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Comparison of Robotics, Functional Electrical Stimulation, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction After Stroke: A Randomized Controlled Trial

Open AccessPublished:November 15, 2014DOI:https://doi.org/10.1016/j.apmr.2014.10.022

      Abstract

      Objective

      To compare response to upper-limb treatment using robotics plus motor learning (ML) versus functional electrical stimulation (FES) plus ML versus ML alone, according to a measure of complex functional everyday tasks for chronic, severely impaired stroke survivors.

      Design

      Single-blind, randomized trial.

      Setting

      Medical center.

      Participants

      Enrolled subjects (N=39) were >1 year postsingle stroke (attrition rate=10%; 35 completed the study).

      Interventions

      All groups received treatment 5d/wk for 5h/d (60 sessions), with unique treatment as follows: ML alone (n=11) (5h/d partial- and whole-task practice of complex functional tasks), robotics plus ML (n=12) (3.5h/d of ML and 1.5h/d of shoulder/elbow robotics), and FES plus ML (n=12) (3.5h/d of ML and 1.5h/d of FES wrist/hand coordination training).

      Main Outcome Measures

      Primary measure: Arm Motor Ability Test (AMAT), with 13 complex functional tasks; secondary measure: upper-limb Fugl-Meyer coordination scale (FM).

      Results

      There was no significant difference found in treatment response across groups (AMAT: P≥.584; FM coordination: P≥.590). All 3 treatment groups demonstrated clinically and statistically significant improvement in response to treatment (AMAT and FM coordination: P≤.009). A group treatment paradigm of 1:3 (therapist/patient) ratio proved feasible for provision of the intensive treatment. No adverse effects.

      Conclusions

      Severely impaired stroke survivors with persistent (>1y) upper-extremity dysfunction can make clinically and statistically significant gains in coordination and functional task performance in response to robotics plus ML, FES plus ML, and ML alone in an intensive and long-duration intervention; no group differences were found. Additional studies are warranted to determine the effectiveness of these methods in the clinical setting.

      Keywords

      List of abbreviations:

      AMAT (Arm Motor Ability Test), AMAT-F (AMAT Function scale), AMAT S/E (Arm Motor Ability Test for shoulder/elbow), AMAT S/E-F (AMAT S/E Function scale), AMAT W/H (Arm Motor Ability Test for wrist/hand), AMAT W/H-F (AMAT W/H Function scale), FES (functional electrical stimulation), FM (Fugl-Meyer), ML (motor learning)
      An audio podcast accompanies this article.
      Treatment methods using motor learning (ML) principles for the treatment of persistent upper-limb dysfunction after stroke have been reported in the literature.
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      Kinematic and clinical analyses of upper-extremity movements after constraint-induced movement therapy in patients with stroke: a randomized controlled trial.
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      A randomized controlled trial of modified constraint-induced movement therapy for elderly stroke survivors: changes in motor impairment, daily functioning, and quality of life.
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      Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke.
      Some have compared the application of ML principles with neurorehabilitation methods (eg, Bobath concept, neurodevelopmental treatment).
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      • et al.
      The effectiveness of the Bobath concept in stroke rehabilitation: what is the evidence?.
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      • Lincoln N.B.
      • Foxall A.
      Comparison of Bobath based and movement science based treatment for stroke: a randomized controlled trial.
      Still, others have used bilateral upper-extremity exercise
      • McCombe-Waller S.
      • Liu W.
      • Whitall J.
      Temporal and spatial control following bilateral versus unilateral training.
      or constraint-induced motor therapies for mild/moderate upper-extremity dysfunction.
      • Wolf S.L.
      • Winstein C.J.
      • Miller J.P.
      • et al.
      Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial.
      • Lin K.C.
      • Chung H.Y.
      • Wu C.Y.
      • et al.
      Constraint-induced therapy versus control intervention in patients with stroke: a functional magnetic resonance imaging study.
      • Wu C.Y.
      • Chen C.L.
      • Tang S.F.
      • Lin K.C.
      • Huang Y.Y.
      Kinematic and clinical analyses of upper-extremity movements after constraint-induced movement therapy in patients with stroke: a randomized controlled trial.
      • Wu C.Y.
      • Chen C.L.
      • Tsai W.C.
      • Lin K.C.
      • Chou S.H.
      A randomized controlled trial of modified constraint-induced movement therapy for elderly stroke survivors: changes in motor impairment, daily functioning, and quality of life.
      • Lin K.C.
      • Wu C.Y.
      • Wei T.H.
      • Lee C.Y.
      • Liu J.S.
      Effects of modified constraint-induced movement therapy on reach-to-grasp movements and functional performance after chronic stroke: a randomized controlled study.
      • Lin K.C.
      • Wu C.Y.
      • Liu J.S.
      A randomized controlled trial of constraint-induced movement therapy after stroke.
      • Lin K.C.
      • Chang Y.F.
      • Wu C.Y.
      • Chen Y.A.
      Effects of constraint-induced therapy versus bilateral arm training on motor performance, daily functions, and quality of life in stroke survivors.
      • Gauthier L.V.
      • Taub E.
      • Perkins C.
      • Ortmann M.
      • Mark V.W.
      • Uswatte G.
      Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke.
      Most of these studies showed promising results, but stroke survivors did not recover normative function, and gains were statistically significant but small.
      In addition to ML-based treatment strategies, technology-based upper-limb therapies (eg, robotics training, functional electrical stimulation [FES]) have also produced some positive results. Treatment with robotics has shown statistically significant gains in measures of impairment for chronic stroke survivors,
      • Fasoli S.E.
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      Effects of robotic therapy on motor impairment and recovery in chronic stroke.
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      Robotic therapy for chronic motor impairments after stroke: follow-up results.
      • Volpe B.T.
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      • Rykman-Berland A.
      • et al.
      Intensive sensorimotor arm training mediated by therapist or robot improves hemiparesis in patients with chronic stroke.
      • Lo A.C.
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      • Richards L.G.
      • et al.
      Robot-assisted therapy for long-term upper-limb impairment after stroke.
      • Ang K.K.
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      • Chua K.S.
      • et al.
      A clinical study of motor imagery-based brain-computer interface for upper limb robotic rehabilitation.
      • Reinkensmeyer D.J.
      • Maier M.A.
      • Guigon E.
      • et al.
      Do robotic and non-robotic arm movement training drive motor recovery after stroke by a common neural mechanism? Experimental evidence and a computational model.
      but some reported gains were not considered clinically significant according to an outcome measure of coordination.
      • Page S.J.
      • Fulk G.D.
      • Boyne P.
      Clinically importance differences for the upper-extremity Fugl-Meyer in minimally to moderately impaired, chronic stroke.
      At the same time, surface FES was reported beneficial with chronic stroke subjects according to measures of impairment.
      • Chan M.K.
      • Tong R.K.
      • Chung K.Y.
      Bilateral upper limb training with functional electric stimulation in patients with chronic stroke.
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      Techniques to improve function of the arm and hand in chronic hemiplegia.
      Although robotics and FES have each shown promise, there is a paucity of information regarding the comparative benefit. Additionally, there is little evidence of whether or not a treatment paradigm using a combination of ML therapy and technology-based therapy would be superior to ML alone, according to a homogeneous measure of the performance of actual complex functional tasks of everyday life; rather, a number of reported outcome measures contain a mixture of impairment items and functional task items. Finally, many studies have focused on mildly to moderately impaired stroke survivors, with significantly less attention paid to the severely impaired (≤36 points on the upper-limb motor Fugl-Meyer [FM] score
      • Duncan P.W.
      • Goldstein L.B.
      • Matchar D.
      • Divine G.W.
      • Feussner J.
      Measurement of motor recovery after stroke. Outcome assessment and sample size requirements.
      ). Therefore, in consideration of all these issues together, the purpose of this study was to investigate, for severely impaired, chronic stroke survivors, the comparative response to treatment using shoulder/elbow robotics plus ML versus wrist/hand FES plus ML versus ML alone according to a measure of actual complex functional tasks of everyday life.

