Figures
Abstract
Background
Physical therapy (PT) is one of the key disciplines in interdisciplinary stroke rehabilitation. The aim of this systematic review was to provide an update of the evidence for stroke rehabilitation interventions in the domain of PT.
Methods and Findings
Randomized controlled trials (RCTs) regarding PT in stroke rehabilitation were retrieved through a systematic search. Outcomes were classified according to the ICF. RCTs with a low risk of bias were quantitatively analyzed. Differences between phases poststroke were explored in subgroup analyses. A best evidence synthesis was performed for neurological treatment approaches. The search yielded 467 RCTs (N = 25373; median PEDro score 6 [IQR 5–7]), identifying 53 interventions. No adverse events were reported. Strong evidence was found for significant positive effects of 13 interventions related to gait, 11 interventions related to arm-hand activities, 1 intervention for ADL, and 3 interventions for physical fitness. Summary Effect Sizes (SESs) ranged from 0.17 (95%CI 0.03–0.70; I2 = 0%) for therapeutic positioning of the paretic arm to 2.47 (95%CI 0.84–4.11; I2 = 77%) for training of sitting balance. There is strong evidence that a higher dose of practice is better, with SESs ranging from 0.21 (95%CI 0.02–0.39; I2 = 6%) for motor function of the paretic arm to 0.61 (95%CI 0.41–0.82; I2 = 41%) for muscle strength of the paretic leg. Subgroup analyses yielded significant differences with respect to timing poststroke for 10 interventions. Neurological treatment approaches to training of body functions and activities showed equal or unfavorable effects when compared to other training interventions. Main limitations of the present review are not using individual patient data for meta-analyses and absence of correction for multiple testing.
Citation: Veerbeek JM, van Wegen E, van Peppen R, van der Wees PJ, Hendriks E, Rietberg M, et al. (2014) What Is the Evidence for Physical Therapy Poststroke? A Systematic Review and Meta-Analysis. PLoS ONE 9(2): e87987. https://doi.org/10.1371/journal.pone.0087987
Editor: Terence J. Quinn, University of Glasgow, United Kingdom
Received: October 29, 2013; Accepted: December 30, 2013; Published: February 4, 2014
Copyright: © 2014 Veerbeek et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research project was supported by the Royal Dutch Society for Physical Therapy (KNGF grant no. 8091.1; http://www.fysionet.nl/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Prospective studies have estimated that about 795.000 people in the USA suffer a first or recurrent stroke each year [1]. The prevalence of chronic stroke in the USA is estimated at about 7 million [1], with about 80% of patients with stroke being over the age of 65. The prevalence of stroke is likely to increase in the future due to the aging population. Even though acute stroke care has improved, for example by large-scale application of recombinant tissue plasminogen activator (rTPA) [1], [2] and organized interdisciplinary inpatient stroke care [3], and although mortality rates have been decreasing [1], a large number of patients still remain disabled regardless of the time that has elapsed poststroke. Only 12% of the patients with stroke are independent in basic activities of daily living (ADL) at the end of the first week [4]. In the long term, 25–74% of patients have to rely on human assistance for basic ADLs like feeding, self-care, and mobility [5].
Interdisciplinary complex rehabilitation interventions [6], [7] are assumed to represent the mainstay of poststroke care [8]. One of the key disciplines in interdisciplinary stroke rehabilitation is physical therapy which is primarily aimed at restoring and maintaining ADLs, usually starting within the first days and often continuing into the chronic phase poststroke [8]. While the interdisciplinary character of stroke rehabilitation is paramount, the availability of specific, up-to-date, and professional evidence-based guidelines for the physical therapy profession is crucial for making adequate evidence-based clinical decisions [9]–[11]. The recommendations in the first Dutch evidence-based ‘Clinical Practice Guideline for physical therapy in patients with stroke’ were based on meta-analyses of 123 randomized controlled trials (RCTs) and date back to 2004 [12]. In view of the tremendous growth in the number of RCTs in this field, it is now necessary to re-establish the “state of the art” concerning the evidence for physical therapy interventions in stroke rehabilitation. This aim is in line with the 2006 Helsingborg Declaration on European Stroke Strategies, which states that stroke rehabilitation should be based on evidence as much as possible [13], [14].
The first aim of the present systematic review was to update our previous meta-analyses of complex stroke rehabilitation interventions in the domain of physical therapy, based on RCTs with a low risk of bias (i.e. a moderate to good methodological quality) with no restrictions to the comparator. Primary outcomes, measured post intervention, were defined at the levels of body functions and/or activities and participation of the International Classification of Functioning, disability and health model (ICF) [15]. The second aim was to explore whether the timing of interventions poststroke moderated the main effects.
Methods
Definitions
In accordance with the definition used by the World Health Organization (WHO), stroke was defined as “rapidly developing clinical symptoms and/or signs of focal, and at times global, loss of cerebral function, with symptoms lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin” [16]. We distinguished four poststroke phases: the hyper acute or acute phase (0–24 hours), the early rehabilitation phase (24 hours until 3 months), the late rehabilitation phase (3–6 months), and the chronic phase (>6 months).
A study was considered an RCT when “the individuals (or other units) followed in the trial were definitely or possibly assigned prospectively to one of two (or more) alternative forms of health care using random allocation” [17].
Physical therapy was defined as “therapeutic modalities frequently used in physical therapy specialty by physical therapists or physiotherapists to promote, maintain, or restore the physical and physiological well-being of an individual” (Medline Subject Heading; MeSH). According to the American Physical Therapy Association (APTA), “physical therapists are health care professionals who maintain, restore, and improve movement, activity, and health, enabling an individual to have optimal functioning and quality of life, while ensuring patient safety and applying evidence to provide efficient and effective care. Physical therapists evaluate, diagnose, and manage individuals of all ages who have impairments, activity limitations, and participation restrictions. In addition, physical therapists are involved in promoting health, wellness, and fitness through risk factor identification and the implementation of services to reduce risk, slow the progression of or prevent functional decline and disability, and enhance participation in chosen life situations.” [18].
Exercise therapy refers to “a regimen or plan of physical activities designed and prescribed for specific therapeutic goals” (MeSH) in the field of physical therapy, intended to restore optimal functioning [19]. For the present meta-analysis, we included the use of technical applications such as robotics, electrostimulation and treadmills with body-weight support.
In line with previous reviews, we defined intensity of practice as the number of hours spent in exercise therapy [12], [19], [20]. Treatment contrast refers to “the amount of time spent on exercise therapy by the experimental group minus that spent by the control group” [20].
Activities of daily living (ADL) are “the daily self-care activities required to function in the home and/or outdoor environment. They may be classified as basic or extended” [21]. Basic ADL covers the ability to perform basic activities of self-care and mobility [21], [22]. These activities are captured by a combination of two or more of the codes d510 (washing oneself), d530 (toileting), d550 (eating), d540 (dressing), b5253 (fecal continence) and b6202 (urinary continence), d410 (changing basic body position), d420 (transferring oneself), and d450 (walking) as listed in the ICF [22]. By contrast, extended ADL “whilst not fundamental to functioning, allow an individual to live independently, e.g. shopping, housekeeping, managing finances, preparing meals, and using transportation” [21].
Study Identification
Our previous search, covering the period up to January 29, 2004, was updated. Relevant publications were identified by searching the electronic databases PubMed (last searched June 28, 2011), EBSCOhost/Excerpta Medica Databank (EMBASE; last searched June 9, 2011), EBSCOhost/Cumulative Index of Nursing and Allied Health Literature (CINAHL; last searched July 14, 2011), Wiley/Cochrane Library (Cochrane Database of Systematic Reviews [CDSR], Cochrane Central Register of Controlled Trials [CENTRAL], Cochrane Methodology Register [CMR], Database of Abstracts of Reviews of Effects [DARE], Health Technology Assessment Database [HTA], NHS Economic Evaluation Database [EED]; last searched July 21, 2011), Physiotherapy Evidence Database (PEDro; last searched August 24, 2011), and SPORTDiscus™ (last searched August 24, 2011). This was done by J.M.V. after two researchers (J.M.V. and J.C.F.K.) had built the search string. The databases were searched by indexing terms and free-text terms used with synonyms and related terms in the title or abstract. We searched for “stroke”, and “exercise” or “physical therapy” or “physiotherapy” or “rehabilitation”, and “randomized controlled trials” or “reviews” (see table 1). Additional searches were performed for specified interventions. The full search strategy can be obtained from the corresponding author. One reviewer (J.M.V.), who was not blinded, screened the titles and abstracts and assessed potentially relevant publications in full-text. In addition, references of included RCTs and relevant reviews like those of the Cochrane Collaboration and the Evidence-Based Review of Stroke Rehabilitation (EBRSR) were screened. Authors of conference abstracts were contacted for full-text publications, if available, and experts in the field were consulted.
Studies were included if they met the following inclusion criteria: (1) the study sample analyzed consisted exclusively of patients with stroke aged 18 years or over; (2) the study was designed as an RCT including those with a two-group parallel, multi-arm parallel, crossover, cluster, or factorial designs; (3) the experimental intervention delivered fitted the domain of physical therapy and aimed to improve body functions and/or activities and participation and/or contextual factors; (4) the comparator was usual care, another intervention, the same intervention with a different dose, or no intervention; (5) the outcomes were measured post intervention and belonged to the domain of physical therapy (see the section on “Intervention categories and outcome domains”); and (6) the full-text publication was written in English, French, German, Spanish, Portuguese, or Dutch.
A review protocol was not published. An ethics statement was not required for this work.
Data Extraction
One reviewer (J.M.V.) extracted the following information from the included RCTs using two forms developed in advance: first author, year of publication, number of patients in each group, eligibility criteria, stroke characteristics including poststroke phase, intervention characteristics, outcome measures, timing of assessment, the authors’ conclusions and the post intervention, and if applicable follow-up, point measures and measures of variability for each of the reported outcomes. Study authors were contacted in case the published results could not be used in the meta-analyses, e.g. when ranges were given instead of standard deviations (SDs) or interquartile ranges (IQRs), or results were only presented in graphs. The extracted data for the meta-analyses were cross-checked in random order. Duplicate publications were included, but counted as one RCT.
Intervention Categories and Outcome Domains
Based on consensus between the authors, physical therapy interventions for the rehabilitation of patients with stroke were divided into: (1) interventions related to gait and mobility-related functions and activities, including novel methods focusing on efficient resource use, such as circuit class training and caregiver-mediated exercises; (2) interventions related to arm-hand activities; (3) interventions related to activities of daily living; (4) interventions related to physical fitness; and (5) other interventions which could not be classified into one of the other categories. In addition, attention was paid to (6) intensity of practice and (7) neurological treatment approaches.
The ICF [15], [23] was used to classify the outcome measures into the following domains: muscle and movement functions (e.g. muscle power functions [b730], control of voluntary movement functions [b760], muscle tone functions [b735]), joint and bone functions (e.g. mobility of joint functions [b710]), sensory functions (e.g. proprioceptive function [b260], touch function [b365], sensory functions related to temperature and other stimuli [b720]), gait pattern functions [b770] (e.g. gait speed, stride length), functions of the cardiovascular and respiratory systems (e.g. heart functions [b410], blood pressure functions [b420], respiration functions [b440], respiratory muscle functions [b445], exercise tolerance functions [b455]), mental functions (e.g. quality of life, depression), balance (e.g. changing basic body position [d410], maintaining a body position [d415]), walking [d450] (e.g. distance, independence, falls), arm-hand activities (e.g. fine hand use [d440], hand and arm use [d445]), basic ADL (e.g. washing oneself [d510], toileting [d520], dressing [d540], eating [d550], urination functions [d620]), extended ADL (e.g. acquisition of goods and services [d620], preparing meals [d630], doing housework [d640], recreation and leisure [d920]), and attitudes (e.g. individual attitudes of immediate or extended family members, like caregiver strain [e410 and e425 respectively]). The primary outcomes were at the body functions and activities and participation levels, while secondary outcomes included contextual factors.
Quality Appraisal
The PEDro checklist was used to assess the risk of bias in the included RCTs [24], [25]. This 11-item list estimates the internal and external validity of an RCT based on 11 items. The items concern eligibility criteria, random allocation, concealment of allocation, group similarity at baseline, blinding of subjects, blinding of therapists, blinding of assessors, availability of key outcome measures of more than 85% of the subjects, intention-to-treat analysis, between-group statistical comparisons, and point measures and measures of variability [24], [25]. Except for item 1, which assesses the generalizability, one point is awarded if a criterion is satisfied. The maximum score is 10 points. For the purpose of this study, we considered RCTs with a score of ≥4 to have a low risk of bias [12]. One reviewer (J.M.V.) scored all RCTs identified in the updated search unblinded and crosschecked the scores with the PEDro database (www.pedro.org.au). In case of disagreement, another reviewer (E.v.W) made the final decision. For RCTs not listed in the PEDro database, two reviewers (J.M.V. and E.v.W.) independently assessed the risk of bias and disagreements were resolved in a consensus meeting.
Analyses
Data from identified RCTs are reported in the results section. Our quantitative analyses only included RCTs with a PEDro score of ≥4. Aggregated data of individual RCTs were pooled when at least two RCTs with a measure in the same outcome category were available for an intervention. Interventions for which pooling was possible were automatically indicated as “strong evidence”, regardless of the direction of the results, because only RCTs with a low risk of bias were included (Level 1) [26]. A “strong evidence” label was also assigned when only one phase III trial was available for a particular intervention. Analogous to our 2004 review, a qualitative analysis was performed for the intervention category “neurological treatment approaches”. Based on an adaptation of the criteria established by Van Tulder et al. [26] the following four levels of evidence were distinguished:
Level 1. Strong evidence – provided by generally consistent findings in multiple, relevant, high-quality RCTs.
Level 2. Moderate evidence – provided by findings in one relevant, high-quality RCT.
Level 3. Limited evidence – provided by generally consistent findings in one or more relevant low-quality RCTs.
Level 4. No or conflicting evidence – if there were no RCTs or if the results were conflicting.
RCTs with a PEDro score of ≥4 are considered to be of high-quality, while a score of <4 is considered as low-quality.
Quantitative Analysis
Studies with a crossover design were considered RCTs. Measurements up to the crossover point were used as post intervention outcomes. Single-session experiments were not included in the quantitative analyses.
Meta-analyses were performed for each intervention for which at least two RCTs with comparable outcomes were identified. Based on post intervention outcomes (means and SDs), the individual effect sizes with their 95% confidence intervals (CI) were calculated as Hedges’ g. The individual Hedges’ g values were pooled to determine the summary effect size (SES; number of SD units) and 95%CI. The I2 statistic was used to determine statistical consistency (between-study variation) [17]. An I2 of >50.0% was considered to reflect substantial heterogeneity [17] and in that case a random-effects model was applied, while a fixed-effect model was applied in case of statistical homogeneity. A significant positive SES indicates that the experimental intervention is beneficial for patients when compared to a comparator. In the same vein, a significant negative SES indicates that the intervention has unfavorable effects for patients when compared to a comparator.
We pre-specified that in case of differences between RCTs in the timing of the interventions after stroke, a possible moderator effect of timing after stroke would be explored (in accordance with the phases described in the “Definitions” section) [27]. The variance between the subgroups was statistically tested in a “fixed-effect or random-effects within, fixed-effects between” model by applying the Q-test based on analysis of variance (ANOVA). Since the number of studies within each subgroup was five or less in nearly all meta-analyses, a pooled estimate of τ2 (variance of the distribution of the true effect sizes within subgroups) across subgroups was used, as separate estimates of τ2 for each subgroup are likely to be imprecise [27]. The SES (95%CI) and number of RCTs for each subgroup were only reported if there were significant differences between the poststroke phases.
In all analyses, the null hypothesis was rejected when the probability value was <0.05 (2-tailed). Following Cohen, the effect sizes were classified into small (<0.2), medium (0.2–0.8), and large (>0.8) [28]. All analyses were performed using Comprehensive Meta-analysis (Biostat, Englewood, New Jersey).
The statistical power of each meta-analysis was calculated post hoc, based on the number of RCTs included, the within-study sample size, the SES, the between-studies variance, and 2-tailed p-value [29]. A power of ≥0.8 was regarded as satisfactory.
Results
Study Identification
The search for relevant RCTs is visualized in figure 1. The final selection of RCTs consisted of 467 studies involving 25 373 patients with stroke; 123 RCTs from the 2004 search and an additional 344 RCTs from the updated search. Most studies included patients in the early rehabilitation phase (n = 198) or chronic phase (n = 202). Three RCTs included patients in the hyper acute or acute rehabilitation phase. For details see tables S1A–S1G in file S1.
Legend: ADL, Activities of daily living; BLETRAC, Bilateral leg training with rhythmic auditory cueing; CPM, Continuous passive motion; PEDro, Physiotherapy evidence database; PT, Physical therapy; RCTs, Randomized controlled trials; ROM, Range of motion.
Quality Appraisal
The risk of bias in RCTs has decreased over time, as shown by the increase in PEDro scores from a median of 5 (IQR 4–6) points for RCTs published till 2004 [12] to 6 (IQR 5–7) for the RCTs published from 2004 to 2011. The median PEDro score of all 467 RCTs was 6 (IQR 5–7).
Analyses
Pooling was possible for 23 physical therapy interventions related to gait and mobility-related functions and activities, for 23 interventions related to arm-hand activities, for two interventions related to ADL in general, for four interventions related to physical fitness, and for inspiratory muscle training which did not fit the other categories (see tables S1A–S1E in file S1). Meta-analyses were also performed for intensity of practice (for details see table S1F in file S1).
Quantitative Analysis
Physical therapy interventions related to gait and mobility-related functions and activities. The results of the meta-analyses for interventions related to gait and mobility-related functions and activities are summarized in figure 2 (for details see table S2A in file S1). Pooling was not possible for bilateral leg training with rhythmic gait cueing [30], mirror therapy for the paretic leg [31], mental practice with motor imagery [32], limb overloading with external weights [33], systematic verbal feedback on gait speed [34], maintenance of ankle dorsiflexion by using a standing frame or night splint [35], manual passive mobilization of the ankle [36], range of motion exercises of the ankle with specially designed equipment [37], ultrasound for the paretic leg [38], segmental muscle vibration for a drop foot [39], whole body vibration [40], and wheel chair propulsion [41].
Legend: A green colored diamond indicates that the summary effect size is significant, while a blue colored diamond indicates that the summary effect size is nonsignificant; CI, Confidence interval; EMG-BF, Electromyographic biofeedback; EMG-NMS, Electromyography-triggered neuromuscular stimulation; FES, Functional electrostimulation; GT, Gait training; NA, Not applicable; NMS, Neuromuscular stimulation; TENS, Transcutaneous electrical nerve stimulation; TT, Treadmill training.
- 1. Early mobilization
Early mobilization out of bed within 24 hours poststroke and stimulating the patient to exercise outside the bed [42] was investigated in two RCTs (N = 103, PEDro score 8) [43], [44], including patients in the hyper acute or acute phase.
A nonsignificant SES was found for complications, neurological deterioration early poststroke, fatigue, independence in basic ADL at 3 months, and discharge home.
- 2. Sitting balance training
Training of balance (i.e. maintaining, achieving, or restoring balance) during sitting [45] was investigated in six RCTs (N = 150, PEDro score range 4 [46] to 8 [47]) [46]–[51], including patients in the early rehabilitation phase [46], [47], [49]–[51] or chronic phase [48].
Overall, pooling of data showed a nonsignificant SES for symmetry while sitting and standing, balance, walking ability, and basic ADL. However, pooling only data of RCTs which investigated training of sitting balance while reaching beyond arm’s length yielded a significant heterogeneous positive SES for sitting balance. Nonsignificant SESs were found for ground reaction force while sitting and hand movement time. Subgroup analyses revealed no significant differences between poststroke phases.
- 3. Sit-to-stand training
Training the transfer from sit-to-stand and vice versa while maintaining balance [52] was investigated in five RCTs (N = 163, PEDro score range 4 [53] to 6 [54]–[56]) [53]–[57], including patients who were unable to perform a sit-to-stand without help in the early rehabilitation phase [53], [54], [56], [57] or chronic phase [55].
Nonsignificant SESs were found for body weight distribution, sit-to-stand, and balance. Subgroup analyses revealed no significant differences between poststroke phases.
- 4. Standing balance training without biofeedback
Training of balance (i.e. maintaining, achieving, or restoring balance) during standing [45] without the use of biofeedback was investigated in four RCTs (N = 199, PEDro score range 4 [58] to 8 [59]) [58]–[61], including patients in the early rehabilitation phase [59]–[61] or chronic phase [58]. The training consisted of standing on surfaces of different compliance with eyes open, optionally combined with eyes closed, or standing in a frame.
Nonsignificant SESs were found for postural sway, sit-to-stand, balance, and walking ability. Subgroup analyses revealed no significant differences between poststroke phases.
- 5. Standing balance training with biofeedback – force and position feedback
The use of a force platform with force sensors to measure the weight on each foot and the center of pressure to subsequently give visual or auditory feedback to the patient [8] was investigated in 12 RCTs (N = 333, PEDro score range 3 [62] to 6 [56], [63]–[67]) [56], [62]–[73], including patients in the early rehabilitation phase [56], [68]–[70], [72], [73], late rehabilitation phase [62]–[64], [67], [71], or chronic phase [66]. In most of the RCTs, patients had to be able to get from a seated to a standing position and be able to stand with or without physical support.
A significant homogeneous positive SES was found for postural sway. Subgroup analyses showed that the effect size was only significant in the chronic phase (n = 1), while the SES for the early rehabilitation phase (n = 6) was not. Nonsignificant SESs were found for motor function of the paretic leg (synergy), comfortable gait speed, step length, cadence, monopedal and bipedal phase, balance, walking ability, and basic ADL. Subgroup analyses revealed no significant differences between poststroke phases for these outcomes.
- 6. Balance training during various activities
Training of balance (i.e. maintaining, achieving, or restoring balance) during various activities [45] was investigated in 11 RCTs (N = 419, PEDro score range 4 [74] to 8 [75], [76]) [74]–[84], including patients in the early rehabilitation phase [76], [77], [80], [83], [84], late rehabilitation phase [74], [75], [82], or chronic phase [78], [79], [81].
Pooling resulted in a significant homogeneous positive SES for basic ADL and a significant heterogeneous positive SES for balance. Nonsignificant SESs were found for comfortable gait speed, falls-efficacy, walking ability, and quality of life. Subgroup analyses revealed no significant differences between poststroke phases.
- 7. Body-weight supported treadmill training
Treadmill training with the patient’s body-weight partially supported by a harness [8] was investigated in 18 RCTs (N = 1158, PEDro score range 4 [85]–[87] to 8 [88]–[91]) [85]–[105], including patients in the early rehabilitation phase [85]–[91], [94], [96], [98], [101], [103], [105] or chronic phase [90], [92], [93], [95], [97], [99], [100], [102], [104]. The patients had to be restricted in their walking ability, except in one study [90].
Meta-analyses showed significant heterogeneous positive SESs for comfortable gait speed and walking distance. Nonsignificant SESs were found for motor function of the paretic leg (synergy), maximum gait speed, stride length, cadence, aerobic capacity, energy expenditure, balance, walking ability, and quality of life. Subgroup analyses revealed no significant differences between poststroke phases.
- 8. Electromechanical-assisted gait training
Gait training using an apparatus which guides the walking cycle by electromechanical driven footplates or exoskeleton [8], [106], [107] was investigated in 16 RCTs (N = 766, PEDro score range 4 [108], [109] to 8 [110], [111]) [96], [102], [108]–[123], including patients in the early rehabilitation phase [96], [110], [113]–[115], [118]–[123], late rehabilitation phase [109], or chronic phase [102], [108], [112], [116]. For the purpose of this review, the meta-analyses for electromechanical-assisted gait training were subdivided into two groups: (a) without functional electrostimulation and (b) with functional electrostimulation.
- a. Electromechanical-assisted gait training without functional electrostimulation
Electromechanical-assisted gait training without functional electrostimulation was investigated in 16 RCTs (N = 766) [96], [102], [108]–[110], [112]–[123].
Pooling resulted in significant homogeneous positive SESs for maximum gait speed, walking distance, peak heart rate, and basic ADL. Nonsignificant SESs were found for neurological functions, motor function of the paretic leg (synergy), muscle strength, comfortable gait speed, cadence, step length, heart rate at rest, balance, walking ability, extended ADL, and quality of life. Subgroup analyses showed significant differences between poststroke phases. The analysis for comfortable gait speed showed that only patients in the early rehabilitation phase who were dependent in walking benefited from electromechanical-assisted gait training. As regards balance, a significant homogeneous positive SES was found for the early rehabilitation phase (n = 4), a significant negative effect size for the late rehabilitation phase (n = 1), and a nonsignificant SES for the chronic phase (n = 4). As regards walking ability, a significant homogeneous positive SES was found for patients in the early rehabilitation phase (n = 12), a significant negative effect size for the late rehabilitation phase (n = 1), and a nonsignificant homogeneous negative SES for the chronic phase (n = 3).
- b. Electromechanical-assisted gait training with functional electrostimulation
Electromechanical-assisted gait training with functional electrostimulation was investigated in three RCTs (N = 149) [112], [113], [118].
When data of these RCTs were pooled, significant homogeneous positive SESs were found for balance and walking ability (only for patients in the early rehabilitation phase). The statistical analyses for maximum gait speed and basic ADL resulted in nonsignificant SESs. Subgroup analyses for maximum gait speed revealed that patients in the early rehabilitation phase (dependent in walking; n = 1) significantly benefitted from electromechanical-assisted gait training with functional electrostimulation, while a nonsignificant effect was found for patients with chronic stroke (independent in walking; n = 1).
- 9. Speed dependent treadmill training (without body-weight support)
Speed dependent treadmill training without a harness to partially support the body-weight was investigated in 13 RCTs (N = 610, PEDro score range 4 [124], [125] to 8 [126], [127]) [92], [124]–[136], including patients in the early rehabilitation phase [127], [129], [136]; late rehabilitation phase [130], or chronic phase [92], [124]–[126], [128], [131], [132], [134], [135].
Pooling the results of individual RCTs showed significant homogeneous positive SESs for maximum gait speed and step width. For comfortable gait speed, gait speed endurance, stride length, cadence, VO2max, balance, and walking ability nonsignificant SESs were found. Subgroup analyses revealed no significant differences between poststroke phases.
- 10. Overground walking
Overground walking [137] was investigated in 19 RCTs (N = 1008, PEDro score range 2 [138] to 8 [89], [103], [139]–[143]) [86], [87], [89], [103], [109], [112], [119], [122], [123], [125], [138]–[150], including patients in the early rehabilitation phase [86], [89], [119], [122], [123], late rehabilitation phase [109], [140], [148], [150], or chronic phase [112], [125], [138], [139], [142], [144]–[147], [149].
