It is estimated that the prevalence of cerebral palsy (CP) in the United States and United Kingdom is roughly two to three cases per 1000 births.1,2 A survey within the Oxford region of England indicated that more than half of all children with CP have increased muscle tone in one or both of the upper limbs (information supplied by the UK Network of CP Registers and Surveys [UKCP], 2001).
The hand is typically affected, to the detriment of the performance of activities of daily living. The stereotypical posture of wrist flexion and ulnar deviation, coupled with finger and thumb flexion into the palm, hinders grasp and release. Impairments in the upper extremities in CP may include muscle tone abnormality, imbalance between muscle agonists and antagonists, spasticity, alignment problems, decreased strength, and impaired motor control.3,4 The combination of these primary impairments can and have been targeted for various rehabilitation strategies, including surgery,5–7 casting,8 and medication.9,10
An adjunct therapy, which has gained increasing support since its inception as a treatment for CP in the 1970s,11 is neuromuscular electrical stimulation (NMES). With NMES, electrical stimulation of sufficient intensity generally to produce visible muscle contraction is applied at the muscle motor point. Several case studies have reported improvement in hand function or use following a regimen of NMES treatment.12–15 Two larger studies also described the potential efficacy of NMES in improving function.16,17 Improvement in active wrist movement and performance of timed object manipulation tasks may be maintained after the stimulation protocol is ended.15,17 Indeed, in a series of case studies we observed that the improvements in performance of timed grasping tasks were maintained beyond six months after cessation of NMES treatment (unpublished data).
Thus, there is a suggestion that NMES therapy may have lasting, beneficial effects. Yet, use of NMES treatment may be hindered by the uncertainty regarding the mechanisms by which NMES may facilitate rehabilitation. Electrical stimulation is thought to improve strength,18 reduce spasticity of the antagonist muscle,19 reduce spasticity of the stimulated muscle,20 reduce cocontraction,16 and/or create soft-tissue changes permitting increased range of motion.17 The uncertainty of its impact on different mechanisms contributing to impairment makes targeting of appropriate subjects difficult.
The goal of this study was to quantitatively examine the impact of NMES on potential impairment mechanisms. Specifically, we tested whether a three-month NMES protocol for the wrist reduced wrist flexor muscle spasticity, reduced passive resistance to wrist rotation, reduced coactivation of wrist flexors and extensors, or increased isometric wrist flexion and extension strength.
Nine children (four males, five females), aged five to 15 years, with spastic hemiparesis subsequent to brain injury (eight with CP and one from a brain tumor excised 13 years previously at age two years) participated in the study. Inclusion criteria included spastic hemiparesis, impaired voluntary wrist extension movement, passive range of wrist extension >25 degrees with the fingers curled, sufficient passive supination to bring the forearm to neutral, and sufficient cognitive skills to follow verbal directions. This study was approved by the Northwestern University Institutional Review Board.
Subjects were enrolled in a three-month NMES protocol modeled after a regimen espoused by certain clinicians.21 During the first six weeks, surface NMES was applied in alternating fashion to the wrist extensors (with one electrode targeting both extensor carpi ulnaris and radialis placed proximally on the dorsal side of the forearm and a parallel electrode placed distally) and flexors (with one electrode targeting both flexor carpi ulnaris and radialis placed on the proximal forearm and a parallel electrode place distally). Symmetric biphasic pulses were applied through carbon film electrodes (ValuTrode®, Axelgaard Manufacturing Co., Ltd., Fallbrook, CA) by a two-channel commercial stimulator (NT2000, Bio-Medical Research Ltd., Donegal, Ireland). Stimulation parameters were set according to the previously defined protocol.21 Namely, pulse duration was fixed at 280 μs, stimulation frequency was set to 35 Hz, and a pattern of five seconds extensors on/five seconds extensors off/five seconds flexors on/and five seconds flexors off was employed. Ramp up time was set to 0.5 seconds and ramp down time to zero. The amplitudes were set to maximize wrist movement while still being comfortable for the subject.
NMES sessions, performed by the subjects and their parents in their own homes, consisted of 15-minute periods occurring six days per week. Subjects were instructed to work in synchrony with the stimulation to produce either extension or flexion of the wrist. The families kept a weekly log of stimulation sessions.
