The Effect of Baseline Quadriceps Activation on Changes in Quadriceps Strength After Exercise Therapy in Subjects with Knee Osteoarthritis

Abstract

Objective

The aim of this study was to examine whether pretreatment magnitude of quadriceps activation (QA) helps predict changes in quadriceps strength after exercise therapy in subjects with knee osteoarthritis (OA). We hypothesized that subjects with lower magnitudes of QA (greater failure of muscle activation) would have smaller gains in strength compared to those with higher magnitudes of QA following exercise therapy.

Methods

111 subjects with knee OA (70 ♀) participated in the study. Baseline measures included demographic information, quadriceps muscle strength and QA using a burst-superimposition isometric torque test. Following baseline testing, subjects underwent a 6 week supervised exercise program designed to improve strength, range of motion, balance and agility, and physical function. On completion of the exercise program, quadriceps strength and QA were re-assessed. Multiple regression analysis was used to determine whether baseline QA predicted quadriceps strength scores at the 2 month follow-up period.

Results

Bivariate correlations demonstrated that baseline QA was significantly associated with quadriceps strength at baseline (rho = 0.30, p < 0.01) and 2 month follow-up (rho = 0.23, p = 0.01). Greater magnitude of baseline QA correlated to higher strength. While controlling for baseline quadriceps strength and type of exercise therapy, the level of QA did not predict quadriceps strength at the 2 month follow-up (β = −0.04, p = 0.18).

Conclusions

Baseline QA did not predict changes in quadriceps strength following exercise therapy. Measurement of QA using the CAR method does not appear to be helpful in identifying subjects with knee OA who will have difficulty improving quadriceps strength with exercise therapy. Investigation of other factors that may affect response to exercise therapy is warranted.

Knee osteoarthritis (OA) is a common chronic condition affecting more than 4.3 million older adults in the United States (1). It is a major cause of pain and functional impairment including difficulty with several activities of daily living (1–3). Weakness of the quadriceps muscle is well documented in subjects with knee OA(4–6), is strongly associated with pain, and is an important determinant of disability(4;7). Quadriceps strength is an important factor to target because weakened quadriceps muscles may increase joint stresses from decreased ability to attenuate loads across the joint(8). Additionally, quadriceps weakness may play a role in the etiology and progression of OA(6;8;9).

Multiple factors play a role in the etiology of muscle weakness. In addition to pain and disuse atrophy, reduced quadriceps activation (QA) has been suggested to contribute (4;8;10). The presence of reduced QA (failure to fully activate the muscle) is well established in subjects with knee joint effusions (11;12) and traumatic injuries(10;13–17), and also can be present in knee OA even in the absence of pain and effusion (4;5;7;18). The proposed mechanism for the etiology of reduced QA in knee OA is a damaging cycle. Degenerative changes in the joint may damage articular mechanoreceptors which lead to abnormal processing of sensory information and inhibition of muscle activation. This, in turn, predisposes the quadriceps to weaken which increases risk for more joint damage (4;8). Recently, it has been suggested that reduced QA may have an impact on physical function in subjects with knee OA by moderating the relationship of quadriceps strength to function (19). Subjects with low strength and reduced QA had lower function than those with similar strength but high QA (19).

While exercise leads to increased quadriceps strength along with improved pain and function (20;21), strength deficits remain and overall effect sizes have been variable (10;22). It is possible that the presence of reduced QA could contribute to this lack of robust response. A few studies have suggested some improvement in QA with exercise alone, but results have been inconclusive, and there has not been an attempt to examine how pre-therapy level of QA might affect or predict the degree of response to therapeutic exercise (10;23;24). It may be possible that reduced QA might not allow an individual the capacity to produce enough tension in the muscle during exercise to achieve an exercise training effect, which in turn may limit their responsiveness to an exercise program.

We are specifically interested in looking at how pre-therapy QA levels may affect response to therapeutic exercise in terms of quadriceps strength, which is a key determinant of function in subjects with knee OA. Therefore, the study aim was to examine whether pretreatment magnitude of QA helps predict changes in quadriceps strength after exercise therapy in subjects with knee OA. We hypothesized that subjects with lower magnitudes of QA (greater failure of muscle activation) would have smaller gains in strength compared to those with higher magnitudes of QA following exercise therapy.