The meta-analyses resulted in a significant homogeneous positive SES for anxiety in independently walking patients and a significant homogeneous negative SES for aerobic capacity in patients unable to walk dependently. Nonsignificant SESs were found for comfortable gait speed, maximum gait speed, walking distance, stride length, stride time, cadence, gait pattern symmetry, peak heart rate (patients unable to walk dependently), diastolic blood pressure (independently walking patients), systolic blood pressure (independent walking patients), balance, number of falls (independently walking patients), depression (independently walking patients), walking ability, and basic and extended ADL. Subgroup analyses revealed a significant difference in effects between poststroke phases for walking distance, cadence, stride length, balance, and walking ability. As regards walking distance, a significant homogeneous positive SES was found for independently walking patients in the chronic phase (n = 4) and a significant homogeneous negative SES for patients in the early rehabilitation phase who were unable to walk independently (n = 5). As regards cadence, a nonsignificant SES was found in the late rehabilitation phase (n = 2) and a significant negative effect size in the chronic phase (n = 1). As regards stride length, a nonsignificant effect size was found in the early rehabilitation phase, and a significant positive effect size was found in the late rehabilitation phase and chronic phase (all n = 1). As regards balance, a significant positive effect size was found in the late rehabilitation phase (n = 1) and a nonsignificant SES in the chronic phase (n = 4). As regards walking ability, a nonsignificant SES was found in the early rehabilitation phase (n = 6), a significant positive effect size in the late rehabilitation phase (n = 1), and a significant homogeneous positive SES in the chronic phase (n = 5).
- 11. Rhythmic gait cueing
Rhythmic auditory cueing to improve the gait pattern [8], [151] was investigated in six RCTs (N = 231, PEDro score range 3 [151]–[153] to 7 [154]) [151]–[156], including patients in the early rehabilitation phase [151], [153]–[155] or chronic phase [152], [156].
Only the RCTs including patients in the early rehabilitation phase could be pooled. Nonsignificant SESs were found for gait speed, cadence, stride length, and gait pattern symmetry.
- 12. Community walking
Training of walking in a community environment like a shopping mall or park [157] was investigated in three RCTs (N = 94, PEDro score range 6 [157], [158] to 8 [126]) [126], [157], [158], including patients in the early rehabilitation phase [157] or chronic phase [126], [158].
Pooling the data from the individual RCTs resulted in nonsignificant SESs for maximum gait speed, walking distance, and balance confidence. Subgroup analyses revealed no significant differences between poststroke phases.
- 13. Virtual reality mobility training
Training of mobility in a virtual environment using computer technology which enables patients to interact with this environment and receive feedback about the performance of movements and activities [159], [160] was investigated in six RCTs (N = 150, PEDro score range 5 [161], [162] to 7 [163]) [161]–[167], including patients in the early rehabilitation phase.
The meta-analyses showed nonsignificant SESs for comfortable gait speed, maximum gait speed, step length, and walking ability.
- 14. Circuit class training
Supervised circuit class training focused on gait and mobility-related functions and activities, in which patients train in groups in various work stations [168], [169], was investigated in eight RCTs (N = 359, PEDro score range 5 [146] to 8 [75], [142], [149], [170], [171]) [75], [81], [142], [143], [146], [170]–[173], including patients in the early rehabilitation phase [170], late rehabilitation phase [75], [171], [173], or chronic phase [81], [142], [146], [172].
Pooling resulted in significant homogeneous positive SESs for walking distance, balance, walking ability, and physical activity. Nonsignificant SESs were found for muscle strength, gait speed, self-efficacy, depression, number of falls, basic and extended ADL, and quality of life. Subgroup analyses revealed no significant differences between poststroke phases.
- 15. Caregiver-mediated exercises
Training of gait and mobility-related functions and activities with a caregiver under the auspices of a physical therapist [174] was investigated in three RCTs (N = 350, PEDro score range 4 [144] to 8 [174], [175]) [144], [174], [175], including patients in the early rehabilitation phase [174], [175] or chronic phase [144].
The meta-analyses resulted in significant homogeneous positive SESs for basic ADL and caregiver strain. A nonsignificant SES was found for extended ADL. Subgroup analyses revealed no significant differences between poststroke phases.
- 16. Orthosis for walking
The use of a splint or orthosis (ankle foot orthosis [AFO] or knee ankle foot orthosis [KEVO]) for walking was investigated in four RCTs (N = 137, PEDro score range 2 [176] to 7 [177]) [85], [176]–[178], which included patients in the early rehabilitation phase [85] or chronic phase [177], [178]. The poststroke phase was unclear for one RCT [176].
After pooling, a nonsignificant SES for comfortable gait speed was found when comparing walking with an orthosis with walking without an orthosis. Subgroup analyses revealed no significant differences between poststroke phases.
- 17. Water-based exercises
Water-based exercises are defined as “a therapy programme using the properties of water, designed by a suitably qualified physical therapist, to improve function, ideally in a purpose-built and suitably heated hydrotherapy pool” [179]. These exercises were investigated in three RCTs (N = 65, PEDro score range 5 [180], [181] to 6 [182]) [180]–[182], which all included patients in the chronic phase.
A significant homogeneous positive SES was found for muscle strength and a nonsignificant SES for balance.
- 18. Interventions for somatosensory functions of the paretic leg
Interventions designed to decrease or resolve impairments of the somatosensory functions of the paretic leg by e.g. electrostimulation or exposure to different stimuli such as texture, shape, temperature, or position [183], [184] were investigated in six RCTs (N = 151, PEDro score range 5 [185] to 8 [186]) [60], [185]–[189], including patients in the early rehabilitation phase [60], [187], [189], late rehabilitation phase [186], [188], or chronic phase [185].
The meta-analyses resulted in nonsignificant SESs for motor function of the paretic leg (synergy), gait speed, and balance. Subgroup analyses revealed no significant differences between poststroke phases.
- 19. Electrostimulation of the paretic leg
Electrostimulation of peripheral nerves and muscles with external electrodes [190] can be applied during training of activities, but also when just functions, like ankle dorsiflexion, are trained in a non-functional manner. For the purpose of this review, electrostimulation was divided into (a) neuromuscular stimulation (NMS); (b) electromyography-triggered neuromuscular stimulation (EMG-NMS); and (c) transcutaneous electrical nerve stimulation (TENS). Electrostimulation of the paretic leg was investigated in 26 RCTs (N = 814, PEDro score range 2 [176] to 8 [186], [191], [192]) [113], [118], [176], [186], [191]–[213], including patients in the early rehabilitation phase [113], [118], [192], [195], [196], [199]–[201], [203], [204], [206], [208], [212], late rehabilitation phase [186], [193], [197], [209], or chronic phase [194], [198], [202], [205], [207], [210], [213]. The RCT investigating the combination of EMG-NMS and NMS was not included in the meta-analyses [195]. The electrostimulation was not applied when outcomes were measured.
- a. NMS
NMS of the paretic leg was investigated in 18 RCTs (N = 551) [113], [118], [176], [191]–[194], [196]–[198], [201]–[204], [206]–[208], [213].
Pooling resulted in significant homogeneous positive SESs for motor function of the paretic leg (synergy), muscle strength, and muscle tone. Nonsignificant SESs were found for active range of motion, gait speed, cadence, step and stride length, gait symmetry, balance, walking ability, and basic ADL. Subgroup analyses revealed no significant differences between poststroke phases.
- b. EMG-NMS
EMG-NMS of the paretic leg was investigated in two RCTs (N = 68) [199], [209].
The meta-analyses resulted in nonsignificant SESs for muscle tone and basic ADL. Subgroup analyses revealed no significant differences between phases poststroke.
- c. TENS
TENS of the paretic leg was investigated in five RCTs (N = 349) [186], [200], [205], [210]–[212].
Meta-analyses showed significant homogeneous positive SESs for muscle strength and walking ability, while nonsignificant SESs were found for muscle tone, active range of motion, gait speed, and walking distance. Subgroup analyses revealed no significant differences between poststroke phases.
- 20. Electromyographic biofeedback for the paretic leg
Electromyographic biofeedback (EMG-BF) involves registering the muscle activity by surface electrodes that are applied to the skin covering the muscles of interest [214], [215]. A biofeedback apparatus converts the recorded muscle activity (EMG) into visual or auditory information. EMG-BF for the paretic leg was investigated in 11 RCTs (N = 254, PEDro score range 2 [216] to 7 [217]) [152], [194], [216]–[224], including patients in the early rehabilitation phase [216], [219], [224] or chronic phase [152], [194], [217], [218], [220], [222], [223].
Pooling resulted in nonsignificant SESs for range of motion, gait speed, step and stride length, and EMG activity. Subgroup analyses revealed no significant differences between poststroke phases.
Physical therapy interventions related to arm-hand activities.
The results of the meta-analyses for interventions related to arm-hand activities are summarized in figure 3 (for details see table S2B in file S1). Pooling was not possible for immobilization of the paretic arm (i.e. “forced-use”) [225], [226], wrist robotics [227], [228], wrist-hand robotics [229], continuous passive motion for the paretic shoulder [230], subsensory threshold electrical and vibration stimulation of the paretic arm [231], circuit class training [143], [182], passive bilateral arm training [232], and using a mechanical arm trainer [233], [234].
Legend: A green colored diamond indicates that the summary effect size is significant, while a blue colored diamond indicates that the summary effect size is nonsignificant; CI, Confidence Interval; CIMT, Constraint-induced movement therapy; EMG-BF, Electromyographic biofeedback; EMG-NMS, Electromyography-triggered neuromuscular stimulation; GHS, Glenohumeral subluxation; HSP, Hemiplegic shoulder pain; mCIMT, modified Constraint-induced movement therapy; NA, Not applicable; NMS, Neuromuscular stimulation; TENS, Transcutaneous electrical nerve stimulation.
- 1. Therapeutic positioning of the paretic arm
Therapeutic positioning of the paretic arm, without the use of splints, with the purpose of maintaining range of motion and preventing harmful positions of the paretic arm [8] was investigated in five RCTs (N = 140, PEDro score range 6 [235], [236] to 7 [237]–[239]) [235]–[239], which all included patients in the early rehabilitation phase.
A significant homogeneous positive SES was found for passive range of motion of shoulder external rotation. Nonsignificant SESs were found for passive range of motion of shoulder internal rotation, external rotation contracture of the shoulder, pain at rest and while moving, and basic ADL.
- 2. Reflex-inhibiting positions and immobilization techniques for the paretic wrist and hand
The use of reflex-inhibiting positions or local immobilization of the wrist and hand by splints or plaster to (1) prevent or decrease an increased muscle tone or (2) to maintain or increase the range of motion of wrist and/or finger extension [8] were investigated in eight RCTs (N = 197, PEDro score range 3 [240] to 8 [241], [242]) [240]–[247], including patients in the early rehabilitation phase [241], [242], late rehabilitation phase [240], or chronic phase [243]–[247].
Meta-analyses resulted in nonsignificant SESs for passive range of motion, muscle tone, and pain. Subgroup analyses revealed no significant differences between poststroke phases.
- 3. Air-splints around the paretic arm
Air-splints give external pressure around the paretic limb and are primarily used to reduce an increased muscle tone [248], [249] and/or hand edema. Five RCTs investigated the effect of air-splints (N = 285, PEDro score range 4 [250], [251] to 8 [252]) [250]–[255], including patients in the early rehabilitation phase [250], [252], [254] or late rehabilitation phase [255]. The poststroke phase was unclear in one RCT [253].
Pooling resulted in nonsignificant SESs for motor function of the paretic arm (synergy), muscle tone, somatosensory functions, pain, and arm-hand activities. However, subgroup analyses revealed a significant homogeneous negative SES for muscle tone for patients in the early rehabilitation phase (n = 1, with 2 comparisons) and a significant homogeneous positive effect size for patients in the late rehabilitation phase (n = 1).
- 4. Supportive techniques or devices for the prevention or treatment of glenohumeral subluxation and/or hemiplegic shoulder pain
Supportive techniques – like strapping – or devices – like a sling or arm orthosis – for the prevention or treatment of glenohumeral subluxation and/or hemiplegic shoulder pain [256] were investigated in three RCTs (N = 142, PEDro score range from 4 [257] to 7 [258], [259]) [257]–[259], including patients in the early rehabilitation phase.
In the meta-analyses, nonsignificant SESs were found for motor function of the paretic arm and for pain.
- 5. Bilateral arm training
During bilateral arm training, movement patterns or activities are performed with both hands simultaneously but independent from each other and could be cyclic [8], [260]. This type of training was investigated in 22 RCTs (N = 823, PEDro score range 2 [261], [262] to 8 [263]) [261]–[282], including patients in the early rehabilitation phase [263], [265], [272], late rehabilitation phase [273], or chronic phase [261], [262], [264], [265], [267]–[271], [274]–[282]. The poststroke phase was unknown for one RCT [266].
The meta-analyses yielded nonsignificant SESs for motor function of the paretic arm (synergy), muscle strength, arm-hand activities, self-reported arm-hand use in daily life, and basic ADL. Subgroup analyses revealed no significant differences between poststroke phases.
- 6. Original or modified Constraint-induced movement therapy
Original or modified Constraint-Induced Movement Therapy (CIMT or mCIMT respectively) consists of immobilization of the non-paretic arm and is combined with repetitive task-specific training of the paretic arm, including shaping techniques [8].
(m)CIMT was investigated in 41 RCTs (N = 1342, PEDro score range 2 [261], [262], [283]–[285] to 8 [286]) [225], [226], [261], [262], [264], [270], [278], [282]–[318], including patients in the early rehabilitation phase [225], [226], [288], [293], [295], [299], [305], [309], [310], [312], [318], late rehabilitation phase [284], [289], [297], or chronic phase [261], [262], [264], [270], [278], [282], [283], [285]–[287], [290]–[292], [294], [296], [300]–[304], [307], [308], [313]–[317].
Different categories can be distinguished, depending on the duration of the immobilization of the paretic arm and the intensity of task-specific practice: (a) original CIMT, (b) high-intensity mCIMT, (c) low-intensity mCIMT, and (d) immobilization of the non-paretic arm (i.e. “forced-use”).
- a. Original CIMT
Original CIMT is applied for 2 to 3 weeks and consists of (1) immobilization of the non-paretic arm with a padded mitt for 90% of the waking hours; (2) task-oriented training with a high number of repetitions for 6 hours a day; and (3) behavioral strategies to improve both compliance and transfer of the activities practiced from the clinical setting to the patient’s home environment. Original CIMT was investigated in one RCT (N = 222) [297], [298], which included patients in the late rehabilitation phase.
Significant positive effect sizes were found for arm-hand activities, self-reported amount of arm-hand use in daily life, and self-reported quality of arm-hand movement in daily life. Due to the size of the study sample and the low risk of bias, this result is classified as level 1 evidence.
- b. High-intensity mCIMT
High-intensity mCIMT consists of (1) immobilization of the non-paretic arm with a padded mitt during 90% of the waking hours and (2) between 3 and 6 hours of task-oriented training a day. High-intensity mCIMT was investigated in 17 RCTs (N = 512) [261], [270], [285]–[287], [290], [291], [295], [296], [299], [304], [305], [308], [310]–[312], [314], [318], including patients in the early rehabilitation phase [295], [299], [305], [310], [312], [318] or chronic phase [261], [270], [285]–[287], [290], [291], [296], [304], [308], [314].
Pooling resulted in significant homogeneous positive SESs for arm-hand activities and self-reported quality of arm-hand movement in daily life. In addition, a significant heterogeneous positive SES was found for self-reported amount of the arm-hand use in daily life. Nonsignificant SESs were found for motor function of the paretic arm (synergy) and basic ADL. Subgroup analyses revealed a significant difference between poststroke phases for basic ADL. A significant positive effect size was found for the early rehabilitation phase (n = 1) and a nonsignificant effect size for the chronic phase (n = 1).
- c. Low-intensity mCIMT
Low-intensity mCIMT consists of (1) immobilization of the non-paretic arm with a padded mitt during >0% to <90% of the waking hours and (2) between 0 and 3 hours of task-oriented training a day. Low-intensity mCIMT was investigated in 23 RCTs (N = 627) [262], [264], [278], [280], [282]–[284], [288], [289], [292]–[294], [300]–[303], [307], [309]–[313], [315], [317], including patients in the early rehabilitation phase [288], [293], [309], [312], late rehabilitation phase [284], [289], or chronic phase [262], [264], [278], [282], [283], [292], [294], [300]–[303], [307], [313], [315]–[317].
The meta-analyses yielded significant homogeneous positive SESs for motor function of the paretic arm (synergy), arm-hand activities, self-reported amount of arm-hand use in daily life, self-reported quality of arm-hand movement in daily life, and basic ADL. A nonsignificant SES was found for arm-related quality of life. Subgroup analyses for motor function of the paretic arm (synergy) showed that the positive effects were significant for the early rehabilitation phase (n = 1) and chronic phase (n = 12), but not for the late rehabilitation phase (n = 2).
- 7. Robot-assisted arm training
Robotic devices allow repetitive, interactive, high intensity training of the paretic arm and/or hand [8], [319]. Training with robotic devices was investigated in 22 RCTs (N = 648, PEDro score range 4 [227], [320]–[322] to 8 [323]) [227]–[229], [273], [320]–[338], including patients in the early rehabilitation phase [321], [322], [324], [325], [329], [331], [332], [336], [337], late rehabilitation phase [273], or chronic phase [227]–[229], [320], [323], [326]–[328], [330], [333]–[335], [338].
For the purpose of this review, robotic devices are classified on the basis of the joints they target: (a) shoulder-elbow robots; (b) elbow-wrist robots; and (c) shoulder-elbow-wrist-hand robots.
- a. Shoulder-elbow robotics
Shoulder-elbow robots used in a unilateral mode were applied in 15 RCTs (N = 546) [273], [322], [324], [326]–[328], [330]–[338].
Pooling resulted in significant homogeneous positive SESs for motor function of the proximal part of the paretic arm (synergy), muscle strength, and pain. Nonsignificant SESs were found for motor function of the paretic arm, motor function of the distal part of the paretic arm, muscle tone, arm-hand activities, basic ADL, and quality of life. Subgroup analyses revealed no significant differences between poststroke phases.
- b. Elbow-wrist robotics
Elbow-wrist robots used in a bilateral mode were investigated in two RCTs (N = 62) [323], [329].
Meta-analyses showed significant homogeneous positive SESs for motor function of the paretic arm (synergy) and muscle strength. Subgroup analyses revealed no significant differences between phases poststroke.
- c. Shoulder-elbow-wrist-hand robotics
Shoulder-elbow-wrist-hand robots were investigated in two RCTs (N = 39) [320], [321].
Pooling the data resulted in nonsignificant SESs for both motor function of the paretic arm (synergy) and muscle strength of the distal part of the arm. Subgroup analyses revealed no significant differences between poststroke phases.
- 8. Mental practice with motor imagery
Mental practice of motor actions and/or activities for the purpose of improving their performance [8], [339] combined with physical practice, was investigated in 14 RCTs (N = 424, PEDro score range 4 [340], [341] to 7 [342]–[345]) [340]–[352], including patients in the early rehabilitation phase [340]–[342], [344], [345], [351] or chronic phase [346]–[350], [352], [353].
The meta-analyses showed a significant heterogeneous positive SES for arm-hand activities and nonsignificant SESs for motor function of the paretic arm (synergy), muscle strength, and basic ADL. Subgroup analyses revealed no significant differences between poststroke phases.
- 9. Mirror therapy for the paretic arm
During mirror therapy, the patient looks in a mirror placed perpendicular to the body. Looking in the mirror creates the suggestion that the patient is observing movements of the affected arm. Mirror therapy was investigated in seven RCTs (N = 255, PEDro score range 5 [349], [354] to 8 [355]) [349], [354]–[359], including patients in the early rehabilitation phase [359], late rehabilitation phase [357], [358], or chronic phase [349], [354]–[356].
Pooling resulted in nonsignificant SESs for motor function of the paretic arm (synergy), muscle tone, pain, and arm-hand activities. Subgroup analyses revealed a significant positive effect size for arm-hand activities in the late rehabilitation phase (n = 1) and a nonsignificant SES in the chronic phase (n = 2).
- 10. Virtual reality training for the paretic arm
Training of the arm and hand in a virtual environment using computer technology which enables patients to interact with this environment and receive feedback about the performance of movements and activities [159], [360] was investigated in 15 RCTs (N = 357, PEDro score range 3 [361]–[365] to 8 [366]) [360]–[375], including patients in the early rehabilitation phase [360], [363], [364], [373], [375], late rehabilitation phase [369], [370], or chronic phase [361], [362], [365]–[368], [371], [372], [374].
Pooling resulted in a significant homogeneous positive SES for basic ADL and a significant homogeneous negative SES for muscle tone. Nonsignificant SESs were found for motor function of the paretic arm (synergy) and arm-hand activities. Subgroup analyses revealed no significant differences between poststroke phases.
- 11. Electrostimulation of the paretic arm
Electrostimulation of peripheral nerves and muscles with external electrodes [190] can be applied during training of activities, but also when just functions, like wrist extension, are trained in a non-functional manner. For the purpose of the present review, electrostimulation was divided into (a) neuromuscular stimulation (NMS); (b) electromyography-triggered neuromuscular stimulation (EMG-NMS); and (c) transcutaneous electrical nerve stimulation (TENS). Electrostimulation of the paretic arm was investigated in 49 RCTs (N = 1521, PEDro score range 3 [376]–[379] to 8 [380]) [200], [267], [271], [321], [328], [376]–[423], including patients in the early rehabilitation phase [200], [321], [376], [380], [381], [383], [384], [386], [387], [389]–[392], [395], [402], [404], [405], [407], [413], [415]–[417], [419], [420], [422], late rehabilitation phase [382], [398]–[400], [406], [418], or chronic phase [267], [271], [328], [377]–[379], [393], [394], [396], [397], [401], [403], [408]–[412], [414], [421], [423]. The electrostimulation was not applied when outcomes were measured.
- a. NMS
NMS of the paretic arm was investigated in 22 RCTs (N = 894) [376], [380], [381], [383]–[386], [389]–[392], [396], [398], [400], [402], [404], [406], [407], [410], [417]–[421].
- a1. Wrist and finger extensors
Meta-analyses showed nonsignificant SESs for motor function of the paretic arm (synergy), active range of motion, muscle strength, and arm-hand activities. Subgroup analyses revealed no significant differences between poststroke phases.
- a2. Wrist and finger flexors and extensors
The meta-analyses yielded significant homogeneous positive SESs for motor function of the paretic arm (synergy) and muscle strength, while the SES for arm-hand activities was nonsignificant.
- a3. Shoulder muscles
Pooling resulted in a significant heterogeneous positive SES for shoulder subluxation, while nonsignificant SESs were found for motor function of the paretic arm (synergy), range of motion, and pain. Subgroup analyses revealed no significant differences between poststroke phases.
- b. EMG-NMS
EMG-NMS of the paretic arm was investigated in 25 RCTs (N = 492) [267], [271], [321], [328], [378], [379], [387], [393]–[395], [397], [399], [401], [403]–[405], [408]–[414], [416], [422], [423].
- b1. Wrist and finger extensors
The meta-analyses resulted in significant homogeneous positive SESs for motor function of the paretic arm (synergy) and arm-hand activities. A significant heterogeneous positive SES was found for active range of motion. The SESs for muscle strength and muscle tone were nonsignificant. Subgroup analyses revealed no significant differences between poststroke phases.
- b2. Wrist and finger flexors and extensors
Pooling showed nonsignificant SESs for motor function of the paretic arm (synergy) and arm-hand activities. Subgroup analyses revealed no significant differences between poststroke phases.
- c. TENS
TENS of the paretic arm was investigated in four RCTs (N = 484) [200], [377], [382], [388], [415].
Pooling resulted in nonsignificant SESs for both muscle tone and basic ADL. Subgroup analyses revealed no significant differences between poststroke phases.
- 12. Electromyographic biofeedback of the paretic arm
Electromyographic biofeedback (EMG-BF) involves the muscle activity being registered by surface electrodes which are applied to the skin covering the muscles of interest [214], [215]. A biofeedback apparatus converts the recorded muscle activity (EMG) into visual or auditory information. EMG-BF for the paretic arm was investigated in 11 RCTs (N = 317, PEDro score range 2 [424] to 7 [425], [426]) [219], [424]–[433], including patients in the early rehabilitation phase [219], [425], [430], late rehabilitation phase [426], [429], [432], [433], or chronic phase [427], [428], [431]. The phase poststroke was unclear for one RCT [424].
Meta-analyses resulted in nonsignificant SESs for motor function of the paretic arm (synergy), active range of motion, and arm-hand activities. Subgroup analyses revealed no significant differences between poststroke phases.
- 13. Trunk restraint
Fixing the trunk externally during reaching and grasping prevents compensatory movements of the trunk [434]. Trunk restraint was investigated in four RCTs (N = 86, PEDro score range 4 [435] to 8 [436]) [314], [434]–[436], which all included patients in the chronic phase.
The meta-analyses showed a significant homogeneous negative SES for self-reported amount of arm-hand use in daily life. A nonsignificant SES was found for active range of motion and arm-hand activities.
- 14. Interventions for somatosensory functions of the paretic arm
Interventions designed to decrease or resolve impairments in somatosensory functions of the paretic arm by e.g. electrostimulation or exposure to different stimuli like texture, shape, temperature or position [183], [184] were investigated in 12 RCTs (N = 580, PEDro score range 3 [377], [388] to 9 [437]) [188], [250], [251], [255], [377], [388], [398], [437]–[443], including patients in the early rehabilitation phase [250], [440], [443], late rehabilitation phase [188], [255], [398], [437], or chronic phase [377], [438], [439], [441], [442].
Meta-analyses showed significant homogeneous positive SESs for somatosensory functions and muscle tone. The analyses resulted in nonsignificant SESs for motor function of the paretic arm (synergy), muscle strength, pain, arm-hand activities, and basic ADL. Subgroup analyses revealed no significant differences between poststroke phases.
Physical therapy interventions for physical fitness.
Planned and structured physical exercises aiming to improve physical fitness can be divided into programs primarily targeting (1) strength of the paretic leg; (2) strength of the paretic arm; (3) aerobic capacity; and (4) a combination of strength and aerobic capacity [8], [444], [445]. The results of the meta-analyses are summarized in figure 4 (for details see table S2C in file S1).
Legend: A green colored diamond indicates that the summary effect size is significant, while a blue colored diamond indicates that the summary effect size is nonsignificant; CI, Confidence interval; NA, Not applicable.
- 1. Strength exercises for the paretic leg
Progressive active exercises against resistance for the paretic leg were investigated in 19 RCTs (N = 786, PEDro score range 2 [446] to 8 [172], [447]) [172], [446]–[464], including patients in the early rehabilitation phase [448], [452], [456], [457], [461], [463], [464], late rehabilitation phase [449], or chronic phase [172], [446], [447], [450], [451], [453]–[455], [458], [460], [462].