For the second six-week period, only the wrist extensors were stimulated. The stimulation pattern consisted of 10 seconds on/10 seconds off. When a subject was able to achieve full wrist extension against gravity with the aid of the stimulation, the subject and his or her guardians were instructed to increase resistance to wrist extension during the stimulation by having the subject grasp small objects or weights. The subject continued to assist the NMES in generating wrist extension. NMES session length was extended to 30 minutes, but the stimulation parameters and weekly frequency were kept the same as during the first six weeks.
Five testing sessions were conducted during the course of the treatment. Two occurred prior to initiation of the NMES, one took place at six weeks after initiation and two more were held at the end of the NMES treatment. Testing sessions were conducted in a laboratory at the Rehabilitation Institute of Chicago.
For each testing session, peak active wrist extension range of motion against gravity was first measured with a standard goniometer. The hand was then secured to a servomotor to perform the rest of the tests, as described in previous studies.22–24 Briefly, the subject was seated at a table and the forearm was stabilized in a neutral orientation between pronation and supination with respect to the table by a custom device through which the arm was placed. The hand was then placed through a U-shaped piece containing a vacuum pillow. This arrangement was connected to the shaft of the servomotor, with which the flexion-extension axis of the wrist was aligned. Thus, rotation of the shaft produced equivalent rotation of the wrist and vice versa. Angular position, rotational velocity, and torque were measured throughout the trials with a position encoder (HA625-2500, DynaTECH, Elm Grove Village, IL), tachometer (PMI Motion Technologies, Radford, VA), and torque transducer (TRT-200, Transducer Techniques, Temecula, CA).
Activity of the wrist flexors and extensors was monitored with two surface electromyography (EMG) electrodes (DelSys Inc., Boston, MA). The active electrodes, containing two parallel metal bars spaced one centimeter apart, were placed on the forearm over the muscle bellies of flexor carpi radialis and extensor carpi radialis longus (and brevis), respectively. The voltage signal from each electrode was amplified by either 1000 or 10,000 times prior to sampling. For each experiment, the EMG signals, along with joint torque, angular position, and angular velocity, were sampled at 500 Hz following low-pass filtering at 250 Hz.
We first determined passive limits of wrist flexion and extension by manually rotating the wrist. The middle 75% of this passive range was used for all subsequent testing for each session for a given subject.
Spasticity was examined through constant-velocity rotations of the wrist. The wrist was rotated from the testing flexion limit to the testing extension limit, held in extension for two seconds, and then returned to flexion under computer control of the servomotor. Two rotational speeds were employed: 10 degrees per second, a value sufficiently slow to preclude generation of a stretch reflex, and 300 degrees per second, a speed sufficient to elicit a stretch reflex in individuals with spasticity.22
Voluntary wrist extension movement was examined with the same experimental setup, with the forearm in the same posture. Subjects were asked to extend the wrist to the testing extension limit while the servomotor maintained a zero-torque, no-load state.
The final trials assessed isometric wrist extension and flexion torque. For extension, two wrist angles were employed, one at the testing flexion limit and the other halfway between the testing flexion and extension limits, to enable assessment of a possible interaction between posture and change in torque after the NMES training. Isometric flexion was measured with the wrist at 20 degrees of flexion, a posture conducive to torque production.25 Subjects were instructed to push their hand as hard as possible in the desired direction.
The sampled EMG data was notch-filtered at 60 Hz and then full-wave rectified. An envelope for the EMG data for each trial was found by low-pass filtering the rectified signals at 10 Hz using a digital, finite impulse response (FIR) filter. The EMG envelopes for a given testing session were normalized using the largest value recorded during the session. The joint torque, velocity, and angle data were also low-pass filtered at 10 Hz with an FIR filter.
Spasticity was quantified using the torque and angle data, through the following algorithm.22 Torque was integrated with respect to time during the stretch and hold phases of the movement. This value was divided by the elapsed time to create an average torque. As the average torque recorded during the slower rotations (10 degrees per second) was assumed to represent the passive resistance to stretch, this value was subtracted from the value obtained during the faster rotations (300 degrees per second) to obtain the average reflex torque.
Passive resistance to stretch was estimated from the periods during the slower rotations when the hand was at rest, either at the flexion limit prior to initiation of the trial or at the extension limit just prior to the initiation of the return of the wrist from extension back to flexion. Torque values were averaged across a 200-ms window to obtain a mean response. The standard deviation was also computed to ensure that the torque values were fairly constant across the window (standard deviation <0.03 N-m).