      Methods

       Study design

      This was a randomized controlled trial comparing response to treatment across 3 different treatment groups: robotics plus ML, FES plus ML, and ML. Subjects in all 3 groups received treatment for 5h/d for 5d/wk for 12 weeks (60 treatment visits). Measures were acquired at pre- and posttreatment.

       Participants

      There were 174 phone inquiries regarding the study. Of these, 135 did not meet criteria for an in-person screen (fig 1). Thirty-nine subjects participated in an in-person screen. Study inclusion criteria included persistent (>1y), upper-extremity impairment; at least a trace muscle contraction in the wrist extensors; single unilateral stroke; mobility and function sufficient for independent performance of activities (eg, toileting, eating lunch during the treatment days); stable medical condition; no other prior neurologic condition; and ability to follow 2-step commands. The study was conducted under the oversight of the institutional review board of the medical center. All subjects provided informed consent prior to study participation.
      Figure thumbnail gr1
      Fig 1Consolidated Standards of Reporting Trials diagram. Depiction of subject selection, group allocation, attrition and data analysis. Abbreviations: FES ML, FES plus ML group; ML, ML group; ROB ML, robotics plus ML group.

       Technology

      Robotics training was implemented using the InMotion2 Shoulder-Elbow Robot.a This robotic device is a 2-degrees-of-freedom system that is back-drivable and impedance-controlled to allow for near-frictionless movement in a horizontal plane. The robot used the QNX real-time operating system,b which allowed for high-performance control and integrated graphics. Subjects were seated comfortably in a chair with their hemiplegic forearm and hand supported by a forearm cradle and cone-shaped hand support. Training movements were shoulder/elbow movements of flexion/extension and horizontal shoulder movements from a center target to and from 8 points located on a circle around the center point.
      FES was provided with the commercially available EMS+2 stimulatorc and surface gel electrodes (flexible PALS surface electrodesd). The EMS+2 is a portable, battery-operated, 2-channel surface electrical stimulator that delivers a biphasic, symmetrical, rectangular output for each of the 2 available channels. The stimulation parameters were as follows: 300-millisecond pulse width, 40Hz, and amplitude varied according to subject tolerance. The muscles stimulated included wrist and finger flexors/extensors and forearm supinators/pronators.

       Interventions

      The goal of training was recovery of the movement components composing functional tasks and recovery of performance of the whole complex task. Treatment was based on ML principles including the following: movement practice as close to normative as possible,
      • Nudo R.J.
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      • Milliken G.W.
      • Jenkins W.M.
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      Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys.
      high number of repetitions,
      • Butefisch C.
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      • Denzler P.
      • Mauritz K.H.
      Repetitive training of isolated movements improves the outcome of motor rehabilitation of the centrally paretic hand.
      • Dean C.M.
      • Shepherd R.B.
      Task-related training improves performance of seated reaching tasks after stroke. A randomized controlled trial.
      • Elbert T.
      • Pantev C.
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      • Taub E.
      Increased cortical representation of the fingers of the left hand in string players.
      • Pascual-Leone A.
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      Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers.
      attention to the motor task,
      • Singer R.
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      To be aware or not aware? What to think about while learning and performing a motor skill.
      and training specificity.
      • Plautz E.J.
      • Milliken G.W.
      • Nudo R.J.
      Effects of repetitive motor training on movement representations in adult squirrel monkeys: role of use versus learning.
      Progression of training was based on the recovery of volitional capability and motor task difficulty, according to the motor task difficulty hierarchy shown in appendix 1. ML exercises were provided for training-isolated joint movement coordination of the scapula, shoulder, elbow, forearm, wrist, fingers, and thumb; task component movements; and whole arm/hand functional training (appendix 2).
      Examples of practiced task components are reaching, grasp preparation, and grasp release. To encourage participation, functional tasks that were meaningful to the subject were used. We used a 1:3 group therapy paradigm, whereby 1 therapist treated a group of 3 subjects for 5h/d. There were 3 interventionists; each one was assigned to 1 of the 3 treatment groups. Standardization of treatment was addressed through weekly meetings that included identification of subject impairments and consensus of treatment addressing each given impairment.
      Those in the robotics plus ML group used the robot for 1.5h/d. For the remainder of the day they were provided with ML without technologies (3.5h). Similarly, those in the FES plus ML group used FES for 1.5h/d. The ML group was provided with the ML intervention for 5h/d.

