Motor Training of Upper Extremity with Functional. Electrical Stimulation in Early Stroke Rehabilitation

Transcription

1 FES in early stroke rehabilitation 1 Motor Training of Upper Extremity with Functional Electrical Stimulation in Early Stroke Rehabilitation Sabine Mangold 1, PhD; Corina Schuster 2, MPTSc; Thierry Keller 1,3, PhD; Andrea Zimmermann- Schlatter 2, MPTSc; Thierry Ettlin 2, MD 1 Balgrist University Hospital, Spinal Cord Center, Zurich, Switzerland 2 Reha Rheinfelden, Rheinfelden, Switzerland 3 Automatic Control Laboratory, Swiss Federal Institute of Technology (ETH) in Zurich, Switzerland Address for correspondence: Dr. Sabine Mangold Balgrist University Hospital Spinal Cord Center / Research Forchstrasse Zurich Switzerland smangold@balgrist.unizh.ch Tel Fax Running title: FES in early stroke rehabilitation

2 FES in early stroke rehabilitation 2 ABSTRACT Background. Functional electrical stimulation (FES) allows active exercises in stroke patients with upper extremity paralysis. Objective. To investigate the effect of motor training with FES on motor recovery in acute and subacute stroke patients with severe to complete arm and/or hand paralysis. Methods. 23 acute and subacute stroke patients were randomly assigned to the intervention (n=12) and control group (n=11). Distributed over four weeks, FES training replaced twelve conventional training sessions in the intervention group. An Extended Barthel Index (EBI) subscore assessed the performance of activities of daily living. The Chedoke McMaster Stroke Assessment (CMSA) measured hand and arm function and shoulder pain; the modified Ashworth scale (MAS) assessed resistance to passive movement. Assessments were performed prior to and following the end of the training period. Results. The EBI subscore and CMSA arm score improved significantly in both groups. The CMSA hand function improved significantly in the FES group. Resistance to passive movement of finger and wrist flexors increased significantly in the FES group. However, shoulder pain did not change significantly. None of the outcome measures demonstrated significant gain differences between either groups. Conclusions. We did not find clear evidence for superiority or inferiority of FES. Comparisons with other studies led to the conclusion that the number of sessions should be doubled to achieve superiority. Key words: Electric Stimulation, Cerebrovascular Stroke, Hemiplegia, Upper Extremity

3 FES in early stroke rehabilitation 3 INTRODUCTION Impaired motor control of the upper extremity is one of the most frequent consequences of stroke. Only 13% of the subjects examined in the first two weeks did not suffer arm paralysis, 1 and six months after the injury, severe motor deficits remain in 30% 66% of stroke survivors. 2 In order to improve arm function, standard therapeutic interventions are used, such as Bobath therapy, 3 constraint-induced therapy, 4 and task specific motor relearning program. 5 Although further research is needed to find out which method is superior to others, there is evidence that strategies which impose a higher level of activity in the paretic muscles should be preferred. 6 This is an ambitious demand for stroke subjects with very little voluntary function of the paretic limb. One method that does not need any voluntary muscle function during motor tasks is functional electrical stimulation (FES). In the last years, various therapeutic objectives were achieved through FES, such as facilitation of voluntary movements, improvement of manual dexterity and activities of daily living (ADL), 7-11 and reduction of shoulder pain 12 and spasticity. 13 These studies demonstrated that electrical stimulation has positive effects on upper limb motor function. However, in some studies, FES was applied in addition to conventional therapy or was compared with placebo therapy, reducing the certainty as to whether FES effects can be attributed to either the additional therapeutic time for motor training or the application of the particular method. Thus, more studies are necessary to provide the same amount of motor training to the intervention and control group. Moreover, in standard rehabilitation, there are limitations in the provision of additional therapeutic

