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NEW Delivery Of Stroke Rehabilitation to Optimize Functional Recovery
NEW Delivery Of Stroke Rehabilitation to Optimize Functional Recovery

1. Upper Extremity Function - General Principles and Therapies

Notes
  • Many therapy approaches can be used together and may provide some synergistic benefits. Research supporting these recommendations often combines multiple interventions, applying them simultaneously in both studies and practice.
  • When using specific therapeutic interventions, appropriately trained health professionals should follow established protocols whenever they are available.
  • The choice of therapy will vary depending on the severity of impairments in each individual with stroke. This should be considered when creating a personalized rehabilitation plan
  • Interventions should be tailored to each individual with stroke, and often, multiple therapies can be considered for a single person.
  • Evidence Grading System: For some areas of stroke rehabilitation, the same topic area may have different evidence for early and later stages of rehabilitation and recovery. In these instances, the levels of evidence will be stated separately for each time interval. For the purposes of these recommendations ‘early’ refers to strength of evidence for therapies applicable to individuals with stroke who are less than 6 months post stroke, and ‘late’ refers to strength of evidence for therapies applicable to individuals with stroke who are more than 6 months from index stroke event.
1.1 General Principles
  1. Individuals should engage in training that is meaningful, engaging, repetitive, progressively adapted, task-specific and goal-oriented to enhance motor control and restore sensorimotor function [Strong recommendation; High quality of evidence].  
  2. Training should encourage the use of the individuals’ affected extremity during functional tasks and be designed to simulate partial or whole skills required in activities of daily living (ADLs) (e.g. folding, buttoning, pouring, and lifting) [Strong recommendation; High quality of evidence].  
1.2 Specific Therapies
  1. Range of motion exercises (passive and active assisted) that include placement of the upper extremity in a variety of appropriate and safe positions should be considered [Strong recommendation; Low quality of evidence]. 
  2. Functional Electrical Stimulation (FES) involving electrical stimulation in combination with task-oriented training of the upper extremity is recommended to improve motor function [Strong recommendation; Moderate quality of evidence]. 
  3. High intensity Constraint-Induced Movement Therapy (CIMT) (i.e., immobilization of the non-paretic upper extremity during 90% of waking hours and 3-6 hours of task-oriented training per day is recommended for a select group of individuals with stroke who demonstrate at least 20 degrees of active wrist extension and 10 degrees of active finger extension, with minimal sensory deficits and normal cognition [Early - Strong recommendation; High quality of evidence; Late - Strong recommendation; High quality of evidence]. 
  4. Mirror therapy may be considered to improve motor and ADL function [Strong recommendation; Moderate quality of evidence]. 
  5. Sensory stimulation modalities (e.g., transcutaneous electrical nerve stimulation [TENS], and acupuncture) may be considered to improve upper extremity function [Conditional recommendation; Low quality of evidence]. 
  6. Biofeedback in the form of visual and/or auditory signals during exercises of the upper extremity is recommended to improve motor function [Strong recommendation; High quality of evidence]. 
  7. Individuals with stroke should be encouraged to engage in mental imagery practice to enhance upper extremity sensorimotor recovery as an adjunct to upper extremity rehabilitation [Strong recommendation; Moderate quality of evidence]. 
  8. Virtual reality, including both immersive technologies such as head mounted or robotic interfaces and non-immersive technologies such as gaming devices, may be considered as adjunct tools to other rehabilitation therapies, to provide additional opportunities for engagement, feedback, repetition, intensity and task-oriented training [Strong recommendation; Moderate quality of evidence].
  9. Therapists should consider supplementary training programs aimed at increasing the active movement and functional use of the affected upper extremity between therapy sessions, such as Graded Repetitive Arm Supplementary Program (GRASP), suitable for use during hospitalization and at home [Early - Strong recommendation; Moderate quality of evidence; Late- Strong recommendation; Low quality of evidence]. 
  10. Strength training is recommended for individuals with mild to moderate upper extremity impairment for improvement in upper extremity motor function [Strong recommendation; High quality of evidence].  
  11. Bilateral upper extremity training should be considered for individuals with some active movement in the affected upper extremity to improve upper extremity motor function [Early – Strong recommendation; Moderate quality of evidence; Late – Strong recommendation; High quality of evidence]. 
  12. Training in compensatory techniques and provision of adaptive equipment may be considered for individuals with stroke who are unable to produce any voluntary muscle activity in the affected upper extremity to optimize independence with ADLs [Strong recommendation; Low quality of evidence].  
  13. Retraining trunk control should be considered to improve function of the affected arm and hand [Strong recommendation; Moderate quality of evidence]. 
  14. Trunk restraint (i.e., physical restraint) is recommended to decrease compensatory movements during reaching tasks to improve upper extremity function [Strong recommendation; High quality of evidence].
 
