http://informahealthcare.com/bij ISSN: 0269-9052 (print), 1362-301X (electronic) Brain Inj, 2014; 28(2): 203–210 ! 2014 Informa UK Ltd. DOI: 10.3109/02699052.2013.860472
ORIGINAL ARTICLE
Repetitive facilitative exercise under continuous electrical stimulation for severe arm impairment after sub-acute stroke: A randomized controlled pilot study Megumi Shimodozono1, Tomokazu Noma2, Shuji Matsumoto1, Ryuji Miyata1, Seiji Etoh1, & Kazumi Kawahira1 1
Abstract
Keywords
Objective: To investigate the effectiveness of repetitive facilitative exercise (RFE) under surface neuromuscular electrical stimulation (NMES) in patients with post-stroke hemiplegia. Methods: This randomized, controlled, observer-blinded, pilot trial randomized 27 adults with severe arm impairment [Fugl-Meyer Arm scale (FMA) 20] due to stroke of 3–13 weeks duration into three groups and provided treatment on a 4-week, 40 minutes/day, 5 days/week schedule. The RFE-under-NMES group were given 100–150 repetitions of standardized movements of shoulder, elbow and wrist joints of their affected arm with concurrent lowamplitude NMES for each corresponding musculature. The RFE group was given the same exercise regimen but without NMES. The control group was treated with a conventional arm rehabilitation programme without NMES. FMA was assessed at baseline and 4 weeks. Results: All 27 participants (nine in each group) completed the trial. At 4 weeks, the RFE-under-NMES group evidenced significantly greater improvement compared with the control group on the FMA (p ¼ 0.003), but not with the RFE group (p ¼ 0.092). The RFE group showed improvement compared with the control group, but it was not significant (p ¼ 0.199). Conclusions: RFE under NMES is feasible in clinical settings and may be more effective than conventional rehabilitation in lessening arm impairment after sub-acute stroke.
Facilitation, hemiplegia, repetition, rehabilitation, RFE, upper extremity
Introduction Repetitive facilitative exercise (RFE), a combination of high repetition rate and neurofacilitation, is a recently developed approach to rehabilitation of stroke-related limb impairment [1–3]. More specifically, the therapist harnesses muscle spindle stretch and skin-generated reflexes to assist the patient’s efforts to move an affected joint. Previous work has demonstrated that RFE, at least during the sub-acute phase of stroke, may be more effective than conventional rehabilitation in lessening impairment and improving arm motor function [2, 3]. However, efficacy for severe arm impairment remains unknown because inclusion criteria in previous studies was limited to relatively mild-to-moderate impairment (Brunnstrom stage III) [3]. Neuromuscular electrical stimulation (NMES) to the paretic arm has been proposed to improve movement affected by central nervous system lesions [4–7], but showed borderline effects on arm recovery according to recent systematic reviews [8–10]. Electrical stimulation (ES) can be used by patients with Correspondence: Megumi Shimodozono, Department of Rehabilitation and Physical Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 3930-7, Takachiho, Makizono-cho, Kirishima city, Kagoshima, 899-6603, Japan. Tel: +81-995-78-2077. Fax: +81-995-64-4045. E-mail: [email protected]
History Received 27 May 2013 Revised 23 September 2013 Accepted 25 October 2013 Published online 3 December 2013
hemiparesis who do not have sufficient residual movement to take part in volitional, active repetitive movement therapy [5]. However, when ES is associated with voluntary effort or movement—EMG-triggered ES or volitionally activated ES— the therapeutic effect might be enhanced compared with use of non-triggered electrical stimulation (cyclic NMES) [11]. To achieve motor recovery, volitional and repetitive task-specific training with gradual increases in difficulty is important [8, 12]. However, it is not only difficult but also ineffective for patients with severe arm impairment to perform repetitive taskspecific training even when functional electrical stimulation (FES) is employed [6, 13]. These observations motivated the idea that concurrent RFE and NMES may provide a more effective approach to rehabilitation than either modality alone, because effects of NMES may be enhanced by asking a patient with severe impairment to accompany the motion in terms of thought and, if possible, by actively tensing their muscles [6]. Here, more specifically, a novel approach ‘RFE under low-amplitude continuous NMES’ is proposed. The ‘low-amplitude continuous NMES’ used generates slight and continuous contraction in targeted paretic muscle but does not induce ‘passive’ limb/ joint movement while the patient remains at rest. This condition was selected to produce stretch reflex easily during RFE, even in the severely paretic (‘flaccid’) muscle.
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Department of Rehabilitation and Physical Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan and 2Department of Rehabilitation, Kagoshima University Hospital Kirishima Rehabilitation Center, Kagoshima, Japan
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The reflected movement would assist the patient’s efforts to move the affected joint and repetition of elicited movement may improve motor recovery [2, 3]. Thus, it is hypothesized that a novel approach, RFE under low-amplitude continuous NMES (RFE under NMES), is feasible for patients with severe arm impairment in the subacute phase of stroke. In addition, it was hypothesized that participants in the RFE-under-NMES programme or RFE programme alone will, at the end of training, show significantly larger improvements in motor control (motor impairment) of their severely affected arm than those assigned to conventional therapy. One of the most widely recognized and clinically relevant measures of motor impairment after stroke is the Fugl-Meyer Assessment [14–16]. The authors, therefore, conducted a randomized, controlled, observer-blinded, pilot trial to compare improvement in voluntary motor control—evaluated by the Fugl-Meyer Assessment Scale for arm (FMA)—in the sub-acute stages of stroke with severe arm impairment during a 4-week, 5 days/week, time-matched regimen of RFE under NMES, RFE alone or a conventional rehabilitation programme.
Methods
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interventions: (1) RFE-under-NMES, (2) RFE or (3) conventional rehabilitation (Figure 1) via a computer-generated blocked randomization sequence with a block size of 9. An independent researcher not involved in recruitment or measurement managed and concealed the randomization procedure. Participants were blinded to the study hypotheses. All procedures complied with the 1975 Declaration of Helsinki, as revised in 2008. Approval was received from the ethics committees of the study site and written informed consent was obtained from each participant. Interventions All participants, regardless of their group assignment, underwent training in 40-minute sessions on a 4-week, 5-day/week schedule. In addition, all participants performed 30 minutes/ day of dexterity-related training—that is, object-related reachto-grasp training—immediately after each treatment session. The total time of treatment for the arm was the same between the three groups. Patients also continued participating in a standard inpatient rehabilitation programme that included activities of daily living, physical therapy, mobility training and speech therapy.
Participants This study recruited 27 patients from the inpatient rehabilitation centre of a university hospital in Japan (Figure 1). Inclusion criteria were: (1) a new, single CT-confirmed stroke of 3–13 weeks duration; (2) severe arm impairment, FMA 20; and (3) an ability to follow simple directions. Exclusion criteria were (1) contraindication for ES, such as a pacemaker implant; (2) arm contractures or pain; (3) preexisting arm impairment; (4) cerebellar lesion; (5) unstable medical status; (6) perceptual, apraxic or cognitive deficits that would prevent adequate study participation; or (7) inability to provide informed consent. Design The study was a 4-week, randomized, observer-blinded, pilot trial. Participants were randomized to one of three Figure 1. Study recruitment and randomization. RFE, repetitive facilitative exercise; NMES, neuromuscular electrical stimulation.
