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Persistent Muscle Inhibition after Anterior Cruciate Ligament Reconstruction: Role of Reflex Excitability

HARKEY, MATTHEW S.; LUC-HARKEY, BRITTNEY A.; LEPLEY, ADAM S.; GRINDSTAFF, TERRY L.; GRIBBLE, PHILLIP; BLACKBURN, J. TROY; SPANG, JEFFREY T.; PIETROSIMONE, BRIAN

Medicine & Science in Sports & Exercise: December 2016 - Volume 48 - Issue 12 - p 2370–2377
doi: 10.1249/MSS.0000000000001046
CLINICAL SCIENCES
Free

Purpose Persistent voluntary quadriceps activation deficits are common after anterior cruciate ligament reconstruction (ACLR), but the direct causes are unclear. The primary purpose of this study was to determine whether spinal reflex excitability deficits are present in individuals with a history of ACLR, and secondarily to determine whether spinal reflex excitability predicts which individuals possess full voluntary quadriceps activation.

Methods One hundred and forty-seven individuals (74 healthy and 73 ACLR) participated in this cross-sectional case–control study. Quadriceps spinal reflex excitability was quantified using the Hoffmann reflex normalized to the maximal muscle response (H:M ratio). Voluntary quadriceps activation was evaluated with the burst superimposition technique and calculated via the central activation ratio (CAR). Separate 2 × 2 ANCOVA tests were used to compare between-limb and between-group differences for H:M ratio and CAR. A receiver operating characteristic curve was used to determine the accuracy of H:M ratio to predict if ACLR participants present with full voluntary activation (CAR ≥ 0.95).

Results The ACLR H:M ratio was not different between limbs or compared with the healthy group (P > 0.05). Although ACLR CAR was lower bilaterally compared with the healthy group (P < 0.001), it did not differ between limbs. The H:M ratio has poor accuracy for predicting which individuals exhibit full voluntary activation (receiver operating characteristic area under the curve = 0.52, 95% CI = 0.37,0.66; odds ratio = 2.2, 95% CI = 0.8, 5.9).

Conclusions Spinal reflex excitability did not differ between limbs in individuals with ACLR or compared with healthy participants. The level of quadriceps spinal reflex excitability has poor accuracy at predicting which ACLR individuals would demonstrate full voluntary quadriceps activation.

1Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC; 2Human Movement Science Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC; 3Department of Kinesiology, University of Connecticut, Storrs, CT; 4Physical Therapy Department, Creighton University, Omaha, NE; 5Department of Rehabilitation Sciences, University of Kentucky, Lexington, KY; and 6Department of Orthopaedics, School of Medicine, University of North Carolina at Chapel Hill, NC

Address for correspondence: Matthew Harkey, M.S., Doctoral Candidate, University of North Carolina at Chapel Hill, CB# 8700, 209 Fetzer Hall, Chapel Hill, NC 27599; E-mail: harkey@unc.edu.

Submitted for publication October 2015.

Accepted for publication July 2016.

Quadriceps strength deficits are common after anterior cruciate ligament (ACL) injury and reconstruction (ACLR), with a recent literature review indicating that the majority of individuals return to physical activity with side-to-side strength deficits of 23% in the injured limb compared with the uninjured limb (20). Individuals who sustain an ACL injury and undergo ACLR also report significantly reduced quality of life compared with people without a knee injury (2,3). In addition, approximately one-third of patients that undergo ACLR will develop a radiographic evidence of knee osteoarthritis within a decade of their initial injury (23). Quadriceps weakness is a modifiable clinical impairment that has been linked to self-reported disability and the development of osteoarthritis after ACLR (26,32,39). Therefore, determining the best therapeutic methods for targeting quadriceps weakness after ACLR may provide an avenue for increasing quality of life and preventing the early onset of knee osteoarthritis. However, regaining quadriceps strength after ACLR may be limited by decreased voluntary activation (22). In fact, improving voluntary activation is positively associated with increasing quadriceps strength (22,34). Targeting impaired voluntary activation after ACLR may lead to improved muscle strength for maintaining an acceptable quality of life and preserving long-term knee health.

