Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke

Bernhard Elsner; Joachim Kugler; Marcus Pohl; Jan Mehrholz

doi:10.1002/14651858.CD009645.pub3

. 2016 Mar 21;2016(3):CD009645. doi: 10.1002/14651858.CD009645.pub3

Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke

Bernhard Elsner ^1,^2,^✉, Joachim Kugler ³, Marcus Pohl ⁴, Jan Mehrholz ^3,⁵

Editor: Cochrane Stroke Group

PMCID: PMC6464909 PMID: 26996760

Abstract

Background

Stroke is one of the leading causes of disability worldwide. Functional impairment, resulting in poor performance in activities of daily living (ADLs) among stroke survivors is common. Current rehabilitation approaches have limited effectiveness in improving ADL performance, function, muscle strength and cognitive abilities (including spatial neglect) after stroke, but a possible adjunct to stroke rehabilitation might be non‐invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve ADL performance, arm and leg function, muscle strength and cognitive abilities (including spatial neglect), dropouts and adverse events in people after stroke.

Objectives

To assess the effects of tDCS on ADLs, arm and leg function, muscle strength and cognitive abilities (including spatial neglect), dropouts and adverse events in people after stroke.

Search methods

We searched the Cochrane Stroke Group Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2015, Issue 2), MEDLINE (1948 to February 2015), EMBASE (1980 to February 2015), CINAHL (1982 to February 2015), AMED (1985 to February 2015), Science Citation Index (1899 to February 2015) and four additional databases. In an effort to identify further published, unpublished and ongoing trials, we searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers.

Selection criteria

This is the update of an existing review. In the previous version of this review we focused on the effects of tDCS on ADLs and function. In this update, we broadened our inclusion criteria to compare any kind of active tDCS for improving ADLs, function, muscle strength and cognitive abilities (including spatial neglect) versus any kind of placebo or control intervention.

Data collection and analysis

Two review authors independently assessed trial quality and risk of bias (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports.

Main results

We included 32 studies involving a total of 748 participants aged above 18 with acute, postacute or chronic ischaemic or haemorrhagic stroke. We also identified 55 ongoing studies. The risk of bias did not differ substantially for different comparisons and outcomes.

We found nine studies with 396 participants examining the effects of tDCS versus sham tDCS (or any other passive intervention) on our primary outcome measure, ADLs after stroke. We found evidence of effect regarding ADL performance at the end of the intervention period (standardised mean difference (SMD) 0.24, 95% confidence interval (CI) 0.03 to 0.44; inverse variance method with random‐effects model; moderate quality evidence). Six studies with 269 participants assessed the effects of tDCS on ADLs at the end of follow‐up, and found improved ADL performance (SMD 0.31, 95% CI 0.01 to 0.62; inverse variance method with random‐effects model; moderate quality evidence). However, the results did not persist in a sensitivity analysis including only trials of good methodological quality.

In six of 23 studies (26%), dropouts, adverse events or deaths that occurred during the intervention period were reported, and the proportions of dropouts and adverse events were comparable between groups (risk difference (RD) 0.01, 95% CI ‐0.02 to 0.03; Mantel‐Haenszel method with random‐effects model; low quality evidence; analysis based only on studies that reported either on dropouts, or on adverse events, or on both). However, this effect may be underestimated due to reporting bias.

Authors' conclusions

At the moment, evidence of very low to moderate quality is available on the effectiveness of tDCS (anodal/cathodal/dual) versus control (sham/any other intervention) for improving ADL performance after stroke. However, there are many ongoing randomised trials that could change the quality of evidence in the future. Future studies should particularly engage those who may benefit most from tDCS after stroke and in the effects of tDCS on upper and lower limb function, muscle strength and cognitive abilities (including spatial neglect). Dropouts and adverse events should be routinely monitored and presented as secondary outcomes. They should also address methodological issues by adhering to the Consolidated Standards of Reporting Trials (CONSORT) statement.

Plain language summary

Direct electrical current to the brain to improve rehabilitation outcomes

Review question

We reviewed the evidence about the effect of direct electrical current to the brain (transcranial direct current stimulation, tDCS) to reduce impairment in activities of daily living (ADLs), arm and leg function, muscle strength and cognitive abilities (including spatial neglect), dropouts and adverse events in people after stroke.

Background

Stroke is one of the leading causes of disability worldwide. Most strokes take place when a blood clot blocks a blood vessel leading to the brain. Without a proper blood supply, the brain quickly suffers damage, which can be permanent. This damage often causes impairment of ADLs and motor function among stroke survivors. Current rehabilitation strategies have limited effectiveness in improving these impairments. One possibility for enhancing the effects of rehabilitation might be the addition of non‐invasive brain stimulation through a technique known as transcranial direct current stimulation (tDCS). This technique can alter how the brain works and may be used to reduce impairment of ADLs and function. However, the effectiveness of this intervention for improving rehabilitation outcomes is still unknown.

Search date

The review is current to February 2015.

Study characteristics

We included 32 studies involving a total of 748 participants aged above 18 with acute, postacute or chronic ischaemic or haemorrhagic stroke. The mean age in the experimental groups ranged from 43 years up to 70 years and from 45 years up to 75 years in the control groups. The level of participants' impairment ranged from severe to moderate. The majority of studies were conducted in an inpatient setting. Different stimulation types (anodal, cathodal, dual) of tDCS with different stimulation durations and dosages were administered and compared with sham tDCS or an active control intervention. Sham tDCS means that the stimulation is switched off covertly in the first minute of the intervention.

Key results

This review found that tDCS might enhance ADLs, but it is still uncertain if arm and leg function, muscle strength and cognitive abilities may be improved. Proportions of adverse events and people discontinuing the treatment were comparable between groups. Included studies differed in terms of type, location and duration of stimulation, amount of current delivered, electrode size and positioning as well as type and location of stroke. Future research is needed in this area to foster the evidence base of these findings, especially regarding arm and leg function, muscle strength and cognitive abilities (including spatial neglect).

Quality of the evidence

The quality of evidence for tDCS for improving ADLs was very low to moderate. It was low for upper extremity function and low for adverse events and people discontinuing the treatment.

Summary of findings

Background

Description of the condition

Every year, 15 million people worldwide suffer from stroke (WHO 2011), and of those, nearly six million die (Mathers 2011). Another five million people are left permanently disabled every year (WHO 2011). Hence, stroke is one of the leading causes of death worldwide and has a considerable impact on disease burden (WHO 2011). Stroke affects function and many activities of daily living (ADLs). Three out of four patients have an impairment in performing ADLs at hospital admission, and only about one‐third of patients who have completed rehabilitation have achieved normal neurological function (Jørgensen 1999). Every second patient does not regain function of the affected arm six months after stroke (Kwakkel 2003). Three out of four people with stroke suffer from working memory impairment and may thus experience executive dysfunction (Riepe 2004). Based on the rating by people with stroke, carers and health professionals, improving cognition after stroke is the number one research priority after stroke (Pollock 2012). Therefore, neurological rehabilitation, including effective training strategies, is needed (especially therapies tailored to patients' and carers' needs) to facilitate recovery and to reduce the burden of stroke (Barker 2005).

Description of the intervention

Transcranial direct current stimulation (tDCS) is a non‐invasive method used to modulate cortical excitability by applying a direct current to the brain (Bindman 1964; Nowak 2009; Purpura 1965). Stimulation of the central nervous system by tDCS is inexpensive when compared with repetitive transcranial magnetic stimulation (rTMS) and epidural stimulation (Hesse 2011).

How the intervention might work

Transcranial direct current stimulation (tDCS) usually is delivered via saline‐soaked surface sponge electrodes, which are connected to a direct current stimulator of low intensity (Lang 2005). Three different applications might be used: 1) the anodal electrode may be placed over the presumed area of interest of the brain with the cathodal electrode placed above the contralateral orbit (anodal stimulation, A‐tDCS); 2) the cathodal electrode may be placed over the presumed area of interest of the brain with the anodal electrode placed above the contralateral orbit (cathodal stimulation, C‐tDCS) (Hesse 2011); or 3) anodal stimulation and cathodal stimulation may be applied simultaneously (dual‐tDCS) (Lindenberg 2010). Primarily resulting from a shift of the resting potential of the brain's neurons, tDCS using anodal stimulation might lead to increased cortical excitability, whereas cortical stimulation might lead to decreased excitability (Bindman 1964; Floel 2010; Purpura 1965). Stimulation lasting for longer than five minutes might induce significant after‐effects (which probably are mainly due to changes in synaptic mechanisms), which could last up to several hours (Nitsche 2001; Nitsche 2003). These effects probably are 1) anatomically specific (referring to how the electrodes are positioned and which way the current takes to reach the targeted brain areas); 2) activity selective and task specific (meaning that neuronal networks active during a certain activity are preferentially stimulated by tDCS); and 3) input selective (meaning that tDCS would alter the neuronal system's input and thereby enhance information processing) (Bikson 2013). The facilitating effect of tDCS could be used to facilitate motor learning in healthy people (Boggio 2006; Jeffery 2007; Nitsche 2001; Nitsche 2003; Reis 2009) and appears to be a promising option in rehabilitation after stroke.

Why it is important to do this review

The previous version of this review suggested that, among people with stroke, tDCS with or without simultaneous upper extremity training, has led to greater improvement in arm motor function when compared with sham tDCS alone (Elsner 2013). Some pilot studies have even reported improvement in ADLs, such as, turning over playing cards, picking up beans with a spoon, and manipulating light and heavy objects with the arm (Fregni 2005; Hummel 2005; Kim 2009). However, these findings were not supported by a large‐scale multicentre randomised controlled trial (RCT), which did not find any effects on measures of ADL (Hesse 2011). There is contradictory evidence on the additional effect of tDCS on lower extremity function and gait (Cha 2014; Fusco 2014; Geroin 2011; Tahtis 2012). There are indications that tDCS might also improve working memory or neglect by modulating excitability of the corresponding brain areas (Au‐Yeung 2014; Jo 2008; Kang 2008a; Ko 2008; Park 2013; Sunwoo 2013). However, in a systematic review of RCTs about the effects of tDCS on aphasia, no evidence of an effect was found (Elsner 2015). Despite the fact that adverse effects associated with the application of tDCS have been reported rarely so far, concerns about the safety of tDCS regarding its impact on cerebral autoregulation have recently emerged (List 2015; Nitsche 2015).

To date, studies of tDCS have tended to include small sample sizes. Currently, no systematic review has comprehensively synthesised the findings of available RCTs. Therefore, a systematic review of RCTs investigating the effectiveness and acceptability of tDCS for improving ADLs, motor function and cognitive abilities (including spatial neglect) in people with stroke is required.

Objectives

To assess the effects of transcranial direct current stimulation (tDCS) on activities of daily living (ADLs), arm and leg function, muscle strength and cognitive abilities (including spatial neglect), dropouts and adverse events in people after stroke.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) and randomised controlled cross‐over trials, from which we analysed only the first period as a parallel‐group design. We did not include quasi‐RCTs.

Types of participants

We included adult participants (over 18 years of age) who had experienced a stroke. We used the World Health Organization (WHO) definition of stroke (Hatano 1976), or a clinical definition, if not specifically stated (i.e. signs and symptoms persisting longer than 24 hours). We included participants regardless of initial level of impairment, duration of illness, or gender.

Types of interventions

This is the update of an existing review. In the previous version of this review we focused on the effects of transcranial direct current stimulation (tDCS) on activities of daily living (ADLs) and function. In this update, we broadened our inclusion criteria to compare any kind of active tDCS for improving ADLs, function, muscle strength and cognitive abilities (including spatial neglect) versus any kind of placebo or control intervention (i.e. sham tDCS, no intervention or conventional motor rehabilitation). We defined active tDCS as the longer‐lasting (lasting longer than one minute) application of a direct current to the brain to stimulate the affected hemisphere, or to inhibit the healthy hemisphere. We defined sham tDCS as short‐term direct current stimulation (lasting less than one minute; this is approximately the time it usually takes to fade in and fade out the current in sham‐controlled tDCS trials in order to produce perceivable sensations on the skin similar to active tDCS (Gandiga 2006), or placement of electrodes with no direct current applied. If more than one active or sham or control group investigated the same content, we combined these into one group each (e.g. if two sham control groups were included, we combined them into a single sham group for comparison with the active group).

Types of outcome measures

Primary outcomes

The primary outcome was activities of daily living (ADLs), regardless of their outcome measurement. However, we prioritised generally accepted outcome measures in the following order to facilitate quantitative pooling.

Frenchay Activities Index (FAI) (Schuling 1993).
Barthel ADL Index (BI) (Mahoney 1965).
Rivermead ADL Assessment (Whiting 1980).
Modified Rankin Scale (mRS) (Bonita 1988).
Functional Independence Measure (FIM) (Hamilton 1994).

We analysed primary outcomes according to their time point of measurement as follows: 1) at the end of the study period; and 2) at follow‐up: from three to 12 months after the study end. In cases where included studies reported ADLs in other measures than those mentioned above, all review authors discussed and reached consensus about the outcome measures to be included in the primary outcome analysis.

Secondary outcomes

In this update we defined secondary outcomes as upper limb function, lower limb function, muscle strength, cognitive abilities (including spatial neglect), dropouts and adverse events (including death from all causes), with appropriate measures as reported in the studies. We preferred interval‐scaled outcome measures rather than ordinal‐scaled or nominal‐scaled ones. We prioritised secondary outcome measures as follows.

For upper limb function:

Action Research Arm Test (ARAT) (Lyle 1981);
Fugl‐Meyer Score (Fugl‐Meyer 1975);
Nine‐Hole Peg Test (NHPT) (Sharpless 1982); and
Jebsen Taylor Hand Function Test (JTT) (Jebsen 1969).

For lower limb function:

walking velocity (in metres per second);
walking capacity (metres walked in six minutes); and
Functional Ambulation Categories (FAC) (Holden 1984).

For muscle strength:

grip force (measured by handheld dynamometer) (Boissy 1999); and
Motricity Index Score (Demeurisse 1980).

For cognitive abilities, such as working memory, attention and spatial neglect:

Montreal Cognitive Assessment (Nasreddine 2005);
Clock Drawing Test (Goodglass 1983);
Executive Function (Assessments have been described in Chung 2013);
target cancellation (Molenberghs 2011);
line bisection (Molenberghs 2011);
other measures of cognitive abilities; and
other measures of spatial neglect.

Depending on the measurements provided in the included trials, all review authors discussed and reached consensus about which outcome measures should be included in the analysis of secondary outcomes.

Search methods for identification of studies

See the 'Specialized register' section in the Cochrane Stroke Group module. We searched for relevant trials in all languages and arranged translation of trial reports where necessary.

Electronic searches

According to the increased scope of this update we re‐ran our searches with updated search strategies of the Cochrane Stroke Group Trials Register (March 2015) and the following electronic bibliographic databases.

Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2015, Issue 2) (Appendix 1).
MEDLINE (1948 to February 2015) (Appendix 2).
EMBASE (1980 to February 2015) (Appendix 3).
CINAHL (1982 to February 2015) (Appendix 4).
AMED (1985 to February 2015) (Appendix 5).
Science Citation Index (Web of Science) (1899 to February 2015) (Appendix 6).
Physiotherapy Evidence Database (PEDro) at http://www.pedro.org.au/ (March 2015) (Appendix 7).
Rehabdata at www.naric.com/?q=REHABDATA (1956 to March 2015) (Appendix 8).
Compendex (1969 to May 2013) (Appendix 9).
Inspec (1969 to March 2015) (Appendix 10).

