greater quadriceps performance.
Methods
Study Design
This was a cross-sectional observational analysis of a larger clinical trial (ClinicalTrials.gov Identifier NCT04504344) examining the acute effects of transcranial direct current stimulation on corticospinal excitability and quadriceps muscle performance. To control for the effects of knee impairments (i.e. knee range of motion, knee effusion, and knee pain), enrollment of individuals after ACLR took place no sooner than 4 months from ACLR and after achieving a “quiet knee” defined as achieving full knee range of motion, minimal to no knee effusion/pain, and ambulating without a visual gait deviation. This is a first clinical milestone after ACLR and marks the transition to more aggressive knee strengthening and progression of weight bearing exercises. This clinical milestone was selected to remove potential confounders (e.g. pain, effusion) that affect neural drive.27
Participants were involved in level I/II sports (i.e. involved in cutting, pivoting, jumping sports for greater than 50 hours per year) prior to injury and planned to return to level I/II sports.28 Exclusion criteria included: 1) multiple ligament reconstruction, 2) osteo-chondral procedures, 3) any previous lower extremity surgery, and 4) previous ACL injury. We did not control for meniscal procedures or graft type. Metal or implants in the head or neck, history of neurological disease, seizures, severe migraines, and concussion within the last 6 months are transcranial magnetic stimulation (TMS) specific exclusion criteria. This study was approved by our institution’s Institutional Review Board and all subjects completed informed consent.
Quadriceps Muscle Performance Measures
All quadriceps performance measures were examined bilaterally. Participants were seated on an isokinetic dynamometer (HUMAC NORM, CSMi, Stoughton, MA) with hips flexed to 90° and knee flexed to 60°. Three submaximal isometric contractions were performed to warm up (participants were instructed to perform isometric quadriceps contraction at 50%, 75%, and 100% effort), followed by three maximal voluntary isometric contractions (MVIC), each lasting 5 seconds. Verbal instruction for MVICs were provided as “kick out as hard and as fast as you can.” Verbal encouragement and visual feedback of the time-torque curve were provided to ensure maximal effort during each MVIC. Peak isometric torque normalized to body weight, and rate of torque development (RTD) were analyzed. For RTD, we calculated the slope of the torque-time curve over the first 100ms and 100-200ms for each MVIC. The highest RTD over the three trials was used for analysis.
Measures of Corticospinal Excitability
Electromyography (EMG) data was collected using an MA-300 system (Motion Lab Systems, Baton Rouge, LA) sampled at 5000 Hz. Surface EMG electrodes (bar shaped double differential preamplifiers) were placed over the muscle bellies of the vastus medialis bilaterally per Seniam placement recommendations.29 Skin preparation (shaved if hair present, isopropyl alcohol to clean/abrade the skin) preceded electrode placement. Wraps were utilized to stabilize the electrodes and improve electrode to skin contact. All data were acquired through Signal Software (Cambridge Electronic Design Limited, Cambridge, England).
Measures of CSE using single pulse TMS with a double cone coil (Magstim bistim, Magstim®, West Wales, UK), were examined bilaterally while the participant was seated on an isokinetic dynamometer with the knee positioned at 60 degrees. The nonsurgical side was tested first in the ACLR group and randomly in the control group. All TMS measures were obtained while the participant maintained a quadriceps torque at 5% of their MVIC via visual feedback. The vertex of the skull was identified by measuring the distance from the inion to the nasion and the distance from the tragus of each ear. This location was used as a starting point to locate the “hot spot” which is defined as the location of the coil where TMS elicits the greatest EMG response to the vastus medialis. The vastus medialis muscle was chosen based on the fact that the majority of studies in this area have examined the vastus medialis. Additionally, there is evidence that one quadriceps muscle can act as a surrogate for the other quadriceps muscles.30
Two measures of CSE were examined. First, active motor thresholds (AMT) were determined. The AMT is defined as the lowest stimulator output required to obtain motor evoked potentials greater than or equal to 100 μV in at least 5 of 10 consecutive TMS pulses. Second, stimulus-response (SR) curves were generated obtaining MEPs at 90%-140% of the individual’s active motor threshold. Each participant received five pulses in 10% increments from 90-140%. The average peak-to-peak amplitude of each MEP elicited at a given percentage of AMT were plotted as a stimulus-response curve. Using Microsoft excel (Microsoft Corp., Redmond, WA) a linear function was applied to the data and the slope of the linear function was used for analysis (Slope).