It has been hypothesized that decreased voluntary activation in people with knee injuries is caused by the persistent inhibition of the uninjured muscles surrounding an injured joint, termed arthrogenic muscle inhibition (AMI) (8). Historically, persistent AMI is theorized to be caused by an ongoing reflex inhibition of the uninjured musculature surrounding an injured joint (1,8,11,28,33). Acute human knee effusion models (9,28,29) and animal experiments (5) have provided evidence that altered afferent stimuli are propagated to the central nervous system from a distended, injured, or surgically reconstructed joint, which causes decreased spinal reflex excitability via pre- and postsynaptic inhibitory mechanisms (28). Although AMI may be a natural protective mechanism that guards against muscle force exerted to an acutely injured joint, persistent AMI has been described as a factor that limits the ability to increase muscle strength with therapeutic exercise (8). Measuring spinal reflex excitability after joint injury provides insight into mechanistic alterations that may contribute to decreased force output and inhibited voluntary quadriceps activation (27). Previous work using artificial joint effusion demonstrates that knee joint swelling results in immediate inhibitory effects as seen by decreased spinal reflex excitability (9,28,29). In addition, Lepley et al.(19) tracked longitudinal changes in spinal reflex excitability and identified acute deficits at a mean of 37 d after initial injury and within 15 d after ACLR compared with control participants. Interestingly, within this small cohort, the acute deficits in spinal reflex excitability appear to subside 6 months after injury (19). Although decreased quadriceps spinal reflex excitability is evident immediately after joint effusion and injury, there is little evidence to support that deficits in spinal reflex excitability exist in ACLR individuals that return to physical activity (17,19,31,36) with persistent deficits in voluntary quadriceps activation (7). In addition, although previous authors (8,11) have hypothesized that altered spinal reflex excitability is a potential mechanism responsible for persistent decreased voluntary quadriceps activation, there is currently no evidence to indicate that ACLR individuals with higher spinal reflex excitability are more likely to demonstrate full voluntary quadriceps activation.

Therefore, the primary purpose of this study was to determine whether deficits in spinal reflex excitability are present between the injured and the uninjured limbs in individuals greater than 6 months after ACLR as well as compared with limbs of a healthy cohort. Secondarily, we sought to determine whether spinal reflex excitability could identify ACLR participants who demonstrated full voluntary quadriceps activation. On the basis of the previous evidence indicating acute declines in spinal reflex excitability after joint effusion and injury (9,19,28,29) and previous theory attributing persistent deficits in voluntary quadriceps activation to ongoing reflex inhibition (8), we hypothesize that 1) persistent declines in spinal reflex excitability would be present in ACLR participants and 2) spinal reflex excitability would demonstrate high accuracy for predicting which ACLR participants attained full voluntary quadriceps activation.

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METHODS

Design

In this cross-sectional case–control study, spinal reflex excitability and voluntary quadriceps activation testing were conducted bilaterally in ACLR and healthy participants. The dominant limb was chosen as the reference injured limb for the healthy participants and was defined as the self-reported limb that the participant preferred to use for kicking a ball (19). All main outcome measures were collected during a single data collection session. ACLR and healthy participants were recruited at two different universities for a multisite cross-sectional descriptive laboratory study. Data collection was conducted using similar methodology in two research laboratories at different universities that were under the direction of the senior author (BP).

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Participants

All participants were between 18 and 35 yr old, self-reported participating in physical activity for at least 20 min 3 days per week, and did not report any history of injury to either leg within 6 months before study participation. The participants in the healthy group reported no history of lower extremity surgery on either limb. ACLR participants demonstrated a history of unilateral ACLR at least 6 months before study enrollment, no history of ACL graft rupture or revision surgery, and clearance by a physician to return to physical activity. All participants provided written informed consent, and the institutional review board at the two universities where the data were collected approved the study.

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Instrumentation

Spinal reflex excitability testing

The two laboratories used slightly different stimulating electrode configurations based on available equipment. A proportion of the participants (n = 100; ACLR = 50, healthy = 50) were tested using a unipolar stimulating electrode setup, with a stimulator module (STM100A, BIOPAC Systems, Inc., Goleta, CA) and a 200-V maximum stimulus adaptor (STMISOC, BIOPAC Systems, Inc.), which delivered a 1-ms square wave stimulus to the femoral nerve via a 2-mm shielded disk stimulating electrode (EL2524S, BIOPAC Systems, Inc.) and a dispersive electrode placed over the ipsilateral hamstring. The remainder of participants (n = 47; ACLR = 23, healthy = 24) were tested with a bipolar stimulating electrode setup, which used a stimulator module (STMSOLA, BIOPAC Systems, Inc.) that delivered a 1-ms square wave to the femoral nerve via a 4-cm bipolar bar stimulating electrode (ELSTM1, BIOPAC Systems, Inc.). An MP150 data acquisition system (BIOPAC Systems, Inc.) and Acqknowledge BIOPAC Software was used to visualize the EMG signals and to manipulate the electrical stimulus. Spinal reflex excitability was normalized using a participant specific measure of maximal muscle response (27) to minimize variability in the measurement from two different laboratories. For all participants, Ag/AgCl electrodes (EL503, BIOPAC Systems, Inc.) were used to collect the EMG signal that was sampled at 2000 Hz with a gain of 1000 (EMG100C, BIOPAC Systems, Inc.).