RFE group The overall aspects of the RFE programme have been described previously [2, 3, 17, 18] and are only summarized here. Briefly, repetitive facilitative techniques were used to elicit movement of the shoulder, elbow and wrist in a manner designed to minimize synergistic movements. This technique involved the use of rapid passive stretching of the muscles in conjunction with tapping and rubbing the skin to assist in generating contraction of the targeted muscles. Participants were directed to concentrate on generating movement of the joint being treated while avoiding contraction of non-targeted muscles. Therapists supplemented the subject’s efforts as necessary to achieve full range of motion (ROM). Subjects’ efforts were directed with commands such as ‘bend/extend’ or ‘one, two, three . . .’.
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DOI: 10.3109/02699052.2013.860472
This study utilized three specific patterns at three joints: (1) shoulder flexion with the elbow bent at 90 in the supine position, (2) elbow extension in the supine position and (3) wrist dorsiflexion and forearm pronation with extension of the fingers in the supine position. Principles for selection and treatment using these three patterns included: (1) an emphasis on the proximal musculature given its role in stabilizing distal movements, (2) reduction of spasticity in elbow flexors and wrist flexors by reciprocal innervation, (3) gradual increases in movement from easier to more difficult with a goal of maintaining movement purity and avoiding synergy and (4) consideration of difficulties in eliciting separate movement of each finger for patients with severe impairment. Exercises were performed as two-to-three sets of 50 repetitions with an intervening 1–2 minute rest period. Thus, a total of 300–450 repetitions were performed during each session. Each RFE session was concluded with 30 minutes of object-related training involving activities such as reaching to grasp blocks of differing sizes with the affected arm or the use of arm skateboards or weighted sanders. Assistance with an unaffected limb was permitted. RFE-under-NMES group The RFE programme performed with this group was the same as that with the RFE group. In addition, constant lowamplitude NMES was simultaneously applied during RFE sessions. NMES was delivered using a portable surface neuromuscular stimulator (Trio 300, Ito Co., Ltd., Tokyo). The surface electrodes were arranged over the following muscles according to the three RFE patterns (i.e. three treated areas): anterior part of the deltoid muscle during shoulder flexion, triceps during elbow extension and wrist extensors (extensor digitorum communis) during wrist dorsiflexion and forearm pronation (Figure 2). The stimulation pulse was a symmetrical biphasic waveform, with a pulse width of 250 ms
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and frequency of 20 Hz. Intensity of the electrical current was adjusted to produce slight contraction of the target muscle without inducing obvious limb/joint movement while the subject remained at rest and subjectively comfortable. This low-amplitude NMES was continuously applied to the targeted musculature during RFE, but not provided with on/ off mode, EMG-triggered or position-triggered. As was true for the RFE participants, each session was concluded with an additional 30 minutes of object-related training. Control group Participants in the control group underwent a conventional arm rehabilitation programme of their involved limb on a dose-matched 5 days/week, 40-minutes/day, 4-week schedule as with those receiving RFE. Sessions consisted of (1) ROM exercises; (2) passive, assistive, active and progressive resistive exercise; (3) the use of skateboards or weighted sanders; and (4) pinching or grasping blocks of various sizes. As with the RFE or RFE-under-NMES participants, each control session was concluded with an additional 30 minutes of object-related training. Substantial efforts were made to ensure that the control and intervention groups were similar in terms of time spent in therapy sessions. Therapists recorded therapy duration (time), content and compliance in detail for each session with all groups. The duration, frequency and type of therapy provided to the control group were chosen to be consistent with those generally provided to patients with this level of motor impairment. Outcome measures The primary outcome measure used to assess motor impairment was FMA [14]. The FMA has a maximum score of 66, which indicates optimal recovery, and its psychometric
Figure 2. An example of repetitive facilitative exercise (RFE) under continuous surface neuromuscular electrical stimulation (NMES) to elicit right-wrist dorsiflexion. The patient is positioned with wrist flexion and forearm supination in the supine position. Surface electrodes are attached over the extensor digitorum communis. Intensity of electrical current is adjusted to produce slight contraction of the target muscle without obvious wrist/ finger movement while the subject remains at rest. (1) To induce forearm pronation and wrist extension with finger extension, the therapist holds the thumb in his/her hand, quickly pulls the 3rd, 4th and 5th fingers using the 2nd and 3rd fingers of his/her other hand and taps the ulnar side of the knuckle using his/her 1st finger (arrow). Simultaneously the therapist says, ‘Turn your hand and forearm as if you were stopping traffic’ and the patient attempts to perform wrist extension, forearm pronation and finger extension. (2) When the patient begins to show wrist extension and forearm pronation with extension of the fingers, the therapist provides slight resistance to the patient’s hand using his/her thumb and fingers. (3) The therapist’s right hand follows the voluntary motion of the patient. The therapist controls his/her assistance or slight resistance according to the patient’s voluntary motion. This pattern is repeated in two sets of 50 repetitions separated by a 1–2 minute rest period.
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properties have been shown to be satisfactory in patients with stroke [15, 16]. Greater motor severity as indicated by lower FMA scores is correlated with lower functional ability, such as spontaneous arm use for feeding, dressing and grooming [19]. Secondary outcome measures included active ROMs and the modified Ashworth scale (MAS) [20]. Active ROMs were measured for flexion at the shoulder and for extension at the elbow and wrist of the affected arm with a goniometer. This study assessed tone of the elbow and wrist flexors using MAS (range 0–5), which has been shown to be reliable in the assessment of arm spasticity [21]. This study also assessed adverse effects of treatment, such as muscle fatigue or local pain, by recording responses to questions asked of the patients. Outcome measures were assessed at the start of the trial and at its 4-week conclusion. A trained and experienced therapist who had no other contact with the study served as a blinded evaluator. Statistical analysis Non-parametric statistics were used for the analyses, because not all data met the criterion of normality. The primary endpoint was the outcome at trial conclusion (4 weeks). Change scores were calculated for all outcome measures (FMA, active ROMs and MAS) by taking the difference between baseline and 4 weeks. The Kruskal-Wallis procedure was used as a global test of differences in improvement among the three groups. When a significant p-value (p50.05) was obtained, post-hoc comparisons were performed using the MannWhitney U-test with Bonferroni correction (p50.05/n, where n ¼ 3 was the number of comparisons made).
Baseline characteristics were compared using the KruskalWallis test for continuous and ordinal variables or the chisquare test for observed frequencies and p Values50.05 were considered to be statistically significant. This study presents results as mean and standard deviation or median and range as appropriate. SPSS (version 19.0 software for Mac OS X) was employed for statistical analyses.
