Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke

  • Review
  • Intervention

Authors

  • Bernhard Elsner,

    Corresponding author
    1. Technical University Dresden, Department of Public Health, Dresden Medical School, Dresden, Sachsen, Germany
    • Bernhard Elsner, Department of Public Health, Dresden Medical School, Technical University Dresden, Fetscherstr. 74, Dresden, Sachsen, 01307, Germany. brnhrd.lsnr@googlemail.com.

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  • Joachim Kugler,

    1. Technical University Dresden, Department of Public Health, Dresden Medical School, Dresden, Sachsen, Germany
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  • Marcus Pohl,

    1. Klinik Bavaria Kreischa, Abteilung Neurologie und Fachübergreifende Rehabilitation, Kreischa, Germany
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  • Jan Mehrholz

    1. Technical University Dresden, Department of Public Health, Dresden Medical School, Dresden, Sachsen, Germany
    2. Private Europäische Medizinische Akademie der Klinik Bavaria in Kreischa GmbH, Wissenschaftliches Institut, Kreischa, Germany
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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 In an effort to identify further published, unpublished and ongoing trials, we searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers.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.

Résumé scientifique

Stimulation transcrânienne par courant direct (tDCS) pour améliorer la fonction motrice et les activités de la vie quotidienne chez les patients après un accident vasculaire cérébral (AVC)

Contexte

L'AVC est l'une des principales causes d'invalidité dans le monde. La déficience fonctionnelle, entraînant de mauvaises performances dans les activités de la vie quotidienne chez les survivants d'AVC, est fréquente. Les approches de rééducation actuelles suite à un AVC ont une efficacité limitée dans l'amélioration de la vie quotidienne et la performance fonctionnelle, mais un complément à la rééducation après un AVC pourrait être la stimulation cérébrale non invasive par stimulation transcrânienne par courant direct (tDCS) afin de modifier l'excitabilité corticale et d'améliorer ainsi les performances et la fonction.

Objectifs

Évaluer les effets de tDCS sur les activités générales de la vie quotidienne et la fonction motrice chez les patients victimes d'un AVC.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le groupe Cochrane sur les accidents vasculaires cérébraux (mars 2013), le registre Cochrane des essais contrôlés (CENTRAL) ( La Bibliothèque Cochrane , mai 2013), MEDLINE (de 1948 à mai 2013), EMBASE (de 1980 à mai 2013), CINAHL (de 1982 à mai 2013), AMED (1985 à mai 2013), Science Citation Index (de 1899 à mai 2013) et quatre bases de données supplémentaires. En vue d'identifier d'autres essais publiés, non publiés et en cours, nous avons cherché dans des registres d'essais et les références bibliographiques, recherché manuellement des actes de conférence et contacté les auteurs et les fabricants d'équipements.

Critères de sélection

Nous avons uniquement inclus des essais contrôlés randomisés (ECR) et des essais contrôlés randomisés croisés (dans lesquels nous avons uniquement analysé la première période selon un schéma en groupes parallèles) ayant comparé la stimulation transcrânienne par courant direct (tDCS) à une thérapie témoin chez des adultes atteints d'un accident vasculaire cérébral (AVC) pour améliorer les performances de la vie quotidienne et la fonction motrice.

Recueil et analyse des données

Deux auteurs de la revue ont indépendamment évalué la qualité des essais et extrait les données. Si nécessaire, nous avons contacté les auteurs des études pour obtenir des informations supplémentaires. Nous avons recueilli des informations sur les sorties d'étude et sur les effets indésirables dans les rapports d'essais.

