Neurorehabilitation and Neural Repair

http://nnr.sagepub.com/ Combining Afferent Stimulation and Mirror Therapy for Rehabilitating Motor Function, Motor Control, Ambulation, and Daily Functions After Stroke
Keh-chung Lin, Pai-chuan Huang, Yu-ting Chen, Ching-yi Wu and Wen-ling Huang Neurorehabil Neural Repair 2014 28: 153 originally published online 8 November 2013 DOI: 10.1177/1545968313508468 The online version of this article can be found at: http://nnr.sagepub.com/content/28/2/153

Published by:
http://www.sagepublications.com

On behalf of:

American Society of Neurorehabilitation

Additional services and information for Neurorehabilitation and Neural Repair can be found at: Email Alerts: http://nnr.sagepub.com/cgi/alerts Subscriptions: http://nnr.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav

>> Version of Record - Jan 10, 2014 OnlineFirst Version of Record - Nov 8, 2013 What is This?

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

research-article2013

508468

NNRXXX10.1177/1545968313508468Neurorehabilitation and Neural RepairLin et al

Clinical Reasearch Article

Combining Afferent Stimulation and Mirror Therapy for Rehabilitating Motor Function, Motor Control, Ambulation, and Daily Functions After Stroke
Keh-chung Lin, ScD1,2, Pai-chuan Huang, ScD3, Yu-ting Chen, MS3, Ching-yi Wu, ScD3, and Wen-ling Huang, MS4

Neurorehabilitation and Neural Repair 2014, Vol. 28(2) 153 162 The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1545968313508468 nnr.sagepub.com

Abstract Background. Mirror therapy (MT) and mesh glove (MG) afferent stimulation may be effective in reducing motor impairment after stroke. A hybrid intervention of MT combined with MG (MT + MG) may broaden aspects of treatment benefits. Objective. To demonstrate the comparative effects of MG + MT, MT, and a control treatment (CT) on the outcomes of motor impairments, manual dexterity, ambulation function, motor control, and daily function. Methods. Forty-three chronic stroke patients with mild to moderate upper extremity impairment were randomly assigned to receive MT + MG, MT, or CT for 1.5 hours/day, 5 days/week for 4 weeks. Outcome measures were the Fugl-Meyer Assessment (FMA) and muscle tone measured by Myoton-3 for motor impairment and the Box and Block Test (BBT) and 10-Meter Walk Test (10 MWT) for motor function. Secondary outcomes included kinematic parameters for motor control and the Motor Activity Log and ABILHAND Questionnaire for daily function. Results. FMA total scores were significantly higher and synergistic shoulder abduction during reach was less in the MT + MG and MT groups compared with the CT group. Performance on the BBT and the 10 MWT (velocity and stride length in self-paced task and velocity in as-quickly-as-possible task) were improved after MT + MG compared with MT. Conclusions. MT + MG improved manual dexterity and ambulation. MT + MG and MT reduced motor impairment and synergistic shoulder abduction more than CT. Future studies may integrate functional task practice into treatments to enhance functional outcomes in patients with various levels of motor severity. The long-term effects of MG + MT remain to be evaluated. Keywords stroke rehabilitation, mirror therapy, electrical stimulation, kinematics, activities of daily living

Introduction
Stroke has become the most frequent cause of adult-onset disability and costs a tremendous amount of related care expense.1 About 65% of people after stroke experience difficulty in incorporating the affected hand into activities.1 Several novel and theory-based rehabilitation interventions have been developed to improve motor recovery of the upper extremity (UE).2 Among novel interventions, mirror therapy (MT) was beneficial and comparatively low cost.2 Substantial evidence showed that MT reduced UE motor impairment, as measured by the Fugl-Meyer Assessment (FMA). Reduced impairments might result from recruiting the premotor cortex or balancing neural activation within the primary motor cortex toward the affected hemisphere.2-4 The benefits in certain aspects of outcomes are inconclusive, however; for instance, Cacchio et al5 found MT improved hand function, but others2 reported no significant effect. Results of research on the effects of MT on

spasticity, ambulation function, and daily function have been inconsistent.5-10 Another compelling approach is afferent sensory stimulation applied to the UE, which was beneficial for motor recovery, as demonstrated by the FMA.11 One type of afferent stimulation is provided by the mesh glove (MG; PrizmMedical Inc, Oakwood, GA). The MG uses a 2-channel electrical stimulator to provide synchronous or reciprocal sensory stimulation with variant amplitudes and can
1 2

National Taiwan University, Taipei, Taiwan National Taiwan University Hospital, Taipei, Taiwan 3 Chang Gung University, Taoyuan, Taiwan 4 Chang Gung Medical Foundation, Taoyuan, Taiwan Corresponding Author: Ching-yi Wu, Department of Occupational Therapy and Graduate Institute of Behavioral Sciences, College of Medicine, Chang Gung University, 259 Wenhua 1st Rd, Taoyuan 333, Taiwan. Email: cywu@mail.cgu.edu.tw

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

154

Neurorehabilitation and Neural Repair 28(2) and joint motion/synergy patterns has occurred21,25,26 and infer possible reorganization of the brain after treatment.27,28 No previous research, to our knowledge, has addressed change in the motor control mechanism after MT. The present study combined MG stimulation with MT (MT + MG) and compared the efficacy of MT + MG, MT, and a control therapy (CT) on motor impairment, as measured by the FMA and Myoton-3, and on motor function, as measured by the Box and Block Test (BBT) and 10-Meter Walk Test (10-MWT). Also investigated were strategies of motor control indicated by kinematic parameters and function in daily life situations measured by the Motor Activity Log (MAL) and ABILHAND questionnaire. Possible adverse effects, including pain and fatigue, were monitored.