Results Participant characteristics Figure 1 illustrates the recruitment process. One hundred and forty-one candidates were screened for participation over the study’s recruitment period (Figure 1). Of these, 108 did not meet the inclusion criteria and six declined to give their consent. The remaining 27 were enrolled in the study, with nine randomly assigned to RFE under NMES, nine to RFE alone and nine to the control group. There were no drop-outs within the 4-week study period. Thus, data from 27 patients (nine patients in each group) were available for analysis (Figure 1). No adverse treatment effects, such as burns, skin allergic responses or muscle fatigue, were noted. The three groups did not differ significantly in terms of demographic characteristics—age, gender, stroke duration and stroke location—at entry or baseline measures of FMAs, active ROMs and MASs (Table I). Outcome measures Table II presents differences of outcome measures between baseline and 4 weeks under treatment as mean and standard deviation, median and range. Table II also shows comparisons among the three groups.
Table I. Baseline characteristics of participants (n ¼ 27)a.
Mean age, years Sex, male Time since stroke, weeks Side of motor deficit, right Type of stroke Infarction Haemorrhage Stroke location Basal ganglia Thalamus Internal capsule/corona radiata Territory of middle cerebral artery Cortex Brainstem FMA Active ROM Shoulder flexion Elbow extension Wrist extension MAS Elbow flexors Wrist flexors
Control group (n ¼ 9)
RFE group (n ¼ 9)
RFE-under-NMES group (n ¼ 9)
61.4 15.6 5 (56) 6.7 2.7 1 (11)
61.9 13.6 9 (100) 6.8 2.0 6 (67)
61.1 11.3 6 (67) 6.2 2.7 5 (56)
3 (33) 6 (67)
5 (56) 4 (44)
7 (78) 2 (22)
5 (56) 1 (11) 0 (0) 2 (22) 0 (0) 1 (11) 8.7 5.7
3 (33) 1 (11) 2 (22) 2 (22) 0 (0) 1 (11) 8.2 3.0
2 (22) 1 (11) 3 (33) 2 (22) 0 (0) 1 (11) 11.4 5.9
0.44b
5.1 15.3 1.4 4.3 0.0 0.0
4.8 10.8 21.3 37.8 1.8 5.3
8.1 20.1 10.2 29.9 2.1 4.8
0.71b 0.65b 0.74b
0.9 1.1 1.0 1.1
1.2 0.8 1.3 1.5
1.3 1.1 1.1 1.1
0.59b 0.93b
p Value 0.99b 0.26c 0.63b 0.15c 0.57c 0.98c
RFE, repetitive facilitative exercise; NMES, neuromuscular electrical stimulation; FMA, Fugl-Meyer Arm Motor Scale; ROM, Range of motion; MAS, Modified Ashworth Scale. a Values are mean standard deviation or number (percentage). b Kruskal-Wallis test. c 2 test.
Repetitive facilitation under electrostimulation
b
a
Wrist flexors
RFE, repetitive facilitative exercise; NMES, neuromuscular electrical stimulation; FMA, Fugl-Meyer Arm Motor Scale; ROM, range of motion; MAS, modified Ashworth scale. Values are mean standard deviation and median (range in parentheses). Change scores were created by subtracting baseline score from outcome score at 4 weeks. p Values indicate significance level of changes in outcome measures among the three groups using the Kruskal-Wallis test. *p50.017 vs control group (post-hoc test using the Mann-Whitney U-test with Bonferroni correction).
0.871
0.653
0.0 1.1, 0 (2–2) 0.1 1.2, 0 (2–2) 0.3 0.9, 0 (1–2) 0.6 1.3, 0 (1–3) 1.3 1.1, 2 (0–3) 1.3 1.5, 1 (0–4) MAS Elbow flexors
Wrist dorsiflexion
Elbow extension
0.9 1.1, 1 (0–3) 1.0 1.1, 1 (0–3)
0.4 0.9, 0 (1–2) 0.3 1.5, 0 (2–3)
1.2 0.8, 1 (0–2) 1.3 1.5, 1 (0–4)
1.6 1.1, 2 (0–3) 1.9 1.3, 2 (0–4)
1.3 1.1, 1 (0–3) 1.1 1.1, 1 (0–3)
1.0 1.0, 1 (0–3) 1.2 0.8, 1 (0–2)
0.352
0.034
0.057
37.4 43.4, 30 (0–144) 68.6 35.5, 80 (0–110)* 16.1 30.5, 0 (0–93) 28.4 37.5, 10 (0–93) 31.1 39.9, 15 (0–90) 5.7 17.0, 0 (0–51) 4.8 10.8, 0 (0–33) 21.3 37.8, 0 (0–101) 1.8 5.3, 0 (0–16) 17.2 33.7, 0 (0–98) 16.2 30.9, 0 (0–90) 0.8 2.3, 0 (0–7) Active ROM Shoulder flexion
5.1 15.3, 0 (0–46) 1.4 4.3, 0 (0–13) 0.0 0.0, 0 (0–0)
12.1 32.5, 0 (1–98) 14.8 31.2, 0 (0–90) 0.8 2.3, 0 (0–7)
33.2 44.8, 10 (0–126) 52.4 50.6, 85 (0–117) 7.4 17.2, 0 (0–51)
8.1 20.1, 0 (0–61) 10.2 29.9, 0 (0–90) 2.1 4.8, 0 (0–14)
45.6 49.9, 30 (0–144) 78.8 24.9, 82 (27–110) 18.2 30.5, 0 (0–93)
0.014 18.4 15.7, 15 (6–57)* 29.9 13.7, 27 (14–63) 9.7 9.1, 9 (0–30) 8.2 3.0, 8 (4–14) 13.2 7.9, 11 (6–32) FMA
8.7 5.7, 6 (4–18)
4.6 5.2, 4 (5–14)
17.9 9.5, 15 (5–36)
11.4 5.9, 13 (4–20)
Difference Week 4 Baseline Difference Baseline Week 4 Baseline
Difference
207
Fugl-Meyer arm motor scale
Week 4
RFE-under-NMES group (n ¼ 9) RFE group (n ¼ 9) Control group (n ¼ 9)
Table II. Changes in outcome measures at the end of treatment in the three groups (n ¼ 27)a.
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Comparison among the three groups, p Valueb
DOI: 10.3109/02699052.2013.860472
The RFE-under-NMES group displayed a median increase of 15 points at the end of training on the study’s primary outcome variable, the FMA, relative to median increases of 9- and 4-points in the RFE and control groups, respectively. The difference in the median increases between the RFE-under-NMES and RFE groups was 6-points and the difference between the RFE-under-NMES and control groups was 11-points. There were significant differences among the three groups over time (p ¼ 0.014). The post-hoc test revealed a significant increase with RFE-under-NMES compared with the control group (p ¼ 0.003), but not with RFE alone (p ¼ 0.092). The RFE-only group performed better, but not significantly better, than the control group (median of 5-points; p ¼ 0.199). Active range of motion The RFE-under-NMES group displayed a median increase of 80 in elbow extension at the end of training on active ROM, relative to 15 and 0 increases in the RFE and control groups, respectively. The difference in the median increases between the RFE-under-NMES and RFE groups was 65 and the difference between the RFE-under-NMES and control groups was 80 . There were significant differences over time among the three groups (p ¼ 0.034). The post-hoc test revealed a significant increase with RFE-under-NMES compared with the control group (p ¼ 0.011), but not with RFE alone (p ¼ 0.081). RFE alone performed better, but not significantly better, than the control group (p ¼ 0.308). With shoulder flexion and wrist dorsiflexion, however, there were no significant differences among the groups over time (p ¼ 0.057 and p ¼ 0.352, respectively) (Table II). Modified Ashworth scale There were no significant differences in elbow flexion or wrist flexion among the groups over time (p ¼ 0.653 and p ¼ 0.871, respectively) (Table II).