1.3 Adaptive Equipment
  1. Adaptive equipment (e.g., long-handled shoehorn, adaptive cutting board for one-handed use, adapted guitar foot strummer) designed to improve safety and upper extremity function may be considered if other methods of performing specific functional tasks are not available or alternative methods of performing tasks cannot be learned [Strong recommendation; Low quality of evidence].
Section 1 Clinical Considerations
  1. Functional dynamic orthoses for the upper extremity may be offered to individuals with stroke to facilitate repetitive task-specific training.
  2. Non-invasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) could be considered as an adjunct to upper extremity rehabilitation. Note while these interventions are not yet available/approved for use in stroke in Canada the evidence for their use continues to be strengthened.
Rationale +-

Upper extremity function is frequently reduced following stroke, limiting the individual with stroke’s ability to perform basic ADLs, such as dressing and bathing. While many individuals with stroke will regain their pre-stroke upper extremity function, a portion of those with initial weakness, will not. To address the needs of these individuals, several therapeutic techniques have been developed for those whose upper extremity movement had been impacted by stroke. 

Individuals with stroke have faced challenges in receiving equitable access to individualized rehabilitation for upper extremity function, especially in the community following hospital discharge. Individuals with stroke highlight the importance of education on upper extremity rehabilitation, home exercises, adaptive devices, and the potential cost of devices and funding options. Including family members and caregivers in this education is also valuable and helpful.

Performance Measures +-

System Indicators

  1. Access to stroke rehabilitation services 7 days per week for inpatient care.
  2. Proportion of individuals within a stroke region who access an inpatient and community-based stroke rehabilitation as part of their episode of care for a stroke event.

Process Indicators

  1. Median length of time from stroke admission in an acute care hospital to assessment of rehabilitation potential by a rehabilitation healthcare professional.
  2. Median length of time spent on a dedicated stroke rehabilitation unit during inpatient rehabilitation.
  3. Median hours per day of direct task-specific therapy provided by the interdisciplinary stroke team. 
  4. Average days per week of direct task specific therapy provided by the interdisciplinary stroke team (target is a minimum of five days).

Patient-Oriented Indicators   

  1. Extent of change in arm and hand functional status scores using a standardized assessment tool from admission to an inpatient or community-based rehabilitation program to discharge.
  2. Extent of change (improvement) in functional status scores using a standardized assessment tool from admission to an inpatient or community-based rehabilitation program to discharge.
  3. Modified Rankin Score at 3 months, 6 months and one year following stroke.
 
Implementation Resources and Knowledge Transfer Tools +-

Resources and tools listed below that are external to Heart & Stroke and the Canadian Stroke Best Practice Recommendations may be useful resources for stroke care. However, their inclusion is not an actual or implied endorsement by the Canadian Stroke Best Practices team or Heart & Stroke. The reader is encouraged to review these resources and tools critically and implement them into practice at their discretion.