Enrollment

Potentially eligible participants (n = 168) Excluded (n = 83) Not meeting inclusion criteria (n = 42) Randomized (n = 43)

Allocation

MG+MT (n = 14) Analyzed (n = 14)

MT (n = 14) Analyzed (n = 14)

CT (n = 15) Analyzed (n = 14)

Figure 1. Flow diagram shows enrollment of patients and completion of study according to the CONSORT statement.
Abbreviations: CT, control therapy; MG, mesh glove; MT, mirror therapy.

Analysis

Methods Participants
The study recruited 43 patients (11 women) with stroke from 4 medical centers who had met the following criteria: (a) onset of an ischemic or hemorrhagic stroke of at least 6 months duration; (b) the ability to reach Brunnstrom stage III or above in the proximal and distal part of the arm; (c) no severe spasticity in any joints of the affected arm (Modified Ashworth Scale 2)29; (d) no serious cognitive deficits (Mini-Mental State Examination score > 24)30; (e) no serious vision or visual perception deficits (score of 0 on the best gaze and visual subtest of the National Institutes of Health Stroke Scale)31; (f) no history of other neurologic, neuromuscular, or orthopedic disease; and (g) no participation in other studies concurrent with this study. Participants signed informed consent forms approved by the institutional review boards of the participating facilities.

provide stimulation of the entire hand. The MG can be used to reduce muscle hypertonia and facilitate residual movement, which may ameliorate motor impairment and increase volitional activity of the hand and arm in stroke patients.12,13 A study by Zehr et al14 also suggests that stimulation of the superficial radial nerve at the wrist may increase dorsiflexion bilaterally in the stance-swing transition of ambulation. Providing MG stimulation might also result in plastic changes in the primary motor cortex15 and induce a longlasting effect on motor cortical excitability.16-18 Combining 2 treatment protocols has been advocated as a way to improve treatment efficacy.19-21 MG stimulation could be used to supplement other treatment,22 such as MT, to normalize muscle tone and enhance hand or ambulation function. Besides, the possible mechanism of brain plasticity underlying MG is similar to the mechanism behind MT, in that the primary motor cortex might be activated. Adding MG to MT might further augment cortical reorganization.19,20 MG stimulation added to MT improved manual dexterity and ability to transfer skill during daily activities.23 However, this pilot study did not recruit a control group and therefore could not estimate a possible gained value, if any, in providing this new approach. The present study included a larger sample of stroke patients, a control group that received task-oriented therapy, and further explored the possible benefits of MT coupled with MG. This study used the Myoton-3 myometer to objectively assess the treatment effects on muscle tone in the UE instead of a subjective measure such as the Modified Ashworth Scale (MAS).24 This study also included kinematic analyses to obtain objective information on spatial and temporal characteristics (eg, movement time, displacement, and joint recruitment) of UE movements. Kinematic analysis helps us understand whether a true change in the end point control

Design
The study was a single-blind, randomized, pretest and posttest control group design (Figure 1). Participants were stratified into 4 strata according to the side of lesion and the level of motor impairment (the cutoff point was 40 in total scores of the FMA UE subtest32). A set of numbered envelopes containing cards indicating the allocated group was prepared for each stratum. When a new eligible participant was registered, an envelope was randomly extracted, and the relevant therapist was informed of the group allocation. Four certified occupational therapists were trained in the administration of these 3 protocols by 2 primary investigators to conduct consistent intervention. Outcome measurements were administered at baseline and immediately after the intervention by 2 trained occupational therapists. The evaluators were unaware of group allocation, and the participants were blinded to the study hypotheses.

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

Lin et al

155 unaffected hand. Then, the MG was applied on the affected hand. The MG protocol depended on the muscle tone of the participants. Participants with a MAS score of 2 points in any joint of the affected hand received 2-step electrical stimulation. The first step was 80% of the conscious sensory threshold that was a subthreshold, and the second step was at the conscious sensory threshold. Each step lasted about 30 minutes. Participants with a MAS score lower than 2 points received 3-step electrical stimulation. The first 2 steps were the same as that mentioned above, and step 3 was stimulation above the threshold, defined by 120% of the conscious sensory threshold. Each step took 20 minutes.16 The subthreshold stimulation could decrease spasticity, and stimulation at the threshold or higher could improve awareness of the hand and enhance volitional activity.16,18,33 CT Group. The CT group received 1.5 hours of therapeutic activities equivalent in duration and intensity to the MT + MG and MT groups, based on task-oriented treatment principles. Tasks used for practice were selected in accord with the abilities of the participants. In addition to functional task practice, this group also received warm-up similar to the other 2 groups.

Figure 2. The intervention setup of mesh-glove stimulation combined with mirror therapy.

Interventions
All participants received a 1.5-hour training session per day, 5 days/week for 4 weeks. The treatments were provided during the daily occupational therapy sessions. All other routine interdisciplinary stroke rehabilitation was continued as usual. MT Protocol.The MT protocol included 10 minutes of warm-up, 1 hour of mirror box training, and 20 minutes of functional task practice. The warm-up activities included stretching and passive range of motion exercises. During the mirror box training, a mirror box that reflected the image of the unaffected arm was placed in the participants midsagittal plane. Participants were required to symmetrically move both hands as simultaneously as possible while watching the reflection of the unaffected arm in the mirror as if it were the affected one. To ensure that the participants focused on the reflection, the unaffected arm was placed in the mirror box, and vision of the affected arm was occluded by a vertical board placed beside the mirror box. The activities consisted of transitive (eg, gross motor tasks, such as reaching out to put a cup on a shelf, or fine motor tasks, such as picking up marbles) and intransitive movements (eg, gross motor movements, such as pronation and supination, or fine motor movements, such as finger opposition). After the mirror box training, functional task practice was provided according to task-oriented treatment principles. MG Stimulation Combined With MT. The protocols of the MT + MG group were similar to the MT group (ie, 10 minutes of warm-up, 1 hour of mirror box training, and 20 minutes of functional task practice). The MT + MG group also wore the MG during mirror box training (Figure 2). For safety reasons, the conscious sensory threshold, with a feeling of tingling on palmar and dorsal sides, was set on the