We developed the MEDLINE search strategy with the help of the Cochrane Stroke Group Trials Search Co‐ordinator and adapted it for the other databases.

We also searched the following ongoing trials and research registers (June 2015).

Stroke Trials Registry (www.strokecenter.org/trials/).
Current Controlled Trials (www.controlled‐trials.com/).
ClinicalTrials.gov (http://clinicaltrials.gov).
EU Clinical Trials Register (www.clinicaltrialsregister.eu/).
WHO International Clinical Trials Registry Platform (http://apps.who.int/trialsearch/).

Searching other resources

We carried out the following additional searches to identify further published, unpublished and ongoing trials not available in the aforementioned databases.

Handsearched the following relevant conference proceedings, which had not already been searched by the Cochrane Stroke Group.
1. 3rd, 4th, 5th, 6th and 7th World Congress of NeuroRehabilitation (2002, 2006, 2008, 2010, 2012 and 2014).
2. 1st, 2nd, 3rd, 4th, 5th and 6th World Congress of Physical and Rehabilitation Medicine (2001, 2003, 2005, 2007, 2009, 2011 and 2013).
3. Deutsche Gesellschaft für Neurotraumatologie und Klinische Neurorehabilitation (2001 to 2014).
4. Deutsche Gesellschaft für Neurologie (2000 to 2014).
5. Deutsche Gesellschaft für Neurorehabilitation (1999 to 2014).
6. 1st, 2nd and 3rd Asian Oceania Conference of Physical and Rehabilitation Medicine (2008, 2010, 2012 and 2014).
Screened reference lists from relevant reviews, articles and textbooks.
Contacted authors of identified trials and other researchers in the field.
Used Science Citation Index Cited Reference Search for forward tracking of important articles.
Contacted the following equipment manufacturers (June 2015).
1. Activatek, Salt Lake City, USA (www.activatekinc.com).
2. Changsha Zhineng Electronics, Changsha City, Hunan, China (www.cszhineng.diytrade.com).
3. DJO Global, Vista, USA (www.djoglobal.com).
4. Grindhouse (www.grindhousewetware.com).
5. Magstim, Spring Gardens, UK (www.magstim.com).
6. Neuroconn, Ilmenau, Germany (www.neuroconn.de).
7. Neuroelectrics, Barcelona, Spain (www.neuroelectrics.com).
8. Newronika, Milano, Italy (www.newronika.it).
9. Soterix Medical, New York City, USA (www.soterixmedical.com).
10. Trans Cranial Technologies, Hong Kong (www.trans‐cranial.com).
Searched Google Scholar (http://scholar.google.com/) (June 2015).

Data collection and analysis

Selection of studies

One review author (BE) read the titles and abstracts of records identified by the electronic searches and eliminated obviously irrelevant studies. We retrieved the full‐text of the remaining studies, and two review authors (JK and BE) independently ranked the studies as relevant, possibly relevant or irrelevant according to our inclusion criteria (types of studies, participants and aims of interventions). Two review authors (JM and MP) then examined whether the possibly relevant publications fit the population, intervention, comparison, outcome (PICO) strategy of our study question. We included all trials rated as relevant, or possibly relevant, and excluded all trials ranked as irrelevant. We resolved disagreements by discussion with all review authors. If we needed further information to resolve disagreements concerning including or excluding a study, we contacted the trial authors and requested the required information. We recorded the selection process in sufficient detail to complete a PRISMA flow diagram (Moher 2009), and listed in the Characteristics of excluded studies table all studies that did not match our inclusion criteria regarding types of studies, participants and aims of interventions.

Data extraction and management

Two review authors (BE and JM) independently extracted trial and outcome data from the selected trials. If one of the review authors was involved in an included trial, another review author extracted trial and outcome data from that trial. In accordance with the 'Risk of bias' tool implemented in Review Manager 5 (RevMan 2014), we used checklists to independently assess:

methods of random sequence generation;
methods of allocation concealment;
blinding of assessors;
use of an intention‐to‐treat (ITT) analysis;
adverse effects and dropouts;
important differences in prognostic factors;
participants (country, number of participants, age, gender, type of stroke, time from stroke onset to study entry and inclusion and exclusion criteria);
comparison (details of interventions in treatment and control groups, duration of treatment and details of cointerventions in the groups);
outcomes; and
their time point of measurement.

Further, we extracted data on initial ADL ability or initial functional ability, or both.

BE and JM checked the extracted data for agreement. If necessary, we contacted trialists to obtain more information.

Assessment of risk of bias in included studies

Two review authors (JM and MP) independently assessed the risk of bias in the included trials according to Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). We assessed the risk of bias according to the following domains.

Random sequence generation.
Allocation concealment.
Blinding of participants and personnel.
Blinding of outcome assessment.
Incomplete outcome data.
Selective outcome reporting.
Other bias.

We judged each potential source of bias as high, low or unclear and provide a quote from the study report together with a justification for our judgement in the 'Risk of bias' table. We summarised the risk of bias judgements across different studies for each of the domains listed. We resolved disagreements in methodological assessment by reaching consensus through discussion by all review authors. We contacted trialists to ask for clarification and to request missing information.

Measures of treatment effect

For all outcomes that were continuous data, we entered means and standard deviations (SDs). We calculated a pooled estimate of the mean difference (MD) with 95% confidence intervals (CIs). If studies did not use the same outcomes, we calculated standardised mean differences (SMDs) instead of MDs. For all binary outcomes, we calculated risk differences (RDs) with 95% CIs. In case different scales measured the same outcome but in some scales a higher value indicated better performance and in other scales a lower value indicated better performance, we multiplied the values of the corresponding scales by ‐1 to ensure a consistent direction of the effect across all outcome measurements.

For all statistical comparisons we used the current version of Review Manager 5 (RevMan 2014).

Assessment of heterogeneity

We used the I² statistic to assess heterogeneity. We used a random‐effects model, regardless of the level of heterogeneity. Thus, when heterogeneity occurred, we could not violate the preconditions of a fixed‐effect model approach.

Data synthesis

GRADE and 'Summary of findings' table

We created two 'Summary of findings' tables using the following outcomes.

Primary outcome measure: ADLs at the end of the intervention period ‐ absolute values. Measures of activities of daily living. Scale from: 0 to infinity
Primary outcome measure: ADLs at the end of the intervention period ‐ change scores. Measures of activities of daily living. Scale from: 0 to infinity.
Primary outcome measure: ADLs until the end of follow‐up. Measures of activities of daily living. Scale from: 0 to infinity. Follow‐up: mean 3 months.
Secondary outcome measure: upper extremity function at the end of the intervention period ‐ absolute values. Clinical measures of upper extremity function. Scale from: 0 to infinity.
Secondary outcome measure: upper extremity function at the end of the intervention period ‐ change scores. Clinical measures of upper extremity function. Scale from: 0 to infinity.
Secondary outcome measure: upper extremity function to the end of follow‐up ‐ absolute values. Clinical measures of upper extremity function. Scale from: 0 to infinity. Follow‐up: mean 3 months.
Secondary outcome measure: dropouts, adverse events and deaths during the intervention period. Number of adverse events, dropouts and deaths during the intervention period.

We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta‐analyses for the prespecified outcomes (Atkins 2004). We used methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011c) using GRADEproGDT software (GRADEpro). We justified all decisions to down‐ or up‐grade the quality of studies using footnotes, and we made comments to aid the reader's understanding of the review where necessary.

Subgroup analysis and investigation of heterogeneity

If at least two studies were available for each group (tDCS/sham), we conducted planned analyses of the following subgroups for our primary outcome of ADL.

Duration of illness: acute/subacute phase (the first week after stroke and the second to the fourth week after stroke, respectively) versus the postacute phase (from the first to the sixth month after stroke) versus the chronic phase (more than six months after stroke).
Type of stimulation: cathodal versus anodal and position of electrodes/location of stimulation.
Type of control intervention: active (e.g. conventional therapy) versus passive (sham tDCS or no intervention).

All stratified (subgroup) analyses were accompanied by appropriate tests for interaction (statistical tests for subgroup differences as described in the Cochrane Handbook for Systematic Review of Interventions (Higgins 2011b), as implemented in Review Manager 5 (RevMan 2014).

Sensitivity analysis

We incorporated a post hoc sensitivity analysis for methodological quality to test the robustness of our results. We analysed concealed allocation, blinding of assessors, and ITT.

Results

Description of studies

Results of the search

2013 version

For the 2013 version of this review, we identified 6226 potentially relevant trials through electronic searching; we considered 92 full papers and included 15 trials with 455 participants (Boggio 2007a; Bolognini 2011; Fregni 2005a; Fusco 2013a; Geroin 2011; Hesse 2011; Khedr 2013; Kim 2009; Kim 2010; Lindenberg 2010; Mahmoudi 2011; Nair 2011; Qu 2009; Rossi 2013; Wu 2013a).

2015 version

In this update, we identified a total of 2295 records through the searches. After screening titles and abstracts, we obtained the full‐text of 52 articles. After further assessment, we determined that 17 new studies met the review inclusion criteria, and three studies are awaiting classification, as more information is required. We identified 55 ongoing pilot and large‐scale randomised trials with a cumulative estimated enrolment of 3339 participants (mean (SD) sample size: 65 (53); median sample size: 45; range of sample size: 6‐250). The majority of ongoing studies are performed in the USA, Brazil, Belgium, France, the Netherlands, and Germany.

The flow of references is shown in Figure 1.

Study flow diagram. Please note that the number of full‐texts is not necessarily equal to the number of studies (e.g. The studies Di Lazzaro 2014a and Di Lazzaro 2014b have been presented in a single full‐text. Moreover there often are several full‐texts of a single trial (e.g. as is the case for Hesse 2011 or Nair 2011).

Included studies

Design

We included 32 studies involving a total of 748 participants in the qualitative analysis (see Characteristics of included studies). All studies investigated the effects of transcranial direct current stimulation (tDCS) versus sham tDCS, except Cha 2014 and Qu 2009, which compared tDCS with physical therapy alone. Eleven trials with 105 participants were randomly assigned cross‐over trials (Au‐Yeung 2014; Boggio 2007a; Fregni 2005a; Fusco 2013a; Jo 2008; Kang 2008a; Kim 2009; Ko 2008; Mahmoudi 2011; Sohn 2013; Sunwoo 2013), whereas the remaining 21, with 643 participants, were RCTs (Ang 2012; Bolognini 2011; Cha 2014; Di Lazzaro 2014a; Di Lazzaro 2014b; Fusco 2014; Geroin 2011; Hesse 2011; Khedr 2013; Kim 2010; Lee 2014; Lindenberg 2010; Nair 2011; Park 2013; Qu 2009; Rossi 2013; Tahtis 2012; Tedesco Triccas 2015b; Viana 2014; Wang 2014; Wu 2013a).

Sample sizes

The sample sizes of included studies ranged from four in Boggio 2007a to 96 in Hesse 2011, with a mean (SD) sample size of 24 (23). The median sample size was 14.

Setting

Ten of the included studies were conducted in the Republic of Korea, six in Italy, three in the USA, three in China, two in Brazil, one in Iran, one in Egypt, one in the UK, one in Singapore, and one in Germany/Italy. In three studies, the country was not stated clearly.

Participants

The proportion of participants with ischaemic stroke ranged from 36% in Sohn 2013 to 100% in Fusco 2014. The mean age in the experimental groups ranged from 43 years in Bolognini 2011 to 70 years in Kang 2008a, and from 45 years in Qu 2009 to 75 years in the control groups (Boggio 2007a). The proportion of women participating in the included studies ranged from 0% in Au‐Yeung 2014 and Boggio 2007a to 71% in Bolognini 2011. See Table 6 for a comprehensive summary of participant characteristics.

1. Patient characteristics.

Study   ID

Experimental:   age,   mean (SD)

Control:   age,   mean (SD)

Experimental:   time   poststroke, mean (SD)

Control:   time   poststroke, mean (SD)

Experimental:   sex, n (%)

Control:   sex, n (%)

Experimental:   lesioned hemisphere,   n (%)

Control:   lesioned hemisphere, n (%)

Experimental:   severity,   mean (SD)

Control:
severity, mean (SD)

Experimental:   lesion cause/   location, n (%)

Control:   lesion cause/   location, n (%)

Handedness,   n (%)

Ang 2012

52 (12) years

56 (10) years

3 (2) years

3 (1) years

4 (40) female

1 (11) female

5 (50)

6 (67)

UE‐FM 35 (8)

UE‐FM 33 (8)

6 (60) ischaemic; 1 (10) cortical, 9 (90) subcortical

7 (78) ischaemic; 9 (100) subcortical

Not stated

Au‐Yeung 2014

63 (6) years

8 (3) years

0 female

5 (50) left

UE‐FM 58 (8); MMSE 29 (2)

8 (80) ischaemic

10 (100) right‐handed

Boggio 2007a

56 (11) years

75 (NA) years

33 (34) months

39 months

3 (100) male

1 (100) male

2 (67) left

1 (100) left

MRC 4.2 (0.53)

MRC 4.7 (NA)

3 (100) ischaemic and subcortical

1 (100) ischaemic and subcortical

12 (100) right‐handed

Bolognini 2011

43 (13) years

51 (15) years

44 (31)
months

26 (18) months

4 (57) female

5 (71) female

4 (57) left

BI 18.13 (2.42)

BI 14.33 (5.46)

2 (29) haemorrhagic, 5 (71) ischaemic

7 (100) ischaemic

14 (100) right‐handed

Cha 2014

60 (11) years

58 (10) years

14 (5) months

15 (4) months

Not stated

4 (40) left

5 (50) left

Brunnstrom 5 (1)

Not stated

Di Lazzaro 2014a

66 (16) years

71 (14) years

3 (1) days

2 (29) female

3 (43) female

3 (43) left

NIHSS 7 (5)

NIHSS 7 (4)

7 (100) ischaemic; 3 (43) subcortical; 4 (57) corticosubcortical

7 (100) ischaemic; 2 (29) subcortical, 5 (71) corticosubcortical

Not stated

Di Lazzaro 2014b

61 (16) years

69 (12) years

3 (2) days

3 (1) days

4 (40) female

6 (60) male

2 (20) left

6 (60) left

NIHSS 6 (3)

NIHSS 6 (2)

10 (100) ischaemic; 4 (40) subcortical, 6 (60) corticosubcortical

Not stated

Fregni 2005a

54 (17) years

27 (24) months

2 (33) female

3 (50) left

MRC 4.18 (0.37)

Cause not clearly stated by the authors

6 (100) right‐handed

Fusco 2013a

44 (16) years

65 (22) years

31 (13) days

25 (5) days

3 (60) female

1 (25) female

3 (60) left

2 (50) left

Grasp force 17.83 (7.45) kg

5 (100) ischaemic

3 (75) ischaemic, 1 (25) haemorrhagic

9 (100) right‐handed

Fusco 2014

56 (15) years

60 (12) years

19 (8) days

3 (60) female

3 (50) female

2 (40) left

2 (33) left

BI 33 (22)

BI 51 (34)