Health Care Provider Information

Resources for Individuals with Stroke, Families and Caregivers 

Summary of the Evidence +-

Evidence Table and Reference List 1

Task-Specific Training

Task-specific training involves the repeated practice of functional tasks, which combines the elements of intensity of practice and functional relevance. The tasks should be challenging and progressively adapted and should involve active participation. French et al.14 included the results from 11 randomized controlled trials (RCTs) in a Cochrane review that included an upper extremity rehabilitation component. Repetitive task-specific training was associated with a small treatment effect on arm and hand function, assessed post intervention. (standardized mean difference [SMD]=0.25, 95% CI 0.01 to 0.49, p=0.045 and SMD=0.25, 95% CI 0.00 to 0.51, p=0.05, respectively). The benefits appeared to persist up to 6 months follow-up. Patients treated from 16 days to 6 months post stroke derived the greatest value. In contrast to these findings, in an earlier systematic review of motor recovery following stroke, Langhorne et al.15 identified 8 RCTs of repetitive task training, specific to the upper extremity. In these trials, treatment duration varied widely from a total of 20 to 63 hours provided over a 2 week to 11-week period. Therapy was not associated with significant improvements in arm function (SMD=0.19, 95% CI -0.01 to 0.38) or hand function (SMD=0.05, 95% CI -0.18 to 0.29). Perhaps the inclusion of trials that evaluated repetitive task training in addition to task-oriented training was, in part, responsible for the null result. In a crossover RCT, Shimodozone et al.16 randomized 49 participants in the sub-acute phase of stroke to one of two groups: 1) repetitive facilitative exercise (RFE), or 2) control-conventional rehabilitation program. Both groups received 40 min sessions 5x/wk. for 4 weeks of their allocated treatment. Both groups performed 30 min/day of dexterity-related training immediately after each treatment session and continued their participation in a standard inpatient rehabilitation program. Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment (FMA) were assessed at baseline, and at week 2 and 4. After 4 weeks of treatment, significantly greater improvements on the ARAT (p=0.009) and FMA (p=0.019) were demonstrated by the RFE group compared to the control group.

Functional Electrical Stimulation

While functional electrical stimulation (FES) has been investigated extensively in the rehabilitation of the lower extremity and for preventing/treating shoulder subluxation, there is a smaller literature base for its use as a modality to improve upper extremity function. In a network meta-analysis, Tenberg et al.17 included 5 trials that examined active electrical stimulation and reported the treatment was not associated with a significant improvement in motor function (SMD=0.63, 95% CI -0.01 to 1.27); however, when combined with task-specific training, the effect was enhanced (SMD=1.03, 95% CI 0.51 to 1.55, n=12 trials). Khan et al.18 included 25 studies examining FES-based interventions for the upper extremity including both open and closed loop systems. There was significantly greater improvement in upper motor function using electromyography (EMG)-controlled FES compared with brain-computer interface (BCI)-controlled and manually controlled FES systems. Mean difference for the FMA was 14.14, (95% CI 11.72 to 16.6) vs. 5.6 (95% CI 3.77 to 7.5) for manually controlled FES and 5.37 (95% CI (4.2 to 6.6) for BCI-controlled FES. However, only data from between 3 and 5 trials were available for pooled analyses. A similar pattern was evident for mean difference in ARAT scores with a mean difference of 11.9 (95% CI 8.8 to 14.9) for EMG-controlled FES.

Eraifej et al.19 included the results of 20 RCTs in a systematic review that evaluated the ability of FES to improve ADL and motor function. Pooling data from 8 trials, there was no significant difference between groups (FES and usual care) in ADL performance (SMD=0.64, 95% CI -0.02 to 1.30, p=0.06); however, in sub group analysis including 5 trials, persons who received FES during the acute phase of stroke (within 2 months) did improve their ADL performance with FES (SMD=1.24, 95% CI 0.46 to 2.03, p=0.002). FES was associated with significant improvement in FMA scores (MD=6.72, 95% CI 1.76, 11.68, p=0.008). Vafadar et al.20 pooled the results from 10 trials evaluating the use of FES for the rehabilitation of shoulder subluxation, pain, and upper arm motor function. Pooling the results from 5 trials, FES was not associated with significant improvements in arm motor function when initiated early post stroke, compared with conventional therapy (SMD=0.36, 95% CI -0.27 to 0.99, p=0.26). Pooling of results was not possible for an evaluation of FES in the chronic stage of stroke.