       Primary outcome measure: Arm Motor Ability Test

      All measures were acquired at pre- and posttreatment. There was 1 assessor, who was blinded to the group assignment of the subject. The primary outcome measure was the Arm Motor Ability Test (AMAT), which is a homogenous measure of functional tasks of everyday living.
      • Kopp B.
      • Kunkel A.
      • Flor H.
      • et al.
      The Arm Motor Ability Test: reliability, validity, and sensitivity to change of an instrument for assessing disabilities in activities of daily living.
      The AMAT consists of 13 complex functional tasks, which are videotaped and timed for performance. Examples of the AMAT tasks of everyday living are as follows: pick up and drink from a mug and pick up comb and comb hair.

       Secondary measures

      Because the robotics and FES technologies were focused on shoulder/elbow or wrist/hand, respectively, we used 2 AMAT subscales: AMAT for shoulder/elbow (AMAT S/E) and AMAT for wrist/hand (AMAT W/H). The AMAT S/E and AMAT W/H subscales were scored by recording the time of the shoulder/elbow movements or the wrist/hand movements, respectively, performed during each AMAT task performance. These subscales have shown good validity and reliability (AMAT S/E intraclass correlation coefficient: .82; AMAT W/H intraclass correlation coefficient: .96).
      • Daly J.J.
      • Hogan N.
      • Perepezko E.M.
      • et al.
      Response to upper-limb robotics and functional neuromuscular stimulation following stroke.
      The FM coordination scale is a measure of limb joint movement coordination,
      • Fugl-Meyer A.R.
      • Jääskö L.
      • Leyman I.
      • Olsson S.
      • Steglind S.
      The post-stroke hemiplegic patient. 1. A method for evaluation of physical performance.
      with good validity and intra- and interrater reliability, used in most upper-limb rehabilitation studies of stroke.
      • Duncan P.W.
      • Propst M.
      • Nelson S.G.
      Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident.
      In addition to using the overall FM upper-limb motor score, we generated values for the shoulder/elbow movement items and wrist/hand items, summing them for each participant into the subscale scores of FM for shoulder/elbow and FM for wrist/hand, respectively.
      In addition to the quantitative timed AMAT used for the primary measure, the AMAT can be scored using an ordinal, observational scale (0–5 points; AMAT Function scale [AMAT-F]). To investigate clinical significance within groups, we used the AMAT-F for which others have reported that a gain of .21 points is indicative of clinical significance.
      • Harvey R.L.
      • Winstein C.J.
      Everest Trial Group
      Design for the everest randomized trial of cortical stimulation and rehabilitation for arm function following stroke.
      • Page S.J.
      • Levin L.
      • Hermann V.
      • Dunning K.
      • Levine P.
      Longer versus shorter daily durations of electrical stimulation during task-specific practice in moderately impaired stroke.
      The AMAT-F has shown correlation with the clinically meaningful FM score.
      • Chae J.
      • Labatia I.
      • Yang G.
      Upper limb motor function in hemiparesis: concurrent validity of the Arm Motor Ability test.

       Statistical analyses

      Analyses were completed using the IBM SPSS version 19.0 statistical software package.e Baseline measures were compared across the 3 treatment groups for the AMAT and FM coordination scale using the nonparametric Kruskal-Wallis test. For the primary study question of group treatment difference on the AMAT, the Kruskal-Wallis test was used on the improvement scores (pre-post). Additionally, 95% confidence intervals for mean differences for pairwise comparisons were completed. A similar group analysis was conducted on the secondary measure of the FM coordination scale. For the additional secondary within-group analyses, we made pre-/posttreatment comparisons within each group using the Wilcoxon signed-rank test. A 95% Hodges-Lehman confidence interval was included for estimating the median change from pre- to posttreatment. To correct for multiple testing, sets of related hypotheses were grouped together,
      • Miller Jr., R.G.
      Simultaneous statistical inference.
      and then the Holm Bonferroni stepdown correction method was used to determine statistical significance.
      • Holm S.
      A simple sequentially rejective Bonferroni test procedure.
      For the secondary measure, the ordinal AMAT-F measure and the subscales of AMAT S/E Function scale (AMAT S/E-F) and AMAT W/H Function scale (AMAT W/H-F), we calculated the following descriptive statistics: mean AMAT-F score for each individual across the task scores for both pre- and posttreatment, change score, and group means and change score. We inspected each group change score relative to the value of 0.21 point (clinically significant change for the AMAT-F).

      Results

      A total of 39 subjects enrolled in this study, with all but 1 subject in the severe range of impairment, according to the upper-extremity motor FM score ≤36 points
      • Duncan P.W.
      • Goldstein L.B.
      • Matchar D.
      • Divine G.W.
      • Feussner J.
      Measurement of motor recovery after stroke. Outcome assessment and sample size requirements.
      (table 1). The attrition rate was 10% (4/39) (see fig 1). There were 4 subjects who enrolled (2 in the ML alone group, 2 in the FES plus ML group) but did not complete the study. Their characteristics did not alter the relative subject characteristics across groups, and the characteristics are as follows: sex (FES plus ML group: 1 woman and 1 man; ML alone group: 2 men), stroke type (FES plus ML: cortical [n=1] and subcortical [n=1]; ML alone group: cortical [n=2]), years poststroke (FES plus ML group: 1–3y [n=2]; ML alone: 1–3y [n=1] and injury >4y [n=1]), and age (FES plus ML group: 50–81y [n=2]; ML alone group: 50–81y [n=2]). The reasons for their withdrawing from the study were things such as transportation and family issues. A total of 35 subjects completed the study (see fig 1). The analyses subsequently reported were conducted on those who completed the study. No adverse events occurred as a result of participation in the study.
      Table 1Subject characteristics
      GroupStroke TypeYears PoststrokeAge Range (y)SexBaseline FM Upper- Limb Score (SD)
      CorticalSubcorticalBothBrainstem1–3≥421–4950–81MaleFemale
      ML612283296523.58±5.86
      FES plus ML6330102397522.85±6.92
      Robotics plus ML34419321010222.62±5.66
      NOTE. Values for stroke type, years poststroke, age range, and sex are n.
      Prior to beginning treatment, there was no statistically significant difference among the 3 treatment groups based on baseline AMAT (P≥.866) or baseline FM score (P≥.966).

