Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke
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 and function 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 and function.
Objectives
To assess the effects of tDCS on generic activities of daily living (ADLs) and motor function in people with stroke.
Search methods
We searched the Cochrane Stroke Group Trials Register (March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, May 2013), MEDLINE (1948 to May 2013), EMBASE (1980 to May 2013), CINAHL (1982 to May 2013), AMED (1985 to May 2013), Science Citation Index (1899 to May 2013) 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 In an effort to identify further published, unpublished and ongoing trials, we searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers.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
We included only randomised controlled trials (RCTs) and randomised controlled cross‐over trials (from which we analysed only the first period as a parallel‐group design) that compared tDCS versus control in adults with stroke for improving ADL performance and function.
Data collection and analysis
Two review authors independently assessed trial quality (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 15 studies involving a total of 455 participants. Analysis of six studies involving 326 participants regarding our primary outcome, ADL, showed no evidence of an effect in favour of tDCS at the end of the intervention phase (mean difference (MD) 5.31 Barthel Index (BI) points; 95% confidence interval (CI) ‐0.52 to 11.14; inverse variance method with random‐effects model), whereas at follow‐up (MD 11.13 BI points; 95% CI 2.89 to 19.37; inverse variance method with random‐effects model), we found evidence of an effect. However, the confidence intervals were wide and the effect was not sustained when only studies with low risk of bias were included. For our secondary outcome, upper limb function, we analysed eight trials with 358 participants, which showed evidence of an effect in favour of tDCS at the end of the intervention phase (MD 3.45 Upper Extremity Fugl‐Meyer Score points (UE‐FM points); 95% CI 1.24 to 5.67; inverse variance method with random‐effects model) but not at the end of follow‐up three months after the intervention (MD 9.23 UE‐FM points; 95% CI ‐13.47 to 31.94; inverse variance method with random‐effects model). These results were sensitive to inclusion of studies at high risk of bias. Adverse events were reported and the proportions of dropouts and adverse events were comparable between groups (risk difference (RD) 0.00; 95% CI ‐0.02 to 0.03; Mantel‐Haenszel method with random‐effects model).
Authors' conclusions
At the moment, evidence of very low to low quality is available on the effectiveness of tDCS (anodal/cathodal/dual) versus control (sham/any other intervention) for improving ADL performance and function after stroke. Future research should investigate the effects of tDCS on lower limb function and should address methodological issues by routinely reporting data on adverse events and dropouts and allocation concealment, and by performing intention‐to‐treat analyses.
PICOs
Plain language summary
Direct electrical current to the brain to reduce impairment in function and activities of daily living (ADLs) after stroke
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 activities of daily living (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. This review of 15 trials involving 455 participants found evidence of very low to low quality on the effectiveness of tDCS in enhancing rehabilitation outcomes regarding ADL and function. These results are imprecise, and the effect was not sustained when only studies of high methodological quality were included. Proportions of adverse events were comparable between groups. Future research is needed in this area to improve the generalisability of these findings, especially regarding lower limb function.
Authors' conclusions
Summary of findings
| Transcranial direct current stimulation (tDCS) for function and activities of daily living (ADLs) in patients after stroke | ||||||
| Patient or population: patients with function and activities of daily living (ADLs) after stroke | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Transcranial direct current stimulation (tDCS) | |||||
| Generic activities of daily living at the end of the intervention phase, absolute values | Mean generic activities of daily living at the end of the intervention phase; absolute value in the intervention groups was | 435 | ⊕⊝⊝⊝ | |||
| Generic activities of daily living until the end of follow‐up, absolute values | Mean generic activities of daily living until the end of follow‐up; absolute value in the intervention groups was | 99 | ⊕⊕⊝⊝ | |||
| Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) at the end of the intervention phase | Mean upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) at the end of the intervention phase in the intervention groups was | 302 | ⊕⊕⊝⊝ | |||
| Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) to the end of follow‐up | Mean upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) to the end of follow‐up in the intervention groups was | 68 | ⊕⊝⊝⊝ | |||
| Dropouts, adverse events and deaths during intervention phase | Study population | See comment | 427 | ⊕⊕⊕⊕ | Risks were calculated from pooled risk differences | |
| 21 per 1000 | 26 per 1000 | |||||
| Moderate | ||||||
| 0 per 1000 | 0 per 1000 | |||||
| *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). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| 1Downgraded because of unclear and high risk of bias in included studies. | ||||||
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 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). Therefore, neurological rehabilitation, including effective training strategies, is needed (especially therapies tailored to patients' and carers' needs) to facilitate motor 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). tDCS is usually 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), or (2) vice versa (cathodal stimulation, C‐tDCS) (Hesse 2011), or (3) (1) and (2) may be applied simultaneously (dual‐tDCS) (Lindenberg 2010). Depending on the type of stimulation (anodal or cathodal), tDCS might lead to increased or decreased cortical excitability, respectively (Bindman 1964; Purpura 1965). This may result from a shift of the resting potential of the brain's neurons (Floel 2010; Purpura 1965). Stimulation lasting for longer than five minutes might induce significant after‐effects, which could last up to several hours (Nitsche 2001; Nitsche 2003). Anodal stimulation might lead to depolarisation of the neuronal membranes and therefore to greater cortical excitability, and vice versa (Bindman 1964). This effect could be used to facilitate motor learning in healthy people (Boggio 2006; Jeffery 2007; Reis 2009) and appears to be a promising option in rehabilitation after stroke.
Recent research suggests that, among people with stroke, tDCS combined with simultaneous upper extremity training might lead to greater improvement in arm motor function when compared with sham tDCS alone (Boggio 2007; Hummel 2006; Kim 2010). Some recent pilot studies even report 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, according to another pilot study, the additional effect of tDCS when combined with gait training in an electromechanical gait trainer remains unknown (Geroin 2011).
Why it is important to do this review
To date, studies of tDCS have tended to include small sample sizes. Currently, no systematic review has synthesised the findings of available trials. Therefore, a systematic review of trials investigating the effectiveness and acceptability of tDCS is required.
Objectives
To assess the effects of tDCS on generic activities of daily living (ADLs) and motor function in people with 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 or a clinical definition, if not specifically stated, that is, 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
We compared any kind of active tDCS for improving motor function or ADLs 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 without producing any perceivable sensations on the skin (Gandiga 2006)) or placement of electrodes with no direct current applied. If more than one active or sham or control groups, respectively, investigated the same content, we combined these into one group each (e.g. if two sham control groups were included, we collapsed them into a single sham group for comparison with the active group).
Types of outcome measures
Outcome measures do not form part of the eligibility criteria.
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.
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Frenchay Activities Index (FAI) (Schuling 1993).
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Barthel ADL Index (BI) (Mahoney 1965).
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Rivermead ADL Assessment (Whiting 1980).
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Modified Rankin Scale (mRS) (Bonita 1988).
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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 phase, and (2) at follow‐up from three to 12 months after the study end. In cases where included studies report 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
We defined secondary outcomes as upper limb function, lower limb function, muscle strength, 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:
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Action Research Arm Test (ARAT) (Lyle 1981);
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Fugl‐Meyer Score (Fugl‐Meyer 1975);
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Nine‐Hole Peg Test (NHPT) (Sharpless 1982); and
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Jebsen Taylor Hand Function Test (JTHFT) (Jebsen 1969).