Discussion This study represents the first randomized controlled trial of RFE combined with simultaneous, continuous NMES compared with duration-matched RFE alone or conventional rehabilitation in the treatment of stroke-related severe arm impairment. At least for subjects with sub-acute stroke, RFE under NMES produced significantly better improvement in the primary outcome variable, FMA, compared with conventional rehabilitation. Active ROM in the elbow joint also showed significant improvement, but spasticity, as measured with MAS, appeared unaltered by either intervention. In addition, this pilot study demonstrated practicality or feasibility of this treatment regimen and of the research project overall. Motor performance The RFE-under-NMES programme demonstrated both statistically and clinically significant improvement over conventional rehabilitation because the minimal clinically important difference of the FMA is 6.6 [22]. The greater improvement
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could not be due solely to the high degree of repetition of the facilitative technique itself because the lessening of motor impairment as measured by FMA or active ROM in the RFE group was not significantly greater than that of the control group. Further, there were no statistically significant differences in improvement between the RFE-under-NMES group and the RFE group. It remains unclear whether differences in improvements were due to NMES itself or the concurrent application of RFE. However, it is believed that the combination of the two was required for the observed difference in improvement because more positive results were found when ES to the arm was triggered by voluntary movement than when non-triggered simple electrical muscle stimulation was used [11]. It has been difficult to improve arm recovery in patients with severe impairment due to stroke; recovery of movement remains a problem [23]. Although traditional treatment methods for patients with severe impairment have included passive and traditional facilitation techniques, the benefits are far more limited than one would like [24]. Recently, a number of interventions have been developed in which robotic therapy provides a large beneficial effect, with limited evidence that ES and other interventions provide large improvement in function [23, 25]. The lessening of motor impairment with the RFE-underNMES treatment is consistent with results obtained from previous studies that used ES for patients with stroke [5, 6, 10, 11]. In the present study, however, there are differences both in the application of ES and in the severity of motor impairment. There have been few studies investigating efficacy of ES on a severely impaired arm in the sub-acute stage of stroke: 3 weeks of cyclic ES application (during which the patients focused on the movement and imitated the function of the arm) to the deltoid muscle, supraspinatus and wrist extensors on the affected arm for 30 minutes/day led to improved motor recovery that persisted for at least 6 months [26]. In the acute stage of stroke, a minimum of 10 hours (30 minutes, 5-times per week for a period of 4 weeks) of NMES in combination with regular rehabilitation improves the recovery of arm function [27]. The total dose of ES, 13.3 hours in the current study, may support this previous finding. Optimal stimulation parameters, dosage and optimal exercise combined with ES remain to be investigated in the future. Mechanism of RFE under NMES for lessening motor impairment Sub-motoric stimulation of the upper paretic extremity has been used primarily to reduce spasticity and secondarily to improve motor activation through increased afferent inputs [6, 28, 29]. The low-amplitude intensity of NMES was selected because it was postulated that it might be important for motor recovery to repeat active-assistive movement— concurrent combination of patient efforts to move and facilitative technique under continuous ES—compared with mere passive movement (motoric/cyclic ES). This hypothesis is based on Hebbian long-term potentiation and other mechanisms that determine synaptic efficacy [30]. In addition, electrically mediated repetitive movement facilitates motor relearning to make use of central neuroplasticity [6].
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Anti-spastic effects might also contribute to the benefits of treatment as electrical contraction of paretic musculature leads to reciprocal inhibition of spastic antagonists through the stimulation of spinal interneurons [6]. In the present study, there were no significant differences in spasticity measured by MAS either within (data not shown) or between groups. This might be due to a relatively low grade of spasticity, even in the initiation of the current intervention. Clinical applicability of RFE under NMES RFE, although requiring intense therapist involvement, has an advantage in that it requires no equipment and can be performed anywhere once a therapist has mastered the techniques, which are based on those that are already a part of their training [3]. As shown in the present study, however, it might be inadequate for patients with severe motor impairment to realize improvement solely with use of RFE. It might be relatively easy for a therapist to select or adjust the amount of ES assistance during RFE; the therapist can select appropriate joints to be treated or adjust electrical intensity according to the clinical symptoms, such as severity of motor impairment or general physical and cognitive condition of the patient [6]. In addition, a surface neuromuscular stimulator is relatively moderately priced and portable. It may be beneficial to start with a programme including RFE under NMES in the case of severe impairment (i.e. active EMG not generated) and, when motor control has improved, switch to a programme including EMG-triggered ES for functional training [6]. In the RFE-under-NMES session, taking an elbow extension pattern for example, there is an elbow flexion movement accompanied with relaxation of the triceps between two repetitions of elbow extension. The elbow flexion movement might be inhibited by NMES continuously applied to the targeted muscle (triceps). In the authors’ experience, however, this problem was not encountered, for two reasons. The NMES was adjusted to low-enough amplitude so as not to induce obvious limb/joint movement and the opposite movement was primarily a passive one performed by the therapist. Application involving an interval without NMES (i.e. off mode) during the opposite movement may be preferable, but would result in a more complicated method. The present study revealed no adverse side-effects such as local pain, muscle fatigue or increased muscle tone. The specific NMES parameters that are optimal for reducing motor deficits in the neurologically impaired hand remain unclear, although previous work has examined variable patterns of stimulation and the fatigue effects of NMES in the arm [4]. To avoid muscle fatigue during muscle strengthening it is important to optimize the stimulation strategy because a high intensity of stimulation and stimulation frequencies higher than 50 Hz accelerate the rate and level of fatigue [6]. Limitations The major limitation was a small sample size with probability of imbalance at baseline since the pilot study was designed to make an initial assessment of the feasibility and to calculate required sample size for further study. All participants
DOI: 10.3109/02699052.2013.860472
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tolerated interventions of RFE or RFE under NMES well and there were no adverse effects. Using the SD in FMA of 11 and the mean difference of changes in FMA of 14 found in this investigation would result in the requirement for a study with two independent groups (control group vs RFE-underNMES group) and a power of 80% to have 11 subjects in each group. Similarly, using the SD in FMA of 7 and the mean difference of changes in FMA of 7 found in this investigation would result in the requirement for a study with two independent groups (control group vs RFE group) and a power of 80% to have 32 subjects in each group. The study has a number of other limitations. Mixtures of stroke location and type, as well as varying levels of impairment and the restriction of participants to the subacute stages of stroke render generalization to other situations difficult. Other weaknesses are a lack of follow-up after the end of treatment and the inability, thus far, to assess the sustainability of these findings.