Outcome Measures
This study included clinical measures for motor impairment, motor function, daily function, and adverse effects, and kinematic data for motor control. All measures have been reported to be adequately reliable and valid.24,34-38 Primary Outcomes Motor impairment. The UE subscale of FMA total score was used to evaluate several dimensions of motor impairments. The FMA measures the movements and reflexes of the UEs and coordination/speed on a 3-point ordinal scale (0 = cannot perform; 1 = can perform partially; 2 = can perform fully).34 We used myotonometric measurements obtained with the Myoton-3 device (Muomeetria AS, Tallinn, Estonia) to assess the tone of skeletal muscles. The Myotone-3, which is placed perpendicular to the skin surface above the muscle to be tested, produces a short impulse on the muscle. An acceleration transducer records the damped oscillations of the muscle response. The muscle tone values of the biceps, flexor carpi radialis, and flexor carpi ulnaris were recorded.24 Motor function. The BBT was used to assess manual dexterity. A box is separated into 2 equal sides. Subjects used the affected hand to move as many blocks as possible, one at a time, from one side to the other in 60 seconds. The number of blocks is calculated at the end of the test.35

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

156 The 10-MWT was used to assess the mobility function, measuring the time and the numbers of strides required to walk 10 meters under 2 conditions: (a) each participants self-pace (self-pace) and (b) the quickest speed that each participant could walk (as quickly as possible [AQAP]).36 The velocity and stride length of the participant were calculated. Secondary Outcomes Daily function.The MAL is a semistructured interview that assesses subjective report of 30 common daily tasks evaluating the frequency of affected UE use. It consists of subscales assessing the amount of use (AOU) and quality of movement (QOM). The MAL uses a 6-point ordinal scale, with higher scores indicating better performance.37 The ABILHAND questionnaire is a self-report assessment of UE function that consists of 23 bilateral activities in daily life. Patients were asked to estimate their difficulty in performing each activity using a 3-point ordinal scale. The higher the scores, the more difficulty the patients feel.38 The Rasch model was used to estimate a linear ability for each patient and linear difficulty for each item.38 Motor control.The experimental task required participants to press a desk bell with their affected hand as quickly as possible. Participants sat on a height-adjustable, straight-backed chair with the seat height set to 100% of the lower leg length. The tested arm was pronated, and the hand rested on the edge of the table in a neutral position with 90 flexion at the elbow joint. The desk bell was placed in the midline of the table. The bell distance, measuring from the medial border of the axilla to the bell, was standardized to 125% of the participants functional arm length (defined as from the medial border of the axilla to the distal wrist crease39). If the maximum distance the participant could reach was less than 125% of the functional arm length, the bell distance was adjusted to the maximum reachable distance. The instruction to the participants was, When you hear the start signal ring, please use the index finger of the affected hand to reach and press the bell as fast as possible. After a practice trial, 3 trials were performed. A 7-camera motion capture system (VICON MX, Oxford Metrics Inc, Oxford, UK) at a sampling frequency of 120 Hz was used with a personal computer to record kinematic data. Three channels of analog signals were collected simultaneously: one for instruction of movement start and the others for target bells. Markers were placed on the acromion, middle of humerus, lateral epicondyle, styloid process of ulna and radius, and index nail of the affected side. Movement onset was defined as a rise of tangential wrist velocity above 5% of its peak value. Movement offset was defined as a fall of tangential wrist velocity below 5% of its peak value. Movement was digitally low-pass filtered at 5

Neurorehabilitation and Neural Repair 28(2) Hz using a second-order Butterworth filter with forward and backward pass. Kinematic data were processed with an analysis program coded by LabVIEW language (National Instruments, Inc, Austin, TX). Kinematic variables included normalized movement time and normalized movement units to represent end point control, and joint recruitment, including normalized shoulder flexion, normalized elbow extension, and maximum shoulder abduction, to describe movement patterns. Movement time, which refers to the execution time of the reaching movement and is the interval between movement onset and offset, was a variable to represent temporal efficiency.40,41 Movement unit was defined as 1 acceleration and 1 deceleration, which refers to motor smoothness.40,41 Joint recruitment was defined as the difference of shoulder flexion or elbow extension from movement onset and movement offset, and maximum shoulder abduction during each reaching motion. Maximum shoulder abduction and elbow flexion are 2 critical components of the flexor synergy pattern often exhibited by patients with stroke.42,43 Reduced maximum shoulder abduction with enhanced elbow extension indicates a diminished synergy pattern.42 Because bell distance varied, depending on the individuals arm length, and therefore influenced reaching distance (defined as the distance between the initial index marker position at resting and the target desk bell), all variables, except for maximum shoulder abduction, were normalized to reaching distance. Possible adverse effects.Self-reported assessments on pain and fatigue severity were administered immediately after the first and last treatment sessions to evaluate adverse effects. The evaluator presented the question, What did you feel in terms of pain/fatigue severity during the treatment today? The participant responded on an 11-point ordinal scale (0 = no pain/fatigue; 10 = the most severe pain/fatigue).