Peak active wrist extension movement was determined for the trials performed without a load. The starting angle was subtracted from the peak angle to yield the net wrist extension range of motion.
Peak isometric torque in either the extension or flexion direction was determined for each isometric trial. The initial, resting torque was subtracted from the peak recorded torque to obtain the maximal voluntary torque. The change in voluntary torque in post-treatment trials versus the pre-treatment baseline was expressed as a percentage of the pre-treatment values.
The normalized EMG envelopes were examined to quantify the degree of coactivation. During isometric extension, we computed average values for the EMG envelopes recorded during a 200-ms window centered on the peak torque value. The resulting ratio of average flexor EMG to average extensor EMG during the windowed period was used as a measure of coactivation. A value of zero signifies no coactivation, while a value of one signifies that flexors are activated to the same extent as extensors.
The two testing sessions prior to initiation of treatment were usually held within one or two weeks of each other, as were the two sessions at the end of testing. Due to their proximity in time and the fact that treatment status was not altered between the two sessions in each pair, it was assumed that variability between these sessions was not related to the NMES protocol. Thus, data from testing sessions one and two were averaged, as were data from sessions four and five, to create single pre- and posttreatment values for each measurement for each subject. Subsequent post hoc analysis confirmed the lack of significant difference in testing session between the data sets that were combined.
Peak wrist extension range of motion against gravity, spasticity, passive torque, isometric torque generation, coactivation, and active wrist extension range of motion were compared at baseline prior to treatment, after six weeks of treatment, and post-treatment using repeated-measures analyses of variance. In cases where the treatment time proved significant, post hoc analysis was performed using Tukey tests. For the isometric extension torque and passive torque variables, a second factor, wrist posture with two levels, was included in the analysis. To obtain an overall significance level of α = 0.05, the significance level for each statistical test was set at 0.01, in accordance with the Bonferroni correction.
Eight of the nine subjects completed three months of the NMES program. One subject was forced to quit the program after two months due to unrelated medical problems. The daily logs of stimulation sessions kept by the subjects and their families suggested that compliance with the protocol was excellent for the eight subjects who completed the program (>90% of all assigned stimulation sessions were performed).
Voluntary Wrist Extension
The program of NMES was effective in increasing voluntary wrist extension range of motion against gravity by an average of 34 ± 20 degrees (p = 0.002) (Fig. 1). Seven of the eight subjects exhibited significant gains (>15 degrees), with an average increase of 38 ± 17 degrees. Each of these seven subjects could voluntarily extend the wrist beyond neutral after three months of the NMES protocol.
The pattern of improvement was highly variable, with some subjects achieving the bulk of the increase in wrist extension range of motion at six weeks, while others had no improvement until after the six-week mark (Fig. 2). Across subjects (excluding subject 7), mean increase in wrist extension range of motion was 14 ± 22 degrees at six weeks, as opposed to the 38 degrees at three months, and this change did not reach statistical significance (p = 0.15).
The increase in wrist extension range of motion was largely mirrored by that seen during the no-load wrist extension movement in the testing device. The improvement for the unloaded condition, however, was not significant (6.6 ± 13.5 degrees, p = 0.181), due in large measure to a ceiling effect on performance that was imposed by the extension limit. With no load, several subjects were able to either attain or approach this extension limit even before initiation of the NMES treatment.
No significant trend in change in spasticity was seen either at six weeks or post-treatment for the group as a whole (increase of 0.02 ± 0.08 N-m at 6 weeks and an increase of 0.03 ± 0.14 N-m post-treatment, p = 0.66) or for the seven subjects demonstrating improvement (increase of 0.01 ± 0.09 N-m at six weeks and an increase of 0.01 ± 0.14 N-m post-treatment, p = 0.89). Some subjects did exhibit a slight increase while others had a slight decrease or no discernible change. The subject who exhibited little improvement in wrist extension range of motion had by far the largest spasticity measure (greater than twice the magnitude of all others). The stretch reflex response for this subject remained active during the hold phase of the stretch, even though stretch velocity was zero (Fig. 3). The spasticity measure did not decrease for this subject during the period of the NMES program.