Statistical Analysis
A one-way analysis of variance (ANOVA) was used to determine between group differences (ACLR male (ACLR M), ACLR female (ACLR F), Control male (Control M), Control female (Control F)) on corticospinal excitability and quadriceps performance measures. When a significant difference was found post-hoc Bonferroni analyses were used to determine where differences lied. We also calculated effect sizes (Cohen’s d) between groups on all measures.31 A small effect was defined as d ≥ 0.20, a medium effect d ≥ 0.50, and a large effect d ≥ 0.80.
We performed separate linear regressions within the ACLR group and within the control group to identify relationships between CSE (i.e. AMT and Slope) and all quadriceps performance measures (PT, RTD100, RTD200).
Results
Demographics
Twenty subjects with ACLR (11 female, 9 male) and 20 age-, sex-, and activity-matched controls (11 female, 9 male) participated in this study (Table 1). There were no significant differences between groups in age (ACLR 23.9±6.3 years, controls 23.7 ± 5.9 years, p=0.94), height (ACLR 1.7 ± 0.1m, controls 1.7±0.1m, p=0.57), mass (ACLR 71.25 ± 12.26 kg, controls 71.66 ± 10.20, p=0.91), or BMI (ACLR 24.3 ± 3.3, controls 25.0±3.4, p=0.50). There were no significant differences between ACLR females and ACLR males in age, mass, BMI, or time since surgery (p≥0.124). There was a difference in height between ACLR females and ACLR males (ACLR F 1.6 ± 0.05m, ACLR M 1.8 ± 0.06m, p<0.001).
Table 1.
Demographics
| Category | Control (n=20) | ACL (n=20) | P- value |
|
|---|---|---|---|---|
| F(n=11) | M(n=9) | |||
| Age, years (mean ± SD) | 23.7 ± 5.9 | 23.9 ±6.3 | 0.939 | |
| 24.6±7.4 | 22.89 ± 4.9 | 0.553 | ||
| Height, m (mean ± SD) | 1.7 ± 0.1 | 1.7 ± 0.1 | 0.566 | |
| 1.6 ± 0.1 | 1.8 ± 0.1 | <0.001 | ||
| Mass, kg (mean ± SD) | 71.7 ±10.2 | 71.3 ± 12.3 | 0.909 | |
| 67.1 ± 13.0 | 76.4±9.6 | 0.093 | ||
| BMI, kg/m2 (mean ± SD) | 25.0 ± 3.4 | 24.3 ±3.3 | 0.498 | |
| 24.7±3.9 | 23.8±2.4 | 0.566 | ||
| Time since surgery, months (mean ± SD) | - | 5.4±1.1 | - | |
| 5.7±1.3 | 5.0±0.5 | 0.124 | ||
| Activity Level, n (%) | Level I, 10(50%) Level II, 10(50%) |
Level I, 13 (65%) Level II, 7 (35%) |
- | |
| Level I, 6(55%) Level II, 5(45%) |
Level I, 7(78%) Level II, 2(22%) |
|||
| Graft type | - | BPTB, 14 (70%) HS, 2 (10%) QT, 1 (5%) Allograft, 3 (15%) |
- | |
| BPTB, 7 (63%) HS, 1 (9%) QT, 1 (9%) Allograft, 2 (19%) |
BPTB, 7 (78%) HS, 1 (11%) Allograft, 1 (11%) |
|||
SD, Standard deviation
Corticospinal excitability
There were no significant between group differences in AMT on either side (p≥0.395). There were significant between group differences in the slope of the stimulus-response curve of the surgical side (p=0.007), (Table 2). Post-hoc Bonferroni tests revealed significantly higher slopes in ACLR males, indicating greater CSE, than all females (ACLR females p=0.028, female controls p=0.007). While the difference between ACLR males and control males did not reach statistical significance (p=0.075), there was a large effect with a confidence interval that did not cross zero (1.04; 95% CI 0.01-1.97). Effect sizes for all individual group comparisons for both measures of CSE can be found in Table 3.