5 (100) ischaemic

6 (100) ischaemic

9 (73) right‐handed

Geroin 2011

64 (7) years

63 (6) years

26 (6) months

27 (5) months

2 (20) female

4 (40) female

Not stated by the authors

ESS 79.6 (4.1)

ESS 79.6 (2.7)

10 (100) ischaemic;
4 (40) cortical, 3 (30) corticosubcortical, 3 (30) subcortical

10 (100) ischaemic;  5 (50) cortical, 3 (30) corticosubcortical, 2 (20) subcortical

Not stated by the authors

Hesse 2011

65 (10) years

66 (10) years

4 (2) weeks

26 (41) female

11 (34) female

35 (55) left

16 (50) left

BI 34.15 (6.97); UE‐FM 7.85 (3.58)

BI 35.0 (7.8); UE‐FM 8.2 (4.4)

64 (100) ischaemic; 29 (45) TACI, 20 (31) PACI, 15 (23) LACI

32 (100) ischaemic; 13 (41) TACI, 13 (41) PACI, 6 (18) LACI

Not stated by the authors

Jo 2008

48 (9) years

2 (1) months

3 (30) female

10 (100) right

Not reported

4 (40) ischaemic

Not stated by the authors

Kang 2008a

70 (3) years

544 (388) days

4 (40) female

7 (70) right

21 (1) MMSE

7 (70) ischaemic

Not stated by the authors

Khedr 2013

59 (9) years

57 (8) years

13 (5) days

9 (33) female

5 (38) female

12 (44) left

6 (46) left

BI 32.76 (10.75)

BI 31.1 (12.6)

27 (100) ischaemic; 12 (44) cortical, 5 (19) corticosubcortical, 10 (37) subcortical

13 (100) ischaemic; 6 (42) cortical, 3 (23) corticosubcortical, 4 (31) subcortical

Not stated by the authors

Kim 2009

63 (13) years

6 (3) weeks

7 (70) female

8 (80) left

MRC between 3 and 5 for the all paretic finger flexors and extensors

8 (80) infarction, 2 (20) haemorrhage

Not stated by the authors

Kim 2010

54 (15) years

63 (9) years

27 (21) days

23 (8) days

2 (18) female

3 (43) female

7 (64) left

2 (29) left

BI 71.77 (23.86)  UE‐FM 34.7 (15.0)

BI 67.9 (22.4)  UE‐FM 41.0 (13.0)

11 (100) ischaemic;
3 (27) cortical, 3 (27) corticosubcortical, 5 (71) subcortical

7 (100) ischaemic;  2 (29) cortical, 1 (14) corticosubcortical, 4 (57) subcortical

Not stated by the authors

Ko 2008

62 (9) years

29‐99 days

5 (33) female

15 (100) right

19 per cent deviation (11)

10 (66) ischaemic

15 (100) right‐handed

Lee 2014

62 (11) years

61 (14) years

18 (8) days

17 (6) days

17 (44) female

9 (45) female

19 (49) left

13 (65)

UE‐FM 37 (23)

UE‐FM 35 (22)

21 (54) ischaemic; 21 (54) cortical; 18 (46) subcortical

14 (70) ischaemic; 10 (50) cortical; 10 (50) subcortical

Not stated by the authors

Lindenberg 2010

62 (15) years

56 (13) years

31 (21) months

40 (23) months

2 (20) female

3 (30) female

6 (60) left

7 (70) left

UE‐FM 38.2 (13.3)

UE‐FM 39.8 (11.5)

10 (100) ischaemic

19 (95) right‐handed, 1 (5) both‐handed

Mahmoudi 2011

61 (14) years

8 (5) months

3 (33) female

6 (60) left, 3 (30) right, 1 (10) brainstem

JTT (without handwriting): 12.3 (7.3) s

10 (100) ischaemic

Not stated by the authors

Nair 2011

61 (12) years

56 (15) years

33 (20) months

28 (28) months

2 (29) female

3 (43) female

3 (43) left

5 (71) left

UE‐FM 30 (11)

UE‐FM 31 (10)

7 (100) ischaemic;  5 (71) cortical and corticosubcortical, 2 (29) subcortical

7 (100) ischaemic;  4 (56) cortical and corticosubcortical, 3 (43) subcortical

14 (100) right‐handed

Park 2013

65 (14) years

66 (11) years

29 (19) days

25 (17) days

6 (67) female

2 (40) female

2 (33) left

2 (40) left

NIHSS 8 (3)

NIHSS 10 (3)

4 (67) ischaemic

3 (60) ischaemic

Not stated by the authors

Qu 2009

45 (11) years

45 (14) years

6 (range 3 to 36) months

4 (range 3 to 12) months

4 (16) female

3 (12) female

14 (56) left

13 (52) left

BI 64 (17)

BI 72 (22)

10 (40) haemorrhagic, 15 (60) infarction

Not stated by the authors

Rossi 2013

66 (14) years

70 (14) years

2 days

13 (52) female

11 (44) female

18 (72) left

16 (64) left

UE‐FM 4.1 (6.4)

FM 4.6 (7.8)

25 (100) ischaemic;  1 (4) cortical, 17 (68) corticosubcortical, 7 (28) subcortical

25 (100) ischaemic; 2 (8) cortical, 18 (72) corticosubcortical, 5 (20) subcortical

Not stated by the authors

Sohn 2013

58 (15) years

63 (17) days

2 (18) female

6 (55) left

Not stated by the authors

4 (36) ischaemic

Not stated by the authors

Sunwoo 2013

63 (13) years

28 (60) months

6 (60) female

10 (100) left

MMSE 28 (2)

7 (70) ischaemic

10 (100) right‐handed

Tahtis 2012

67 (12) years

56 (12) years

20 (5) days

25 (11) days

2 (29) female

1 (14) female

3 (43) left

MRS 2 (1)

MRS 3 (1)

7 (100) ischaemic; 4 (57) cortical, 3 (43) subcortical

7 (100) ischaemic; 3 (43) cortical; 4 (57) subcortical

Not stated by the authors

Tedesco Triccas 2015b

64 (10) years

63 (14) years

25 (31) months

13 (16) months

5 (42) female

4 (33) female

6 (50) left

5 (45) left

UE‐FM 28 (19)

UE‐FM 37 (14)

3 (25) ischaemic; 3 (25) cortical, 9 (75) subcortical

9 (81) ischaemic; 4 (36) cortical; 7 (64) subcortical

22 (96) right‐handed

Viana 2014

56 (10) years

55 (12) years

32 (18) months

35 (20) months

1 (10) female

3 (30) female

5 (50) left

3 (30) left

UE‐FM 41 (16)

UE‐FM 39 (17)

9 (90) ischaemic

10 (100) ischaemic

19 (95) right‐handed

Wang 2014

54 (14) years

52 (9) years

Not explicitly stated, but all participants were enrolled between 1 and 4 weeks poststroke

1 (16) female

1 (33) female

2 (33) left

0 left

FIM 59 (18)

FIM 74 (8)

6 (100) ischaemic

3 (100) ischaemic

Not stated by the authors

Wu 2013a

46 (11) years

49 (13) years

5 (3) months

11 (24) female

10 (22) female

24 (53) left

23 (51) left

BI 55 (range 0 to 85)  UE‐FM 12.3 (5.5)

BI 55 (range 25 to 95)  UE‐FM 11.8 (8.2)

27 (60) ischaemic, 18 (40) haemorrhagic

26 (58) ischaemic, 19 haemorrhagic (42)

