Efficacy Of Constraint-induced Movement Therapy And Electrical Stimulation On Upper Limbs Function Of Children With Hemiplegic Cerebral Palsy:a Controlled Trial

IntroductionThe prevalence of cerebral palsy is about2-4%o in China. It is the most common cause of severe physical disabilities in childhood, in which hemiplegia is accounted for36%of children with cerebral palsy. Children with hemiplegic cerebral palsy usually have the independent walking ability and intellectual capacity to attend regular school. However, impaired hand function restricts their activity and participation in lifestyle, educational, leisure, and later vocational roles.Typically, the upper limb in children with hemiplegic cerebral palsy is more involved than the lower, with impairments of spasticity, sensation, and reduced strength. Muscle weakness and alterations in passive stiffness are often present, resulting in important imbalances. Such imbalances can contribute to movement slowness and inefficiency and limit active movement, inhibiting the use of the involved arm in daily life activities and restraining acquisition and development of motor functions. As a result of often failing to use the involved hand and learning to perform most tasks exclusively with their noninvolved hand (ie, developmental disregard), children who suffered from hemiplegic cerebral palsy have major hand dysfunction problems. Disregard may lead to further impairment in the developmentof neuronal circuitry.Several treatment approaches have been used to improve hand function in hemiplegic cerebral palsy.±These interventions include occupational therapy, neurodevelopmental therapy, strength training, conductive education, motor learning, constraint-induced movement therapy, hand-arm bimanual intensive training, casting, electrical stimulation, botulinum toxin A, and surgery. All of the recent studies reported positive results of constraint therapy, although the studies also showed it was not beneficial to improve muscle strength, tone and sensation. The main principle of constraint therapy includes restraint of the noninvolved hand and intensive practice with the involved hand during a specified time period. Thus, constraint therapy has recently regained attention and seemed promising as a potential intervention for children with hemiplegic cerebral palsy. However, the variability in the type of restraint, the restraint duration, the length of the intervention, the intensity of practice, and evaluation measures further weakens the evidence and makes it difficult to draw conclusions about efficacy and dosage. Further, another systematic review and meta-analysis conducted by Sakzewski et al found that no one treatment approach seemed to be superior. Overall, the use of constraint in pediatrics appears promising yet the evidence is still weak.Interestingly,’based on the studies and our clinical practice, electrical stimulation with the involved limb can result in improved muscle strength and tone in a relatively short time period. Electrical stimulation is often used in conjunction with other types of treatments in clinical practice. Kamper et al also reported that electrical stimulation affected wrist extension by improving the strength of the wrist extensor muscles, possibly through decreased flexor co-activation on upper limb impairment in eight children with cerebral palsy. This observation suggests that the involved upper limb is amenable to treatment and that constraint therapy plus electrical stimulation may be more beneficial to improve function. However, no clinical randomized control trials on constraint therapy plus electrical stimulation to treat upper limb dysfunction in children with hemiplegic cerebral palsy have been reported in the literature. Occupational therapy is apparent frequently used for treatment of children with hemiplegic cerebral palsy in clinical practice. However, strong evidence for efficacy of occupational therapy is still lacking. Meanwhile, in order to evaluate and understand the efficacy of these techniques, the outcome measurements include not only body structure and function (e.g. strength, muscle tone and range of movement), but also activity and participation (e.g. upper extremity function, bimanual hand performance, social life ability, and quality of life), and objective tools (e.g. surface electromyography, functional magnetic resonance imaging and bone mineral density test), and in relation to individual client and family goals should be included.Therefore, the objective of this study were to compare the efficacy of constraint therapy, constraint therapy plus electrical stimulation, and occupational therapy at three dimensions (involved hand structure and function, bimanual hand performance, social life ability and perceived changes by family), and to learn about the mechanism of action and the characteristic changes of muscle recruitment and coordination measured by surface electomyography, as a means to treat the impaired hand in Chinese children with hemiplegic cerebral palsy.MethodsStudy designThis study was a randomized, single-blind, controlled