Constraint Induced Movement Therapy

Traditional constraint induced movement therapy (CIMT) involves restraint of the unaffected arm for at least 90 percent of waking hours, in addition to a minimum of 6 hours a day of intense upper extremity (UE) training of the affected arm every day for two weeks. This form of therapy may be effective for a select group of patients who demonstrate some degree of active wrist and arm movement and have minimal sensory or cognitive deficits.  Evidence from the VECTORS trial 21 suggests that traditional (intensive) CIMT should not be used for individuals in the first month post stroke, and in fact may be associated with worse outcomes. Patients who were randomized to receive 3 hours of intensive therapy in addition to wearing a constraint for 6 hours/day had lower ARAT scores at 3 months compared with patients who had received conventional occupational therapy or standard CIMT for two hours each day.  In the largest RCT of conventional CIMT 22 which included 222 patients, recruited  3-9 months post stroke, patients in the CIMT group had significantly greater improvement in  Wolf Motor Function Tests (WMFT) scores and Motor Activity Log (MAL) (Amount of Use [AOU] and Quality of Movement [QOM] subscores) at 12 months, compared with patients in the control group who received usual care, which could range from no therapy to a formal structured therapy program. 

Modified constraint-induced movement therapy (mCIMT) is a more feasible therapy option when resources are limited. In the most common variation of traditional CIMT, the unaffected arm is restrained with a padded mitt or arm sling for 5 hours a day, and with half-hour blocks of 1:1 therapy provided for up to 10 weeks.23 The results from several good-quality RCTs suggest that patients who received mCIMT in the subacute or chronic phase of stroke experienced greater functional recovery compared with patients who received traditional occupational therapy. In the EXPLICIT trial24 58 participants in the acute phase of stroke were randomized to a usual care group of a modified CIMT (mCIMT), which involved restraint for 3 hours, 5 days a week for 3 weeks in addition to 60 minutes of supervised intensive graded practice focused on improving task-specific use of the paretic arm and hand. There was significantly greater improvement in the mCIMT group on ARAT scores, the primary outcome, from baseline to 5, 8- and 12-weeks following treatment, but not at 26 weeks. There were no significant differences between groups on impairment measures, such as the FMA of the arm, or Motricity Index scores. 

Liu et al.25 included the results of 16 RCTs examining mCIMT or CIMT in the acute or subacute stage of stroke and reported significantly greater gains in ARAT, Barthel Index, FMA, and MAL Log scores (AOU, QOM) compared with the control condition. A Cochrane review26 included the results from 42 RCTs examining both CIMT and mCIMT, across the spectrum of the stroke recovery continuum. Overall, neither form of CIMT (traditional nor modified) was associated with a significant improvement in standardized measures of disability (SMD=0.24, 95% CI -0.05 to 0.52) at the end of treatment, or at 6 to 12 months follow-up (SMD=-0.21, 95% CI -0.57 to 0.16), compared with usual care. CIMT was associated with significant improvements in arm motor function, dexterity and measures of arm motor impairment. The results from this review are difficult to interpret since trials of all forms of CIMT were included as were patients in all stages of stroke recovery. Another recent systematic review, Gao et al.27 included the results of 44 RCTs including 1,779 individuals and examined the benefits of 4 categories of CIMT, which varied by time of constraint (≤4 hours to >10 hours/day). Compared with conventional therapy alone, CIMT provided for between 4 and 6 hours daily was associated with the most improvements in motor and ADL performance. In contrast, Tenberg et al.17 reported that high-intensity CIMT was associated with significantly greater improvement in motor function assessed at the end of the treatment period compared to other active interventions (SMD=0.86, 95% CI 0.40-1.32).