       AMAT measure

       Group comparison

      For the primary measure (AMAT), there was no significant difference across groups regarding treatment response (P≥.584). Similarly, for the secondary measures of the AMAT S/E and AMAT W/H subscales, there was no difference across groups in treatment response (P≥.786 and P≥.288, respectively) (table 2).
      Table 2No significant difference between groups for AMAT measure of complex function
      AMAT MeasureComparison GroupsPretreatment (s)Posttreatment (s)Mean Change Score (s)Mean Difference 95% CI (s)P
      AMATML vs FES+MLML: 1794±479

      FES+ML: 1868±501
      ML: 1417±637

      FES+ML: 1367±566
      377

      501
      −124 (−430 to 182).584
      ML vs ROB+MLML: 1794±479

      ROB+ML: 1868±597
      ML: 1417±637

      ROB+ML: 1463±573
      377

      405
      −28 (−334 to 278).972
      ROB+ML vs FES+MLROB+ML: 1868±597

      FES+ML: 1868±501
      ROB+ML: 1463±573

      FES+ML: 1367±566
      405

      501
      −96 (−395 to 206).712
      AMAT S/EML vs FES+MLML: 931±288

      FES+ML: 956±285
      ML: 709±316

      FES+ML: 707±263
      222

      249
      −27 (−194 to 141).917
      ML vs ROB+MLML: 931±288

      ROB+ML: 979±286
      ML: 709±316

      ROB+ML: 711±267
      222

      268
      −46 (−213 to 122).786
      ROB+ML vs FES+MLROB+ML: 979±286

      FES+ML: 956±285
      ROB+ML: 711±267

      FES+ML: 707±263
      268

      249
      18 (−146 to 182).960
      AMAT W/HML vs FES+MLML: 864±250

      FES+ML: 912±245
      ML: 682±326

      FES+ML: 660±320
      182

      252
      −70 (−257 to 117).631
      ML vs ROB+MLML: 864±250

      ROB+ML: 890±325
      ML: 682±326

      ROB+ML: 751±320
      182

      139
      43 (−143 to 231).831
      ROB+ML vs FES+MLROB+ML: 890±325

      FES+ML: 912±245
      ROB+ML: 751±320

      FES+ML: 660±320
      139

      252
      −113 (−297 to 69).288
      NOTE. Values are mean ± SD or as otherwise indicated.
      Abbreviations: CI, confidence interval; FES+ML, FES plus ML group; ML, ML group; ROB+ML, robotics plus ML group.

       Within-group improvement

      All 3 treatment groups demonstrated a statistically significant improvement according to the AMAT, AMAT S/E, and AMAT W/H, after adjusting for multiple tests (P≤.009) (table 3).
      Table 3Within-group gains in functional task performance (AMAT) for each of the 3 treatment groups
      Treatment GroupFunctional Task MeasurePretreatment (s)Posttreatment (s)Median Difference (95% CI) (s)P
      MLAMAT1794±4791417±637−277 (−341 to −217).003
      Adjusted P value.
      AMAT S/E931±288709±316−209 (−284 to −155).003
      Adjusted P value.
      AMAT W/H864±250682±326−144 (−344 to −51).009
      Adjusted P value.
      FES plus MLAMAT1868±5011367±566−415 (−655 to −290).002
      Adjusted P value.
      AMAT S/E956±285707±263−206 (−387 to −115).002
      Adjusted P value.
      AMAT W/H912±245660±320−232 (−374 to −133).003
      Adjusted P value.
      Robotics plus MLAMAT1868±5971463±573−402 (−509 to −298).002
      Adjusted P value.
      AMAT S/E979±286711±267−262 (−339 to −208).002
      Adjusted P value.
      AMAT W/H890±325751±320−119 (−207 to −72).003
      Adjusted P value.
      NOTE. Values are mean ± SD or as otherwise indicated.
      Abbreviation: CI, confidence interval.
      Adjusted P value.

       Coordination impairment secondary measures

       Group comparison

      For the secondary measures of joint coordination (FM scale, FM scale for shoulder/elbow, FM scale for wrist/hand), there was no significant difference across groups regarding treatment response (FM scale: P≥.590; FM scale for shoulder/elbow: P≥.979; FM scale for wrist/hand: P≥.340) (table 4).
      Table 4No significant difference between groups according to gain in coordination (FM scale)
      Functional Task MeasureGroups ComparedPretreatment (points)Posttreatment (points)Mean Change Score for Each GroupGroup Mean Difference (95% CI) (points)P
      FM scaleML vs FES+MLML: 23.6±5.8

      FES+ML: 23.5±6.5
      ML: 33.5±8.3

      FES+ML: 32.3±7.9
      9.9

      8.8
      1.1 (−4.1 to 6.2).867
      ML vs ROB+MLML: 23.6±5.8

      ROB+ML: 23.6±5.9
      ML: 33.5±8.3

      ROB+ML: 31.3±6.2
      9.9

      7.7
      2.2 (−3.1 to 7.2).590
      ROB+ML vs FES+MLROB+ML: 23.6±5.9

      FES+ML: 23.5±6.5
      ROB+ML: 31.3±6.2

      FES+ML: 32.3±7.9
      7.7

      8.8
      1.1 (−4.0 to 6.0).877
      FM scale for shoulders/elbowsML vs FES+MLML: 12.7±2.9

      FES+ML: 12.7±3.5
      ML: 16.4±3.9

      FES+ML: 16.5±3.9
      3.7

      3.8
      0.1 (−2.6 to 2.2).979
      ML vs ROB+MLML: 12.7±2.9

      ROB+ML: 12.9±1.9
      ML: 16.4±3.9

      ROB+ML: 16.6±2.5
      3.7

      3.7
      0 (−2.5 to 2.4).999
      ROB+ML vs FES+MLROB+ML: 12.9±1.9

      FES+ML: 12.7±3.5
      ROB+ML: 16.6±2.5

      FES+ML: 16.5±3.9
      3.7

      3.8
      0.1 (−2.2 to 2.6).984
      FM scale for wrists/handsML vs FES+MLML: 9.1±2.6

      FES+ML: 8.8±3.5
      ML: 14.7±4.7

      FES+ML: 13.4±4.2
      5.6

      4.6
      1 (−2.3 to 4.5).728
      ML vs ROB+MLML: 9.1±2.6

      ROB+ML: 8.3±4.3
      ML: 14.7±4.7

      ROB+ML: 12.0±4.1
      5.6

      3.7
      1.9 (−1.4 to 5.4).340
      ROB+ML vs FES+MLROB+ML: 8.3±4.3

      FES+ML: 8.8±3.5
      ROB+ML: 12.0±4.1

      FES+ML: 13.4±4.2
      3.7

      4.6
      0.9 (−2.4 to 4.2).777
      NOTE. Values are mean ± SD or as otherwise indicated.
      Abbreviations: CI, confidence interval; FES+ML, FES plus ML group; ML, ML group; ROB+ML, robotics plus ML group.