Data Analysis
Data were analyzed with SPSS 19.0 software (SPSS Inc, Chicago, IL). We calculated that a sample size of 42 was needed for an 80% likelihood in detecting a group difference with a type I error of .05, based on the previous pilot study showing that MT combined with afferent stimulation resulted in improvements with effect sizes of approximately .50.23 Baseline differences among groups were analyzed by analysis of variance for continuous data and by 2 for categorical data. To control the variance among groups in the pretest scores, analysis of covariance was used to compare the treatment effects among groups on different end points at posttest. The pretest performance was the covariate, group was the independent variable, and posttest performance was the dependent variable. No multiple testing

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

Lin et al
Table 1. Characteristics of Study Participants (N = 43). Variable Gender, n Male Female Age (years), X (SD) Side of brain lesion, n Right Left Months after stroke onset, X (SD) Years of education, X (SD) Brunnstroms stage, X (SD) Proximal Distal MMSE, X (SD) MT + MG (n = 14) 11 3 55.79 (14.59) 8 6 22.71 (13.62) 10.54 (5.01) 4.25 (0.64) 4.11 (0.86) 27.62 (2.47) MT (n = 14) 10 4 56.01 (12.53) 6 8 18.50 (11.61) 11.07 (4.75) 4.25 (0.64) 4.00 (0.83) 27.91 (1.76) CT (n = 15) 11 4 53.34 (10.12) 8 7 17.80 (10.56) 11.17 (3.71) 4.17 (0.62) 4.10 (0.83) 28.21 (2.15) Statistica 0.02

157

P Value .90 .82 .74 .50 .93 .85 .94 .77

0.21 0.62

0.70 0.08 0.33 0.12 0.26

Abbreviations: MT + MG, mirror therapy combined with mesh glove; MT, mirror therapy; CT, control treatment; MMSE, Mini-Mental State Examination. a Statistic associated with 2 test or the Fisher exact test for categorical variables, 1-way analysis of variance for continuous variables, and nonparametric test for ordinal variables.

corrections were made to restrain the type II error considering the early stage of intervention development. Post hoc analysis using highly significant differences was used to evaluate the difference of each group. The 2 was calculated for each outcome variable to index the magnitude of group differences. The 2 value represents the variability in the dependent variable (posttest performance) that can be explained by the independent variable (group). A large effect is represented by an 2 of at least 0.14, a moderate effect by an 2 of 0.06, and a small effect by an 2 of 0.01. The level of statistical significance () was set at .05 for all comparisons.44

Results
The study recruited 43 participants (mean age = 55.0 years). The MT + MG and the MT group consisted of 14 participants each, and the CT group consisted of 15 participants. After the treatment programs, the Myoton and kinematic data were missing for 2 participants. There were no significant differences in demographic characteristics among groups (Table 1). Group differences were not significant for pain (F2,39 = 1.65, P = .06) and fatigue (F2,39 = 3.05, P = .21). Primary Outcomes.Table 2 reports the descriptive and inferential results, except the kinematic performance. Total FMA scores were significantly different, with a large effect among the 3 groups (F2,40 = 3.35, P = .045, 2 = .147). Post hoc analyses revealed that the MT + MG and the MT groups were significantly higher than the CT group for the FMA total score (P = .0032 and .0031, respectively). Group differences in the muscle tone were not significant.

Significant and large effects on motor function were measured by the BBT (F2,40 = 4.39, P = .019, 2 = .184) and the 10-MWT (velocity of self-pace: F2,40 = 5.02, P = .011, 2 = .205; stride of self-pace: F2,40 = 7.13, P = .002, 2 = .268; velocity of AQAP: F2,40 = 4.06, P = .025, 2 = .176). No significant difference was found in stride length of the AQAP subscores in the10-MWT. Post hoc analyses revealed that the MT + MG and the CT group improved more than the MT group in the BBT (P = .007 and P = .036, respectively). The MG + MT group showed larger improvements than the MT group on the velocity of selfpaced ambulation (P = .004), the stride of self-paced ambulation (P = .016), and the velocity of AQAP (P = .014). The CT group showed larger improvements than the MT group on the velocity of self-paced ambulation (P = .031), the stride of self-paced ambulation (P = .016), and the velocity of AQAP (P = .023). Secondary Outcomes.For daily function, no significant group effects were found on the ABILHAND or on the AOU and QOM of the MAL. Table 3 reports the descriptive and inferential results for the kinematic performance. The results revealed significant and large effects on normalized shoulder flexion (F2,38 = 3.43, P = .043, 2 = .157) and reduction of maximum shoulder abduction during reach (F2,38 = 4.55, P = .017, 2 = .198) among the 3 groups. Post hoc analyses revealed that the MG + MT (P = .008) and the MT groups (P = .023) showed significantly greater reduction of maximum shoulder abduction than the CT group. The CT group showed larger improvements than the MT group on normalized shoulder flexion (P = .0013). Small and nonsignificant effects were found on normalized movement time, normalized movement unit, and the normalized elbow extension.