Mirror Therapy 

Mirror therapy is a technique that uses visual feedback about motor performance to enhance upper extremity function following stroke and reduce pain. Evidence from a Cochrane review,28 which included the results from 62 RCTs, including mirror therapy for both the upper and lower extremity indicated a modest improvement in upper extremity motor function compared with the control group at the end of the intervention (SMD=0.46, 95% CI 0.23-0.69, 31 trials). A systematic review and network meta-analysis 29 included the results of 37 RCTs assessing mirror therapy, alone or in combination with electrical stimulation. Overall, mirror therapy was associated with significantly greater improvement in the FMA and Functional Independence Measure (FIM) scores compared with conventional therapy, while mirror therapy + electrical stimulation + conventional therapy provided for ≤ 4 weeks was more effective than conventional therapy only for improving FMA scores (SMD=0.38, 95% CI 0.22–0.55). In a meta-analysis 30 including the results from 11 RCTs, mirror therapy was associated with significantly increased motor function compared with the control condition (SMD=0.51, 95%CI 0.29-0.73).

Biofeedback

In a systematic review & network meta-analysis, 17 which included 37 treatment classes comparing a variety of interventions compared with nonspecific/multimodal active upper extremity therapy, 5 interventions were found to be superior when assessment was conducted at the end of the intervention period. Among them was biofeedback (SMD=0.45, 95% CI 0.16-1.74), although it was used without a co-intervention in only a single trial.

Mental Practice 

Mental practice is the process whereby an individual repeatedly rehearses tasks mentally without physically performing them, with the goal of improving actual performance. In a Cochrane review which included the results of 25 RCTs, Barclay-Goddard et al. 31 reported when used in addition to other therapies, mental practice was associated with a significant improvement in measures of upper extremity activity and impairment (SMD=0.66, 95% CI 0.39-0.94 and SMD=0.59, 95% CI 0.3-0.87, respectively), compared with conventional therapy, but not when used by itself, compared with conventional therapy.

Virtual Reality 

A systematic review 32 included the results from 43 RCTS evaluating the effectiveness of virtual reality (VR)-supported exercise therapy for upper extremity motor rehabilitation in stroke. In 16 RCT’s, commercial games were used and in 27 RCT’s, programs designed for rehabilitation were used. VR interventions were associated with significantly higher upper-extremity motor function scores (SMD=0.45, 95% CI 0.21 to 0.68). The effect size was significantly greater in trials that provided therapy for >15 hours (SMD=0.92, 95% CI 0.35 to 1.49) vs. ≤15 hours (SMD= −0.10, 95% CI −0.35 to 0.15). VR interventions were also associated with significantly higher FIM scores (SMD=0.23, 95% CI 0.06-0.40), but not Barthel Index scores (SMD=0.20, 95% CI −0.16 to 0.55), Box & Block test scores, Action Research Arm Test scores, or Wolf Motor Function Test scores. 

Laver et al. 33 included the results of 22 RCTs in a Cochrane review examining the effectiveness of virtual reality, mainly using commercially available gaming consoles. Compared with conventional treatment, virtual reality interventions were not associated with significant improvements in measures of upper extremity function, at either the end of treatment, or at 3 months, (SMD=0.07, 95% CI -0.05 to 0.20 and SMD=0.11, 95% CI -0.10 to 0.32, respectively). However, when virtual reality was used in addition to usual care (providing a higher dose of therapy for those in the intervention group) there was a statistically significant difference between groups (SMD= 0.49, 0.21 to 0.77, 10 studies). When assessments were conducted using the FMA (upper extremity) at the end of treatment, there was a significant treatment effect of virtual reality. The results from several recent RCTs 34-37 indicated that virtual reality was not associated with significant improvements in ARAT scores, or a variety of other outcomes, including Canadian Occupational Performance Measure, Stroke Impact Scale, FIM, or FMA.