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Voluntary quadriceps activation

Voluntary quadriceps activation was assessed in the same manner between laboratories, yet equipment slightly varied based on laboratory availability. Torque was evaluated on either a Biodex System III dynamometer (Biodex Medical Systems; n = 100, Shirley, NY) or a Humac Norm dynamometer (CSMi Solutions, Stoughton, MA; n = 48). The torque signal was collected at 1000 or 600 Hz using an analog-to-digital convertor (model USB-6251; National Instruments) and low-pass filtered with a 50-Hz zero-phase shift fourth-order Butterworth filter. The central activation ratio (CAR) for each participant was calculated by normalizing the maximal voluntary torque to the superimposed torque collected on the same dynamometer. Two 7 × 13-cm self-adhesive stimulating electrodes were placed on the proximal vastus lateralis and distal vastus medialis (35). The electrodes were connected to an electrical stimulator (S48 Stimulator and SIU8T isolation unit; Grass Technologies, Natus Neurology, Warwick, RI) to deliver an electrical stimulus to the quadriceps (10 pulse train, 0.6 ms pulse duration, 100 Hz, and 125 V intensity) (35).

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Procedures

Spinal reflex excitability testing

Quadriceps spinal reflex excitability was quantified bilaterally via the Hoffmann reflex (H-reflex) normalized to the maximal muscle response (H:M ratio) (6). All participants were positioned supine on a padded treatment plinth with their arms at their side and their knee supported by a bolster in 15° of flexion. EMG data were collected via two pregelled electrodes positioned 1.75 mm apart over the distal belly of the vastus medialis (9), with a ground electrode placed on the medial malleolus. Before EMG electrode placement, the collection area was shaved, debrided, and cleaned with alcohol. To elicit the H-reflex, an electrical stimulus was delivered to the femoral nerve in the femoral triangle. Stimulus intensity was increased in 0.2 V increments until the maximal peak-to-peak H-reflex amplitude was obtained (10). The maximal muscle response was determined by increasing the stimulus intensity by 1.0 V increments until the peak-to-peak amplitude of the muscle response did not continue to increase with increasing stimulus intensity (10). The five largest H-reflex amplitudes were normalized to the average of five maximal muscle responses to derive an average H:M ratio (29).

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Voluntary quadriceps activation testing

Voluntary quadriceps activation was assessed using the superimposed burst (SIB) technique and quantified via the CAR during maximal voluntary isometric knee extension contraction (MVIC) (12). Participants were positioned in a dynamometer with their hips and knees at 85° and 90° of flexion, respectively (30). The distal shank was secured to the dynamometer arm with a strap (31). Participants began with isometric warm-ups at a self-estimated 25%, 50%, and 75% of their maximal effort before performing MVIC. Participants then performed three to five practice MVIC while they were instructed to push into the lever arm of the dynamometer as hard and as fast as possible and hold it for approximately 3 s. We determined that the participant was capable of producing an MVIC once the peak torque differed by less than 10 N·m across three successive practice MVIC trials (19). Using a custom software program (LabVIEW, National Instruments), the torque value was displayed on a 22-inch computer screen (ThinkVision, Lenovo) for the participants in real time during the MVIC. An MVIC threshold was determined from the mean of the peak torque values from the three largest practice MVIC trials, which would be used to ensure that participants produced maximal contractions during the activation testing trials (15). At least 1 min of rest was provided between each maximal contraction to prevent participant fatigue.

For the voluntary quadriceps activation testing, two threshold lines were displayed on the screen: 1) the mean of the three previous MVIC and 2) the second line displayed 10% above the threshold line (24). The participants were instructed to “push out on the lever arm as hard and fast as possible” while visualizing the torque output and trying to reach the second target line (24). Once their torque production surpassed the first MVIC threshold line, which indicated the production of maximal effort, and their torque dropped by 1 N·m (24), the custom program automatically triggered the delivery of the SIB, and the increase in torque after stimulus delivery was recorded. The torque-based automated trigger for stimulus delivery has been demonstrated to be a reliable method for measuring voluntary quadriceps activation and improves the confidence that maximal effort is produced during testing compared with the traditional manual stimulus delivery methods (15,21,24). Voluntary quadriceps activation was quantified by calculating the ratio of peak voluntary MVIC torque to the peak torque produced after the SIB (CAR = MVIC / [MVIC + SIB]) (12,15,21). On the basis of previously reported standards (30,37,38), a voluntary quadriceps activation threshold was set at a CAR of 0.95 to dichotomize the ACLR participants into a group with full voluntary activation (i.e., CAR ≥ 0.95) and a group presenting with quadriceps inhibition (i.e., CAR < 0.95). This distinction of participants with full voluntary quadriceps activation or quadriceps inhibition was used as a dichotomous variable during the statistical analysis.