Pooling resulted in significant homogeneous positive SESs for muscle strength, muscle tone, and spatiotemporal gait pattern parameters like cadence, stride length, and symmetry. Nonsignificant SESs were found for motor function of the paretic leg (synergy), comfortable gait speed, maximum gait speed, walking distance, aerobic capacity, heart rate work, workload, physical cost index, walking ability, basic ADL, and quality of life. Subgroup analyses revealed no significant differences between poststroke phases.
- 2. Strength exercises for the paretic arm
Progressive active exercises against resistance for the paretic arm were investigated in nine RCTs (N = 327, PEDro score range 2 [465] to 7 [99], [466]) [99], [446], [451], [462], [465]–[469], including patients in the early rehabilitation phase [465], [466], [468] or chronic phase [99], [446], [451], [462], [467], [469].
Pooling the data resulted in nonsignificant SESs for motor function of the paretic arm (synergy), muscle strength, range of motion, and pain. Subgroup analyses revealed no significant differences between poststroke phases.
- 3. Cardiorespiratory exercises
Interventions focusing on maintenance or improvement of the aerobic capacity by training large muscle groups, for example while walking overground or on a treadmill, or cycling on an ergometer, were investigated in 13 RCTs (N = 531, PEDro score range 4 [470], [471] to 8 [88], [127], [447], [459]) [88], [104], [124], [127], [132]–[135], [182], [447], [459], [470]–[477], including patients in the early rehabilitation phase [88], [127], [472], [477] or chronic phase [104], [132], [182], [447], [470], [471], [474]–[476].
Pooling resulted in significant homogeneous positive SESs for aerobic capacity and workload, and significant heterogeneous positive SESs for respiratory functions such as forced expiratory volume in 1 second (FEV1). Nonsignificant SESs were found for motor function of the paretic leg (synergy), muscle strength, comfortable gait speed, maximum gait speed, heart rate at rest and during work, diastolic and systolic blood pressure, physical cost index, body composition, blood variables, sitting and standing balance, and walking ability. Subgroup analyses showed significant differences between poststroke phases for resting heart rate: a significant SES was found for the early rehabilitation phase (n = 2) and a nonsignificant SES for the chronic phase (n = 2).
- 4. Mixed strength and cardiorespiratory exercises
Training regimes which combined both strength and cardiorespiratory exercises were investigated in 13 RCTs (N = 608, PEDro score range 3 [478] to 8 [140], [447], [479]) [140], [142], [143], [146], [171], [447], [459], [478]–[487], including patients in the early rehabilitation phase [479]–[481], [486], [487], late rehabilitation phase [140], [171], or chronic phase [142], [146], [447], [478], [482], [485].
Significant homogeneous positive SESs were found for motor function of the paretic leg (synergy), muscle strength of the leg, comfortable gait speed, maximum gait speed, walking distance, aerobic capacity, heart rate during work, balance, physical activity, and quality of life. Nonsignificant SESs were found for motor function of the paretic arm (synergy), muscle strength of the arm, physical cost index, depression, walking ability, arm-hand activities, and basic and extended ADL. Subgroup analyses revealed no significant differences between poststroke phases.
Physical therapy interventions related to activities of daily living.
The results of the meta-analyses for interventions related to activities of daily living are summarized in figure 5 (for details see table S2D in file S1). Pooling was not possible for strategy training for apraxia [488].
Legend: A green colored diamond indicates that the summary effect size is significant, while a blue colored diamond indicates that the summary effect size is nonsignificant; CI, Confidence interval; NA, Not applicable.
- 1. Interventions for apraxia: gestural training
Gestural training has been developed for patients with apraxia to teach them to regain tasks and handling of objects by using gestures [489]. This training method was investigated in two RCTs (N = 46) [489], [490], including patients in the chronic phase.
Pooling showed a significant homogeneous positive SES for gesture comprehension. Nonsignificant SESs were found for ideational and ideomotor apraxia.
- 2. Leisure therapy
Leisure therapy focuses on the execution of individual and social activities at home or in the home environment [491], [492]. This therapy was investigated in five RCTs (N = 641) [491]–[496], including patients who were to be discharged home or were already living at home in the early rehabilitation phase [492], [495], late rehabilitation phase [494], or chronic phase [491], [496].
The meta-analyses resulted in a significant heterogeneous positive SES for participation in leisure activities, while nonsignificant SESs were found for depression, mood, and quality of life. Subgroup analyses revealed significant differences between groups for participation in leisure activities: there was a significant homogeneous positive SES for the early rehabilitation phase (n = 1, with 2 comparisons), a nonsignificant SES size for the late rehabilitation phase (n = 1, with 2 comparisons), and a nonsignificant effect size for the chronic phase (n = 1).
Other physical therapy interventions.
The results of the meta-analyses for other physical therapy interventions are summarized in figure 6 (for details see table S2E in file S1).
Legend: C, Control group; CI, Confidence interval; E, Experimental group.
- 1. Inspiratory muscle training
Inspiratory muscle training was investigated in two RCTs (N = 66, PEDro score range 4 [497] to 7 [498]) [497], [498], including patients in the late rehabilitation phase [498] or chronic phase [497].
Pooling was possible for maximal inspiratory pressure, which resulted in a nonsignificant SES. Subgroup analyses revealed a difference between poststroke phases. A significant positive effect size was found in the chronic phase (n = 1) and a nonsignificant SES in the late rehabilitation phase (n = 1, with 2 comparisons).
Intensity of practice.
The analyses of high-intensity exercise therapy involved pooled data of the RCTs reporting on a treatment contrast between the experimental and control groups in terms of time spent in exercise therapy without the use of extensive equipment [19], [20]. The results of the meta-analyses for high-intensity exercise therapy are summarized in figure 7 (for details see table S2F in file S1).
Legend: ADL, Activities of daily living; C, Control group; CI, Confidence interval; E, Experimental group.
High-intensity exercise therapy.
In total, 80 RCTs were identified which used a treatment contrast in terms of time (N = 5776, PEDro score range 2 [465] to 8 [43], [44], [75], [127], [139], [171], [172], [174], [175], [443], [479], [499]–[509]) [43], [44], [51], [53]–[55], [60], [61], [74], [75], [80], [83], [84], [119], [127], [139], [144], [145], [147]–[149], [152], [156], [158], [171], [172], [174], [175], [178], [180], [189], [250], [307], [439], [440], [443], [458], [463]–[466], [468], [471]–[474], [477]–[482], [486], [494], [499]–[526], including patients in the hyper acute or acute rehabilitation phase, early rehabilitation phase, late rehabilitation phase, or chronic phase. In most of the RCTs, the interventions focused on the lower limb (n = 78). The mean treatment contrast amounted 17 hours over 10 weeks, indicating that on average the experimental groups received an additional therapy time of 17 hours when compared to the control groups.
Pooling the data resulted in significant homogeneous positive SESs for motor function of the paretic leg (synergy), motor function of the paretic arm (synergy), muscle strength of the leg, comfortable gait speed, maximum gait speed, muscle tone, and quality of life. Significant heterogeneous SESs were found for depression and anxiety, balance, and basic ADL. Meta-analyses for muscle strength of the arm, mental health of the patient, falls efficacy, walking ability, arm-hand activities, extended ADL, number of falls, and mental health of the caregiver resulted in nonsignificant SESs. The subgroup analysis for walking distance showed significantly different effects between phases, with a significant homogeneous positive SES for the chronic phase (n = 4), a nonsignificant SES for the early rehabilitation phase (n = 5), and a nonsignificant effect size for a group including patients regardless of timing poststroke (n = 1).
Neurological treatment approaches.
Neurodevelopmental Treatment (NDT/Bobath) was delivered in 75 RCTs (N = 3502). For the purpose of the present review, the effects of NDT were analyzed in three different categories: (a) NDT vs. another intervention; (b) NDT vs. NDT plus another intervention; and (c) NDT vs. augmented NDT (for details see table S1G in file S1).
- 1. NDT vs. another intervention
NDT was compared with another type of intervention in 37 RCTs (N = 1670, PEDro score range 4 [108], [276], [527] to 8 [323], [366], [505]) [50], [82], [108], [118], [154], [264], [269], [270], [272], [273], [276], [278], [280]–[282], [301]–[303], [305], [313], [315], [316], [323], [326], [333], [366], [432], [457], [468], [505], [527]–[534].
Strong evidence for equal effectiveness compared to another intervention was found for muscle strength of the arm and depression. In addition, there was strong evidence for unfavorable effects of NDT on motor function (synergy), gait speed, spatiotemporal gait pattern functions, kinematics of the arm, arm-hand activities, self-reported arm-hand activities in daily life, basic ADL, and quality of life. There was moderate evidence that NDT is equally effective as another intervention regarding strength of the knee muscles, maximal weight bearing on the paretic leg, coordination, stability of the shoulder joint, shoulder pain, health beliefs, walking distance, and balance. Moderate evidence was found for an unfavorable effect of NDT on length of stay. Insufficient evidence was found for muscle strength of the leg, grip strength, muscle tone, brain activity, walking ability, and extended ADL.
- 2. NDT vs. NDT plus another intervention
NDT was compared with NDT plus another intervention in 33 RCTs (N = 1106, PEDro score range 2 [138] to 8 [88], [186], [191]) [49], [51], [59], [64], [66], [80], [88], [96], [123], [129], [138], [148], [151], [158], [186], [191], [199], [203], [217], [246], [331], [357], [390], [395], [399], [400], [413], [419], [433], [524], [535], [536].
There was strong evidence that NDT alone has unfavorable effects compared to NDT plus another intervention as regards motor function (synergy), muscle strength of the arm, walking speed, spatiotemporal gait pattern functions like stride length, muscle tone, range of motion, balance, walking ability, arm-hand activities, and basic ADL. Strong evidence was found that they are equally effective for gait kinematics. Moderate evidence was found for unfavorable effect of NDT when compared to NDT plus another intervention on muscle strength of the leg, walking distance, coordination, EMG contraction, shoulder subluxation, neglect, and aerobic capacity. Moderate evidence was found for equal effectiveness regarding symmetry while sitting, standing, performing sit-to-stand and reaching; depression; and ability to change posture from sit to stand and vice versa.
- 3. NDT vs. augmented NDT
The effect of more time spent in NDT versus less time spent in NDT was investigated in 6 RCTs (N = 786, PEDro score range 6 [513], [517] to 8 [503]–[505]) [503]–[505], [513], [517], [519].
There was strong evidence that NDT is equally effective as augmented NDT for the outcomes muscle strength, walking ability, arm-hand activities, basic ADL, and extended ADL. There was moderate evidence that augmented NDT is beneficial for motor function (synergy) and range of motion. In addition, moderate evidence was found for equal effectiveness regarding pain, depression, balance, sit-to-stand, handicap, and quality of life.
Discussion
Interdisciplinary complex stroke rehabilitation is one of the fastest growing fields in stroke research [537]. With regard to physical therapy interventions, the present review shows that the number of RCTs has almost quadrupled in the past 10 years. Our meta-analyses suggest that there is strong evidence for 30 out of 53 interventions for beneficial effects on one or more outcomes. For a large proportion of the outcomes there is strong evidence that experimental interventions accomplish equal results when compared to ‘conventional therapy’, suggesting that the same results can be obtained with the control intervention, while no adverse events were reported. The generally small to medium SESs, indicating differential effects between 5 and 15%, mainly relate to those functions and activities specifically trained in the intervention, and are restricted to the period of intervention alone. While these findings were – globally – similar to the review from 2004, a comparison of the present results with the results of our previous review shows clear changes [12]. The main change lies in the increased number of interventions to which ‘strong evidence’ could be assigned and an increase in the number of outcomes for which the findings are statistically significant. In addition, shifts are observed for a few ‘strong evidence’ interventions with significant positive effects in 2004. For example, speed dependent treadmill training now shows neutral results for walking ability; rhythmic auditory cueing of gait currently shows neutral results for gait speed and stride length; and training of standing balance now also shows neutral results. In contrast to the 2004 review which reported no significant effects at the participation level, now mixed strength and cardiovascular exercises and leisure therapy show a favorable effect at the participation level. In general, exploring the possible moderator effect of poststroke timing largely did not show significant differences in effects. Higher intensity of practice proves to be an important aspect of effective physical therapy. This review also highlights that well controlled, dose-matched trials with significant effects in favor of the experimental intervention have been rather scarce (e.g. [76], [81], [110]). The above findings suggest that intensity of practice is a key factor in meaningful training after stroke, and that more practice is better [8]. This implies that our previous conclusion that high-intensity practice is better still holds [12], and that an additional therapy time of 17 hours over 10 weeks is necessary to find significant positive effects at both the body function level and activities and participation level of the ICF. In national clinical guidelines for stroke in the United Kingdom and the Netherlands, it is recommended that patients should be enabled to exercise at least 45 minutes on each weekday as long as there are rehabilitation goals and the patient tolerates this intensity [184], [538]. However, there is a big contrast between the recommended and actual applied therapy time. A survey in the Netherlands showed that patients with stroke admitted to a hospital stroke unit only received a mean of 22 minutes of physical therapy on weekdays [539]. Similarly, in the United Kingdom inpatients received 30.6 minutes physical therapy per day on which this therapy was given [540]. Contrary to previous reviews which concluded that neurological treatment approaches (NDT/Bobath) were not superior [12], [541], the present review demonstrates that neurological treatment approaches are less effective when compared to focused interventions such as mCIMT, bilateral arm training, or strengthening when applied in a task-specific way.
Repetition is an important principle in motor learning which reflects the Hebbian learning rule that connections between neurons are strengthened when they are simultaneously active (i.e., long term potentiation) [542]. An earlier review has shown that repetitive task training is a key modality of effective training in stroke [543]. This repetition aspect relates to “an active motor sequence performed repetitively within a single training session, with practice aiming towards a clear functional goal” [543]. However, this does not mean that each repetition should be identical to the previous ones. Instead, is suggested that implementing slight variation between repetitions is more successful [544]. Although we did not analyze ‘repetition’ separately, this modality is a feature included in many focused interventions for which strong evidence was found in the present review. For example, CIMT and gait training are both characterized by a high number of repetitions executed within a single treatment session, serving a functional goal.
To facilitate application of the findings presented in the current review in daily practice, it is necessary to further specify for which interventions there is strong evidence that patients benefit from this therapeutic intervention and for which outcome this evidence is valid. Therefore, figure 8 graphically displays the outcomes classified according to the ICF, with corresponding interventions for which is strong evidence that they significantly affect those outcomes. It should be noted that the clinical applicability of some interventions like electromechanical-assisted gait training and robot-assisted arm training is questionable, due to the accompanying high costs of the equipment. For these interventions, there are often alternative ‘strong evidence’ interventions available.
Legend: A green point indicates that the intervention has a significant positive effect on the outcome, while a red point indicates that the intervention has a significant negative effect on the outcome; *, shoulder external rotation; **, dependent walking patients in the early rehabilitation phase; ▵, dependent walking patients when compared to electromechanical-assisted gait training or BWSTT; □, independent walking patients; BWSTT, Body-weight supported treadmill training; CIMT, Constraint-induced movement therapy; EMG-NMS, Electromyography-triggered neuromuscular stimulation; ES, Electrostimulation; mCIMT, modified Constraint-induced movement therapy; NMS, Neuromuscular stimulation; prox., Proximal; TENS, Transcutaneous electrical nerve stimulation.
The large number of interventions and outcomes for which nonsignificant SESs were found in the meta-analyses (i.e. neutral results) suggests that for many forms of exercise therapy the same patient outcomes can be obtained with the control intervention. This implies that the physical therapist, in cooperation with the patient, has to decide for each individual patient which of these interventions is the optimal treatment option. In this clinical decision-making process, that preferably should be based on existing knowledge about the functional prognosis for outcome [22], [545], also resource use and possible alternative interventions should be taken into account.
It should also be noted that we found three significant negative SESs. The first being for overground walking (aerobic capacity; for dependent walking patients in the early rehabilitation phase when compared to electromechanical-assisted gait training or body-weight supported treadmill training), the second for virtual reality training for the paretic arm (muscle tone), and the third for trunk restraint (self-reported amount of arm-hand use in daily life). However, the meta-analysis for all these outcomes showed insufficient statistical power, suggesting that more trials are needed. Furthermore, although a negative SES was found for both overground walking and virtual reality training for the upper paretic limb, these interventions also show beneficial effects on one or more other outcomes. Therefore, we recommend that when physical therapists select one of these interventions, they should regularly monitor the outcomes which are at risk for being adversely affected by the intervention.
(In)stability of Results in Trials
A comparison between the current results and those of our previous meta-analyses [12] shows that some interventions for which strong evidence was reported in 2004, such as rhythmic auditory cueing of gait, no longer have the same level of evidence, whereas other interventions with initially only indicative findings or no evidence, such as EMG-NMS for the paretic arm, now show significant positive small to moderate effect sizes. This finding reflects a lack of robustness of existing evidence favoring or disfavoring an intervention when new trials are added to the current pool of studies. In our opinion, this (in)stability of current evidence depends on several factors. First, differential effects seem to be largely dependent on the content and dose-matching of the therapy given in the control group [6], [546]. In a number of trials, the content and dosage of therapy applied in the control group is poorly defined. ‘Usual care’ frequently reflects the existing guidelines, suggesting that the patients in the control group received treatment according to the best available evidence at that moment. Obviously, researchers hypothesize that the added value of the experimental intervention will considerably exceed the existing standards of care, acknowledging that comparison of an experimental intervention with a real ‘sham’ or placebo intervention is not desirable in stroke rehabilitation, and is in most Western countries not allowed for medical ethical reasons. Second, many primary outcome measures do not appropriately reflect the underlying biological rationale for the content of the experimental therapy [547], whereas other outcomes may be rather insensitive to the changes introduced by physical therapy [548]. To improve comparability between trials applying the same intervention, international consensus about outcomes and timing of (follow-up) measurements is urgently needed [8], [549]. Third, of the 326 meta-analyses we performed, the statistical power was sufficient for only 58 meta-analyses divided over 28 interventions (e.g. training of sitting balance and (m)CIMT) and intensity of practice. The instability of SESs over time and hence the current level of evidence is mainly due to the low number of small-sized phase II trials [550]. The dominance of rather positive phase II trials in physical therapy may well reflect publication bias, since low-powered negative trials are less likely to be published [551]. In contrast, recent sufficiently powered phase III and IV trials in physical therapy, such as those on the impact of shoulder-elbow robotics [335] and body-weight supported treadmill training [91] yielded less positive findings than the previously published phase II trials on these type of interventions [552]. However, one may also argue that in small numbered monocenter trials, therapists are more committed to the trial than in multicenter trials. Fourth, heterogeneity of patient samples could have played a role [553]–[555]. Not only can differences between studies in inclusion criteria, resulting in between-study heterogeneity, play a role, but also within-study heterogeneity, especially in larger trials which tend to have less strict inclusion criteria. As referred to above, the therapeutic content of the experimental intervention applied was often poorly defined, since most journals do not allow publication of treatment protocols [556], preventing researchers from properly reporting on treatment content due to word limitations, replicating studies, or judging if interventions are sufficiently comparable to allow meta-analyses. Finally, the observed shifts in evidence may reflect the improved methodological quality of studies due to the introduction of the CONSORT Statement for reporting RCTs [557]. In the present review, the median PEDro score was found to have increased from 5 (IQR 4–6) for RCTs published before 2004 [12] to 6 (IQR 5–7) in the subsequent period. This finding suggests increased efforts by researchers to reduce bias in clinical trials [558], [559].
Deficiencies in the Focus of Trials
Remarkably, only three RCTs started their intervention within the first days poststroke, despite evidence that most patients are physical inactive early poststroke [560] as well as the growing evidence of a greater potential for neuroplasticity in the first three to four weeks poststroke [561]. One may assume that giving appropriate training within this window of increased homeostatic neuroplasticity may enhance motor recovery. Although our subgroup analyses suggest that timing poststroke is only a significant moderator of effect sizes in a small number of interventions, this is based on very few trials that started in this critical phase of the first days or weeks poststroke.
While the strength of evidence is growing for certain physical therapy interventions, the cost-effectiveness of these interventions has so far hardly been subject of investigation [562], [563], and long-term outcomes have often not been systematically measured at fixed times post intervention. In addition, even though the main effects of intensity of practice are in favor of high-intensity training, there is still a paucity of well-controlled dose-response RTCs in the field of physical therapy directly investigating the impact of intensity of practice [19], [353].
How to Proceed?
While acknowledging that interdisciplinary collaboration is a key aspect of stroke rehabilitation [3], we think it is important that each discipline should take responsibility to further extend the specific contribution of different types of therapy in the interdisciplinary care, in terms of evidence and implementation. Therefore, a roadmap is needed to prioritize research in the domain of physical therapy. In determining research priorities, different perspectives ought to be considered, like those of patients and their caregivers, clinicians, researchers and policy-makers [564], [565].
In our opinion, this roadmap should contain the following elements: (1) investigating dose-response relations in exercise therapy, in which the experimental and control groups receive the same type of intervention but with different dosage [566]; (2) investigating resource-efficient interventions to augment physical therapy and allow early supported discharge such as telerehabilitation [567] and caregiver-mediated exercises [174]; (3) investigating the benefits of an (very) early start of physical therapy poststroke [560] and continuation of poststroke therapy in the weekends; (4) investigating the cost-effectiveness of interventions and numbers needed to treat; (5) investigating the effectiveness of interventions which have so far only been investigated in phase II trials and from which patients may benefit; (6) investigating interventions that are used by physical therapists but have not been investigated in RCTs, like the effectiveness of falls prevention programs and physical fitness training in the context of secondary prevention. Finally, (7) investigating the mechanisms behind motor learning and stroke recovery, which are still poorly understood. Only translational research is able to bridge the gap between the effects of an intervention that have been found and the underlying mechanisms that may contribute to therapy-induced poststroke recovery. In order to understand what actually changes during stroke recovery, we need to discriminate between recovery of body functions (restitution) and learning to use compensation strategies in accomplishing tasks [568], [569]. In this respect, new therapeutic approaches in which physical exercise is combined with innovative treatments enhancing neuroplasticity in crucial (early) time windows, such as transcranial Direct Current Stimulation [570], [571], repetitive Transcranial Magnetic Stimulation [572], or neuropharmacological interventions [573], may be promising.
Stroke rehabilitation intervention research in the domain of physical therapy can be organized using a step-wise approach [6], [546]: interventions with positive effects in the first explorative stages on relevant consensus-based outcomes should become the subject of high-quality phase III and IV trials. In all cases, subgroups of patients should be selected which, from a biological perspective, would benefit the most from the intervention, while taking into account “the sensitive period for response to intervention” [574].
Implementation of research findings into daily practice is essential to improve quality of care, but is also challenging. First of all, because physical therapy as part of complex interdisciplinary stroke rehabilitation, contains several interrelated components that may be targeted at different levels (i.e., at service, operator, and/or treatment level) [8], [575], [576]. Second, physical therapy typically entails a cyclical process involving (1) assessment, to identify and quantify the patient’s needs; (2) goal setting, to define realistic and attainable goals for improvement; (3) intervention, to assist in the achievement of goals; and (4) reassessment, to assess progress against agreed goals [8]. For all of these four steps, a broad scientific base is available but the evidence is dynamic. Due to this complexity and it’s dynamics, a country wide postbachelor physical therapy course was started in 2008 in the Netherlands in which the different aspects of evidence-based practice in stroke are educated [541]. This one year course includes themes such as: (1) how to make clinical decisions; (2) how to measure outcome and clinical change; (3) how to estimate the individual prognosis for outcome at the activities level; and (4) how to select the best intervention. In addition, in this course special attention is paid to assumed pathophysiology and underlying working mechanisms of recovery poststroke. However, effective but efficient methods for physical therapists to keep their knowledge and skill level up-to-date in the long term needs further investigation.
Limitations
Although this systematic review was performed with the greatest of care, there are some methodological limitations like the language restriction, not hand-searching conference proceedings, missing outcome data [577], not performing meta-analyses of individual patient data [578], and the lack of both a correction for multiple testing and systematic investigation of reporting bias. In addition, the observational nature of the subgroup analyses means they should be interpreted with caution, as it is known that subgroup analyses in meta-analyses can be less highly powered than analyses for main effects [29], [579], [580].
Conclusion
In summary, the body of knowledge about physical therapy in stroke rehabilitation is still growing. This is evident both from the increased number of published RCTs with a low risk of bias, resulting in strong evidence for many physical therapy modalities, and from the exploration of innovative ways for efficient use of resources like circuit class training. This endorses the central role of physical therapy in interdisciplinary evidence-based stroke rehabilitation. Further confirmation of the evidence for physical therapy after stroke, and facilitating the transfer to clinical practice, requires a better understanding of (neurophysiological) mechanisms, including neuroplasticity, that drive stroke recovery, as well as the impact of physical therapy interventions on these underlying mechanisms. Thus, well-designed RCTs should address questions like: Which patients benefit most from a specific intervention? At what time poststroke should interventions be initiated? What are the underlying mechanisms that drive improvement of sensorimotor control? What are the preferred intervention characteristics, including the optimal dosage? And are interventions cost-effective? Subsequent meta-analyses should analyze the evidence using individual participant data. Finally, implementation strategies should be further explored in order to optimize the transfer of scientific knowledge into clinical practice.
The high growth in the number of RCTs on physical therapy stroke rehabilitation makes it virtually impossible for individual physical therapists to identify and ascertain the content of each relevant science citation indexed study. There is therefore a need for a worldwide continuing – online – update of the summarized evidence, discussed in the context of interdisciplinary stroke care.
Supporting Information
File S1.