Table 2.
CSE (mean ± SD)
| Group | Surgical | Non-surgical | ||
|---|---|---|---|---|
| AMT | Slope | AMT | Slope | |
| ACLR M | 43.11 ± 8.80 | 0.073 ± 0.038 | 39.89±8.62 | 0.074±0.030 |
| ACLR F | 46.18 ± 12.71 | 0.035 ± 0.027 | 47.09±12.25 | 0.043±0.046 |
| Control M | 43.44 ± 8.53 | 0.038 ± 0.023 | 43.25±6.86 | 0.042±0.030 |
| Control F | 42.00 ± 8.28 | 0.028 ± 0.025 | 42.73±7.85 | 0.030±0.027 |
| p-value | 0.787 | 0.007 | 0.395 | 0.052 |
SD, standard deviation; AMT, Active motor threshold; Slope, slope of the stimulus response curve
Table 3.
CSE Effect Sizes (Cohen’s d, 95% CI)
| Surgical | Non-surgical | |||
|---|---|---|---|---|
| AMT | Slope | AMT | Slope | |
| ACLR M-ACLR F | −0.28 (−1.15, 0.62) | 1.19 (0.19, 2.09) | −0.67 (−1.54, 0.26) | 0.78 (−0.16, 1.66) |
| ACLR M-Control F | 0.13 (−0.86, 1.01) | 1.36 (0.33, 2.27) | −0.35(−1.22, 0.56) | 1.55 (0.49, 2.48) |
| ACLR M-Control M | −0.04 (−0.96, 0.89) | 1.04 (0.01, 1.97) | −0.43(−1.37, 0.56) | 1.07 (0.03, 2.00) |
| ACLR F – Control F | 0.39 (−0.47, 1.22) | 0.27 (−0.58, 1.10) | 0.42 (−0.44, 1.25) | 0.34 (−0.51, 1.17) |
| ACLR F – Control M | 0.25 (−0.65, 1.12) | −0.12 (−1.00,0.77) | 0.37 (−0.56, 1.27) | 0.03 (−0.86, 0.91) |
AMT, Active motor threshold; Slope, slope of the stimulus response curve
Quadriceps function
There were significant differences between groups on all surgical limb quadriceps performance measures (Table 4 and Table 5). ACLR females produced lower surgical limb PT than control males (ACLR F 1.6Nm/kg, Control M 2.78 Nm/kg, p=0.03). ACLR females also had slower surgical limb RTD100 than controls regardless of sex (ACLR F 319.1 Nm/s, Control F 816.3Nm/s, Control M 807.1Nm/s, p<0.004), and slower surgical limb RTD200 than controls regardless of sex (ACLR F 215.9Nm/s, Control F 538.2Nm/s, Control M 501.5Nm/s, p<0.001). ACLR males demonstrated lower RTD200 (336.8Nm/s) than female controls (p=0.007).
Table 4.
Quadriceps function (mean ± SD)
| Group | Surgical | Non-surgical | ||||
|---|---|---|---|---|---|---|
| PT (Nm/kg) |
RTD100 (Nm/s) |
RTD200 (Nm/s) |
PT (Nm/kg) |
RTD100 (Nm/s) |
RTD200 (Nm/s) |
|
| ACLR M | 2.3 ± 0.7 | 638.6 ± 298.6 | 336.8 ± 119.0 | 3.1±0.7 | 892.4±378.2 | 597.0±160.0 |
| ACLR F | 1.6 ± 0.8 | 319.1 ± 161.4 | 215.9 ± 111.5 | 2.3±0.6 | 482.6±263.4 | 373.6±118.7 |
| Control M | 2.8 ± 1.0 | 807.1 ± 449.7 | 501.5 ± 82.0 | 2.7±1.1 | 773.2±311.7 | 580.7±145.3 |
| Control F | 2.2 ± 1.0 | 816.3 ± 308.0 | 538.2 ± 168.2 | 2.2±1.0 | 711.6±310.2 | 503.7±154.7 |
| p-value | 0.041 | 0.002 | <0.001 | 0.113 | 0.042 | 0.005 |
SD, Standard deviation; PT, Peak torque; RTD100, rate of torque development from onset to 100ms; RTD200, rate of torque development from 100-200ms
Table 5.