Résultats principaux

Nous avons inclus 15 études impliquant 455 participants. Les analyses de six études, portant sur 326 participants, concernant notre critère de jugement principal, les activités de la vie quotidienne (AVQ), n’ont montré aucune preuve d'un effet en faveur de tDCS à la fin de la phase d'intervention (différence moyenne (DM) à 5,31 index de Barthel (BI) points; intervalle de confiance (IC) de 0,52 à 11,14; de la méthode de variance inverse avec modèle à effets aléatoires), tandis que lors du suivi (DM 11,13 BI points; IC à 95%, entre 2,89 à 19,37; la méthode de variance inverse avec modèle à effets aléatoires), nous avons trouvé des preuves d'un effet. Cependant, les intervalles de confiance étaient larges et l'effet était pas maintenu lorsque seules les études à faible risque de biais ont été inclues. Pour notre critère de jugement secondaire, la fonction des membres supérieurs, nous avons analysé huit essais totalisant 358 participants, qui rapportaient des preuves d'un effet en faveur de tDCS à la fin de la phase d'intervention (DM à 3,45 points sur le score Upper Extremity Fugl-Meyer (points UE-FM); IC à 95% de 1,24 à 5,67; la méthode de variance inverse avec modèle à effets aléatoires), mais pas à la fin du suivi de trois mois après l'intervention (DM 9,23 points UE-FM; IC à 95% - de 13,47 à 31,94 ; de la méthode de variance inverse avec modèle à effets aléatoires). Ces résultats étaient sensibles à l'inclusion d'études présentant un risque de biais élevé. Les effets indésirables étaient rapportés et le nombre d’abandon et d’effets indésirables étaient comparables entre les groupes (différence de risques (DR) à 95% 0,00; IC à 95% -de 0,02 à 0,03; méthode de Mantel-Haenszel avec modèle à effets aléatoires).

Conclusions des auteurs

À l'heure actuelle, les preuves de faible à très faible qualité sont disponibles sur l'efficacité des tDCS (anodique/cathodique/double) par rapport à un contrôle (témoin/toute autre intervention) pour améliorer les performances des activités de la vie quotidienne et la fonction après un AVC. Des recherches devraient étudier les effets de tDCS sur la fonction des membres inférieurs et devraient examiner les questions méthodologiques en rapportant régulièrement les données sur les effets indésirables, les abandons et l'assignation secrète et en réalisant des analyses en intention de traiter.

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.

Résumé simplifié

Courant électrique direct dans le cerveau pour réduire la déficience de la fonction motrice et des activités de la vie quotidienne après un accident vasculaire cérébral (AVC)

L'AVC est l'une des principales causes d'invalidité dans le monde. La plupart des AVC se produisent quand un caillot de sang bloque un vaisseau sanguin menant au cerveau. Sans un approvisionnement de sang adéquat, le cerveau subit rapidement des dommages qui peuvent être permanents et engendrent souvent une déficience des activités de la vie quotidienne et de la fonction motrice chez les survivants d’AVC. Les stratégies de rééducation actuelles ont une efficacité limitée dans l'amélioration de ces troubles. Une possibilité pour améliorer les effets de la rééducation pourrait être l'ajout de la stimulation cérébrale non invasive réalisée par une technique dénommée stimulation transcrânienne par courant direct (transcranial direct current stimulation, tDCS). Cette technique consiste à manipuler les fonctions cérébrales et peut être utilisée pour réduire les troubles des activités de la vie quotidienne et de la fonction motrice. Cependant, l'efficacité de cette intervention pour améliorer les résultats de la réadaptation reste inconnue. Cette revue de 15 essais, impliquant 455 participants, a trouvé des preuves de faible à très faible qualité sur l'efficacité de tDCS pour améliorer les résultats de la réadaptation concernant la vie quotidienne et la fonction motrice. Ces résultats sont imprécis et l'effet n’était pas maintenu lorsque seules les études de bonne qualité méthodologique étaient inclues. Les proportions d'effets indésirables étaient comparables entre les groupes. Des recherches supplémentaires sont nécessaires dans ce domaine pour généraliser ces résultats, en particulier en ce qui concerne la fonction des membres inférieurs.

Notes de traduction

Traduit par: French Cochrane Centre 14th January, 2014
Traduction financée par: Minist�re Fran�ais des Affaires sociales et de la Sant�, Instituts de Recherche en Sant� du Canada, Minist�re de la Sant� et des Services Sociaux du Qu�bec, Fonds de recherche du Qu�bec Sant� et Institut National d'Excellence en Sant� et en Services Sociaux

Summary of findings(Explanation)

Summary of findings for the main comparison. Transcranial direct current stimulation (tDCS) for function and activities of daily living (ADLs) in patients after stroke
  1. 1Downgraded because of unclear and high risk of bias in included studies.
    2Lower confidence limit includes clinically irrelevant difference.
    3Funnel plot shows asymmetry in the absence of substantial heterogeneity (I2 > 50%).
    4Lower confidence limit includes clinically irrelevant difference.
    5Downgraded because of a considerable proportion of unclear or high risk of bias.
    6Downgraded because of a considerable proportion of unclear risk of bias.
    7Downgraded because of small sample size and a very wide confidence interval, including no differences between groups.