Conclusion A combination of RFE and concurrent low-amplitude continuous NMES may be associated with additional recovery following motor impairment in patients with severe arm impairment in the sub-acute phase of stroke. A further multicentre randomized clinical trial would require at least 11 participants in order to demonstrate a clinically meaningful difference in arm motor recovery between the conventional arm rehabilitation group and the RFE-under-NMES group.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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ORIGINAL ARTICLE
Repetitive facilitative exercise under continuous electrical stimulation for severe arm impairment after sub-acute stroke: A randomized controlled pilot study Megumi Shimodozono1, Tomokazu Noma2, Shuji Matsumoto1, Ryuji Miyata1, Seiji Etoh1, & Kazumi Kawahira1 1
Abstract
Keywords
Objective: To investigate the effectiveness of repetitive facilitative exercise (RFE) under surface neuromuscular electrical stimulation (NMES) in patients with post-stroke hemiplegia. Methods: This randomized, controlled, observer-blinded, pilot trial randomized 27 adults with severe arm impairment [Fugl-Meyer Arm scale (FMA) 20] due to stroke of 3–13 weeks duration into three groups and provided treatment on a 4-week, 40 minutes/day, 5 days/week schedule. The RFE-under-NMES group were given 100–150 repetitions of standardized movements of shoulder, elbow and wrist joints of their affected arm with concurrent lowamplitude NMES for each corresponding musculature. The RFE group was given the same exercise regimen but without NMES. The control group was treated with a conventional arm rehabilitation programme without NMES. FMA was assessed at baseline and 4 weeks. Results: All 27 participants (nine in each group) completed the trial. At 4 weeks, the RFE-under-NMES group evidenced significantly greater improvement compared with the control group on the FMA (p ¼ 0.003), but not with the RFE group (p ¼ 0.092). The RFE group showed improvement compared with the control group, but it was not significant (p ¼ 0.199). Conclusions: RFE under NMES is feasible in clinical settings and may be more effective than conventional rehabilitation in lessening arm impairment after sub-acute stroke.
Facilitation, hemiplegia, repetition, rehabilitation, RFE, upper extremity
Introduction Repetitive facilitative exercise (RFE), a combination of high repetition rate and neurofacilitation, is a recently developed approach to rehabilitation of stroke-related limb impairment [1–3]. More specifically, the therapist harnesses muscle spindle stretch and skin-generated reflexes to assist the patient’s efforts to move an affected joint. Previous work has demonstrated that RFE, at least during the sub-acute phase of stroke, may be more effective than conventional rehabilitation in lessening impairment and improving arm motor function [2, 3]. However, efficacy for severe arm impairment remains unknown because inclusion criteria in previous studies was limited to relatively mild-to-moderate impairment (Brunnstrom stage III) [3]. Neuromuscular electrical stimulation (NMES) to the paretic arm has been proposed to improve movement affected by central nervous system lesions [4–7], but showed borderline effects on arm recovery according to recent systematic reviews [8–10]. Electrical stimulation (ES) can be used by patients with Correspondence: Megumi Shimodozono, Department of Rehabilitation and Physical Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 3930-7, Takachiho, Makizono-cho, Kirishima city, Kagoshima, 899-6603, Japan. Tel: +81-995-78-2077. Fax: +81-995-64-4045. E-mail: [email protected]
History Received 27 May 2013 Revised 23 September 2013 Accepted 25 October 2013 Published online 3 December 2013
hemiparesis who do not have sufficient residual movement to take part in volitional, active repetitive movement therapy [5]. However, when ES is associated with voluntary effort or movement—EMG-triggered ES or volitionally activated ES— the therapeutic effect might be enhanced compared with use of non-triggered electrical stimulation (cyclic NMES) [11]. To achieve motor recovery, volitional and repetitive task-specific training with gradual increases in difficulty is important [8, 12]. However, it is not only difficult but also ineffective for patients with severe arm impairment to perform repetitive taskspecific training even when functional electrical stimulation (FES) is employed [6, 13]. These observations motivated the idea that concurrent RFE and NMES may provide a more effective approach to rehabilitation than either modality alone, because effects of NMES may be enhanced by asking a patient with severe impairment to accompany the motion in terms of thought and, if possible, by actively tensing their muscles [6]. Here, more specifically, a novel approach ‘RFE under low-amplitude continuous NMES’ is proposed. The ‘low-amplitude continuous NMES’ used generates slight and continuous contraction in targeted paretic muscle but does not induce ‘passive’ limb/ joint movement while the patient remains at rest. This condition was selected to produce stretch reflex easily during RFE, even in the severely paretic (‘flaccid’) muscle.
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Department of Rehabilitation and Physical Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan and 2Department of Rehabilitation, Kagoshima University Hospital Kirishima Rehabilitation Center, Kagoshima, Japan
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The reflected movement would assist the patient’s efforts to move the affected joint and repetition of elicited movement may improve motor recovery [2, 3]. Thus, it is hypothesized that a novel approach, RFE under low-amplitude continuous NMES (RFE under NMES), is feasible for patients with severe arm impairment in the subacute phase of stroke. In addition, it was hypothesized that participants in the RFE-under-NMES programme or RFE programme alone will, at the end of training, show significantly larger improvements in motor control (motor impairment) of their severely affected arm than those assigned to conventional therapy. One of the most widely recognized and clinically relevant measures of motor impairment after stroke is the Fugl-Meyer Assessment [14–16]. The authors, therefore, conducted a randomized, controlled, observer-blinded, pilot trial to compare improvement in voluntary motor control—evaluated by the Fugl-Meyer Assessment Scale for arm (FMA)—in the sub-acute stages of stroke with severe arm impairment during a 4-week, 5 days/week, time-matched regimen of RFE under NMES, RFE alone or a conventional rehabilitation programme.
Methods
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interventions: (1) RFE-under-NMES, (2) RFE or (3) conventional rehabilitation (Figure 1) via a computer-generated blocked randomization sequence with a block size of 9. An independent researcher not involved in recruitment or measurement managed and concealed the randomization procedure. Participants were blinded to the study hypotheses. All procedures complied with the 1975 Declaration of Helsinki, as revised in 2008. Approval was received from the ethics committees of the study site and written informed consent was obtained from each participant. Interventions All participants, regardless of their group assignment, underwent training in 40-minute sessions on a 4-week, 5-day/week schedule. In addition, all participants performed 30 minutes/ day of dexterity-related training—that is, object-related reachto-grasp training—immediately after each treatment session. The total time of treatment for the arm was the same between the three groups. Patients also continued participating in a standard inpatient rehabilitation programme that included activities of daily living, physical therapy, mobility training and speech therapy.
Participants This study recruited 27 patients from the inpatient rehabilitation centre of a university hospital in Japan (Figure 1). Inclusion criteria were: (1) a new, single CT-confirmed stroke of 3–13 weeks duration; (2) severe arm impairment, FMA 20; and (3) an ability to follow simple directions. Exclusion criteria were (1) contraindication for ES, such as a pacemaker implant; (2) arm contractures or pain; (3) preexisting arm impairment; (4) cerebellar lesion; (5) unstable medical status; (6) perceptual, apraxic or cognitive deficits that would prevent adequate study participation; or (7) inability to provide informed consent. Design The study was a 4-week, randomized, observer-blinded, pilot trial. Participants were randomized to one of three Figure 1. Study recruitment and randomization. RFE, repetitive facilitative exercise; NMES, neuromuscular electrical stimulation.