4 FES in early stroke rehabilitation 4 time, thus, integration of the new approach in the normal clinical treatment schedule is more feasible than an additional application. In order to comply with these demands, we applied FES under the realistic rehabilitation conditions of our country, i.e. not taking additional time in the clinical routine and not exceeding the normal rehabilitation period. We examined stroke patients with severe to complete paralysis of the arm and/or hand in their acute or subacute phase, because there is little voluntary function of the paretic limb. Hence sophisticated methods to achieve activity at a higher level during exercise are needed. Until now, the effects of FES on this group of patients have not been sufficiently examined. Accordingly, our purpose was to compare motor recovery in severely affected stroke patients in early rehabilitation who were treated with FES or conventional motor training under normal clinical conditions. METHODS Subjects Subjects were recruited from an inpatient rehabilitation stroke center. The local ethics committee approved the study protocol, and informed written consent to participate in the study was obtained from all subjects. In cases of writing disability, one witness confirmed the subject s informed consent. First-time stroke survivors admitted to the rehabilitation center were screened for eligibility. They were included if they met the following criteria: 18 years or older; first cerebrovascular accident (CVA) happened at least 2 and maximum 18 weeks ago; brain in-

5 FES in early stroke rehabilitation 5 farct or brain hemorrhage localized in the cortex, sub-cortex or stem ganglia; severe hemiparesis to complete hemiplegia of the arm and/or hand (maximum values of the Chedoke McMaster Stroke Assessment (CMSA) for the arm and hand: 3); with or without aphasia; ability to understand the study and to provide informed consent; ability to sit in a wheelchair or on a chair with no contact to the back rest. Subjects were excluded in the cases of: a pace-maker or other stimulation devices; reanimation with cardiac stimulation; pregnancy; epilepsy or similar neurological disorders; prosthesis of bones or joints in the local region of the electrical treatment; skin injuries, rash, burns, fresh scars, or inflammations at the place of stimulation; former CVA or other brain impairments; severe impairment of sensitivity and proprioception (according to clinical estimation); shoulder-hand-syndrome on the affected side; constant, strong pain in the shoulder of the affected side (CMSA value for painful shoulder: 1-3); considerable subluxation (>20 mm) of the affected shoulder joint. Therapies and FES intervention Subjects included in the 4-week training program were randomly assigned to the intervention (FES and conventional training) or to the control group (conventional training) using a computer-generated randomization list. In both groups, three to five 45 minute occupational therapy sessions for the upper extremity training were scheduled per week and adapted to the patient s resilience via a number of accompanying therapies, including: conventional physiotherapy, speech therapy, creative therapy, and neuropsychological training.

6 FES in early stroke rehabilitation 6 In the intervention group, FES made up three of the occupational therapy training sessions per week. If the patient had more functional training sessions per week, they were carried out in conventional therapeutic form. Conventional occupational therapy for upper extremity training mainly comprised mobilization and selective movements of the shoulder, hand, and arm, and grasping exercises, supported by the therapist if necessary. To a small degree, ADL (e.g. mixing cream, pouring water into a glass) and sensitivity training were practiced, as supported by the therapist or performed bimanually. FES was carried out with the portable system Compex Motion 14 using standard selfadhesive surface electrodes. The programmable FES system, including four currentregulated stimulation channels, was used to generate custom-made movement sequences. Proximal muscles (e.g. anterior deltoid muscle, m. triceps brachii) as well as distal muscles (finger extensors and finger flexors) were integrated into the stimulation sequence in order to reach, grasp, and release an object. Therapists selected the muscles to be stimulated with respect to the following criteria: muscles that a) had priority for the individual s current rehabilitation process and b) helped in the grasp process (reach, grasp, and release an object). If necessary, therapists manually treated spasticity, used a help arm to reduce gravity, and provided manual assistance to support the grasp action and to prevent movements that might cause damage such as pathologic scapula movements. Before the FES treatment period, stimulation thresholds for each muscle and the set-up were determined in a one hour single FES session. If the patients arm function changed during the 4-week FES training, stimulation programs and supporting measures were adapted.