Quad Performance Effect Sizes (Cohen’s d, 95% CI)
| Surgical | Non-surgical | |||||
|---|---|---|---|---|---|---|
| PT | RTD100 | RTD200 | PT | RTD100 | RTD200 | |
| ACLR M-ACLR F | 0.94 (−0.03, 1.82) | 1.37 (0.34, 2.29) | 1.05 (0.07, 1.94) | 1.27 (0.26, 2.17) | 1.28 (0.27, 2.19) | 1.61 (0.54, 2.55) |
| ACLR M-Control F | 0.09 (−0.79, 0.97) | −0.58 (−1.46, 0.34) | −1.36 (−2.27, −0.33) | 0.49 (−0.47, 1.40) | 0.71 (−0.22, 1.59) | 0.59 (−0.33, 1.47) |
| ACLR M-Control M | −0.58 (−1.49, 0.39) | −0.44 (−1.35, 0.51) | −1.61 (−2.59, −0.48) | 1.04 (0.06, 1.92) | 0.34 (−0.60, 1.26) | 0.11 (−0.82, 1.03) |
| ACLR F – Control F | −0.67 (−1.50, 0.21) | −2.02 (−2.96,−0.93) | −2.26 (−3.23, −1.12) | 0.12(−0.72,0.95) | −1.22(−2.08,−0.27) | −0.94 (−1.79,−0.03) |
| ACLR F – Control M | −1.32(−2.23,−0.30) | −1.51(−2.44,−0.46) | −2.87 (−3.98,−1.52) | −0.41(−1.28,0.50) | −1.02(−1.90,−0.04) | −1.58(−2.51,−0.51) |
PT, Peak torque; RTD100, rate of torque development from onset to 100ms; RTD200, rate of torque development from 100-200ms
On the non-surgical side significant between group differences were present only on RTD100 (p=0.042) and RTD200 (p=0.005). Post-hoc testing revealed the differences in the non-surgical side RTD100 lie between ACLR F and ACLR M (ACLR F 482.6 Nm/s, ACLR M 892.4 Nm/s, p=0.039). For RTD200 the ACLR F group differed from both groups of males (ACLR F 373.6 Nm/s; ACLR M 597.0 Nm/s, p=0.009; Control M 580.7Nm/s, p=0.018) but not from female controls (Control F 503.7 Nm/s, p=0.252).
Relationships between CSE and quadriceps performance
There was a significant positive association on the surgical limb between the slope of the stimulus-response curve and PT in the ACLR group (p=0.009, R2=0.324) (Figure 1). We found no significant relationships between CSE and any measure of quadriceps function on the nonsurgical limb (p≥0.79) or in the control group (p≥0.053). There were no significant relationships between AMT and quadriceps performance in either group (p≥0.172).
Figure 1.
Association between slope of the stimulus response curve and surgical limb peak torque after ACLR.
Discussion
Males demonstrated higher CSE (specifically the slope of the stimulus-response curve) relative to females after ACLR and better quadriceps function relative to females after ACLR. Our hypotheses were partially supported. Females had lower CSE than males after ACLR but females after ACLR did not differ significantly from controls. Also, females after ACLR had worse quadriceps function than controls and males after ACLR depending on the measure being investigated. Finally, higher excitability was associated with higher peak quadriceps torque normalized to body weight. The findings taken together indicate that neural drive is lower in females recovering from ACLR compared to males and this lower neural drive may be contributing to poorer quadriceps performance.