       Within-group improvement

      All 3 treatment groups demonstrated a statistically significant within-group improvement according to the FM scale, FM scale for shoulder/elbow, and FM scale for wrist/hand after adjusting for multiple tests (P≤.007) (table 5).
      Table 5Within-group gains in impaired coordination (FM) for each of the 3 treatment groups
      Treatment GroupCoordination MeasurePretreatment (points)Posttreatment (points)Median Gain Score (95% CI) (points)PMean Gain Score
      MLFM23.6±5.833.5±8.39 (7.5–12.5).003
      Significant according to adjusted P value.
      11
      FM scale for shoulders/elbows12.7±2.916.4±3.93.5 (2.5–4.5).003
      Significant according to adjusted P value.
      4
      FM scale for wrists/hands9.1±2.614.7±4.75 (4.0–7.5).003
      Significant according to adjusted P value.
      6
      FES+MLFM23.5±6.532.3±7.98 (5.5–12).002
      Significant according to adjusted P value.
      10
      FM scale for shoulders/elbows12.7±3.516.5±3.94 (2.0–6.0).005
      Significant according to adjusted P value.
      4
      FM scale for wrists/hands8.8±3.513.4±4.25 (2.0–7.0).003
      Significant according to adjusted P value.
      5
      ROB+MLFM23.6±5.931.3±6.27.8 (4.5–11).003
      Significant according to adjusted P value.
      8
      FM scale for shoulders/elbows12.9±1.916.6±2.53.5 (2.5–5.0).002
      Significant according to adjusted P value.
      3
      FM scale for wrists/hands8.3±4.312.0±4.14.0 (1.5–5.0).007
      Significant according to adjusted P value.
      4
      NOTE. Values are mean ± SD or as otherwise indicated.
      Abbreviations: CI, confidence interval; FES+ML, FES plus ML group; ML, ML group; ROB+ML, robotics plus ML group.
      Significant according to adjusted P value.

       Descriptive statistics for the AMAT-F scale

      Table 6 provides descriptive statistics for the ordinal AMAT-F scale, AMAT S/E–F, and AMAT W/H–F for each of the 3 groups. Pre-/posttreatment change scores for all measures were >.21 point, which is considered the minimum value for clinically important improvement. All scores, except for 2 change scores, were less than or equal to twice the minimum value for clinically important improvement. The 2 individual participant change scores, which were the smallest, were in the robotics group plus ML group (AMAT-F, .37 point; AMAT W/H–F: .26 point).
      Table 6AMAT-Function ordinal measure descriptive statistics showing clinically significant change scores
      Clinically significant improvement is >.21 points.
      Treatment GroupPretreatmentPosttreatmentChange Score
      Clinically significant improvement is >.21 points.
      a. AMAT function measure
       ML1.82±0.482.30±0.770.48±0.34
       FES+ML1.78±0.532.22±0.620.44±0.24
       ROB+ML1.75±0.602.13±0.560.37±0.25
      b. AMAT S/E function measure
       ML2.12±0.532.55±0.670.43±0.23
       FES+ML2.04±0.522.47±0.560.42±0.35
       ROB+ML2.00±0.572.44±0.420.44±0.30
      c. AMAT W/H function measure
       ML1.37±0.571.89±0.930.53±0.61
       FES+ML1.42±0.671.92±0.710.50±0.27
       ROB+ML1.35±0.731.60±0.820.26±0.21
      NOTE. Values are mean ± SD.
      Abbreviations: FES+ML, FES plus ML group; ML, ML group; ROB+ML, robotics plus ML group.
      Clinically significant improvement is >.21 points.

       Descriptive statistics for the FM coordination scale

      Descriptive statistics for the FM coordination measure provide some additional insight into the level of clinically significant change for the subjects in each of the treatment groups. In the robotics plus ML and FES plus ML groups there were 75% and 92% of subjects, respectively, with a clinically significant gain in coordination impairment (≥4.25 points on the FM coordination scale). For the ML alone group, 100% of subjects were equal to or beyond a clinically significant gain. No subjects in the study worsened. Highest FM gain score for a participant in each group was: FES plus ML (25 points); robotics plus ML (15 points); and ML alone (18 points).

      Discussion

       Direct comparison of shoulder/elbow robotics, wrist/hand FES, and ML

      To our knowledge, this is the first study of chronic stroke survivors making a comparison of robotics and FES and a direct comparison of either technology with intensive ML. We found no significant difference among the 3 groups in terms of treatment response, according to a measure of 13 complex functional tasks and an impairment measure of joint coordination. This could have been because all 3 groups received treatment that was based on ML principles (eg, as close to normative practice as is possible, focused attention on the task, high number of daily practice repetitions of motor task components, whole-task practice of functionally meaningful tasks, and generalization of movement component practice to >1 type of whole-task practice). In preliminary work, we reported that emphasis of shoulder/elbow robotics treatment resulted in significantly greater gains in AMAT S/E versus treatment with FES emphasis for the wrist/hand. We also found the converse; that is, emphasis of wrist/hand FES treatment resulted in significantly greater gain in AMAT W/H versus treatment with emphasis on shoulder/elbow robotics.
      • Daly J.J.
      • Hogan N.
      • Perepezko E.M.
      • et al.
      Response to upper-limb robotics and functional neuromuscular stimulation following stroke.
      However, that sample size was very small (n=6 and n=6, respectively).
      • Daly J.J.
      • Hogan N.
      • Perepezko E.M.
      • et al.
      Response to upper-limb robotics and functional neuromuscular stimulation following stroke.
      The current results did not bear out our findings from that preliminary work. Because all 3 groups had the benefit of comprehensive coordination training, any unique advantage of either robotics or FES could have been superseded by the importance of the general framework and principles of treatment. It could be that the hours of ML without the technologies served to consolidate newly learned joint coordination that was gained through the use of either robotics or FES. Alternatively, a larger sample size may show a significant group difference.

