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Adam S. Lepley and Lindsey K. Lepley

Context: Arthrogenic muscle inhibition (AMI) continues to be a limiting factor in joint rehabilitation as the inability to volitionally activate muscle significantly dampens recovery. New evidence acquired at higher brain centers and in clinical populations continues to reshape our perspective of what AMI is and how to treat it. This review aims to stimulate discussion about the far-reaching effects of AMI by exploring the interconnected pathways by which it evolves. Objectives: To discuss how reflexive inhibition can lead to adaptations in brain activity, to illustrate how changes in descending motor pathways limit our ability to contract muscle following injury, and to summarize the emerging literature on the wide-reaching effects of AMI on other interconnected systems. Data Sources: The databases PubMed, SPORTDiscus, and Web of Science were searched for articles pertaining to AMI. Reference lists from appropriate articles were cross-referenced. Conclusion: AMI is a sequential and cumulative neurological process that leads to complex clinical impairments. Originating with altered afferent information arising from an injured joint, patients experience changes in afferent information, reflexive muscle inhibition, deficiencies in somatosensation, neuroplastic compensations in higher brain centers, and ultimately decreased motor output to the muscle surrounding the joint. Other aspects of clinical function, like muscle structure and psychological responses to injury, are also impaired and influenced by AMI. Removing, or reducing, AMI should continue to be a focus of rehabilitation programs to assist in the optimization of health after joint injury.

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Lindsey K. Lepley and Timothy A. Butterfield

Eccentric exercise is able to mechanically engage muscle, initiating strain-sensing molecules that promote muscle recovery by inducing beneficial adaptations in neural activity and muscle morphology, 2 critical components of muscle function that are negatively altered after injury. However, due to misinterpreted mathematic modeling and in situ and in vitro stretch protocols, a dogma that exposing muscle to eccentric exercise is associated with injury has been perpetuated in the literature. In response, clinicians have been biased toward using concentric exercise postinjury to improve the recovery of muscle function. Unfortunately, this conventional approach to rehabilitation does not restore muscle function, and reinjury rates remain high. Here, the authors present experimental evidence and theoretical support for the idea that isolated eccentric exercise is ideally suited to combat muscle inhibition and muscle strains and is an attractive alternative to concentric exercise.

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Lindsey K. Lepley and Riann M. Palmieri-Smith

Clinical Scenario:

Interventions aimed at safely overloading the quadriceps muscle after anterior cruciate ligament (ACL) reconstruction are essential to reducing quadriceps muscle weakness that often persists long after the rehabilitation period. Despite the best efforts of clinicians and researchers to improve ACL rehabilitation techniques, a universally effective intervention to restore preinjury quadriceps strength has yet to be identified. A muscle’s force-producing capacity is most optimal when an external force exceeds that of the muscle while the muscle lengthens. Hence, the potential to improve muscle strength by overloading the tissue is greater with eccentric strengthening than with concentric strengthening. Traditionally, the application of early postoperative high-intensity eccentric resistance training to the ACL-reconstructed limb has been contraindicated, as there is potential for injury to the ACL graft, articular cartilage, or surrounding soft-tissue structures. However, recent evidence suggests that the application of early, progressive, high-force eccentric resistance exercises to the involved limb can be used to safely increase muscle volume and strength in ACL-reconstructed individuals. As a result, eccentric strengthening may be another attractive alternative to traditional concentric strengthening to improve quadriceps strength after ACL reconstruction.

Focused Clinical Question:

In patients who have undergone ACL reconstruction, is there evidence to suggest that eccentric exercise positively affects postoperative quadriceps strength?

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Timothy A. Butterfield and Lindsey K. Lepley

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Steven M. Davi, Colleen K. Woxholdt, Justin L. Rush, Adam S. Lepley, and Lindsey K. Lepley

Context: Traditionally, quadriceps activation failure after anterior cruciate ligament reconstruction (ACLR) is estimated using discrete isometric torque values, providing only a snapshot of neuromuscular function. Sample entropy (SampEn) is a mathematical technique that can measure neurologic complexity during the entirety of contraction, elucidating qualities of neuromuscular control not previously captured. Objective: To apply SampEn analyses to quadriceps electromyographic activity in order to more comprehensively characterize neuromuscular deficits after ACLR. Design: Cross-sectional. Setting: Laboratory. Participants: ACLR: n = 18; controls: n = 24. Interventions: All participants underwent synchronized unilateral quadriceps isometric strength, activation, and electromyography testing during a superimposed electrical stimulus. Main Outcome Measures: Group differences in strength, activation, and SampEn were evaluated with t tests. Associations between SampEn and quadriceps function were evaluated with Pearson product–moment correlations and hierarchical linear regressions. Results: Vastus medialis SampEn was significantly reduced after ACLR compared with controls (P = .032). Vastus medialis and vastus lateralis SampEn predicted significant variance in activation after ACLR (r2 = .444; P = .003). Conclusions: Loss of neurologic complexity correlates with worse activation after ACLR, particularly in the vastus medialis. Electromyographic SampEn is capable of detecting underlying patterns of variability that are associated with the loss of complexity between key neurophysiologic events after ACLR.