For lower limb function:
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walking velocity (in metres per second);
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walking capacity (metres walked in six minutes); and
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Functional Ambulation Categories (FAC) (Holden 1984).
For muscle strength:
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grip force (measured by handheld dynamometer) (Boissy 1999); and
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Motricity Index Score (Demeurisse 1980).
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 published in languages other than English.
Electronic searches
We searched the Cochrane Stroke Group Trials Register (March 2013) and the following electronic bibliographic databases:
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Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, May 2013) (Appendix 1);
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MEDLINE (1948 to May 2013) (Appendix 2);
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EMBASE (1980 to May 2013) (Appendix 2);
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CINAHL (1982 to May 2013) (Appendix 3);
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AMED (1985 to May 2013) (Appendix 2);
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Science Citation Index (Web of Science) (1899 to May 2013) (Appendix 4);
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Physiotherapy Evidence Database (PEDro) at http://www.pedro.org.au/ (May 2013) (Appendix 5);
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Rehabdata at www.naric.com/?q=REHABDATA (1956 to May 2013) (Appendix 6);
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Compendex (1969 to May 2013).(Appendix 7); and
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Inspec (1969 to May 2013) (Appendix 2).
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 (March 2013):
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Stroke Trials Registry (www.strokecenter.org/trials/);
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Current Controlled Trials (www.controlled‐trials.com/);
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ClinicalTrials.gov (http://clinicaltrials.gov);
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EU Clinical Trials Register (www.clinicaltrialsregister.eu/); and
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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.
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Handsearched the following relevant conference proceedings, which had not already been searched by the Cochrane Stroke Group:
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3rd, 4th, 5th, 6th and 7th World Congress of NeuroRehabilitation (2002, 2006, 2008, 2010 and 2012);
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1st, 2nd, 3rd, 4th, 5th and 6th World Congress of Physical and Rehabilitation Medicine (2001, 2003, 2005, 2007, 2009 and 2011);
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Deutsche Gesellschaft für Neurotraumatologie und Klinische Neurorehabilitation (2001 to 2012);
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Deutsche Gesellschaft für Neurologie (2000 to 2012);
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Deutsche Gesellschaft für Neurorehabilitation (1999 to 2012); and
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1st, 2nd and 3rd Asian Oceania Conference of Physical and Rehabilitation Medicine (2008, 2010 and 2012).
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Screened reference lists from relevant reviews, articles and textbooks.
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Contacted authors of identified trials and other researchers in the field.
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Used Science Citation Index Cited Reference Search for forward tracking of important articles.
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Contacted the following equipment manufacturers (April 2013):
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Activatek, Salt Lake City, USA (www.activatekinc.com);
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Changsha Zhineng Electronics, Changsha City, Hunan, China (www.cszhineng.diytrade.com);
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DJO Global, Vista, USA (www.djoglobal.com);
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Grindhouse (www.grindhousewetware.com);
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Magstim, Spring Gardens, UK (www.magstim.com);
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Neuroconn, Ilmenau, Germany (www.neuroconn.de);
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Neuroelectrics, Barcelona, Spain (www.neuroelectrics.com);
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Newronika, Milano, Italy (www.newronika.it);
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Soterix Medical, New York City, USA (www.soterixmedical.com); and
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Trans Cranial Technologies, Hong Kong (www.trans‐cranial.com).
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Searched Google Scholar (http://scholar.google.com/) (April 2013).
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 PICO (population, intervention, comparison, outcome) 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 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. According to the 'Risk of bias' tool implemented in RevMan 5.2 (RevMan 2012), we used checklists to independently assess:
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methods of random sequence generation;
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methods of allocation concealment;
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blinding of assessors;
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use of an intention‐to‐treat (ITT) analysis;
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adverse effects and dropouts;
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important differences in prognostic factors;
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participants (country, number of participants, age, gender, type of stroke, time from stroke onset to study entry and inclusion and exclusion criteria);
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comparison (details of interventions in treatment and control groups, duration of treatment and details of co‐interventions in the groups);
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outcomes; and
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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 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 are 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.
For all statistical comparisons we used the current version of RevMan 5.2 (RevMan 2012).
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.
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:
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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);
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type of stimulation: cathodal versus anodal and position of electrodes/location of stimulation; and
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type of control intervention (sham tDCS, conventional therapy or nothing).
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 RevMan 5.2 (RevMan 2012)).
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
See Characteristics of included studies, Characteristics of excluded studies, Characteristics of studies awaiting classification and Characteristics of ongoing studies. We identified a total of 3505 unique records through the searches. After screening titles and abstracts, we excluded 3413 records and obtained the full text of the remaining 92 articles. After further assessment, we determined that 15 studies met the review inclusion criteria, and three studies are awaiting classification, as more information is required. We identified 29 ongoing trials. The flow of references is shown in Figure 1.
Study flow diagram.
Included studies
We included 15 studies involving a total of 455 participants (Boggio 2007a; Bolognini 2011; Fregni 2005a; Fusco 2013; Geroin 2011; Hesse 2011; Khedr 2013; Kim 2009; Kim 2010; Lindenberg 2010; Mahmoudi 2011; Nair 2011; Qu 2009; Rossi 2013; Wu 2013) (see Characteristics of included studies). All studies investigated the effects of tDCS versus sham tDCS, except Qu 2009 and Wu 2013, which compared tDCS with physical therapy alone. Six trials with 53 participants were randomly assigned cross‐over trials (Boggio 2007a; Bolognini 2011; Fregni 2005a; Fusco 2013; Kim 2009; Mahmoudi 2011), whereas the remaining nine, with 437 analysed participants, were RCTs (Geroin 2011; Hesse 2011; Khedr 2013; Kim 2010; Lindenberg 2010; Nair 2011; Qu 2009; Rossi 2013; Wu 2013). Eight studies included one intervention group and one control group (Bolognini 2011; Geroin 2011; Lindenberg 2010; Kim 2009; Nair 2011; Qu 2009; Rossi 2013; Wu 2013), whereas five studies had two intervention groups and one control group (Boggio 2007a; Fregni 2005a; Hesse 2011; Khedr 2013; Kim 2010) and two studies had three intervention groups and one control group (Fusco 2013; Mahmoudi 2011). Geroin 2011 was the only study that examined the effects of tDCS on gait and lower limb function, whereas the remaining 14 included studies examined the effects of tDCS on upper limb function. Three of the included studies were conducted in Italy, two each in China, the Republic of Korea and the USA and one each in Brazil, Egypt, Germany/Italy and Iran. In two studies, the country was not stated. The experimental groups received A‐tDCS (Boggio 2007a; Bolognini 2011; Fregni 2005a; Fusco 2013; Geroin 2011; Hesse 2011; Khedr 2013; Kim 2009; Kim 2010; Mahmoudi 2011; Rossi 2013), C‐tDCS (Boggio 2007a; Fregni 2005a; Fusco 2013; Hesse 2011; Khedr 2013; Kim 2010; Mahmoudi 2011; Nair 2011; Qu 2009; Wu 2013) or dual‐tDCS (Fusco 2013; Lindenberg 2010; Mahmoudi 2011), and the control groups of all included studies except Qu 2009 and Wu 2013 received sham‐tDCS (S‐tDCS) or physical therapy, respectively, as a control intervention. A widely used outcome was the Barthel Index (BI) and the Upper Extremity Fugl‐Meyer Score (UE‐FM). For a comprehensive summary of participant characteristics, please see Table 1; for a comprehensive summary of intervention characteristics, dropouts and adverse events, please see Table 2.