7 FES in early stroke rehabilitation 7 Each FES training session consisted of a program including repetitive grasping functions. After the system was donned, stimulation current amplitudes were individually set for each muscle group to achieve sufficient functional contraction force without pain or discomfort. The stimulation frequency was 25 Hz. The pulse width varied between 0 and 250 microseconds to achieve controlled muscle contraction. Every reach-grasp-release cycle consisted of different steps, e.g. stretching the arm with hand opening, hand closing, arm moving back etc., triggered by a push button. Figure 1 shows a typical cycle. The subjects were encouraged to make volitional attempts to reach, open the hand, and close the hand simultaneously with the stimulation. They could either trigger the stimulation sequence themselves or the therapist performed this task, indicating verbally to the subject when the next step was initiated. Grasping objects were used such as a small bottle, ball, tube, tin, glass, or handkerchief. At the end of the treatment the system was doffed. The FES session lasted 45 min, consisting of about min donning, other preparations (e.g. treating spasticity), and doffing, leaving min for functional training. Figure 1 should be placed here Assessments For baseline comparability, the following data were assessed: patients age, gender, time poststroke, affected side, diagnosis (hemorrhagic or nonhemorrhagic stroke), and hemineglect. Additionally, the Extended Barthel Index (EBI) was selected to determine

8 FES in early stroke rehabilitation 8 the level of independence with respect to ADL and the CMSA to assess motor recovery of the paretic upper limb. The EBI contains 16 items (each rated with 0 to 4 points), including ADL, mobility, bowel and bladder functions, communication, cognitive, and social functions. Baseline outcome measures were assessed twice in both groups, i.e. eight days and one day before the beginning of the 4-week program. Post-treatment assessments were performed at the end of the 4-week program. Follow-up measurements (six months after the beginning of the treatment) will be published when all patients have finished followup. An EBI subscore, including four items focusing on upper extremity function (Table 1), and the arm and hand function CMSA score of the paretic arm were selected as primary outcome measures. Each CMSA item score ranges from no or almost no voluntary muscle activity (1 point) to mean normal arm respectively hand function regarding to movement control over its full extent and movement coordination (7 points). As secondary outcome measures, the item shoulder pain of the CMSA and the modified Ashworth scale (MAS) were chosen. Shoulder pain ranges from constantly strong shoulder pain in the shoulder and other parts (1 point) to no shoulder pain and no prognostic indicators (7 points). The MAS measures non-voluntary resistance against passive movement. It ranges from no increase in muscle tone (0 point) to rigidity of the affected parts in flexion or extension (5 points). The following muscles were assessed with the MAS: finger flexors, finger extensors, wrist flexors, wrist extensors, pronators, supinators, elbow flexors, and elbow extensor.

9 FES in early stroke rehabilitation 9 The nursing staff assessed the EBI, and two trained physiotherapists performed the CMSA and MAS. Due to practicality, blinding of patients and assessors was not feasible. The reliability and validity of the CMSA, 15 EBI, 16 and MAS 17,18 have been confirmed. Table 1 should be placed here Data analysis Data analysis was performed by intention-to-treat. Analysis of Kurtosis and Skewness was done for age, time poststroke, and number of occupational therapy sessions of upper extremity training to select adequate statistical tests for the evaluation of baseline comparability. Baseline comparability was evaluated with the following statistical tests: Age was tested with the independent t-test (Levene s test for equality of variances). Time poststroke and number of occupational therapy sessions were evaluated with the 2-tailed Mann- Whitney U test for nonparametric data because they were not normally distributed. This test was also used for EBI and CMSA scores (mean baseline values), because they are ordinal parameters. The number of subjects in each group was compared with the χ 2 - test. Pearson 2-sided χ 2 -test was used to evaluate proportional differences in both groups regarding gender, diagnosis (hemorrhagic or non-hemorrhagic stroke), affected side, dominant arm affected, and hemineglect.