MATERIALS AND METHODS

The data reported here were drawn from an ongoing randomized clinical trial comparing two exercise rehabilitation regimens for subjects with knee OA. The current longitudinal study looks at associations using baseline and 2 month follow-up data.

Subjects

One hundred and forty two subjects with knee OA were eligible for the study. Subjects were eligible if they completed baseline measurement of quadriceps strength and QA, 12 sessions of exercise therapy over 6 weeks, and a strength measurement at 2 months from baseline. Subjects were included in the study if they were 40 years of age and older, met the 1986 American College of Rheumatology (ACR) clinical criteria for knee OA and had grade II or greater Kellgren and Lawrence radiographic changes in the tibiofemoral joint(25;26). Subjects were excluded from the study if they: 1) had conditions that would place them at risk for injury during the exercise training program (e.g. requiring an assistive device for ambulation, history of two or more falls in the previous year, unable to ambulate 100 feet independently), 2) had undergone total knee arthroplasty, 3) exhibited uncontrolled hypertension, 4) had history of cardiovascular disease, 5) had history of neurological disorders that affect lower extremity function (e.g. stroke, peripheral neuropathy), 6) had conditions that would place them at risk for re-injury during quadriceps strength testing (e.g. recent corticosteroid injection to the quadriceps or patellar tendons, quadriceps or patellar tendon rupture, patellar fracture), or 7) reported vision problems that affected performance of basic mobility tasks. All subjects signed an informed consent form approved by the University of Pittsburgh Institutional Review Board prior to participation in the study.

Exercise therapy intervention

Subjects were randomized to receive one of two types of exercise therapies. The standard exercise therapy consisted of lower extremity stretching, range of motion and strengthening exercises, as well as aerobic exercise. The experimental exercise therapy included all of the above plus dynamic agility and balance training activities. (see Appendix) Physical therapists supervised 12 sessions of therapy over 6 weeks.

Testing procedure

Data for each subject were collected during 2 testing sessions. Baseline testing included completion of demographic and health history questionnaires, knee radiographs and measurement of quadriceps muscle strength and QA. Two month from baseline testing consisted of measurement of quadriceps muscle strength.

Quadriceps strength and the magnitude of QA were measured using a burst-superimposition maximum isometric quadriceps torque test. This procedure has been shown to yield reliable quadriceps muscle torque measurements by other investigators (27), and in our own laboratory (intraclass correlation coefficients for intratester reliability [between 1 and 3 days] = 0.97 and intertester reliability [same day] = 0.82). Because most subjects had bilateral knee involvement, an involved-to-uninvolved limb comparison was not possible. Therefore, we elected to test the limb that subjects reported as being the most symptomatic limb with regard to pain and functional limitation.

Subjects sat on an isokinetic dynamometer (Biodex System 3 Pro, Shirley, NY) with the test knee positioned in 60° of flexion. Electrodes were placed proximally over the vastus lateralis muscle belly and distally over the vastus medialis muscle belly. A thigh strap, waist strap, and 2 chest straps were then secured to stabilize the subject in the dynamometer chair.

Once the subject was prepared for testing, we employed a process of potentiating the quadriceps muscles to maximize the subject’s ability to produce maximum torque output (28). In addition, this process familiarized the subjects with both the electrical stimulus to be used during testing, and the maximum voluntary isometric torque test procedure, which would help minimize the potential for learning effects on the test results. During the first step in the process, subjects practiced producing 3–5 second voluntary isometric quadriceps contractions against the force arm of the dynamometer at 50%, 75%, and 100% effort. Next, subjects received 3 successive trains of electrical stimulation (pulse duration = 600 µsec, pulse interval = 10 msec, train duration = 100 msec), separated by 30-second time intervals, applied to the resting muscle at amplitudes of 40V, 60V, and 100V. If the 100V stimulus when applied to the resting muscle did not produce at least 25% of the practice maximum voluntary torque, we increased the stimulus to 130V to ensure the stimulus would be adequate to show failure of muscle activation if it existed. If the resting electrically stimulated torque did not achieve a value of at least 25% of the practice maximum voluntary torque after increasing the stimulus amplitude to 130V, we concluded the stimulus was not adequate for accurate QA measurement and the subject’s data was not included in the final analysis.