trial. After signing the consent form by their parents, all children with hemiplegic cerebral palsy were randomly divided into three groups:constraint therapy, constraint therapy plus electrical stimulation, and occupational therapy group. To minimize uneven distribution of known variables, subjects were allocated in an unbiased manner by a random number produced by computerized method of minimization. The stratification included the age (≤4years,>4years) and globe rating scale scores (≤5,>5).ParticipantsChildren aged2to14years with hemiplegic cerebral palsy were eligible for the study. The inclusion criteria were:(1) the ability to extend the wrist≥20°and the metacarpophalangeal joint10°from full flexion,(2) a20%-80%difference between the involved and noninvolved hand on the globe rating scale scores,(3) informed consent form could be got from parents and to comply with study instructions. The exclusion criteria were:(1) any health problems that are not associated with cerebral palsy,(2) contractures that limit functional arm and hand use,(3) uncontrolled seizures,(4) received botulinum toxin injection in the upper limb during the last6months or who wish to receive it within the period of study,(5) orthopedic surgery on their involved upper limb,(6) visual and balance problems that would prevent themfrom carrying out the intervention or assessment,(7) prior exposure to constraint therapy,(8) received interventions such as baclofen, dantrium and artane, etc.From January2009to December2010,75of164children with hemiplegic cerebral palsy from the Department of Neurology and Rehabilitation, Guangzhou Children’s Hospital, were recruited into this study. Seven children did not finish this study due to their inability to continue with the assessment protocol. The final cohort comprised68children (25boys,43girls). At the baseline assessment, the age of these children ranged from24months to149months (55months±33).Outcome measurementsDemographic characteristics and functional performance were obtained at the baseline visit, including age, gender, the difference between the involved and noninvolved hand on the globe rating scale scores, and the Gross Motor Function Classification System level.Outcome measurements included the active range of movement of the wrist extension measured by a goniometer while children maintained the wrist full flexion as the zero position, modified Ashworth scale, hand-grip strength measured with sphygmomanometry, nine-hole peg test, upper extremity functional test, grasping and visual-motor integration subtests of the Peabody motor developmental scales, globe rating scale, social life ability scale for Chinese infant-junior school student, and surface electromyography. They were assessed before treatment and two weeks, three months and six months after treatment. Outcome measurements were assessed by three independent evaluators who were not aware of the treatment group of each patient. Adverse events associated with constraint-induced movement therapy and electrical stimulation were also assessed at intervention and each follow-up session. Constraint-induced movement therapyAfter baseline assessments, participants underwent two weeks of modified constraint-induced movement therapy with splint of the noninvolved hand. The splint extended from below the elbow to the fingertips. The children can use the hand for support or forbreaking a fall. The intervention lasted for3hours one session,5days a week for2weeks at Guangzhou Children’s Hospital, with groups of2to4children. Time out of the splint during the3-hour period was allowed only for designated activities (eg, toileting) and could not exceed30minutes per day. At the end of each day, each child went home with an exercise program to practice with the involved hand (with the restraint) for1hour. This home exercise program was extended to2hours per day for6months after the intervention, and parents completed activity logs to monitor compliance.Electrical stimulationElectrical stimulation was applied for20minutes5times a week for2weeks on extensor carpi radialis and extensor digitorum of the affected upper limb. The active electrode was placed on the motor point and the inactive electrode was placed distally over the same muscle group. Frequencies were set at50Hz, Pulse rate30pulses per second with300μs of amplitude, and the amplitude to a maximum of100mA. ON time was set to12seconds with1second of rise and decay and an OFF time of12seconds.Occupational therapyThe occupational therapy program lasted for3hours one session,5days a week for2weeks. Meanwhile, therapists taught participants and caregivers the program, and then it was carried by the family after2weeks of intervention. At the end of each day, each child went home with an exercise program to practice for1hour. This home exercise program was extended to2hours per day for6months after the intervention, and parents completed activity logs to monitor compliance.Statistical AnalysisAnalysis was performed using the Statistical Package of Social Science version16.0(SPSS Inc., Chicago, IL, USA). The Kruskal-Wallis test