       Considerations of extent of recovery, level of impairment, and treatment duration/intensity for severely impaired chronic stroke survivors

      This study contributes to the literature in the extent of improvement that was shown in the FM joint coordination measure for all 3 groups of more severely involved participants in the chronic phase (>1y after stroke). In our consideration of the literature here, we are focusing on studies of others that enrolled stroke survivors at ≥6 months poststroke because some have reported spontaneous or endogenous recovery up to 3 to 6 months after stroke, which could confound a study of group difference.

       Contrasting response to treatment for the less impaired subjects in other studies versus the more impaired subjects in the current work

      Our study cohort was in the severely impaired category (baseline upper-limb motor FM score ≤36 points). Even still, compared with the work of others for mild to moderately impaired stroke survivors, the gain scores in our study of the severely impaired were either comparable (robotics plus ML group), higher (ML alone group), or almost twice as high (FES plus ML group) as that reported for the less impaired. For example, for mild to moderately impaired chronic stroke survivors, FM gains were reported in response to treatment as follows. In robotics therapy, gains reported ranged from 3.36 to 9 points.
      • Fasoli S.E.
      • Krebs H.I.
      • Stein J.
      • Frontera W.R.
      • Hughes R.
      • Hogan N.
      Robotic therapy for chronic motor impairments after stroke: follow-up results.
      • Takahashi C.D.
      • Der-Yeghiaian L.
      • Le V.
      • Motiwala R.R.
      • Cramer S.C.
      Robot-based hand motor therapy after stroke.
      • Hu X.L.
      • Tong K.Y.
      • Song R.
      • Zheng X.J.
      • Leung W.W.
      A comparison between electromyography-driven robot and passive motion device on wrist rehabilitation for chronic stroke.
      In FES therapy, a 5-point gain was reported.
      • de Kroon J.R.
      • Ijzerman M.J.
      Electrical stimulation of the upper extremity in stroke: cyclic versus EMG-triggered stimulation.
      In ML or exercise, gains of 6 to 8 points were reported.
      • Lin K.C.
      • Chung H.Y.
      • Wu C.Y.
      • et al.
      Constraint-induced therapy versus control intervention in patients with stroke: a functional magnetic resonance imaging study.
      • Wu C.Y.
      • Chen C.L.
      • Tsai W.C.
      • Lin K.C.
      • Chou S.H.
      A randomized controlled trial of modified constraint-induced movement therapy for elderly stroke survivors: changes in motor impairment, daily functioning, and quality of life.
      • Lin K.C.
      • Chang Y.F.
      • Wu C.Y.
      • Chen Y.A.
      Effects of constraint-induced therapy versus bilateral arm training on motor performance, daily functions, and quality of life in stroke survivors.
      • Lin K.C.
      • Wu C.Y.
      • Liu J.S.
      • Chen Y.T.
      • Hsu C.J.
      Constraint-induced therapy versus dose-matched control intervention to improve motor ability, basic/extended daily functions, and quality of life in stroke.
      • Page S.J.
      • Levine P.
      • Khoury J.C.
      Modified constraint-induced therapy combined with mental practice: thinking through better motor outcomes.
      In contrast with those studies of lesser impaired individuals, the current study focused on severely impaired stroke survivors and yielded the following results for FM mean gains: the robotics plus ML group yielded 8 points, the FES plus ML group yielded 9 points, and the ML alone group yielded 11 points. In terms of clinically important difference, other studies
      • Page S.J.
      • Fulk G.D.
      • Boyne P.
      Clinically importance differences for the upper-extremity Fugl-Meyer in minimally to moderately impaired, chronic stroke.
      have suggested that the estimated clinically important difference for the upper-extremity FM coordination scale ranges from 4.25 to 7.25 points in scores. Our results for all 3 groups were beyond those values for the severely impaired. In addition, our gain scores for the AMAT-F scale (see table 6) were more than twice the clinically significant value of .21 point for the ML alone and FES plus ML groups and were greater than clinically significant for the robotics plus ML group.

       Potential effect of treatment intensity (number of sessions, hours/session)