Corticospinal excitability
We used the slope of the stimulus response curve to represent CSE, with higher slopes indicating greater excitability and greater cortical drive to the quadriceps muscle. ACLR males had higher CSE on the slope measure than all females (ACLR and controls) with a large effect size while ACLR females did not remarkably differ from controls. To our knowledge, the slope measure for CSE after ACLR has only been reported in one other study, which had methodological differences preventing comparisons between our findings and theirs.32 For example, Héroux and Tremblay examined the slope of the stimulus response curve during a resting condition and used two different coils. On the surface our results differ from the one existing study that identified sex differences in cortical excitability, which found a main effect of sex with higher excitability in females than males as measured by MEP amplitude at 120% of motor threshold.22 While MEP and slope both provide measures of CSE, it is difficult to make any comparison between them. In contrast to MEP amplitude measure at one single intensity, SR curve provides a more robust measure of corticospinal excitability across inputs of differing TMS intensities. Our results were also contrary to our hypothesis that ACLR females would have lower CSE than controls, but they are consistent with our hypothesis that ACLR females would have lower CSE than ACLR males. The CSE difference between sexes after ACLR in our sample seems to be driven by higher CSE in males and given the large effect sizes between ACLR groups on all quadriceps function measures, the higher CSE in males may be an adaptive upregulation of the nervous system contributing to better quadriceps performance in males after ACLR. Thus, there may be a barrier that prevents this adaptive response in females after ACLR. Future research should elucidate potential factors that may contribute to this physiologic sex difference.
Quadriceps Function
There were significant differences between ACLR females and controls on all surgical limb quadriceps performance measures and large effect sizes between ACLR males and ACLR females on all quadriceps performance measures regardless of limb. These findings support our hypothesis that ACLR females perform worse than ACLR males and controls. While we would expect lower quadriceps performance than controls in the timepoint we are investigating, primarily 4-6 months after surgery, the differences between males and females after ACLR are particularly remarkable.
Despite knowledge that female athletes sustain ACL ruptures far more frequently than males, there is a paucity of research into differences between males and females after ACLR regarding quadriceps performance. Two studies reported significant differences in peak torque normalized to body mass between males and females after ACLR.8,11 Hunnicutt et al. reported significant differences between males and females regardless of limb in peak isokinetic torque at 60°/s 3- and 6- months post-ACLR.11 Schwery et al. found differences between males and females in isometric PT at 3-, 6- and 9-months after ACLR regardless of limb.8 Neither of those two studies reported on RTD; however, Kuenze et al. found differences between males and females after ACLR in PT for both limbs, and in RTD100 and RTD200 for the surgical limb.9 While our findings were not statistically significant between males and females after ACLR, we found large effect sizes across all quadriceps measures regardless of limb, which is consistent with previous findings.
Neural factors (motor unit discharge rate and recruitment) and peripheral muscle physiology both influence RTD.33-35 Some authors have interpreted early basic science studies in this area as indicative that RTD100 and RTD200 are more dependent on either neural drive or muscle physiology. Additional research is needed to determine if these phases separately represent muscle physiology and/or central drive, but our results indicate that females after ACLR may have deficits in both mechanisms as they performed slower on both RTD measures.
Clinical Implications
We found a positive relationship between the slope measure (higher slope indicates higher CSE) and quadriceps PT. The slope measure has not been studied in this population, but our findings are consistent with previous work that found negative relationships between motor threshold (higher motor threshold indicates lower CSE) and quadriceps function.23,25 This supports the theory that higher CSE (steeper slope) contributes to greater capacity for motor output and is consistent with previous data. Using brain stimulation (i.e. transcranial direct current stimulation or repetitive TMS) or behavioral strategies to improve the excitability of the corticospinal tract may be a testable target to improve quadriceps muscle performance after ACLR. These modalities/strategies may be even more important for females after ACLR.
Deficits in quadriceps strength have implications for long term outcomes after ACLR including higher reinjury risk,13 and lower patient reported function.16,17 Within our study, females demonstrate less excitability and worse quadriceps performance relative to males. Based on these findings, females may have greater need of interventions targeting cortical drive to upregulate the central nervous system and address quadriceps performance deficits after ACLR.
In addition to the sex differences in CSE, females after ACLR exhibited slower RTD100 and RTD200 than males after ACLR. In clinical practice females after ACLR may benefit from additional exercise interventions that target RTD. However, further research is necessary to determine if practice patterns include differences in how females and males are rehabilitated after ACLR and if rehabilitation should be different for females to mitigate the differences we found in CSE and RTD.