| Study | Experimental: | Control: | Experimental: | Control: | Experimental: | Control: | Experimental: | Control: | Experimental: | Control: severity, mean (SD) | Experimental: | Control: | Handedness, n (%) |
| 56 (11.14) years | 75 (NA) years | 33 (33.78) 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 | |
| 42.57 (12.87) years | 50.86 (14.96) years | 44.43 (31.31) months | 26.00 (18.36) months | 4 (57) female | 5 (71) female | 4 (57) left | 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 | |
| 53.67 (16.64) years | 27.08 (24.37) months | 2 (33) female | 3 (50) left | MRC 4.18 (0.37) | Cause not clearly stated by the authors | 6 (100) right‐handed | |||||||
| 44.40 (15.90) years | 65.00 (22.26) years | 30.80 (13.48) days | 25.25 (4.99) 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 | ||
| 63.6 (6.7) years | 63.3 (6.4) years | 25.7 (6.0) months | 26.7 (5.1) months | 2 (20) female | 4 (40) female | Not stated by the authors | 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; | Not stated by the authors | |
| 64.65 (9.55) years | 65.6 (10.3) years | 3.6 (1.61) weeks | 3.8 (1.5) 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 | |
| 59.00 (9.41) years | 57 (7.5) years | 13.08 (5.13) days | 12.6 (4.6) 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 | |
| 62.80 (13.16) years | 6.40 (3.17) 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 | |||||||
| 54.33 (14.97) years | 62.9 (9.2) years | 27.36 (21.45) days | 22.9 (7.5) days | 2 (18) female | 3 (43) female | 7 (64) left | 2 (29) left | BI 71.77 (23.86) | BI 67.9 (22.4) | 11 (100) ischaemic; 3 (27) cortical, 3 (27) corticosubcortical, 5 (71) subcortical | 7 (100) ischaemic; | Not stated by the authors | |
| 61.7 (14.7) years | 55.8 (12.9) years | 30.5 (21.4) months | 40.3 (23.4) 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 | 10 (100) ischaemic | 19 (95) right‐handed, 1 (5) both‐handed | |
| 60.8 (14.11) years | 8.3 (5.45) months | 3 (33) female | 6 (60) left, 3 (30) right, 1 (10) brainstem | JTHFT (without handwriting): 12.3 (7.3) s | 10 (100) ischemic | Not stated by the authors | |||||||
| 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; | 7 (100) ischaemic; | 14 (100) right‐handed | |
| 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 | 10 (40) haemorrhagic, 15 (60) infarction | Not stated by the authors | |
| 66.1 (14.3) years | 70.3 (13.5) years | 2 days | 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; | 25 (100) ischaemic; 2 (8) cortical, 18 (72) corticosubcortical, 5 (20) subcortical | Not stated by the authors | |
| 45.9 (11.2) years | 49.3 (12.6) years | 4.9 (3.0) months | 4.9 (2.9) months | 11 (24) female | 10 (22) female | 24 (53) left | 23 (51) left | BI 55 (range 0 to 85) | BI 55 (range 25 to 95) | 27 (60) ischaemic, 18 (40) haemorrhagic | 26 (58) ischaemic, 19 haemorrhagic (42) | Not stated by the authors | |
BBT: Box and Block Test
BI: Barthel Index
ESS: European Stroke Scale
LACI: lacunar stroke
MRC: Medical Research Council
NA: not applicable
PACI: partial anterior circulation stroke
SD: standard deviation
TACI: total anterior circulation stroke
UE‐FM: Upper Extremity Fugl‐Meyer Score
| Study | Type of stimulation (polarity) | Electrode position and size | Treatment intensity | Base treatment | Dropouts | Reasons for dropouts and adverse events in the experimental group | Reasons for dropouts and adverse events in the control group | Adverse events | Source of information | |
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere | 1 mA for 20 minutes | A‐tDCS, C‐tDCS or S‐tDCS 4 days once a day | None | None | NA | NA | None | Published | |
| C‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the non‐lesioned hemisphere | |||||||||
| S‐tDCS | Not described by the authors | 1 mA for 30 seconds | ||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere | 2 mA for 40 minutes | Base treatment + A‐tDCS or S‐tDCS 5 days a week for 2 consecutive weeks | CIMT up to 4 hours/d for 5 days a week for 2 consecutive weeks | 7 (33%) | Frustration and tiredness during assessments (Bolognini 2013); these participants have been excluded from analysis and presentation of results | None | Published and unpublished | ||
| S‐tDCS | 2 mA for 30 seconds | |||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere | 1.5 mA for 15 minutes | 1 active tDCS (A‐tDCS, C‐tDCS, dual‐tDCS) and 1 S‐tDCS session in 2 consecutive days | None | None | NA | NA | 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 | ||||||||
| S‐tDCS | Not described by the authors | |||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere | 1 mA for 20 minutes | Each participant underwent A‐tDCS, C‐tDCS and S‐tDCS once, separated by at least 48 hours of rest | None | None | NA | NA | None | Published | |
| C‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the non‐lesioned hemisphere | 1 mA for 20 minutes | ||||||||
| S‐tDCS | Not described by the authors | 1 mA for 30 seconds | ||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere | 1.5 mA for 7 minutes | Base treatment + A‐tDCS or S‐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 | NA | NA | None | Published | |
| S‐tDCS | 0 mA for 7 minutes | |||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere | 2 mA for 20 minutes | Base treatment + A‐tDCS, C‐tDCS or S‐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: 1 (14%) during intervention phase 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: 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 | ||||||||
| S‐tDCS | As in the A‐tDCS or the C‐tDCS group (changing consecutively) | 0 mA for 20 minutes | ||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere | 2 mA for 25 minutes | Base treatment + A‐tDCS, C‐tDCS or S‐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 | NA | NA | None | Published | |
| C‐tDCS | Saline‐soaked 35 cm² sponge electrodes, cathode over M1 of the non‐lesioned hemisphere | 2 mA for 25 minutes | ||||||||
| S‐tDCS | Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere | 2 mA for 2 minutes | ||||||||
| A‐tDCS | Saline‐soaked 25 cm² sponge electrodes, anode over M1 of the lesioned hemisphere | 1 mA for 20 minutes | Each participant underwent A‐tDCS and S‐tDCS, separated by at least 24 hours of rest | None | None | NA | NA | None | Published and unpublished | |
| S‐tDCS | 1 mA for 30 seconds | |||||||||
| A‐tDCS | Saline‐soaked 25 cm² sponge electrodes over M1 of the lesioned hemisphere (as confirmed by MEP) | 2 mA for 20 minutes | Base treatment + A‐tDCS, C‐tDCS or S‐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 | No dropouts | 2 | Published | |
| C‐tDCS | Saline‐soaked 25 cm² sponge electrodes over M1 of the non‐lesioned hemisphere (confirmed by MEP) | 2 mA for 20 minutes | ||||||||
| S‐tDCS | Saline‐soaked 25 cm² sponge electrodes over M1 of the lesioned hemisphere (confirmed by MEP) | 2 mA for 1 minutes | ||||||||
| 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 S‐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 | NA | NA | None | Published | |
| S‐tDCS | 1.5 mA for 30 seconds | |||||||||
| A‐tDCS1 | Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere and cathode placed over the contralateral orbit | 1 mA for 20 minutes | Each participant underwent A‐tDCS1, A‐tDCS2, C‐tDCS, dual‐tDCS and S‐tDCS once with a washout period of at least 96 hours | None | None | NA | NA | Not clearly stated, most likely none | Published | |
| A‐tDCS2 | Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere and cathode placed 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 | 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 | ||||||||
| S‐tDCS | Not described by the authors | 1 mA for 30 seconds | ||||||||
| C‐tDCS | Saline‐soaked sponge electrodes with the cathode over M1 of the lesioned hemisphere | 1 mA for 30 minutes | Base‐treatment + C‐tDCS or S‐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 | NA | NA | None | Published | |
| S‐tDCS | Not described by the authors | For 30 minutes | ||||||||
| C‐tDCS | Saline‐soaked 18 cm² sponge electrodes over primary sensorimotor cortex of the lesioned hemisphere | 0.5 mA for 20 minutes, once a day for 5 consecutive days for 4 weeks | NA | None | NA | NA | 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 | ||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere | 2 mA for 20 minutes | Once a day for 5 consecutive days | Not described by the authors | None | NA | NA | None | Published | |
| S‐tDCS | 2 mA for 30 seconds | |||||||||
| C‐tDCS | Saline‐soaked 24.75 cm² sponge electrodes over primary sensorimotor cortex of the lesioned hemisphere | 1.2 mA for 20 minutes | Once daily 5 days a week for 4 weeks | Quote: "Both groups received a conventional physical therapy program | None | NA | NA | None | Published | |
| S‐tDCS | 1.2 mA for 30 seconds | |||||||||
A‐tDCS: anodal direct current stimulation.