      Emerging empirical evidence is supporting long-held clinical observation; that is, for recovery of persistent discoordination after stroke, many hours of specifically formulated practice are required.
      • Butefisch C.
      • Hummelsheim H.
      • Denzler P.
      • Mauritz K.H.
      Repetitive training of isolated movements improves the outcome of motor rehabilitation of the centrally paretic hand.
      • Plautz E.J.
      • Milliken G.W.
      • Nudo R.J.
      Effects of repetitive motor training on movement representations in adult squirrel monkeys: role of use versus learning.
      • Lohse K.R.
      • Lang C.E.
      • Boyd L.A.
      Is more better? Using metadata to explore dose-response relationships in stroke rehabilitation.
      • Daly J.J.
      • Ruff R.L.
      Evidence-based construction and measurement of efficacious gait and upper limb functional interventions after stroke; a case for combination interventions.
      The current study included intensive practice of coordinated tasks (5h/session, 60 sessions); this treatment intensity may help to explain the larger gains reported here in coordination and function for these severely involved stroke survivors. Although Kraft et al
      • Kraft G.H.
      • Fitts S.S.
      • Hammond M.C.
      Techniques to improve function of the arm and hand in chronic hemiplegia.
      studied only 6 subjects in its FES group, they also provided 3 months of treatment, which may explain their high FM mean gain (8 points).
      For our other 2 treatment groups (robotics plus ML and ML alone), treatment intensity may also explain gains that were greater for our severely impaired individuals than that reported by other researchers for severely impaired stroke survivors. For example, for severely impaired stroke survivors, others reported FM gains in response to robotics ranging only from 1.2 to 5 points,
      • Lo A.C.
      • Guarino P.D.
      • Richards L.G.
      • et al.
      Robot-assisted therapy for long-term upper-limb impairment after stroke.
      • Lum P.S.
      • Burgar C.G.
      • Shor P.C.
      • Majmundar M.
      • Van der Loos M.
      Robot-assisted movement training compared with conventional therapy techniques for the rehabilitation of upper-limb motor function after stroke.
      • Finley M.A.
      • Fasoli S.E.
      • Dipietro L.
      • et al.
      Short-duration robotic therapy in stroke patients with severe upper-limb motor impairment.
      • Fazekas G.
      • Horvath M.
      • Troznai T.
      • Toth A.
      Robot-mediated upper limb physiotherapy for patients with spastic hemiparesis: a preliminary study.
      and ML alone was reported to have produced only a 4-point FM gain in 46 participants who were more severely impaired.
      • Lo A.C.
      • Guarino P.D.
      • Richards L.G.
      • et al.
      Robot-assisted therapy for long-term upper-limb impairment after stroke.
      In the current study, more hours of treatment were provided than for these cited studies. Given the results reported here (robotics plus ML group: FM gain of 8; ML alone: FM gain of 11), it is reasonable to consider that greater treatment intensity is needed for the more severely impaired using those 2 types of interventions (ML alone or robotics plus ML groups) to achieve the greater FM score gains.
      The current clinical practice milieu prevents the provision of long-duration, high-intensity treatment; therefore, this new information is an important contribution to the literature. One reason for the lack of provision of long-duration interventions in standard clinical care is the out-of-date belief that no more recovery can occur after 3 to 6 months poststroke. In contrast with these inaccurate beliefs, our results are consistent with others who have demonstrated the possibility of motor recovery beyond that time period, through the application of a variety of treatment methods.
      • McCombe-Waller S.
      • Liu W.
      • Whitall J.
      Temporal and spatial control following bilateral versus unilateral training.
      • Wolf S.L.
      • Winstein C.J.
      • Miller J.P.
      • et al.
      Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial.
      • Fasoli S.E.
      • Krebs H.I.
      • Stein J.
      • Frontera W.R.
      • Hughes R.
      • Hogan N.
      Robotic therapy for chronic motor impairments after stroke: follow-up results.
      • Volpe B.T.
      • Lynch D.
      • Rykman-Berland A.
      • et al.
      Intensive sensorimotor arm training mediated by therapist or robot improves hemiparesis in patients with chronic stroke.
      • Lo A.C.
      • Guarino P.D.
      • Richards L.G.
      • et al.
      Robot-assisted therapy for long-term upper-limb impairment after stroke.
      • Ang K.K.
      • Guan C.
      • Chua K.S.
      • et al.
      A clinical study of motor imagery-based brain-computer interface for upper limb robotic rehabilitation.
      • Reinkensmeyer D.J.
      • Maier M.A.
      • Guigon E.
      • et al.
      Do robotic and non-robotic arm movement training drive motor recovery after stroke by a common neural mechanism? Experimental evidence and a computational model.
      • Chan M.K.
      • Tong R.K.
      • Chung K.Y.
      Bilateral upper limb training with functional electric stimulation in patients with chronic stroke.
      • Hu X.L.
      • Tong K.Y.
      • Song R.
      • Zheng X.J.
      • Leung W.W.
      A comparison between electromyography-driven robot and passive motion device on wrist rehabilitation for chronic stroke.
      • Page S.J.
      • Levine P.
      • Khoury J.C.
      Modified constraint-induced therapy combined with mental practice: thinking through better motor outcomes.
      • Lum P.S.
      • Burgar C.G.
      • Shor P.C.
      • Majmundar M.
      • Van der Loos M.
      Robot-assisted movement training compared with conventional therapy techniques for the rehabilitation of upper-limb motor function after stroke.
      • Finley M.A.
      • Fasoli S.E.
      • Dipietro L.
      • et al.
      Short-duration robotic therapy in stroke patients with severe upper-limb motor impairment.
      • Fazekas G.
      • Horvath M.
      • Troznai T.
      • Toth A.
      Robot-mediated upper limb physiotherapy for patients with spastic hemiparesis: a preliminary study.
      • Boyd L.A.
      • Winstein C.J.
      Impact of explicit information on implicit motor-sequence learning following middle cerebral artery stroke.
      • Piron L.
      • Turolla A.
      • Agostini M.
      • et al.
      Motor learning principles for rehabilitation: a pilot randomized controlled study in post stroke patients.
      • Hanlon R.E.
      Motor learning following unilateral stroke.
      • Yen J.G.
      • Wang R.Y.
      • Chen H.H.
      • Hong C.T.
      Effectiveness of modified constraint-induced movement therapy on upper limb function in stroke subjects.
      • Byl N.
      • Roderick J.
      • Mohamed O.
      • et al.
      Effectiveness of sensory and motor rehabilitation of the upper limb following the principles of neuroplasticity: patients stable poststroke.
      • Krebs H.I.
      • Hogan N.
      • Volpe B.T.
      • Aisen M.L.
      • Edelstein L.
      • Diels C.
      Overview of clinical trials with MIT-MANUS: a robot-aided neuro-rehabilitation facility.
      • Lum P.S.
      • Burgar C.G.
      • Shor P.C.
      Evidence for improved muscle activation patterns after retraining of reaching movements with the MIME robotic system in subjects with post-stroke hemiparesis.
      • Ferraro M.
      • Palazzolo J.J.
      • Krol J.
      • Krebs H.I.
      • Hogan N.
      • Volpe B.T.
      Robot-aided sensorimotor arm training improves outcome in patients with chronic stroke.
      • Lo A.C.
      • Guarino P.
      • Krebs H.I.
      • et al.
      Multicenter randomized trial of robot-assisted rehabilitation for chronic stroke: methods and entry characteristics for VA ROBOTICS.

       Functional task improvement

      Although many research studies report significant gains in impairment, there is less information available regarding the recovery of actual functional tasks in response to experimental interventions, according to a homogenous measure of complex functional task performance (ie, everyday functional tasks). In the current work, the statistically significant improvement within each group for the AMAT (13 complex function tasks) can be explained in a number of ways. First, the high gain in the FM score in all 3 groups may have been sufficiently robust to produce a significant improvement in a measure of 13 actual complex function tasks. Second, the purposeful application of fundamental ML principles could explain both the relatively high gains in coordination (FM score) and AMAT gains. Third, the protocol was specific in practice of joint movement components within the context of actual task practice. (supplemental video S1 shows recovery of coordination and functional capability; available online only at http://www.archives-pmr.org/.)