Contains Supporting Tables. TABLE S1A. Title: Summary of physical therapy interventions – gait and mobility-related functions and activities. Legend: +, significant positive SES; = , nonsignficant SES; –, significant negative SES; ADL, Activities of daily living; C, Chronic phase; d, day(s); ER, Early rehabilitation phase; EMG, Electromyographic (H)AR, (hyper)acute rehabilitation phase; min, minutes; LR, Late rehabilitation phase; mos, months; RCTs, Randomized controlled trials; SES, Summary effect size; wk, week(s). TABLE S1B. Title: Summary of physical therapy interventions – arm-hand activities. Legend: +, significant positive SES; = , nonsignficant SES; –, significant negative SES; ?, unclear; ADL, Activities of daily living; C, Chronic phase; d, day(s); CIMT, Constraint-induced movement therapy; ER, Early rehabilitation phase; (H)AR, (hyper)acute rehabilitation phase; LR, Late rehabilitation phase; min, minutes; mCIMT, modified Constraint-induced movement therapy; mos, months; RCTs, Randomized controlled trials; wk, week(s); SES, Summary effect size. TABLE S1C. Title: Summary of physical therapy interventions – physical fitness. Legend: +, significant positive SES; = , nonsignficant SES; ?, unclear; ADL, Activities of daily living; C, Chronic phase; d, day(s); ER, Early rehabilitation phase; (H)AR, (hyper)acute rehabilitation phase; LR, Late rehabilitation phase; RCTs, Randomized controlled trials; min, minutes; mos, months; SES, Summary effect size; wk, week(s). TABLE S1D. Title: Summary of physical therapy interventions – activities of daily living. Legend: +, significant positive SES; = , nonsignficant SES; C, Chronic phase; d, day(s); ER, Early rehabilitation phase; (H)AR, (hyper)acute rehabilitation phase; LR, Late rehabilitation phase; min, minutes; mos, months; RCTs, Randomized controlled trials; SES, Summary effect size; wk, week(s). TABLE S1E. Title: Summary of physical therapy interventions – other. Legend: = , nonsignficant SES; C, Chronic phase; d, day(s); ER, Early rehabilitation phase; (H)AR, (hyper)acute rehabilitation phase; LR, Late rehabilitation phase; min, minutes; mos, months; RCTs, Randomized controlled trials; SES, Summary effect size; wk, week(s). TABLE S1F. Title: Summary of physical therapy interventions – intensity of practice. Legend: ?, unclear; +, significant positive SES; = , nonsignficant SES; ADL, Activities of daily living; C, Chronic phase; ER, Early rehabilitation phase; (H)AR, (hyper)acute rehabilitation phase; h, hours; LR, Late rehabilitation phase; RCTs, Randomized controlled trials; SES, Summary effect size; wk, weeks. TABLE S1G. Title: Summary of physical therapy interventions – neurological treatment approaches. Legend: +, significant positive effect; = , nonsignficant effect; –, significant negative effect; ?, unclear; ADL, Activities of daily living; BWSTT, Body-weight supported treadmill training; C, Chronic phase; EMG-BF, Electromyographic biofeedback; EMG, Electromyograpic; EMG-NMS, Electromyography-triggered neuromuscular stimulation; ER, Early rehabilitation phase; (H)AR, (hyper)acute rehabilitation phase; LR, Late rehabilitation phase; mCIMT, modified Constraint-induced movement therapy; NDT, Neurodevelopmental treatment; NMS, Neuromuscular stimulation; RCTs, Randomized controlled trials; SES, Summary effect size; TENS, Transcutaneous electrical nerve stimulation. TABLE S2A. Title: Summary of the evidence for physical therapy interventions – gait and mobility-related functions and activities. Legend: 10MWT, 10-meter walk test; 12MWT, 12-minute walk test; 3MWT, 3-minute walk test; 5MWT, 5-meter walk test; 6MWT, 6-minute walk test; 8MWT, 8-meter walk test; AAP, Adelaide activities profile; ABC, Activities-specific balance confidence scale; ADL, Activities of daily living; BBA, Brunel balance assessment; BBS, Berg balance scale; BI, Barthel index; BP, Blood pressure; BWD, Body-weight distribution; C, Chronic phase; CI, Confidence interval; CSS, Composite spasticity scale; CNS, Canadian neurological scale; DB, Dynamic balance; DST, Double support time; EFAP, Emory functional ambulation profile; EMS, Elderly mobility scale; ER, Early rehabilitation phase; FAC, Functional ambulation categories; FAI, Frenchay activities index; FES-I, Falls-efficacy scale; FIM, Functional independence measure; FMA, Fugl-meyer assessment; FR, Functional reach; FSST, Four square step test; GDS-15, Geriatric depression scale - 15;GRF, Ground reaction force; HADS, Hospital anxiety and depression scale; HR, Heart rate; LLFDI, Late life function and disability instrument; LR, Late rehabilitation phase; LRT, Lateral reach test; MAS, Modified ashworth scale; MAS*, Motor assessment scale; mEFAP, modified Emory functional ambulation profile; MI, Motricity index; MMAS*, modified Motor assessment scale; MRC, Medical research council; mRS, modified Rankin scale; NA, Not applicable; NEADL, Nottingham extended ADL index; NHP, Nottingham health profile; NIHSS, National institutes of health stroke scale; NS, Not significant; PADS, Physical activity and disability scale; PASIPD, Physical activity scale for individuals with physical disabilities; PASS, Postural assessment scale for stroke; QoL, Quality of life; RMI, Rivermead mobility index; RMA, Rivermead motor assessment; RMA GF, RMA gross function; RMA LT, RMA leg and trunk; ROM, Range of motion; RPE, Rating of perceived exertion; S, Significant; SA-SIP30, Stroke-adapted 30-item version of the sickness impact profile; SAS, Stroke activities scale; SES, Summary effect size; SF-36, 36-Item short form health survey; SB, Static balance; SI, Spasticity index; SIS, Stroke impact scale; SPPB, Short physical performance battery; SST, Single-support time; ST, Step test; STREAM, Stroke rehabilitation assessment of movement instrument; STS, Sit-to-stand; TCT, Trunk control test; TIS, Trunk impairment scale; TMS, Toulouse motor scale; TUG, Timed up and go test; WAQ, Walking ability questionnaire; WD, Walking distance; WQ, Walking quality; WS, Walking speed gait analysis. TABLE S2B. Title: Summary of the evidence for physical therapy interventions – arm-hand activities. Legend: 10CMT, 10-cup moving test; ADL, Activities of daily living; AFT, Arm function test; AMAT, Arm motor ability test; ARAT, Action research arm test; BBT, Box and block test; BI, Barthel index; C, Chronic phase; CAHAI, Chedoke arm and hand activity inventory; CI, Confidence interval; CMMSA, Chedoke-McMaster stroke assessment; ER, Early rehabilitation phase;FE, Functional evaluation; FIM, Functional independence measure; FMC, Fine motor control; FMA, Fugl-meyer assessment; FTHUE, Functional test for the hemiplegic upper extremity; GP, Grip power; GS, Grip strength; JTHFT, Jebsen-Taylor hand function test; LR, Late rehabilitation phase; MAL, Motor activity log; MAS, Modified ashworth scale; MAS*, Motor assessment scale; mFMA, modified Fugl-meyer assessment; MP, Motor power; MRC, Medical research council; MSS, Motor status scale; mBI, modified Barthel index; NA, Not applicable; NS, Not significant; NSA, Nottingham sensory assessment; PPT, Perdue pegboard test; PS, Pinch strength; ROM, Range of motion; S, Significant; SES, Summary effect size; SIS, Stroke impact scale; TEMPA, Test d’evaluation des membres supérieurs de personnes agéés; UEFT, Upper extremity function test; VAS, Visual analogue scale; WFMT, Wolf motor function test. TABLE S2C. Title: Summary of the evidence for physical therapy interventions – physical fitness. Legend: 10MWT, 10-meter walk test; 12MWT, 12-minute walk test; 5MWT, 5-meter walk test; 6MWT, 6-minute walk test; ADL, Activities of daily living; ARAT, Action research arm test; BBS, Berg balance scale; BI, Barthel index; BMI, Body mass index; BP, Blood pressure; C, Chronic phase; CI, Confidence interval; CMMSA, Chedoke-McMaster stroke assessment; EQ, EuroQoL 5D; ER, Early rehabilitation phase; FAP, Functional ambulation profile; FEV1, Forced expiratory volume in 1 second; FIM, Functional independence measure; FMA, Fugl-meyer assessment; FR, Functional reach; FSST, Four square step test; FTHUE, Functional test for the hemiplegic upper extremity; GF, Grip force; GS, Grip strength; HADS, Hospital anxiety and depression scale; HR, Heart rate; IADL, Instrumental ADL; JTHFT, Jebsen-Taylor hand function test; LLFDI, Late life function and disability instrument; LR, Late rehabilitation phase; MAS, Modified ashworth scale; NA, Not applicable; NEADL, Nottingham extended ADL index; NHPT, Nine hole peg test; NS, Not significant; O2cost, Oxygen cost; PADS, physical activities and disability scale; PASIPD, Physical activity scale for individuals with physical disabilities; PF, Pinch force; PPT, Perdue pegboard test; RER, Respiratory exchange ratio; RMA GF, Rivermead motor assessment gross function; RMI, Rivermead mobility index; S, Significant; SES, Summary effect size; SF-36, 36-item Short form health survey; SLC90, Symptom checklist-90-R; STS, Sit-to-stand; TMS, Tolouse motor scale; TUG, Timed up and go test; VE, Ventilatory exchange; VO2max, Ventilatory oxygen uptake, WD, Walking distance; WS, WQ, Walking questionnaire; Walking speed gait analysis. TABLE S2D. Title: Summary of the evidence for physical therapy interventions – activities of daily living. Legend: *1 RCT with 2 comparisons; NLQ, Nottingham leisure questionnaire; BDI, Beck depression inventory; C, Chronic phase; CES-D, Centre for epidemiologic studies for depression scale; CI, Confidence interval; ER, Early rehabilitation phase; GHQ, General health questionnaire; GWBS, General well-being scale; LR, Late rehabilitation phase; NA, Not applicable; NS, Not significant; TLAS, Total leisure activities score; TLS, Total leisure score; S, Significant; SES, Summary effect size; SIP, Stroke impact profile; SA-SIP30, Stroke-adapted 30-item version of the sickness impact profile; WDI, Wakefield depression inventory. TABLE S2E. Title: Summary of the evidence for physical therapy interventions – other. Legend: CI, Confidence interval; C, Chronic phase; LR, Late rehabilitation phase; MIP, Maximal inspiratory pressure; S, Significant; SES, Summary effect size. TABLE S2F. Title: Summary of the evidence for physical therapy interventions – intensity of practice. Legend: 10MWT, 10-meter walk test; 5MWT, 5-meter walk test; ABC, Activities-specific balance confidence scale; ADL, Activities of daily living; ARAT, Action research arm test; BBS, Berg balance scale; BDI, Beck depression inventory; BI, Barthel index; C, Chronic phase; CI, Confidence interval; COOP scale, Dartmouth primary care cooperative information functional health assessment; ER, Early rehabilitation phase; FAC, Functional ambulation categories; FAI, Frenchay activities index; FES-I, Falls-efficacy scale; FIM, Functional independence measure; FMA, Fugl-meyer assessment; FR, Functional reach; FSST, Four square step test; FTHUE, Functional test for the hemiplegic upper extremity; GDS, Geriatric depression scale –15; GHQ, General health questionnaire; GS, Grip strength; HADS, Hospital anxiety and depression scale; IADL, Instrumental ADL; LHS, London handicap scale; LR, Late rehabilitation phase; MAS, Modified ashworth scale; mBI, modified Barthel index; MI, Motricity index; mRMI, modified Rivermead mobility index; NA, Not applicable; NEADL, Nottingham extended ADL index; NHP, Nottingham health profile; NHPT, Nine hole peg test; NS, Not significant; PASS, Postural assessment scale for stroke; POR, profile of recovery; PS, Pinch strength; RMA, Rivermead motor assessment; RMI, Rivermead mobility index; S, Significant; SCL-90, Symptom checklist-90-R; SES, Summary effect size; SF-36, 36-item Short form health survey; SIP, Stroke impact scale, SIS, Stroke impact scale; ST, Step test; STREAM, Stroke rehabilitation assessment of movement instrument; WD, Walking distance; WS, Walking speed gait analysis.
https://doi.org/10.1371/journal.pone.0087987.s001
(PDF)
Acknowledgments
We would like to thank Hans Ket, medical information specialist at the VU University library, for his contribution to the literature search, and Frank van Hartingsveld MSc, teacher at Amsterdam School of Health Professions ASHP, for supervising students who crosschecked the data extracted for the meta-analyses. Also, we would like to thank Karin Heijblom as representative and clinical guidelines portfolio holder of the Royal Dutch Society for Physical Therapy and Jan Klerkx for language editing.
References
- 1. Roger V, Go A, Lloyd-Jones D, Adams R, Berry J, et al. (2011) Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation 123: e18–e209.
- 2.
Wardlaw J, Murray V, Berge E, Del Zoppo G (2009) Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev: CD000213.
- 3.
Stroke Unit Trialists' Collaboration (2007) Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev: CD000197.
- 4. Wade D, Hewer R (1987) Functional abilities after stroke: measurement, natural history and prognosis. J Neurol Neurosurg Psychiatry 50: 177–182.
- 5. Miller E, Murray L, Richards L, Zorowitz R, Bakas T, et al. (2010) Comprehensive overview of nursing and interdisciplinary rehabilitation care of the stroke patient: a scientific statement from the American Heart Association. Stroke 41: 2402–2448.
- 6.
Medical Research Council (2000) A framework for development and evaluation of RCTs for complex interventions to improve health.
- 7. Langhorne P, Legg L (2003) Evidence behind stroke rehabilitation. J Neurol Neurosurg Psychiatry 74 Suppl 4iv18–iv21.
- 8. Langhorne P, Bernhardt J, Kwakkel G (2011) Stroke rehabilitation. Lancet 377: 1693–1702.
- 9. Grimshaw J, Eccles M, Russell I (1995) Developing clinically valid practice guidelines. J Eval Clin Pract 1: 37–48.
- 10. Grimshaw J, Freemantle N, Wallace S, Russell I, Hurwitz B, et al. (1995) Developing and implementing clinical practice guidelines. Qual Health Care 4: 55–64.
- 11. Grol R, Grimshaw J (2003) From best evidence to best practice: effective implementation of change in patients' care. Lancet 362: 1225–1230.
- 12. Van Peppen R, Kwakkel G, Wood-Dauphinee S, Hendriks H, Van der Wees P, et al. (2004) The impact of physical therapy on functional outcomes after stroke: what's the evidence? Clin Rehabil 18: 833–862.
- 13. Kjellström T, Norrving B, Shatchkute A (2007) Helsingborg Declaration 2006 on European stroke strategies. Cerebrovasc Dis 23: 231–241.
- 14. Norrving B (2007) The 2006 Helsingborg Consensus Conference on European Stroke Strategies: Summary of conference proceedings and background to the 2nd Helsingborg Declaration. Int J Stroke 2: 139–143.
- 15.
World Health Organization (2001) International Classification of Functioning, Disability and Health: ICF. Geneva.
- 16. Hatano S (1976) Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ 54: 541–553.
- 17.
Higgins J, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]: The Cochrane Collaboration.
- 18.
American Physical Therapy Association (2011) Today's Physical Therapist: A Comprehensive Review of a 21st-Century Health Care Profession.
- 19. Veerbeek J, Koolstra M, Ket J, Van Wegen E, Kwakkel G (2011) Effects of augmented exercise therapy on outcome of gait and gait-related activities in the first 6 months after stroke: a meta-analysis. Stroke 42: 3311–3315.
- 20. Kwakkel G, Van Peppen R, Wagenaar R, Wood-Dauphinee S, Richards C, et al. (2004) Effects of augmented exercise therapy time after stroke: a meta-analysis. Stroke 35: 2529–2539.
- 21.
World Confederation for Physical Therapy (2013) World Confederation for Physical Therapy (WCPT) Glossary. Available: http://wwwwcptorg/glossary.
- 22. Veerbeek J, Kwakkel G, Van Wegen E, Ket J, Heymans M (2011) Early prediction of outcome of activities of daily living after stroke: a systematic review. Stroke 42: 1482–1488.
- 23. Geyh S, Cieza A, Schouten J, Dickson H, Frommelt P, et al. (2004) ICF Core Sets for stroke. J Rehabil Med 36: 135–141.
- 24. Moseley A, Herbert R, Sherrington C, Maher C (2002) Evidence for physiotherapy practice: a survey of the Physiotherapy Evidence Database (PEDro). Aust J Physiother 48: 43–49.
- 25. Sherrington C, Herbert R, Maher C, Moseley A (2000) PEDro. A database of randomized trials and systematic reviews in physiotherapy. Man Ther 5: 223–226.
- 26. Van Tulder M, Cherkin D, Berman B, Lao L, Koes B (1999) The effectiveness of acupuncture in the management of acute and chronic low back pain. A systematic review within the framework of the Cochrane Collaboration Back Review Group. Spine (Phila Pa 1976) 24: 1113–1123.
- 27.
Borenstein M, Hedges L, Higgins J, Rothstein R (2009) Subgroup analyses. Introduction to meta-analysis. New Jersey: John Wiley & Sons, Ltd. 149–186.
- 28.
Cohen J (1977) Statistical power analysis for the behavioural sciences. New York: Academic Press.
- 29. Hedges L, Pigott T (2001) The power of statistical tests in meta-analysis. Psychol Methods 6: 203–217.
- 30. Johannsen L, Wing A, Pelton T, Kitaka K, Zietz D, et al. (2010) Seated bilateral leg exercise effects on hemiparetic lower extremity function in chronic stroke. Neurorehabil Neural Repair 24: 243–253.
- 31. Sütbeyaz S, Yavuzer G, Sezer N, Koseoglu B (2007) Mirror therapy enhances lower-extremity motor recovery and motor functioning after stroke: a randomized controlled trial. Arch Phys Med Rehabil 88: 555–559.
- 32. Malouin F, Richards C, Durand A, Doyon J (2009) Added value of mental practice combined with a small amount of physical practice on the relearning of rising and sitting post-stroke: a pilot study. J Neurol Phys Ther 33: 195–202.
- 33. Pomeroy V, Evans B, Falconer M, Jones D, Hill E, et al. (2001) An exploration of the effects of weighted garments on balance and gait of stroke patients with residual disability. Clin Rehabil 15: 390–397.
- 34. Dobkin B, Plummer-D'Amato P, Elashoff R, Lee J (2010) International randomized clinical trial, stroke inpatient rehabilitation with reinforcement of walking speed (SIRROWS), improves outcomes. Neurorehabil Neural Repair 24: 235–242.
- 35. Robinson W, Smith R, Aung O, Ada L (2008) No difference between wearing a night splint and standing on a tilt table in preventing ankle contracture early after stroke: a randomised trial. Aust J Physiother 54: 33–38.
- 36. Kluding P, Santos M (2008) Effects of ankle joint mobilizations in adults poststroke: a pilot study. Arch Phys Med Rehabil 89: 449–456.
- 37. Rydwik E, Eliasson S, Akner G (2006) The effect of exercise of the affected foot in stroke patients–a randomized controlled pilot trial. Clin Rehabil 20: 645–655.
- 38. Ansari N, Naghdi S, Bagheri H, Ghassabi H (2007) Therapeutic ultrasound in the treatment of ankle plantarflexor spasticity in a unilateral stroke population: a randomized, single-blind, placebo-controlled trial. Electromyogr Clin Neurophysiol 47: 137–143.
- 39. Paoloni M, Mangone M, Scettri P, Procaccianti R, Cometa A, et al. (2010) Segmental muscle vibration improves walking in chronic stroke patients with foot drop: a randomized controlled trial. Neurorehabil Neural Repair 24: 254–262.
- 40. Van Nes I, Latour H, Schils F, Meijer R, Van Kuijk A, et al. (2006) Long-term effects of 6-week whole-body vibration on balance recovery and activities of daily living in the postacute phase of stroke: a randomized, controlled trial. Stroke 37: 2331–2335.
- 41. Barrett J, Watkins C, Plant R, Dickinson H, Clayton L, et al. (2001) The COSTAR wheelchair study: a two-centre pilot study of self-propulsion in a wheelchair in early stroke rehabilitation. Collaborative Stroke Audit and Research. Clin Rehabil 15: 32–41.
- 42. Bernhardt J, Indredavik B, Dewey H, Langhorne P, Lindley R, et al. (2007) Mobilisation 'in bed' is not mobilisation. Cerebrovasc Dis 24: 157–158.
- 43. Bernhardt J, Dewey H, Thrift A, Collier J, Donnan G (2008) A very early rehabilitation trial for stroke (AVERT): phase II safety and feasibility. Stroke 39: 390–396.
- 44. Langhorne P, Stott D, Knight A, Bernhardt J, Barer D, et al. (2010) Very early rehabilitation or intensive telemetry after stroke: a pilot randomised trial. Cerebrovasc Dis 29: 352–360.
- 45. Pollock A, Durward B, Rowe P, Paul J (2000) What is balance? Clin Rehabil 14: 402–406.
- 46. Ibrahimi N, Tufel S, Singh H, Maurya M (2010) Effect of sitting balance training under varied sensory input on balance and quality of life in stroke patients. Ind J Physiother Occup Ther 4: 40–45.
- 47. Dean C, Channon E, Hall J (2007) Sitting training early after stroke improves sitting ability and quality and carries over to standing up but not to walking: a randomised trial. Aust J Physiother 53: 97–102.
- 48. Dean C, Shepherd R (1997) Task-related training improves performance of seated reaching tasks after stroke. A randomized controlled trial. Stroke 28: 722–728.
- 49. De Sèze M, Wiart L, Bon-Saint-Côme A, Debelleix X, De Sèze M, et al. (2001) Rehabilitation of postural disturbances of hemiplegic patients by using trunk control retraining during exploratory exercises. Arch Phys Med Rehabil 82: 793–800.
- 50. Mudie M, Winzeler-Mercay U, Radwan S, Lee L (2002) Training symmetry of weight distribution after stroke: a randomized controlled pilot study comparing task-related reach, Bobath and feedback training approaches. Clin Rehabil 16: 582–592.
- 51. Pollock A, Durward B, Rowe P, Paul J (2002) The effect of independent practice of motor tasks by stroke patients: a pilot randomized controlled trial. Clin Rehabil 16: 473–480.
- 52. Janssen W, Bussmann H, Stam H (2002) Determinants of the sit-to-stand movement: a review. Phys Ther 82: 866–879.
- 53. Britton E, Harris N, Turton A (2008) An exploratory randomized controlled trial of assisted practice for improving sit-to-stand in stroke patients in the hospital setting. Clin Rehabil 22: 458–468.
- 54. Barreca S, Sigouin C, Lambert C, Ansley B (2004) Effects of extra training on the ability of stroke survivors tp perform an independent ist-to-stand: a randomized controlled trial. J Geriatr Phys Ther 27: 59–68.
- 55. Tung F, Yang Y, Lee C, Wang R (2010) Balance outcomes after additional sit-to-stand training in subjects with stroke: a randomized controlled trial. Clin Rehabil 24: 533–542.
- 56. Varoqui D, Froger J, Pelissier J, Bardy B (2011) Effect of coordination biofeedback on (re)learning preferred postural patterns in post-stroke patients. Motor Control 15: 187–205.
- 57. Engardt M, Ribbe T, Olsson E (1993) Vertical ground reaction force feedback to enhance stroke patients' symmetrical body-weight distribution while rising/sitting down. Scand J Rehabil Med 25: 41–48.
- 58. Bayouk J, Boucher J, Leroux A (2006) Balance training following stroke: effects of task-oriented exercises with and without altered sensory input. Int J Rehabil Res 29: 51–59.
- 59. Bagley P, Hudson M, Forster A, Smith J, Young J (2005) A randomized trial evaluation of the Oswestry Standing Frame for patients after stroke. Clin Rehabil 19: 354–364.
- 60. Morioka S, Yagi F (2003) Effects of perceptual learning exercises on standing balance using a hardness discrimination task in hemiplegic patients following stroke: a randomized controlled pilot trial. Clin Rehabil 17: 600–607.
- 61. Allison R, Dennett R (2007) Pilot randomized controlled trial to assess the impact of additional supported standing practice on functional ability post stroke. Clin Rehabil 21: 614–619.
- 62. Chen I, Cheng P, Chen C, Chen S, Chung C, et al. (2002) Effects of balance training on hemiplegic stroke patients. Chang Gung Med J 25: 583–590.
- 63. Sackley C, Lincoln N (1997) Single blind randomized controlled trial of visual feedback after stroke: effects on stance symmetry and function. Disabil Rehabil 19: 536–546.
- 64. Yavuzer G, Eser F, Karakus D, Karaoglan B, Stam H (2006) The effects of balance training on gait late after stroke: a randomized controlled trial. Clin Rehabil 20: 960–969.
- 65. Eser F, Yavuzer G, Karakus D, Karaoglan B (2008) The effect of balance training on motor recovery and ambulation after stroke: a randomized controlled trial. Eur J Phys Rehabil Med 44: 19–25.
- 66. Gok H, Alptekin N, Geler-Kulcu D, Dincer G (2008) Efficacy of treatment with a kinaesthetic ability training device on balance and mobility after stroke: a randomized controlled study. Clin Rehabil 22: 922–930.
- 67. Goljar N, Burger H, Rudolf M, Stanonik I (2010) Improving balance in subacute stroke patients: a randomized controlled study. Int J Rehabil Res 33: 205–210.
- 68. Shumway-Cook A, Anson D, Haller S (1988) Postural sway biofeedback: its effect on reestablishing stance stability in hemiplegic patients. Arch Phys Med Rehabil 69: 395–400.
- 69. Grant T, Brouwer B, Culham E (1997) Balance retraining following acute stroke: a comparison of two methods. Can J Rehabil 11: 69–73.
- 70. Walker C, Brouwer B, Culham E (2000) Use of visual feedback in retraining balance following acute stroke. Phys Ther 80: 886–895.
- 71. Geiger R, Allen J, O'Keefe J, Hicks R (2001) Balance and mobility following stroke: effects of physical therapy interventions with and without biofeedback/forceplate training. Phys Ther 81: 995–1005.
- 72. Kerdoncuff V, Durufle A, Petrilli S, Nicolas B, Robineau S, et al. (2004) [Interest of visual biofeedback training in rehabilitation of balance after stroke]. Ann Readapt Med Phys 47: 169–176.
- 73. Heller F, Beuret-Blanquart F, Weber J (2005) [Postural biofeedback and locomotion reeducation in stroke patients]. Ann Readapt Med Phys 48: 187–195.
- 74. Merkert J, Butz S, Nieczaj R, Steinhagen-Thiessen E, Eckardt R (2011) Combined whole body vibration and balance training using Vibrosphere(R): Improvement of trunk stability, muscle tone, and postural control in stroke patients during early geriatric rehabilitation. Z Gerontol Geriatr 44: 256–261.
- 75. Holmgren E, Gosman-Hedström G, Lindström B, Wester P (2010) What is the benefit of a high-intensive exercise program on health-related quality of life and depression after stroke? A randomized controlled trial. Adv Physiother 12: 115–124.
- 76. Karthikbabu S, Nayak A, Vijayakumar K, Misri Z, Suresh B, et al. (2011) Comparison of physio ball and plinth trunk exercises regimens on trunk control and functional balance in patients with acute stroke: a pilot randomized controlled trial. Clin Rehabil 25: 709–719.
- 77. Cheng P, Wu S, Liaw M, Wong A, Tang F (2001) Symmetrical body-weight distribution training in stroke patients and its effect on fall prevention. Arch Phys Med Rehabil 82: 1650–1654.
- 78. Bonan I, Yelnik A, Colle F, Michaud C, Normand E, et al. (2004) Reliance on visual information after stroke. Part II: Effectiveness of a balance rehabilitation program with visual cue deprivation after stroke: a randomized controlled trial. Arch Phys Med Rehabil 85: 274–278.
- 79. McClellan R, Ada L (2004) A six-week, resource-efficient mobility program after discharge from rehabilitation improves standing in people affected by stroke: placebo-controlled, randomised trial. Aust J Physiother 50: 163–167.