Limitations
This study had limitations most notably of sample size and power. This was a secondary analysis of a larger clinical trial that was not powered to detect differences between measures of CSE and quadriceps performance on a more robust 2x2 analysis and may not have been powered to detect differences on all measures in our statistical analysis. Future research should further investigate sex differences in cortical physiology and quadriceps performance after ACLR in larger samples to confirm our findings and reduce exposure to type I and II error. We did not include inhibitory outcomes in our study for the sake of feasibility specifically with regards to the time necessary for each data collection. Future studies should investigate inhibitory outcomes between males and females after ACLR. Another limitation is the heterogeneity in time from ACLR to testing. Participants ranged from approximately 4 months to 8 months post ACLR, which may have affected our results. However, all participants had to meet our “quiet knee” criteria and had not returned to sport at the time of testing. Lastly, we only investigated CSE to the vastus medialis muscle. The majority of studies examining CSE in individuals after ACLR used the vastus medialis as the target muscle, but there is also evidence of alterations of CSE to the rectus femoris.36 Future research should evaluate CSE differences in all quadriceps muscles after ACLR.
Acknowledgements
We would like to thank Abbey Finkill, Anah Nizar, Kevin Barry, Paige Lawton, Paige Schoelkopf and Sean Ip for their assistance in data collection and processing.
References
- 1.Hewett TE, Myer GD, Ford KR. Anterior cruciate ligament injuries in female athletes: Part 1, mechanisms and risk factors. Am J Sports Med. 2006;34(2):299–311. doi: 10.1177/0363546505284183 [DOI] [PubMed] [Google Scholar]
- 2.Zech A, Hollander K, Junge A, et al. Sex differences in injury rates in team-sport athletes: A systematic review and meta-regression analysis. J Sport Health Sci. 2022;11(1):104–114. doi: 10.1016/j.jshs.2021.04.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Prodromos CC, Han Y, Rogowski J, et al. A Meta-analysis of the Incidence of Anterior Cruciate Ligament Tears as a Function of Gender, Sport, and a Knee Injury–Reduction Regimen. Arthrosc J Arthrosc Relat Surg. 2007;23(12):1320–1325.e6. doi: 10.1016/j.arthro.2007.07.003 [DOI] [PubMed] [Google Scholar]
- 4.Renstrom P, Ljungqvist A, Arendt E, et al. Non-contact ACL injuries in female athletes: an International Olympic Committee current concepts statement. Br J Sports Med. 2008;42(6):394–412. doi: 10.1136/bjsm.2008.048934 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Smith HC, Vacek P, Johnson RJ, et al. Risk factors for anterior cruciate ligament injury: a review of the literature - part 1: neuromuscular and anatomic risk. Sports Health. 2012;4(1):69–78. doi: 10.1177/1941738111428281 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ageberg E, Forssblad M, Herbertsson P, Roos EM. Sex Differences in Patient-Reported Outcomes After Anterior Cruciate Ligament Reconstruction: Data From the Swedish Knee Ligament Register. Am J Sports Med. 2010;38(7):1334–1342. doi: 10.1177/0363546510361218 [DOI] [PubMed] [Google Scholar]
- 7.Arundale AJH, Capin JJ, Zarzycki R, et al. Functional and Patient-Reported Outcomes Improve Over the Course of Rehabilitation: A Secondary Analysis of the ACL-SPORTS Trial. Sports Health. 2018;10(5):441–452. doi: 10.1177/1941738118779023 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Schwery NA, Kiely MT, Larson CM, et al. Quadriceps Strength following Anterior Cruciate Ligament Reconstruction: Normative Values based on Sex, Graft Type and Meniscal Status at 3, 6 & 9 Months. Int J Sports Phys Ther. 2022;17(3):434–444. doi: 10.26603/001c.32378 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Kuenze C, Lisee C, Birchmeier T, et al. Sex differences in quadriceps rate of torque development within 1 year of ACL reconstruction. Phys Ther Sport. 2019;38:36–43. doi: 10.1016/j.ptsp.2019.04.008 [DOI] [PubMed] [Google Scholar]