Not stated by the authors

Study   ID	Type of intervention/   stimulation (polarity)	Electrode position and size	Reference electrode position	Treatment intensity		Base treatment	Dropouts	Adverse events	Source of information
Ang 2012	Dual‐tDCS	Saline‐soaked sponge electrodes with the anode placed over M1 of the affected hemisphere and the cathode placed over M1 the unaffected hemisphere (size not stated)		1 mA for 20 minutes	20 minutes of Dual‐tDCS or sham tDCS followed by 8 minutes of evaluation prior to base treatment	60 minutes of therapy using EEG‐based MI‐BCI with robotic feedback with the MIT‐Manus 5 times a week for 2 weeks	None	Not described by the authors	Published
	Sham tDCS			1 mA for 30 seconds
Au‐Yeung 2014	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	1 mA for 20 minutes	A‐tDCS, C‐tDCS and sham tDCS once in random order with at least 5 days wash‐out period	None	None	Not described by the authors	Published
	C‐tDCS	Saline‐soaked 35 cm² sponge electrodes over the M1 of the non‐lesioned hemisphere		1 mA for 20 minutes
	Sham tDCS	Saline‐soaked 35 cm² sponge electrodes over M1 of both hemispheres		1 mA for 10 seconds
Boggio 2007a	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	1 mA for 20 minutes	A‐tDCS, C‐tDCS or sham tDCS 4 days once a day	None	None	None	Published
	C‐tDCS	Saline‐soaked 35 cm² sponge electrodes over the M1 of the non‐lesioned hemisphere
	Sham tDCS	Not described by the authors		1 mA for 30 seconds
Bolognini 2011	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes; with the anode placed over M1 of the lesioned hemisphere and the cathode over M1 of the non‐lesioned hemisphere		2 mA for 40 minutes	Base treatment + A‐tDCS or sham tDCS 5 days a week for 2 consecutive weeks	CIMT up to 4 hours/day for 5 days a week for 2 consecutive weeks	7 (33%) due to frustration and tiredness during assessments (Bolognini 2013 [pers comm]); these participants have been excluded from analysis and presentation of results	None	Published and unpublished
	Sham tDCS			2 mA for 30 seconds
Cha 2014	A‐tDCS	Water‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	1 mA for 20 minutes	Base treatment + A‐tDCS for 20 minutes	Basic training for improving function of upper and lower extremities for 30 minutes per day, 5 times a week for four weeks	None	Not reported	Published
	PT	NA		NA	NA
Di Lazzaro 2014a	Dual‐tDCS	anode over M1 of the lesioned hemisphere and cathode over M1 of the non‐lesioned hemisphere,		2 mA for 40 min	Dual‐tDCS or sham tDCS on 5 continuous days	None	None	Not reported	Published
	Sham tDCS			2 mA for 30 sec
Di Lazzaro 2014b	Dual‐tDCS	anode over M1 of the lesioned hemisphere and cathode over M1 of the non‐lesioned hemisphere,		2 mA for 40 min	Base treatment + dual‐tDCS or sham tDCS on 5 continuous days	CIMT for at least 90% of waking hours, including 1.5 hours per day arm training	None	Not reported	Published
	Sham tDCS			2 mA for 30 sec
Fusco 2013a	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	1.5 mA for 15 minutes	1 active tDCS (A‐tDCS, C‐tDCS, dual‐tDCS) and 1 sham tDCS session in 2 consecutive days	None	None	None	Published and unpublished
	C‐tDCS	Saline‐soaked 35 cm² sponge electrodes over the M1 of the non‐lesioned hemisphere		1.5 mA for 15 minutes
	Dual‐tDCS	Saline‐soaked 35 cm² sponge electrodes with the anode over M1 of the lesioned hemisphere and the cathode over M1 of the non‐lesioned hemisphere		1.5 mA for 15 minutes
	Sham tDCS	Not described by the authors
Fusco 2014	C‐tDCS	Saline‐soaked 35 cm² gel‐sponge electrodes with the cathode over M1 of the non‐lesioned hemisphere	Above the  right shoulder	1.5 mA for 10 min	Each participant underwent C‐tDCS and sham tDCS on 5 consecutive days each week for 2 weeks prior to a rehabilitative session in randomised order	Patient‐tailored motor rehabilitation focusing on recovery of upper limb for 45 minutes twice a day	2 (14%); reasons not described by the authors	Not reported	Published
	Sham tDCS			not described			1 (7%); emergency transfer to another hospital
Fregni 2005a	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	1 mA for 20 minutes	Each participant underwent A‐tDCS, C‐tDCS and sham tDCS once, separated by at least 48 hours of rest	None	None	None	Published
	C‐tDCS	Saline‐soaked 35 cm² sponge electrodes over the M1 of the non‐lesioned hemisphere		1 mA for 20 minutes
	Sham tDCS	Not described by the authors		1 mA for 30 seconds
Geroin 2011	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	1.5 mA for 7 minutes	Base treatment + A‐tDCS or sham tDCS 5 days a week for 2 consecutive weeks	50‐minute training sessions 5 days a week for 2 consecutive weeks, consisting of 20 minutes of robot‐assisted gait training and 30 minutes of lower limb strength and joint mobilisation training	None	None	Published
	Sham tDCS			0 mA for 7 minutes
Hesse 2011	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	2 mA for 20 minutes	Base treatment + A‐tDCS, C‐tDCS or sham tDCS 5 days a week for 6 consecutive weeks	20 minutes of robot‐assisted arm training 5 days a week for 6 consecutive weeks	11 (11%); 7 dropouts in the EXP‐groups: 1 (14%) during intervention period due to pneumonia and 6 (86%) until 3 months of follow‐up (2 deaths due to myocardial infarction and stent surgery, 3 due to being unavailable and 1 due to refusal of further enrolment); 4 dropouts in the CTL group: 3 (75%) due to being not available and 1 (25%) due to refusal of further enrolment	None	Published
	C‐tDCS	Saline‐soaked 35 cm² sponge electrodes over M1 of the non‐lesioned hemisphere		2 mA for 20 minutes
	Sham tDCS	As in the A‐tDCS or the C‐tDCS group (changing consecutively)		0 mA for 20 minutes
Jo 2008	A‐tDCS	Saline‐soaked 25 cm² sponge electrodes over DLPFC of the non‐lesioned hemisphere	Over the contralateral supraorbital forehead	2 mA for 30 minutes	A‐tDCS once and sham tDCS once or vice versa, separated by at least 48 hours of resting period	None	None	6 Quote: "Transient aching or burning sensations were reported in six cases, and transient skin redness at the electrode contact site was reported in three cases."	Published
	Sham tDCS			2 mA for 10 seconds
Kang 2008a	A‐tDCS	25 cm² electrodes over the left DLPFC	Over the contralateral supraorbital forehead	2 mA for 20 minutes	A‐tDCS and sham tDCS or vice versa, separated by at least 48 hours of resting period	None	Not described	Not described	Published
	Sham tDCS	25 cm² electrodes over the left DLPFC	Over the contralateral supraorbital forehead	2 mA for 1 minute
Khedr 2013	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	2 mA for 25 minutes	Base treatment + A‐tDCS, C‐tDCS or sham tDCS for 6 consecutive days after	Rehabilitation program within 1 hour after each tDCS session, starting with passive movement and range of motion exercise up to active resistive exercise	None	None	Published
	C‐tDCS	Saline‐soaked 35 cm² sponge electrodes, cathode over M1 of the non‐lesioned hemisphere	Over the contralateral supraorbital forehead	2 mA for 25 minutes
	Sham tDCS	Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	2 mA for 2 minutes
Kim 2009	A‐tDCS	Saline‐soaked 25 cm² sponge electrodes, anode over M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	1 mA for 20 minutes	Each participant underwent A‐tDCS and sham tDCS, separated by at least 24 hours of rest	None	None	None	Published and unpublished
	Sham tDCS			1 mA for 30 seconds
Kim 2010	A‐tDCS	Saline‐soaked 25 cm² sponge electrodes over M1 of the lesioned hemisphere (as confirmed by MEP)	Over the contralateral supraorbital forehead	2 mA for 20 minutes	Base treatment + A‐tDCS, C‐tDCS or sham tDCS 5 days a week for 2 consecutive weeks at the beginning of each therapy session	Occupational therapy according to a standardised protocol aimed at improving paretic hand function for 30 minutes 5 days a week for 2 consecutive weeks	2 of 20; 1 participant discontinued treatment because of dizziness and another because of headache (authors did not state corresponding groups)	2	Published
	C‐tDCS	Saline‐soaked 25 cm² sponge electrodes over M1 of the non‐lesioned hemisphere (confirmed by MEP)	Over the contralateral supraorbital forehead	2 mA for 20 minutes
	Sham tDCS	Saline‐soaked 25 cm² sponge electrodes over M1 of the lesioned hemisphere (confirmed by MEP)	Over the contralateral supraorbital forehead	2 mA for 1 minutes
Ko 2008	A‐tDCS	Saline‐soaked 25 cm² surface sponge electrodes over right (lesioned) PPC	Over the contralateral supraorbital forehead Over the contralateral supraorbital forehead	2 mA for 20 minutes	A‐tDCS once and sham tDCS once or vice versa, separated by at least 48 hours of resting period	None	Not described	None	Published
	Sham tDCS			2 mA for 10 seconds
Lee 2014	C‐tDCS	Saline‐soaked 25 cm² surface sponge electrodes over hand area of M1 of the non‐lesioned hemisphere	Over the contralateral supraorbital forehead	2 mA for 20 minutes	20 minutes per day, 5 times per week for 3 weeks	Occupational therapy for 30 minutes per day, 5 times per week for 3 weeks	3 of 42 (7%); 2 medical problems; 1 refused to participate	No major adverse events	Published
						Virtual reality therapy for 30 minutes per day, 5 times per week for 3 weeks
	Virtual Reality	NA		NA	NA	Virtual reality only for 30 minutes per day, 5 times per week for 3 weeks	2 of 22 (9%); 1 refused to participate; 1 early discharge
Lindenberg 2010	Dual‐tDCS	Saline‐soaked 16.3 cm² sponge electrodes with the anode over M1 of the lesioned hemisphere and the cathode over M1 of the non‐lesioned hemisphere		1.5 mA for 30 minutes	Base treatment + dual‐tDCS or sham tDCS at 5 consecutive sessions on 5 consecutive days	Physical and occupational therapy sessions at 5 consecutive sessions on 5 consecutive days for 60 minutes, including functional motor tasks	None	None	Published
	Sham tDCS			1.5 mA for 30 seconds
Mahmoudi 2011	A‐tDCS1	Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere	Over the contralateral orbit	1 mA for 20 minutes	Each participant underwent A‐tDCS1, A‐tDCS2, C‐tDCS, dual‐tDCS and sham tDCS once with a wash‐out period of at least 96 hours	None	None	Not clearly stated, most likely none	Published
	A‐tDCS2	Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere	On the contralateral deltoid muscle	1 mA for 20 minutes
	C‐tDCS	Saline‐soaked 35 cm² sponge electrodes, cathode over M1 of the non‐lesioned hemisphere	Over M1 of the lesioned hemisphere	1 mA for 20 minutes
	Dual‐tDCS	Saline‐soaked 35 cm² sponge electrodes with the anode over M1 of the lesioned hemisphere and the cathode over M1 of the non‐lesioned hemisphere		1 mA for 20 minutes
	Sham tDCS	Not described by the authors		1 mA for 30 seconds
Nair 2011	C‐tDCS	Saline‐soaked sponge electrodes with the cathode over M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	1 mA for 30 minutes	Base‐treatment + C‐tDCS or sham tDCS for 5 consecutive daily sessions, each at the beginning of the base treatment sessions	Occupational therapy (PNF; shoulder abduction, external rotation, elbow extension, forearm pronation) for 5 consecutive daily sessions (60 minutes each)	None	None	Published
	Sham tDCS	Not described by the authors		For 30 minutes
Park 2013	A‐tDCS	Sponge electrodes with the anode positioned over the bilateral prefrontal cortex	at the non‐dominant arm	2 mA for 30 minutes	Base‐treatment + A‐tDCS or sham tDCS for 5 days a week for approximately 18 days	Computer‐assisted cognitive rehabilitation (CACR) with the ComCog program (15 minute attention and 15 minute memory training)	Unclear	None	Published
	Sham tDCS			2 mA for 30 seconds
Qu 2009	C‐tDCS	Saline‐soaked 18 cm² sponge electrodes over primary sensorimotor cortex of the lesioned hemisphere	Unclear	0.5 mA for 20 minutes, once a day for 5 consecutive days for 4 weeks		NA	None	None	Published
	PT	NA		Physical therapy according to the Bobath, Brunnstrom and Rood approaches for 40 minutes twice a day for 5 consecutive days for 4 weeks
Rossi 2013	A‐tDCS	Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere	Over the contralateral supraorbital forehead	2 mA for 20 minutes	Once a day for 5 consecutive days	Not described by the authors	None	None	Published
	Sham tDCS			2 mA for 30 seconds
Sohn 2013	A‐tDCS	25 cm² sponge electrodes over M1 of the affected hemisphere	Not described	2 mA for 10 minutes	A‐tDCS or sham tDCS once	None	Unclear	Unclear	Published
	Sham tDCS			2 mA for 20 seconds
Sunwoo 2013	Dual‐tDCS	Saline‐soaked 25 cm² sponge electrodes over the right posterior parietal cortex (PPC) plus cathodal tDCS over the left PPC	Over the contralateral supraorbital forehead	1 mA for 20 minutes	Each participant underwent dual‐tDCS, A‐tDCS and sham tDCS once with a wash‐out period of at least 24 hours	None	None	3 (30%) suffered from mild headache after dual‐tDCS, which disappeared spontaneously	Published
	A‐tDCS	Saline‐soaked 25 cm² sponge electrodes over the right PPC plus sham tDCS over the left PPC		For A‐tDCS: 1 mA for 20 minutes For sham tDCS: 1 mA for 10 seconds
	Sham tDCS	Saline‐soaked 25 cm² sponge electrodes over the right PPC plus sham tDCS over the left PPC		1 mA for 10 seconds
Tahtis 2012	Dual‐tDCS	Saline‐soaked 25 cm² electrodes with the anode placed over the leg area of the lesioned hemisphere and the cathode placed over leg area of the non‐lesioned hemisphere	Not described	2 mA for 15 minutes	Dual‐tDCS or sham tDCS once	None	Unclear	None	Published
	Sham tDCS			2 mA for < 30 seconds
Tedesco Triccas 2015b	A‐tDCS	Saline‐soaked  35 cm² sponge electrodes with the anode placed over M1 of the affected hemisphere	Over the contralateral supraorbital forehead	1 mA for 20 minutes	Base therapy plus tDCS or sham tDCS for 18 sessions during 8 weeks (approximately 2 to 3 sessions per week)	Robotic arm training with the ArmeoSpring device (60 minutes per session) for 18 sessions during 8 weeks (approximately 2 to 3 sessions per week)	1 out of 12 (8%) in the A‐tDCS group due to a skin reaction after receiving four sessions of A‐tDCS	6 out of 12 (50%) in the A‐tDCS group reported adverse events such as pain, burning or headache after receiving A‐tDCS	Published/unpublished
	Sham tDCS			1 mA for 20 seconds
Viana 2014	A‐tDCS	Saline‐soaked  35 cm² sponge electrodes with the anode placed over M1 of the affected hemisphere	Over the contralateral supraorbital forehead	2 mA for 13 minutes	Base therapy + A‐tDCS or sham tDCS 3 times a week for 5 weeks	Virtual reality training using Nintendo Wii (Games used: Wii Sports resort, Wii Play Motion, Let's Tap) aiming at movements of shoulder, elbow, wrist, hand and fingers; each game was played for 15 minutes (total time per training session: 60 minutes); passive stretching exercises were performed before and after each training session	None	None	Published
	Sham tDCS			2 mA for 30 seconds
Wang 2014	Dual‐tDCS	35 cm² electrodes with the anode placed over M1 of the affected hemisphere	Over contralateral M1	1 mA for 20 minutes	Dual‐tDCS or sham‐tDCS once	Placebo methylphenidate 1 hour prior to stimulation	Unclear	No major adverse events; 3 participants (50%) from the dual‐tDCS group reported mild tingling sensation with tDCS stimulation	Published
						20 mg MP 1 hour prior to stimulation
	Sham‐tDCS			1 mA for 10 seconds
Wu 2013a	C‐tDCS	Saline‐soaked 24.75 cm² sponge electrodes over primary sensorimotor cortex of the lesioned hemisphere	Over the shoulder on the unaffected side	1.2 mA for 20 minutes	Once daily 5 days a week for 4 weeks	Quote: "Both groups received a conventional physical therapy program for 30 minutes twice daily, including maintaining good limb position, chronic stretching via casting or splinting, physical  modalities and techniques, and movement training"	None	None	Published
	Sham tDCS			1.2 mA for 30 seconds

tDCS versus any type of placebo or passive control intervention for improving function, and activities of daily living, cognitive abilities and neglect in people after stroke
Patient or population: people with improving function, and activities of daily living, cognitive abilities and neglect after stroke  Settings: unspecified  Intervention: tDCS versus any type of placebo or passive control intervention
Outcomes	*Illustrative comparative risks (95% CI): Corresponding risk tDCS versus any type of placebo or passive control intervention**			No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
Primary outcome measure: ADLs at the end of the intervention period ‐ absolute values   Measures of activities of daily living. Scale from: 0 to infinity	The mean primary outcome measure: ADLs at the end of the intervention period ‐ absolute values in the intervention groups was  0.24 standard deviations higher   (0.03 to 0.44 higher)			396  (9 studies)	⊕⊕⊕⊝  moderate¹	SMD 0.24 (0.03 to 0.44); however, this effect was not sustained when including only studies with adequate allocation concealment (Table 8)
Primary outcome measure: ADLs at the end of the intervention period ‐ change scores   Measures of activities of daily living. Scale from: 0 to infinity.	The mean primary outcome measure: ADLs at the end of the intervention period ‐ change scores in the intervention groups was  0.46 standard deviations higher   (0.75 lower to 1.67 higher)			11  (1 study)	⊕⊝⊝⊝  very low^1,2,3	SMD 0.46 (‐0.75 to 1.67)
Primary outcome measure: ADLs until the end of follow‐up   Measures of activities of daily living. Scale from: 0 to infinity Follow‐up: mean 3 months	The mean primary outcome measure: ADLs until the end of follow‐up in the intervention groups was  0.31 standard deviations higher   (0.01 to 0.62 higher)			269  (6 studies)	⊕⊕⊕⊝  moderate⁴	SMD 0.31 (0.01 to 0.62); however, this effect was not sustained when including only studies with adequate allocation concealment (Table 9)
Secondary outcome measure: upper extremity function at the end of the intervention period ‐ absolute values Clinical measures of upper extremity function. Scale from: 0 to infinity	The mean secondary outcome measure: upper extremity function at the end of the intervention period ‐ absolute values in the intervention groups was  0.11 standard deviations higher   (0.17 lower to 0.39 higher)			431  (12 studies)	⊕⊕⊝⊝  low^1,2	SMD 0.11 (‐0.17 to 0.39)
Secondary outcome measure: upper extremity function at the end of the intervention period ‐ change scores Clinical measures of upper extremity function. Scale from: 0 to infinity	The mean secondary outcome measure: upper extremity function at the end of the intervention period ‐ change scores in the intervention groups was  0.32 standard deviations higher   (0.51 lower to 1.15 higher)			53  (4 studies)	⊕⊕⊝⊝  low^1,2	SMD 0.32 (‐0.51 to 1.15)
Secondary outcome measure: upper extremity function to the end of follow‐up ‐ absolute values Clinical measures of upper extremity function. Scale from: 0 to infinity Follow‐up: mean 3 months	The mean secondary outcome measure: upper extremity function to the end of follow‐up ‐ absolute values in the intervention groups was  0.01 standard deviations higher   (0.48 lower to 0.50 higher)			187  (4 studies)	⊕⊕⊝⊝  low^2,3	SMD 0.01 (‐0.48 to 0.50)
Secondary outcome measure: dropouts, adverse events and deaths during the intervention period Number of adverse events, dropouts and deaths during the intervention period	Study population		See comment	664  (23 studies)	⊕⊕⊝⊝  low^1,2	Risks were calculated from pooled risk differences
	20 per 1000	48 per 1000   (10 to 80)
	Moderate
	0 per 1000	0 per 1000   (0 to 0)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  ADL: activities of daily living; CI: Confidence interval; SMD: standardised mean difference; tDCS: transcranial direct current stimulation
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

tDCS versus any type of active control intervention for improving function activities of daily living, cognitive abilities and neglect in people after stroke
Patient or population: people with improving function, activities of daily living, cognitive abilities and neglect after stroke  Settings: unspecified  Intervention: tDCS versus any type of active control intervention
Outcomes	*Illustrative comparative risks (95% CI) Corresponding risk tDCS versus any type of active control intervention**			No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
Primary outcome measure: ADLs at the end of the intervention period, absolute values   Measures of activities of daily living. Scale from: 0 to 100	The mean primary outcome measure: ADLs at the end of the intervention period, absolute values in the intervention groups was  0 higher   (10.04 lower to 10.04 higher)			50  (1 study)	⊕⊝⊝⊝  very low^1,2,3
Secondary outcome measure: upper extremity function at the end of the intervention period  Clinical measures of upper extremity function. Scale from: 0 to 66	The mean secondary outcome measure: upper extremity function at the end of the intervention period in the intervention groups was  19 higher   (9.38 to 28.62 higher)			20  (1 study)	⊕⊕⊝⊝  low^1,2
Secondary outcome measure: lower extremity function at the end of the intervention period   Clinical measures of lower extremity function. Scale from: 0 to 34	The mean secondary outcome measure: lower extremity function at the end of the intervention period in the intervention groups was  5.3 higher   (0.75 to 9.85 higher)			20  (1 study)	⊕⊕⊝⊝  low^1,2
Secondary outcome measure: dropouts, adverse events and deaths during the intervention period  Adverse events, dropouts and deaths during the intervention period	Study population		See comment	70  (2 studies)	See comment	Risks were calculated from pooled risk differences
	See comment	See comment
	Moderate
	0 per 1000	‐2147483648 per 1000   (‐2147483648 to ‐2147483648)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  ADL: activities of daily living; CI: Confidence interval; tDCS: transcranial direct current stimulation
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Sensitivity analysis	Studies included in analysis	Effect estimate
All studies with proper allocation concealment	Hesse 2011; Khedr 2013; Kim 2010; Tedesco Triccas 2015b; Wu 2013a	(SMD 0.24, 95% CI ‐0.07 to 0.56; participants = 290; studies = 5; I² = 36%; inverse variance method with random‐effects model)
All studies with proper blinding of outcome assessor for primary outcome absolute values	Bolognini 2011; Di Lazzaro 2014a; Di Lazzaro 2014b; Hesse 2011; Khedr 2013; Kim 2010; Lee 2014; Tedesco Triccas 2015b; Wu 2013a	(SMD 0.24, 95% CI 0.03 to 0.44; participants = 396; studies = 9; I² = 0%; inverse variance method with random‐effects model)
All studies with proper blinding of outcome assessor for primary outcome change values	Fusco 2014	(SMD 0.46, 95% CI ‐0.75 to 1.67; participants = 11; studies = 1; I² = 0%; inverse variance method with random‐effects model)
All studies with intention‐to‐treat analysis	Di Lazzaro 2014a; Di Lazzaro 2014b; Hesse 2011; Khedr 2013; Wu 2013a	(SMD 0.31, 95% CI 0.05 to 0.56; participants = 259; studies = 5; I² = 0%; inverse variance method with random‐effects model)