10 FES in early stroke rehabilitation 10 The Wilcoxon Signed Ranks Test was applied to examine pre-post changes in each group, comparing mean baseline values with the values at the end of the 4-week program. The differences of functional gains between both groups were analyzed with the Mann Whitney U test. All statistical analyses were performed with SPSS 11.5 for Windows (SPSS, Chicago, IL). Results were accepted as statistically significant at p The minimal clinically important difference (MCID) was defined as a change of at least 9% of the maximum score of the scale. 19 With this 9% threshold, the MCID for the EBI subscore was 1.4 points, for each CMSA item score 0.6, and for each MAS item score 0.45 points. Additionally, effect sizes (Cohen's d) of the primary outcome measures were determined for each group (within-group changes) and for gain differences between both groups. Cohen's d was calculated using the means (m) and standard deviations (σ) of the pretreatment and post-treatment values respectively the gains of both groups. The calculation was performed with the Microsoft Office Excel 2003 software using the following formula: Cohen's d = m 1 -m 2 /σ pooled where σ pooled = [(σ 1 ²+σ 2 ²)/2] Based on the measured effect sizes, an alpha level of 0.5, and a test power of 0.8, the optimal group size was derived from a table. 20

11 FES in early stroke rehabilitation 11 RESULTS Baseline data 23 subjects were enrolled, 11 in the control and 12 in the FES group. All subjects completed the study. Subjects baseline characteristics are shown in Table 2 and 3. Baseline comparability was confirmed for all demographic data and primary outcome measures except one: The FES group had a significantly higher EBI subscore than the control group (p=0.013). Table 2 should be placed here Therapy sessions Nine patients participated in 11 to 12 FES sessions. Singular skipping of treatment was due to causes unrelated to FES. Three subjects stopped FES after 3 to 7 FES sessions. One of them could not tolerate the stimulation intensity that was necessary for a functional muscle contraction; another stopped FES because he developed high finger flexors tonus during the session, although not stimulated. In their remaining therapy sessions, these subjects received conventional therapy. In total, the subjects in the control group had 8-15 therapy sessions (median 13) and in the FES group (median 13), including FES and conventional therapy sessions. The number of therapy sessions was not significantly different in either group (p=0.38).

12 FES in early stroke rehabilitation 12 Movement quality FES generated distinct finger and arm movements, but the therapist had to provide manual support when reaching the object and hand opening. Hand closure and retracting the arm were not manually supported. All subjects used the help arm to reduce gravity. Primary outcome measures The FES group showed significant improvements in all primary outcome measures (EBI subscore, CMSA arm and hand) from pre-treatment to post-treatment (Table 3; Figure 2). This was also true for the control group with the exception that CMSA hand function only barely reached the level of significance (p=0.06). Gains from pre-treatment to posttreatment were not significantly different between either group (Table 3; Figure 2). Table 3 should be placed here Figure 2 should be placed here Clinical importance according to the MCID was found for the following primary outcome measures (Table 3): In the control group, the gains of the median EBI subscore (3 points) and CMSA arm score (1 point) were clinically important, and in the FES group

13 FES in early stroke rehabilitation 13 the EBI subscore (1.5 points). Group differences of median EBI subscore gains (1.5 points higher in the control group) and of the CMSA arm score gains (1 point higher in the control group) were clinically important. Cohen proposed labeling effect sizes of 0.2 as small, 0.5 as medium, and 0.8 or higher as large. 21 According to this classification, pre-post effect sizes of the primary outcome measures were small to high (Table 4), and effect sizes of gain differences between groups were small to medium (0.27 to 0.62). Hence, for medium effect sizes, "=0.05, and test power = 0.8, the optimum sample size would be 50 subjects per group and for small effect sizes 310 subjects per group. 20 Table 4 should be placed here Secondary outcome measures The baseline MAS score was 0 for 22 subjects for finger extensors, wrist extensors, and supinators. Finger flexors, wrist flexors, and pronators had median baseline values between 1.25 and 3, and elbow extensors a median value of 0 in the FES group and 0.5 in the control group. Nine subjects in each group had a baseline CMSA shoulder pain score of 6 (without pain but having at least one prognostic indicator such as very low arm function or abnormal positioning of the scapula). With the small sample size, secondary outcome measures did not show significant changes within each group from pre-treatment to post-treatment, with the exception of a significant and clinically important increase of the MAS of finger and wrist flexors in the