- 10.Kuenze C, Pietrosimone B, Lisee C, et al. Demographic and surgical factors affect quadriceps strength after ACL reconstruction. Knee Surg Sports Traumatol Arthrosc. 2019;27(3):921–930. doi: 10.1007/s00167-018-5215-9 [DOI] [PubMed] [Google Scholar]
- 11.Hunnicutt JL, Xerogeanes JW, Tsai LC, et al. Terminal knee extension deficit and female sex predict poorer quadriceps strength following ACL reconstruction using all-soft tissue quadriceps tendon autografts. Knee Surg Sports Traumatol Arthrosc. 2021;29(9):3085–3095. doi: 10.1007/s00167-020-06351-4 [DOI] [PubMed] [Google Scholar]
- 12.Kim DK, Park WH. Sex differences in knee strength deficit 1 year after anterior cruciate ligament reconstruction. J Phys Ther Sci. 2015;27(12):3847–3849. doi: 10.1589/jpts.27.3847 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Grindem H, Snyder-Mackler L, Moksnes H, et al. Simple decision rules can reduce reinjury risk by 84% after ACL reconstruction: The Delaware-Oslo ACL cohort study. Br J Sports Med. 2016;50(13):804–808. doi: 10.1136/bjsports-2016-096031 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Adams D, Logerstedt D, Hunter-Giordano A, et al. Current concepts for anterior cruciate ligament reconstruction: A criterion-based rehabilitation progression. J Orthop Sports Phys Ther. 2012;42(7):601–614. doi: 10.2519/jospt.2012.3871 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Brinlee AW, Dickenson SB, Hunter-Giordano A, Snyder-Mackler L. ACL Reconstruction Rehabilitation: Clinical Data, Biologic Healing, and Criterion-Based Milestones to Inform a Return-to-Sport Guideline. Sports Health. 2021;XX(X):1–10. doi: 10.1177/19417381211056873 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Chaput M, Palimenio M, Farmer B, et al. Quadriceps Strength Influences Patient Function More Than Single Leg Forward Hop During Late-Stage ACL Rehabilitation. Int J Sports Phys Ther. 2021;16(1):145–155. doi: 10.26603/001c.18709 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Zwolski C, Schmitt LC, Quatman-Yates C, et al. The Influence of Quadriceps Strength Asymmetry on Patient-Reported Function at Time of Return to Sport After Anterior Cruciate Ligament Reconstruction. Am J Sports Med. 2015;43(9):2242–2249. doi: 10.1177/0363546515591258 [DOI] [PubMed] [Google Scholar]
- 18.Snyder-Mackler L, Delitto A, Bailey SL, Stralka SW. Strength of the quadriceps femoris muscle and functional recovery after reconstruction of the anterior cruciate ligament. A prospective, randomized clinical trial of electrical stimulation. J Bone Joint Surg Am. 1995;77(8):1166–1173. doi: 10.2106/00004623-199508000-00004 [DOI] [PubMed] [Google Scholar]
- 19.Lisee C, Lepley AS, Birchmeier T, et al. Quadriceps Strength and Volitional Activation After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis. Sports Health. 2019;11(2):163–179. doi: 10.1177/1941738118822739 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Tengman E, Brax Olofsson L, Stensdotter AK, et al. Anterior cruciate ligament injury after more than 20 years. II. Concentric and eccentric knee muscle strength. Scand J Med Sci Sports. 2014;24(6):e501–509. doi: 10.1111/sms.12215 [DOI] [PubMed] [Google Scholar]
- 21.Lepley AS, Ericksen HM, Sohn DH, Pietrosimone BG. Contributions of neural excitability and voluntary activation to quadriceps muscle strength following anterior cruciate ligament reconstruction. The Knee. 2014;21(3):736–742. doi: 10.1016/j.knee.2014.02.008 [DOI] [PubMed] [Google Scholar]