Following the series of electrical stimuli, formal measurements of maximum voluntary isometric quadriceps strength and QA were initiated. Subjects were asked to exert as much force as possible while extending the knee against the fixed force arm of the dynamometer and to hold each maximal contraction for 3–5 seconds. During the maximal contraction the train of electrical stimuli (amplitude = 100V or 130V, pulse duration = 600 µsec, pulse interval = 10 msec, train duration = 100 msec) was applied to determine the extent of muscle activation. To maximize their ability to produce maximum torque output during the test, the examiner provided intense verbal encouragement to subjects and provided with real time visual feedback of the torque trace displayed on a computer monitor. A torque target line, placed at a torque level slightly greater than the peak torque produced during the practice maximum voluntary isometric contraction, was also visible on the computer monitor. If subjects exceeded this torque target during a given trial, the target was reset at a higher level for the next trial. To optimize the measurement of a maximum contraction, subjects completed 3–6 trials with 1–1 ½ minutes of rest between trials until the level of voluntary torque produced decreased compared to the prior trials.

The magnitude of QA was calculated using the quadriceps central activation ratio (CAR), which is a ratio of the highest maximum voluntary torque produced prior to delivery of the electrical stimulus divided by the highest torque produced when the electrical stimulus was superimposed on the maximum voluntary contraction (29). Full QA is represented by a CAR equal to 1 as the superimposed electrical stimulus does not result in a further increase in torque compared to the maximum voluntary torque. When failure of full QA is present, the electrical stimulus will recruit previously inactive muscle fibers to fire and the torque produced with the superimposed electrical stimulus will surpass that of the maximum voluntary torque, a CAR less than 1.

To ensure adequate measurement of QA, the data had to meet certain criteria. In addition to recording the maximum torque produced before and during the delivery of electrical stimulus, we recorded the magnitude of the torque just prior to the time the stimulus was delivered to determine if there was a drop from the maximum torque. A significant drop in torque before the electrical stimulus was delivered could affect the accuracy of the QA calculation. We used the data from the trial with the highest maximum voluntary torque prior to the delivery of the electrical stimulus, as long as the subject was able to maintain that torque within 5% at the time the electrical stimulus was applied. If the drop in torque was greater than 5% at the time the electrical stimulus was delivered, we used values from the next highest maximum voluntary torque trial with a drop less than or equal to 5%, as long as the voluntary torque achieved was at least 95% of the overall maximum voluntary torque. If there were no trials with a maximum voluntary torque within 95% of the overall voluntary maximum and with a drop in torque less than or equal to 5% when the electrical stimulus was delivered, we concluded the data was not appropriate for accurate QA measurement and excluded that subject from the analysis. Our outcome measure of strength at 2 month follow-up was simply the highest maximum voluntary torque produced out of all the trials performed at the 2 month follow-up testing session.

Other factors potentially associated with QA and quadriceps strength

We recorded several other factors that could potentially be associated with level of QA and quadriceps strength for consideration as covariates. Demographic factors included gender, age, height, weight, and number of years with a diagnosis of knee OA. Clinical factors included knee pain during the burst-superimposition testing procedure, the severity of radiographic knee OA, and medication use. Knee pain during the test was measured using a verbal 0–10 numeric pain scale, with 0 representing no pain and 10 representing the worst pain imaginable. The severity of radiographic knee OA was rated by an experienced rheumatologist, using the method described by Kellgren and Lawrence (26). Medication use related to the management of knee OA was determined by the information collected on the demographic and health history questionnaire. Additionally, we recorded the torque produced when the electrical stimulus was applied to the resting muscle, called the resting e-stim torque.

Data analysis

We first examined descriptive statistics to assess for outliers and data distributions. Then we calculated bivariate correlation coefficients to look at associations among quadriceps strength, QA and potential covariates. Pearson correlation coefficients were used between normally distributed continuous variables and Spearman rho coefficients were used for categorical and non-normally distributed continuous variables. We planned to use the variables that concomitantly associated with QA and quadriceps strength as covariates in the multivariable regression analysis.