Date	Event	Description
28 September 2015	New citation required and conclusions have changed	The conclusions have changed: there is evidence of an effect of transcranial direct current stimulation for improving activities of daily living, but not for arm function.
28 September 2015	New search has been performed	The scope of the updated review has broadened since the previous version. This was in response to a request from the Cochrane Stroke Group to incorporate evidence relating to cognitive function (including neglect) into this update. We have rerun and expanded the searches to February 2015 and revised the text as appropriate. We have included 32 trials involving 748 participants in this update compared with 15 trials with 455 participants in the last version of this review from 2013.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Primary outcome measure: ADLs at the end of the intervention period	10		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1 Absolute values	9	396	Std. Mean Difference (IV, Random, 95% CI)	0.24 [0.03, 0.44]
1.2 Change scores	1	11	Std. Mean Difference (IV, Random, 95% CI)	0.46 [‐0.75, 1.67]
2 Primary outcome measure: ADLs until the end of follow‐up	6	269	Std. Mean Difference (IV, Random, 95% CI)	0.31 [0.01, 0.62]
3 Secondary outcome measure: upper extremity function at the end of the intervention period	16		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
3.1 Absolute values	12	431	Std. Mean Difference (IV, Random, 95% CI)	0.11 [‐0.17, 0.39]
3.2 Change scores	4	53	Std. Mean Difference (IV, Random, 95% CI)	0.32 [‐0.51, 1.15]
4 Secondary outcome measure: upper extremity function to the end of follow‐up	5		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
4.1 Absolute values	4	187	Std. Mean Difference (IV, Random, 95% CI)	0.01 [‐0.48, 0.50]
4.2 Change scores	1	18	Std. Mean Difference (IV, Random, 95% CI)	1.49 [0.40, 2.59]
5 Secondary outcome measure: lower extremity function at the end of the intervention period	4		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
5.1 Absolute values	2	50	Std. Mean Difference (IV, Random, 95% CI)	0.20 [‐1.26, 1.67]
5.2 Change scores	2	25	Std. Mean Difference (IV, Random, 95% CI)	0.81 [‐0.02, 1.65]
6 Secondary outcome measure: muscle strength at the end of the intervention period	10		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
6.1 Absolute values	8	272	Std. Mean Difference (IV, Random, 95% CI)	0.14 [‐0.11, 0.38]
6.2 Change values	2	41	Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐2.12, 2.23]
7 Secondary outcome measure: muscle strength at the end of follow‐up	3	156	Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.26, 0.41]
8 Secondary outcome measure: cognitive abilities at the end of the intervention period	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
9 Secondary outcome measure: dropouts, adverse events and deaths during the intervention period	23	664	Risk Difference (M‐H, Random, 95% CI)	0.01 [‐0.02, 0.03]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Planned analysis: duration of illness ‐ acute/subacute phase versus postacute phase for ADLs at the end of the intervention period	10		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1 Acute/subacute phase (the first week after stroke and the second to the fourth week after stroke	4	213	Std. Mean Difference (IV, Random, 95% CI)	0.22 [‐0.07, 0.51]
1.2 Postacute phase (from the first to the sixth month after stroke)	2	140	Std. Mean Difference (IV, Random, 95% CI)	0.30 [‐0.22, 0.82]
1.3 Chronic phase (from the sixth month after stroke)	4	93	Std. Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.41, 0.40]
2 Planned analysis: effects of type of stimulation (A‐tDCS/C‐tDCS/dual‐tDCS) and location of stimulation (lesioned/non‐lesioned hemisphere) on ADLs at the end of the intervention period (study groups collapsed)	10		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
2.1 A‐tDCS over the lesioned hemisphere	5	164	Std. Mean Difference (IV, Random, 95% CI)	‐0.04 [‐0.35, 0.27]
2.2 C‐tDCS over the lesioned hemisphere	6	301	Std. Mean Difference (IV, Random, 95% CI)	0.33 [0.10, 0.57]
2.3 Dual‐tDCS (A‐tDCS over the lesioned and C‐tDCS over the non‐lesioned hemisphere)	2	33	Std. Mean Difference (IV, Random, 95% CI)	0.30 [‐0.39, 0.99]
3 Planned analysis: type of control intervention (sham tDCS, conventional therapy or nothing)	10		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
3.1 Sham tDCS	8	337	Std. Mean Difference (IV, Random, 95% CI)	0.23 [0.01, 0.46]
3.2 Active control intervention	2	109	Std. Mean Difference (IV, Random, 95% CI)	0.14 [‐0.24, 0.53]

Methods	Study design: RCT Number of dropouts: none Number of adverse effects: none (Ang 2015 [pers comm]) Deaths: none ITT: yes
Participants	Country: Singapore Sample size: 19 participants; mean age (SD) 54 (10) years; mean UE‐FM (SD) 34 (8) Inclusion criteria: not explicitly stated Exclusion criteria: history of seizures; major depression; implants that interfered with tDCS; being able to operate an EEG‐based motor imagery brain‐computer interface (MI‐BCI); further therapy aiming at improving function in the affected upper limb
Interventions	2 arms: Dual‐tDCS with the anode placed over M1 of the affected hemisphere and the cathode placed over M1 the unaffected hemisphere (1 mA for 20 minutes) followed by 8 minutes of evaluation and 60 minutes of therapy using EEG‐based MI‐BCI with robotic feedback with the MIT‐Manus device 5 times a week for 2 weeks Sham tDCS with the anode placed over M1 of the affected hemisphere and the cathode placed over M1 the unaffected hemisphere (1 mA for 30 seconds) followed by 8 minutes of evaluation and 60 minutes of therapy using EEG‐based MI‐BCI with robotic feedback with the MIT‐Manus device 5 times a week for 2 weeks
Outcomes	Outcomes were measured at baseline, at the end of intervention period at 2 weeks and at 2 week follow‐up: UE‐FM Online MI‐BCI performance event‐related desynchronisation laterality coefficient
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	People were randomised by "A randomization stratification generated using a computer‐generated random sequence" (Ang 2015 [pers comm])
Allocation concealment (selection bias)	Unclear risk	Quote: "Interventions of the subjects were applied by an engineer and a research assistant respectively. For tDCS, the research assistant was the only person who knew the randomization sequence for the subjects allocation" (Ang 2015 [pers comm])
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants were blinded; personnel were not blinded (Ang 2015 [pers comm])
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "Yes, the outcome assessors for Fugl‐Meyer were blinded to group allocation" (Ang 2015 [pers comm])
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	Not all of the secondary outcome measures listed in the published trial protocol have been reported, but will be presented in further publications (RMT of affected M1; grip strength; BBT; MRI parameters)

Methods	Study design: randomised controlled cross‐over trial Number of dropouts: none Number of adverse effects: not described Deaths: none ITT: yes
Participants	Country: China Sample size: 10 participants; mean age (SD) 63 (6) years; mean UE‐FM (SD) 58 (8) Inclusion criteria: not explicitly stated; participants were recruited from a convenience sample from two patient self help groups for stroke; participants were < 80 years of age; had a single stroke more than a year prior to enrolment and had weakness in the affected upper limb and could perform a pincer grip with the index finger Exclusion criteria: not explicitly stated, but people excluded were either illiterate in Chinese, had a history of other neurologic disorders, metal in the head, musculoskeletal pathologies affecting movements in the upper limbs, had aphasia or < 18 points on the MMSE
Interventions	Each participant underwent all of the following conditions: A‐tDCS over M1 of the affected hemisphere (1 mA for 20 minutes) plus sham tDCS over M1 of the unaffected hemisphere (1 mA for 10 seconds) once C‐tDCS over M1 of the unaffected hemisphere (1 mA for 20 minutes) plus sham tDCS over M1 of the affected hemisphere (1 mA for 10 seconds) once Sham tDCS over M1 of the unaffected hemisphere plus sham tDCS over M1 of the affected hemisphere (1 mA for 10 seconds) once
Outcomes	Outcomes were measured at baseline and at the end of intervention period Primary outcome measures: Purdue pegboard test (hand dexterity) Color‐word Stroop test (selective attention) Secondary outcome measures: Pinch grip strength (handheld digital dynamometer) Fatigue (NRS)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The sequence was determined in advance for each subject by drawing lots from an envelope"
Allocation concealment (selection bias)	Unclear risk	Quote: "The sequence was determined in advance for each subject by drawing lots from an envelope"
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Unclear risk	Participants were blinded, but personnel were not. Quote: "It was the third investigator (C.Y.) who set the tDCS parameters for both channels and operated the machine behind the subject throughout the experimental procedure"
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants were blinded, but personnel were not. Quote: "It was the third investigator (C.Y.) who set the tDCS parameters for both channels and operated the machine behind the subject throughout the experimental procedure"
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Outcome assessors were blinded. Quote: "Two other investigators (J.W. and E.C.) who were blinded to the allocated tDCS conditions then  assessed the baseline motor status of the subjects’ paretic upper limb"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Outcome assessors were blinded. Quote: "Two other investigators (J.W. and E.C.) who were blinded to the allocated tDCS conditions then  assessed the baseline motor status of the subjects’ paretic upper limb"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Unclear risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Unclear risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

Methods	Study design: randomised sham‐controlled cross‐over trial Dropouts: none Adverse effects: none Deaths: none ITT: yes Duration: 16 weeks
Participants	Country: Brazil Number of participants: 4 Age: (mean ± SD) 60.75 ± 13.15 years Gender: 0 female Type of stroke: not described, most likely ischaemic stroke Time poststroke: (mean ± SD) 34.5 ± 27.74 months Severity: mean muscle strength of the finger flexors (MRC) 3.8; mean ASS 0.5 Inclusion criteria: not clearly stated, but all participants had chronic, subcortical stroke, were right‐handed and had their stroke at least 12 months before study enrolment Exclusion criteria: not stated
Interventions	Characteristics: 4 weekly sessions of A‐tDCS (1 mA) over the hand area of M1 of the lesioned hemisphere, or C‐tDCS (1 mA) over the hand area of M1 of the non‐lesioned hemisphere or sham tDCS over the hand area of M1 of the lesioned hemisphere for 20 minutes with at least 2 weeks of rest between stimulation conditions
Outcomes	Outcomes used: duration of JTT in seconds Time point(s) of measurement: at baseline, after the first and after the fourth session of each treatment condition
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Procedure not described, quote: "The order of these conditions was counterbalanced and randomised across subjects"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants were blinded; blinding of personnel was not described
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "A blinded rater evaluated motor function using the Jebsen‐Taylor Hand Function Test"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

Methods	Study design: randomised controlled multicentre trial Dropouts: 7 Adverse effects: none Deaths: not stated ITT: no
Participants	Country: not stated Number of participants: 14 participants from the outpatient population of 3 neurological research units Age: (mean ± SD) 46.71 ± 14.08 years Gender: 9 female (64%) Type of stroke: 2 haemorrhagic (14%) Time poststroke: (mean ± SD) 35.21 ± 26.45 months Severity: moderate to severe hemiparesis, as indexed by UE‐FM (mean score 26, range 8 to 50) Inclusion criteria: ischaemic or haemorrhagic first‐ever stroke, stroke onset > 6 months before the study, functional inclusion criteria as defined by the EXCITE trial Exclusion criteria: pre stroke motor impairment affecting the upper limbs, moderate to severe major depression, previous CIMT and/or tDCS and contraindications regarding CIMT and/or tDCS
Interventions	Number of arms: 2 14‐day CIMT with shaping techniques + A‐tDCS (2 mA, 40 minutes) over the lesioned primary motor cortex (M1) 14‐day CIMT with shaping techniques + sham tDCS (40 minutes) over the lesioned primary motor cortex (M1)
Outcomes	Outcomes used: Motor assessments: duration of JTT in seconds, handgrip strength, MAL, UE‐FM Visual analogue scales for anxiety and pain/discomfort, questionnaire for adverse effects Time point of measurement: day 1, day 5, day 10 (end of treatment) and at 2 and 4 weeks of follow‐up
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation list (Bolognini 2013 [pers comm])
Allocation concealment (selection bias)	Unclear risk	The principal investigator, who took no part in data collection, nor in participants' evaluations, nor in treatment, knew the randomisation list and performed allocation (Bolognini 2013 [pers comm])
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Unclear risk	Participants were blinded; blinding of personnel was not described
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants were blinded; blinding of personnel was not described
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Quote: "The assessment of motor functions and the administration of the functional scales and questionnaires were performed by a trained staff, blinded to group assignment"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "The assessment of motor functions and the administration of the functional scales and questionnaires were performed by a trained staff, blinded to group assignment"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	Dropouts due to frustration and tiredness during assessment, quote: "Five patients (2 in the active group and 3 in the sham group) did not complete the JHFT. Two patients (1 in the active group and 1 in the sham group) did not complete the HS task." These participants have been excluded from analysis and presentation of results"
Incomplete outcome data (attrition bias)   Objective outcome measures	Unclear risk	Dropouts due to frustration and tiredness during assessment, quote: "Five patients (2 in the active group and 3 in the sham group) did not complete the JHFT. Two patients (1 in the active group and 1 in the sham group) did not complete the HS task." These participants have been excluded from analysis and presentation of results"
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

Methods	Study design: randomised double‐blind sham‐controlled cross‐over trial Dropouts: none Adverse effects: none Deaths: none ITT: yes
Participants	Country: not clearly stated Number of participants: 6 participants with chronic stroke neuroimaging‐proofed diagnosis; all were right‐handed and all had their strokes at least 12 months before the study Age: (mean ± SD) 53.7 ± 16.6 years Gender: 4 women (66%) Type of stroke: not stated Time poststroke: 27.1 months (range 12 to 72 months) Severity: motor strength (mean ± SD) 4.18 ± 0.37; ASS (mean ± SD) 0.83 ± 0.75 Inclusion criteria: not clearly stated Exclusion criteria: not clearly stated, but the authors referred to Hummel 2005, where the exclusion criteria were as follows: severe depression, history of severe alcohol or drug abuse, severe language disturbances, particularly of a receptive nature, or serious cognitive deficits (MMSE < 23/30 points)
Interventions	Characteristics: each participant underwent 3 different conditions for 20 minutes, separated by at least 48 hours of rest A‐tDCS of the lesioned hemisphere's M1 (1 mA). C‐tDCS of the non‐lesioned hemisphere's M1 (1 mA). Sham tDCS (electrode montage not stated by the authors).
Outcomes	Outcomes used: duration of JTT in seconds Time point of measurement: at baseline after familiarisation session, during stimulation and directly after stimulation
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants were blinded; blinding of personnel was not described
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Outcome assessor was blinded; quote: "A blinded neuropsychologist—instructed not to communicate with the patient during the task—evaluated patients’ performance"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