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Statistical Analysis

Demographics

Means and standard deviations for age, height, mass, activity level (i.e., Tegner score), and self-reported function (i.e., International Knee Documentation Committee Subjective Knee Evaluation Form) were determined for the ACLR and healthy participants. We also determined the mean and standard deviation of time from surgery for the ACLR participants. Independent t-tests were used to compare age, height, mass, activity level, and self-reported function between ACLR and healthy groups. Further, we also conducted separate independent t-tests to determine whether differences existed in demographics (age, height, mass, activity level, time postsurgery, or self-reported function) or main outcome measures (H:M ratio and CAR) between the two laboratories.

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Spinal reflex excitability and voluntary quadriceps activation limb and group differences

Separate mixed model 2 × 2 repeated-measures ANOVA on limb (injured/dominant vs uninjured/nondominant) and an independent group factor (ACLR vs healthy) were performed to determine differences between limb and group for spinal reflex excitability and voluntary quadriceps activation. If any of the demographic variables were significantly different between laboratories, separate mixed model 2 × 2 ANCOVA were used to determine differences between limb and group while controlling for the variance in demographics that differed between laboratories. Bonferroni-corrected post hoc independent or dependent t-tests (P = 0.05/4 = 0.017) were performed to further examine specific group or limb differences in the presence of a significant interaction.

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Post hoc analysis—association between time postsurgery and main outcome measures

As our cohort has a wide range of time postsurgery and previous investigations have provided evidence that alterations in spinal reflex excitability and voluntary quadriceps activation may be affected by time postsurgery (19), we decided to conduct a post hoc analysis to determine the association between our main outcome measures and time postsurgery in our ACLR participants. Pearson product moment correlations were used to determine bivariate associations between time postsurgery and both spinal reflex excitability and voluntary quadriceps activation.

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Capability of spinal reflex excitability to predict full voluntary activation

A receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of spinal reflex excitability to differentiate ACLR participants with full or inhibited voluntary quadriceps activation, based on our dichotomous variable (CAR ≥ or <0.95) created after CAR testing. In addition, we developed cutoff values for spinal reflexive excitability that would maximize the sensitivity and specificity for prediction of full voluntary quadriceps activation (16). On the basis of previously reported standards (30,37,38), CAR values were used to dichotomize participants in to full (CAR ≥ 0.95) and inhibited (CAR < 0.95) voluntary activation groups. The ROC curve was created by plotting the sensitivity (i.e., positive spinal reflex excitability cutoff correctly predicting a participant with full voluntary activation) and 1-specificity (i.e., negative spinal reflex excitability cutoff correctly predicting a participant with inhibition) for each H:M ratio. The ROC area under the curve (AUC) is a statistic indicating the diagnostic accuracy of the ROC curve and was used to determine the ability of spinal reflex excitability to predict full voluntary quadriceps activation (4). The after criteria indicate the diagnostic accuracy of the AUC: 1.0 = perfect test, 1.0–0.9 = high accuracy, 0.9–0.7 = moderate accuracy, 0.7–0.5 = poor accuracy, and <0.5 = noninformative (4). In addition, using the individual coordinate points of the ROC curve, we determined the specific cutoff of spinal reflexive excitability that maximizes both sensitivity and specificity for predicting full voluntary activation (CAR ≥ 0.95). Using the spinal reflex excitability cutoff that maximized the prediction of full voluntary activation, we determined the odds ratio of a participant having full voluntary activation (CAR ≥ 95). The SPSS software (version 21.0; IBM Corporation) was used to conduct all statistical analyses, with an a priori alpha-level set at 0.05.

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RESULTS

Demographics

Overall, 173 participants (79 healthy and 94 ACLR) were enrolled in this study; however, we were only able to obtain bilateral spinal reflex excitability and voluntary quadriceps activation measurements on 147 participants (74 healthy and 73 ACLR). We excluded 20 participants (4 healthy, 16 ACLR) who chose not to complete spinal reflex excitability testing and 6 participants (1 healthy, 5 ACLR) who chose not to complete voluntary quadriceps activation testing because of the discomfort associated with the electrical stimulus. There were no observed differences in age, mass, height, or activity level between the ACLR and the healthy participants retained in the final analyses; however, ACLR participants presented with decreased self-reported function when compared with the healthy participants (P > 0.05; Table 1). Table 2 displays the demographics and main outcome measures for both laboratories, with mass, activity level, time postsurgery, and injured/dominant H:M ratio differing between the two laboratories. ACLR participants were on average 39.6 ± 38.7 months postsurgery and presented with the after graft type distribution (patellar tendon autograft = 40, semitendinosus/gracilis autograft = 30, and allograft = 3 (Table 1).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

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Spinal reflex excitability differences between limbs and groups

After controlling for mass and activity level, there was no limb–group interaction (F1,142 = 0.17, P = 0.68). In addition, the H:M ratio was not different between limbs (F1,142 = 0.01, P = 0.94; Table 1) or between the ACLR and the healthy participants (F1,142 = 1.0, P = 0.31).