Next we performed multivariable regression to test the hypothesis that magnitude of pre-therapy QA may affect changes in quadriceps strength following a regimen of exercise therapy. Quadriceps strength at 2 month follow-up was our outcome variable. In the first step of the regression we controlled for baseline quadriceps strength and type of exercise therapy. Next we entered our predictor variable, CAR, as a measure of QA. Statistical significance was determined using an alpha level of 0.05. Regression coefficients and standardized beta coefficients for each variable in the final model were calculated and the significance of each was tested under the null hypothesis that the coefficient was not different from zero. Regression diagnostics were performed to assess if our model met the linear regression assumptions of normality, homoscedasticity and linearity.

RESULTS

Of the initial 142 subjects eligible for the study, 24 subjects were excluded because their QA data did not meet our criteria of an adequate QA measurement as stated above. In addition, 7 subjects were excluded because they could not achieve a resting electrically stimulated torque measurement of greater than or equal to 25% of the practice maximum voluntary contraction. Therefore data from 111 subjects were included in the final analysis. The 31 subjects excluded from the analysis were not different in demographic characteristics from the remaining subjects included in the analysis, based on a Wilcoxin test comparison between groups for continuous data and Chi Square for nominal data, at alpha = .05. Descriptive statistics for the 111 subjects are listed in Table 1.

Table 1.

Descriptive statistics for subjects, N=111.

Variable	Mean (SD) or Frequency (%)	Range
Gender		N/A
Female	70 (63.1)
Age	63.7 (9.1)	40–85
Height in cm	167.9 (9.9)	148–196
Weight in kg	84.0 (18.8)	48–160
Time since diagnosis		N/A
< 1 year	17 (15.3)
1–2 years	22 (19.8)
3–5 years	21 (18.9)
5–10 years	19 (17.1)
> 10 years	32 (28.8)
Tib-Fem X-ray grade		N/A
2	14 (12.6)
3	62 (55.9)
4	35 (31.5)
Pat-Fem X-ray grade		N/A
0	2 (1.8)
1	20 (18.0)
2	47 (42.3)
3	29 (26.1)
4	11 (9.9)
Medication use*		N/A
Yes	75 (67.6)
No	36 (32.4)
Exercise therapy type
Standard	55 (49.5)
Perturbation	56 (50.5)
Pain during test	0.50 (1.4)	0–7
Resting E-stim torque (% practice MVC)	53.8 (14.9)	26.4–107.8
Baseline maximum quadriceps strength in Nm	139.5 (53.3)	30–280
Baseline CAR	0.93 (0.06)	0.62–1.00
2 month maximum quadriceps strength in Nm	144.7 (57.0)	25–302

CAR = central activation ratio (measurement of quadriceps activation)

^*Medications included analgesics, NSAIDs, COX-2 inhibitors, glucosamine and chondroitin supplementation, and knee injections of corticosteroids or hyaluronic acid.

Factors related to QA and quadriceps strength

Bivariate correlations among potential covariates, QA and quadriceps strength are shown in Table 2. Gender, age, height, weight, number of years since diagnosis of knee OA, numeric pain rating during the burst-superimposition test, severity of radiographic knee OA, medication use and resting e-stim torque were not significantly correlated with the magnitude of QA as measured by CAR. Quadriceps strength was associated with several of these factors. Men exhibited higher strength than women, younger subjects had higher strength than older subjects, taller subjects had higher strength than shorter subjects, and heavier subjects had higher strength than lighter subjects. Time since diagnosis of knee OA was associated with quadriceps strength indicating that subjects more recently diagnosed tended to have higher strength than those with longstanding disease. A higher level of resting e-stim torque was also related to higher quadriceps strength. There were no significant associations between quadriceps strength and pain during the burst-superimposition test, severity of radiographic knee OA, or medication use.

Table 2.

Bivariate correlations between CAR, quadriceps strength, and potential covariates. When not otherwise stated, the values represent Pearson Correlation coefficients.

