Restoring Symmetry: Clinical Applications of Cross-Education

Jonathan P. Farthing; E. Paul Zehr

Disclosures

Exerc Sport Sci Rev. 2014;42(2):70-75. 

In This Article

Clinical Models of Cross-education

Unilateral orthopedic injury and poststroke hemiparesis represent viable models to test the clinical utility of cross-education because, in each case, there is an injury that temporarily or permanently results in an interlimb asymmetry. The utility of cross-education emerges because one limb is rendered unable to engage in training or movement and chronic training of the less affected or intact side could be used preventatively to offset maladaptation or therapeutically to restore lost function caused by damage.

The Case for Orthopedic Injury

Unilateral orthopedic injury presents a disuse-induced asymmetry as a consequence of necessary treatment (i.e., casting or immobilization). Aside from the pathology of the injury itself, the prolonged disuse results in functional strength loss and atrophy and heavily impacts the nervous system.[33,35] After injury, there are severe decrements in muscle size, strength, and muscle activation,[33,35] and efforts to restore symmetry typically involve targeted rehabilitation of the injured limb only after the immobilization period. Therefore, unilateral orthopedic injury is a potential model to apply cross-education as a therapeutic intervention.

As one example of a common orthopedic injury, distal radius fracture presents with lasting deficits and poor long-term outcomes in high-risk groups.[2,16,34] Fractured limb strength at 3 months postfracture is approximately 50% of the nonfractured side[15,23] and deficits of approximately 12% or more persist even up to a year after the initial injury.[2,34] Wrist fracture represents a logical extension of the preliminary work with wrist cast immobilization models in healthy participants.[12,13] The proposition is that cross-education could be used during the disuse period to offset muscle wasting.

To test the hypothesis, Magnus et al.[23] implemented intense handgrip strength training of the nonfractured limb (progressing up to five sets of eight maximal effort, 3-s handgrip contractions, 3 d wk−1 during recovery from distal radius fracture in women older than 50 yr (mean age, 63 yr). The majority of patients were right handed, and the side of fracture was evenly distributed between dominant and nondominant sides. Training began within 1-wk after fracture, in addition to standard rehabilitation, and the outcomes were compared with those of patients receiving only standard rehabilitation. Standard rehabilitation exercises included active and passive range of motion exercises for the fractured limb only initiated at 9 wk after fracture. The cross-education intervention was shown effective for improving recovery of the fractured limb, where handgrip strength and active range of motion at 12 wk postfracture were significantly greater compared with those of the nontraining control group. During the interval from 9 to 12 wk after fracture, the cross-education group experienced a 34% greater increase in fractured limb strength compared with that in the control group (Fig. 1A) and near complete recovery of range of motion indicative of a more rapid recovery for the fractured limb. This time interval seems particularly important because, alarmingly, the nontraining control group experienced no improvement in fractured limb strength or range of motion up to 3 months postinjury. The cross-education strength training intervention continued up to 6 months, but there was no additional benefit compared with control.

Figure 1.

(A) Fractured limb handgrip strength. Note: Dotted line is Wk 1 nonfractured limb strength. *Significantly different from all other time points. **Significantly different from Wk 9. ***Significantly different from Wk 9 and Wk 12 (adjusted for multiple comparisons, P < 0.05). #Significant difference between groups (Bonferroni adjusted, P < 0.05/3 = 0.017). (B) Nonfractured limb handgrip strength. *Significantly different from Wk 1. **Significantly different from Wk 9 (adjusted for multiple comparisons, P < 0.05). #Significant difference between groups (unadjusted). ##Significant difference between groups (Bonferroni adjusted, P < 0.05/3 = 0.017). Data are means ± SE. Please note that the differential scaling of the y axes in (A) and (B) visually distorts the effect magnitude. (Reprinted from (23). Copyright © 2013 Elsevier. Used with permission.)