GRASP 

Evidence from a single trial evaluating the Graded Repetitive Arm Supplementary Program (GRASP) program suggests that additional therapy, performed outside of regular therapy can improve upper extremity function. 38 In this multi-site RCT, 103 patients recruited an average of 21 days following stroke with upper-extremity FMA scores between 10 and 57, were randomized to participate in a 4 week (one hour/day x 6 days/week) homework-based, self-administered program designed to improve ADL skills through strengthening, range of motion (ROM) and gross and fine motor exercises or to a non-therapeutic education control group  At the end of the treatment period, participants in the GRASP group had significantly higher mean Chedoke Arm & Hand Activity Inventory, ARAT and MAL scores compared with the control group. The improvement was maintained at 3 months follow-up.

Strength Training

Strength training has not been well studied in the context of upper extremity rehabilitation. Hunter et al.39 included 288 participants who had sustained a stroke in the anterior cerebral circulation territory within the previous 2-60 days, with some voluntary muscle contraction in the paretic upper extremity and without full dexterity in the FAST-INdiCATE Trial. Participants were randomized to receive functional strength training (FST) or movement performance therapy (MPT) in addition to conventional rehabilitation for 6 weeks. There was significant improvement in mean ARAT scores at 6 weeks within each group with no significant differences between groups (FST: 24.4 to 34.1 vs. MPT: 26.5 to 34.4, p=0.29). There was no significant difference between groups in mean ARAT scores or mean change scores from baseline, nor were there significant differences between groups in mean WMFT scores or mean change scores at 6 weeks or 6 months. In an older systematic review, including 13 RCTs, Harris & Eng 40 reported that therapy programs including a strength training or resistance training component were associated with significant improvements in motor function (SMD=0.21, 95%CI 0.03–0.39, p=0.03), grip strength (SMD=0.95, 95% CI 0.05 to 1.85, p=0.04), but not performance of ADLs (SMD=0.26, 95% CI -0.10 to 0.63, p=0.16).  Improvements were noted in both the acute and chronic stages of stroke.

Bilateral Arm Training

The results from several systematic reviews and meta-analyses indicate that bilateral arm training is associated with significantly greater improvements in measures of impairment, 41-43 but not necessarily for measures of activity. The greatest benefit was found in patients with mild paresis, in the chronic stage of stroke and when bilateral training was provided as bilateral functional task training, and at high doses. An older Cochrane review44 which has not been updated since 2010, included the results from 18 RCTs, and reported that compared with conventional care, bilateral training was not associated with significantly better scores on measures of arm function, ADL performance or extended ADL, but did improve motor impairment. However, the treatment effect was very much dependent on the outcome used for assessment, the type of bilateral arm training that was provided (e.g., bilateral functional task training, bilateral robot-assisted training, mirror therapy and bilateral training with rhythmic auditory cueing) and the therapy the control group received (unimanual vs. conventional therapy).

Trunk Retraining

Trunk retraining is a type of physical therapy that focuses on exercises designed to improve the control and stability of the torso (trunk) muscles, which are often weakened after a stroke, leading to impaired balance, mobility, and difficulty with daily activities. A Cochrane review 45 included the results from 68 RCTs. Trunk training interventions included core-stability training (isometric strengthening of the trunk muscles), electrical stimulation that targeted ≥ 1 core trunk muscles, selective-trunk training aimed at improving selective movements of the upper and lower part of the trunk, sitting-reaching therapy, 10° steady-tilted platform and weight-shift training. The median duration of therapy was 4 weeks, providing a median of 600 minutes of total training. The intensity of training ranged from 30 minutes to 2,700 minutes (45 hours). Overall, trunk training was associated with a significant improvement in trunk function compared with both dose matched and non-dose matched therapy. Compared with non dose-matched therapy, trunk training was associated with a significant improvement in arm-hand activity, trunk function and ADL performance, while compared with dose-matched therapy, trunk training was not associated with a significant improvement in arm-hand activity or improvement in performance in ADL.