       Patient group delivery of intensive and long-duration intervention

      We found that it was feasible to deliver the study protocol using a group treatment method (1:3 ratio of therapist to patients). The relatively high gain in FM scores for all 3 groups could serve as evidence to support the feasibility of the 1:3 therapist to patient ratio. According to the work of others
      • Kwakkel G.
      • Kollen B.
      • Krebs H.
      Effects of robot-assisted therapy on upper limb recovery after stroke: a systematic review.
      • Norouzi-Gheidari N.
      • Archambault P.S.
      • Fung J.
      Effects of robot-assisted therapy on stroke rehabilitation in upper limbs: systematic review and meta-analysis of the literature.
      and our study therapists' reports, the group treatment paradigm was more reasonably feasible with the use of the robotics or FES technologies because these practice-assist devices could be quickly set up in a manner enabling some independent practice, while the therapist could focus on other participants. This allowed a more calm therapeutic setting and a more satisfying work situation for the therapist.

       Cost considerations

      We calculated the cost of each of the 3 treatment protocols in this study. The following assumptions were used: therapist cost ($98,000, which is the annual salary for an experienced therapist in Ohio where the study was conducted; source: Department of Veterans Affairs and additional local hospital); shoulder/elbow clinical level robot cost ($89,000) and 5-year robot life; annual robot warranty and maintenance ($8000; source: robot distributing company); and FES cost for a 4-channel table top and 2-channel portable system ($4000), with a 5-year equipment life. We used the facts of our protocol (number of visits; duration of sessions for use of each piece of equipment and ML alone; and a ratio of 1:3, therapist to patient). Our calculations yielded the following costs per patient for the entire treatment protocol: ML alone ($4570), FES plus ML ($4604), and robotics plus ML ($5686). These costs are in the ballpark in comparison with the calculations of others
      • Lo A.C.
      • Guarino P.D.
      • Richards L.G.
      • et al.
      Robot-assisted therapy for long-term upper-limb impairment after stroke.
      ; however, our treatment was considerably longer, the cost of our robot was significantly less because we used only 1 type of robot, and the robot cost is for a clinical robot. Our ML alone protocol was less expense than the robotics plus ML protocol by $1116 and less than the FES plus ML protocol by $34. Therefore, if a cost differential of approximately $1000 per patient is considered important, then the FES plus ML protocol and/or the ML alone protocol would be preferable.

       Study limitations

      There were a number of study limitations. First, the sample sizes per group were 11, 12, and 12, respectively. Although there was no significant difference and no indication of a trend in group difference, a larger sample size might have shown group differences. Second, this was a research trial. To determine whether the 1:3 ratio of therapist to patients is practical and beneficial in clinical practice, this treatment paradigm would require testing in a clinical environment. Third, in this study, FES and robotics were differentially targeted to either wrist/hand or shoulder/elbow, respectively; therefore, this study did not make a direct comparison of either robotics versus FES for shoulder/elbow or robotics versus FES for wrist/hand. Rather, this study design was selected and funded based on 2 assumptions. The first assumption was that FES may be preferable for wrist/hand intervention because it can be applied quickly and easily to wrist/hand flexors and extensors, and notably, it provides practice of an actual muscle contraction. In contrast, robotics can encourage and enable less therapeutic passive participation. The second assumption was that robotics may be preferable for shoulder/elbow intervention because it can be quickly and easily set up to support and guide movement of the complex shoulder/elbow movement components composing the reach task. In contrast, FES would have required time-consuming application of multiple electrodes for scapular and limb muscles and control of complex precision timing of multiple muscle activations for the greatest effectiveness.
      Fourth, because of limitations in resources, it was not feasible to acquire follow-up data. However, others have documented good maintenance of gains after ML, robotics, and FES. For severely impaired individuals, robotics,
      • Lo A.C.
      • Guarino P.D.
      • Richards L.G.
      • et al.
      Robot-assisted therapy for long-term upper-limb impairment after stroke.
      ML (intensive therapy
      • Lo A.C.
      • Guarino P.D.
      • Richards L.G.
      • et al.
      Robot-assisted therapy for long-term upper-limb impairment after stroke.
      ), and FES
      • Thorsen R.
      • Cortesi M.
      • Jonsdottir J.
      • et al.
      Myoelectrically driven functional electrical stimulation may increase motor recovery of upper limb in poststroke subjects: a randomized controlled pilot study.
      produced gains in response to treatment that were maintained at follow-up. With these reported maintenance gains taken together, along with our high gains after treatment, it is reasonable to consider that gains may have been maintained in the current study. However, further study is required to quantitatively compare follow-up maintenance across groups.

      Conclusions

      Severely impaired chronic stroke subjects (>1y) with persistent upper-extremity dysfunction can make clinically significant gains in joint movement coordination and functional task performance in response to the 3 tested interventions (ML, combined robotics and ML, combined FES and ML) in an intensive and long-duration intervention. There was no difference in treatment response across the 3 intervention groups according to measures of joint movement coordination or complex functional task performance. It was feasible in the research laboratory to deliver effective group treatment for severely impaired stroke survivors in a 1:3 (therapist/patient) ratio.

      Suppliers

      • a.
        Interactive Motion Technologies.
      • b.
        QNX Software Systems.
      • c.
        Staodyn, Inc.
      • d.
        Axelgaard Manufacturing Co, Ltd.
      • e.
        IBM Corporation.

      Appendix 1. Upper-Limb Training Protocol: Treatment Progression Hierarchy for Coordinated Movement Practice

      Figure thumbnail fx1

      Appendix 2. Examples of Functional Tasks Practiced During Training Sessions

      • Stir food in a bowl.
      • Place objects in kitchen cupboard.
      • Carry objects (unilateral and bilateral).
      • Write with pen/pencil.
      • Type at computer.
      • Sweep with broom.
      • Throw ball.
      • Swing a golf club.
      • Sand wood.

      Supplementary Data

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        Archives of Physical Medicine and RehabilitationVol. 101Issue 4
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          In the article by McCabe et al, Comparison of Robotics, Functional Electrical Stimulation, and Motor Learning Methods for Treatment of Persistent Upper Extremity Dysfunction After Stroke: A Randomized Controlled Trial, published in Archives of Physical Medicine and Rehabilitation 2015;96:981-90 ( https://www.archives-pmr.org/article/S0003-9993(14)01228-3/fulltext ), Table 5 contained an error. In the last column (‘Mean Gain Score’), row one (ML Group, FM Score) the value is shown as 11 points on the FM scale.
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