14 FES in early stroke rehabilitation 14 FES group (Table 3). However, no secondary outcome measures demonstrated significant or clinically important gain differences between either group. DISCUSSION We investigated changes of upper extremity function in stroke subjects with severe paralysis. Control subjects received conventional upper extremity motor training. Distributed over four weeks, FES training replaced twelve conventional therapy sessions in the intervention group. The total number of therapy sessions did not differ significantly. Primary outcome measures, i.e. the EBI subscore and the CMSA (arm and hand), improved significantly in both groups except the CMSA hand score in the control group (p=0.06). According to the MCID, only the gains of the EBI subscore in the control group (3 points) and FES group (1.5 points) and the gain of the CMSA arm score in the control group (1 point) were clinically important. Having 0 to 2 points per EBI item at baseline, a change of 1.5 points on the EBI subscore indicates subject fluxuation in one or two items from inability to performance of some tasks; or from needing significant assistance to minor assistance; or from requiring minor assistance to achieving independence with adaptive equipment (Table 1). In their baseline CMSA arm score, all subjects but one had 1 or 2 points. For subjects starting at 1 point, an increase of 1 point indicated the achievement of the ability to resist passive shoulder abduction and to extend the elbow with facilitation. For those who had these functions at baseline, a change of 1 point indicated the ability to touch the chin and the contralateral knee.

15 FES in early stroke rehabilitation 15 The statistic findings are in accordance with other studies, showing significant improvements with only conventional therapy or additional electrical stimulation within several weeks during the acute phase, as pertaining to the voluntary muscle function of the affected upper limb and on ADL. 7,22 The effect sizes are in the same magnitude found in comparable studies, e.g for the Barthel Index 23 or 0.73 for the Fugl-Meyer gain scores. 24 We found no significant differences between functional improvements of the intervention and the control group; but there were clinically important group differences of median EBI subscore and CMSA arm score, both favoring the control group. In other studies for comparable subjects, group differences of similar functional tests were inconsistent. In these studies, some parameters did not show significant group differences, and other parameters demonstrated significantly better gains in the intervention group when compared to the control group, despite similarly small group sizes. 8,10,24,25 The lack of significant group differences in our study might not only be due to a small group size, but also to the low number of FES sessions. In other studies on acute stroke patients, various frequencies of stimulation sessions were applied: from 24 up to 120 sessions. 8,10,24,25 Furthermore, 25% of our subjects had only seven or less stimulation sessions, reducing the potential effect of FES. The donning and doffing of the system reduced the effective time for exercises in the FES group, suggesting that control subjects had clinically important, though not statistically significant higher gains of the EBI subscore and CMSA arm score. Baseline differences might also be responsible for these results. The proportion of subjects with hemineglect was higher in the FES group, reducing the motor recovery potential. 26 The dominant hand was more frequently affected in the control group. Due to higher motor awareness of the dominant hand, 27 the dominant side pos-

16 FES in early stroke rehabilitation 16 sibly had the potential for greater improvement. Furthermore, the control group had a significantly lower EBI subscore than the FES group at baseline. As the EBI is a bimanual assessment, the control group possibly had lower values because dominant hands were more frequently affected. This could be a reason for a better EBI subscore gain in the control group because the non-dominant, non-affected hand started from lower dexterity than the dominant, non-affected hand, resulting in a better improvement potential. Considering either that the stimulation of antagonist muscles might decrease spastic muscle tonus via reciprocal inhibition or that the stimulation fatigues spastic muscles, it was theorized that electrical stimulation could help reducing spasticity. However, resistance to passive movement showed no significant gain differences between both groups in our study. This corresponds to the results of other studies with the same group of subjects. 8,25 Stroke is often associated with shoulder pain. In stroke patients with severe sensorimotor deficits, the occurrence increases from 18% in the first week to 29% after one month and to 47% after six months. 28 At baseline, most of our subjects were without shoulder pain. There was no significant change of shoulder pain within the groups during the 4- week program and no significant gain difference between either group. Electrical stimulation can be used to treat shoulder pain, but our stimulation protocol was not adjusted to this special objective. Furthermore, beneficial effects of FES become obvious in subjects who already have developed shoulder pain 29 and not in groups including only few subjects with shoulder pain. 12,30,31 Our study was performed with a small group of patients, and group imbalances weakened the validity of the inter-group comparisons. Hence, the following conclusions have to be appraised in this context.