	Baseline CAR (rho)	Baseline quad strength	2 month quad strength
Gender (rho)	0.06	−0.67**	−0.64**
Age	−0.03	−0.37**	−0.39**
Height	−0.05	0.65**	0.63**
Weight	0.16	0.49**	0.48**
Time since knee OA diagnosis (rho)	0.05	−0.22*	−0.20*
Pain during testing (rho)	−0.17	−0.09	−0.05
Tibial-femoral radiographic grade (rho)	0.14	−0.03	−0.01
Patellofemoral radiographic grade (rho)	0.08	−0.12	−0.13
Medication use (rho)	−0.02	0.10	0.09
Resting E-stim torque	−0.09	0.76**	0.74**
Exercise therapy type (rho)	−0.07	0.13	0.10
Baseline CAR (rho)	--	0.30**	0.23*
Baseline quad strength	--	--	0.96**

^**p<0.01

^*p<0.05

CAR = central activation ratio (measurement of quadriceps activation)

(rho) = Spearman rho coefficient was calculated for variables not normally distributed

Relationship of QA magnitude and strength after exercise therapy

Bivariate correlations demonstrated QA was associated with quadriceps strength at baseline (rho = 0.30, p < 0.01) and 2 month follow-up (rho = 0.23, p = 0.01). Greater QA correlated to higher strength. Table 3 shows the results of the linear regression on quadriceps strength at 2 month follow-up. While controlling for baseline quadriceps strength and type of exercise therapy, the level of QA did not add to the prediction of quadriceps strength outcome (β = −0.04, p = 0.18). We did not include any of the other potential factors as covariates since none of them were associated with QA. Variance inflation factors were less than 10 indicating no multicollinearity. Observation of residual plots demonstrated that our model fit the linear regression model assumptions of normality, homoscedasticity and linearity.

Table 3.

Linear regression model on quadriceps strength at 2 month follow-up.

Variable	R2	Adj R2	DF	p	B	Beta	p
Overall model	0.92	0.92	3, 107	<0.01
Constant					32.14	--	0.15
Exercise type					−2.68	−0.02	0.38
Baseline quadriceps strength					1.04	0.98	<0.01
Baseline CAR					−33.74	−0.04	0.18

DF = degrees of freedom, B = unstandardized coefficients, Beta = standardized coefficients

DISCUSSION

Consistent with prior research(4), we found that lower QA is associated with lower quadriceps strength. Interestingly, our results indicated that pretreatment level of QA did not predict quadriceps strength after exercise therapy in subjects with knee OA. While greater reduction of QA was related to weaker quadriceps, the reduction did not appear to affect how subjects responded to exercise therapy in terms of quadriceps strength. Our sample had a wide range in changes in strength (− 54 to + 52 Nm, mean change of 5.2 ± 15.9 Nm). However, QA did not contribute to predicting the variance of this change. This leads us to believe that other factors may be more important in determining who responds best to strengthening regimens. Further study is needed to examine other potential factors such as subject effort, motivation and compliance with the exercise therapy.

Our mean CAR is slightly lower (0.93 vs. 0.94–0.95) and our prevalence of reduced QA is slightly higher (50% vs. 40–44%) than values reported for healthy elderly adults using similar testing protocols (30;31). In comparison, healthy middle aged individuals had a 25% incidence of reduced QA(5), and about 10% of healthy younger subjects did not achieve a CAR > 0.95 (30;31). Knee OA may increase the likelihood of muscle activation deficits, although the magnitude of QA is not substantially lower than estimates due to age-related changes. It is possible that activation deficits first occur early in the disease course when their clinical impact is minimal, but can predispose to quadriceps weakness, further joint damage from a less stable joint, and further decrease in activation as time and disease progress. A recent study reported that both the level of QA and lean muscle cross-sectional area of the quadriceps are significantly associated with quadriceps strength in limbs with and without end-stage knee OA, but relative contributions differ. The level of QA explained a greater percentage of variance in quadriceps strength in limbs with end-stage knee OA, while lean muscle cross-sectional area explained a larger proportion of the variance in quadriceps strength in uninvolved limbs (32). However, this study utilized a cross-sectional design so it is uncertain how QA, if left untreated, affects quadriceps strength, joint damage, or joint instability over time. The data from our study seems to indicate that QA does not have an influence on strength gains when subjects participate in an exercise program.