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Justin L. Rush, Lindsey K. Lepley, Steven Davi, and Adam S. Lepley

Context: Altered quadriceps activation is common following anterior cruciate ligament reconstruction (ACLR), and can persist for years after surgery. These neural deficits are due, in part, to chronic central nervous system alterations. Transcranial direct current stimulation (tDCS) is a noninvasive modality, that is, believed to immediately increase motor neuron activity by stimulating the primary motor cortex, making it a promising modality to use improve outcomes in the ACLR population. Objective: To determine if a single treatment of tDCS would result in increased quadriceps activity and decreased levels of self-reported pain and dysfunction during exercise. Design: Randomized crossover design. Setting: Controlled laboratory. Patients: Ten participants with a history of ACLR (5 males/5 females, 22.9 [4.23] y, 176.57 [12.01] cm, 80.87 [16.86] kg, 68.1 [39.37] mo since ACLR). Interventions: Active tDCS and Sham tDCS. Main Outcome Measures: Percentage of maximum electromyographic data of vastus medialis and lateralis, voluntary isometric strength, percentage of voluntary activation, and self-reported pain and symptom scores were measured. The 2 × 2 repeated-measures analysis of variance by limb were performed to explain the differences between time points (pre and post) and condition (tDCS and sham). Results: There was a significant time main effect for quadriceps percentage of maximum electromyographic of vastus medialis (F9,1 = 11.931, P = .01) and vastus lateralis (F9,1 = 9.132, P = .01), isometric strength (F9,1 = 5.343, P = .046), and subjective scores for pain (F9,1 = 15.499, P = .04) and symptoms (F9,1 = 15.499, P = .04). Quadriceps percentage of maximum electromyographic, isometric strength, and voluntary activation showed an immediate decline from pre to post regardless of tDCS condition. Subjective scores improved slightly after each condition. Conclusions: One session of active tDCS did not have an immediate effect on quadriceps activity and subjective scores of pain and symptoms. To determine if tDCS is a valid modality for this patient population, a larger scale investigation with multiple treatments of active tDCS is warranted.

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Julie P. Burland, Adam S. Lepley, Marc Cormier, Lindsay J. DiStefano, and Lindsey K. Lepley

Context: Altered neural signaling is known to have a direct impact on psychological wellness. Therefore, disruptions in neural signaling after anterior cruciate ligament reconstruction may influence psychological dysfunction, in some cases manifesting as learned helplessness. Helplessness is a psychological paradigm that presents as altered neuromuscular control, reduced motivation, and psychological deficits. Objectives: The authors sought to evaluate the relationship between helplessness, neural activity, and quadriceps function at different time points after anterior cruciate ligament reconstruction. Evidence Acquisition: Twenty-nine individuals with unilateral anterior cruciate ligament reconstruction were categorized into early group (<2 y, age: 19.13 [2.18] y; height: 1.77 [0.11] m; mass: 76.903 [11.87] kg) or late group (>2 y, age: 22 [23] y; height: 1.67 [0.07] m; mass: 65.66 [11.33] kg). Quadriceps function (activation and strength), spinal-reflexive and corticospinal excitability (active motor thresholds and motor evoked potentials), and helplessness were obtained. A principal component analysis was performed by group (early and late) to identify which factors of helplessness were most associated with neural activity and quadriceps function. Pearson product moment correlation analyses were performed by group to determine associations between individual components and main outcomes. Evidence Synthesis: In the early group, cognitive readiness was associated with quadriceps strength of the injured limb (r2 = .513, P = .004), and self-awareness/management was associated with motor threshold of the injured limb (r2 = .238, P = .05). In the late group, intrinsic helplessness was associated with motor output of injured limb (r2 = .653, P = .01). Conclusion: Helplessness is made up of several attributional constructs, which are altered at different phases of recovery. Helplessness constructs interact differently with neural activity and quadriceps function across time. These findings are preliminary and do not establish a causal link between neural alterations and learned helplessness. Future studies should serially evaluate both changes in neural activity and learned helplessness attributes throughout recovery.

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Lindsey K. Lepley, Abbey C. Thomas, Scott G. McLean, and Riann M. Palmieri-Smith


As individuals returning to activity after anterior cruciate ligament reconstruction (ACLr) likely experience fatigue, understanding how fatigue affects knee-muscle activation patterns during sport-like maneuvers is of clinical importance. Fatigue has been suggested to impair neuromuscular control strategies. As a result, fatigue may place ACLr patients at increased risk of developing posttraumatic osteoarthritis (OA).


To determine the effects of fatigue on knee-muscle activity post-ACLr.


Case control.


University laboratory.


12 individuals 7–10 mo post-ACLr (7 male, 5 female; age 22.1 ± 4.7 y; 1.8 ± 0.1 m; mass 77.7 ± 11.9 kg) and 13 controls (4 male, 9 female; age 22.9 ± 4.3 y; 1.7 ± 0.1 m; mass 66.9 ± 9.8 kg).