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

158
Pretest ( X SD) MT + MG MT CT MT + MG MT CT F Posttest ( X SD) ANCOVA P .15 .21 .045a .13 .88 .20 .02a .01a .002a .03a .46 .46 .55 .81 2 (n = 14) 31.86 (4.77) 13.57 (6.90) 45.43 (9.23) (n = 14) 14.41 (1.86) 15.85 (2.19) 14.15 (2.47) 12.00 (11.11) (n = 14) 0.557 (0.234) 0.377 (0.120) 0.772 (0.293) 0.453 (0.151) (n = 14) 1.00 (1.05) 1.09 (1.18) 29.14 (8.74) (n = 14) 30.50 (4.00) 13.71 (7.37) 44.21 (10.69) (n = 13) 13.39 (2.23) 14.13 (2.38) 13.57 (2.56) 16.43 (14.41) (n = 14) 0.707 (0.317) 0.444 (0.144) 0.916 (0.418) 0.496 (0.163) (n = 14) 1.35 (1.07) 1.31 (1.02) 38.43 (12.91) (n = 15) 31.13 (4.36) 12.67 (7.66) 43.80 (10.68) (n = 14) 13.87 (3.45) 15.41 (2.61) 13.15 (7.13) 15.73 (14.38) (n = 15) 0.580 (0.268) 0.415 (0.118) 0.796 (0.383) 0.522 (0.235) (n = 15) 0.86 (0.97) 0.97 (1.02) 28.00 (14.27) (n = 14) 34.43 (4.91) 16.50 (6.67) 50.93 (9.41) (n = 14) 14.16 (1.67) 15.45 (3.20) 14.34 (2.49) 17.29 (12.38) (n = 14) 0.658 (0.284) 0.430 (0.130) 0.878 (0.355) 0.523 (0.206) (n = 14) 1.23 (0.89) 1.22 (1.02) 33.07 (11.27) (n = 14) 33.57 (3.99) 16.29 (5.62) 49.86 (8.97) (n = 13) 12.90 (1.98) 15.17 (1.59) 13.75 (2.16) 16.93 (16.46) (n = 14) 0.697 (0.314) 0.431 (0.145) 0.914 (0.441) 0.491 (0.178) (n = 14) 1.43 (1.09) 1.61 (1.19) 40.64 (13.25) (n = 15) 32.73 (3.83) 14.40 (7.53) 47.13 (10.12) (n = 14) 12.56 (1.64) 15.20 (2.46) 12.28 (6.15) 19.93 (15.23) (n = 15) 0.649 (0.251) 0.443 (0.098) 0.873 (0.378) 0.522 (0.119) (n = 15) 1.14 (1.25) 1.18 (1.10) 34.13 (14.18) F2,40 2.004 1.614 3.350 F2,38 2.200 0.129 1.68 4.392 F2,40 5.020 7.129 4.061 0.787 F2,40 0.796 0.617 0.215 .09 .08 .15 .11 .007 .083 .18 .21 .27 .18 .04 .04 .03 .01

Table 2. Descriptive and Inferential Statistics for Clinical Outcome Measures.

Variable

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

FMA Proximal Distal Total Myoton Biceps Flexor carpi radialis Flexor carpi ulnaris BBT affected hand 10 MWT Self-paced velocity (m/s) Self-paced stride length (m) AQAP velocity (m/s) AQAP stride length (m) MAL AOU QOM ABILHAND total score

Abbreviations: ANCOVA, analysis of covariance; MT + MG, mirror therapy combined with mesh glove; MT, mirror therapy; CT, control treatment; FMA, Fugl-Meyer Assessment; BBT, Box and Block Test; 10 MWT, 10-Meter Walk Test; AQAP, as quickly as possible; MAL, Motor Activity Log; AOU, amount of use; QOM, quality of movement. a P < .05.

Lin et al

159 could alter leg movement via propriospinal neural pathways.54 Improvement in UE motor control may contribute to arm swing and help generate forward propulsion at the foot.55 Our kinematic results revealed that MT + MG or MT might reduce shoulder synergy movements, as indicated by less maximum shoulder abduction42 during elbow extension, compared with the CT group. According to the assumption of motor learning, the neural structures controlling movement are required to adapt to constraints imposed by, at least, physical demands.56 MT restrained arm movement in a size-limited box, which might not allow for a great range of shoulder abduction during task performance. Consequently, the synergy pattern of shoulder abduction might be inhibited. This result can also be cross-validated by our findings of improved total FMA scores, because the FMA involves the ability to perform out-of-synergy movements,34 the scores of the FMA indicated a reduction in shoulder synergy movement.57 In contrast, the CT patients gained a greater amount of shoulder flexion than the MT + MG and MT patients. The CT involved a variety of therapeutic activities requiring shoulder forward flexion and elevation. Accordingly, the CT patients exhibited better improvement in shoulder flexion than patients receiving the other 2 treatments. Task-specific training has been shown to be effective in recovery of movement poststroke.58 No group differences were noted in the muscle tone of the biceps, flexor carpi radialis, and flexor carpi ulnaris. One possibility is that our participants had mild to moderate spasticity (MAS 2) at pretest. Most participants in the MT + MG group received the 3-step MG stimulation protocol to increase awareness of the affected hand and enhance volitional activity rather than the protocol to reduce spasticity,15,17,32 resulting in nonsignificant effects on spasticity. We found no group differences in daily function, which is in accord with previous research.23 However, a scrutiny of the descriptive data showed all groups improved in some activities of daily living outcomes, and additional statistical analysis showed significant differences between pre- and posttreatment for each group (P = .014-.047), indicating that all treatments were beneficial to daily function. Future research might include follow-up assessments to study possible changes in activities of daily living or incorporate more functional task practice into MT + MG or MT to improve function in daily-life situations. As a limitation, our study included only people with mild to moderate motor impairments. Some studies have reported that patients with severe motor deficits achieved more improvements after interventions.59 The evidence for optimal intensity of afferent stimulation (eg, electric current intensity) for stroke rehabilitation is limited.59 Because we found no adverse effects using stimulation at the threshold level, it might be possible to increase the intensity of the electrical stimulation.59