- 80. Howe T, Taylor I, Finn P, Jones H (2005) Lateral weight transference exercises following acute stroke: a preliminary study of clinical effectiveness. Clin Rehabil 19: 45–53.
- 81. Marigold D, Eng J, Dawson A, Inglis J, Harris J, et al. (2005) Exercise leads to faster postural reflexes, improved balance and mobility, and fewer falls in older persons with chronic stroke. J Am Geriatr Soc 53: 416–423.
- 82. Yelnik A, Le Breton F, Colle F, Bonan I, Hugeron C, et al. (2008) Rehabilitation of balance after stroke with multisensorial training: a single-blind randomized controlled study. Neurorehabil Neural Repair 22: 468–476.
- 83. Verheyden G, Vereeck L, Truijen S, Troch M, Lafosse C, et al. (2009) Additional exercises improve trunk performance after stroke: a pilot randomized controlled trial. Neurorehabil Neural Repair 23: 281–286.
- 84. Askim T, Morkved S, Engen A, Roos K, Aas T, et al. (2010) Effects of a community-based intensive motor training program combined with early supported discharge after treatment in a comprehensive stroke unit: a randomized, controlled trial. Stroke 41: 1697–1703.
- 85. Kosak M, Reding M (2000) Comparison of partial body weight-supported treadmill gait training versus aggressive bracing assisted walking post stroke. Neurorehabil Neural Repair 14: 13–19.
- 86. Teixeira da Cunha Filho I, Lim P, Qureshy H, Henson H, Monga T, et al. (2001) A comparison of regular rehabilitation and regular rehabilitation with supported treadmill ambulation training for acute stroke patients. J Rehabil Res Dev 38: 245–255.
- 87. Da Cunha Jr I, Lim P, Qureshy H, Henson H, Monga T, et al. (2002) Gait outcomes after acute stroke rehabilitation with supported treadmill ambulation training: a randomized controlled pilot study. Arch Phys Med Rehabil 83: 1258–1265.
- 88. Eich H, Mach H, Werner C, Hesse S (2004) Aerobic treadmill plus Bobath walking training improves walking in subacute stroke: a randomized controlled trial. Clin Rehabil 18: 640–651.
- 89. Dean C, Ada L, Bampton J, Morris M, Katrak P, et al. (2010) Treadmill walking with body weight support in subacute non-ambulatory stroke improves walking capacity more than overground walking: a randomised trial. J Physiother 56: 97–103.
- 90. Yang Y, Chen I, Liao K, Huang C, Wang R (2010) Cortical reorganization induced by body weight-supported treadmill training in patients with hemiparesis of different stroke durations. Arch Phys Med Rehabil 91: 513–518.
- 91. Duncan PW, Sullivan KJ, Behrman AL, Azen SP, Wu SS, et al. (2011) Body-weight-supported treadmill rehabilitation after stroke. N Engl J Med 364: 2026–2036.
- 92. Visintin M, Barbeau H, Korner-Bitensky N, Mayo N (1998) A new approach to retrain gait in stroke patients through body weight support and treadmill stimulation. Stroke 29: 1122–1128.
- 93. Barbeau H, Visintin M (2003) Optimal outcomes obtained with body-weight support combined with treadmill training in stroke subjects. Arch Phys Med Rehabil 84: 1458–1465.
- 94. Nilsson L, Carlsson J, Danielsson A, Fugl-Meyer A, Hellström K, et al. (2001) Walking training of patients with hemiparesis at an early stage after stroke: a comparison of walking training on a treadmill with body weight support and walking training on the ground. Clin Rehabil 15: 515–527.
- 95. Sullivan K, Knowlton B, Dobkin B (2002) Step training with body weight support: effect of treadmill speed and practice paradigms on poststroke locomotor recovery. Arch Phys Med Rehabil 83: 683–691.
- 96. Werner C, Von Frankenberg S, Treig T, Konrad M, Hesse S (2002) Treadmill training with partial body weight support and an electromechanical gait trainer for restoration of gait in subacute stroke patients: a randomized crossover study. Stroke 33: 2895–2901.
- 97. Suputtitada A, Yooktanan P, Rarerng-Ying T (2004) Effect of partial body weight support treadmill training in chronic stroke patients. J Med Assoc Thai 87 Suppl 2S107–S111.
- 98. Yagura H, Hatakenaka M, Miyai I (2006) Does therapeutic facilitation add to locomotor outcome of body weight–supported treadmill training in nonambulatory patients with stroke? A randomized controlled trial. Arch Phys Med Rehabil 87: 529–535.
- 99. Sullivan K, Brown D, Klassen T, Mulroy S, Ge T, et al. (2007) Effects of task-specific locomotor and strength training in adults who were ambulatory after stroke: results of the STEPS randomized clinical trial. Phys Ther 87: 1580–1602.
- 100. Yen C, Wang R, Liao K, Huang C, Yang Y (2008) Gait training induced change in corticomotor excitability in patients with chronic stroke. Neurorehabil Neural Repair 22: 22–30.
- 101. Franceschini M, Carda S, Agosti M, Antenucci R, Malgrati D, et al. (2009) Walking after stroke: what does treadmill training with body weight support add to overground gait training in patients early after stroke?: a single-blind, randomized, controlled trial. Stroke 40: 3079–3085.
- 102. Westlake K, Patten C (2009) Pilot study of Lokomat versus manual-assisted treadmill training for locomotor recovery post-stroke. J Neuroeng Rehabil 6: 18.
- 103. Ada L, Dean C, Morris M, Simpson J, Katrak P (2010) Randomized trial of treadmill walking with body weight support to establish walking in subacute stroke: the MOBILISE trial. Stroke 41: 1237–1242.
- 104. Moore J, Roth E, Killian C, Hornby T (2010) Locomotor training improves daily stepping activity and gait efficiency in individuals poststroke who have reached a "plateau" in recovery. Stroke 41: 129–135.
- 105. Takami A, Wakayama S (2010) Effects of partial body weight support while training acute stroke patients to walk backwards on a treadmill - a controlled clinical trial using randomized allocation. J Phys Ther Sci 22: 177–187.
- 106.
Mehrholz J, Werner C, Kugler J, Pohl M (2007) Mechanical-assisted training for walking after stroke. Cochrane Database Syst Rev: CD006185.
- 107. Mehrholz J, Pohl M (2012) Electromechanical-assisted gait training after stroke: a systematic review comparing end-effector and exoskeleton devices. J Rehabil Med 44: 193–199.
- 108. Dias D, Lains J, Pereira A, Nunes R, Caldas J, et al. (2007) Can we improve gait skills in chronic hemiplegics? A randomised control trial with gait trainer. Eura Medicophys 43: 499–504.
- 109. Hidler J, Nichols D, Pelliccio M, Brady K, Campbell D, et al. (2009) Multicenter randomized clinical trial evaluating the effectiveness of the Lokomat in subacute stroke. Neurorehabil Neural Repair 23: 5–13.
- 110. Pohl M, Werner C, Holzgraefe M, Kroczek G, Mehrholz J, et al. (2007) Repetitive locomotor training and physiotherapy improve walking and basic activities of daily living after stroke: a single-blind, randomized multicentre trial (DEutsche GAngtrainerStudie, DEGAS). Clin Rehabil 21: 17–27.
- 111. Mehrholz J, Werner C, Hesse S, Pohl M (2008) Immediate and long-term functional impact of repetitive locomotor training as an adjunct to conventional physiotherapy for non-ambulatory patients after stroke. Disabil Rehabil 30: 830–836.
- 112. Peurala S, Tarkka I, Pitkänen K, Sivenius J (2005) The effectiveness of body weight-supported gait training and floor walking in patients with chronic stroke. Arch Phys Med Rehabil 86: 1557–1564.
- 113. Tong R, Ng M, Li L (2006) Effectiveness of gait training using an electromechanical gait trainer, with and without functional electric stimulation, in subacute stroke: a randomized controlled trial. Arch Phys Med Rehabil 87: 1298–1304.
- 114. Husemann B, Muller F, Krewer C, Heller S, Koenig E (2007) Effects of locomotion training with assistance of a robot-driven gait orthosis in hemiparetic patients after stroke: a randomized controlled pilot study. Stroke 38: 349–354.
- 115. Mayr A, Kofler M, Quirbach E, Matzak H, Frohlich K, et al. (2007) Prospective, blinded, randomized crossover study of gait rehabilitation in stroke patients using the Lokomat gait orthosis. Neurorehabil Neural Repair 21: 307–314.
- 116. Hornby T, Campbell D, Kahn J, Demott T, Moore J, et al. (2008) Enhanced gait-related improvements after therapist- versus robotic-assisted locomotor training in subjects with chronic stroke: a randomized controlled study. Stroke 39: 1786–1792.
- 117. Lewek M, Cruz T, Moore J, Roth H, Dhaher Y, et al. (2009) Allowing intralimb kinematic variability during locomotor training poststroke improves kinematic consistency: a subgroup analysis from a randomized clinical trial. Phys Ther 89: 829–839.
- 118. Ng M, Tong R, Li L (2008) A pilot study of randomized clinical controlled trial of gait training in subacute stroke patients with partial body-weight support electromechanical gait trainer and functional electrical stimulation: six-month follow-up. Stroke 39: 154–160.
- 119. Peurala S, Airaksinen O, Huuskonen P, Jakala P, Juhakoski M, et al. (2009) Effects of intensive therapy using gait trainer or floor walking exercises early after stroke. J Rehabil Med 41: 166–173.
- 120. Schwartz I, Sajin A, Fisher I, Neeb M, Shochina M, et al. (2009) The effectiveness of locomotor therapy using robotic-assisted gait training in subacute stroke patients: a randomized controlled trial. PM R 1: 516–523.
- 121. Fisher S, Lucas L, Thrasher T (2011) Robot-assisted gait training for patients with hemiparesis due to stroke. Top Stroke Rehabil 18: 269–276.
- 122. Morone G, Bragoni M, Iosa M, De Angelis D, Venturiero V, et al. (2011) Who may benefit from robotic-assisted gait training? A randomized clinical trial in patients with subacute stroke. Neurorehabil Neural Repair 25: 636–644.
- 123. Chang W, Kim M, Huh J, Lee P, Kim Y (2012) Effects of robot-assisted gait training on cardiopulmonary fitness in subacute stroke patients: a randomized controlled study. Neurorehabil Neural Repair 26: 318–324.
- 124. Ivey F, Hafer-Macko C, Ryan A, Macko R (2010) Impaired leg vasodilatory function after stroke: adaptations with treadmill exercise training. Stroke 41: 2913–2917.
- 125. Olawale O, Jaja S, Anigbogu C, Appiah-Kubi K, Jones-Okai D (2011) Exercise training improves walking function in an African group of stroke survivors: a randomized controlled trial. Clin Rehabil 25: 442–450.
- 126. Langhammer B, Stanghelle J (2010) Exercise on a treadmill or walking outdoors? A randomized controlled trial comparing effectiveness of two walking exercise programmes late after stroke. Clin Rehabil 24: 46–54.
- 127. Kuys S, Brauer S, Ada L (2011) Higher-intensity treadmill walking during rehabilitation after stroke in feasible and not detrimental to walking pattern or quality: a pilot randomized trial. Clin Rehabil 25: 316–326.
- 128. Liston R, Mickelborough J, Harris B, Hann A, Tallis R (2000) Conventional physiotherapy and treadmill re-training for higher-level gait disorders in cerebrovascular disease. Age Ageing 29: 311–318.
- 129. Laufer Y, Dickstein R, Chefez Y, Marcovitz E (2001) The effect of treadmill training on the ambulation of stroke survivors in the early stages of rehabilitation: a randomized study. J Rehabil Res Dev 38: 69–78.
- 130. Pohl M, Mehrholz J, Ritschel C, Ruckriem S (2002) Speed-dependent treadmill training in ambulatory hemiparetic stroke patients: a randomized controlled trial. Stroke 33: 553–558.
- 131. Ada L, Dean C, Hall J, Bampton J, Crompton S (2003) A treadmill and overground walking program improves walking in persons residing in the community after stroke: a placebo-controlled, randomized trial. Arch Phys Med Rehabil 84: 1486–1491.
- 132. Macko R, Ivey F, Forrester L, Hanley D, Sorkin J, et al. (2005) Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke: a randomized, controlled trial. Stroke 36: 2206–2211.
- 133. Ivey F, Ryan A, Hafer-Macko C, Goldberg A, Macko R (2007) Treadmill aerobic training improves glucose tolerance and indices of insulin sensitivity in disabled stroke survivors: a preliminary report. Stroke 38: 2752–2758.
- 134. Luft A, Macko R, Forrester L, Villagra F, Ivey F, et al. (2008) Treadmill exercise activates subcortical neural networks and improves walking after stroke: a randomized controlled trial. Stroke 39: 3341–3350.
- 135. Ivey F, Ryan A, Hafer-Macko C, Macko R (2011) Improved cerebral vasomotor reactivity after exercise training in hemiparetic stroke survivors. Stroke 42: 1994–2000.
- 136. Lau K, Mak M (2011) Speed-dependent treadmill training is effective to improve gait and balance performance in patients with sub-acute stroke. J Rehabil Med 43: 709–713.
- 137.
States R, Pappas E, Salem Y (2009) Overground physical therapy gait training for chronic stroke patients with mobility deficits. Cochrane Database Syst Rev: CD006075.
- 138. Patil P, Rao S (2011) Effects of Thera-Band elastic resistance-assisted gait training in stroke patients: a pilot study. Eur J Phys Rehabil Med 47: 427–433.
- 139. Green J, Forster A, Bogle S, Young J (2002) Physiotherapy for patients with mobility problems more than 1 year after stroke: a randomised controlled trial. Lancet 359: 199–203.
- 140. Salbach N, Mayo N, Wood-Dauphinee S, Hanley J, Richards C, et al. (2004) A task-orientated intervention enhances walking distance and speed in the first year post stroke: a randomized controlled trial. Clin Rehabil 18: 509–519.
- 141. Salbach N, Mayo N, Robichaud-Ekstrand S, Hanley J, Richards C, et al. (2005) The effect of a task-oriented walking intervention on improving balance self-efficacy poststroke: a randomized, controlled trial. J Am Geriatr Soc 53: 576–582.
- 142. Pang M, Eng J, Dawson A, McKay H, Harris J (2005) A community-based fitness and mobility exercise program for older adults with chronic stroke: a randomized, controlled trial. J Am Geriatr Soc 53: 1667–1674.
- 143. Pang M, Harris J, Eng J (2006) A community-based upper-extremity group exercise program improves motor function and performance of functional activities in chronic stroke: a randomized controlled trial. Arch Phys Med Rehabil 87: 1–9.
- 144. Wall J, Turnbull G (1987) Evaluation of out-patient physiotherapy and a home exercise program in the management of gait asymmetry in residual stroke. Neurorehabil Neural Repair 1: 115–123.
- 145. Wade D, Collen F, Robb G, Warlow C (1992) Physiotherapy intervention late after stroke and mobility. BMJ 304: 609–613.
- 146. Dean C, Richards C, Malouin F (2000) Task-related circuit training improves performance of locomotor tasks in chronic stroke: a randomized, controlled pilot trial. Arch Phys Med Rehabil 81: 409–417.
- 147. Lin J, Hsieh C, Lo S, Chai H, Liao L (2004) Preliminary study of the effect of low-intensity home-based physical therapy in chronic stroke patients. Kaohsiung J Med Sci 20: 18–23.
- 148. Yang Y, Yen J, Wang R, Yen L, Lieu F (2005) Gait outcomes after additional backward walking training in patients with stroke: a randomized controlled trial. Clin Rehabil 19: 264–273.
- 149. Yang Y, Wang R, Chen Y, Kao M (2007) Dual-task exercise improves walking ability in chronic stroke: a randomized controlled trial. Arch Phys Med Rehabil 88: 1236–1240.
- 150. Sungkarat S, Fisher B, Kovindha A (2011) Efficacy of an insole shoe wedge and augmented pressure sensor for gait training in individuals with stroke: a randomized controlled trial. Clin Rehabil 25: 360–369.
- 151. Thaut M, McIntosh G, Rice R (1997) Rhythmic facilitation of gait training in hemiparetic stroke rehabilitation. J Neurol Sci 151: 207–212.
- 152. Mandel A, Nymark J, Balmer S, Grinnell D, O'Riain M (1990) Electromyographic versus rhythmic positional biofeedback in computerized gait retraining with stroke patients. Arch Phys Med Rehabil 71: 649–654.
- 153. Schauer M, Mauritz K (2003) Musical motor feedback (MMF) in walking hemiparetic stroke patients: randomized trials of gait improvement. Clin Rehabil 17: 713–722.
- 154. Thaut M, Leins A, Rice R, Argstatter H, Kenyon G, et al. (2007) Rhythmic auditory stimulation improves gait more than NDT/Bobath training in near-ambulatory patients early poststroke: a single-blind, randomized trial. Neurorehabil Neural Repair 21: 455–459.
- 155. Argstatter H, Hillecke T, Thaut M, Bolay H (2007) Music therapy in motor rehabilitation. Evaluation of a musicomedical gait training programfor hemiparetic stroke patients [Musiktherapie in der neurologischen Rehabilitation. Evaluation eines musikmedizinischen Behandlungskonzepts für die Gangrehabilitation von hemiparetischen Patienten nach Schlaganfall]. Neurol Rehabil 13: 159–165.
- 156. Jeong S, Kim M (2007) Effects of a theory-driven music and movement program for stroke survivors in a community setting. Appl Nurs Res 20: 125–131.
- 157. Lord S, McPherson K, McNaughton H, Rochester L, Weatherall M (2008) How feasible is the attainment of community ambulation after stroke? A pilot randomized controlled trial to evaluate community-based physiotherapy in subacute stroke. Clin Rehabil 22: 215–225.
- 158. Park H, Oh D, Kim S, Choi J (2011) Effectiveness of community-based ambulation training for walking function of post-stroke hemiparesis: a randomized controlled pilot trial. Clin Rehabil 25: 451–459.
- 159. Henderson A, Korner-Bitensky N, Levin M (2007) Virtual reality in stroke rehabilitation: a systematic review of its effectiveness for upper limb motor recovery. Top Stroke Rehabil 14: 52–61.
- 160. Saposnik G, Levin M (2011) Virtual reality in stroke rehabilitation: a meta-analysis and implications for clinicians. Stroke 42: 1380–1386.
- 161. Jaffe D, Brown D, Pierson-Carey C, Buckley E, Lew H (2004) Stepping over obstacles to improve walking in individuals with poststroke hemiplegia. J Rehabil Res Dev 41: 283–292.
- 162. You S, Jang S, Kim Y, Hallett M, Ahn S, et al. (2005) Virtual reality-induced cortical reorganization and associated locomotor recovery in chronic stroke: an experimenter-blind randomized study. Stroke 36: 1166–1171.
- 163. Kim J, Jang S, Kim C, Jung J, You J (2009) Use of virtual reality to enhance balance and ambulation in chronic stroke: a double-blind, randomized controlled study. Am J Phys Med Rehabil 88: 693–701.
- 164. Lam Y, Man D, Tam S, Weiss P (2006) Virtual reality training for stroke rehabilitation. NeuroRehabilitation 21: 245–253.
- 165. Yang Y, Tsai M, Chuang T, Sung W, Wang R (2008) Virtual reality-based training improves community ambulation in individuals with stroke: a randomized controlled trial. Gait Posture 28: 201–206.
- 166. Mirelman A, Bonato P, Deutsch J (2009) Effects of training with a robot-virtual reality system compared with a robot alone on the gait of individuals after stroke. Stroke 40: 169–174.
- 167. Mirelman A, Patritti B, Bonato P, Deutsch J (2010) Effects of virtual reality training on gait biomechanics of individuals post-stroke. Gait Posture 31: 433–437.
- 168. Wevers L, Van de Port I, Vermue M, Mead G, Kwakkel G (2009) Effects of task-oriented circuit class training on walking competency after stroke: a systematic review. Stroke 40: 2450–2459.
- 169.
English C, Hillier S (2010) Circuit class therapy for improving mobility after stroke. Cochrane Database Syst Rev: CD007513.
- 170. Blennerhassett J, Dite W (2004) Additional task-related practice improves mobility and upper limb function early after stroke: a randomised controlled trial. Aust J Physiother 50: 219–224.
- 171. Mead G, Greig C, Cunningham I, Lewis S, Dinan S, et al. (2007) Stroke: a randomized trial of exercise or relaxation. J Am Geriatr Soc 55: 892–899.
- 172. Yang Y, Wang R, Lin K, Chu M, Chan R (2006) Task-oriented progressive resistance strength training improves muscle strength and functional performance in individuals with stroke. Clin Rehabil 20: 860–870.
- 173. Mudge S, Barber P, Stott N (2009) Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke: a randomized controlled trial. Arch Phys Med Rehabil 90: 1989–1996.
- 174. Galvin R, Cusack T, O'Grady E, Murphy T, Stokes E (2011) Family-mediated exercise intervention (FAME): evaluation of a novel form of exercise delivery after stroke. Stroke 42: 681–686.
- 175. Kalra L, Evans A, Perez I, Melbourn A, Patel A, et al. (2004) Training carers of stroke patients: randomised controlled trial. BMJ 328: 1099.
- 176.
Wright P, Mann G, Swain I (2004) A comparison of electrical stimulation and the conventional ankle foot orthosis in the correction of a dropped foot following stroke. Final report to funder.
- 177. Beckerman H, Becher J, Lankhorst G, Verbeek A, Vogelaar T (1996) The efficacy of thermocoagulation of the tibial nerve and a polypropylene ankle-foot orthosis on spasticity of the leg in stroke patients: results of a randomized clinical trial. Clin Rehabil 10: 112–120.
- 178. Erel S, Uygur F, Engin Simsek I, Yakut Y (2011) The effects of dynamic ankle-foot orthoses in chronic stroke patients at three-month follow-up: a randomized controlled trial. Clin Rehabil 25: 515–523.
- 179.
Mehrholz J, Kugler J, Pohl M (2011) Water-based exercises for improving activities of daily living after stroke. Cochrane Database Syst Rev: CD008186.
- 180. Aidar F, Silva A, Reis V, Carneiro A, Carneiro-Cotta S (2007) A study of the quality of life in ischemic vascular accidents and its relation to physical activity [Estudio de la calidad de vida en el accidente vascular isquémico y sur relación con la actividad física]. Rev Neurol 45: 518–522.
- 181. Noh D, Lim J, Shin H, Paik N (2008) The effect of aquatic therapy on postural balance and muscle strength in stroke survivors–a randomized controlled pilot trial. Clin Rehabil 22: 966–976.
- 182. Chu K, Eng J, Dawson A, Harris J, Ozkaplan A, et al. (2004) Water-based exercise for cardiovascular fitness in people with chronic stroke: a randomized controlled trial. Arch Phys Med Rehabil 85: 870–874.
- 183.
Doyle S, Bennett S, Fasoli S, McKenna K (2010) Interventions for sensory impairment in the upper limb after stroke. Cochrane Database Syst Rev: CD006331.
- 184.
Intercollegiate Stroke Working Party (2012) National clinical guideline for stroke, 4th edition. London: Royal College of Physicians.
- 185. Torriani C, Mota E, Moreira Sales A, Ricci M, Nishida P, et al. (2008) Effect of foot motor and sensorial stimulation hemiparetic in stroke patients. Rev Neurocienc 16: 25–29.
- 186. Yavuzer G, Oken O, Atay M, Stam H (2007) Effects of sensory-amplitude electric stimulation on motor recovery and gait kinematics after stroke: a randomized controlled study. Arch Phys Med Rehabil 88: 710–714.
- 187. Lynch E, Hillier S, Stiller K, Campanella R, Fisher P (2007) Sensory retraining of the lower limb after acute stroke: a randomized controlled pilot trial. Arch Phys Med Rehabil 88: 1101–1107.
- 188. Wu H, Lin Y, Hsu M, Liu S, Hsieh C, et al. (2010) Effect of thermal stimulation on upper extremity motor recovery 3 months after stroke. Stroke 41: 2378–2380.
- 189. Chen J, Lin C, Wei Y, Hsiao J, Liang C (2011) Facilitation of motor and balance recovery by thermal intervention for the paretic lower limb of acute stroke: a single-blind randomized clinical trial. Clin Rehabil 25: 823–832.
- 190.
Pomeroy V, King L, Pollock A, Baily-Hallam A, Langhorne P (2006) Electrostimulation for promoting recovery of movement or functional ability after stroke. Cochrane Database Syst Rev: CD003241.
- 191. Bakhtiary A, Fatemy E (2008) Does electrical stimulation reduce spasticity after stroke? A randomized controlled study. Clin Rehabil 22: 418–425.
- 192. Ambrosini E, Ferrante S, Pedrocchi A, Ferrigno G, Molteni F (2011) Cycling induced by electrical stimulation improves motor recovery in postacute hemiparetic patients: a randomized controlled trial. Stroke 42: 1068–1073.
- 193. Merletti R, Zelaschi F, Latella D, Galli M, Angeli S, et al. (1978) A control study of muscle force recovery in hemiparetic patients during treatment with functional electrical stimulation. Scand J Rehabil Med 10: 147–154.
- 194. Cozean C, Pease W, Hubbell S (1988) Biofeedback and functional electric stimulation in stroke rehabilitation. Arch Phys Med Rehabil 69: 401–405.
- 195. Winchester P, Montgomery J, Bowman B, Hislop H (1983) Effects of feedback stimulation training and cyclical electrical stimulation on knee extension in hemiparetic patients. Phys Ther 63: 1096–1103.
- 196. Macdonell R, Triggs W, Leikauskas J, Bourque M, Robb K, et al. (1994) Functional electrical stimulation to the affected lower limb and recovery after cerebral infarction. J Stroke Cerebrovasc Dis 4: 155–160.
- 197. Bogataj U, Gros N, Kljajic M, Acimovic R, Malezic M (1995) The rehabilitation of gait in patients with hemiplegia: a comparison between conventional therapy and multichannel functional electrical stimulation therapy. Phys Ther 75: 490–502.
- 198. Burridge J, Taylor P, Hagan S, Wood D, Swain I (1997) The effects of common peroneal stimulation on the effort and speed of walking: a randomized controlled trial with chronic hemiplegic patients. Clin Rehabil 11: 201–210.
- 199. Heckmann J, Mokrusch T, Krockel A, Warnke S, Neundorfer B (1997) EMG-triggered electrical muscle stimulation in the treatment of central hemiparesis after a stroke. Eur J Phys Med Rehabil 7: 138–141.
- 200. Tekeoglu Y, Adak B, Goksoy T (1998) Effect of transcutaneous electrical nerve stimulation (TENS) on Barthel Activities of Daily Living (ADL) index score following stroke. Clin Rehabil 12: 277–280.