Fatigue was induced via repetitive sets of double-leg squats (n = 8), which were interspersed with sets of single-leg landings (n = 3), until squats were no longer possible.

Main Outcome Measures:

2 × 2 repeated-measures ANOVA was used to detect the main effects of group (ACLr, control) and fatigue state (prefatigue, postfatigue) on quadriceps:hamstring cocontraction index (Q:H CCI).


All subjects demonstrated higher Q:H CCI at prefatigue compared with postfatigue (F 1,23 = 66.949, P ≤ .001). Q:H CCI did not differ between groups (F 1,23 = 0.599, P = .447).


The results indicate that regardless of fatigue state, ACLr individuals are capable of restoring muscle-activation patterns similar to those in healthy subjects. As a result, excessive muscle cocontraction, which has been hypothesized as a potential mechanism of posttraumatic OA, may not contribute to joint degeneration after ACLr.

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Cody R. Butler, Kirsten Allen, Lindsay J. DiStefano, and Lindsey K. Lepley

Clinical Scenario: Anterior cruciate ligament (ACL) tear is a devastating knee injury with negative long-term consequences, such as early-onset knee osteoarthritis, biomechanical compensations, and reduced physical activity. Significant reduction in physical activity is a powerful indicator of cardiovascular (CV) disease; therefore, those with a history of ACL injury may be at increased risk for CV disease compared with noninjured individuals. Focused Clinical Question: Do individuals with a history of ACL injury demonstrate negative CV changes compared with those without a history of ACL injury? Summary of Key Findings: Three articles met the inclusion criteria and investigated CV changes after ACL injury. Both cross-sectional studies compared participants with ACL injury with matched controls. Bell et al compared time spent in moderate to vigorous physical activity and step count, whereas Almeida et al compared maximum rate of oxygen consumption, ventilatory thresholds, isokinetic quadriceps strength, and body composition. Collectively, both quantitative studies found that individuals with a history of ACL injury had less efficient CV systems compared with matched controls and/or preoperative data. Finally, a qualitative study of 3506 retired National Football League athletes showed an increased rate of arthritis and knee replacement surgery after an ACL injury when compared with other retired National Football League members, in addition to a >50% increased rate of myocardial infarction. Clinical Bottom Line: A history of ACL injury is a source of impaired physical activity. Preliminary data indicate that these physical activity limitations negatively impair the CV system, and individuals with a history of ACL injury demonstrate lower maximum oxygen consumption, self-reported disability, and daily step count compared with noninjured peers. These complications support the need for greater emphasis on CV wellness. Strength of Recommendation: Consistent findings from 2 cross-sectional studies and 1 survey study suggest level IIB evidence to support that ACL injury is associated with negative CV health.

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Jessica E. Digiacomo, Riann M. Palmieri-Smith, John A. Redman III, and Lindsey K. Lepley

Context: Modifiable and nonmodifiable risk factors have been identified for sustaining a primary anterior cruciate ligament (ACL) injury; however, less research is available examining risk factors for a second injury. Identifying whether bony morphological factors are different (or more exaggerated) among those that experience a secondary ACL injury is critical to understanding if nonmodifiable risk factors are associated with a second injury. Objective: To determine if bony morphology is different among those that experience a secondary ACL reinjury as compared with those that do not. Design: Case-control. Setting: University laboratory. Participants and Interventions: ACL participants were tracked after return to play following primary reconstruction, and if individuals experienced a second ipsilateral injury (ACLx2; n = 14, 8f/6m, 17.9 ± 4.0 y), the primary clinical MRI was analyzed for bony morphological risk factors. ACLx2 participants were matched to individuals (sex, age, height, graft, gender, and activity level) that had undergone reconstruction but did not experience reinjury (ACLx1, n = 14, 8f/6m, 18.7 ± 4.0 y). Ten controls were also enrolled (5m/5f, 20.8 ± 3.9 y) for the purposes of comparing the authors’ ACL data against healthy knees. Main Outcome Measures: Lateral and medial posterior tibial slopes (LPTS, MPTS), notch shape index (NSI), and medial tibial plateau depth of concavity (MDC). Results: All ACL-reconstructed patients (combined ACLx1 and ACLx2 group) had a steeper LPTS than controls (d = 0.87, 95% CI 0.11–1.60, P = .023); however, no difference in LPTS was found between ACLx1 and ACLx2 (P > .05). No differences in MPTS, NSI, and MDC were found between all ACL participants (combined ACLx2 and ACLx1) and controls or between ACLx1 and ACLx2 (P > .05). Conclusions: Compared to healthy individuals, a steeper LPTS is a common bony abnormality in all ACL-injured participants. Individuals that go on to experience a second ipsilateral ACL injury do not have more exaggerated bony morphology than those that do not suggesting that differences in modifiable risk factors at return to play may contribute to reinjury.