was used to compare the differences of age, gender, affected sides (right or left), Gross Motor Function Classification System level, and globe rating scale scores among the three groups. The One-Way AVONA was used to compare the differences of baseline data. Repeated measure analysis of variances was applied to compare the differences of outcome measurements before treatment, at two weeks, three and six months after treatment within each group. Analysis of covariance was used to compare the differences of clinical assessment outcome at two weeks, three and six months after treatment among the three groups (covariate was the baseline data). The correlation of surface electromyography data and hand function was performed with Pearson analyses. Significance was set at the5%level.ResultsDemographic and baseline dataThere were no significant differences in age, gender, affected sides (right or left), and Gross Motor Function Classification System level among the three groups obtained with Kruskal-Wallis test (P>0.05). There were also no significant differences in globe rating scale scores, active range of movement, modified Ashworth scale scores, hand-grip strength, nine-hole peg test scores, upper extremity functional test scores, grasping and visual-motor integration subtests scores of the Peabody motor developmental scales, social life ability scale scores among the three groups obtained with One-Way AVONA (P>0.05).There are significant differences (P<0.05) in integrated EMG of the involved wrist flexor and extensor whereas there are no significant differences (P>0.05) in other surface EMG data, such as root mean square, co-contraction ratio, etc. when grasping maximally at baseline among the three groups obtained with One-Way AVONA.Improvement of involved hand functionAfter two weeks of treatment, all children showed significant increases in the involved hand function (active range of movement, nine-hole peg test, upper extremity functional test scores, P<0.05), the improvement lasted for six months obtained with repeated measure analysis of variances. Although the occupational therapy group improved in grip strength of involved hand from baseline to three and six months obtained with repeated measure analysis of variances (P<0.05), the two constraint groups improved it from baseline to two weeks, three and six months of treatment (P<0.05). The constraint-induced movement therapy plus electrical stimulation group and the occupational therapy group showed significant decreases in wrist tone (modified Ashworth scale scores) from baseline to each follow-up session, as well as decreasing in wrist tone of constraint-induced movement therapy group from baseline to three and six months, obtained with repeated measure analysis of variances (P<0.05).There were no significant differences in active range of movement at each follow-up session among the three groups obtained with analysis of covariance (P>0.05). The constraint-induced movement therapy plus electrical stimulation group showed greater rate of reduction in modified Ashworth scale scores at two weeks of treatment than constraint therapy group, as well as improving in grip strength of involved hand at three and six months of treatment than occupational therapy group, obtained with analysis of covariance (P<0.05). When compared with occupational therapy group, the constraint-induced movement therapy plus electrical stimulation group showed greater rate of improvement in upper extremity functional test and nine-peg hole test scores at each follow-up session obtained with analysis of covariance (P<0.05). The constraint-induced movement therapy group also showed greater rate of improvement in upper extremity functional test and nine-peg hole test scores at each follow-up session obtained with analysis of covariance (P<0.05). in nine-hole peg test at three and six months of treatment than occupational therapy group obtained with analysis of covariance (P<0.05).Changes in Bimanual Hand PerformanceChildren in the three groups improved in bimanual grasping performance (grasping subtests scores of Peabody developmental motor scales) from baseline to each follow-up session obtained with repeated measure analysis of variances (P<0.05). Children in the two constraint therapy groups improved in visual-motor integration ability (visual-motor integration subtests scores of Peabody developmental motor scales) from baseline to each follow-up session, as well as after three and six months of the treatment for the occupational group, obtained with repeated measure analysis of variances (P<0.05).There were no significant differences in bimanual grasping performance (grasping subtests scores of Peabody developmental motor scales) at each follow-up session among the three groups obtained with analysis of covariance (P>0.05). However, the constraint-induced movement therapy plus electrical stimulation group showed greater rate of improvement in visual-motor integration subtest scores than the occupational therapy group at three and six months of treatment (P<0.05).Perceived Changes by CaregiversWhen compared with