Trunk Restraint

Trunk restraint therapy is a rehabilitation technique in which the patient wears a harness or device to stabilize their trunk, preventing excessive compensatory movements, thus forcing them to use their affected upper extremity more effectively.  A systematic review authored by Zhang et al. 46 included the results from 10 RCTs including 255 patients with upper extremity impairment following stroke. Patients received trunk restraint as part of a task-oriented training program or task-oriented training alone for two to 5 days per week, for two to 10 weeks. Trunk restraint was associated with significantly greater improvement in MAL-AOU and MAL-QOM (MD=0.34, 95% CI 0.20-0.47 and MD=0.34, 95% CI 0.18-0.50, respectively), FMA-UL (MD=0.68, 95% CI 0.39-0.98), ARAT (MD=4.3, 95% CI 2.33-6.27and ADL performance (SMD=0.98, 95% CI 0.07 -1.89). The benefits were greatest for patients in the subacute stage of stroke.

Functional Dynamic Orthoses

This hand orthosis is designed to support, stabilize, or assist the movement of a specific joint or body part while also allowing for dynamic movement, such as executing a grasp. Dynamic hand orthoses were associated with significant improvement in ARAT scores (MD= 6.23 points, 95% CI 0.28 to 12.19; 2 trials included) and Box and Block Test (MD=2.99, 95% CI 0.39 to 5.60; 4 trials included) in a systematic review including 4 RCTs (56 patients) with upper extremity impairment following stroke, with no significant improvement in quality of life scores, motor function or grip strength. 47 

Non-invasive Brain Stimulation

Non-invasive brain stimulation using either transcranial direct-current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) have been shown to be beneficial forms of treatment for upper-extremity rehabilitation. 

A large Cochrane review including the results of 67 RCTs including 1,729 participants with stroke compared active anodal or cathodal tDCS vs. sham treatment + an active or passive control treatment comparator. 48 tDCS was associated with significant improvement in ADL performance, measured at the end of the intervention, compared with placebo or passive control interventions (SMD=0.28, 95% CI 0.13 to 0.44, n=19 trials) and at follow-up (SMD=0.31, 95% CI 0.01 to 0.62; 6 trials). tDCS was also associated with a significant improvement in ADL performance, measured after the intervention, compared with an active intervention control (Barthel Index MD=6.59, 95% CI 1.26 to 11.9, 3 trials). Chhatbar et al. 49 included the results from 8 RCTs (213 participants) investigating the role of tDCS (≥5 sessions) in post-stroke recovery of upper extremity, compared with a sham condition.  tDCS was associated with significantly greater improvements in FMA (upper extremity scores) compared with sham treatment (SMD=0.61, 95% CI 0.08 to 1.13, p=0.02). Treatment effects were more pronounced in the chronic vs. acute stage of stroke (SMD=1.23 vs. SMD=0.18). 