C‐tDCS: cathodal direct current stimulation.
CIMT: constraint‐induced movement therapy.
Dual‐tDCS: A‐tDCS and C‐tDCS simultaneously.
MEP: motor‐evoked potentials.
NA: not applicable.
PNF: proprioceptive neuromuscular facilitation.
PT: physical therapy.
SD: standard deviation.
S‐tDCS: sham transcranial direct current stimulation.
We had to exclude four of the included trials from quantitative syntheses (meta‐analyses) because of missing information regarding the first intervention period of the cross‐over trial (Fregni 2005a; Fusco 2013; Kim 2009; Mahmoudi 2011).
Excluded studies
We excluded 23 trials from qualitative assessment (Boggio 2007b; Byblow 2011; Celnik 2009; Edwards 2009; Gandiga 2006; Gurchin 1988; Hummel 2005a; Hummel 2005b; Jayaram 2009; Kasashima 2012; Kharchenko 2001; Kitisomprayoonkul 2012; Kumar 2011; Kwon 2012; Lefebvre 2013; Madhavan 2011; Manganotti 2011; Ochi 2013; Paquette 2011; Sheliakin 2006; Stagg 2012a; Takeuchi 2012; Zimerman 2012), mainly because they were not RCTs, or because their outcomes did not measure function or ADLs (see Characteristics of excluded studies).
Risk of bias in included studies
We provided information about the risk of bias in Characteristics of included studies. To complete the rating of methodological quality, we contacted all principal investigators of the included trials and of trials awaiting classification to request further information about methodological issues, if necessary. We made contact via letter and email, including email reminders once a month if we received no response. Some trialists provided all requested information, and some did not answer our requests. We used the 'Risk of bias' tool, as implemented in RevMan 5.2, to assess risk of bias according to the aspects listed under Methods. Two review authors (BE and JM) independently assessed risk of bias of the included trials, and two other review authors (JK and MP) checked the extracted data for agreement. Information on risk of bias on study level is provided in Figure 2. All review authors discussed disagreements and, if necessary, sought arbitration by another review author. A detailed description of risk of bias can be found in Characteristics of included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Eight of the 15 included studies (47%) described a low risk of bias for sequence generation (Bolognini 2011; Geroin 2011; Fusco 2013; Hesse 2011; Khedr 2013; Kim 2010; Lindenberg 2010; Wu 2013), whereas six studies (40%) described a low risk of bias for allocation concealment (Geroin 2011; Fusco 2013; Hesse 2011; Khedr 2013; Kim 2010; Wu 2013).
Blinding
Eleven of the 15 included studies (73%) described low risk of bias for blinding of participants and personnel (Boggio 2007a; Bolognini 2011; Geroin 2011; Hesse 2011; Khedr 2013; Kim 2009; Kim 2010; Lindenberg 2010; Nair 2011; Rossi 2013; Wu 2013), and 12 studies (80%) described low risk of bias for blinding of outcome assessment (Boggio 2007a; Bolognini 2011; Fregni 2005a; Geroin 2011; Hesse 2011; Khedr 2013; Kim 2010; Lindenberg 2010; Mahmoudi 2011; Nair 2011; Rossi 2013; Wu 2013), whereas two studies were determined to have high risk of bias (Fusco 2013; Kim 2009).
Incomplete outcome data
Thirteen of the 15 included studies (87%) were at low risk of bias for incomplete outcome data (Boggio 2007a; Fregni 2005a; Fusco 2013; Geroin 2011; Hesse 2011; Khedr 2013; Kim 2009; Lindenberg 2010; Mahmoudi 2011; Nair 2011; Qu 2009; Rossi 2013; Wu 2013), whereas one was at high risk (Kim 2010).
Selective reporting
Thirteen of the 15 included studies (87%) were at low risk of bias for selective outcome reporting (Boggio 2007a; Fregni 2005a; Fusco 2013; Geroin 2011; Hesse 2011; Khedr 2013; Kim 2009; Lindenberg 2010; Mahmoudi 2011; Nair 2011; Qu 2009; Rossi 2013; Wu 2013), and one study (7%) was at high risk (Kim 2010).
Effects of interventions
Comparison 1. Primary outcome measure: tDCS for improvement of generic ADLs versus any type of placebo or control intervention
Outcome 1.1. Generic ADLs at the end of the intervention phase, absolute values
We found five studies with 286 participants examining the effects of tDCS on generic ADLs, as measured by BI after stroke (Hesse 2011; Khedr 2013; Kim 2010; Qu 2009; Wu 2013). We found no evidence of effect regarding ADL performance when data were analysed with collapsed intervention groups, as stated in Methods (i.e. A‐tDCS and/or C‐tDCS versus S‐tDCS; MD 5.31 BI points; 95% CI ‐0.52 to 11.14; inverse variance method with random‐effects model; very low quality evidence), and the confidence intervals are wide. The funnel plot of Analysis 1.1 can be found in Figure 3.
Funnel plot of comparison: 1 Primary outcome measure: tDCS for improvement of generic ADLs versus any type of placebo or control intervention, outcome: 1.1 Generic ADLs at the end of the intervention phase, absolute values (BI points).
Outcome 1.2. Generic ADLs until the end of follow‐up, absolute values (at least three months after the end of the intervention phase)
Three studies with 99 participants were included (Khedr 2013; Kim 2010; Rossi 2013); investigators measured the effects of tDCS on ADLs by BI at the end of follow‐up. We found evidence of effect regarding ADL performance when data were analysed with collapsed intervention groups (MD 11.13 BI points; 95% CI 2.89 to 19.37; inverse variance method with random‐effects model; very low quality evidence), but the confidence intervals were wide. Upon inspecting the funnel plot of Analysis 1.2 graphically, we found no asymmetry (Figure 4).