The mean QA in our sample was 0.93 ± 0.06 with a median of 0.95 and a range of 0.62–1.00. This is higher than several prior studies which reported means of 0.81 (10), 0.66 (18) , and a median of 0.73 (4). The difference in mean QA in our study compared with others may be related to differences in methodology. Some studies used different techniques (4;10;18;23), and not all describe a procedure with sufficient practice, motivation and feedback(10;18), which is important for eliciting maximum voluntary effort and accurate estimation of QA. One study that did use the same burst superimposition technique with CAR, as well as procedures to optimize accurate QA measurement, found similar QA to our values with a mean CAR of 0.93(5). In addition, the prevalence of failure of full QA, as defined by CAR < 0.95 (5;30;31),was 50% in that study as well as in our analysis.

Overall, the difference in values for QA among studies implies that the precise magnitude cannot be directly compared across studies using different stimulus parameters and testing procedures. Some believe that the burst-superimposition method may be the best method for measuring QA(29;33) while others have contested this viewpoint, in favor of twitch-interpolation.(34;35) At any rate, it should also be acknowledged that our finding that baseline QA using the CAR method does not predict change in strength after exercise may not necessarily apply to other methods of measuring QA, such as the twitch interpolation method. To our knowledge, examining whether baseline QA predicts changes in strength following rehabilitation in subjects with knee OA has not been studied.

The experience of pain during testing could affect measurements of QA and quadriceps strength if it inhibited a subject from exerting full volitional effort. However, we found that the pain reported by subjects during testing was not correlated with either QA or quadriceps strength. Most subjects reported no pain during testing and only 4 subjects reported a pain of 5 or higher on the 0–10 numeric pain rating scale. This suggests that knee pain was not a significant confounder in our study.

Knee effusions have been shown to prevent full muscle activation (11;12). We did not have data on the presence or size of knee effusions in our sample, so we were not able to examine this factor as a potential confounder. However, a prior study did not find an association between joint effusion and QA or quadriceps strength in subjects with knee OA (19). It is plausible that the low prevalence and small size of effusions in subjects with knee OA are not enough to significantly induce activation failure as is observed in other populations. Therefore, we do not believe our results were confounded by this factor.

While the burst superimposition test has been shown to be sensitive to detect failure of muscle activation (29;33), and has been widely used (5;15;17;30;31;36), there remain limitations to the test. Recently, some investigators have suggested that CAR overestimates the actual degree of muscle activation because the relationship between percentage of maximum voluntary effort and CAR appears curvilinear and not strictly linear.(34;37) This poses complexities for the analysis and comparison of QA data. We optimized our measurement of QA by providing adequate practice, verbal encouragement and visual feedback to the subjects, using an adequate stimulus, and taking the best of several trials. But can we really know if all the subjects were exerting their maximum effort? Low CAR may be due to sub-maximal voluntary effort in addition to intrinsic inhibition of muscle activation. Additionally, to further ensure accurate measurement of QA, we only included data that met strict criteria. A number of potential subjects were not included in the study because they were not able to maintain a maximum voluntary contraction long enough for delivery of the electrical stimulus to measure QA, despite practice trials, verbal encouragement and visual feedback. Given the time, effort and difficulties associated with administering this test, the utility may be limited in a knee OA population where the magnitude of activation deficits appears modest. However, in populations with significant trauma to the joint and greater activation deficits such as following total knee arthroplasty (36;38), the utility may be greater.

In conclusion, pretreatment magnitude of QA, using the CAR method, did not help predict quadriceps strength following exercise therapy. Measurement of QA using the CAR method, does not appear to be helpful in identifying subjects with knee OA who will have difficulty improving quadriceps strength with exercise therapy. It is not known if these results would apply when QA is measured using twitch interpolation methods. Investigation of other factors that may affect response to exercise therapy is warranted.

Appendix

Appendix 1.