17 FES in early stroke rehabilitation 17 In acute, severely affected stroke patients, our stimulation protocol (12 sessions with 30 min stimulation time) does not induce superior improvements compared to the same amount of conventional upper extremity motor training. We assume that within normal rehabilitation conditions in our country, it would be necessary for people to continue FES themselves at home. This would probably require a simpler stimulation protocol. Further studies have to be carried out to identify the required minimum number of FES training sessions and the efficiency of different stimulation protocols. ACKNOWLEDGMENTS The authors thank physicians of the Reha Rheinfelden in Switzerland for assessing subjects for eligibility, occupational therapists, physiotherapists, and nursery staff for thoroughly carrying out the treatment and assessment, and all patients for their participation in the study. This work was supported in part by the National Center of Competence NCCR: Plasticity and Repair. REFERENCES 1. Parker VM, Wade DT, Langton Hewer R. Loss of arm function after stroke: measurement, frequency and recovery. Int Rehabil Med. 1986;8(2):69-73.

18 FES in early stroke rehabilitation Kwakkel G, Kollen BJ, van der Grond J, Prevo AJ. Probability of regaining dexterity in the flaccid upper limb: impact of severity of paresis and time since onset in acute stroke. Stroke. 2003;34(9): Bobath B. Adult hemiplegia: evaluation and treatment. London, United Kingdom: Heinemann Medical Books; Morris DM, Taub E, Mark VW. Constraint-induced movement therapy: characterizing the intervention protocol. Eura Medicophys. 2006;42(3): Langhammer B, Stanghelle JK. Bobath or motor relearning programme? A comparison of two different approaches of physiotherapy in stroke rehabilitation: a randomized controlled study. Clin Rehabil. 2000;14(4): Woldag H, Hummelsheim H. Evidence-based physiotherapeutic concepts for improving arm and hand function in stroke patients: a review. J Neurol. 2002;249(5): Berner YN, Lif Kimchi O, Spokoiny V, Finkeltov B. The effect of electric stimulation treatment on the functional rehabilitation of acute geriatric patients with stroke--a preliminary study. Arch Gerontol Geriatr. 2004;39(2): Popovic MB, Popovic DB, Sinkjaer T, Stefanovic A, Schwirtlich L. Clinical evaluation of functional electrical therapy in acute hemiplegic subjects. J Rehabil Res Dev. 2003;40(5): Popovic MB, Popovic DB, Schwirtlich L, Sinkjaer T. Functional electrical therapy (FET): clinical trial in chronic hemiplegic subjects. Neuromodulation. 2004;7(2):

19 FES in early stroke rehabilitation Popovic MR, Thrasher TA, Zivanovic V, Takaki J, Hajek V. Neuroprosthesis for retraining reaching and grasping functions in severe hemiplegic patients. Neuromodulation. 2005;8(1): Popovic DB, Popovic MB, Sinkjaer T, Stefanovic A, Schwirtlich L. Therapy of paretic arm in hemiplegic subjects augmented with a neural prosthesis: a cross-over study. Can J Physiol Pharmacol. 2004;82(8-9): Chae J, Yu DT, Walker ME, et al. Intramuscular electrical stimulation for hemiplegic shoulder pain: a 12-month follow-up of a multiple-center, randomized clinical trial. Am J Phys Med Rehabil. 2005;84(11): Ring H, Rosenthal N. Controlled study of neuroprosthetic functional electrical stimulation in sub-acute post-stroke rehabilitation. J Rehabil Med. 2005;37(1): Popovic MR, Keller T. Modular transcutaneous functional electrical stimulation system. Med Eng Phys. 2005;27(1): Gowland C, Stratford P, Ward M, et al. Measuring physical impairment and disability with the Chedoke-McMaster Stroke Assessment. Stroke. 1993;24(1): Jansa J, Pogacnik T, Gompertz P. An evaluation of the Extended Barthel Index with acute ischemic stroke patients. Neurorehabil Neural Repair. 2004;18(1): Gregson JM, Leathley M, Moore AP, Sharma AK, Smith TL, Watkins CL. Reliability of the Tone Assessment Scale and the modified Ashworth Scale as clinical tools for assessing poststroke spasticity. Arch Phys Med Rehabil. 1999;80(9):