Methods	Study design: double‐blinded, sham‐controlled, randomised cross‐over study Dropouts: none Adverse effects: none Deaths: none ITT: yes
Participants	Country: Italy Number of participants: 9 Age (mean ± SD): 53.5 ± 20.7 years Gender: 4 (57%) female Type of stroke: 8 (89%) ischaemic, 1 (11%) haemorrhagic Time poststroke (mean ± SD): 28.3 ± 10.4 days Severity (mean ± SD): grip strength 17.83 ± 7.45 kg Inclusion criteria: cortical or subcortical first‐ever stroke (radiologically confirmed), possibility to perform pinch/grip test Exclusion criteria: history of chronic disabling pathologies of the upper limb; spasticity; presence of pacemaker or severe cardiovascular conditions; a history of tumour, prior neurosurgical brain intervention, severe cardiovascular conditions (including the presence of a pacemaker), a diagnosis of epilepsy or major psychiatric disorders
Interventions	Each participant underwent 1 of the following different stimulation conditions in 2 consecutive sessions on 2 consecutive days in random order (sham tDCS was obligatory) A‐tDCS for 15 minutes at 1.5 mA over M1 of the lesioned hemisphere C‐tDCS for 15 minutes at 1.5 mA over M1 of the non‐lesioned hemisphere Dual‐tDCS for 15 minutes at 1.5 mA, with the anode over M1 of the lesioned hemisphere and the cathode over M1 of the non‐lesioned hemisphere Sham tDCS (dosage and application not clearly stated, probably as in the other groups)
Outcomes	Outcomes were measured at baseline and at the end of intervention period Nine‐Hole Peg Test‐index (quote: "9HPT‐index=velocity LS/velocity HS∗100") Maximum pinch and grasp force in kg (measured by specific dynamometers according to the Jamar method, with a higher value indicating greater pinch and grasp force) Patient satisfaction as measured by the Quebec User Evaluation of Satisfaction with Assistive Technology
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "For the random sequence generation, we used the RAND function in Matlab"
Allocation concealment (selection bias)	Low risk	Quote: "Specifically, patients were asked to take a sealed envelope from a box, containing a piece of paper with the assignment, which was concealed until the envelope was opened"
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Unclear risk	Quote: "Patients were blinded while physicians and assessors knew the treatment (real or sham)"
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Quote: "Patients were blinded while physicians and assessors knew the treatment (real or sham)"
Blinding of outcome assessment (detection bias)   Subjective outcome measures	High risk	Quote: "Patients were blinded while physicians and assessors knew the treatment (real or sham)"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Unclear risk	Quote: "Patients were blinded while physicians and assessors knew the treatment (real or sham)"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

Methods	Method: RCT Number of dropouts: 3 (2 (14%) in the experimental group, 1 (7%) in the control group) Number of adverse effects: not reported Deaths: not described ITT: no
Participants	Country: Italy Sample size: 11 participants (5 in the experimental and 6 in the control group) Inclusion criteria: admission to stroke unit; age between 18 and 83 years; ischaemic stroke in the MCA area confirmed by MRI or CT; time since stroke less than 30 days; no history of severe cognitive impairment; written informed consent Exclusion criteria: inability to perform a motor rehabilitation training; haemorrhagic stroke or multiple foci of ischaemia; previous stroke; diagnosis of major psychiatric disorders; epilepsy; history of tumour; pacemaker; uncontrolled arrhythmias; non‐stabilised heart diseases; dementia or severe aphasia
Interventions	2 arms C‐tDCS (1.5 mA for 10 minutes) over M1 of the unaffected hemisphere on 5 consecutive days each week for 2 weeks prior to a rehabilitative session Sham tDCS (not described) over M1 of the unaffected hemisphere on 5 consecutive days each week for 2 weeks prior to a rehabilitative session
Outcomes	Outcomes were measured at baseline, after the end of intervention period, 1 month after the intervention period and at the end of inpatient rehabilitation (75 to 110 days) Canadian Neurological Scale Barthel Index 9‐hole peg test Grasp and pinch force Upper extremity Fugl‐Meyer Assessment Timed Up and Go Test 6‐Minute Walking Test 10‐Meter Walking Test Rivermead Mobility Index Functional Ambulation Categories
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomization was created in accordance with a binary sequence previously generated using MATLAB R2007b Software (TheMatworks Inc., USA)"
Allocation concealment (selection bias)	Unclear risk	Not described by the authors
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Unclear risk	Quote: "The patient was blind to the type of stimulation. An unblinded investigator administered the stimulation"
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Quote: "The patient was blind to the type of stimulation. An unblinded investigator administered the stimulation"
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Quote: "The patient was blind to the type of stimulation, as well as the physician performing the assessments"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "The patient was blind to the type of stimulation, as well as the physician performing the assessments"
Incomplete outcome data (attrition bias)   Subjective outcome measures	High risk	Quote: "Two patients of EG dropped out from the study (one at the first and the other one at the second session). Also one patient of control group dropped out for an emergency transfer to another hospital." These participants have not been analysed
Incomplete outcome data (attrition bias)   Objective outcome measures	High risk	Quote: "Two patients of EG dropped out from the study (one at the first and the other one at the second session). Also one patient of control group dropped out for an emergency transfer to another hospital." These participants have not been analysed
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

Methods	Study design: pilot RCT Dropouts: none Adverse effects: none Deaths: none ITT: yes
Participants	Country: Italy Number of participants: 30 outpatients Age: (mean ± SD) 62.7 ± 6.4 years Gender: 7 females (23%) Type of stroke: unilateral ischaemic stroke Time poststroke: (mean ± SD) 26.4 ± 5.5 months Severity: mean ESS score 79.93 (minimum score: 0, maximum score: 100; a completely healthy person would have a score of 100) Inclusion criteria: at least 12 months from first unilateral ischaemic stroke, age < 75 years, ESS score ≥ 75 and ≤ 85, MMSE‐score ≥ 24, ability to maintain standing position without aid for at least 5 minutes, ability to walk independently for at least 15 minutes with the use of walking aids Exclusion criteria: history of seizures, EEG suspect of elevated cortical excitability, metallic implants within the brain and previous brain neurosurgery, medications altering cortical excitability or with a presumed effect of brain plasticity, posterior circulation stroke, deficits of somatic sensations involving the paretic lower limb, presence of vestibular disorders/paroxysmal vertigo, severe cognitive or communicative disorders, cardiovascular comorbidity, rehabilitation treatment 3 months before study enrolment
Interventions	Number of arms: 3; all participants underwent 50‐minute training sessions 5 times a week for 2 consecutive weeks and 1 of the following interventions Robot‐assisted gait training + A‐tDCS of the lesioned hemisphere over the presumed leg area (1.5 mA for 7 minutes) Robot‐assisted gait training + sham tDCS of the lesioned hemisphere over the presumed leg area (for 7 minutes) Overground walking exercises according to the Bobath approach
Outcomes	Primary outcomes: six‐minute walking test, 10‐metre walking test Secondary outcomes: GAITRite system, FAC, RMI, MI leg subscore and MAS Time point of measurement: at baseline, after treatment and at two weeks follow‐up
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "After baseline evaluation, patients were allocated to one of three treatment groups according to a simple software‐generated randomisation scheme"
Allocation concealment (selection bias)	Low risk	Quote: "We allocated patients to one of the three treatment arms according to a restricted randomisation scheme. One of the investigators checked correct patient allocation according to the randomisation list. After unmasking at the end of the study, we checked that no errors had been made in allocation" (Smania 2013 [pers comm])
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Unclear risk	Quote: "Asking the assessor to make an educated guess tested the success of blinding. The therapists were aware of the type of treatment received by the patients. Patients were aware of the type of treatment who underwent but they were not aware about the type of stimulation (Group 1 stimulation vs Group 2 sham stimulation)" (Smania 2013 [pers comm])
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Quote: "Asking the assessor to make an educated guess tested the success of blinding. The therapists were aware of the type of treatment received by the patients. Patients were aware of the type of treatment who underwent but they were not aware about the type of stimulation (Group 1 stimulation vs Group 2 sham stimulation)" (Smania 2013 [pers comm])
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Quote: "All patients were evaluated by the same examiner (an experienced internal coworker) who was not aware of the treatment received by the patients"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "All patients were evaluated by the same examiner (an experienced internal coworker) who was not aware of the treatment received by the patients"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes stated in the methods section were reported, except muscle tone as measured by MAS

Methods	Study design: double‐blind randomised sham‐controlled multicentre trial Dropouts: 11 (11%) Adverse effects: none Deaths: 2 (2%) due to heart infarction and during stent surgery ITT: yes, 85 participants completed the study (89%)
Participants	Country: Germany/Italy Number of participants: 96 stroke participants from 3 study centres Mean age: 65.0, range 39 to 79 years Gender: 37 female (39%) Type of stroke: all ischaemic, 45 of 96 (47%) right‐hemispheric stroke Time poststroke: (mean ± SD) A‐tDCS group: 3.4 ± 1.8 weeks; C‐tDCS group: 3.8 ± 1.4 weeks; sham tDCS group: 3.8 ± 1.5 weeks Severity: at least wheelchair‐mobile participants, who had severe flaccid upper limb paresis with no (MRC 0) or minimal (MRC 1) volitional hand and finger extensor activity. 24 had an upper limb UE‐FM (range 0 to 66) < 18 and were unable to transfer 3 wooden blocks from 1 compartment to the other in the Box and Block test Inclusion criteria: age 18 to 79 years, first supratentorial ischaemic stroke with a stroke interval of 3 to 8 weeks' duration, and with participation in a comprehensive inpatient rehabilitation programme Exclusion criteria: history of epileptic seizures, EEG suspect of elevated cortical excitability, metallic implants in the brain, preceding brain surgery, sensitive scalp skin, anticonvulsant or neuroleptic medications
Interventions	Number of arms: 3; each participant practiced for 6 weeks every working day for 20 minutes with the arm robot (AT) and simultaneously received one of the following interventions: A‐tDCS (2 mA) with the anode positioned over the presumed hand area of the lesioned hemisphere C‐tDCS (2 mA) with the cathode positioned over the presumed hand area of the non‐lesioned hemisphere Sham tDCS (0 mA) with consecutive changing of the positions of arms (1) and (2)
Outcomes	Primary outcome: sensory and motor integrity, degree of synergy as assessed by UE‐FM assessment score (0 to 66, 0 = no movement, 66 = full motion) Secondary outcomes: upper limb muscle strength (MRC; 0 to 5, 0 = plegic, 5 = full power), muscle tone (MAS; 0 to 5, 0 = no increase, 5 = affected part rigid in flexion or extension), BI, upper limb function (as assessed by Box and Block test, the transfer of as many wooden blocks as possible with the affected hand from 1 compartment to the other within 1 minute, with a high value indicating good function) Time point of measurement: study onset, end of the 6‐week intervention and 3 months of follow‐up
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Following a telephone call, an independent person randomly allocated eligible patients to 1 of the 3 groups by drawing a lot out of an envelope containing 96 lots, indicating A, B, and C"
Allocation concealment (selection bias)	Low risk	Quote: "Following a telephone call, an independent person randomly allocated eligible patients to 1 of the 3 groups by drawing a lot out of an envelope containing 96 lots, indicating A, B, and C. He then informed the locally responsible person about the group assignment and the study started the next day"
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	Participants and personnel were blinded
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants and personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Quote: "To ensure blinded evaluation of the FMS, videos of the assessment, where the patients sat on a chair and a mirror was placed 45° behind them, were sent to an experienced therapist off site" and "Two experienced physiotherapists, blinded with respect to group assignment, assessed the secondary parameters together" and "The blinding was maintained at all measurement points"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "To ensure blinded evaluation of the FMS, videos of the assessment, where the patients sat on a chair and a mirror was placed 45° behind them, were sent to an experienced therapist off site" and "Two experienced physiotherapists, blinded with respect to group assignment, assessed the secondary parameters together" and "The blinding was maintained at all measurement points"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	1 dropout occurred during the study period as the result of pneumonia, and 10 after the end of the intervention period until follow‐up (6 were caused by being unavailable, 2 resulted from refusal to further participate and 2 were caused by cardiac conditions). ITT analysis was performed
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	1 dropout occurred during the study period as the result of pneumonia, and 10 after the end of the intervention period until follow‐up (6 were caused by being unavailable, 2 resulted from refusal to further participate and 2 were caused by cardiac conditions). ITT analysis was performed
Selective reporting (reporting bias)	Low risk	All outcomes reported in the methods section and in the published trial protocol reported

Methods	Method: Randomised cross‐over trial Number of dropouts: none Number of adverse effects: 6 Deaths: none ITT: yes
Participants	Country: Republic of Korea Sample size: 10 participants Inclusion criteria: Unilateral right hemispheric stroke, younger than 70 years; noticeable cognitive disorder after stroke; written informed consent Exclusion criteria: Seizures; metal implants in the head, cardiac pacemaker; history of neuropsychiatric diseases
Interventions	Each participant underwent one of the following treatments: single session of A‐tDCS over the DLPFC of the non‐lesioned hemisphere (2 mA for 30 minutes) followed by a single session sham tDCS over the DLPFC of the non‐lesioned hemisphere (2 mA for 10 seconds), separated by at least 48 hours wash‐out period single session sham tDCS over the DLPFC of the non‐lesioned hemisphere (2 mA for 10 seconds) followed by single A‐tDCS over the DLPFC of the non‐lesioned hemisphere (2 mA for 30 minutes), separated by at least 48 hours wash‐out period
Outcomes	Outcomes were measured at baseline and at the end of intervention period Response accuracy Recognition accuracy Response time of a two‐back verbal working memory task
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The order of stimulation was randomly assigned for all participants"
Allocation concealment (selection bias)	Unclear risk	Not described by the authors
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants have been blinded by sham tDCS; blinding of personnel not stated
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Not described by the authors, however all outcome data were acquired by a computerised assessment during cognitive tasks
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All randomised participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

Methods	Method: randomised cross‐over trial Dropouts: none Adverse effects: none (Paik 2015 [pers comm]) Deaths: none ITT: yes, all participants completed the study
Participants	Country: Republic of Korea Sample size: 10 people with stroke aged 48 to 84 years Inclusion criteria: not explicitly stated; written informed consent Exclusion criteria: cerebellar or brainstem lesion; metallic body implant; pacemaker; cochlear implant; history of seizure; unstable medical condition; inability to perform outcome tasks; Na+ or Ca++ channel blockers
Interventions	Each participant underwent one of the following treatments A‐tDCS over the left DLPFC (2 mA for 20 minutes) followed by sham tDCS over the left DLPFC (2 mA for 1 minute), separated by at least 48 hours wash‐out period Sham tDCS over the left DLPFC (2 mA for 1 minute) followed by A‐tDCS over the left DLPFC (2 mA for 20 minutes), separated by at least 48 hours wash‐out period
Outcomes	Outcomes were measured at baseline, at the end of intervention period and at 3 hours postintervention Attention (Go/No‐Go test)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "We applied random order using computerized program. Randominzation program is freely available in the Internet." (Paik 2015 [pers comm]) Comment: However, Patient‐ID and first session stimulation type were continuously alternated, as can be seen in Table 6
Allocation concealment (selection bias)	Unclear risk	Not described by the authors
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants were blinded; blinding of personnel not stated
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Outcome assessor was blinded; quote: "Both patients and the investigator that carried out the behavioral measurements were unaware of the type of intervention, because tDCS and sham were administered by another investigator who did not participate in the behavioral task or data analysis"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All randomised participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported. There was no published a priori trial protocol (Paik 2015 [pers comm])