- 22.Zarzycki R, Morton SM, Charalambous CC, et al. Corticospinal and intracortical excitability differ between athletes early after ACLR and matched controls. J Orthop Res Off Publ Orthop Res Soc. 2018;36(11):2941–2948. doi: 10.1002/jor.24062 [DOI] [PubMed] [Google Scholar]
- 23.Bodkin SG, Norte GE, Hart JM. Corticospinal excitability can discriminate quadriceps strength indicative of knee function after ACL-reconstruction. Scand J Med Sci Sports. 2019;29(5):716–724. doi: 10.1111/sms.13394 [DOI] [PubMed] [Google Scholar]
- 24.Lepley AS, Gribble PA, Thomas AC, et al. Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: A 6-month longitudinal investigation. Scand J Med Sci Sports. 2015;25(6):828–839. doi: 10.1111/sms.12435 [DOI] [PubMed] [Google Scholar]
- 25.Zarzycki R, Morton SM, Charalambous CC, et al. Examination of Corticospinal and Spinal Reflexive Excitability During the Course of Postoperative Rehabilitation After Anterior Cruciate Ligament Reconstruction. J Orthop Sports Phys Ther. 2020;50(9):516–522. doi: 10.2519/jospt.2020.9329 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Scheurer SA, Sherman DA, Glaviano NR, et al. Corticomotor function is associated with quadriceps rate of torque development in individuals with ACL surgery. Exp Brain Res. 2020;238(2):283–294. doi: 10.1007/s00221-019-05713-w [DOI] [PubMed] [Google Scholar]
- 27.Palmieri-Smith RM, Thomas AC, Wojtys EM. Maximizing Quadriceps Strength After ACL Reconstruction. Clin Sports Med. 2008;27(3):405–424. doi: 10.1016/j.csm.2008.02.001 [DOI] [PubMed] [Google Scholar]
- 28.Hefti F, Müller W, Jakob RP, Stäubli HU. Evaluation of knee ligament injuries with the IKDC form. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 1993;1(3–4):226–234. doi: 10.1007/BF01560215 [DOI] [PubMed] [Google Scholar]
- 29.Hermens HJ, Freriks B, Disselhorst-Klug C, Rau G. Development of recommendations for SEMG sensors and sensor placement procedures. J Electromyogr Kinesiol Off J Int Soc Electrophysiol Kinesiol. 2000;10(5):361–374. doi: 10.1016/s1050-6411(00)00027-4 [DOI] [PubMed] [Google Scholar]
- 30.Temesi J, Gruet M, Rupp T, et al. Resting and active motor thresholds versus stimulus-response curves to determine transcranial magnetic stimulation intensity in quadriceps femoris. J Neuroengineering Rehabil. 2014;11:40. doi: 10.1186/1743-0003-11-40 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Cohen J. A power primer. Psychol Bull. 1992;112(1):155–159. doi: 10.1037//0033-2909.112.1.155 [DOI] [PubMed] [Google Scholar]
- 32.Héroux ME, Tremblay F. Corticomotor excitability associated with unilateral knee dysfunction secondary to anterior cruciate ligament injury. Knee Surg Sports Traumatol Arthrosc. 2006;14(9):823–833. doi: 10.1007/s00167-006-0063-4 [DOI] [PubMed] [Google Scholar]
- 33.Aagaard P, Simonsen EB, Andersen JL, et al. Increased rate of force development and neural drive of human skeletal muscle following resistance training. J Appl Physiol. 2002;93(4):1318–1326. doi: 10.1152/japplphysiol.00283.2002 [DOI] [PubMed] [Google Scholar]
- 34.Aagaard P, Magnusson PS, Larsson B, et al. Mechanical muscle function, morphology, and fiber type in lifelong trained elderly. Med Sci Sports Exerc. 2007;39(11):1989–1996. doi: 10.1249/mss.0b013e31814fb402 [DOI] [PubMed] [Google Scholar]
- 35.Maffiuletti NA, Aagaard P, Blazevich AJ, et al. Rate of force development: physiological and methodological considerations. Eur J Appl Physiol. 2016;116(6):1091–1116. doi: 10.1007/s00421-016-3346-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Ward SH, Pearce A, Bennell KL, et al. Quadriceps cortical adaptations in individuals with an anterior cruciate ligament injury. The Knee. 2016;23(4):582–587. doi: 10.1016/j.knee.2016.04.001 [DOI] [PubMed] [Google Scholar]