Funnel plot of comparison: 1 Primary outcome measure: tDCS for improvement of generic ADLs versus any type of placebo or control intervention, outcome: 1.2 Generic ADLs until the end of follow‐up, absolute values (BI points).
Comparison 2. Secondary outcome measure: tDCS for improvement of upper limb function versus any type of placebo or control intervention, dropouts and adverse events (including death from all causes)
Outcome 2.1. Upper extremity function as measured by Fugl‐Meyer (UE‐FM) at the end of the intervention phase
Seven trials with a total of 302 participants (Bolognini 2011; Hesse 2011; Kim 2010; Lindenberg 2010; Nair 2011; Rossi 2013; Wu 2013) used UE‐FM as a measure of function at the end of the intervention phase (Analysis 2.1). Evidence of effect regarding function favoured tDCS when data were analysed with collapsed intervention groups (MD 3.45 UE‐FM units; 95% CI 1.24 to 5.67; inverse variance method with random‐effects model). Upon graphical inspection of the funnel plot of Analysis 2.1, we found no evidence of small study effects (Figure 5).
Funnel plot of comparison: 2 Secondary outcome measure: tDCS for improvement of upper limb function versus any kind of placebo or control intervention, dropouts, outcome: 2.1 Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) at the end of the intervention phase (UE‐FM points).
Outcome 2.2. Upper extremity function as measured by Fugl‐Meyer (UE‐FM) to the end of follow‐up (at least three months after the end of the intervention phase)
Two studies with a total of 68 participants (Kim 2010; Rossi 2013) used UE‐FM as a measure of function at the end of follow‐up (Analysis 2.2). We found no evidence of effect regarding function when data were analysed with collapsed intervention groups (i.e. A‐tDCS and/or C‐tDCS versus S‐tDCS; MD 9.23 UE‐FM points; 95% CI ‐13.47 to 31.94; inverse variance method with random‐effects model; I² = 90%).
Outcome 2.3. Dropouts, adverse events and deaths during the intervention phase
In three of 11 studies (18%), dropouts, adverse events or deaths that occurred during the intervention phase were reported (Bolognini 2011; Hesse 2011; Kim 2010), whereas the remaining studies reported no dropouts, adverse events or deaths. We found no evidence of effect regarding differences in dropouts, adverse effects and deaths between intervention and control groups (risk difference (RD) 0.00; 95% CI ‐0.02 to 0.03; Mantel‐Haenszel method with random‐effects model).
Comparison 3. Subgroup analyses
Outcome 3.1. Planned analysis: duration of illness—acute/subacute versus postacute phase for ADLs at the end of the intervention phase
In a planned subgroup analysis, we analysed the effects of tDCS on the primary outcome of ADLs in the acute/subacute and postacute phases (Analysis 3.1). We found no evidence for different effects of tDCS between subgroups (Chi² = 0.80, df = 1 (P = 0.37), I² = 0%).
Subgroup 3.1.1. Acute/subacute phase (the first week after stroke and the second to the fourth week after stroke, respectively)
Three studies with 146 participants were included (Hesse 2011; Khedr 2013; Kim 2010). We found no evidence of effect regarding differences in ADL performance between intervention and control groups when data were analysed with collapsed intervention groups, as stated in the protocol (i.e. A‐tDCS or C‐tDCS or dual‐tDCS versus S‐tDCS; MD 5.23 BI points; 95% CI ‐3.74 to 14.21; inverse variance method with random‐effects model).
Subgroup 3.1.2. Postacute phase (from the first to the sixth month after stroke)
We included two studies with 140 participants (Qu 2009; Wu 2013). We found evidence of differences in effect of tDCS regarding ADL performance between tDCS‐ and control groups when data were analysed with collapsed intervention groups, as stated in the protocol (i.e. A‐tDCS or C‐tDCS or dual‐tDCS versus S‐tDCS; MD 10.78 BI points; 95% CI 2.53 to 19.02; inverse variance method with random‐effects model).
Outcome 3.2. 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 phase
We performed a planned subgroup analysis regarding the location of electrode positioning and hence of stimulation (Analysis 3.2). No studies investigated the effects of A‐tDCS over the non‐lesioned hemisphere. We found no evidence of differences in effects of location and type of stimulation regarding ADL performance between subgroups (Chi² = 0.67, df = 2 (P = 0.72), I² = 0%).
Subgroup 3.2.1. A‐tDCS over the lesioned hemisphere
Three studies with 104 participants were included (Hesse 2011; Khedr 2013; Kim 2010). We found no evidence of differences in effects regarding ADL performance between A‐tDCS and S‐tDCS groups (MD 4.92 BI points; 95% CI ‐6.54 to 16.39; inverse variance method with random‐effects model).
Subgroup 3.2.2. C‐tDCS over the non‐lesioned hemisphere
We included three studies with 102 participants (Hesse 2011; Khedr 2013; Kim 2010). We found evidence of differences in effect regarding ADL performance between C‐tDCS and the S‐tDCS groups, but the confidence intervals were wide (MD 8.31 BI points; 95% CI 1.11 to 15.50; inverse variance method with random‐effects model).
Subgroup 3.2.3. C‐tDCS over the lesioned hemisphere
We included two studies with 140 participants (Qu 2009; Wu 2013). We found evidence of differences in effect regarding ADL performance between C‐tDCS and S‐tDCS groups, but the confidence intervals were wide (MD 10.78 BI points; 95% CI 2.53 to 19.02; inverse variance method with random‐effects model).
Outcome 3.3. Planned sensitivity analysis regarding types of control interventions (S‐tDCS/conventional therapy/no intervention)
This planned subgroup analysis was omitted because all included studies except Qu 2009 used S‐tDCS as the control intervention. See Differences between protocol and review.
Sensitivity analyses
We conducted a sensitivity analysis of methodological quality to test the robustness of our results. We repeated the analysis of our primary outcome, ADL performance at the end of the intervention phase and at the end of follow‐up, and considered only studies with correctly concealed allocation, blinding of assessors and ITT. The effects of tDCS on ADL performance at follow‐up were not sustained when we included only studies with low risk of bias. Detailed results can be found in Table 3 and Table 4.
| Sensitivity analysis | Studies included in analysis | Effect estimate |
| All studies with proper allocation concealment | (MD 6.93; 95% CI ‐0.23 to 14.10; inverse variance method with random‐effects model) | |
| All studies with proper blinding of outcome assessor for primary outcome | (MD 5.31; 95% CI ‐0.52 to 11.14; inverse variance method with random‐effects model) | |
| All studies with intention‐to‐treat analysis | (MD 4.92; 95% CI ‐1.31 to 11.15; inverse variance method with random‐effects model) |
BI: Barthel Index.
CI: confidence interval.
MD: mean difference.
| Sensitivity analysis | Studies included in analysis | Effect estimate |
| All studies with proper allocation concealment | (MD 16.38 BI points; 95% CI 6.09 to 26.68; inverse variance method with random‐effects model) | |
| All studies with proper blinding of outcome assessor for primary outcome | (MD 11.16 BI points; 95% CI 2.89 to 19.43; inverse variance method with random‐effects model) | |
| All studies with intention‐to‐treat analysis | (MD 11.31 BI points; 95% CI ‐1.55 to 24.18; inverse variance method with random‐effects model) |
BI: Barthel Index.