Exercise Therapy Procedures

Exercise Description	Exercise Dosage/Progression
Calf Stretching: Subject stands in front of wall with hands supporting body against the wall. For the limb being stretched, the hip is extended, the knee is extended and the foot is placed flat on the floor. The contralateral limb rests on the floor for stability with the hip and knee comfortably flexed and the foot resting comfortably on the floor. The patient slowly leans forward toward the wall, keeping the foot flat and maintained in slight supination, and keeping the knee extended, until a stretch discomfort is felt by the subject in the calf muscles.	2 repetitions, each of 30 seconds duration. Performed on both limbs. Range can be increased during 30 second period if subject reports stretch discomfort has decreased.
Hamstring Stretching: The therapist stabilizes the contralateral limb on the plinth and moves the stretching limb in a straight leg raise position, flexing the hip until a stretch discomfort is felt by the subject in the hamstrings while keeping the knee in full extension. The range can be increased during the 30 second period if the patient reports that the stretch discomfort has decreased.	2 repetitions, each of 30 seconds duration. Performed on both limbs. Range can be increased during 30 second period if subject reports stretch discomfort has decreased.
Prone Quadriceps Stretching: The subject lies on the treatment table in prone. The therapist stabilizes the contralateral limb on the plinth. The knee of the stretching limb is placed in 90 degrees of flexion, then the therapist extends the hip until a stretch discomfort is felt by the subject in the quadriceps.	2 repetitions, each of 30 seconds duration. Performed on both limbs. Range can be increased during 30 second period if subject reports stretch discomfort has decreased.
Long-Sitting Knee Flexion and Extension: The subject is positioned in long-sitting on the treatment table. The therapist instructs the subject to flex the knee as far as possible by sliding the foot along the treatment table toward the pelvis. The subject holds the flexed position for 3–5 seconds. A belt, towel, or a strap may be used by the subject to assist with bending the knee. The therapist then instructs the subject to extend the knee by sliding the foot along the treatment table toward the end of the table. The subject holds the fully extended position for 3–5 seconds.	Repetitions are progressed from a minimum of 10 to a maximum of 30 reps. Exercise is repeated on the opposite limb.
Quadriceps setting: The subject is positioned in long sitting with the knee extended. Therapist instructs the subject to isometrically contract the quadriceps muscles bilaterally as vigorously as possible without reproducing pain. The subject is instructed to hold the contraction for 3–5 seconds.	Exercise is progressed from 10 contractions to 30 contractions as tolerated.
Supine straight leg raises: The subject is positioned in supine on the treatment table. The contralateral knee is flexed so that the foot is resting comfortably in a foot flat position on the table. The therapist instructs the subject to raise the exercise limb with the knee maintained in full extension to the height of the contralateral flexed knee position, then lower the limb back to the table	Exercise is progressed from 10 to 30 reps. When subject can do 30 reps without added weight, a 1 pound cuff weight is added. Resistance is progressed by adding 1 pound when the subject can do 30 reps at the current resistance. Exercise is performed on each limb.
Prone straight leg raises: The subject is positioned in prone on the treatment table. The therapist instructs the subject to raise the exercise limb with the knee maintained in full extension as high as possible, then lower the limb back to the table.	Exercise is progressed from 10 to 30 reps. When subject can do 30 reps without added weight, a 1 pound cuff weight is added. Resistance is progressed by adding 1 pound when the subject can do 30 reps at the current resistance. Exercise is performed on each limb.
Seated knee extension isometrics: The subject is seated on a leg extension exercise device with the knee positioned in a comfortable flexed position between 90° and 60° of flexion. The subject is instructed to push against the force pad of the extension device as vigorously as possible without reproducing pain symptoms. The subject is instructed to hold the contraction for 3–5 seconds.	Exercise is progressed from 10 contractions to 30 contractions as soon as possible (by the 3rd treatment visit). Exercise is performed on each limb.
Single Limb Seated Leg Press: The subject is positioned in sitting on a leg press machine with the exercise limb fixed to the foot platform. The subject is instructed to extend and flex knees in a range of motion from 0° to 45° of flexion against . The exercise should be repeated on the other leg.	A resistance equivalent to 70% of the one repetition maximum should be used for training. Subject attempt to perform 3 sets of 10 reps at this resistance. When the subject can perform 3 sets of 10 reps, resistance should be advanced 1 plate (4.54 kg.). Additional plate is added when 3 sets of 10 reps are achieved with current resistance. A new 1 repetition maximum should be established every 2 weeks (every 4th visit). The minimum resistance is then 70% of the newly established 1 repetition maximum.