RFE group The overall aspects of the RFE programme have been described previously [2, 3, 17, 18] and are only summarized here. Briefly, repetitive facilitative techniques were used to elicit movement of the shoulder, elbow and wrist in a manner designed to minimize synergistic movements. This technique involved the use of rapid passive stretching of the muscles in conjunction with tapping and rubbing the skin to assist in generating contraction of the targeted muscles. Participants were directed to concentrate on generating movement of the joint being treated while avoiding contraction of non-targeted muscles. Therapists supplemented the subject’s efforts as necessary to achieve full range of motion (ROM). Subjects’ efforts were directed with commands such as ‘bend/extend’ or ‘one, two, three . . .’.
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DOI: 10.3109/02699052.2013.860472
This study utilized three specific patterns at three joints: (1) shoulder flexion with the elbow bent at 90 in the supine position, (2) elbow extension in the supine position and (3) wrist dorsiflexion and forearm pronation with extension of the fingers in the supine position. Principles for selection and treatment using these three patterns included: (1) an emphasis on the proximal musculature given its role in stabilizing distal movements, (2) reduction of spasticity in elbow flexors and wrist flexors by reciprocal innervation, (3) gradual increases in movement from easier to more difficult with a goal of maintaining movement purity and avoiding synergy and (4) consideration of difficulties in eliciting separate movement of each finger for patients with severe impairment. Exercises were performed as two-to-three sets of 50 repetitions with an intervening 1–2 minute rest period. Thus, a total of 300–450 repetitions were performed during each session. Each RFE session was concluded with 30 minutes of object-related training involving activities such as reaching to grasp blocks of differing sizes with the affected arm or the use of arm skateboards or weighted sanders. Assistance with an unaffected limb was permitted. RFE-under-NMES group The RFE programme performed with this group was the same as that with the RFE group. In addition, constant lowamplitude NMES was simultaneously applied during RFE sessions. NMES was delivered using a portable surface neuromuscular stimulator (Trio 300, Ito Co., Ltd., Tokyo). The surface electrodes were arranged over the following muscles according to the three RFE patterns (i.e. three treated areas): anterior part of the deltoid muscle during shoulder flexion, triceps during elbow extension and wrist extensors (extensor digitorum communis) during wrist dorsiflexion and forearm pronation (Figure 2). The stimulation pulse was a symmetrical biphasic waveform, with a pulse width of 250 ms
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and frequency of 20 Hz. Intensity of the electrical current was adjusted to produce slight contraction of the target muscle without inducing obvious limb/joint movement while the subject remained at rest and subjectively comfortable. This low-amplitude NMES was continuously applied to the targeted musculature during RFE, but not provided with on/ off mode, EMG-triggered or position-triggered. As was true for the RFE participants, each session was concluded with an additional 30 minutes of object-related training. Control group Participants in the control group underwent a conventional arm rehabilitation programme of their involved limb on a dose-matched 5 days/week, 40-minutes/day, 4-week schedule as with those receiving RFE. Sessions consisted of (1) ROM exercises; (2) passive, assistive, active and progressive resistive exercise; (3) the use of skateboards or weighted sanders; and (4) pinching or grasping blocks of various sizes. As with the RFE or RFE-under-NMES participants, each control session was concluded with an additional 30 minutes of object-related training. Substantial efforts were made to ensure that the control and intervention groups were similar in terms of time spent in therapy sessions. Therapists recorded therapy duration (time), content and compliance in detail for each session with all groups. The duration, frequency and type of therapy provided to the control group were chosen to be consistent with those generally provided to patients with this level of motor impairment. Outcome measures The primary outcome measure used to assess motor impairment was FMA [14]. The FMA has a maximum score of 66, which indicates optimal recovery, and its psychometric
Figure 2. An example of repetitive facilitative exercise (RFE) under continuous surface neuromuscular electrical stimulation (NMES) to elicit right-wrist dorsiflexion. The patient is positioned with wrist flexion and forearm supination in the supine position. Surface electrodes are attached over the extensor digitorum communis. Intensity of electrical current is adjusted to produce slight contraction of the target muscle without obvious wrist/ finger movement while the subject remains at rest. (1) To induce forearm pronation and wrist extension with finger extension, the therapist holds the thumb in his/her hand, quickly pulls the 3rd, 4th and 5th fingers using the 2nd and 3rd fingers of his/her other hand and taps the ulnar side of the knuckle using his/her 1st finger (arrow). Simultaneously the therapist says, ‘Turn your hand and forearm as if you were stopping traffic’ and the patient attempts to perform wrist extension, forearm pronation and finger extension. (2) When the patient begins to show wrist extension and forearm pronation with extension of the fingers, the therapist provides slight resistance to the patient’s hand using his/her thumb and fingers. (3) The therapist’s right hand follows the voluntary motion of the patient. The therapist controls his/her assistance or slight resistance according to the patient’s voluntary motion. This pattern is repeated in two sets of 50 repetitions separated by a 1–2 minute rest period.
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properties have been shown to be satisfactory in patients with stroke [15, 16]. Greater motor severity as indicated by lower FMA scores is correlated with lower functional ability, such as spontaneous arm use for feeding, dressing and grooming [19]. Secondary outcome measures included active ROMs and the modified Ashworth scale (MAS) [20]. Active ROMs were measured for flexion at the shoulder and for extension at the elbow and wrist of the affected arm with a goniometer. This study assessed tone of the elbow and wrist flexors using MAS (range 0–5), which has been shown to be reliable in the assessment of arm spasticity [21]. This study also assessed adverse effects of treatment, such as muscle fatigue or local pain, by recording responses to questions asked of the patients. Outcome measures were assessed at the start of the trial and at its 4-week conclusion. A trained and experienced therapist who had no other contact with the study served as a blinded evaluator. Statistical analysis Non-parametric statistics were used for the analyses, because not all data met the criterion of normality. The primary endpoint was the outcome at trial conclusion (4 weeks). Change scores were calculated for all outcome measures (FMA, active ROMs and MAS) by taking the difference between baseline and 4 weeks. The Kruskal-Wallis procedure was used as a global test of differences in improvement among the three groups. When a significant p-value (p50.05) was obtained, post-hoc comparisons were performed using the MannWhitney U-test with Bonferroni correction (p50.05/n, where n ¼ 3 was the number of comparisons made).
Baseline characteristics were compared using the KruskalWallis test for continuous and ordinal variables or the chisquare test for observed frequencies and p Values50.05 were considered to be statistically significant. This study presents results as mean and standard deviation or median and range as appropriate. SPSS (version 19.0 software for Mac OS X) was employed for statistical analyses.