20 FES in early stroke rehabilitation Pandyan AD, Johnson GR, Price CI, Curless RH, Barnes MP, Rodgers H. A review of the properties and limitations of the Ashworth and modified Ashworth Scales as measures of spasticity. Clin Rehabil. 1999;13(5): Hsieh YW, Wang CH, Wu SC, Chen PC, Sheu CF, Hsieh CL. Establishing the minimal clinically important difference of the Barthel Index in stroke patients. Neurorehabil Neural Repair. 2007;21(3): Bortz J, Lienert GA. Kurzgefasste Statistik für die klinische Forschung. Leitfaden für die verteilungsfreie Analyse kleiner Stichproben. Berlin, Germany: Springer-Verlag; Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale, NJ: Lawrence Earlbaum Associates; Yozbatiran N, Donmez B, Kayak N, Bozan O. Electrical stimulation of wrist and fingers for sensory and functional recovery in acute hemiplegia. Clin Rehabil. 2006;20(1): Houlden H, Edwards M, McNeil J, Greenwood R. Use of the Barthel Index and the Functional Independence Measure during early inpatient rehabilitation after single incident brain injury. Clin Rehabil. 2006;20(2): Chae J, Bethoux F, Bohine T, Dobos L, Davis T, Friedl A. Neuromuscular stimulation for upper extremity motor and functional recovery in acute hemiplegia. Stroke. 1998;29(5): Powell J, Pandyan AD, Granat M, Cameron M, Stott DJ. Electrical stimulation of wrist extensors in poststroke hemiplegia. Stroke. 1999;30(7):

21 FES in early stroke rehabilitation Siekierka-Kleiser EM, Kleiser R, Wohlschläger AM, Freund HJ, Seitz RJ. Quantitative assessment of recovery from motor hemineglect in acute stroke patients. Cerebrovasc Dis. 2006;21(5-6): Daprati E, Sirigu A. Laterality effects on motor awareness. Neuropsychologia. 2002;40(8): Ratnasabapathy Y, Broad J, Baskett J, Pledger M, Marshall J, Bonita R. Shoulder pain in people with a stroke: a population-based study. Clin Rehabil. 2003;17(3): Church C, Price C, Pandyan AD, Huntley S, Curless R, Rodgers H. Randomized controlled trial to evaluate the effect of surface neuromuscular electrical stimulation to the shoulder after acute stroke. Stroke. 2006;37(12): Chantraine A, Baribeault A, Uebelhart D, Gremion G. Shoulder pain and dysfunction in hemiplegia: effects of functional electrical stimulation. Arch Phys Med Rehabil. 1999;80(3): Renzenbrink GJ, IJzerman MJ. Percutaneous neuromuscular electrical stimulation (P-NMES) for treating shoulder pain in chronic hemiplegia. Effects on shoulder pain and quality of life. Clin Rehabil. 2004;18(4):

22 Figure 1. Typical grasping cycle. FES in early stroke rehabilitation 22

23 FES in early stroke rehabilitation 23 Legend to Figure 1: Six push button signals trigger this grasping cycle to allow an individual timing. The dashed plateau lines within one step indicate that the stimulation remains constant until the next step is triggered. Steps are the following: 1 st signal: Anterior deltoid muscle, m. triceps brachii, and finger extensors are activated; the arm stretches forwards with hand open to reach an object. 2 nd signal: Arm remains stretched and hand closes to grasp an object. 3 rd signal: Hand remains closed, and arm muscles relax. 4 th signal: Arm stretches to the front, fingers still being closed. 5 th signal: Arm remains stretched and hand is opened in order to release the object. 6 th signal: Stops the stimulation of arm muscles, bringing the arm passively back to the resting position. Then, the cycle can be started anew.

24 FES in early stroke rehabilitation 24 Figure 2. Box plot of the pre-treatment and post-treatment values of the Extended Barthel Index subscore.