Methods	Study design: RCT (parallel assignment) Dropouts: none Adverse effects: none Deaths: none ITT: yes, all participants completed the study
Participants	Country: Egypt Number of participants: 40 outpatients Age: (mean ± SD) years Gender: 14 females (35%) Type of stroke: acute single thromboembolic non‐haemorrhagic infarction, documented by MRI Time poststroke: (mean ± SD) 17.1 ± 3.6 days Severity: (range) 7 to 13 on NIHSS Exclusion criteria: extensive infarction (all territories of MCA), severe flaccid hemiplegia, head injury, neurological disease other than stroke, renal or hepatic impairment, previous administration of tranquilliser, inability to give informed consent, no MEP recorded from FDI muscle of the affected hand
Interventions	3 arms: A‐tDCS, 25 minutes at 2 mA daily for 6 consecutive days on M1 of the lesioned hemisphere, delivered by saline‐soaked pads (5 × 7 cm) C‐tDCS, 25 minutes at 2 mA daily for 6 consecutive days on M1 of the non‐lesioned hemisphere, delivered by saline‐soaked pads (5 × 7 cm) Sham tDCS, 25 minutes daily (with a short ramp‐up and ramp‐down of the current at the beginning and at the end of each session) for 6 consecutive days on M1 of the lesioned hemisphere
Outcomes	NIHSS at baseline, at the end of the intervention period and at 1, 2 and 3‐month follow‐up (0 to 42, with higher scores indicating a more severe stroke) OMCASS at baseline, at the end of the intervention period and at 1, 2 and 3‐month follow‐up (0 to 100, with higher scores indicating no clinical impairment due to stroke) BI at baseline, at the end of the intervention period and at 1, 2 and 3‐month follow‐up (0 to 100, with higher scores indicating better global function) Muscle strength according to MRC at the end of the intervention period, at 1, 2 and 3‐month follow‐up (0 to 5, with higher scores indicating higher muscle strength) Cortical excitability (as measured by RMT and AMT) at the end of the intervention period, at 1, 2 and 3‐month follow‐up (with greater intensity indicating a higher threshold)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Each patient was given a serial number from a computer‐generated randomisation table"
Allocation concealment (selection bias)	Low risk	Quote: "Group allocations (Anodal, Cathodal, or Sham) were placed in serially numbered, opaque closed envelopes ... and each patient was placed in the appropriate group after opening the corresponding sealed envelope"
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	Participants and therapists were blinded
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants and therapists were blinded
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Outcome assessor was blinded
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Outcome assessor was blinded
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	All randomised participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All randomised participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Low risk	All outcomes stated in the study protocol and listed in the methods section of the publication have been reported

Methods	Study design: single‐blinded, sham‐controlled, randomised cross‐over study Dropouts: none Adverse effects: none Deaths: none ITT: yes
Participants	Country: Republic of Korea Number of participants: 10 subacute participants Age: (mean) 62.8 years Gender: seven female (70%) Type of stroke: first‐ever stroke, as confirmed by MRI; 2 had haemorrhagic stroke (20%) Time poststroke: (mean) 6.4 weeks, range 3 to 12 weeks Severity: participants could grasp and release independently; degree of strength according to MRC was ≥ 3 but < 5 for all paretic finger flexors and extensors. Participants did not have a family history of seizure, could understand the purpose of the study and did not have any deformities or contractures of the fingers, hands, elbows and shoulders Inclusion criteria: not explicitly stated Exclusion criteria: not explicitly stated
Interventions	Each participant underwent 2 different stimulation conditions, each for 20 minutes, separated by at least 24 hours of rest A‐tDCS (1 mA) over the primary motor cortex of the first dorsal interossei muscle of the lesioned hemisphere Sham tDCS over the primary motor cortex of the first dorsal interossei muscle of the lesioned hemisphere
Outcomes	Box and Block test (the transfer of as many wooden blocks as possible with the lesioned hand from 1 compartment to the other within 1 minute, with a high value indicating good function) and finger acceleration measurement (in g, with a higher value indicating higher acceleration) at baseline, at 5 minutes of stimulation, immediately and at 30 and 60 minutes after stimulation Visual analogue scales to assess attention and fatigue (score 1 to 7; 1 = no attention/fatigue; 7 = highest level of attention/fatigue) at baseline, immediately and at 30 and 60 minutes after stimulation
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "A doctor who works in tDCS's room, he randomised patients on his own sequence" (Kim 2013 [pers comm])
Allocation concealment (selection bias)	Unclear risk	Quote: "A doctor who works in tDCS's room, he randomised patients on his own sequence" (Kim 2013 [pers comm])
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	Both participants and personnel were blinded (Kim 2013 [pers comm])
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Both participants and personnel were blinded (Kim 2013 [pers comm])
Blinding of outcome assessment (detection bias)   Subjective outcome measures	High risk	No blinding of outcome assessors. Quote: "An examiner who was aware of the stimulation method used was instructed not to communicate with patients during the task and evaluated patients’ performances"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding. Quote . Quote: "An examiner who was aware of the stimulation method used was instructed not to communicate with patients during the task and evaluated patients’ performances"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	All randomised participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All randomised participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

PERMALINK

Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke

Bernhard Elsner

Joachim Kugler

Marcus Pohl

Jan Mehrholz

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Assessment of heterogeneity

Data synthesis

GRADE and 'Summary of findings' table

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Results

Description of studies

Results of the search

2013 version

2015 version

1.

Included studies

Design

Sample sizes

Setting

Participants

1. Patient characteristics.

Interventions

2. Demographics of studies, including dropouts and adverse events.

Outcomes

Excluded studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Effects of interventions

Summary of findings for the main comparison. tDCS versus any type of placebo or passive control intervention for improving function, and activities of daily living, cognitive abilities and neglect in people after stroke.

Summary of findings 2. tDCS versus any type of active control intervention for improving function, activities of daily living, cognitive abilities and neglect in people after stroke.

Comparison 1. tDCS versus any type of placebo or passive control intervention

Comparison 1.1 Primary outcome measure: ADLs at the end of the intervention period

1.1.1 Studies presenting absolute values

1.1. Analysis.

1.1.2 Studies presenting change scores

4.

Comparison 1.2 Primary outcome measure: ADLs until the end of follow‐up, absolute values (at least three months after the end of the intervention period)

1.2. Analysis.

Comparison 1.3 Secondary outcome measure: upper extremity function at the end of the intervention period

1.3.1 Studies presenting absolute values

1.3. Analysis.

Methods	Study design: double‐blind sham‐controlled multicentre randomised trial Dropouts: 1 participant discontinued treatment because of dizziness and another because of headache (2 out of 20) during follow‐up Adverse effects: none Deaths: none ITT: no
Participants	Country: Republic of Korea Number of participants: 20 participants from neurorehabilitation units at 2 tertiary university hospitals Age: (mean ± SD) 57.27 ± 4.95 Gender: 7 female (35%) Type of stroke: first‐ever cortical or subcortical ischaemic stroke Time poststroke: (mean ± SD) A‐tDCS group: 34 ± 27.1 days; C‐tDCS: 19.4 ± 9.3 days; sham tDCS: 22.9 ± 7.5 days Severity: mild to moderate motor deficits (MRC score ≥ 2) Inclusion criteria: first‐ever ischaemic strokes in the cortical or subcortical area within the previous 2 months and mild to moderate motor deficits (MRC score ≥ 2) Exclusion criteria: cerebellar or brainstem lesions; presence of a metallic foreign body implant, such as a pacemaker or an artificial cochlea; history of seizure or another unstable medical condition; severe language disturbance; neglect, depression or cognitive deficits (based on the MMSE, 10 of 30 points) that would limit participation; history of severe alcohol or drug abuse; previous stroke that resulted in residual disability; premorbid arm impairment; and hemiplegic shoulder pain; use Na⁺ or Ca²⁺channel blockers or NMDA receptor antagonists
Interventions	Number of arms: 3 Each participant received 10 sessions (5 times per week for 2 weeks during conventional occupational therapy aiming at improving the co‐ordination and strength of the paretic hand) of 1 of the following interventions: A‐tDCS over the primary motor cortex (M1) of the contralateral FDI muscle of the lesioned hemisphere (2 mA for 20 minutes) C‐tDCS over the M1 of the ipsilateral FDI of the non‐lesioned hemisphere (2 mA for 20 minutes) Sham tDCS over the M1 of the contralateral FDI (for 20 minutes)
Outcomes	Outcomes used: FMA 0 to 66 (with higher scores indicating better function) for assessing upper limb motor function and MBI 0 to 100 (with higher scores indicating better global function) Time point of measurement: at baseline, 1 day and 6 months after intervention
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomly assigned to one of the three groups (atDCS, ctDCS or Sham treatment) using a stratified randomisation procedure with permuted block size of 3 and an algorithm that balanced Brunnstrom stages"
Allocation concealment (selection bias)	Low risk	Quote: "Sealed opaque envelopes were used for randomisation"
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	Participants and personnel were blinded
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants and personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Quote: "Two independent raters blinded to the type of intervention performed outcome measurements"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "Two independent raters blinded to the type of intervention performed outcome measurements"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Unclear risk	1 participant of each interventional arm (14% each) discontinued intervention; we excluded these participants from analysis
Incomplete outcome data (attrition bias)   Objective outcome measures	Unclear risk	1 participant of each interventional arm (14% each) discontinued intervention; we excluded these participants from analysis
Selective reporting (reporting bias)	Unclear risk	All outcomes reported in the methods section reported

Methods	Method: RCT Number of dropouts: 5 (3 out of 42 in the experimental groups (7%) and 2 out of 22 in the control group (9%)) Number of adverse effects: no major adverse events Deaths: none ITT: no
Participants	Country: Republic of Korea Sample size: 59 people with stroke (39 in the experimental groups and 20 in the control group) Inclusion criteria: unilateral hemiparesis caused by stroke; first stroke within 1 month prior to enrolment; shoulder motor strength Medical Research Council grade ≤ 2 Exclusion criteria: contraindications to brain stimulation; previous history of brain neurosurgery or epilepsy; metallic implants in the brain; severe cognitive impairment; aphasia interfering with understanding study instructions; poor sitting balance; impaired vision; hemispatial neglect
Interventions	3 arms C‐tDCS over the hand area of M1 over the non‐lesioned hemisphere (2 mA for 20 minutes) during occupational therapy aiming at functional improvement of the affected arm for 30 minutes per day, 5 times a week for 3 weeks; Virtual reality training aiming at functional improvement of the affected arm for 30 minutes per day, 5 times a week for 3 weeks; C‐tDCS plus virtual reality training aiming at functional improvement of the affected arm for 30 minutes per day, 5 times a week for 3 weeks
Outcomes	Outcomes were measured at baseline and at the end of intervention period Modified Ashworth Scale Manual Muscle Testing Manual Function Test Fugl‐Meyer assessment, upper extremity subscale Korean‐Modified Barthel Index
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "All of the enrolled patients were randomly assigned to 1 of 3 groups using a table of random numbers"
Allocation concealment (selection bias)	Unclear risk	Not described by the authors
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	Participants and personnel providing the base treatment were blinded
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants and personnel providing the base treatment were blinded
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Quote: "All evaluations were performed before and immediately after treatment by a single experienced occupational therapist who was not aware of the treatment allocation"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "All evaluations were performed before and immediately after treatment by a single experienced occupational therapist who was not aware of the treatment allocation"
Incomplete outcome data (attrition bias)   Subjective outcome measures	High risk	3 participants out of 42 (7%) in the experimental groups and 2 out of 22 (9%) were lost to follow‐up and excluded from the analysis. 2 out of the 3 losses to follow‐up in the experimental group dropped out due to "medical problem(s)"
Incomplete outcome data (attrition bias)   Objective outcome measures	High risk	3 participants out of 42 (7%) in the experimental groups and 2 out of 22 (9%) were lost to follow‐up and excluded from the analysis. 2 out of the 3 losses to follow‐up in the experimental group dropped out due to "medical problem(s)"
Selective reporting (reporting bias)	Unclear risk	All outcomes listed in the methods section reported

Methods	Study design: sham‐controlled double‐blinded randomised trial Dropouts: not stated Adverse effects: none Deaths: not stated, likely none ITT: not stated
Participants	Country: USA Number of participants: 20 chronic stroke participants Age: (mean ± SD) 55.8 ± 12.9 years Gender: 5 female (25%) Type of stroke: first and only ischaemic stroke Time poststroke: (mean ± SD) 40.3 ± 23.4 months Severity: UE‐FM Score (mean ± SD) 39.8 ± 11.5 Inclusion criteria: ischaemic stroke in the territory of the medial cerebral artery at least 5 months before enrolment; no previous or subsequent strokes; MRC strength grade of 3/5 in extensor muscles of the lesioned upper extremity in the acute phase with at least 15 degrees of active wrist dorsiflexion at enrolment Exclusion criteria: additional neurological or psychiatric disorders; concurrent use of CNS‐affecting drugs
Interventions	Number of arms: 2, each participant underwent 5 consecutive sessions of physical therapy/occupational therapy and 1 of the following interventions Dual‐tDCS: A‐tDCS over M1 of the lesioned hemisphere + C‐tDCS over M1 of the non‐lesioned hemisphere (1.5 mA each, for 30 minutes) Sham tDCS (for 30 minutes)
Outcomes	Primary outcome measure: UE‐FM scores (0 to 66, with higher scores reflecting better motor performance) Secondary outcome measure: WMFT (with lower scores indicating better motor performance) Time point of measurement: at baseline and at 3 and 7 days after the last intervention session
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomly assigned to one of two groups ... using a block randomisation with 3 strata of impairment"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants and personnel were blinded
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "Each patient underwent motor impairment assessments and MRI at baseline and after the intervention, conducted by trained individuals who were blinded to the type of intervention the patients received"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Incomplete outcome data (attrition bias)   Objective outcome measures	Unclear risk	All randomised participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes stated in the methods section were reported

Methods	Study design: sham‐controlled cross‐over randomised trial Dropouts: not stated, most likely none Adverse effects: none Deaths: not stated, most likely none ITT: not stated
Participants	Country: Iran Number of participants: 10 right‐handed stroke participants with no sensory deficits Age: (mean ± SD) 60.8 ± 14.1 years Gender: 3 female (30%) Type of stroke: ischaemic Time poststroke: (mean ± SD) 8.3 ± 5.45, range 1 to 16 months Severity: median Brunnstrom stage 6 Inclusion criteria: single ischaemic stroke with more than 1 month's duration of mild to moderate motor deficit (to ensure that all participants could perform all items on the JTT Exclusion criteria: clinically significant or unstable medical or psychiatric disorder with history of substance abuse, any neuropsychiatric comorbidity other than stroke and contraindications to tDCS
Interventions	Each participant underwent 5 different treatments with at least 4 days of each of the following A‐tDCS of lesioned M1 (with the cathodal electrode positioned at the contralateral supraorbital area, 1 mA for 20 minutes) A‐tDCS of lesioned M1 (with the cathodal electrode positioned at the contralateral deltoid muscle, 1 mA for 20 minutes) C‐tDCS of lesioned M1 (with the anodal electrode positioned at the contralateral supraorbital area, 1 mA for 20 minutes) Dual‐tDCS: A‐tDCS of lesioned M1 + C‐tDCS of non‐lesioned M1 Sham tDCS (20 minutes)
Outcomes	Outcomes used: JTT (with familiarisation sessions) Time points of measurement: at baseline and after stimulation
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The order of these conditions was counterbalanced and randomised across patients"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants probably were blinded; blinding of personnel was not described. Quote: "Patients were then randomised to the double‐blinded, sham‐controlled cross over part of the experiment"
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "A blinded physiatrist—instructed not to communicate with the patients during the task—evaluated patients' performance"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	There were no subjective outcome measures
Incomplete outcome data (attrition bias)   Objective outcome measures	Unclear risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes stated in the methods section were reported