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Voluntary activation differences between limbs and groups

After controlling for mass and activity level, there was no limb–group interaction (F1,142= 1.87, P = 0.17). CAR was significantly lower bilaterally in ACLR participants compared with both limbs of the healthy participants (F1,142 = 16.60, P < 0.001; Table 1); however, there was no difference in CAR between limbs (F1,142 = 0.094, P = 0.76).

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Post hoc analysis—association between time postsurgery and main outcome measures

Although time postinjury was different between laboratories, we were unable to include this time postinjury as a covariate in our primary group by limb ANCOVA, as the time postsurgery variable is only relevant to the ACLR group. In addition, because the cohort of participants in the current study demonstrated a wide range of months after ACLR (6–161 months) and previous work has demonstrated that spinal reflex excitability changes over the first 6 months post ACLR (19), we conducted a post hoc analysis to investigate the bivariate associations between time postsurgery and spinal reflex excitability, as well as between time postsurgery and voluntary quadriceps activation. There were no significant associations between time postsurgery and spinal reflex excitability (r = 0.154, P = 0.194) or voluntary quadriceps activation (r = −0.120, P = 0.311).

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Using spinal reflex excitability to predict full voluntary activation

Spinal reflex excitability demonstrated poor accuracy for predicting the activation status in ACLR participants (AUC = 0.52; 95% confidence interval = 0.37–0.66; Fig. 1). Contrary to our hypothesis, an H:M ratio cutoff of less than 0.22 maximized the sensitivity (0.50) and specificity (0.69) of predicting full voluntary quadriceps activation status. Table 3 depicts the contingency table that dichotomizes the ACLR participants into those above and below the voluntary activation threshold (CAR = 0.95) and the spinal reflex excitability cutoff (H:M ratio = 0.22). The odds ratio of an ACLR participant with spinal reflex excitability below 0.22 to present with full voluntary quadriceps activation is 2.2 (95% confidence interval = 0.83–5.9). This indicates that the odds of having full voluntary quadriceps activation are 2.2 times greater for ACLR participants with spinal reflex excitability below the cutoff when compared with participants above the cutoff.

TABLE 3

TABLE 3

FIGURE 1

FIGURE 1

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DISCUSSION

Persistent AMI influenced by an “ongoing reflex inhibition” has previously been hypothesized to influence long-term declines in voluntary quadriceps activation after knee injury (1,8,11). However, data from the current study demonstrate that spinal reflex excitability in this cohort of 73 ACLR participants was not different between injured and uninjured limbs or compared with a group of 74 healthy participants (Table 1). Despite no differences in spinal reflex excitability between the ACLR and the healthy participants, the ACLR participants presented with bilaterally lower voluntary quadriceps activation at an average of 39.6 months (SD = 38.7 months) after surgery when compared with the healthy participants. In addition, spinal reflex excitability (H:M ratio) demonstrated poor accuracy for discriminating full versus inhibited voluntary quadriceps activation in ACLR participants (ROC AUC = 0.52). Contrary to our hypothesis, ACLR participants with a spinal reflex excitability below the calculated cutoff value (H:M ratio < 0.22) had 2.22× greater odds of presenting with full voluntary quadriceps activation compared with ACLR participants above the established cutoff score (H:M ratio ≥ 0.22). However, the 95% confidence interval of the odds ratio crossed 1, indicating that we cannot be certain that lower spinal reflex excitability is predictive of full voluntary quadriceps activation status in ACLR individuals. Our post hoc analysis indicated that there was no association between the time postsurgery outcome and the spinal reflex excitability, as well as voluntary quadriceps activation in the cohort that we tested. These findings further develop our understanding regarding the role of neural excitability pathways in influencing persistent voluntary quadriceps activation deficits in individuals with an ACLR.