Results Participant characteristics Figure 1 illustrates the recruitment process. One hundred and forty-one candidates were screened for participation over the study’s recruitment period (Figure 1). Of these, 108 did not meet the inclusion criteria and six declined to give their consent. The remaining 27 were enrolled in the study, with nine randomly assigned to RFE under NMES, nine to RFE alone and nine to the control group. There were no drop-outs within the 4-week study period. Thus, data from 27 patients (nine patients in each group) were available for analysis (Figure 1). No adverse treatment effects, such as burns, skin allergic responses or muscle fatigue, were noted. The three groups did not differ significantly in terms of demographic characteristics—age, gender, stroke duration and stroke location—at entry or baseline measures of FMAs, active ROMs and MASs (Table I). Outcome measures Table II presents differences of outcome measures between baseline and 4 weeks under treatment as mean and standard deviation, median and range. Table II also shows comparisons among the three groups.
Table I. Baseline characteristics of participants (n ¼ 27)a.
Mean age, years Sex, male Time since stroke, weeks Side of motor deficit, right Type of stroke Infarction Haemorrhage Stroke location Basal ganglia Thalamus Internal capsule/corona radiata Territory of middle cerebral artery Cortex Brainstem FMA Active ROM Shoulder flexion Elbow extension Wrist extension MAS Elbow flexors Wrist flexors
Control group (n ¼ 9)
RFE group (n ¼ 9)
RFE-under-NMES group (n ¼ 9)
61.4 15.6 5 (56) 6.7 2.7 1 (11)
61.9 13.6 9 (100) 6.8 2.0 6 (67)
61.1 11.3 6 (67) 6.2 2.7 5 (56)
3 (33) 6 (67)
5 (56) 4 (44)
7 (78) 2 (22)
5 (56) 1 (11) 0 (0) 2 (22) 0 (0) 1 (11) 8.7 5.7
3 (33) 1 (11) 2 (22) 2 (22) 0 (0) 1 (11) 8.2 3.0
2 (22) 1 (11) 3 (33) 2 (22) 0 (0) 1 (11) 11.4 5.9
0.44b
5.1 15.3 1.4 4.3 0.0 0.0
4.8 10.8 21.3 37.8 1.8 5.3
8.1 20.1 10.2 29.9 2.1 4.8
0.71b 0.65b 0.74b
0.9 1.1 1.0 1.1
1.2 0.8 1.3 1.5
1.3 1.1 1.1 1.1
0.59b 0.93b
p Value 0.99b 0.26c 0.63b 0.15c 0.57c 0.98c
RFE, repetitive facilitative exercise; NMES, neuromuscular electrical stimulation; FMA, Fugl-Meyer Arm Motor Scale; ROM, Range of motion; MAS, Modified Ashworth Scale. a Values are mean standard deviation or number (percentage). b Kruskal-Wallis test. c 2 test.
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b
a
Wrist flexors
RFE, repetitive facilitative exercise; NMES, neuromuscular electrical stimulation; FMA, Fugl-Meyer Arm Motor Scale; ROM, range of motion; MAS, modified Ashworth scale. Values are mean standard deviation and median (range in parentheses). Change scores were created by subtracting baseline score from outcome score at 4 weeks. p Values indicate significance level of changes in outcome measures among the three groups using the Kruskal-Wallis test. *p50.017 vs control group (post-hoc test using the Mann-Whitney U-test with Bonferroni correction).
0.871
0.653
0.0 1.1, 0 (2–2) 0.1 1.2, 0 (2–2) 0.3 0.9, 0 (1–2) 0.6 1.3, 0 (1–3) 1.3 1.1, 2 (0–3) 1.3 1.5, 1 (0–4) MAS Elbow flexors
Wrist dorsiflexion
Elbow extension
0.9 1.1, 1 (0–3) 1.0 1.1, 1 (0–3)
0.4 0.9, 0 (1–2) 0.3 1.5, 0 (2–3)
1.2 0.8, 1 (0–2) 1.3 1.5, 1 (0–4)
1.6 1.1, 2 (0–3) 1.9 1.3, 2 (0–4)
1.3 1.1, 1 (0–3) 1.1 1.1, 1 (0–3)
1.0 1.0, 1 (0–3) 1.2 0.8, 1 (0–2)
0.352
0.034
0.057
37.4 43.4, 30 (0–144) 68.6 35.5, 80 (0–110)* 16.1 30.5, 0 (0–93) 28.4 37.5, 10 (0–93) 31.1 39.9, 15 (0–90) 5.7 17.0, 0 (0–51) 4.8 10.8, 0 (0–33) 21.3 37.8, 0 (0–101) 1.8 5.3, 0 (0–16) 17.2 33.7, 0 (0–98) 16.2 30.9, 0 (0–90) 0.8 2.3, 0 (0–7) Active ROM Shoulder flexion
5.1 15.3, 0 (0–46) 1.4 4.3, 0 (0–13) 0.0 0.0, 0 (0–0)
12.1 32.5, 0 (1–98) 14.8 31.2, 0 (0–90) 0.8 2.3, 0 (0–7)
33.2 44.8, 10 (0–126) 52.4 50.6, 85 (0–117) 7.4 17.2, 0 (0–51)
8.1 20.1, 0 (0–61) 10.2 29.9, 0 (0–90) 2.1 4.8, 0 (0–14)
45.6 49.9, 30 (0–144) 78.8 24.9, 82 (27–110) 18.2 30.5, 0 (0–93)
0.014 18.4 15.7, 15 (6–57)* 29.9 13.7, 27 (14–63) 9.7 9.1, 9 (0–30) 8.2 3.0, 8 (4–14) 13.2 7.9, 11 (6–32) FMA
8.7 5.7, 6 (4–18)
4.6 5.2, 4 (5–14)
17.9 9.5, 15 (5–36)
11.4 5.9, 13 (4–20)
Difference Week 4 Baseline Difference Baseline Week 4 Baseline
Difference
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Fugl-Meyer arm motor scale
Week 4
RFE-under-NMES group (n ¼ 9) RFE group (n ¼ 9) Control group (n ¼ 9)
Table II. Changes in outcome measures at the end of treatment in the three groups (n ¼ 27)a.
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Comparison among the three groups, p Valueb
DOI: 10.3109/02699052.2013.860472
The RFE-under-NMES group displayed a median increase of 15 points at the end of training on the study’s primary outcome variable, the FMA, relative to median increases of 9- and 4-points in the RFE and control groups, respectively. The difference in the median increases between the RFE-under-NMES and RFE groups was 6-points and the difference between the RFE-under-NMES and control groups was 11-points. There were significant differences among the three groups over time (p ¼ 0.014). The post-hoc test revealed a significant increase with RFE-under-NMES compared with the control group (p ¼ 0.003), but not with RFE alone (p ¼ 0.092). The RFE-only group performed better, but not significantly better, than the control group (median of 5-points; p ¼ 0.199). Active range of motion The RFE-under-NMES group displayed a median increase of 80 in elbow extension at the end of training on active ROM, relative to 15 and 0 increases in the RFE and control groups, respectively. The difference in the median increases between the RFE-under-NMES and RFE groups was 65 and the difference between the RFE-under-NMES and control groups was 80 . There were significant differences over time among the three groups (p ¼ 0.034). The post-hoc test revealed a significant increase with RFE-under-NMES compared with the control group (p ¼ 0.011), but not with RFE alone (p ¼ 0.081). RFE alone performed better, but not significantly better, than the control group (p ¼ 0.308). With shoulder flexion and wrist dorsiflexion, however, there were no significant differences among the groups over time (p ¼ 0.057 and p ¼ 0.352, respectively) (Table II). Modified Ashworth scale There were no significant differences in elbow flexion or wrist flexion among the groups over time (p ¼ 0.653 and p ¼ 0.871, respectively) (Table II).