CI: confidence interval.
MD: mean difference.
Discussion
Summary of main results
This review focused on evaluating the effectiveness of tDCS (A‐tDCS/C‐tDCS/dual‐tDCS) versus control (S‐tDCS, any other approach or no intervention) for improving generic activities of daily living (ADLs) and function after stroke. We included 15 trials with a total of 455 participants. We found five studies with 286 participants examining the effects of tDCS on our primary outcome measure, generic ADLs, as measured by the Barthel Index (BI) after stroke. We found no evidence of effect regarding ADL performance at the end of the intervention phase (MD 5.31 BI points; 95% CI ‐0.52 to 11.14; inverse variance method with random‐effects model), and the confidence intervals were wide. The funnel plot shows no evidence of a small study effect. Three studies with 99 participants assessed the effects of tDCS on ADLs by measuring BI at the end of follow‐up. Evidence suggested an effect regarding ADL performance (MD 11.13 BI points; 95% CI 2.89 to 19.37; inverse variance method with random‐effects model), but the confidence intervals were wide, and the effect was not sustained when we included only studies with low risk of bias. Upon inspecting the funnel plot graphically, we found no asymmetry.
One of our secondary outcome measures was function: seven trials with a total of 302 participants measured function using Upper Extremity Fugl‐Meyer Scores (UE‐FM) at the end of the intervention phase, revealing evidence of an effect in favour of tDCS (MD 3.45 UE‐FM unit; 95% CI 1.24 to 5.67; inverse variance method with random‐effects model). Regarding the effects of tDCS on function at the end of follow‐up, we identified two studies with a total of 68 participants that showed no evidence of effect (MD 9.23 UE‐FM points; 95% CI ‐13.47 to 31.94; inverse variance method with random‐effects model). In three of 11 studies (18%), dropouts, adverse events or deaths occurring during the intervention phase were reported. We found no evidence of an effect regarding differences in dropouts, adverse effects and deaths between intervention and control groups (risk difference (RD) 0.00; 95% CI ‐0.02 to 0.03; Mantel‐Haenszel method with random‐effects model).
A summary of this review's main findings can be found in summary of findings Table for the main comparison.
Overall completeness and applicability of evidence
The results of this review appear seem to be generalisable to other settings in industrialised countries. However, some factors suggest uncertainty in generalisations. These include the following.
-
Most of the studies included participants with first‐time ever stroke.
-
Most participants suffered from ischaemic stroke.
Hence, the results may be of limited applicability for people with recurrent and haemorrhagic stroke.
Moreover, completeness of evidence is lacking regarding studies on the effects of tDCS on lower limb function.
Quality of the evidence
Based on our assessments of the quality of evidence provided in summary of findings Table for the main comparison, we downgraded risk of bias and the imprecision of effect estimates that included no difference in the comparators or that failed to exclude clinically unimportant differences between them. We also found heterogeneity regarding trial design (parallel‐group or cross‐over design, two or three intervention groups), therapy variables (type of stimulation, location of stimulation, dosage of stimulation) and participant characteristics (age, time poststroke, severity of stroke/initial functional impairment).
Potential biases in the review process
The methodological rigour of Cochrane reviews minimises bias during the process of conducting systematic reviews. However, some aspects of this review represent an 'open door' to bias, such as eliminating obviously irrelevant publications according to titles and abstracts on the determination of only one review author (BE). This encompasses the possibility of unintentionally ruling out relevant publications. Another possibility is that publication bias could have affected our results. With the funnel plot for our main outcome of ADLs (at the end of the intervention phase) showing asymmetry by visual inspection in the absence of substantial heterogeneity (I² statistic > 50%), publication bias may have occurred (Figure 3) (Sterne 2011).
Another potential source for the introduction of bias is that two of the review authors (JM and MP) were involved in conducting and analysing the largest of the included trials (Hesse 2011). However, they did not participate in extracting outcome data and determining risk of bias of this trial. They were replaced by another review author (JK), so that the introduction of bias is unlikely in this case.
We had to exclude four trials from quantitative synthesis (meta‐analysis) because of missing information regarding treatment order (i.e. the first intervention period of the cross‐over trial) (Fregni 2005a; Fusco 2013; Kim 2009; Mahmoudi 2011). However, the results of these trials are consistent with the results of comparisons made in our meta‐analyses, and it is therefore unlikely that the results of these studies would have altered our results.
Agreements and disagreements with other studies or reviews
As far as we know, another recently published systematic review of quasi‐randomised and properly randomised controlled trials has examined the effects of A‐tDCS on upper limb motor recovery in stroke patients (Butler 2013). The review authors included eight trials with 168 participants, and their analysis revealed evidence of an effect of tDCS on upper limb function (SMD 0.49; 95% CI 0.18 to 0.81), mainly measured by the Jebsen Taylor Hand Function Test (JTHFT). These results are similar to the results of our analyses regarding the effects of tDCS (combined) on upper limb function as measured by UE‐FM. Two other recently published systematic reviews include meta‐analyses dealing with the topic of tDCS for improving function after stroke (Bastani 2012; Jacobson 2012). Bastani 2012 examined the effects of A‐tDCS on cortical excitability (as measured by transcranial magnet stimulation (TMS)) and function (mainly measured by JTHFT) in healthy volunteers and people with stroke. Their analysis of the effects of A‐tDCS over the lesioned hemisphere, based mainly on results of randomised cross‐over studies, yielded no evidence of effect (SMD 0.39; 95% CI ‐0.17 to 0.94; inverse variance method with fixed‐effects model). Jacobson 2012, a review about the effects of A‐tDCS and C‐tDCS on healthy volunteers, stated that the anodal‐excitation and cathodal‐inhibition (AeCi) dichotomy is relatively consistent regarding the effects of tDCS on function in healthy volunteers. However, in our analysis on people with stroke, we found evidence of an effect of C‐tDCS over the non‐lesioned as well as over the lesioned hemisphere, which seems to be contradictory to the AeCi dichotomy for healthy volunteers but is in accordance with the findings of another recent trial, aimed at comparing the lesion‐ and stimulation‐specific effects of tDCS in healthy volunteers and stroke patients (Suzuki 2012). However, we found no evidence of effect for A‐tDCS over the lesioned hemisphere in our planned subgroup analysis, which is consistent with the findings of Bastani 2012, but not with the findings of Suzuki 2012.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Funnel plot of comparison: 1 Primary outcome measure: tDCS for improvement of generic ADLs versus any type of placebo or control intervention, outcome: 1.1 Generic ADLs at the end of the intervention phase, absolute values (BI points).
Funnel plot of comparison: 1 Primary outcome measure: tDCS for improvement of generic ADLs versus any type of placebo or control intervention, outcome: 1.2 Generic ADLs until the end of follow‐up, absolute values (BI points).
Funnel plot of comparison: 2 Secondary outcome measure: tDCS for improvement of upper limb function versus any kind of placebo or control intervention, dropouts, outcome: 2.1 Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) at the end of the intervention phase (UE‐FM points).
Comparison 1 Primary outcome measure: tDCS for improvement of generic ADLs versus any type of placebo or control intervention, Outcome 1 Generic ADLs at the end of the intervention phase, absolute values.
Comparison 1 Primary outcome measure: tDCS for improvement of generic ADLs versus any type of placebo or control intervention, Outcome 2 Generic ADLs until the end of follow‐up, absolute values.