- 201. Newsam C, Baker L (2004) Effect of an electric stimulation facilitation program on quadriceps motor unit recruitment after stroke. Arch Phys Med Rehabil 85: 2040–2045.
- 202. Chen S, Chen Y, Chen C, Lai C, Chiang W, et al. (2005) Effects of surface electrical stimulation on the muscle-tendon junction of spastic gastrocnemius in stroke patients. Disabil Rehabil 27: 105–110.
- 203. Yan T, Hui-Chan C, Li L (2005) Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke: a randomized placebo-controlled trial. Stroke 36: 80–85.
- 204. Yavuzer G, Geler-Kulcu D, Sonel-Tur B, Kutlay S, Ergin S, et al. (2006) Neuromuscular electric stimulation effect on lower-extremity motor recovery and gait kinematics of patients with stroke: a randomized controlled trial. Arch Phys Med Rehabil 87: 536–540.
- 205. Ng S, Hui-Chan C (2007) Transcutaneous electrical nerve stimulation combined with task-related training improves lower limb functions in subjects with chronic stroke. Stroke 38: 2953–2959.
- 206. Ferrante S, Pedrocchi A, Ferrigno G, Molteni F (2008) Cycling induced by functional electrical stimulation improves the muscular strength and the motor control of individuals with post-acute stroke. Europa Medicophysica-SIMFER 2007 Award Winner. Eur J Phys Rehabil Med 44: 159–167.
- 207. Janssen T, Beltman J, Elich P, Koppe P, Konijnenbelt H, et al. (2008) Effects of electric stimulation-assisted cycling training in people with chronic stroke. Arch Phys Med Rehabil 89: 463–469.
- 208. Kojovic J, Djuric-Jovicic M, Dosen S, Popovic M, Popovic D (2009) Sensor-driven four-channel stimulation of paretic leg: functional electrical walking therapy. J Neurosci Methods 181: 100–105.
- 209. Mesci N, Ozdemir F, Kabayel D, Tokuc B (2009) The effects of neuromuscular electrical stimulation on clinical improvement in hemiplegic lower extremity rehabilitation in chronic stroke: a single-blind, randomised, controlled trial. Disabil Rehabil 31: 2047–2054.
- 210. Ng SS, Hui-Chan CW (2009) Does the use of TENS increase the effectiveness of exercise for improving walking after stroke? A randomized controlled clinical trial. Clin Rehabil 23: 1093–1103.
- 211. Hui-Chan C, Ng S, Mak M (2009) Effectiveness of a home-based rehabilitation programme on lower limb functions after stroke. Hong Kong Med J 15: 42–46.
- 212. Yan T, Hui-Chan C (2009) Transcutaneous electrical stimulation on acupuncture points improves muscle function in subjects after acute stroke: a randomized controlled trial. J Rehabil Med 41: 312–316.
- 213. Cheng J, Yang Y, Cheng S, Lin P, Wang R (2010) Effects of combining electric stimulation with active ankle dorsiflexion while standing on a rocker board: a pilot study for subjects with spastic foot after stroke. Arch Phys Med Rehabil 91: 505–512.
- 214. Moreland J, Thomson M, Fuoco A (1998) Electromyographic biofeedback to improve lower extremity function after stroke: a meta-analysis. Arch Phys Med Rehabil 79: 134–140.
- 215.
Woodford H, Price C (2007) EMG biofeedback for the recovery of motor function after stroke. Cochrane Database Syst Rev: CD004585.
- 216. John J (1986) Failure of electrical myofeedback to augment the effects of physiotherapy in stroke. Int J Rehabil Res 9: 35–45.
- 217. Jonsdottir J, Cattaneo D, Recalcati M, Regola A, Rabuffetti M, et al. (2010) Task-oriented biofeedback to improve gait in individuals with chronic stroke: motor learning approach. Neurorehabil Neural Repair 24: 478–485.
- 218. Basmajian J, Kukulka C, Narayan M, Takebe K (1975) Biofeedback treatment of foot-drop after stroke compared with standard rehabilitation technique: effects on voluntary control and strength. Arch Phys Med Rehabil 56: 231–236.
- 219. Hurd W, Pegram V, Nepomuceno C (1980) Comparison of actual and simulated EMG biofeedback in the treatment of hemiplegic patients. Am J Phys Med 59: 73–82.
- 220. Binder S, Moll C, Wolf S (1981) Evaluation of electromyographic biofeedback as an adjunct to therapeutic exercise in treating the lower extremities of hemiplegic patients. Phys Ther 61: 886–893.
- 221. Mulder T, Hulstijn W, Van der Meer J (1986) EMG feedback and the restoration of motor control. A controlled group study of 12 hemiparetic patients. Am J Phys Med 65: 173–188.
- 222. Colborne G, Olney S, Griffin M (1993) Feedback of ankle joint angle and soleus electromyography in the rehabilitation of hemiplegic gait. Arch Phys Med Rehabil 74: 1100–1106.
- 223. Intiso D, Santilli V, Grasso M, Rossi R, Caruso I (1994) Rehabilitation of walking with electromyographic biofeedback in foot-drop after stroke. Stroke 25: 1189–1192.
- 224. Bradley L, Hart B, Mandana S, Flowers K, Riches M, et al. (1998) Electromyographic biofeedback for gait training after stroke. Clin Rehabil 12: 11–22.
- 225. Ploughman M, Corbett D (2004) Can forced-use therapy be clinically applied after stroke? An exploratory randomized controlled trial. Arch Phys Med Rehabil 85: 1417–1423.
- 226. Hammer A, Lindmark B (2009) Is forced use of the paretic upper limb beneficial? A randomized pilot study during subacute post-stroke recovery. Clin Rehabil 23: 424–433.
- 227. Hu X, Tong K, Song R, Zheng X, Leung W (2009) A comparison between electromyography-driven robot and passive motion device on wrist rehabilitation for chronic stroke. Neurorehabil Neural Repair 23: 837–846.
- 228. Kutner N, Zhang R, Butler A, Wolf S, Alberts J (2010) Quality-of-life change associated with robotic-assisted therapy to improve hand motor function in patients with subacute stroke: a randomized clinical trial. Phys Ther 90: 493–504.
- 229. Takahashi C, Der-Yeghiaian L, Le V, Motiwala R, Cramer S (2008) Robot-based hand motor therapy after stroke. Brain 131: 425–437.
- 230. Lynch D, Ferraro M, Krol J, Trudell C, Christos P, et al. (2005) Continuous passive motion improves shoulder joint integrity following stroke. Clin Rehabil 19: 594–599.
- 231. Stein J, Hughes R, D'Andrea S, Therrien B, Niemi J, et al. (2010) Stochastic resonance stimulation for upper limb rehabilitation poststroke. Am J Phys Med Rehabil 89: 697–705.
- 232. Stinear C, Barber P, Coxon J, Fleming M, Byblow W (2008) Priming the motor system enhances the effects of upper limb therapy in chronic stroke. Brain 131: 1381–1390.
- 233. Wang T, Wang X, Wang H, He X, Su J, et al. (2007) Effects of ULEM apparatus on motor function of patients with stroke. Brain Inj 21: 1203–1208.
- 234. Hesse S, Werner C, Pohl M, Merholz J, Puzich U, et al. (2008) Mechanical arm trainer for the treatment of the severely affected arm after a stroke: a single-blinded randomized trial in two centers. Am J Phys Med Rehabil 87: 779–788.
- 235. Turton A, Britton E (2005) A pilot randomized controlled trial of a daily muscle stretch regime to prevent contractures in the arm after stroke. Clin Rehabil 19: 600–612.
- 236. Gustafsson L, McKenna K (2006) A programme of static positional stretches does not reduce hemiplegic shoulder pain or maintain shoulder range of motion–a randomized controlled trial. Clin Rehabil 20: 277–286.
- 237. Dean C, Mackey F, Katrak P (2000) Examination of shoulder positioning after stroke: A randomised controlled pilot trial. Aust J Physiother 46: 35–40.
- 238. Ada L, Goddard E, McCully J, Stavrinos T, Bampton J (2005) Thirty minutes of positioning reduces the development of shoulder external rotation contracture after stroke: a randomized controlled trial. Arch Phys Med Rehabil 86: 230–234.
- 239. De Jong L, Nieuwboer A, Aufdemkampe G (2006) Contracture preventive positioning of the hemiplegic arm in subacute stroke patients: a pilot randomized controlled trial. Clin Rehabil 20: 656–667.
- 240. Rose V, Shah S (1980) A comparative study on the immediate effects of hand orthosis on reduction of hypertonus. Aust Occup Ther J 34: 59–64.
- 241. Lannin N, Cusick A, McCluskey A, Herbert H (2007) Effects of splinting on wrist contracture after stroke: a randomized controlled trial. Stroke 38: 111–116.
- 242. Bürge E, Kupper D, Finckh A, Ryerson S, Schnider A, et al. (2008) Neutral functional realignment orthosis prevents hand pain in patients with subacute stroke: a randomized trial. Arch Phys Med Rehabil 89: 1857–1862.
- 243. Carey J (1990) Manual stretch: effect on finger movement control and force control in stroke subjects with spastic extrinsic finger flexor muscles. Arch Phys Med Rehabil 71: 888–894.
- 244. Langlois S, Pederson L, MacKinnon J (1991) The effects of splinting on the spastic hemiplegic hand: report of a feasible study. Can J Occup Ther 58: 17–25.
- 245. Sheehan J, Winzeler-Mercay U, Mudie M (2006) A randomized controlled pilot study to obtain the best estimate of the size of the effect of a thermoplastic resting splint on spasticity in the stroke-affected wrist and fingers. Clin Rehabil 20: 1032–1037.
- 246. Heidari M, Eghlidi Z, About Talebi S, Hosseini S, Rahimifard H, et al. (2011) Comparison of mobilizing and immobilizing splints on hand motor function in stroke patients: a randomized clinical trial. QOM University Med Sci J 4: 48–53.
- 247. Suat E, Engin S, Nilgun B, Yavuz Y, Fatma U (2011) Short- and long-term effects of an inhibitor hand splint in poststroke patients: a randomized controlled trial. Top Stroke Rehabil 18: 231–237.
- 248. Robichaud J, Agostinucci J, Van der Linden D (1992) Effect of air-splint application on soleus muscle motoneuron reflex excitability in nondisabled subjects and subjects with cerebrovascular accidents. Phys Ther 72: 176–183.
- 249. Johnstone M (1989) Current advances in the use of pressure splints in the management of adult hemiplegia. Physiotherapy 75: 381–384.
- 250. Feys H, De Weerdt W, Selz B, Cox Steck G, Spichiger R, et al. (1998) Effect of a therapeutic intervention for the hemiplegic upper limb in the acute phase after stroke: a single-blind, randomized, controlled multicenter trial. Stroke 29: 785–792.
- 251. Feys H, De Weerdt W, Verbeke G, Steck G, Capiau C, et al. (2004) Early and repetitive stimulation of the arm can substantially improve the long-term outcome after stroke: a 5-year follow-up study of a randomized trial. Stroke 35: 924–929.
- 252. Platz T, Van Kaick S, Mehrholz J, Leidner O, Eickhof C, et al. (2009) Best conventional therapy versus modular impairment-oriented training for arm paresis after stroke: a single-blind, multicenter randomized controlled trial. Neurorehabil Neural Repair 23: 706–716.
- 253. Poole J, Whitney S, Hangeland N, Baker C (1990) The effectiveness of inflatable pressure splints on motor function in stroke patients. Occup Ther J Res 10: 360–366.
- 254. Roper T, Redford S, Tallis R (1999) Intermittent compression for the treatment of the oedematous hand in hemiplegic stroke: a randomized controlled trial. Age Ageing 28: 9–13.
- 255. Cambier D, De Corte E, Danneels L, Witvrouw E (2003) Treating sensory impairments in the post-stroke upper limb with intermittent pneumatic compression. Results of a preliminary trial. Clin Rehabil 17: 14–20.
- 256.
Ada L, Foongchomcheay A, Canning C (2005) Supportive devices for preventing and treating subluxation of the shoulder after stroke. Cochrane Database Syst Rev: CD003863.
- 257. Appel C, Mayston M (2011) Perry (2011) Feasibility study of a randomized controlled trial protocol to examine clinical effectiveness of shoulder strapping in acute stroke patients. Clin Rehabil 25: 833–843.
- 258. Hanger H, Whitewood P, Brown G, Ball M, Harper J, et al. (2000) A randomized controlled trial of strapping to prevent post-stroke shoulder pain. Clin Rehabil 14: 370–380.
- 259. Griffin A, Bernhardt J (2006) Strapping the hemiplegic shoulder prevents development of pain during rehabilitation: a randomized controlled trial. Clin Rehabil 20: 287–295.
- 260. Mudie M, Matyas T (2000) Can simultaneous bilateral movement involve the undamaged hemisphere in reconstruction of neural networks damaged by stroke? Disabil Rehabil 22: 23–37.
- 261. Hayner K, Gibson G, Giles G (2010) Comparison of constraint-induced movement therapy and bilateral treatment of equal intensity in people with chronic upper-extremity dysfunction after cerebrovascular accident. Am J Occup Ther 64: 528–539.
- 262. Wu C, Hsieh Y, Lin K, Chuang L, Chang Y, et al. (2010) Brain reorganization after bilateral arm training and distributed constraint-induced therapy in stroke patients: a preliminary functional magnetic resonance imaging study. Chang Gung Med J 33: 628–638.
- 263. Morris J, Van Wijck F, Joice S, Ogston S, Cole I, et al. (2008) A comparison of bilateral and unilateral upper-limb task training in early poststroke rehabilitation: a randomized controlled trial. Arch Phys Med Rehabil 89: 1237–1245.
- 264. Van der Lee J, Wagenaar R, Lankhorst G, Vogelaar T, Deville W, et al. (1999) Forced use of the upper extremity in chronic stroke patients: results from a single-blind randomized clinical trial. Stroke 30: 2369–2375.
- 265. Mudie M, Matyas T (2001) Responses of the densely hemiplegic upper extremity to bilateral training. Neurorehabil Neural Repair 15: 129–140.
- 266. Platz T, Bock S, Prass K (2001) Reduced skilfulness of arm motor behaviour among motor stroke patients with good clinical recovery: does it indicate reduced automaticity? Can it be improved by unilateral or bilateral training? A kinematic motion analysis study. Neuropsychologia 39: 687–698.
- 267. Cauraugh J, Kim S (2002) Two coupled motor recovery protocols are better than one: electromyogram-triggered neuromuscular stimulation and bilateral movements. Stroke 33: 1589–1594.
- 268. Cauraugh J, Kim S (2003) Progress toward motor recovery with active neuromuscular stimulation: muscle activation pattern evidence after a stroke. J Neurol Sci 207: 25–29.
- 269. Luft A, McCombe-Waller S, Whitall J, Forrester L, Macko R, et al. (2004) Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial. JAMA 292: 1853–1861.
- 270. Suputtitada A, Suwanwela N, Tumvitee S (2004) Effectiveness of constraint-induced movement therapy in chronic stroke patients. J Med Assoc Thai 87: 1482–1490.
- 271. Cauraugh J, Kim S, Duley A (2005) Coupled bilateral movements and active neuromuscular stimulation: intralimb transfer evidence during bimanual aiming. Neurosci Lett 382: 39–44.
- 272. Desrosiers J, Bourbonnais D, Corriveau H, Gosselin S, Bravo G (2005) Effectiveness of unilateral and symmetrical bilateral task training for arm during the subacute phase after stroke: a randomized controlled trial. Clin Rehabil 19: 581–593.
- 273. Lum P, Burgar C, Van der Loos M, Shor P, Majmundar M, et al. (2006) MIME robotic device for upper-limb neurorehabilitation in subacute stroke subjects: A follow-up study. J Rehabil Res Dev 43: 631–642.
- 274. Summers J, Kagerer F, Garry M, Hiraga C, Loftus A, et al. (2007) Bilateral and unilateral movement training on upper limb function in chronic stroke patients: A TMS study. J Neurol Sci 252: 76–82.
- 275. Cauraugh J, Kim S, Summers J (2008) Chronic stroke longitudinal motor improvements: cumulative learning evidence found in the upper extremity. Cerebrovasc Dis 25: 115–121.
- 276. McCombe Waller S, Liu W, Whitall J (2008) Temporal and spatial control following bilateral versus unilateral training. Hum Mov Sci 27: 749–758.
- 277. Cauraugh J, Coombes S, Lodha N, Naik S, Summers J (2009) Upper extremity improvements in chronic stroke: coupled bilateral load training. Restor Neurol Neurosci 27: 17–25.
- 278. Lin K, Chang Y, Wu C, Chen Y (2009) Effects of constraint-induced therapy versus bilateral arm training on motor performance, daily functions, and quality of life in stroke survivors. Neurorehabil Neural Repair 23: 441–448.
- 279. Stoykov M, Lewis G, Corcos D (2009) Comparison of bilateral and unilateral training for upper extremity hemiparesis in stroke. Neurorehabil Neural Repair 23: 945–953.
- 280. Lin K, Chen Y, Chen C, Wu C, Chang Y (2010) The effects of bilateral arm training on motor control and functional performance in chronic stroke: a randomized controlled study. Neurorehabil Neural Repair 24: 42–51.
- 281. Whitall J, Waller S, Sorkin J, Forrester L, Macko R, et al. (2011) Bilateral and unilateral arm training improve motor function through differing neuroplastic mechanisms: a single-blinded randomized controlled trial. Neurorehabil Neural Repair 25: 118–129.
- 282. Wu C, Chuang L, Lin K, Chen H, Tsay P (2011) Randomized trial of distributed constraint-induced therapy versus bilateral arm training for the rehabilitation of upper-limb motor control and function after stroke. Neurorehabil Neural Repair 25: 130–139.
- 283. Page S, Sisto S, Levine P, Johnston M, Hughes M (2001) Modified constraint induced therapy: a randomized feasibility and efficacy study. J Rehabil Res Dev 38: 583–590.
- 284. Atteya A (2004) Effects of modified constraint induced therapy on upper limb function in subacute stroke patients. Neurosciences (Riyadh) 9: 24–29.
- 285. Kim D, Cho Y, Hong J, Song J, Chung H, et al. (2008) Effect of constraint-induced movement therapy with modified opposition restriction orthosis in chronic hemiparetic patients with stroke. NeuroRehabilitation 23: 239–244.
- 286. Dahl A, Askim T, Stock R, Langorgen E, Lydersen S, et al. (2008) Short- and long-term outcome of constraint-induced movement therapy after stroke: a randomized controlled feasibility trial. Clin Rehabil 22: 436–447.
- 287. Taub E, Miller N, Novack T, Cook 3rd E, Fleming W, et al. (1993) Technique to improve chronic motor deficit after stroke. Arch Phys Med Rehabil 74: 347–354.
- 288. Dromerick A, Edwards D, Hahn M (2000) Does the application of constraint-induced movement therapy during acute rehabilitation reduce arm impairment after ischemic stroke? Stroke 31: 2984–2988.
- 289. Page S, Sisto S, Johnston M, Levine P (2002) Modified constraint-induced therapy after subacute stroke: a preliminary study. Neurorehabil Neural Repair 16: 290–295.
- 290. Wittenberg G, Chen R, Ishii K, Bushara K, Eckloff S, et al. (2003) Constraint-induced therapy in stroke: magnetic-stimulation motor maps and cerebral activation. Neurorehabil Neural Repair 17: 48–57.
- 291. Alberts J, Butler A, Wolf S (2004) The effects of constraint-induced therapy on precision grip: a preliminary study. Neurorehabil Neural Repair 18: 250–258.
- 292. Page S, Sisto S, Levine P, McGrath R (2004) Efficacy of modified constraint-induced movement therapy in chronic stroke: a single-blinded randomized controlled trial. Arch Phys Med Rehabil 85: 14–18.
- 293. Page S, Levine P, Leonard A (2005) Modified constraint-induced therapy in acute stroke: a randomized controlled pilot study. Neurorehabil Neural Repair 19: 27–32.
- 294. Yen J, Wang R, Chen H, Hong C (2005) Effectiveness of modified constraint-induced movement therapy on upper limb function in stroke subjects. Acta Neurol Taiwan 14: 16–20.
- 295. Ro T, Noser E, Boake C, Johnson R, Gaber M, et al. (2006) Functional reorganization and recovery after constraint-induced movement therapy in subacute stroke: case reports. Neurocase 12: 50–60.
- 296. Brogardh C, Sjolund B (2006) Constraint-induced movement therapy in patients with stroke: a pilot study on effects of small group training and of extended mitt use. Clin Rehabil 20: 218–227.
- 297. Wolf S, Winstein C, Miller J, Taub E, Uswatte G, et al. (2006) Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. JAMA 296: 2095–2104.
- 298. Wolf S, Thompson P, Winstein C, Miller J, Blanton S, et al. (2010) The EXCITE stroke trial: comparing early and delayed constraint-induced movement therapy. Stroke 41: 2309–2315.
- 299. Boake C, Noser E, Ro T, Baraniuk S, Gaber M, et al. (2007) Constraint-induced movement therapy during early stroke rehabilitation. Neurorehabil Neural Repair 21: 14–24.
- 300. Lin K, Wu C, Wei T, Lee C, Liu J (2007) Effects of modified constraint-induced movement therapy on reach-to-grasp movements and functional performance after chronic stroke: a randomized controlled study. Clin Rehabil 21: 1075–1086.
- 301. Wu C, Chen C, Tang S, Lin K, Huang Y (2007) Kinematic and clinical analyses of upper-extremity movements after constraint-induced movement therapy in patients with stroke: a randomized controlled trial. Arch Phys Med Rehabil 88: 964–970.
- 302. Wu C, Chen C, Tsai W, Lin K, Chou S (2007) A randomized controlled trial of modified constraint-induced movement therapy for elderly stroke survivors: changes in motor impairment, daily functioning, and quality of life. Arch Phys Med Rehabil 88: 273–278.
- 303. Wu C, Lin K, Chen H, Chen I, Hong W (2007) Effects of modified constraint-induced movement therapy on movement kinematics and daily function in patients with stroke: a kinematic study of motor control mechanisms. Neurorehabil Neural Repair 21: 460–466.
- 304. Gauthier L, Taub E, Perkins C, Ortmann M, Mark V, et al. (2008) Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke. Stroke 39: 1520–1525.
- 305. Myint J, Yuen G, Yu T, Kng C, Wong A, et al. (2008) A study of constraint-induced movement therapy in subacute stroke patients in Hong Kong. Clin Rehabil 22: 112–124.
- 306. Myint M, Yuen F, Yu K, Kng P, Wong M, et al. (2008) Use of constraint-induced movement therapy in Chinese stroke patients during the sub-acute period. Hong Kong Med J 14: 40–42.
- 307. Page S, Levine P, Leonard A, Szaflarski J, Kissela B (2008) Modified constraint-induced therapy in chronic stroke: results of a single-blinded randomized controlled trial. Phys Ther 88: 333–340.
- 308. Sawaki L, Butler A, Leng X, Wassenaar P, Mohammad Y, et al. (2008) Constraint-induced movement therapy results in increased motor map area in subjects 3 to 9 months after stroke. Neurorehabil Neural Repair 22: 505–513.
- 309. Azab M, Al-Jarrah M, Nazzal M, Maayah M, Sammour M, et al. (2009) Effectiveness of constraint-induced movement therapy (CIMT) as home-based therapy on Barthel Index in patients with chronic stroke. Top Stroke Rehabil 16: 207–211.
- 310. Brogardh C, Vestling M, Sjolund B (2009) Shortened constraint-induced movement therapy in subacute stroke - no effect of using a restraint: a randomized controlled study with independent observers. J Rehabil Med 41: 231–236.
- 311. Brogardh C, Lexell J (2010) A 1-year follow-up after shortened constraint-induced movement therapy with and without mitt poststroke. Arch Phys Med Rehabil 91: 460–464.
- 312. Dromerick A, Lang C, Birkenmeier R, Wagner J, Miller J, et al. (2009) Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS): a single-center RCT. Neurology 73: 195–201.
- 313. Lin K, Wu C, Liu J, Chen Y, Hsu C (2009) Constraint-induced therapy versus dose-matched control intervention to improve motor ability, basic/extended daily functions, and quality of life in stroke. Neurorehabil Neural Repair 23: 160–165.
- 314. Woodbury M, Howland D, McGuirk T, Davis S, Senesac C, et al. (2009) Effects of trunk restraint combined with intensive task practice on poststroke upper extremity reach and function: a pilot study. Neurorehabil Neural Repair 23: 78–91.
- 315. Abu Tariah H, Almalty A, Sbeih, Al-Oraibi S (2010) Constraint induced movement therapy for stroke survivors in Jordon: a home-based model. Int J Ther Rehab 17: 638–646.
- 316. Lin K, Chung H, Wu C, Liu H, Hsieh Y, et al. (2010) Constraint-induced therapy versus control intervention in patients with stroke: a functional magnetic resonance imaging study. Am J Phys Med Rehabil 89: 177–185.
- 317. Sun S, Hsu C, Sun H, Hwang C, Yang C, et al. (2010) Combined botulinum toxin type A with modified constraint-induced movement therapy for chronic stroke patients with upper extremity spasticity: a randomized controlled study. Neurorehabil Neural Repair 24: 34–41.
- 318. Wang Q, Zhao J, Zhu Q, Li J, Meng P (2011) Comparison of conventional therapy, intensive therapy and modified constraint-induced movement therapy to improve upper extremity function after stroke. J Rehabil Med 43: 619–625.
- 319.
Mehrholz J, Platz T, Kugler J, Pohl M (2008) Electromechanical and robot-assisted arm training for improving arm function and activities of daily living after stroke. Cochrane Database Syst Rev: CD006876.
- 320. Housman S, Scott K, Reinkensmeyer D (2009) A randomized controlled trial of gravity-supported, computer-enhanced arm exercise for individuals with severe hemiparesis. Neurorehabil Neural Repair 23: 505–514.
- 321. Mayr A, Kofler M, Saltuari L (2008) [ARMOR: an electromechanical robot for upper limb training following stroke. A prospective randomised controlled pilot study]. Handchir Mikrochir Plast Chir 40: 66–73.
- 322. Volpe B, Krebs H, Hogan N, Edelstein OTR L, Diels C, et al. (2000) A novel approach to stroke rehabilitation: robot-aided sensorimotor stimulation. Neurology 54: 1938–1944.
- 323. Hsieh Y, Wu C, Liao W, Lin K, Wu K, et al. (2011) Effects of treatment intensity in upper limb robot-assisted therapy for chronic stroke: a pilot randomized controlled trial. Neurorehabil Neural Repair 25: 503–511.
- 324. Aisen M, Krebs H, Hogan N, McDowell F, Volpe B (1997) The effect of robot-assisted therapy and rehabilitative training on motor recovery following stroke. Arch Neurol 54: 443–446.