No significant changes at either six weeks or post-treatment were detected in passive resistance to imposed wrist rotation (p = 0.40). Across subjects, at the flexion limit, a mean increase in extension torque of 0.02 ± 0.08 N-m (p = 0.54) was observed following the NMES protocol (0.02 ± 0.08 N-m for the seven subjects exhibiting improvement) and at the extension limit, a mean decrease of flexion torque of 0.02 ± 0.11 N-m (p = 0.65) was detected after treatment (0.03 ± 0.11 N-m for the subjects with improvement in wrist extension range of motion). The subject exhibiting no improvement in wrist extension had the largest passive torques.
The seven subjects showing improved wrist extension against gravity did demonstrate a significant increase in extensor strength across wrist postures (p = 0.003) (Fig. 4). The percentage of increase in wrist extensor strength was 113 ± 128%. There was no significant difference in the percentage of increase between the flexed and mid-range postures (p = 0.46). At six weeks, the increase in wrist extensor strength was 44 ± 102%, but this difference was not statistically significant (p = 0.13). Conversely, wrist flexion torque showed no significant change at either six weeks (p = 0.70) or post-treatment (p = 0.32).
There was a trend toward a reduction in coactivation for six of the seven subjects who exhibited improved voluntary wrist extension range of motion. The ratio of flexor EMG to extensor EMG dropped from 0.62 to 0.36 (40%) for these six subjects after the NMES treatment period, although the change in coactivation only approached statistical significance (p = 0.07). Normalized flexor EMG activity during isometric extension, however, did decrease significantly (p = 0.006) post-treatment for these six subjects, although there was no change at six weeks (p = 0.67). The normalized magnitude of extensor EMG was slightly reduced after treatment as well (by 15%), although this reduction was not statistically significant (p = 0.11). It should be noted, however, that one of the subjects (subject 3) demonstrating improved wrist extension showed the opposite trend, namely, increased flexor activity during extension post-treatment (Fig. 5).
In addition to alterations in EMG magnitude, alterations in EMG patterns toward those typically recorded in neurologically intact individuals were occasionally observed. For example, fusion of extensor activity and reduction of alternating bursts of flexor and extensor EMG could be seen, and these alterations coincided with improved performance (Fig. 6).
In accordance with other studies,16,17 the majority (seven of eight) of subjects did demonstrate improvement in active wrist extension range of motion following the NMES program. The rate of improvement in wrist extension varied greatly among the subjects. Some demonstrated little change in wrist extension range of motion at six weeks, but considerable increase at three months, while for others, wrist extension range of motion largely reached a plateau after six weeks. The rate of improvement appears to coincide with the level of impairment, as those subjects with the greatest initial wrist extension showed the best improvement at six weeks.
Increases in active wrist extension occurred despite a lack of correspondence between alterations in spasticity and voluntary wrist extension range of motion, in contrast to what has been reported for adult hemiparetic subjects.19 In fact, the NMES treatment had no significant effect on spasticity in general. Thus, it is possible for improvements in motor control to occur without reduction in spasticity. It is true, however, that the subject with the greatest degree of flexor spasticity was the same individual who failed to demonstrate significant improvement in wrist extension range of motion. Intersubject comparison of spasticity is admittedly difficult because our spasticity measure is dependent on muscle size as well as activation level. Yet, this subject who did not improve did not have the strongest voluntary flexion, thereby suggesting that the large spastic response derived from hyperexcitability of the motor neurons. Thus, for subjects with high levels of spasticity, it may prove efficacious to treat the wrist flexors, with botulinum toxin A, for example,26 prior to initiation of the NMES program.