Discussion
The present study demonstrated that patients in the MT + MG and MT groups performed better compared with those in the CT group in the reduction of motor impairment. Combining MT with MG stimulation showed additional effects on manual dexterity of the affected hand, self-paced ambulation, and velocity of quickly paced ambulation compared with MT alone. Relative to CT, MT + MG and MT reduced maximum shoulder abduction during forward reach, which is regarded as reducing a critical component of the flexor synergy pattern. However, CT increased shoulder flexion more than the other groups. For daily function, we found no group differences immediately after the 4-week interventions. There was no adverse effect as measured by self-reported pain and fatigue. Compared with the CT group, the MT + MG and MT groups showed improved motor impairment as indicated by the FMA total scores, in line with previous research on MT.2,6,10 As an explanation for the treatment effects, the visual input during MT could substitute for absent or reduced proprioceptive input from the affected body side45 and, consequently, helped recruit the premotor cortex or balance the neural activation within the primary motor cortex toward the affected hemisphere to facilitate motor improvements.3,4,46 We found MT combined with MG stimulation provided additional benefits on manual dexterity compared with MT alone, consistent with the findings of a pilot study on MT combined with somatosensory stimulation23 and studies related to electrical stimulation.47,48 The extra benefit on manual dexterity is very encouraging, considering its importance for activities of daily living49 and that previous studies of MT showed unclear results on manual dexterity.2,6 MG stimulation might induce rapid plastic change in sensorimotor regions of the cortex16,17,50 related to the hand to which the stimulation was applied and modulate the intracortical -aminobutyric acid pathways that reduce intracortical inhibition in the motor cortex of the ipsilesional hemisphere.48 Combining MT with MG could provide cross-modal inputs (ie, sensation from electric stimulation and visual image input from the mirror) during training that may modulate activation of the somatosensory cortex and facilitate dexterity recovery.21,51 Another important finding is that combining MT with MG demonstrated significant improvements on ambulation function measured by the 10-MWT compared with MT alone. This finding is consistent with a pilot study23 and some studies of electrical stimulation on the UE.12,52 Stimulation of cutaneous nerves of the hand could elicit an interlimb reflex response in muscles across the body that is believed to be related to motor coordination between arms and legs during walking.14,53 In addition, arm integration during reciprocal activities, which were part of the training,

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

160
Pretest MT (n = 13) 0.0032 (0.0015) 0.0153 (0.0113) 0.1470 (0.0412) 0.0691 (0.0391) 0.1432 (0.0253) 0.0039 (0.0023) 0.0202 (0.0160) 0.1450 (0.0263) 0.0802 (0.0195) 0.1316 (0.0250) 0.0033 (0.0013) 0.0137 (0.0082) 0.1469 (0.0265) 0.0720 (0.0375) 0.1333 (0.0258) CT (n = 14) MT + MG (n = 14) MT (n = 13) 0.0033 (0.0017) 0.0154 (0.0108) 0.1313 (0.0247) 0.0708 (0.0351) 0.1328 (0.0229) Posttest CT (n = 14) 0.0030 (0.0014) 0.0131 (0.0079) 0.1582 (0.0336) 0.0821 (0.0211) 0.1474 (0.0303) F2,38 0.713 1.006 3.432 0.279 4.554 ANCOVA P .50 .38 .04a .76 .02a 2 .04 .05 .16 .02 .20 0.0050 (0.0056) 0.0270 (0.0391) 0.1490 (0.0287) 0.0624 (0.0505) 0.1526 (0.0415)

Table 3. Descriptive and Inferential Statistics for Analysis of Kinematics Performance.

Variable

MT + MG (n = 14)

Wrist Nmt (s/mm) Wrist nMU (unit/mm) nShoulder flex (/mm) nElbow ext (/mm) Max shoulder abd (/mm)

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

Abbreviations: ANCOVA, analysis of covariance; MT + MG, mirror therapy combined with mesh glove; MT, mirror therapy; CT, control treatment; nMT, normalized movement time; nMU, normalized motor unit; nShoulder flex, normalized angle recruitment of shoulder flexion; nElbow ext, normalized angle recruitment of elbow extension; Max shoulder abd, maximum angle recruitment of shoulder abduction. a P < .05.