Methods	Method: RCT Number of dropouts: unclear Number of adverse effects: none Deaths: none ITT: unclear
Participants	Country: Republic of Korea Sample size: 11 participants Inclusion criteria: not explicitly stated; newly diagnosed with radiologically confirmed stroke; written informed consent Exclusion criteria: patients with metal in the head or with skin lesions in the electrode area; significant aphasia
Interventions	2 arms A‐tDCS to the bilateral prefrontal cortex (2 mA for 30 minutes) with the cathode positioned at the non‐dominant arm + computer‐assisted cognitive rehabilitation five times a week for 18.5 days Sham tDCS with the anode positioned over the bilateral prefrontal cortex (2 mA for 30 seconds) with the cathode positioned at the non‐dominant arm + computer‐assisted cognitive rehabilitation five times a week for 17.8 days
Outcomes	Outcomes were measured at baseline and at study end Korean Version of the MMSE Seoul Computerized Neuropsychological Test (SCNT)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The patients were randomly assigned to two groups"
Allocation concealment (selection bias)	Unclear risk	Not described by the authors
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Unclear risk	Patients were blinded; whereas blinding of personnel was not clearly described by the authors: "The tDCS and the cognitive function test were performed by two independent personnel"
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Patients were blinded; whereas blinding of personnel was not clearly described by the authors: "The tDCS and the cognitive function test were performed by two independent personnel"
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Unclear risk	Quote: "The tDCS and the cognitive function test were performed by two independent personnel"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "The tDCS and the cognitive function test were performed by two independent personnel."
Incomplete outcome data (attrition bias)   Subjective outcome measures	Unclear risk	All randomised participants apparently completed the study; no treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Unclear risk	All randomised participants apparently completed the study; no treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	Not all of the 10 dimensions of the Seoul Computerized Neuropsychological Test (SCNT), as stated in the methods section, have been reported

Methods	Study design: RCT Dropouts: none Adverse effects: not reported Deaths: none ITT: yes Duration: 1 month
Participants	Country: China Number of participants: 50 Age: tDCS (mean ± SD): 45 (11), control: 45 (14) years Gender: tDCS: 21 (84%) male, control: 22 (88%) male Type of stroke: 15 (60%) ischaemic Time poststroke: tDCS: 6 months (3 to 36), control: 4 months (3 to 12) Severity: tDCS: FMA 12 (5 to 44), BI 64 (17), control: FMA 5 (2 to 35), BI: 72 ± 22 Inclusion criteria: admitted to hospital between June 2008 and June 2009 and MRI‐confirmed stroke Exclusion criteria: not stated
Interventions	2 arms C‐tDCS over lesioned M1 (0.5 mA for 20 minutes) once a day for 5 consecutive days, for 1 month + physical therapy (40 minutes/session, twice a day, for 5 times a week) Physical therapy (40 minutes/session, twice a day, for 5 times a week)
Outcomes	Outcomes used: MAS, FMA, BI Time points of measurement: at baseline and at the end of the intervention period
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Subjects were randomly assigned using a computer‐generated randomisation list by a single investigator" (Wu 2013b [pers comm])
Allocation concealment (selection bias)	Unclear risk	Quote: "The assigned random number was inputted into the stimulator device by the same investigator. She did not participate in other parts of the study" (Wu 2013b [pers comm])
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Unclear risk	Quote: "All other investigators, subjects, and outcome assessors remained blinded to group allocation until the completion of the final statistical analyses" (Wu 2013b [pers comm])
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Quote: "All other investigators, subjects, and outcome assessors remained blinded to group allocation until the completion of the final statistical analyses" (Wu 2013b [pers comm])
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Unclear risk	See "Blinding of participants and personnel"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	See "Blinding of participants and personnel"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All participants apparently completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Unclear risk	All outcomes from the methods section were reported

Methods	Study design: single‐centre, randomised, double‐blind, sham‐controlled trial Dropouts: none Adverse effects: none Deaths: none ITT: yes, all participants completed the study
Participants	Country: Italy Number of participants: 50 Inclusion criteria: age between 18 and 80 years and an acute ischaemic lesion in the territory of the MCA, a score between 6 and 20 at the NIHSS and a UE‐FM score between 15 and 55 Exclusion criteria: pre stroke mRS > 1, thrombolysis, history of seizure, advanced systemic diseases coexistent neurological/psychiatric diseases, current treatment with antidepressants, antipsychotics or benzodiazepines Age: (mean ± SD) tDCS‐group: 66.1 (± 14.3); sham group: 70.3 (± 13.5) years Gender: tDCS group: 12 male (48%), sham group: 14 male (56%) Time poststroke: 2 days Severity according NIHSS at baseline: tDCS‐group: 15.4 (± 4.9); sham group: 14.1 (± 3.5)
Interventions	Number of arms: 2; each participant underwent 1 of the following conditions 5 daily sessions of A‐tDCS to M1 of the lesioned hemisphere (2 mA for 20 minutes) 5 daily sessions of sham tDCS (for 20 minutes)
Outcomes	Primary outcomes: UE‐FM at baseline, at the end of intervention and at 3 month follow‐up  Secondary outcomes: NIHSS at baseline, at the end of intervention and at 3 month follow‐up; mRS at baseline, at the end of intervention and at 3‐month follow‐up
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation scheme was generated by a computer program (Koch 2013 [pers comm])
Allocation concealment (selection bias)	Unclear risk	Allocation was performed by a third person via telephone (Koch 2013 [pers comm])
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	Personnel were blinded to the type of treatment (Koch 2013 [pers comm])
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Personnel were blinded to the type of treatment (Koch 2013 [pers comm])
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Evaluators were blinded (Koch 2013 [pers comm])
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Evaluators were blinded (Koch 2013 [pers comm])
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	All participants completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All participants completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Low risk	All outcomes were stated as mentioned in preceding conference papers

Methods	Study design: RCT Number of dropouts: 1 in the A‐tDCS group (skin reaction due to tDCS) Number of adverse effects: 1 in the A‐tDCS group (skin reaction due to tDCS) Deaths: none ITT: no
Participants	Country: UK Sample size: 22 participants Inclusion criteria: aged 18 and above; clinical diagnosis of first‐ever stroke, confirmed by a neurologist/stroke specialist; time since stroke > 2 weeks prior to enrolment; upper and fore‐arm and hand paresis (MRC > 2); minimal spasticity (MAS ≤ 2); partial shoulder flexion with gravity; good sitting balance; informed consent Exclusion criteria: MMSE < 24; other neurological conditions; shoulder pain resulting from shoulder flexion > 90°; epilepsy; metal implants in the skull or brain; previous brain neurosurgery; medications that influence cortical excitability; previous adverse effects when stimulated with tDCS; pregnancy
Interventions	2 arms A‐tDCS over M1 of the affected hemisphere (1 mA for 20 minutes) during the first 20 minutes of a 60 minute robotic training session with the ArmeoSpring device for 18 sessions during 8 weeks (approximately 2 to 3 sessions per week) Sham tDCS over M1 of the affected hemisphere (1 mA for 20 minutes) during the first 20 minutes of a 60 minute robotic training session with the ArmeoSpring device for 18 sessions during 8 weeks (approximately 2 to 3 sessions per week)
Outcomes	Outcomes were measured at baseline and at the end of intervention and at 3 months follow‐up Primary outcomes: UE‐FM Secondary outcomes: ARAT MAL SIS 3.0
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Block randomisation was used with a computer program called 'random allocation software'"
Allocation concealment (selection bias)	Low risk	Quote: "To conceal allocation, an independent person placed the printed papers of sham/real in sealed opaque envelopes according to block randomisation. As soon as a participant enrolled in the study, the researcher made a telephone call to the independent person who then stated whether ‘real’ or ‘sham’ was to be administered to the participant"
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Unclear risk	Participants apparently were blinded, but blinding of personnel not stated
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Participants apparently were blinded, but blinding of personnel not stated
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Quote: "Three blinded assessors, trained qualified physiotherapists with experience in stroke assessment and neurological rehabilitation carried out clinical assessments. In addition to the clinical assessor, video recorded FMA and ARAT assessments were also scored by an additional blinded clinical assessor"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "Three blinded assessors, trained qualified physiotherapists with experience in stroke assessment and neurological rehabilitation carried out clinical assessments. In addition to the clinical assessor, video recorded FMA and ARAT assessments were also scored by an additional blinded clinical assessor"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Unclear risk	1 participant in the A‐tDCS group dropped out (1 out of 23; 4%) because of a skin reaction due to tDCS, whereas in the sham group there were no dropouts. Quote: "After four intervention sessions, a participant with chronic stroke dropped out of the trial due to a skin reaction after receiving four real tDCS sessions"
Incomplete outcome data (attrition bias)   Objective outcome measures	Unclear risk	1 participant in the A‐tDCS group dropped out (1 out of 23; 4 %) because of a skin reaction due to tDCS, whereas in the sham group there were no dropouts. Quote: "After four intervention sessions, a participant with chronic stroke dropped out of the trial due to a skin reaction after receiving four real tDCS sessions"
Selective reporting (reporting bias)	Unclear risk	All outcome measures listed in the methods section have been reported. All outcome measures from the published study protocol have been reported, except measures of cortical excitability

Methods	Study design: RCT with parallel‐group design Dropouts: none Adverse effects: none Deaths: none ITT: yes Duration: 1 month
Participants	Country: China Number of participants: 90 Age: mean (SD) C‐tDCS: 45.9 (11.2), sham tDCS 49.3 (12.6) years Gender: C‐tDCS: 34 (76%) male, sham tDCS: 35 (78%) male Type of stroke: C‐tDCS: 27 (60%) ischaemic, sham tDCS: 26 (58%) ischaemic Time poststroke in months: mean (SD) C‐tDCS: 4.9 (3.0); sham tDCS 4.9 (2.9) Severity: FMA for C‐tDCS: 12 (4 to 26) and 8 (3 to 34), BI for C‐tDCS 55 (0 to 85) and 55 (25 to 95) for sham tDCS Inclusion criteria: time since stroke > 2 months, first‐ever stroke, muscle tone at wrist and elbow with MAS score ≥ 1 and ≤ 3, no history of Botox or other invasive treatment in the previous 6 months, use of spasmolytics resulting in an adverse event or maximised dosing without effect and no severe cognitive or mood disorders Exclusion criteria: unstable vital signs or unstable, progressive or severe neurological disease, heart condition or hypertension
Interventions	2 arm Physical therapy twice daily for 30 minutes each, C‐tDCS over M1 lesioned (1.2 mA for 20 minutes once daily, 5 days per week for 4 weeks) Physical therapy twice daily for 30 minutes each, sham tDCS over M1 lesioned (1.2 mA for 30 seconds once daily, 5 days per week for 4 weeks)
Outcomes	Outcomes used: MAS (range from 0 to 4, with a score of 4 reflecting the highest possible muscle tone), UE‐FM (0 to 66, with higher scores reflecting better motor performance) and MBI (0 to 105, with higher scores reflecting better ADL performance) Time points of measurement: at baseline, at the end of the intervention period and at 4‐week follow‐up
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Subjects were randomly assigned using a computer‐generated randomisation list by a single investigator"
Allocation concealment (selection bias)	Low risk	Quote: "The assigned random number was inputted into the stimulator device by the same investigator. She did not participate in other parts of the study. The device automatically generated active or sham tDCS according to the parity of the random number"
Blinding of participants and personnel (performance bias)   Subjective outcome measures	Low risk	Quote: "All other investigators, subjects, and outcome assessors remained blinded to group allocation until the completion of the final statistical analyses"
Blinding of participants and personnel (performance bias)   Objective outcome measures	Low risk	Quote: "All other investigators, subjects, and outcome assessors remained blinded to group allocation until the completion of the final statistical analyses"
Blinding of outcome assessment (detection bias)   Subjective outcome measures	Low risk	Quote: "All other investigators, subjects, and outcome assessors remained blinded to group allocation until the completion of the final statistical analyses"
Blinding of outcome assessment (detection bias)   Objective outcome measures	Low risk	Quote: "All other investigators, subjects, and outcome assessors remained blinded to group allocation until the completion of the final statistical analyses"
Incomplete outcome data (attrition bias)   Subjective outcome measures	Low risk	All participants completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Incomplete outcome data (attrition bias)   Objective outcome measures	Low risk	All participants completed the study. No treatment withdrawals, no losses to follow‐up, no trial group changes and no major adverse events were stated
Selective reporting (reporting bias)	Low risk	All outcomes from the methods section and from the published trial protocol were reported

Study	Reason for exclusion
Boggio 2007b	Not a genuine RCT
Bradnam 2012	Not a genuine RCT
Byblow 2011	Not a genuine RCT, irrelevant outcome: motor evoked potential
Celnik 2009	Outcome number of correct key presses clinically not relevant
Danzl 2012	Sham group was stimulated more than 1 minute
Edwards 2009	Not a genuine RCT
Gandiga 2006	Not a genuine RCT
Giacobbe 2013	Irrelevant outcome measure movement kinematics
Goh 2015	Irrelevant Outcome: motor evoked potential
Gurchin 1988	Irrelevant intervention: transcranial alternating current stimulation
Hummel 2005a	Not a genuine RCT
Hummel 2005b	Not a genuine RCT
Jayaram 2009	Irrelevant outcome for review question 'motor evoked potentials'
Kasashima 2012	Irrelevant outcome for review question 'event‐related desynchronisation'
Kharchenko 2001	Irrelevant Intervention for review question 'transcranial alternating current stimulation'
Kitisomprayoonkul 2012	Irrelevant outcome for review question 'sensation'
Kumar 2011	Irrelevant intervention for review question: study did not evaluate impact of tDCS on upper limb/lower limb function and/or ADLs
Kwon 2012	Not a genuine RCT
Lee 2012	Irrelevant patients
Lefebvre 2013	Not a genuine randomised controlled cross‐over trial
Lefebvre 2015	Not a genuine randomised controlled cross‐over trial
Madhavan 2011	Irrelevant outcome for review question 'accuracy index'
Manganotti 2011	Not a genuine RCT
Ochi 2013	Irrelevant comparison for review question: A‐tDCS versus C‐tDCS with no control group
Paquette 2011	Irrelevant intervention for review question: tDCS was contaminated with rTMS at each stimulation session
Sheliakin 2006	Not a genuine RCT
Stagg 2012a	Irrelevant outcome for review question 'response time'
Takeuchi 2012	Irrelevant outcome for review question 'bimanual co‐ordination', as measured by tapping task
Zimerman 2012	Not a genuine randomised controlled cross‐over trial