Discussion This study represents the first randomized controlled trial of RFE combined with simultaneous, continuous NMES compared with duration-matched RFE alone or conventional rehabilitation in the treatment of stroke-related severe arm impairment. At least for subjects with sub-acute stroke, RFE under NMES produced significantly better improvement in the primary outcome variable, FMA, compared with conventional rehabilitation. Active ROM in the elbow joint also showed significant improvement, but spasticity, as measured with MAS, appeared unaltered by either intervention. In addition, this pilot study demonstrated practicality or feasibility of this treatment regimen and of the research project overall. Motor performance The RFE-under-NMES programme demonstrated both statistically and clinically significant improvement over conventional rehabilitation because the minimal clinically important difference of the FMA is 6.6 [22]. The greater improvement
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could not be due solely to the high degree of repetition of the facilitative technique itself because the lessening of motor impairment as measured by FMA or active ROM in the RFE group was not significantly greater than that of the control group. Further, there were no statistically significant differences in improvement between the RFE-under-NMES group and the RFE group. It remains unclear whether differences in improvements were due to NMES itself or the concurrent application of RFE. However, it is believed that the combination of the two was required for the observed difference in improvement because more positive results were found when ES to the arm was triggered by voluntary movement than when non-triggered simple electrical muscle stimulation was used [11]. It has been difficult to improve arm recovery in patients with severe impairment due to stroke; recovery of movement remains a problem [23]. Although traditional treatment methods for patients with severe impairment have included passive and traditional facilitation techniques, the benefits are far more limited than one would like [24]. Recently, a number of interventions have been developed in which robotic therapy provides a large beneficial effect, with limited evidence that ES and other interventions provide large improvement in function [23, 25]. The lessening of motor impairment with the RFE-underNMES treatment is consistent with results obtained from previous studies that used ES for patients with stroke [5, 6, 10, 11]. In the present study, however, there are differences both in the application of ES and in the severity of motor impairment. There have been few studies investigating efficacy of ES on a severely impaired arm in the sub-acute stage of stroke: 3 weeks of cyclic ES application (during which the patients focused on the movement and imitated the function of the arm) to the deltoid muscle, supraspinatus and wrist extensors on the affected arm for 30 minutes/day led to improved motor recovery that persisted for at least 6 months [26]. In the acute stage of stroke, a minimum of 10 hours (30 minutes, 5-times per week for a period of 4 weeks) of NMES in combination with regular rehabilitation improves the recovery of arm function [27]. The total dose of ES, 13.3 hours in the current study, may support this previous finding. Optimal stimulation parameters, dosage and optimal exercise combined with ES remain to be investigated in the future. Mechanism of RFE under NMES for lessening motor impairment Sub-motoric stimulation of the upper paretic extremity has been used primarily to reduce spasticity and secondarily to improve motor activation through increased afferent inputs [6, 28, 29]. The low-amplitude intensity of NMES was selected because it was postulated that it might be important for motor recovery to repeat active-assistive movement— concurrent combination of patient efforts to move and facilitative technique under continuous ES—compared with mere passive movement (motoric/cyclic ES). This hypothesis is based on Hebbian long-term potentiation and other mechanisms that determine synaptic efficacy [30]. In addition, electrically mediated repetitive movement facilitates motor relearning to make use of central neuroplasticity [6].
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Anti-spastic effects might also contribute to the benefits of treatment as electrical contraction of paretic musculature leads to reciprocal inhibition of spastic antagonists through the stimulation of spinal interneurons [6]. In the present study, there were no significant differences in spasticity measured by MAS either within (data not shown) or between groups. This might be due to a relatively low grade of spasticity, even in the initiation of the current intervention. Clinical applicability of RFE under NMES RFE, although requiring intense therapist involvement, has an advantage in that it requires no equipment and can be performed anywhere once a therapist has mastered the techniques, which are based on those that are already a part of their training [3]. As shown in the present study, however, it might be inadequate for patients with severe motor impairment to realize improvement solely with use of RFE. It might be relatively easy for a therapist to select or adjust the amount of ES assistance during RFE; the therapist can select appropriate joints to be treated or adjust electrical intensity according to the clinical symptoms, such as severity of motor impairment or general physical and cognitive condition of the patient [6]. In addition, a surface neuromuscular stimulator is relatively moderately priced and portable. It may be beneficial to start with a programme including RFE under NMES in the case of severe impairment (i.e. active EMG not generated) and, when motor control has improved, switch to a programme including EMG-triggered ES for functional training [6]. In the RFE-under-NMES session, taking an elbow extension pattern for example, there is an elbow flexion movement accompanied with relaxation of the triceps between two repetitions of elbow extension. The elbow flexion movement might be inhibited by NMES continuously applied to the targeted muscle (triceps). In the authors’ experience, however, this problem was not encountered, for two reasons. The NMES was adjusted to low-enough amplitude so as not to induce obvious limb/joint movement and the opposite movement was primarily a passive one performed by the therapist. Application involving an interval without NMES (i.e. off mode) during the opposite movement may be preferable, but would result in a more complicated method. The present study revealed no adverse side-effects such as local pain, muscle fatigue or increased muscle tone. The specific NMES parameters that are optimal for reducing motor deficits in the neurologically impaired hand remain unclear, although previous work has examined variable patterns of stimulation and the fatigue effects of NMES in the arm [4]. To avoid muscle fatigue during muscle strengthening it is important to optimize the stimulation strategy because a high intensity of stimulation and stimulation frequencies higher than 50 Hz accelerate the rate and level of fatigue [6]. Limitations The major limitation was a small sample size with probability of imbalance at baseline since the pilot study was designed to make an initial assessment of the feasibility and to calculate required sample size for further study. All participants
DOI: 10.3109/02699052.2013.860472
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tolerated interventions of RFE or RFE under NMES well and there were no adverse effects. Using the SD in FMA of 11 and the mean difference of changes in FMA of 14 found in this investigation would result in the requirement for a study with two independent groups (control group vs RFE-underNMES group) and a power of 80% to have 11 subjects in each group. Similarly, using the SD in FMA of 7 and the mean difference of changes in FMA of 7 found in this investigation would result in the requirement for a study with two independent groups (control group vs RFE group) and a power of 80% to have 32 subjects in each group. The study has a number of other limitations. Mixtures of stroke location and type, as well as varying levels of impairment and the restriction of participants to the subacute stages of stroke render generalization to other situations difficult. Other weaknesses are a lack of follow-up after the end of treatment and the inability, thus far, to assess the sustainability of these findings.
Conclusion A combination of RFE and concurrent low-amplitude continuous NMES may be associated with additional recovery following motor impairment in patients with severe arm impairment in the sub-acute phase of stroke. A further multicentre randomized clinical trial would require at least 11 participants in order to demonstrate a clinically meaningful difference in arm motor recovery between the conventional arm rehabilitation group and the RFE-under-NMES group.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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