the results before the treatment, the perceived changes by caregivers (globe rating scale scores) improved significantly after two weeks, three and six months of the treatment for the two constraint therapy groups, as well as after three and six months of the treatment for the occupational group, obtained with repeated measure analysis of variances (P<0.05). The two constraint therapy groups showed significant increases in social life ability scores at three and six months obtained with repeated measure analysis of variances (P<0.05), but the occupational group showed better only at six months (P<0.05).There were no significant differences in social life ability scores at each follow-up session among the three groups obtained with analysis of covariance (P>0.05). However, the two constraint therapy groups showed greater rate of improvement in globe rating scale scores than occupational therapy group at two weeks, three and six months obtained with analysis of covariance (P<0.05).Changes of Surface Electromyography DataWhen compared with the results before the treatment in grasping maximally used by the involved hand, the root mean square of both hands, integrated electromyography and co-contraction ratio of the involved hand changed significantly after two weeks, three and six months of the treatment for all the children, as well as reducting in integrated electromyography of the noninvolved hand after six months of the treatment, obtained with repeated measure analysis of variances (P<0.05). There were no significant differences in root mean square and integrated electromyography of the two wrists’flexors and the noninvolved wrist extensors at each follow-up session among the three groups, when grasping maximally used by the involved hand, obtained with analysis of covariance (P>0.05). However, the constraint-induced movement therapy plus electrical stimulation group showed greater rate of improvement in integrated electromyography of the involved wrist extensors, and co-contraction ratio than occupational therapy group and constraint-induced movement therapy group at three and six months, as well as improving in root mean square of the involved wrist extensors than occupational therapy group, obtained with analysis of covariance (P<0.05).When grasping maximally used by the noninvolved hand, all the children changed significantly in the root mean square of both involved hand and wrist extensors of noninvolved hand from baseline to each follow-up session, as well as reducting in integrated electromyography of wrist extensors of the involved hand after six months of treatment for constraint-induced movement therapy plus electrical stimulation group, obtained with repeated measure analysis of variances (P<0.05). When compared with the results before the treatment in grasping maximally used by the noninvolved hand, there were no significant changes in integrated electromyography of both involved wrist flexors and noninvolved hand, and co-contraction ratio after two weeks, three and six months of the treatment for all the children obtained with repeated measure analysis of variances (P>0.05).There were no significant differences in co-contraction ratio, root mean square, and integrated electromyography at each follow-up session among the three groups, when grasping maximally used by the noninvolved hand, obtained with analysis of covariance (P>0.05).Correlation between Surface Electromyography Data and Hand FunctionWhen grasping maximally used by the involved hand, the improvement of upper extremity functional test socres was positively correlated with the increase of integrated electromyography in the involved wirst after six months of treatment for all the children, as well as correlating between the improvement of grip strength and the increase of integrated electromyography of the involved wrist extensors, obtained with Pearson analysis (P<0.05)Conclusions1、Constraint therapy plus electrical stimulation, or constraint therapy, or occupational therapy, improves involved hand function, bimanual hand performance, social life ability, perceived changes by family in children with hemiplegic cerebral palsy, as well as strengthening recruitment and coordination of involved hand, and isolated movement control ability of bimanual hand when grasping maximally used by the affected hand. The globe function improvement of involved arm and hand was improved by the increase of wrist strength.2、 Constraint therapy plus electrical stimulation is the most effective in improving hand performace, visual-motor integration, and motor unit recruitment and synchronization. Use of constraint therapy is advantageous in improving involved hand function and perceived changes.3、 Electrical stimulation may lead to better response to constraint-induced movment therapy. The mechanism may be proposed by the overload principle, resulting in greater muscle strength by increasing motor unit recruitment and synchronization, selective recruitment of type Ⅱ fibres (fast twitch, large diameter fibres), and wrist coordination, causing improved synaptic efficiency of the muscle.