Comparison 2 Secondary outcome measure: tDCS for improvement of upper limb function versus any type of placebo or control intervention, dropouts and adverse events (including death from all causes), Outcome 1 Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) at the end of the intervention phase.
Comparison 2 Secondary outcome measure: tDCS for improvement of upper limb function versus any type of placebo or control intervention, dropouts and adverse events (including death from all causes), Outcome 2 Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) to the end of follow‐up.
Comparison 2 Secondary outcome measure: tDCS for improvement of upper limb function versus any type of placebo or control intervention, dropouts and adverse events (including death from all causes), Outcome 3 Dropouts, adverse events and deaths during intervention phase.
Comparison 3 Subgroup analyses, Outcome 1 Planned analysis: duration of illness—acute/subacute phase versus postacute phase for ADLs at the end of the intervention phase.
Comparison 3 Subgroup analyses, Outcome 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 phase.
| Transcranial direct current stimulation (tDCS) for function and activities of daily living (ADLs) in patients after stroke | ||||||
| Patient or population: patients with function and activities of daily living (ADLs) after stroke | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Transcranial direct current stimulation (tDCS) | |||||
| Generic activities of daily living at the end of the intervention phase, absolute values | Mean generic activities of daily living at the end of the intervention phase; absolute value in the intervention groups was | 435 | ⊕⊝⊝⊝ | |||
| Generic activities of daily living until the end of follow‐up, absolute values | Mean generic activities of daily living until the end of follow‐up; absolute value in the intervention groups was | 99 | ⊕⊕⊝⊝ | |||
| Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) at the end of the intervention phase | Mean upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) at the end of the intervention phase in the intervention groups was | 302 | ⊕⊕⊝⊝ | |||
| Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) to the end of follow‐up | Mean upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) to the end of follow‐up in the intervention groups was | 68 | ⊕⊝⊝⊝ | |||
| Dropouts, adverse events and deaths during intervention phase | Study population | See comment | 427 | ⊕⊕⊕⊕ | Risks were calculated from pooled risk differences | |
| 21 per 1000 | 26 per 1000 | |||||
| Moderate | ||||||
| 0 per 1000 | 0 per 1000 | |||||
| *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). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| 1Downgraded because of unclear and high risk of bias in included studies. | ||||||
| Study | Experimental: | Control: | Experimental: | Control: | Experimental: | Control: | Experimental: | Control: | Experimental: | Control: severity, mean (SD) | Experimental: | Control: | Handedness, n (%) |
| 56 (11.14) years | 75 (NA) years | 33 (33.78) 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 | |
| 42.57 (12.87) years | 50.86 (14.96) years | 44.43 (31.31) months | 26.00 (18.36) months | 4 (57) female | 5 (71) female | 4 (57) left | 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 | |
| 53.67 (16.64) years | 27.08 (24.37) months | 2 (33) female | 3 (50) left | MRC 4.18 (0.37) | Cause not clearly stated by the authors | 6 (100) right‐handed | |||||||
| 44.40 (15.90) years | 65.00 (22.26) years | 30.80 (13.48) days | 25.25 (4.99) 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 | ||
| 63.6 (6.7) years | 63.3 (6.4) years | 25.7 (6.0) months | 26.7 (5.1) months | 2 (20) female | 4 (40) female | Not stated by the authors | 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; | Not stated by the authors | |
| 64.65 (9.55) years | 65.6 (10.3) years | 3.6 (1.61) weeks | 3.8 (1.5) 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 | |
| 59.00 (9.41) years | 57 (7.5) years | 13.08 (5.13) days | 12.6 (4.6) 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 | |
| 62.80 (13.16) years | 6.40 (3.17) 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 | |||||||
| 54.33 (14.97) years | 62.9 (9.2) years | 27.36 (21.45) days | 22.9 (7.5) days | 2 (18) female | 3 (43) female | 7 (64) left | 2 (29) left | BI 71.77 (23.86) | BI 67.9 (22.4) | 11 (100) ischaemic; 3 (27) cortical, 3 (27) corticosubcortical, 5 (71) subcortical | 7 (100) ischaemic; | Not stated by the authors | |
| 61.7 (14.7) years | 55.8 (12.9) years | 30.5 (21.4) months | 40.3 (23.4) 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 | 10 (100) ischaemic | 19 (95) right‐handed, 1 (5) both‐handed | |
| 60.8 (14.11) years | 8.3 (5.45) months | 3 (33) female | 6 (60) left, 3 (30) right, 1 (10) brainstem | JTHFT (without handwriting): 12.3 (7.3) s | 10 (100) ischemic | Not stated by the authors | |||||||
| 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; | 7 (100) ischaemic; | 14 (100) right‐handed | |
| 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 | 10 (40) haemorrhagic, 15 (60) infarction | Not stated by the authors | |
| 66.1 (14.3) years | 70.3 (13.5) years | 2 days | 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; | 25 (100) ischaemic; 2 (8) cortical, 18 (72) corticosubcortical, 5 (20) subcortical | Not stated by the authors | |
| 45.9 (11.2) years | 49.3 (12.6) years | 4.9 (3.0) months | 4.9 (2.9) months | 11 (24) female | 10 (22) female | 24 (53) left | 23 (51) left | BI 55 (range 0 to 85) | BI 55 (range 25 to 95) | 27 (60) ischaemic, 18 (40) haemorrhagic | 26 (58) ischaemic, 19 haemorrhagic (42) | Not stated by the authors | |
| BBT: Box and Block Test | |||||||||||||
| Study | Type of stimulation (polarity) | Electrode position and size | Treatment intensity | Base treatment | Dropouts | Reasons for dropouts and adverse events in the experimental group | Reasons for dropouts and adverse events in the control group | Adverse events | Source of information | |
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere | 1 mA for 20 minutes | A‐tDCS, C‐tDCS or S‐tDCS 4 days once a day | None | None | NA | NA | None | Published | |
| C‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the non‐lesioned hemisphere | |||||||||
| S‐tDCS | Not described by the authors | 1 mA for 30 seconds | ||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere | 2 mA for 40 minutes | Base treatment + A‐tDCS or S‐tDCS 5 days a week for 2 consecutive weeks | CIMT up to 4 hours/d for 5 days a week for 2 consecutive weeks | 7 (33%) | Frustration and tiredness during assessments (Bolognini 2013); these participants have been excluded from analysis and presentation of results | None | Published and unpublished | ||
| S‐tDCS | 2 mA for 30 seconds | |||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere | 1.5 mA for 15 minutes | 1 active tDCS (A‐tDCS, C‐tDCS, dual‐tDCS) and 1 S‐tDCS session in 2 consecutive days | None | None | NA | NA | 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 | ||||||||
| S‐tDCS | Not described by the authors | |||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere | 1 mA for 20 minutes | Each participant underwent A‐tDCS, C‐tDCS and S‐tDCS once, separated by at least 48 hours of rest | None | None | NA | NA | None | Published | |