Lin et al

161
8. Ezendam D, Bongers RM, Jannink MJ. Systematic review of the effectiveness of mirror therapy in upper extremity function. Disabil Rehabil. 2009;31:2135-2149. 9. Rothgangel AS, Braun SM, Beurskens AJ, Seitz RJ, Wade DT. The clinical aspects of mirror therapy in rehabilitation: a systematic review of the literature. Int J Rehabil Res. 2011;34:1-13. 10. Lee MM, Cho HY, Song CH. The mirror therapy program enhances upper-limb motor recovery and motor function in acute stroke patients. Am J Phys Med Rehabil. 2012;91:689-696. 11. Hankey GJ, Pomeroy VM, King LM, Pollock A, Baily-Hallam A, Langhorne P. Electrostimulation for promoting recovery of movement or functional ability after stroke: systematic review and meta-analysis. Stroke. 2006;37:2441-2442. 12. Peurala SH, Pitkanen K, Sivenius J, Tarkka IM. Cutaneous electrical stimulation may enhance sensorimotor recovery in chronic stroke. Clin Rehabil. 2002;16:709-716. 13. Dimitrijevic MM, Stokic DS, Wawro AW, Wun CCC. Modification of motor control of wrist extension by meshglove electrical afferent stimulation in stroke patients. Arch Phys Med Rehabil. 1996;77:252-258. 14. Zehr EP, Klimstra M, Dragert K, et al. Enhancement of arm and leg locomotor coupling with augmented cutaneous feedback from the hand. J Neurophysiol. 2007;98:1810-1814. 15. Christova M, Rafolt D, Golaszewski S, Gallasch E. Outlasting corticomotor excitability changes induced by 25 Hz whole-hand mechanical stimulation. Eur J Appl Physiol. 2011;111:3051-3059. 16. Golaszewski SM, Bergmann J, Christova M, et al. Increased motor cortical excitability after whole-hand electrical stimulation: a TMS study. Clin Neurophysiol. 2010;121:248-254. 17. Golaszewski SM, Bergmann J, Christova M, et al. Modulation of motor cortex excitability by different levels of wholehand afferent electrical stimulation. Clin Neurophysiol. 2012;123:193-199. 18. Dimitrijevic MM, Soroker N, Pollo FE. Mesh glove electrical stimulation. Sci Med. 1996;3:54. 19. Cauraugh JH. Coupled rehabilitation protocols and neural plasticity: upper extremity improvements in chronic hemiparesis. Restor Neurol Neurosci. 2004;22:337-347. 20. Whitall J. Stroke rehabilitation research: time to answer more specific questions? Neurorehabil Neural Repair. 2004; 18:3-8. 21. Sathian K. Mirror, mirror, move my manu! Neurorehabil Neural Repair. 2009;23:207-208. 22. Laufer Y, Elboim-Gabyzon M. Does sensory transcutane ous electrical stimulation enhance motor recovery following a stroke? A systematic review. Neurorehabil Neural Repair. 2011;25:799-809. 23. Lin KC, Chen YT, Huang PC, et al. Effect of mirror therapy combined with somatosensory stimulation on motor recovery and daily function in stroke patients: a pilot study [published online September 29, 2012]. J Formos Med Assoc. doi:10.1016/j.jfma.2012.08.008. 24. Chuang LL, Wu CY, Lin KC, Lur SY. Quantitative mechanical properties of the relaxed biceps and triceps brachii muscles in patients with subacute stroke: a reliability study of the myoton-3 myometer. Stroke Res Treat. 2012;2012:617694.

Conclusions
This study is unique in demonstrating the comparative effects of MT + MG, MT alone, and task-oriented therapy on a variety of motor and functional outcomes. MT + MG and MT alone improved motor impairment and reduced the critical component of synergy patterns (ie, shoulder abduction) more than CT. MT + MG yields broader aspects of motor recovery. Our study showed the benefits of combining MT and MG stimulation for improving manual dexterity and ambulation function. In addition, all treatments here showed benefits in daily function. Future research may address the dosing issue by studying the effects of stimulation intensity and integrating functional task practice in the MT + MG protocol in an attempt to optimize the effects on daily function. Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported in part by the National Health Research Institutes (NHRI-EX101-9920PI and NHRI-EX101-10010PI), the National Science Council (NSC-100-2314-B-002-008-MY3 and NSC99-2314-B-182-014-MY3), and the Healthy Ageing Research Center at Chang Gung University (EMRPD1B0371) in Taiwan.

References
1. Dobkin BH. Rehabilitation after stroke. N Engl J Med. 2005;352:1677-1684. 2. Michielsen ME, Selles RW, van der Geest JN, et al. Motor recovery and cortical reorganization after mirror therapy in chronic stroke patients: a phase II randomized controlled trial. Neurorehabil Neural Repair. 2011;25:223-233. 3. Michielsen ME, Smits M, Ribbers GM, et al. The neuronal correlates of mirror therapy: an fMRI study on mirror induced visual illusions in patients with stroke. J Neurol Neurosurg Psychiatry. 2011;82:393-398. 4. Altschuler EL, Wisdom SB, Stone L, et al. Rehabilitation of hemiparesis after stroke with a mirror. Lancet. 1999;353:20352036. 5. Cacchio A, De Blasis E, De Blasis V, Santilli V, Spacca G. Mirror therapy in complex regional pain syndrome type 1 of the upper limb in stroke patients. Neurorehabil Neural Repair. 2009;23:792-799. 6. Dohle C, Pullen J, Nakaten A, Kust J, Rietz C, Karbe H. Mirror therapy promotes recovery from severe hemiparesis: a randomized controlled trial. Neurorehabil Neural Repair. 2009;23:209-217. 7. Thieme H, Mehrholz J, Pohl M, Behrens J, Dohle C. Mirror therapy for improving motor function after stroke. Cochrane Database Syst Rev. 2012;(3):CD008449.