- 325. Volpe B, Krebs H, Hogan N, Edelsteinn L, Driels C, et al. (1999) Robot training enhances motor outcome in patients with stroke maintained over 3 years. Neurology 53: 1874–1876.
- 326. Lum P, Burgar C, Shor P, Majmundar M, Van der Loos M (2002) Robot-assisted movement training compared with conventional therapy techniques for the rehabilitation of upper-limb motor function after stroke. Arch Phys Med Rehabil 83: 952–959.
- 327. Stein J, Krebs H, Frontera W, Fasoli S, Hughes R, et al. (2004) Comparison of two techniques of robot-aided upper limb exercise training after stroke. Am J Phys Med Rehabil 83: 720–728.
- 328. Daly J, Hogan N, Perepezko E, Krebs H, Rogers J, et al. (2005) Response to upper-limb robotics and functional neuromuscular stimulation following stroke. J Rehabil Res Dev 42: 723–736.
- 329. Hesse S, Werner C, Pohl M, Rueckriem S, Mehrholz J, et al. (2005) Computerized arm training improves the motor control of the severely affected arm after stroke: a single-blinded randomized trial in two centers. Stroke 36: 1960–1966.
- 330. Kahn L, Zygman M, Rymer W, Reinkensmeyer D (2006) Robot-assisted reaching exercise promotes arm movement recovery in chronic hemiparetic stroke: a randomized controlled pilot study. J Neuroeng Rehabil 3: 12.
- 331. Masiero S, Celia A, Rosati G, Armani M (2007) Robotic-assisted rehabilitation of the upper limb after acute stroke. Arch Phys Med Rehabil 88: 142–149.
- 332. Rabadi M, Galgano M, Lynch D, Akerman M, Lesser M, et al. (2008) A pilot study of activity-based therapy in the arm motor recovery post stroke: a randomized controlled trial. Clin Rehabil 22: 1071–1082.
- 333. Volpe B, Lynch D, Rykman-Berland A, Ferraro M, Galgano M, et al. (2008) Intensive sensorimotor arm training mediated by therapist or robot improves hemiparesis in patients with chronic stroke. Neurorehabil Neural Repair 22: 305–310.
- 334. Ellis M, Sukal-Moulton T, Dewald J (2009) Progressive shoulder abduction loading is a crucial element of arm rehabilitation in chronic stroke. Neurorehabil Neural Repair 23: 862–869.
- 335. Lo A, Guarino P, Richards L, Haselkorn J, Wittenberg G, et al. (2010) Robot-assisted therapy for long-term upper-limb impairment after stroke. N Engl J Med 362: 1772–1783.
- 336. Masiero S, Armani M, Rosati G (2011) Upper-limb robot-assisted therapy in rehabilitation of acute stroke patients: focused review and results of new randomized controlled trial. J Rehabil Res Dev 48: 355–366.
- 337. Burgar C, Lum P, Scremin A, Garber S, Van der Loos H, et al. (2011) Robot-assisted upper-limb therapy in acute rehabilitation setting following stroke: Department of Veterans Affairs multisite clinical trial. J Rehabil Res Dev 48: 445–458.
- 338. Conroy S, Whitall J, Dipietro L, Jones-Lush L, Zhan M, et al. (2011) Effect of gravity on robot-assisted motor training after chronic stroke: a randomized trial. Arch Phys Med Rehabil 92: 1754–1761.
- 339.
Barclay-Goddard R, Stevenson T, Poluha W, Thalman L (2011) Mental practice for treating upper extremity deficits in individuals with hemiparesis after stroke. Cochrane Database Syst Rev: CD005950.
- 340. Müller K, Bütefisch C, Seitz R, Hömberg V (2007) Mental practice improves hand function after hemiparetic stroke. Restor Neurol Neurosci 25: 501–511.
- 341. Liu K (2009) Use of mental imagery to improve task generalisation after a stroke. Hong Kong Med J 15: 37–41.
- 342. Liu K, Chan C, Lee T, Hui-Chan C (2004) Mental imagery for promoting relearning for people after stroke: a randomized controlled trial. Arch Phys Med Rehabil 85: 1403–1408.
- 343. Page S, Levine P, Leonard A (2007) Mental practice in chronic stroke: results of a randomized, placebo-controlled trial. Stroke 38: 1293–1297.
- 344. Braun S, Beurskens A, Kleynen M, Oudelaar B, Schols J, et al. (2012) A multicenter randomized controlled trial to compare subacute 'treatment as usual' with and without mental practice among persons with stroke in Dutch nursing homes. J Am Med Dir Assoc 13: e1–7.
- 345. Ietswaart M, Johnston M, Dijkerman HC, Joice S, Scott CL, et al. (2011) Mental practice with motor imagery in stroke recovery: randomized controlled trial of efficacy. Brain 134: 1373–1386.
- 346. Page S (2000) Imagery improves upper extremity motor function in chronic stroke patients: a pilot study. Occup Ther J Res 20: 200–215.
- 347. Page S, Levine P, Sisto S, Johnston M (2001) Mental practice combined with physical practice for upper-limb motor deficit in subacute stroke. Phys Ther 81: 1455–1462.
- 348. Page S, Levine P, Leonard A (2005) Effects of mental practice on affected limb use and function in chronic stroke. Arch Phys Med Rehabil 86: 399–402.
- 349. Cacchio A, De Blasis E, Necozione S, Di Orio F, Santilli V (2009) Mirror therapy for chronic complex regional pain syndrome type 1 and stroke. N Engl J Med 361: 634–636.
- 350. Page S, Szaflarski J, Eliassen J, Pan H, Cramer S (2009) Cortical plasticity following motor skill learning during mental practice in stroke. Neurorehabil Neural Repair 23: 382–388.
- 351. Riccio I, Iolascon G, Barillari MR, Gimigliano R, Gimigliano F (2010) Mental practice is effective in upper limb recovery after stroke: a randomized single-blind cross-over study. Eur J Phys Rehabil Med 46: 19–25.
- 352. Ferreira H, Leite Lopes M, Luiz R, Cardoso L, Andre C (2011) Is visual scanning better than mental practice in hemispatial neglect? Results from a pilot study. Top Stroke Rehabil 18: 155–161.
- 353. Page S, Dunning K, Hermann V, Leonard A, Levine P (2011) Longer versus shorter mental practice sessions for affected upper extremity movement after stroke: a randomized controlled trial. Clin Rehabil 25: 627–637.
- 354. Altschuler E, Wisdom S, Stone L, Foster C, Galasko D, et al. (1999) Rehabilitation of hemiparesis after stroke with a mirror. Lancet 353: 2035–2036.
- 355. Michielsen M, Selles R, Van der Geest J, Eckhardt M, Yavuzer G, et al. (2011) Motor recovery and cortical reorganization after mirror therapy in chronic stroke patients: a phase II randomized controlled trial. Neurorehabil Neural Repair 25: 223–233.
- 356. Rothgangel A, Morton A, Van der Hout J, Beurskens A (2004) Phantoms in the brain: spiegeltherapie bij chronische CVA-patiënten: een pilot-study. Ned Tijdschr Fysiother 114: 36–40.
- 357. Yavuzer G, Selles R, Sezer N, Sutbeyaz S, Bussmann JB, et al. (2008) Mirror therapy improves hand function in subacute stroke: a randomized controlled trial. Arch Phys Med Rehabil 89: 393–398.
- 358. Cacchio A, De Blasis E, De Blasis V, Santilli V, Spacca G (2009) Mirror therapy in complex regional pain syndrome type 1 of the upper limb in stroke patients. Neurorehabil Neural Repair 23: 792–799.
- 359. Dohle C, Pullen J, Nakaten A, Kust J, Rietz C, et al. (2009) Mirror therapy promotes recovery from severe hemiparesis: a randomized controlled trial. Neurorehabil Neural Repair 23: 209–217.
- 360. Saposnik G, Teasell R, Mamdani M, Hall J, McIlroy W, et al. (2010) Effectiveness of virtual reality using Wii gaming technology in stroke rehabilitation: a pilot randomized clinical trial and proof of principle. Stroke 41: 1477–1484.
- 361. Carey J, Kimberley T, Lewis S, Auerbach E, Dorsey L, et al. (2002) Analysis of fMRI and finger tracking training in subjects with chronic stroke. Brain 125: 773–788.
- 362. Carey J, Durfee W, Bhatt E, Nagpal A, Weinstein S, et al. (2007) Comparison of finger tracking versus simple movement training via telerehabilitation to alter hand function and cortical reorganization after stroke. Neurorehabil Neural Repair 21: 216–232.
- 363. Piron L, Tonin P, Atzori A, Zucconi C, Massaro C, et al. (2003) The augmented-feedback rehabilitation technique facilitates the arm motor recovery in patients after a recent stroke. Stud Health Technol Inform 94: 265–267.
- 364.
Piron L, Tombolini A, Turolla C, Zucconi C, Agostini M, et al.. (2007) Reinforced feedback in virtual environment facilitates the arm motor recovery in patients after a recent stroke. IEEE Xplore: 121–123.
- 365. Sucar L, Luis R, Leder R, Hernandez J, Sanchez I (2010) Gesture therapy: a vision-based system for upper extremity stroke rehabilitation. Conf Proc IEEE Eng Med Biol Soc 2010: 3690–3693.
- 366. Piron L, Turolla A, Agostini M, Zucconi CS, Ventura L, et al. (2010) Motor learning principles for rehabilitation: a pilot randomized controlled study in poststroke patients. Neurorehabil Neural Repair 24: 501–508.
- 367. Jang S, You S, Hallett M, Cho Y, Park C, et al. (2005) Cortical reorganization and associated functional motor recovery after virtual reality in patients with chronic stroke: an experimenter-blind preliminary study. Arch Phys Med Rehabil 86: 2218–2223.
- 368. Broeren J, Claesson L, Goude D, Rydmark M, Sunnerhagen K (2008) Virtual rehabilitation in an activity centre for community-dwelling persons with stroke. The possibilities of 3-dimensional computer games. Cerebrovasc Dis 26: 289–296.
- 369. Crosbie J, Lennon S, McDonough S (2007) Virtual reality in the rehabilitation of the upper limb following hemiplegic stroke: a pilot randomised controlled trial (RCT). UK Stroke Forum Conference 2007: 9.
- 370. Piron L, Turolla A, Tonin P, Piccione F, Lain L, et al. (2008) Satisfaction with care in post-stroke patients undergoing a telerehabilitation programme at home. J Telemed Telecare 14: 257–260.
- 371. Yavuzer G, Senel A, Atay M, Stam H (2008) ''Playstation eyetoy games'' improve upper extremity-related motor functioning in subacute stroke: a randomized controlled clinical trial. Eur J Phys Rehabil Med 44: 237–244.
- 372. Piron L, Turolla A, Agostini M, Zucconi C, Cortese F, et al. (2009) Exercises for paretic upper limb after stroke: a combined virtual-reality and telemedicine approach. J Rehabil Med 41: 1016–1102.
- 373. Da Silva Cameirao M, Bermúdez I Badia S, Duarte E, Verschure P (2011) Virtual reality based rehabilitation speeds up functional recovery of the upper extremities after stroke: a randomized controlled pilot study in the acute phase of stroke using the Rehabilitation Gaming System. Restor Neurol Neurosci 29: 287–298.
- 374. Fischer H, Stubblefield K, Kline T, Luo X, Kenyon R, et al. (2007) Hand rehabilitation following stroke: a pilot study of assisted finger extension training in a virtual environment. Top Stroke Rehabil 14: 1–12.
- 375. Carmeli E, Peleg S, Bartur G, Elbo E, Vatine J (2010) HandTutor(TM) enhanced hand rehabilitation after stroke - a pilot study. Physiother Res Int 16: 191–200.
- 376. Bowman B, Baker L, Waters R (1979) Positional feedback and electrical stimulation: an automated treatment for the hemiplegic wrist. Arch Phys Med Rehabil 60: 497–502.
- 377. Sonde L, Gip C, Fernaeus S, Nilsson C, Viitanen M (1998) Stimulation with low frequency (1.7 Hz) transcutaneous electric nerve stimulation (low-tens) increases motor function of the post-stroke paretic arm. Scand J Rehabil Med 30: 95–99.
- 378. Cauraugh J, Light K, Kim S, Thigpen M, Behrman A (2000) Chronic motor dysfunction after stroke: recovering wrist and finger extension by electromyography-triggered neuromuscular stimulation. Stroke 31: 1360–1364.
- 379. Gabr U, Levine P, Page S (2005) Home-based electromyography-triggered stimulation in chronic stroke. Clin Rehabil 19: 737–745.
- 380. Church C, Price C, Pandyan A, Huntley S, Curless R, et al. (2006) Randomized controlled trial to evaluate the effect of surface neuromuscular electrical stimulation to the shoulder after acute stroke. Stroke 37: 2995–3001.
- 381. Baker L, Parker K (1986) Neuromuscular electrical stimulation of the muscles surrounding the shoulder. Phys Ther 66: 1930–1937.
- 382. Leandri M, Parodi C, Corrieri N, Rigardo S (1990) Comparison of TENS treatments in hemiplegic shoulder pain. Scand J Rehabil Med 22: 69–71.
- 383. Faghri P, Rodgers M, Glaser R, Bors J, Ho C, et al. (1994) The effects of functional electrical stimulation on shoulder subluxation, arm function recovery, and shoulder pain in hemiplegic stroke patients. Arch Phys Med Rehabil 75: 73–79.
- 384. Faghri P (1997) The effects of neuromuscular stimulation-induced muscle contraction versus elevation on hand edema in CVA patients. J Hand Ther 10: 29–34.
- 385. King T (1996) The effect of neuromuscular electrical stimulation in reducing tone. Am J Occup Ther 50: 62–64.
- 386. Chae J, Bethoux F, Bohine T, Dobos L, Davis T, et al. (1998) Neuromuscular stimulation for upper extremity motor and functional recovery in acute hemiplegia. Stroke 29: 975–979.
- 387. Francisco G, Chae J, Chawla H, Kirshblum S, Zorowitz R, et al. (1998) Electromyogram-triggered neuromuscular stimulation for improving the arm function of acute stroke survivors: a randomized pilot study. Arch Phys Med Rehabil 79: 570–575.
- 388. Sonde L, Kalimo H, Fernaeus S, Viitanen M (2000) Low TENS treatment on post-stroke paretic arm: a three-year follow-up. Clin Rehabil 14: 14–19.
- 389. Linn S, Granat M, Lees K (1999) Prevention of shoulder subluxation after stroke with electrical stimulation. Stroke 30: 963–968.
- 390. Powell J, Pandyan A, Granat M, Cameron M, Stott D (1999) Electrical stimulation of wrist extensors in poststroke hemiplegia. Stroke 30: 1384–1389.
- 391. Wang R, Chan R, Tsai M (2000) Functional electrical stimulation on chronic and acute hemiplegic shoulder subluxation. Am J Phys Med Rehabil 79: 385–390.
- 392. Wang R, Yang Y, Tsai M, Wang W, Chan R (2002) Effects of functional electric stimulation on upper limb motor function and shoulder range of motion in hemiplegic patients. Am J Phys Med Rehabil 81: 283–290.
- 393. Cauraugh J, Kim S (2003) Chronic stroke motor recovery: duration of active neuromuscular stimulation. J Neurol Sci 215: 13–19.
- 394. Cauraugh J, Kim S (2003) Stroke motor recovery: active neuromuscular stimulation and repetitive practice schedules. J Neurol Neurosurg Psychiatry 74: 1562–1566.
- 395. Popovic M, Popovic D, Sinkjaer T, Stefanovic A, Schwirtlich L (2003) Clinical evaluation of functional electrical therapy in acute hemiplegic subjects. J Rehabil Res Dev 40: 443–453.
- 396. De Kroon J, IJzerman M, Lankhorst G, Zilvold G (2004) Electrical stimulation of the upper limb in stroke: stimulation of the extensors of the hand vs. alternate stimulation of flexors and extensors. Am J Phys Med Rehabil 83: 592–600.
- 397. Kimberley T, Lewis S, Auerbach E, Dorsey L, Lojovich J, et al. (2004) Electrical stimulation driving functional improvements and cortical changes in subjects with stroke. Exp Brain Res 154: 450–460.
- 398. Mann G, Burridge J, Malone L, Strike P (2005) A pilot study to investigate the effects of electrical stimulation on recovery of hand function and sensation in subacute stroke patients. Neuromodulation 8: 193–202.
- 399. Popovic M, Thrasher T, Zivanovic V, Takaki J, Hajek V (2005) Neuroprosthesis for retraining reaching and grasping functions in severe hemiplegic patients. Neuromodulation 8: 58–72.
- 400. Ring H, Rosenthal N (2005) Controlled study of neuroprosthetic functional electrical stimulation in sub-acute post-stroke rehabilitation. J Rehabil Med 37: 32–36.
- 401. Hara Y, Ogawa S, Muraoka Y (2006) Hybrid power-assisted functional electrical stimulation to improve hemiparetic upper-extremity function. Arch Phys Med Rehabil 85: 977–985.
- 402. Alon G, Levitt A, McCarthy P (2007) Functional electrical stimulation enhancement of upper extremity functional recovery during stroke rehabilitation: a pilot study. Neurorehabil Neural Repair 21: 207–215.
- 403. Bhatt E, Nagpal A, Greer K, Grunewald T, Steele J, et al. (2007) Effect of finger tracking combined with electrical stimulation on brain reorganization and hand function in subjects with stroke. Exp Brain Res 182: 435–447.
- 404. Hemmen B, Seelen H (2007) Effects of movement imagery and electromyography-triggered feedback on arm hand function in stroke patients in the subacute phase. Clin Rehabil 21: 587–594.
- 405. Kowalczewski J, Gritsenko V, Ashworth N, Ellaway P, Prochazka A (2007) Upper-extremity functional electric stimulation-assisted exercises on a workstation in the subacute phase of stroke recovery. Arch Phys Med Rehabil 88: 833–839.
- 406. McDonnell M, Hillier S, Miles T, Thompson P, Ridding M (2007) Influence of combined afferent stimulation and task-specific training following stroke: a pilot randomized controlled trial. Neurorehabil Neural Repair 21: 435–443.
- 407. Alon G, Levitt A, McCarthy P (2008) Functional electrical stimulation (FES) may modify the poor prognosis of stroke survivors with severe motor loss of the upper extremity: a preliminary study. Am J Phys Med Rehabil 87: 627–636.
- 408. Barker R, Brauer S, Carson R (2008) Training of reaching in stroke survivors with severe and chronic upper limb paresis using a novel nonrobotic device: a randomized clinical trial. Stroke 39: 1800–1807.
- 409. Barker R, Brauer S, Carson R (2009) Training-induced changes in the pattern of triceps to biceps activation during reaching tasks after chronic and severe stroke. Exp Brain Res 196: 483–496.
- 410. De Kroon J, IJzerman M (2008) Electrical stimulation of the upper extremity in stroke: cyclic versus EMG-triggered stimulation. Clin Rehabil 22: 690–697.
- 411. Hara Y, Ogawa S, Tsujiuchi K, Muraoka Y (2008) A home-based rehabilitation program for the hemiplegic upper extremity by power-assisted functional electrical stimulation. Disabil Rehabil 30: 296–304.
- 412. Shin H, Cho S, Jeon H, Lee Y, Song J, et al. (2008) Cortical effect and functional recovery by the electromyography-triggered neuromuscular stimulation in chronic stroke patients. Neurosci Lett 442: 174–179.
- 413. Thrasher T, Zivanovic V, McIlroy W, Popovic M (2008) Rehabilitation of reaching and grasping function in severe hemiplegic patients using functional electrical stimulation therapy. Neurorehabil Neural Repair 22: 706–714.
- 414. Chan M, Tong R, Chung K (2009) Bilateral upper limb training with functional electric stimulation in patients with chronic stroke. Neurorehabil Neural Repair 23: 357–365.
- 415. Klaiput A, Kitisomprayoonkul W (2009) Increased pinch strength in acute and subacute stroke patients after simultaneous median and ulnar sensory stimulation. Neurorehabil Neural Repair 23: 351–356.
- 416. Mangold S, Schuster C, Keller T, Zimmermann-Schlatter A, Ettlin T (2009) Motor training of upper extremity with functional electrical stimulation in early stroke rehabilitation. Neurorehabil Neural Repair 23: 184–190.
- 417. Hsu S, Hu M, Wang Y, Yip P, Chiu J, et al. (2010) Dose-response relation between neuromuscular electrical stimulation and upper-extremity function in patients with stroke. Stroke 41: 821–824.
- 418. Koyuncu E, Nakipoglu-Yüzer G, Dogan A, Ozgirgin N (2010) The effectiveness of functional electrical stimulation for the treatment of shoulder subluxation and shoulder pain in hemiplegic patients: A randomized controlled trial. Disabil Rehabil 32: 560–566.
- 419. Fil A, Armutlu K, Atay A, Kerimoglu U, Elibol B (2011) The effect of electrical stimulation in combination with Bobath techniques in the prevention of shoulder subluxation in acute stroke patients. Clin Rehabil 25: 51–59.
- 420. Lin Z, Yan T (2011) Long-term effectiveness of neuromuscular electrical stimulation for promoting motor recovery of the upper extremity after stroke. J Rehabil Med 43: 506–510.
- 421. Sentandreu Mano T, Salom Terradez J, Tomas J, Melendez Moral J, Fuente Fernandez T, et al. (2011) [Electrical stimulation in the treatment of the spastic hemiplegic hand after stroke: a ramdomized study]. Med Clin (Barc) 137: 297–301.
- 422. Shindo K, Fujiwara T, Hara J, Oba H, Hotta F, et al. (2011) Effectiveness of hybrid assistive neuromuscular dynamic stimulation therapy in patients with subacute stroke: a randomized controlled pilot trial. Neurorehabil Neural Repair 25: 830–837.
- 423. Tarkka I, Pitkänen K, Popovic D, Vanninen R, Könönen M (2011) Functional electrical therapy for hemiparesis alleviates disability and enhances neuroplasticity. Tohoku J Exp Med 225: 71–76.
- 424. Bate P, Matyas T (1992) Negative transfer of training following brief practice of elbow tracking movements with electromyographic feedback from spastic antagonists. Arch Phys Med Rehabil 73: 1050–1058.
- 425. Crow J, Lincoln N, Nouri F, De Weerdt W (1989) The effectiveness of EMG biofeedback in the treatment of arm function after stroke. Int Disabil Stud 11: 155–160.
- 426. Armagan O, Tascioglu F, Oner C (2003) Electromyographic biofeedback in the treatment of the hemiplegic hand: a placebo-controlled study. Am J Phys Med Rehabil 82: 856–861.
- 427. Smith K (1979) Biofeedback in strokes. Aust J Physiother 25: 155–161.
- 428. Greenberg S, Fowler Jr R (1980) Kinesthetic biofeedback: a treatment modality for elbow range of motion in hemiplegia. Am J Occup Ther 34: 738–743.
- 429. Basmajian J, Gowland C, Brandstater M, Swanson L, Trotter J (1982) EMG feedback treatment of upper limb in hemiplegic stroke patients: a pilot study. Arch Phys Med Rehabil 63: 613–616.
- 430. Williams J (1982) Use of electromyographic biofeedback for pain reduction in the spastic hemiplegic shoulder: a pilot study. Physiother Can 34: 327–333.
- 431. Inglis J, Donald M, Monga T, Sproule M, Young M (1984) Electromyographic biofeedback and physical therapy of the hemiplegic upper limb. Arch Phys Med Rehabil 65: 755–759.
- 432. Basmajian J, Gowland C, Finlayson M, Hall A, Swanson L, et al. (1987) Stroke treatment: comparison of integrated behavioral-physical therapy vs traditional physical therapy programs. Arch Phys Med Rehabil 68: 267–272.
- 433. Dogan-Aslan M, Nakipoglu-Yuzer G, Dogan A, Karabay I, Ozgirgin N (2010) The effect of electromyographic biofeedback treatment in improving upper extremity functioning of patients with hemiplegic stroke. J Stroke Cerebrovasc Dis 21: 187–192.
- 434. Michaelsen S, Levin M (2004) Short-term effects of practice with trunk restraint on reaching movements in patients with chronic stroke: a controlled trial. Stroke 35: 1914–1919.
- 435. Thielman G (2010) Rehabilitation of reaching poststroke: a randomized pilot investigation of tactile versus auditory feedback for trunk control. J Neurol Phys Ther 34: 138–144.
- 436. Michaelsen S, Dannenbaum R, Levin M (2006) Task-specific training with trunk restraint on arm recovery in stroke: randomized control trial. Stroke 37: 186–192.
- 437. Carey L, Macdonell R, Matyas T (2011) SENSe: Study of the Effectiveness of Neurorehabilitation on Sensation: a randomized controlled trial. Neurorehabil Neural Repair 25: 304–313.
- 438. Heldmann B, Kerkhoff G, Struppler A, Havel P, Jahn T (2000) Repetitive peripheral magnetic stimulation alleviates tactile extinction. Neuroreport 11: 3193–3198.
- 439. Byl N, Roderick J, Mohamed O, Hanny M, Kotler J, et al. (2003) Effectiveness of sensory and motor rehabilitation of the upper limb following the principles of neuroplasticity: patients stable poststroke. Neurorehabil Neural Repair 17: 176–191.
- 440. Chen J, Liang C, Shaw F (2005) Facilitation of sensory and motor recovery by thermal intervention for the hemiplegic upper limb in acute stroke patients: a single-blind randomized clinical trial. Stroke 36: 2665–2669.
- 441. Byl N, Pitsch E, Abrams G (2008) Functional outcomes can vary by dose: learning-based sensorimotor training for patients stable poststroke. Neurorehabil Neural Repair 22: 494–504.
- 442. Wolny T, Saulicz E, Gnat R, Kokosz M (2010) Butler's neuromobilizations combined with proprioceptive neuromuscular facilitation are effective in reducing of upper limb sensory in late-stage stroke subjects: a three-group randomized trial. Clin Rehabil 24: 810–821.
- 443. Hunter S, Hammett L, Ball S, Smith N, Anderson C, et al. (2011) Dose-response study of mobilisation and tactile stimulation therapy for the upper extremity early after stroke: a phase I trial. Neurorehabil Neural Repair 25: 314–322.
- 444. Gordon N, Gulanick M, Costa F, Fletcher G, Franklin B, et al. (2004) Physical activity and exercise recommendations for stroke survivors: an American Heart Association scientific statement from the Council on Clinical Cardiology, Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention; the Council on Cardiovascular Nursing; the Council on Nutrition, Physical Activity, and Metabolism; and the Stroke Council. Stroke 35: 1230–1240.
- 445.
Brazzelli M, Saunders D, Greig C, Mead G (2011) Physical fitness training for stroke patients. Cochrane Database Syst Rev: CD003316.
- 446. Carr M, Jones J (2003) Physiological effects of exercise on stroke survivors. Top Stroke Rehabil 9: 57–64.