| C‐tDCS | Saline‐soaked 35 cm² sponge electrodes over the M1 of the non‐lesioned hemisphere | 1 mA for 20 minutes | ||||||||
| S‐tDCS | Not described by the authors | 1 mA for 30 seconds | ||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere | 1.5 mA for 7 minutes | Base treatment + A‐tDCS or S‐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 | NA | NA | None | Published | |
| S‐tDCS | 0 mA for 7 minutes | |||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere | 2 mA for 20 minutes | Base treatment + A‐tDCS, C‐tDCS or S‐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: 1 (14%) during intervention phase 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: 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 | ||||||||
| S‐tDCS | As in the A‐tDCS or the C‐tDCS group (changing consecutively) | 0 mA for 20 minutes | ||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere | 2 mA for 25 minutes | Base treatment + A‐tDCS, C‐tDCS or S‐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 | NA | NA | None | Published | |
| C‐tDCS | Saline‐soaked 35 cm² sponge electrodes, cathode over M1 of the non‐lesioned hemisphere | 2 mA for 25 minutes | ||||||||
| S‐tDCS | Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere | 2 mA for 2 minutes | ||||||||
| A‐tDCS | Saline‐soaked 25 cm² sponge electrodes, anode over M1 of the lesioned hemisphere | 1 mA for 20 minutes | Each participant underwent A‐tDCS and S‐tDCS, separated by at least 24 hours of rest | None | None | NA | NA | None | Published and unpublished | |
| S‐tDCS | 1 mA for 30 seconds | |||||||||
| A‐tDCS | Saline‐soaked 25 cm² sponge electrodes over M1 of the lesioned hemisphere (as confirmed by MEP) | 2 mA for 20 minutes | Base treatment + A‐tDCS, C‐tDCS or S‐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 | No dropouts | 2 | Published | |
| C‐tDCS | Saline‐soaked 25 cm² sponge electrodes over M1 of the non‐lesioned hemisphere (confirmed by MEP) | 2 mA for 20 minutes | ||||||||
| S‐tDCS | Saline‐soaked 25 cm² sponge electrodes over M1 of the lesioned hemisphere (confirmed by MEP) | 2 mA for 1 minutes | ||||||||
| 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 S‐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 | NA | NA | None | Published | |
| S‐tDCS | 1.5 mA for 30 seconds | |||||||||
| A‐tDCS1 | Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere and cathode placed over the contralateral orbit | 1 mA for 20 minutes | Each participant underwent A‐tDCS1, A‐tDCS2, C‐tDCS, dual‐tDCS and S‐tDCS once with a washout period of at least 96 hours | None | None | NA | NA | Not clearly stated, most likely none | Published | |
| A‐tDCS2 | Saline‐soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere and cathode placed 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 | 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 | ||||||||
| S‐tDCS | Not described by the authors | 1 mA for 30 seconds | ||||||||
| C‐tDCS | Saline‐soaked sponge electrodes with the cathode over M1 of the lesioned hemisphere | 1 mA for 30 minutes | Base‐treatment + C‐tDCS or S‐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 | NA | NA | None | Published | |
| S‐tDCS | Not described by the authors | For 30 minutes | ||||||||
| C‐tDCS | Saline‐soaked 18 cm² sponge electrodes over primary sensorimotor cortex of the lesioned hemisphere | 0.5 mA for 20 minutes, once a day for 5 consecutive days for 4 weeks | NA | None | NA | NA | 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 | ||||||||
| A‐tDCS | Saline‐soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere | 2 mA for 20 minutes | Once a day for 5 consecutive days | Not described by the authors | None | NA | NA | None | Published | |
| S‐tDCS | 2 mA for 30 seconds | |||||||||
| C‐tDCS | Saline‐soaked 24.75 cm² sponge electrodes over primary sensorimotor cortex of the lesioned hemisphere | 1.2 mA for 20 minutes | Once daily 5 days a week for 4 weeks | Quote: "Both groups received a conventional physical therapy program | None | NA | NA | None | Published | |
| S‐tDCS | 1.2 mA for 30 seconds | |||||||||
| A‐tDCS: anodal direct current stimulation. | ||||||||||
| Sensitivity analysis | Studies included in analysis | Effect estimate |
| All studies with proper allocation concealment | (MD 6.93; 95% CI ‐0.23 to 14.10; inverse variance method with random‐effects model) | |
| All studies with proper blinding of outcome assessor for primary outcome | (MD 5.31; 95% CI ‐0.52 to 11.14; inverse variance method with random‐effects model) | |
| All studies with intention‐to‐treat analysis | (MD 4.92; 95% CI ‐1.31 to 11.15; inverse variance method with random‐effects model) | |
| BI: Barthel Index. | ||
| Sensitivity analysis | Studies included in analysis | Effect estimate |
| All studies with proper allocation concealment | (MD 16.38 BI points; 95% CI 6.09 to 26.68; inverse variance method with random‐effects model) | |
| All studies with proper blinding of outcome assessor for primary outcome | (MD 11.16 BI points; 95% CI 2.89 to 19.43; inverse variance method with random‐effects model) | |
| All studies with intention‐to‐treat analysis | (MD 11.31 BI points; 95% CI ‐1.55 to 24.18; inverse variance method with random‐effects model) | |
| BI: Barthel Index. | ||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Generic ADLs at the end of the intervention phase, absolute values Show forest plot | 5 | 286 | Mean Difference (IV, Random, 95% CI) | 5.31 [‐0.52, 11.14] |
| 2 Generic ADLs until the end of follow‐up, absolute values Show forest plot | 3 | 99 | Mean Difference (IV, Random, 95% CI) | 11.16 [2.89, 19.43] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) at the end of the intervention phase Show forest plot | 7 | 302 | Mean Difference (IV, Random, 95% CI) | 3.45 [1.24, 5.67] |
| 1.1 Change scores | 4 | 144 | Mean Difference (IV, Random, 95% CI) | 3.51 [1.35, 5.68] |
| 1.2 Absolute values | 3 | 158 | Mean Difference (IV, Random, 95% CI) | 2.51 [‐5.08, 10.10] |
| 2 Upper extremity function as measured by Fugl‐Meyer Score (UE‐FM) to the end of follow‐up Show forest plot | 2 | 68 | Mean Difference (IV, Random, 95% CI) | 9.22 [‐13.47, 31.90] |
| 2.1 Change scores | 1 | 18 | Mean Difference (IV, Random, 95% CI) | 21.60 [8.50, 34.70] |
| 2.2 Absolute values | 1 | 50 | Mean Difference (IV, Random, 95% CI) | ‐1.60 [‐7.28, 4.08] |
| 3 Dropouts, adverse events and deaths during intervention phase Show forest plot | 11 | 427 | Risk Difference (M‐H, Random, 95% CI) | 0.00 [‐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 phase Show forest plot | 5 | 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, respectively) | 3 | 146 | Mean Difference (IV, Random, 95% CI) | 5.23 [‐3.74, 14.21] |
| 1.2 Postacute phase (from the first to the sixth month after stroke) | 2 | 140 | Mean Difference (IV, Random, 95% CI) | 10.78 [2.53, 19.02] |
| 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 phase Show forest plot | 5 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 2.1 A‐tDCS over the lesioned hemisphere | 3 | 104 | Mean Difference (IV, Random, 95% CI) | 4.92 [‐6.54, 16.39] |
| 2.2 C‐tDCS over the non‐lesioned hemisphere | 3 | 102 | Mean Difference (IV, Random, 95% CI) | 8.31 [1.11, 15.50] |
| 2.3 C‐tDCS over the lesioned hemisphere | 2 | 140 | Mean Difference (IV, Random, 95% CI) | 10.78 [2.53, 19.02] |