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014

162
25. Caimmi M, Carda S, Giovanzana C, et al. Using kinematic analysis to evaluate constraint-induced movement therapy in chronic stroke patients. Neurorehabil Neural Repair. 2008;22:31-39. 26. Feng X, Winters JM. A pilot study evaluating use of a com puter-assisted neurorehabilitation platform for upper-extremity stroke assessment. J Neuroeng Rehabil. 2009;6:15. 27. Kantak SS, Stinear JW, Buch ER, Cohen LG. Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury. Neurorehabil Neural Repair. 2012;26:282-292. 28. Fridman EA, Hanakawa T, Chung M, Hummel F, Leiguarda RC, Cohen LG. Reorganization of the human ipsilesional premotor cortex after stroke. Brain. 2004;127(pt 4):747-758. 29. Bohannon RW, Smith MB. Interrater reliability of a modi fied Ashworth scale of muscle spasticity. Phys Ther. 1987;67: 206-207. 30. Folstein MF, Folstein SE, McHugh PR. Mini-mental state. J Psychiatr Res. 1975;12:189-198. 31. Kasner SE, Cucchiara BL, McGarvey ML, Luciano JM, Liebeskind DS, Chalela JA. Modified National Institutes of Health Stroke Scale can be estimated from medical records. Stroke. 2003;34:568-570. 32. Lum PS, Burgar CG, Shor PC, Majmundar M, Van der Loos M. Robot-assisted movement training compared with conventional therapy techniques for the rehabilitation of upper-limb motor function after stroke. Arch Phys Med Rehabil. 2002;83:952-959. 33. Dimitrijevic MM. Mesh-glove. 1. A method for whole-hand electrical-stimulation in upper motor-neuron dysfunction. Scand J Rehabil Med. 1994;26:183-186. 34. Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. A method for evaluation of physical performance. Scand J Rehabil Med. 1975;7:13-31. 35. Platz T, Pinkowski C, van Wijck F, Kim IH, di Bella P, Johnson G. Reliability and validity of arm function assessment with standardized guidelines for the Fugl-Meyer Test, Action Research Arm Test and Box and Block Test: a multicentre study. Clin Rehabil. 2005;19:404-411. 36. Rossier P, Wade DT. Validity and reliability comparison of 4 mobility measures in patients presenting with neurologic impairment. Arch Phys Med Rehabil. 2001;82:9-13. 37. Uswatte G, Taub E, Morris D, Light K, Thompson PA. The Motor Activity Log-28assessing daily use of the hemiparetic arm after stroke. Neurology. 2006;67:1189-1194. 38. Penta M, Tesio L, Arnould C, Zancan A, Thonnard JL. The ABILHAND questionnaire as a measure of manual ability in chronic stroke patients: Rasch-based validation and relationship to upper limb impairment. Stroke. 2001;32:1627-1634. 39. Wu CY, Chen CL, Tang SF, Lin KC, Huang YY. Kinematic and clinical analyses of upper-extremity movements after constraint-induced movement therapy in patients with stroke: a randomized controlled trial. Arch Phys Med Rehabil. 2007;88: 964-970. 40. Lin KC, Wu CY, Wei TH, Lee CY, Liu JS. Effects of modified constraint-induced movement therapy on reach-to-grasp movements and functional performance after chronic stroke: a randomized controlled study. Clin Rehabil. 2007;21:1075-1086. 41. Lin KC, Wu CY, Chen CL, Chern JS, Hong WH. Effects of object use on reaching and postural balance: a comparison of patients with unilateral stroke and healthy controls. Am J Phys Med Rehabil. 2007;86:791-799.

Neurorehabilitation and Neural Repair 28(2)

42. Messier S, Bourbonnais D, Desrosiers J, Roy Y. Kinematic analysis of upper limbs and trunk movement during bilateral movement after stroke. Arch Phys Med Rehabil. 2006;87:1463-1470. 43. Massie C, Malcolm MP, Greene D, Thaut M. The effects of constraint-induced therapy on kinematic outcomes and compensatory movement patterns: an exploratory study. Arch Phys Med Rehabil. 2009;90:571-579. 44. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: Routledge; 1988. 45. Flor H, Diers M. Sensorimotor training and cortical reorgani zation. NeuroRehabilitation. 2009;25:19-27. 46. Shinoura N, Suzuki Y, Watanabe Y, et al. Mirror ther apy activates outside of cerebellum and ipsilateral M1. NeuroRehabilitation. 2008;23:245-252. 47. Conforto AB, Cohen LG, dos Santos RL, Scaff M, Marie SK. Effects of somatosensory stimulation on motor function in chronic cortico-subcortical strokes. J Neurol. 2007;254:333-339. 48. Celnik P, Hummel F, Harris-Love M, Wolk R, Cohen LG. Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke. Arch Phys Med Rehabil. 2007;88:1369-1376. 49. Kwakkel G, Kollen B. Predicting improvement in the upper paretic limb after stroke: a longitudinal prospective study. Restor Neurol Neurosci. 2007;25:453-460. 50. Chipchase LS, Schabrun SM, Hodges PW. Peripheral elec trical stimulation to induce cortical plasticity: a systematic review of stimulus parameters. Clin Neurophysiol. 2011;122:456-463. 51. Schaefer M, Noennig N, Heinze HJ, Rotte M. Fooling your feelings: artificially induced referred sensations are linked to a modulation of the primary somatosensory cortex. Neuroimage. 2006;29:67-73. 52. Ng SS, Hui-Chan CW. Transcutaneous electrical nerve stimulation combined with task-related training improves lower limb functions in subjects with chronic stroke. Stroke. 2007;38:2953-2959. 53. Haridas C, Zehr EP. Coordinated interlimb compensatory responses to electrical stimulation of cutaneous nerves in the hand and foot during walking. J Neurophysiol. 2003;90:2850-2861. 54. Stephenson JL, De Serres SJ, Lamontagne A. The effect of arm movements on the lower limb during gait after a stroke. Gait Posture. 2010;31:109-115. 55. Tester NJ, Barbeau H, Howland DR, Cantrell A, Behrman AL. Arm and leg coordination during treadmill walking in individuals with motor incomplete spinal cord injury: a preliminary study. Gait Posture. 2012;36:49-55. 56. Daly JJ, Ruff RL. Construction of efficacious gait and upper limb functional interventions based on brain plasticity evidence and model-based measures for stroke patients. ScientificWorldJournal. 2007;7:2031-2045. 57. van Kordelaar J, van Wegen EE, Kwakkel G. Unraveling the interaction between pathological upper limb synergies and compensatory trunk movements during reach-to-grasp after stroke: a cross-sectional study. Exp Brain Res. 2012;221:251-262. 58. Hubbard IJ, Parsons MW, Neilson C, Carey LM. Task specific training: evidence for and translation to clinical practice. Occup Ther Int. 2009;16:175-189. 59. Conforto AB, Ferreiro KN, Tomasi C, et al. Effects of somatosensory stimulation on motor function after subacute stroke. Neurorehabil Neural Repair. 2010;24:263-272.

Downloaded from nnr.sagepub.com at Universitas Gadjah Mada on March 27, 2014