- 447. Lee M, Kilbreath S, Singh M, Zeman B, Lord S, et al. (2008) Comparison of effect of aerobic cycle training and progressive resistance training on walking ability after stroke: a randomized sham exercise-controlled study. J Am Geriatr Soc 56: 976–985.
- 448. Inaba M, Edberg E, Montgomery J, Gillis MK (1973) Effectiveness of functional training, active exercise, and resistive exercise for patients with hemiplegia. PhysTher 53: 28–35.
- 449. Glasser L (1986) Effects of isokinetic training on the rate of movement during ambulation in hemiparetic patients. Phys Ther 66: 673–676.
- 450. Kim C, Eng J, MacIntyre D, Dawson A (2001) Effects of isokinetic strength training on walking in persons with stroke: a double-blind controlled pilot study. J Stroke Cerebrovasc Dis 10: 265–273.
- 451. Bourbonnais D, Bilodeau S, Lepage Y, Beaudoin N, Gravel D, et al. (2002) Effect of force-feedback treatments in patients with chronic motor deficits after a stroke. Am J Phys Med Rehabil 81: 890–897.
- 452. Moreland J, Goldsmith C, Huijbregts M, Anderson R, Prentice D, et al. (2003) Progressive resistance strengthening exercises after stroke: a single-blind randomized controlled trial. Arch Phys Med Rehabil 84: 1433–1440.
- 453. Ouellette M, LeBrasseur N, Bean J, Phillips E, Stein J, et al. (2004) High-intensity resistance training improves muscle strength, self-reported function, and disability in long-term stroke survivors. Stroke 35: 1404–1409.
- 454.
De Boissezon X, Burlot S, Glezes S, Roques C, Marque P (2005) A randomized controlled trial to compare isokinetic and conventional muscular strengthening in poststroke patients. Isokinet Exerc Sci: 91–92.
- 455. Akbari A, Karimi H (2006) The effect of strengthening exercises in exaggerated muscle tonicity in chronic hemiparesis following stroke. J Med Sci 6: 382–388.
- 456. Tihanyi T, Horvath M, Fazekas G, Hortobagyi T, Tihanyi J (2007) One session of whole body vibration increases voluntary muscle strength transiently in patients with stroke. Clin Rehabil 21: 782–793.
- 457. Bale M, Strand L (2008) Does functional strength training of the leg in subacute stroke improve physical performance? A pilot randomized controlled trial. Clin Rehabil 22: 911–921.
- 458. Flansbjer U, Miller M, Downham D, Lexell J (2008) Progressive resistance training after stroke: effects on muscle strength, muscle tone, gait performance and perceived participation. J Rehabil Med 40: 42–48.
- 459. Lee M, Kilbreath S, Singh M, Zeman B, Davis G (2010) Effect of progressive resistance training on muscle performance after chronic stroke. Med Sci Sports Exerc 42: 23–34.
- 460. Page S, Levine P, Teepen J, Hartman E (2008) Resistance-based, reciprocal upper and lower limb locomotor training in chronic stroke: a randomized, controlled crossover study. Clin Rehabil 22: 610–617.
- 461. Singh S (2008) Closed versus open kinematic chain exercises on gait performance in subacute stroke patients. Physiother Occup Ther J 1: 73–89.
- 462. Sims J, Galea M, Taylor N, Dodd K, Jespersen S, et al. (2009) Regenerate: assessing the feasibility of a strength-training program to enhance the physical and mental health of chronic post stroke patients with depression. Int J Geriatr Psychiatry 24: 76–83.
- 463. Cooke E, Tallis R, Clark A, Pomeroy V (2010) Efficacy of functional strength training on restoration of lower-limb motor function early after stroke: phase I randomized controlled trial. Neurorehabil Neural Repair 24: 88–96.
- 464. Tihanyi J, Di Giminiani R, Tihanyi T, Gyulai G, Trzaskoma L, et al. (2010) Low resonance frequency vibration affects strength of paretic and non-paretic leg differently in patients with stroke. Acta Physiol Hung 97: 172–182.
- 465. Lippert-Grüner M, Grüner M (1999) Muskelkrafttraining in der Rehabilitation des zentral paretischen Armes. Neurol Rehabil 5: 275–279.
- 466. Donaldson C, Tallis R, Miller S, Sunderland A, Lemon R, et al. (2009) Effects of conventional physical therapy and functional strength training on upper limb motor recovery after stroke: a randomized phase II study. Neurorehabil Neural Repair 23: 389–397.
- 467. Thielman G, Dean C, Gentile A (2004) Rehabilitation of reaching after stroke: task-related training versus progressive resistive exercise. Arch Phys Med Rehabil 85: 1613–1618.
- 468. Winstein C, Rose D, Tan S, Lewthwaite R, Chui H, et al. (2004) A randomized controlled comparison of upper-extremity rehabilitation strategies in acute stroke: A pilot study of immediate and long-term outcomes. Arch Phys Med Rehabil 85: 620–628.
- 469. Thielman G, Kaminski T, Gentile A (2008) Rehabilitation of reaching after stroke: comparing 2 training protocols utilizing trunk restraint. Neurorehabil Neural Repair 22: 697–705.
- 470. Potempa K, Lopez M, Braun L, Szidon J, Fogg L, et al. (1995) Physiological outcomes of aerobic exercise training in hemiparetic stroke patients. Stroke 26: 101–105.
- 471. Kamps A, Schüle K (2005) Cyclic movement training of the lower limb in stroke rehabilitation. Neurol Rehabil 11: S1–S12.
- 472. Katz-Leurer M, Carmeli E, Shochina M (2003) The effect of early aerobic training on independence six months post stroke. Clin Rehabil 17: 735–741.
- 473. Katz-Leurer M, Shochina M (2007) The influence of autonomic impairment on aerobic exercise outcome in stroke patients. NeuroRehabilitation 22: 267–272.
- 474. Lennon O, Carey A, Gaffney N, Stephenson J, Blake C (2008) A pilot randomized controlled trial to evaluate the benefit of the cardiac rehabilitation paradigm for the non-acute ischaemic stroke population. Clin Rehabil 22: 125–133.
- 475. Quaney B, Boyd L, McDowd J, Zahner L, He J, et al. (2009) Aerobic exercise improves cognition and motor function poststroke. Neurorehabil Neural Repair 23: 879–885.
- 476. Dobke B, Schüle K, Diehl W, Kaiser T (2010) Apparativ-assistive Bewegungstherapie in der Schlaganfallrehabilitation. Neurol Rehabil 16: 173–185.
- 477. Toledano-Zarhi A, Tanne D, Carmeli E, Katz-Leurer M (2011) Feasibility, safety and efficacy of an early aerobic rehabilitation program for patients after minor ischemic stroke: A pilot randomized controlled trial. NeuroRehabilitation 28: 85–90.
- 478. Teixeira-Salmela L, Olney S, Nadeau S, Brouwer B (1999) Muscle strengthening and physical conditioning to reduce impairment and disability in chronic stroke survivors. Arch Phys Med Rehabil 80: 1211–1218.
- 479. Duncan P, Studenski S, Richards L, Gollub S, Lai S, et al. (2003) Randomized clinical trial of therapeutic exercise in subacute stroke. Stroke 34: 2173–2180.
- 480. Richards C, Malouin F, Wood-Dauphinee S, Williams J, Bouchard J, et al. (1993) Task-specific physical therapy for optimization of gait recovery in acute stroke patients. Arch Phys Med Rehabil 74: 612–620.
- 481. Duncan P, Richards L, Wallace D, Stoker-Yates J, Pohl P, et al. (1998) A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke. Stroke 29: 2055–2060.
- 482. Rimmer J, Riley B, Creviston T, Nicola T (2000) Exercise training in a predominantly African-American group of stroke survivors. Med Sci Sports Exerc 32: 1990–1996.
- 483. Studenski S, Duncan P, Perera S, Reker D, Lai S, et al. (2005) Daily functioning and quality of life in a randomized controlled trial of therapeutic exercise for subacute stroke survivors. Stroke 36: 1764–1770.
- 484. Lai S, Studenski S, Richards L, Perera S, Reker D, et al. (2006) Therapeutic exercise and depressive symptoms after stroke. J Am Geriatr Soc 54: 240–247.
- 485. Olney S, Nymark J, Brouwer B, Culham E, Day A, et al. (2006) A randomized controlled trial of supervised versus unsupervised exercise programs for ambulatory stroke survivors. Stroke 37: 476–481.
- 486. Letombe A, Cornille C, Delahaye H, Khaled A, Morice O, et al. (2010) Early post-stroke physical conditioning in hemiplegic patients: a preliminary study. Ann Phys Rehabil Med 53: 632–642.
- 487. Outermans J, Van Peppen R, Wittink H, Takken T, Kwakkel G (2010) Effects of a high-intensity task-oriented training on gait performance early after stroke: a pilot study. Clin Rehabil 24: 979–987.
- 488. Donkervoort M, Dekker J, Stehmann-Saris F, Deelman B (2001) Efficacy of strategy training in left hemisphere stroke patients with apraxia: a randomised clinical trial. Neuropsychol Rehabil 11: 549–566.
- 489. Smania N, Girardi F, Domenicali C, Lora E, Aglioti S (2000) The rehabilitation of limb apraxia: a study in left-brain-damaged patients. Arch Phys Med Rehabil 81: 379–388.
- 490. Smania N, Aglioti SM, Girardi F, Tinazzi M, Fiaschi A, et al. (2006) Rehabilitation of limb apraxia improves daily life activities in patients with stroke. Neurology 67: 2050–2052.
- 491. Jongbloed L, Morgan D (1991) An investigation of involvement in leisure activities after a stroke. Am J Occup Ther 45: 420–427.
- 492. Drummond A, Walker M (1995) A randomized controlled trial of leisure rehabilitation after stroke. Clin Rehabil 9: 283–290.
- 493. Drummond A, Walker M (1996) Generalisation of the effects of leisure rehabilitation for stroke patients. Br J Occup Ther 59: 330–334.
- 494. Parker C, Gladman J, Drummond A, Dewey M, Lincoln N, et al. (2001) A multicentre randomized controlled trial of leisure therapy and conventional occupational therapy after stroke. TOTAL Study Group. Trial of Occupational Therapy and Leisure. Clin Rehabil 15: 42–52.
- 495. Nour K, Desrosiers J, Gauthier P, Carbonneau H (2002) Impact of a home leisure educadtional program for older adults who have had a stroke (Home Leisure Educational Program). Ther Recr J 36: 48–64.
- 496. Desrosiers J, Noreau L, Rochette A, Carbonneau H, Fontaine L, et al. (2007) Effect of a home leisure education program after stroke: a randomized controlled trial. Arch Phys Med Rehabil 88: 1095–1100.
- 497. Britto R, Rezende N, Marinho K, Torres J, Parreira V, et al. (2011) Inspiratory muscular training in chronic stroke survivors: a randomized controlled trial. Arch Phys Med Rehabil 92: 184–190.
- 498. Sütbeyaz S, Koseoglu F, Inan L, Coskun O (2010) Respiratory muscle training improves cardiopulmonary function and exercise tolerance in subjects with subacute stroke: a randomized controlled trial. Clin Rehabil 24: 240–250.
- 499. Young J, Forster A (1991) The Bradford community stroke trial: eight week results. Clin Rehabil 5: 283–292.
- 500. Young J, Forster A (1992) The Bradford community stroke trial: results at six months. BMJ 304: 1085–1089.
- 501. Baskett J, Broad J, Reekie G, Hocking C, Green G (1999) Shared responsibility for ongoing rehabilitation: a new approach to home-based therapy after stroke. Clin Rehabil 13: 23–33.
- 502. Gilbertson L, Langhorne P, Walker A, Allen A, Murray G (2000) Domiciliary occupational therapy for patients with stroke discharged from hospital: randomised controlled trial. BMJ 320: 603–606.
- 503. Rodgers H, Mackintosh J, Price C, Wood R, McNamee P, et al. (2003) Does an early increased-intensity interdisciplinary upper limb therapy programme following acute stroke improve outcome? Clin Rehabil 17: 579–589.
- 504. Glasgow Augmented Physiotherapy Study (GAPS) (2004) Can augmented physiotherapy input enhance recovery of mobility after stroke? A randomized controlled trial. Clin Rehabil 18: 529–537.
- 505. Platz T, Eickhof C, Van Kaick S, Engel U, Pinkowski C, et al. (2005) Impairment-oriented training or Bobath therapy for severe arm paresis after stroke: a single-blind, multicentre randomized controlled trial. Clin Rehabil 19: 714–724.
- 506. Davidson I, Hillier V, Waters K, Walton T, Booth J (2005) A study to assess the effect of nursing interventions at the weekend for people with stroke. Clin Rehabil 19: 126–137.
- 507. Harris J, Eng J, Miller W, Dawson A (2009) A self-administered Graded Repetitive Arm Supplementary Program (GRASP) improves arm function during inpatient stroke rehabilitation: a multi-site randomized controlled trial. Stroke 40: 2123–2128.
- 508. Harrington R, Taylor G, Hollinghurst S, Reed M, Kay H, et al. (2010) A community-based exercise and education scheme for stroke survivors: a randomized controlled trial and economic evaluation. Clin Rehabil 24: 3–15.
- 509. Hesse S, Welz A, Werner C, Quentin B, Wissel J (2011) Comparison of an intermittent high-intensity vs continuous low-intensity physiotherapy service over 12 months in community-dwelling people with stroke: a randomized trial. Clin Rehabil 25: 146–156.
- 510. Stern P, McDowell F, Miller J, Robinson M (1970) Effects of facilitation exercise techniques in stroke rehabilitation. Ann Phys Rehabil Med 51: 526–531.
- 511. Smith D, Goldenberg E, Ashburn A, Kinsella G, Sheikh K, et al. (1981) Remedial therapy after stroke: a randomised controlled trial. Br Med J (Clin Res Ed) 282: 517–520.
- 512. Sivenius S, Pyrorala K, Heinonen O, Salonen J, Riekkinen P (1985) The significance of intensity of rehabilitation of stroke–a controlled trial. Stroke 16: 928–931.
- 513. Sunderland A, Tinson D, Bradley E, Fletcher D, Langton Hewer R, et al. (1992) Enhanced physical therapy improves recovery of arm function after stroke. A randomised controlled trial. J Neurol Neurosurg Psychiatry 55: 530–535.
- 514. Werner R, Kessler S (1996) Effectiveness of an intensive outpatient rehabilitation program for postacute stroke patients. Am J Phys Med Rehabil 75: 114–120.
- 515. Logan P, Ahern J, Gladman J, Lincoln N (1997) A randomized controlled trial of enhanced Social Service occupational therapy for stroke patients. Clin Rehabil 11: 107–113.
- 516. Kwakkel G, Wagenaar R, Twisk J, Lankhorst G, Koetsier J (1999) Intensity of leg and arm training after primary middle-cerebral-artery stroke: a randomised trial. Lancet 354: 191–196.
- 517. Lincoln N, Parry R, Vass C (1999) Randomized, controlled trial to evaluate increased intensity of physiotherapy treatment of arm function after stroke. Stroke 30: 573–579.
- 518. Walker M, Gladman J, Lincoln N, Siemonsma P, Whiteley T (1999) Occupational therapy for stroke patients not admitted to hospital: a randomised controlled trial. Lancet 354: 278–280.
- 519. Partridge C, Mackenzie M, Edwards S, Reid A, Jayawardena S, et al. (2000) Is dosage of physiotherapy a critical factor in deciding patterns of recovery from stroke: a pragmatic randomized controlled trial. Physiother Res Int 5: 230–240.
- 520. Andersen H, Eriksen K, Brown A, Schultz-Larsen K, Forchhammer B (2002) Follow-up services for stroke survivors after hospital discharge–a randomized control study. Clin Rehabil 16: 593–603.
- 521. Slade A, Tennant A, Chamerlain M (2002) A randomised controlled trial to determine the effect of intensity of therapy upon length of stay in a neurological rehabilitation setting. J Rehabil Med 34: 260–266.
- 522. Di Lauro A, Pellegrino L, Savastano G, Ferraro C, Fusco M, et al. (2003) A randomized trial on the efficacy of intensive rehabilitation in the acute phase of ischemic stroke. J Neurol 250: 1206–1208.
- 523. Fang Y, Chen X, Lin H, Lin J, Huang R, et al. (2003) A study on additional early physiotherapy after stroke and factors affecting functional recovery. Clin Rehabil 17: 608–617.
- 524. Katz-Leurer M, Sender I, Keren O, Dvir Z (2006) The influence of early cycling training on balance in stroke patients at the subacute stage. Results of a preliminary trial. Clin Rehabil 20: 398–405.
- 525. Langhammer B, Lindmark B, Stanghelle J (2007) Stroke patients and long-term training: is it worthwhile? A randomized comparison of two different training strategies after rehabilitation. Clin Rehabil 21: 495–510.
- 526. Huijgen B, Vollenbroek-Hutten M, Zampolini M, Opisso E, Bernabeu M, et al. (2008) Feasibility of a home-based telerehabilitation system compared to usual care: arm/hand function in patients with stroke, traumatic brain injury and multiple sclerosis. J Telemed Telecare 14: 249–256.
- 527. Gelber D, Josefczyk P, Herman D, Good D, Verhulst S (1995) Comparison of two therapy approaches in the rehabilitation of the pure motor hemiparetic stroke patient. Neurorehabil Neural Repair 9: 191–196.
- 528. Langhammer B, Stanghelle J (2000) Bobath or motor relearning programme? A comparison of two different approaches of physiotherapy in stroke rehabilitation: a randomized controlled study. Clin Rehabil 14: 361–369.
- 529. Langhammer B, Stanghelle J (2003) Bobath or motor relearning programme? A follow-up one and four years post stroke. Clin Rehabil 17: 731–734.
- 530. Richards C, Malouin F, Bravo G, Dumas F, Wood-Dauphinee S (2004) The role of technology in task-oriented training in persons with subacute stroke: a randomized controlled trial. Neurorehabil Neural Repair 18: 199–211.
- 531. Tang Q, Yang Q, Wu Y, Wang G, Huang Z, et al. (2005) Effects of problem-oriented willed-movement therapy on motor abilities for people with poststroke cognitive deficits. Phys Ther 85: 1020–1033.
- 532. Van Vliet P, Lincoln N, Foxall A (2005) Comparison of Bobath based and movement science based treatment for stroke: a randomised controlled trial. J Neurol Neurosurg Psychiatry 76: 503–508.
- 533. Wang R, Chen H, Chen C, Yang Y (2005) Efficacy of Bobath versus orthopaedic approach on impairment and function at different motor recovery stages after stroke: a randomized controlled study. Clin Rehabil 19: 155–164.
- 534. Brock K, Haase G, Rothacher G, Cotton S (2011) Does physiotherapy based on the Bobath concept, in conjunction with a task practice, achieve greater improvement in walking ability in people with stroke compared to physiotherapy focused on structured task practice alone?: a pilot randomized controlled trial. Clin Rehabil 25: 903–912.
- 535. Bütefisch C, Hummelsheim H, Denzler P, Mauritz K (1995) Repetitive training of isolated movements improves the outcome of motor rehabilitation of the centrally paretic hand. J Neurol Sci 130: 59–68.
- 536. Dechaumont-Palacin S, Marque P, De Boissezon X, Castel-Lacanal E, Carel C, et al. (2008) Neural correlates of proprioceptive integration in the contralesional hemisphere of very impaired patients shortly after a subcortical stroke: an FMRI study. Neurorehabil Neural Repair 22: 154–165.
- 537. Chow D, Hauptman J, Wong T, Gonzalez N, Martin N, et al. (2012) Changes in stroke research productivity: a global perspective. Surg Neurol Int 3: 27.
- 538.
Kennisnetwerk CVA Nederland (2012) Zorgstandaard CVA/TIA. Maastricht.
- 539. Otterman N, Van der Wees P, Bernhardt J, Kwakkel G (2012) Physical therapists' guideline adherence on early mobilization and intensity of practice at dutch acute stroke units: a country-wide survey. Stroke 43: 2395–2401.
- 540.
Royal College of Physicians Clinical Effectiveness and Evaluation Unit on behalf of the Intercollegiate Stroke Working Party (2013) Sentinel Stroke Natinoal Audit Programme (SSNAP) – Clinical audit second pilot public report.
- 541. Kollen B, Lennon S, Lyons B, Wheatley-Smith L, Scheper M, et al. (2009) The effectiveness of the Bobath concept in stroke rehabilitation: what is the evidence? Stroke 40: e89–97.
- 542.
Hebb D (1949) Organization of behavior: a neuropsychological theory. New York: John Wiley.
- 543.
French B, Thomas L, Leathley M, Sutton C, McAdam J, et al.. (2007) Repetitive task training for improving functional ability after stroke. Cochrane Database Syst Rev: CD006073.
- 544. Lee T, Swanson L, Hall A (1991) What is repeated in a repetition? Effects of practice conditions on motor skill acquisition. Phys Ther 71: 150–156.
- 545. Kwakkel G, Kollen B (2013) Predicting activities after stroke: what is clinically relevant? Int J Stroke 8: 25–32.
- 546. Dobkin B (2007) Confounders in rehabilitation trials of task-oriented training: lessons from the designs of the EXCITE and SCILT multicenter trials. Neurorehabil Neural Repair 21: 3–13.
- 547. Van Delden A, Peper C, Beek P, Kwakkel G (2013) Match and mismatch between objective and subjective improvements in upper limb function after stroke. Disabil Rehabil 35: 1961–1967.
- 548. O'Connor R, Cano S, Thompson A, Hobart J (2004) Exploring rating scale responsiveness: does the total score reflect the sum of its parts? Neurology 62: 1842–1844.
- 549. Ali M, English C, Bernhardt J, Sunnerhagen K, Brady M (2013) More outcomes than trials: a call for consistent data collection across stroke rehabilitation trials. Int J Stroke 8: 18–24.
- 550. Weaver C, Leonardi-Bee J, Bath-Hextall F, Bath P (2004) Sample size calculations in acute stroke trials: a systematic review of their reporting, characteristics, and relationship with outcome. Stroke 35: 1216–1224.
- 551. Dwan K, Gamble C, Williamson P, Kirkham J (2013) Systematic review of the empirical evidence of study publication bias and outcome reporting bias - an updated review. PLoS One 8: e66844.
- 552. Dobkin B, Duncan P (2012) Should body weight-supported treadmill training and robotic-assistive steppers for locomotor training trot back to the starting gate? Neurorehabil Neural Repair 26: 308–317.
- 553. Muir K (2002) Heterogeneity of stroke pathophysiology and neuroprotective clinical trial design. Stroke 33: 1545–1550.
- 554. Gabler N, Duan N, Liao D, Elmore J, Ganiats T, et al. (2009) Dealing with heterogeneity of treatment effects: is the literature up to the challenge? Trials 10: 43.
- 555. Kent D, Rothwell P, Ioannidis J, Altman D, Hayward R (2010) Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials 11: 85.
- 556. Altman D, Furberg C, Grimshaw J, Rothwell P (2006) Lead editorial: trials - using the opportunities of electronic publishing to improve the reporting of randomised trials. Trials 7: 6.
- 557. Schulz K, Altman D, Moher D (2010) CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol 63: 834–840.
- 558. Hirst A, Altman D (2012) Are peer reviewers encouraged to use reporting guidelines? A survey of 116 health research journals. PLoS One 7: e35621.
- 559.
Turner L, Shamseer L, Altman D, Weeks L, Peters J, et al.. (2012) Consolidated standards of reporting trials (CONSORT) and the completeness of reporting of randomised controlled trials (RCTs) published in medical journals. Cochrane Database Syst Rev: MR000030.
- 560. Bernhardt J, Dewey H, Thrift A, Donnan G (2004) Inactive and alone: physical activity within the first 14 days of acute stroke unit care. Stroke 35: 1005–1009.
- 561. Murphy T, Corbett D (2009) Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci 10: 861–872.
- 562. Keith R (1996) Rehabilitation after stroke: cost-effectiveness analyses. J R Soc Med 89: 631–633.
- 563.
French B, Leathley M, Sutton C, McAdam J, Thomas L, et al.. (2008) A systematic review of repetitive functional task practice with modelling of resource use, costs and effectiveness. Health Technol Assess 12: iii, ix-iii,117.
- 564. Sangvatanakul P, Hillege S, Lalor E, Levi C, Hill K, et al. (2010) Setting stroke research priorities: The consumer perspective. J Vasc Nurs 28: 121–131.
- 565. Pollock A, St George B, Fenton M, Firkins L (2012) Top ten research priorities relating to life after stroke. Lancet Neurol 11: 209.
- 566. Cooke E, Mares K, Clark A, Tallis R, Pomeroy V (2010) The effects of increased dose of exercise-based therapies to enhance motor recovery after stroke: a systematic review and meta-analysis. BMC Med 8: 60.
- 567. Johansson T, Wild C (2011) Telerehabilitation in stroke care–a systematic review. J Telemed Telecare 17: 1–6.
- 568. Levin M, Kleim J, Wolf S (2009) What do motor "recovery" and "compensation" mean in patients following stroke? Neurorehabil Neural Repair 23: 313–319.
- 569. Buma F, Kwakkel G, Ramsey N (2013) Understanding upper limb recovery after stroke. Restor Neurol Neurosci 31: 707–722.
- 570. Williams J, Pascual-Leone A, Fregni F (2010) Interhemispheric modulation induced by cortical stimulation and motor training. Phys Ther 90: 398–410.
- 571.
Elsner B, Kugler J, Pohl M, Merholz J (2012) Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke. Cochrane Database Syst Rev: CD009645.
- 572. Hsu W, Cheng C, Liao K, Lee I, Lin Y (2012) Effects of repetitive transcranial magnetic stimulation on motor functions in patients with stroke: a meta-analysis. Stroke 43: 1849–1857.
- 573. Chollet F, Tardy J, Albucher J, Thalamas C, Berard E, et al. (2011) Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol 10: 123–130.
- 574. Vickrey B, Brott T, Koroshetz W (2013) Research priority setting: a summary of the 2012 NINDS Stroke Planning Meeting Report. Stroke 44: 2338–2342.
- 575. Craig L, Smith L (2008) The interaction between policy and education using stroke as an example. Nurse Educ Today 28: 77–84.
- 576. Smith L, Craig L, Weir C, McAlpine C (2008) Stroke education for healthcare professionals: making it fit for purpose. Nurse Educ Today 28: 337–347.
- 577. Kirkham J, Dwan K, Altman D, Gamble C, Dodd S, et al. (2010) The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews. BMJ 340: c365.
- 578. Riley R, Lambert P, Abo-Zaid G (2010) Meta-analysis of individual participant data: rationale, conduct, and reporting. BMJ 340: c221.
- 579. Hedges L, Pigott T (2004) The power of statistical tests for moderators in meta-analysis. Psychol Methods 9: 426–445.
- 580. Borenstein M, Higgins J (2013) Meta-analysis and subgroups. Prev Sci 14: 134–143.