Earlier work has provided the theoretical basis of AMI as an acute decline in spinal reflex excitability after joint capsule distention or damage to articular structures (9,28,29) and has been described persistent AMI as an ongoing reflex inhibition that decreases muscle contraction surrounding an injured joint to prevent further injury (8). Similar acute declines in spinal reflex excitability have been observed 1 month after the initial ACL injury and 2 wk after ACLR (19). Caution should be taken in extrapolating the long-term effects of spinal reflex excitability deficits from studies that have only evaluated the acute effects of spinal reflex excitability on joint injury or effusion. Because swelling, pain, and initial joint damage are all theorized to create acute declines in spinal reflex excitability, the resolution of these symptoms may alleviate alterations in spinal reflex excitability. A previous longitudinal investigation demonstrated that spinal reflex excitability deficits that were present in the days after knee surgery were absent 6 months postsurgery (19); however, our post hoc analysis demonstrated spinal reflex excitability is not associated with time postsurgery in a cohort of individuals with an ACLR between 6–161 months postsurgery. Although the previously mentioned cohort did not present with spinal reflex alterations at 6 months postsurgery (19), the same cohort presented with lower voluntary quadriceps activation in their ACLR limb when compared with a healthy matched limb. Because the resolution of spinal reflex excitability deficits did not allow for restoration of full voluntary activation in this previous study (19), it suggests that spinal reflex excitability may not influence persistent voluntary activation deficits after ACLR. Our results add to the previous study by demonstrating that ACLR participants, ranging between 6 and 161 months postsurgery (average = 39.6) with function similar to that a of typical ACLR population (25) (International Knee Documentation Committee Subjective Knee Evaluation Form = 84.0 ± 12.8), do not present with spinal reflex excitability differences when compared with their uninjured limb or a reference limb of healthy individuals. In addition, significant persistent deficits in voluntary quadriceps activation were observed bilaterally in our ACLR cohort compared with the healthy group, and spinal reflex excitability demonstrated poor accuracy for predicting which ACLR participants would present with full voluntary quadriceps activation. Because our ACLR cohort presented with significant deficits in voluntary activation, without concurrent changes in spinal reflex excitability, we hypothesize that persistent declines in voluntary quadriceps activation are not influenced by ongoing alterations in reflex excitability; however, cause and effect cannot be established with this cross-sectional investigation. Thus, the chronic activation deficits in voluntary activation could be originating from excitability pathways that differ from spinal reflex pathways.

Although not measured in the present study, alterations in corticomotor excitability (i.e., excitability of pathways between the motor cortex and the quadriceps muscle) have been theorized as a potential origin of persistent voluntary activation deficits after ACLR (33,40). Contrasting with the in spinal reflex excitability findings, corticomotor excitability is not altered immediately after an experimental knee effusion (18), acutely after ACL injury (19), or within 2 wk of ACLR (19). However, during this same study at 6 months after ACLR, when spinal reflex excitability alterations resolved in the ACLR participants, they presented with decreased corticomotor excitability in the injured and uninjured limbs when compared with healthy participants (19). In addition, when ACLR participants were separated into high versus low voluntary quadriceps activation groups (i.e., CAR ≥ or < 0.95, respectively), the low activation group displayed lower corticomotor excitability compared with healthy participants, whereas the high activation group was no different than the healthy participants (31). The results from these previous study studies (18,19,31) may collectively indicate that although corticomotor excitability is not influenced early after injury, differences in corticomotor excitability develop chronically after injury and potentially drive the persistent voluntary quadriceps activation deficits. Therefore, there appears to be a time-dependent relationship between alterations in spinal reflex excitability, corticomotor excitability, and voluntary activation after ACLR. It is possible that spinal reflex excitability contributes to the acute declines in voluntary activation early after injury and surgery, and corticomotor excitability deficits influence the persistent deficits in voluntary activation. In addition, abnormal quadriceps gamma loop function is a neural mechanism theorized to lead to decreased strength and activation in patients after ACLR (13,14). Quadriceps gamma loop dysfunction is present bilaterally after ACLR (13,14) and theorized to be caused by damaged ACL mechanoreceptors leading to altered afferent feedback. Because normal gamma loop function relies on afferent feedback for the recruitment of high-threshold motor units, gamma loop dysfunction may be another explanation of decreased voluntary quadriceps activation leading to muscle weakness (13). Further research is needed to clarify the role of corticomotor excitability and gamma loop dysfunction in modulating persistent declines in voluntary quadriceps activation.

Although our large cohort provides generalizability over a wide range of time postsurgery (6–161 months), the study design was cross sectional, and we were not able to determine how spinal reflex excitability and voluntary activation changed from time points before injury or if alterations in excitability and activation were occurring before injury. Differences were observed in demographics (i.e., mass, activity level, and time postsurgery) and main outcome measures (i.e., injured/dominant H:M ratio) between the two laboratories of this multisite cross-sectional descriptive laboratory study, which may be attributable to the fact that testing was conducted in two different areas of the countries. However, even after controlling for the differences between the laboratories, there were no differences between limb or group for spinal reflex excitability. Although we observed statistically significant deficits in voluntary quadriceps activation between our ACLR individuals and healthy controls, there is no established clinically meaningful difference for voluntary quadriceps activation in participants after ACLR. Thus, although these differences between ACLR and healthy participants produced a moderate effect size (Cohen’s d = 0.75), we are unable to make any claims on the clinical relevance of this 5% difference in voluntary quadriceps activation. In addition, we only were able to use 82% (147/173) of the total number of participants that volunteered for the study because we were unable to elicit an H-reflex for various reasons (failure to complete testing, or participant dropout), which may limit generalizability of the findings. Although knee effusion was not measured in the current study, previous work has indicated that knee effusion affects spinal reflex excitability (9,28). Thus, future studies should determine whether persistent knee effusion is associated with persistent declines in spinal reflex excitability.