25 FES in early stroke rehabilitation 25 Legend to Figure 2: FES = functional electrical stimulation.

26 FES in early stroke rehabilitation 26 Table 1. Extended Barthel Index (subscore). Item Item description Score Is unable. Or: Requires a stomach feed tube and is dependent upon assistance with device 0 Eating and Needs help in cutting, spreading. 2 drinking Is independent with adaptive equipment (e.g. adapted cutlery handles). Is independent. Or: Requires a stomach feed tube, but can handle device independently. 3 4 Is unable. 0 Grooming Needs help with many, but not all procedures. 1 (washing face, combing, shaving, brushing teeth) Needs minor assistance (e.g. opening the toothpaste tube). Or: Is physically independent, but needs supervision. Is independent with adaptive equipment (e.g. extension of the hairbrush handle). 2 3 Is independent. 4 Is unable. 0 Dressing and undressing (including tying shoes, button- Needs help with most, but not all articles of clothing. Or: Needs help with all articles of clothing, but assists actively. Needs help with only a few procedures (e.g. support for tying shoes, donning orthotic devices). Or: Is physically independent, but needs supervision. 1 2

27 FES in early stroke rehabilitation 27 ing up) Is independent (perhaps with assistive devices such as sock aids). 4 Is unable. 0 Bathing self Needs assistance with many, but not all procedures, (e.g. support for transfers; is able to wash the upper part of the body, but not the lower part). Needs minor assistance (e.g. opening dispensers); Or: is physically independent, but needs supervision. Needs adaptive equipment (e.g. bath chair, bath lift), but can use it independently Is independent and needs no adaptive equipment. 4

28 FES in early stroke rehabilitation 28 Table 2. Patients clinical characteristics at baseline and statistical group differences. Control group FES group Group differences (p value) n Age (yrs): mean (SD) 62 (16.2) 57.5 (16.7) 0.74 Female subject: n (%) 4 (36) 2 (17) 0.28 Time poststroke (weeks): 7.3 (5.8; 8.2) 6.7 (6.4; 7.3) 0.56 median (quartiles) Nonhemorrhagic stroke: 9 (82) 10 (83) 0.92 n (%) Right hemiparesis: n (%) 4 (36) 3 (25) 0.55 Dominant arm affected: n 7 (64) 4 (40) 0.28 (%) a Neglect: n (%) 2 (18) 6 (50) 0.11 Extended Barthel Index: 25 (21; 32) 32 (26; 35) 0.14 median (quartiles) FES = functional electrical stimulation. a. There were two missing values in the FES group.

29 FES in early stroke rehabilitation 29 Table 3. Baseline values, gains from pre-treatment to post-treatment, and statistical group differences of primary outcome measures and modified Ashworth scale of two muscles that tend to become spastic. Outcome Control group FES group Group measures (n=11) (n=12) differences (p value) Baseline Gain Baseline Gain Base- Gain median median median median line (quartiles) (quartiles) (quartiles) (quartiles) EBI subscore 5 3** 6 1.5** 0.013* 0.19 (4; 5.5) (1; 3.3) (6; 7) (0.8; 2) CMSA arm 1 1* 2 0* (1; 2) (0; 1) (1; 2) (0; 1) CMSA hand * (2; 2) (0; 1) (1; 2.6) (0; 0.5) MAS finger flexors * (0.8; 2) (-0.5; 0.8) (0.9; 2) (0; 1.1) MAS wrist flexors * (1.5; 3) (0; 1.3) (1; 2.5) (0; 1.1) *p<0.05; **p<0.01

30 FES in early stroke rehabilitation 30 FES = functional electrical stimulation; EBI = Extended Barthel Index; CMSA = Chedoke McMaster Stroke Assessment; MAS = modified Ashworth scale.

31 FES in early stroke rehabilitation 31 Table 4. Effect sizes (Cohen s d) of gains of the primary outcome measures from pretreatment to post-treatment. Outcome measures Effect size (Cohen s d) Control group FES group EBI subscore CMSA arm CMSA hand MCID = minimal clinically important difference, defined as a change of 10% of the maximum score of the scale; ES = Effect size (Cohen s d); FES = functional electrical stimulation; EBI = Extended Barthel Index; CMSA = Chedoke McMaster Stroke Assessment.