Studies have shown that single sessions of cyclic stretching of muscles and ligaments produced by imposed joint rotation can transiently reduce passive joint stiffness in individuals with spasticity.27,28 Thus, it has been suggested that an NMES training paradigm may increase voluntary movement by decreasing passive joint stiffness through repetitive movement of the joint.17 However, we did not detect any changes in passive joint resistance, as characterized by the measured static torques. Again, the subject who did not show extension improvement exhibited the largest passive resistance of all the subjects, although other authors found the greatest improvement in subjects with severe contractures.29 The amount of wrist extension torque required to overcome this passive resistance, however, was less than 0.5 N-m, a value easily obtainable in neurologically intact children of the same age. Rather than being causal, this elevated passive resistance seemed only to be indicative of other limiting factors, as described more fully by Damiano et al.30
An increase in voluntary isometric extensor torque was observed across the subjects who showed improvement. It appears that the greater net extension torque enabled greater wrist extension motion against gravity. Whether the increased net extension torque resulted from muscle tissue or neurological changes remains a question to be answered. Repeated contraction and use of the wrist extensor muscles may have caused the active muscle fibers to hypertrophy, thereby increasing muscle strength. Alternatively, neural adaptations may have led to improvement by reducing flexor coactivation and/or increasing excitation of the wrist extensor muscles. Indeed, another study attributed weakness in children with CP to incomplete activation of the agonist muscle and excessive coactivation of the antagonist.31
Repetitive stimulation of afferent and mixed nerves in the periphery has been shown to transiently increase the excitability of the corresponding sensorimotor cortex.32,33 In nonhuman primate models, repeated sensory input has produced long-term adaptations in sensory cortex.34 Furthermore, sustained voluntary muscle contractions can lead to increased corticomotor excitability of the involved pathways.35 Thus, the NMES therapy, which produces excitation of sensory afferents along with muscle contraction, may promote cortical excitability targeting the motor neurons of interest. The heightened excitability could facilitate recruitment of the desired muscles and thus assist training. While the normalized extensor EMG values measured during isometric extension did not increase following the NMES protocol in this study, it is possible that absolute EMG levels increased. The same percentage of the maximum extensor EMG was recorded during isometric extension, but the maximum itself may have become larger after treatment.
Reduction in coactivation, as measured by normalized flexor EMG during extension, was observed in six of the seven subjects exhibiting increased active wrist extension. The reduction may have resulted from increased reciprocal inhibition, which may be lessened in individuals with neurological injury, such as adults with hemiparesis subsequent to stroke.36–38 In one of these studies, the hemiparetic subjects who were receiving peroneal nerve stimulation as part of gait therapy had normal reciprocal inhibition.37 Hence, stimulation of the peripheral nerves may help to strengthen the interneuronal inhibitory pathways. Another study examining the use of NMES to improve wrist extension in adults following stroke reported a similar reduction in coactivation.39
Generalizability of these results, however, is limited by a number of factors. First, as with many preliminary studies, the subjects served as their own controls. Thus, the observed improvement may not be entirely attributable to the NMES.
It is doubtful, however, that the improvement occurred spontaneously. All subjects were at least five years in age and had received therapy in the past, so the children presented with a fairly stable level of hand function prior to this study. Indeed, another study reported only limited changes in hand function after four years of age in children with hemiplegic CP.40
The children may have benefited strictly from renewed focus on the use of impaired hand. Studies promoting constraint-induced therapy in young children with CP have reported improvement in function.41,42 In hemiparetic adults, the constraint-induced protocol has even been associated with changes in cortical representations of a hand muscle.43,44 While our treatment sessions lasted only 15–30 minutes per day, this training might have prompted greater use of the affected limb outside of treatment. Even the intensive training of a constraint-induced protocol, however, may not be effective when the initial impairment is severe,45,46 as was the case for some of the subjects of this study who did show improvement.
Finally, it is impossible to separate the impact of electrical stimulation from that of actual wrist flexion or extension for this study. While electrical stimulation repetitively excites specific peripheral nerves and sensory organs, movement of the wrist in the intended direction may also generate afferent feedback, which reinforces the activity. A controlled trial comparing the effects of electrical stimulation and mechanical assistance of wrist extension would be beneficial.
This study did not investigate whether the observed improvement in wrist extension improved hand function. Previous studies, however, have suggested that it may, possibly by enabling the use of a better biomechanical position for grasping.13,15,17 Anecdotal evidence of improved wrist control was volunteered by some parents and therapists.
In conclusion, the results of this study do suggest that the prescribed NMES protocol holds promise in improving wrist extension range of motion. This improvement was not associated with a decrease in spasticity or in passive joint stiffness, but rather with an increase in isometric wrist extension torque, most likely arising from reduced coactivation of flexor antagonists. Thus, a large-scale, randomized trial with multiple treatment groups seems warranted.
The authors thank Dr. Maria Deloria Knoll for her advice regarding statistical procedures and Ms. Heidi Waldinger for her input during preparation of the manuscript. The electrical stimulators used in this study were donated by Bio-Medical Research Ltd. (Donegal, Ireland).
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