In conclusion, participants with unilateral ACLR demonstrated lower voluntary quadriceps activation in both limbs compared with healthy participants but did not demonstrate differences in spinal reflex excitability. In addition, spinal reflex excitability has poor accuracy at identifying which ACLR individuals regained full voluntary quadriceps activation after surgery. Therefore, ongoing spinal reflex excitability may not be a mechanism for persistent deficits in voluntary quadriceps activation in patients with an ACLR.

There was no funding source for this study. All authors declare no conflict of interest. The results of the present study do not constitute endorsement by the American College of Sports Medicine.

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REFERENCES

1. Deandrade JR, Grant C, Dixon AS. Joint distension and reflex muscle inhibition in the knee. J Bone Joint Surg Am. 1965;47:313–22.
2. Filbay SR, Ackerman IN, Russell TG, Macri EM, Crossley KM. Health-related quality of life after anterior cruciate ligament reconstruction: a systematic review. Am J Sports Med. 2014;42(5):1247–55.
3. Filbay SR, Culvenor AG, Ackerman IN, Russell TG, Crossley KM. Quality of life in anterior cruciate ligament-deficient individuals: a systematic review and meta-analysis. Br J Sports Med. 2015;49(16):1033–41.
4. Greiner M, Pfeiffer D, Smith RD. Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. Prev Vet Med. 2000;45(1–2):23–41.
5. Hart JM, Bessette M, Choi L, Hogan MV, Diduch D. Sensory response following knee joint damage in rabbits. BMC Musculoskelet Disord. 2014;15:139.
6. Hart JM, Kuenze CM, Diduch DR, Ingersoll CD. Quadriceps muscle function after rehabilitation with cryotherapy in patients with anterior cruciate ligament reconstruction. J Athl Train. 2014;49(6):733–9.
7. Hart JM, Pietrosimone B, Hertel J, Ingersoll CD. Quadriceps activation following knee injuries: a systematic review. J Athl Train. 2010;45(1):87–97.
8. Hopkins JT, Ingersoll CD. Arthrogenic muscle inhibition: a limiting factor in joint rehabilitation. J Sport Rehabil. 2000;9:135–59.
9. Hopkins JT, Ingersoll CD, Krause BA, Edwards JE, Cordova ML. Effect of knee joint effusion on quadriceps and soleus motoneuron pool excitability. Med Sci Sports Exerc. 2001;33(1):123–6.
10. Hopkins JT, Wagie NC. Intrasession and intersession reliability of the quadriceps Hoffmann reflex. Electromyogr Clin Neurophysiol. 2003;43(2):85–9.
11. Iles JF, Stokes M, Young A. Reflex actions of knee joint afferents during contraction of the human quadriceps. Clin Physiol. 1990;10(5):489–500.
12. Kent-Braun JA, Le Blanc R. Quantitation of central activation failure during maximal voluntary contractions in humans. Muscle Nerve. 1996;19(7):861–9.
13. Konishi Y, Fukubayashi T, Takeshita D. Mechanism of quadriceps femoris muscle weakness in patients with anterior cruciate ligament reconstruction. Scand J Med Sci Sports. 2002;12(6):371–5.
14. Konishi Y, Konishi H, Fukubayashi T. Gamma loop dysfunction in quadriceps on the contralateral side in patients with ruptured ACL. Med Sci Sports Exerc. 2003;35(6):897–900.
15. Krishnan C, Allen EJ, Williams GN. Torque-based triggering improves stimulus timing precision in activation tests. Muscle Nerve. 2009;40(1):130–3.
16. Kuenze C, Hertel J, Saliba S, Diduch DR, Weltman A, Hart JM. Clinical thresholds for quadriceps assessment after anterior cruciate ligament reconstruction. J Sport Rehabil. 2015;24(1):36–46.
17. Kuenze CM, Hertel J, Weltman A, Diduch D, Saliba SA, Hart JM. Persistent neuromuscular and corticomotor quadriceps asymmetry after anterior cruciate ligament reconstruction. J Athl Train. 2015;50(3):303–12.
18. Lepley AS, Bahhur NO, Murray AM, Pietrosimone BG. Quadriceps corticomotor excitability following an experimental knee joint effusion. Knee Surg Sports Traumatol Arthrosc. 2015;23(4):1010–7.
19. Lepley AS, Gribble PA, Thomas AC, Tevald MA, Sohn DH, Pietrosimone BG. Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: a 6-month longitudinal investigation. Scand J Med Sci Sports. 2015;25(6):828–39.
20. Lepley LK. Deficits in quadriceps strength and patient-oriented outcomes at return to activity after ACL reconstruction: a review of the current literature. Sports health. 2015;7(3):231–8.