In the Navigated Inhibitory rTMS to Contralesional Hemisphere Trial (NICHE), Harvey et al. 50 randomized 199 patients with a unilateral ischemic or hemorrhagic stroke occurring within three to 12 months of enrollment, with a Chedoke–McMaster assessment stage of 3-6 for both arm and hand, to receive low-frequency (1 Hz) active or sham rTMS to the non-injured motor cortex before each 60-minute therapy sessions, delivered over 6-weeks. At the end of 6 months, 67% of the experimental group and 65% of sham group improved ≥5 points on FMA-upper extremity (the primary outcome). The difference was not statistically significant (p=0.76). There was also no difference between experimental and sham groups in the ARAT (p=0.80) or WMFT (p=0.55) scores. In an extension of the NICHE trial, the Electric Field Navigated 1hz rTMS for Post-stroke Motor Recovery Trial (E-FIT), Edwards et al.51 used the same inclusion criteria and trial protocol (albeit a different sham coil) and randomized an additional 60 patients. Even with the larger sample size, when combining the results from both trials, the combined mean odds of achieving the primary outcome were not significantly higher in the active rTMS group (posterior mean odds ratio [OR]=0.94, 96% credible interval of 0.61–4.80). When including only participants from the E-FIT trial, the percentage of patients in the active rTMS group who achieved the primary outcome was 60% vs. 50% in the sham group (OR=1.49, 95% CI 0.53 to 4.22). A systematic review that included the results from 45 RCTs reported that overall rTMS was associated with significantly greater improvement in upper arm function, assessed using the FMA-UE (SMD=1.12, 95% CI 0.56-1.68, 17 trials), with the benefit persisted up to 5 months following the intervention. 52

Pharmacotherapy & Functional Recovery 

Selective serotonin reuptake inhibitors (SSRIs) have been investigated as a potential modulator of functional recovery post stroke, in patients both with and without mood disorders. Unfortunately, there appears to be increasing evidence that SSRIs do not help to reduce disability or improve independence and may, in fact, be associated with harm. Mead et al. 53 included the results from three large RCTs in a patient-level meta-analysis, which recruited 5,907 patients with persisting focal neurological deficit following acute stroke. All participants were randomized to receive 20 mg fluoxetine daily or placebo for 6 months. Trials included in the review were The Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke (EFFECTS54), the Assessment oF FluoxetINe In sTroke recovery trial (AFFINITY, 55) and the Fluoxetine Or Control Under Supervision (FOCUS) trial. 56 At 6 months, the distribution of modified Rankin Scale (mRS) scores did not differ significantly between groups (common OR=0.96, 95% CI 0.87 to 1.05; GRADE: high quality). Neither was the distribution of scores significantly different between groups at 12 months (common OR=0.98, 95% CI 0.89 to 1.07). Fluoxetine was associated with a significantly increased frequency of seizures (2.64% vs. 1.8%, p=0.03), falls with injury (6.26% vs 4.51%, p=0.03), and fractures (3.15% vs 1.39%, p=0.01). In a Cochrane review, Legg et al. 57 included 76 RCTs including 13,029 participants who had suffered a stroke within the previous 12 months. Trials compared a variety of SSRIs vs. placebo. In most trials, patients were recruited in the early stages of stroke. There was no significant difference between groups in measures of disability (SMD=0.0, 95% CI -0.5 to 0.5, 5 trials; GRADE: high), nor was there a better chance of being independent at the end of treatment (RR=0.98, 95% CI 0.93 to 1.03, 5 trials; GRADE: high). SSRIs were associated with significantly higher risks of seizures and bone fractures.

Sex & Gender Considerations

While women are more likely to survive strokes than men, they tend to experience greater disability. Potential reasons for this imbalance may include greater initial stroke severity, higher pre-stroke disability and older age at stroke onset. 58 Women are also historically underrepresented in research studies. Data are limited with respect to rehabilitation outcomes with respect to sex. MacDonald et al. 59 used administrative data sets including 20,143 patients and compared sex differences in discharge Functional Independence Measure (FIM) scores from inpatient rehabilitation units in Ontario over a 5-year period. While in unadjusted analysis, women had a lower mean FIM score (94.1 vs. 97.8, p < 0.001), after adjusting for baseline characteristics, the difference was no longer significant. There is some evidence that women are under-represented in stroke rehabilitation clinical trials. In a recent systematic review, 60 examining female recruitment in 1,276 randomized trials investigating upper extremity rehabilitation interventions, the overall percentage of women included across all trials was 38.8%. The trials included participants across all stages of stroke chronicity, all rehabilitation settings, and intervention types (pharmacological, traditional and nontraditional rehabilitation therapies, and complementary interventions).

Stroke Resources
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