Standing Hamstring Curls with Cuff Weights: A 1 kg cuff weight is wrapped around the subjects ankle. The subject faces a wall or door. Keeping the thigh on the exercise leg even with the thigh from the support leg, the exercise leg knee is flexed to 90 degrees then slowly lowered back to the start position.	Subject attempts to perform 3 sets of 10 repetitions. When subject can perform all 3 sets at 10 repetitions, another kilogram of resistance is added.
Standing Calf Raises: The subject is positioned in standing with both feet flat on the floor. The subject is instructed to raise up on the toes as high as possible, holding for 1–2 seconds then return to the foot flat position.	When the subject can perform 30 repetitions with body weight, the exercise is performed on a calf machine, starting with 1 plate of resistance (4.54kg). The resistance should be advanced 1 plate when the subject can perform 30 repetitions.
Treadmill Walking: Subjects will walk on a treadmill at a self-selected pace beginning at 1–5 minutes duration and progress to 15 minutes as tolerated.	When the subject reaches 15 minutes on the treadmill, the walking speed should be increased as tolerated.
Balance and Agility Activities for the Experimental Group
Side stepping: Subjects step sideways, moving right to left then left to right, approximately 10–20 ft, repeating 2 times in each direction for a total of 4 times.	The width of steps and the speed of steps are progressed every 1 –2 sessions. The activity is initiated on a level surface and progressed to side stepping over low obstacles when subject performs side stepping on level surfaces without difficulty.
Braiding Activities: Subjects combine front and back cross-over steps while moving laterally. (walking carioca). During each activity subjects will be moving right to left then left to right, approximately 10–20 ft, repeating 2 times in each direction for a total of 4 times.	The activity is progressed by increasing the width of steps and the speed of steps every 1 –2 sessions.
Front and back cross-over steps during forward ambulation: The subject will cross one leg in front of the other, alternating legs with each step, while walking forward approximately 10–20 feet. The subject will then walk backwards to the start position while crossing one leg behind the other, alternating leges with each step.	Two repetitions are performed.. Begin with tandem cross-over steps and progress to full cross-over steps when the subject’s performance improves. The width of steps and the speed of steps can also be progressed every 1–2 sessions.
Shuttle Walking: Plastic pylon markers will be placed at distances of 5ft, 10ft, and 15ft. The subject walks forward to first marker, then return to start by walking backward. Subject then walks to 10ft marker forward, then returns to 5ft marker walking backward. The subject then walks to 15 ft marker, returns to 10 ft marker walking backward, then finish by walking to 15ft marker.	The activity is progressed by increasing the width of steps and the speed of steps every 1 –2 sessions.
Multiple change in direction during walking on therapist command: Therapist directs the subject to either walk forward, backward, sideways, or on diagonal by cueing patient with hand signals. Changes in direction are cued randomly by the therapist.	Duration of exercise bout is approximately 30sec.
Double leg foam balance activity: Subject stands on a soft foam surface with both feet on the ground. Therapist attempts to perturb patient balance in random fashion.	The duration of the activity is approximately 30 seconds. The difficulty is progressed as the patient improves by progress to ball catching with therapist perturbing patient balance while standing on foam, and progress to single leg support if tolerated without knee pain, swelling, buckling.
Tilt board balance training: The subject stands on a tilt board with both feet on the board. The therapist perturbs the tilt board in forward and backward and side to side directions for approximately 30 seconds each.	The difficulty of the activity is progressed by adding ball catching during the perturbations, and progressing to single limb support perturbations if the subject tolerates single limb weight bearing without knee pain, swelling, buckling.
Roller board and platform perturbations:The subject stands with one limb on a stationary platform, the other limb on a roller board.Therapist perturbs roller board in multiple directions, at random, and the subject attempts to resist the perturbations. The activity lasts approximately 30 seconds. The activity is repeated by changing the limbs on the platform and the roller board.	The activity may begin with subject in the semi-seated position, with hips resting on plinth if the subject has difficulty doing the activity in full standing. The activity is progressed to the full standing position when the subject is able to tolerate this position without pain.

Home Exercise Program

Subjects were encouraged to perform their exercises independently at home at least 2x/week on days they were not coming to therapy. The program was essentially the same with some modifications for home. The modifications were as follows:

For the Standard Program

Wall squats were substituted for the seated leg press

Isometric knee extensions were performed against heavy resistance elastic bands that were secured to a chair.

For the Experimental Program

Subjects in the experimental group performed all standard home program activities. In addition, they performed all agility training with the exception of the multiple change in direction during walking on therapist command activity. They also did not perform tilt and rollerboard activities. They performed single leg standing balance.