21. Lepley LK, Palmieri-Smith RM. Pre-operative quadriceps activation is related to post-operative activation, not strength, in patients post-ACL reconstruction. Knee Surg Sports Traumatol Arthrosc. 2016;24(1):236–46.
22. Lepley LK, Wojtys EM, Palmieri-Smith RM. Combination of eccentric exercise and neuromuscular electrical stimulation to improve quadriceps function post-ACL reconstruction. Knee. 2015;22(3):270–7.
23. Luc B, Gribble PA, Pietrosimone BG. Osteoarthritis prevalence following anterior cruciate ligament reconstruction: a systematic review and numbers-needed-to-treat analysis. J Athl Train. 2014;49(6):806–19.
24. Luc BA, Harkey MH, Arguelles GD, Blackburn JT, Ryan ED, Pietrosimone B. Measuring voluntary quadriceps activation: effect of visual feedback and stimulus delivery. J Electromyogr Kinesiol. 2016;26:73–81.
25. Magnussen RA, Verlage M, Flanigan DC, Kaeding CC, Spindler KP. Patient-reported outcomes and their predictors at minimum 10 years after anterior cruciate ligament reconstruction: a systematic review of prospectively collected data. Orthop J Sports Med. 2015;3(3):2325967115573706.
26. Øiestad BE, Juhl CB, Eitzen I, Thorlund JB. Knee extensor muscle weakness is a risk factor for development of knee osteoarthritis. A systematic review and meta-analysis. Osteoarthritis Cartilage. 2015;23(2):171–7.
27. Palmieri RM, Ingersoll CD, Hoffman MA. The Hoffmann reflex: methodologic considerations and applications for use in sports medicine and athletic training research. J Athl Train. 2004;39(3):268–77.
28. Palmieri RM, Tom JA, Edwards JE, et al. Arthrogenic muscle response induced by an experimental knee joint effusion is mediated by pre- and post-synaptic spinal mechanisms. J Electromyogr Kinesiol. 2004;14(6):631–40.
29. Palmieri RM, Weltman A, Edwards JE, et al. Pre-synaptic modulation of quadriceps arthrogenic muscle inhibition. Knee Surg Sports Traumatol Arthrosc. 2005;13(5):370–6.
30. Park J, Hopkins JT. Quadriceps activation normative values and the affect of subcutaneous tissue thickness. J Electromyogr Kinesiol. 2011;21(1):136–40.
31. Pietrosimone BG, Lepley AS, Ericksen HM, Clements A, Sohn DH, Gribble PA. Neural excitability alterations after anterior cruciate ligament reconstruction. J Athl Train. 2015;50(6):665–74.
32. Pietrosimone BG, Lepley AS, Ericksen HM, Gribble PA, Levine J. Quadriceps strength and corticospinal excitability as predictors of disability after anterior cruciate ligament reconstruction. J Sport Rehabil. 2013;22(1):1–6.
33. Pietrosimone BG, McLeod MM, Lepley AS. A theoretical framework for understanding neuromuscular response to lower extremity joint injury. Sports health. 2012;4(1):31–5.
34. Pietrosimone BG, Saliba SA. Changes in voluntary quadriceps activation predict changes in quadriceps strength after therapeutic exercise in patients with knee osteoarthritis. Knee. 2012;19(6):939–43.
35. Pietrosimone BG, Selkow NM, Ingersoll CD, Hart JM, Saliba SA. Electrode type and placement configuration for quadriceps activation evaluation. J Athl Train. 2011;46(6):621–8.
36. Rosenthal MD, Moore JH, Stoneman PD, DeBerardino TM. Neuromuscular excitability changes in the vastus medialis following anterior cruciate ligament reconstruction. Electromyogr Clin Neurophysiol. 2009;49(1):43–51.
37. Stackhouse SK, Dean JC, Lee SC, Binder-MacLeod SA. Measurement of central activation failure of the quadriceps femoris in healthy adults. Muscle Nerve. 2000;23(11):1706–12.
38. Stackhouse SK, Stevens JE, Johnson CD, Snyder-Mackler L, Binder-Macleod SA. Predictability of maximum voluntary isometric knee extension force from submaximal contractions in older adults. Muscle Nerve. 2003;27(1):40–5.
39. Tourville TW, Jarrell KM, Naud S, Slauterbeck JR, Johnson RJ, Beynnon BD. Relationship between isokinetic strength and tibiofemoral joint space width changes after anterior cruciate ligament reconstruction. Am J Sports Med. 2014;42(2):302–11.
40. Ward S, Pearce AJ, Pietrosimone B, Bennell K, Clark R, Bryant AL. Neuromuscular deficits after peripheral joint injury: a neurophysiological hypothesis. Muscle Nerve. 2015;51(3):327–32.
Keywords:

QUADRICEPS; VOLUNTARY ACTIVATION; CENTRAL ACTIVATION RATIO; SPINAL REFLEX; HOFFMANN REFLEX

© 2016 American College of Sports Medicine