The study marks the first "proof-of-principle" example of cross-education applied in an orthopedic clinical setting involving limb fractures. Without measures of brain activation or other markers of neural plasticity, there was no conclusion regarding mechanisms of the sparing effects, but the study demonstrates the potential to offset some of the functional loss after unilateral fracture. Because the intervention did not involve targeted strength training (over and above standard rehabilitation exercises) of the fractured limb after cast removal, the impact of cross-education on subsequent strength training of the fractured limb also remains open for study. Importantly, Magnus et al.[23] demonstrate bilateral strength preservation effects for the cross-education group because the nontraining control group experienced bilateral decrements at 3 months postfracture, indicative of global functional decline (Fig. 1B). The lack of improvement in fractured limb strength of the control group at 3 months after injury (just 45% of nonfractured limb strength) may suggest a heightened risk of reinjury. We propose the wrist fracture as an excellent clinical model to apply cross-education to augment existing therapy, but the results are promising for a wide range of orthopedic injuries involving persistent immobilization. For example, promising recent evidence has emerged in support of cross-education during rehabilitation from knee reconstructive surgery.[29] Optimal rehabilitation strategies may involve a cross-education intervention applied during the immobilization period followed by subsequent training of both limbs after immobilization.

The Case for Stroke

Stroke presents a typical asymmetry of hemiparesis producing more affected (MA) and less affected (LA) sides.[39] Common clinical efforts attempt to modify the activity in the MA limb by stimulating, training, or treating it directly. An alternate and complimentary perspective is to instead attempt to access interlimb neural circuits.[37,38] This allows influencing the MA limb by using pathways from the LA side.

After stroke, weakness of leg flexor and arm extensor muscles is commonly combined with excessive antagonist muscle activity. This presents clinically as hyperexcitable reflex pathways[6,25] and leads to reduced movement at a given joint with decreased ability to generate purposeful torques and functional movement.[5,6] There is a particular dysfunction in reciprocal inhibition between functional antagonists at the wrist[1] and ankle.[8]

The overall goal of neurologic rehabilitation is to restore or promote more functional movement. Resistance training improves muscular strength and functional ability in poststroke hemiparesis without deleterious results,[26,30] including functional relearning to improve arm movement.[9]

Unfortunately, implementation of motor retraining may be compromised for those in critical need of training; namely, those with significant poststroke hemiparesis. In this group, substantial weakness in the MA limb can prevent sufficient activation to gain a training effect.[28] A protocol that could "boost" the ability to recruit targeted motor output on the MA side would be of great benefit.

Unilateral plantarflexion[20] or dorsiflexion[7] resistance training produces bilateral strength gains in neurologically intact participants. These changes in strength can be associated with changes in muscle activation and reflex excitability.[7] Despite these observations, the applicability and translational implications of the cross-education effect have not been much explored in neurologic rehabilitation. As outlined above, Farthing and colleagues[12,13,24] provided an important translational context for this effect when they showed that training the opposite arm could offset muscle wasting associated with immobilization during limb casting or immobilization.

Such also is applicable in poststroke hemiparesis. In a recent study,[8] 19 participants with chronic poststroke weakness performed high-intensity maximal isometric dorsiflexion resistance training (five sets of five maximal 2-s voluntary contractions three times per week for 6 wk) of the LA leg. Voluntary dorsiflexion strength in the trained (LA) leg increased by approximately 34%. In addition, the untrained MA leg showed an approximately 31% increase in strength (schematically illustrated in Fig. 2). Four participants who were unable to generate measurable dorsiflexion torque in the MA leg before training was able to meaningfully activate the untrained dorsiflexors after the intervention. Also, muscle activation was significantly increased bilaterally and reciprocal inhibition between the ankle flexor and extensor muscles was shifted in the direction of that found in the LA leg.

Figure 2.

Unilateral dorsiflexion training increased strength and muscle activation bilaterally after stroke.

This study showed for the first time that significant gains in voluntary strength and muscle activation in the untrained MA leg can be achieved by training the opposite LA limb after stroke. This proof-of-principle study demonstrates the residual plasticity that exists poststroke and is a significant step toward poststroke rehabilitation, specifically in cases of severe hemiparesis, where training the MA limb is not initially possible. We suggest that the clinical sequelae presenting as hemiparesis after stroke should be viewed as physiologically complimentary to the approach taken above with limb casting in orthopedic injury. The net functional effect in both limbs (and expressed most clearly in the MA limb) is a reduction of the sublime coordination normally present and an overall weakening. With this approach, cross-education of the LA limb could be used to initially "boost" muscle activation and strength in the MA limb. In this way, the MA limb then can be functionally recruited and activated in a targeted training paradigm focused on both limbs.

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