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
Settings:
Intervention: transcranial direct current stimulation (tDCS)
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Control Transcranial direct current stimulation (tDCS)
Generic activities of daily living at the end of the intervention phase, absolute values
Barthel Index
 Mean generic activities of daily living at the end of the intervention phase; absolute value in the intervention groups was
6.61 higher
(0.23 to 12.99 higher)
 435
(6 studies)
⊕⊝⊝⊝
very low 1,2,3
 
Generic activities of daily living until the end of follow-up, absolute values
Barthel Index
Follow-up: median 3 months
 Mean generic activities of daily living until the end of follow-up; absolute value in the intervention groups was
11.16 higher
(2.89 to 19.43 higher)
 99
(3 studies)
⊕⊕⊝⊝
low 1,4
 
Upper extremity function as measured by Fugl-Meyer Score (UE-FM) at the end of the intervention phase
Upper Extremity Fugl-Meyer Assessment
 Mean upper extremity function as measured by Fugl-Meyer Score (UE-FM) at the end of the intervention phase in the intervention groups was
3.54 higher
(1.23 to 5.84 higher)
 302
(6 studies)
⊕⊕⊝⊝
low 4,5
 
Upper extremity function as measured by Fugl-Meyer Score (UE-FM) to the end of follow-up
Upper Extremity Fugl-Meyer Assessment
Follow-up: mean 4.5 months
 Mean upper extremity function as measured by Fugl-Meyer Score (UE-FM) to the end of follow-up in the intervention groups was
9.22 higher
(13.47 lower to 31.9 higher)
 68
(2 studies)
⊕⊝⊝⊝
very low 4,5
 
Dropouts, adverse events and deaths during intervention phase
Numbers of dropouts, adverse events and deaths from all causes
Study populationSee comment427
(11 studies)
⊕⊕⊕⊕
high
Risks were calculated from pooled risk differences
21 per 1000 26 per 1000
(1 to 51)
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).
CI: Confidence interval; RR: Risk ratio.
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.

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.

  1. Frenchay Activities Index (FAI) (Schuling 1993).

  2. Barthel ADL Index (BI) (Mahoney 1965).

  3. Rivermead ADL Assessment (Whiting 1980).

  4. Modified Rankin Scale (mRS) (Bonita 1988).

  5. 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:

  1. Action Research Arm Test (ARAT) (Lyle 1981);

  2. Fugl-Meyer Score (Fugl-Meyer 1975);

  3. Nine-Hole Peg Test (NHPT) (Sharpless 1982); and

  4. Jebsen Taylor Hand Function Test (JTHFT) (Jebsen 1969).

For lower limb function:

  1. walking velocity (in metres per second);

  2. walking capacity (metres walked in six minutes); and

  3. Functional Ambulation Categories (FAC) (Holden 1984).

For muscle strength:

  1. grip force (measured by handheld dynamometer) (Boissy 1999); and

  2. 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:

  1. Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, May 2013) (Appendix 1);

  2. MEDLINE (1948 to May 2013) (Appendix 2);

  3. EMBASE (1980 to May 2013) (Appendix 2);

  4. CINAHL (1982 to May 2013) (Appendix 3);

  5. AMED (1985 to May 2013) (Appendix 2);

  6. Science Citation Index (Web of Science) (1899 to May 2013) (Appendix 4);

  7. Physiotherapy Evidence Database (PEDro) at http://www.pedro.org.au/ (May 2013) (Appendix 5);

  8. Rehabdata at www.naric.com/?q=REHABDATA (1956 to May 2013) (Appendix 6);

  9. Compendex (1969 to May 2013).(Appendix 7); and

  10. 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):

  1. Stroke Trials Registry (www.strokecenter.org/trials/);

  2. Current Controlled Trials (www.controlled-trials.com/);

  3. ClinicalTrials.gov (http://clinicaltrials.gov);

  4. EU Clinical Trials Register (www.clinicaltrialsregister.eu/); and

  5. 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.

  1. 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 and 2012);

    2. 1st, 2nd, 3rd, 4th, 5th and 6th World Congress of Physical and Rehabilitation Medicine (2001, 2003, 2005, 2007, 2009 and 2011);

    3. Deutsche Gesellschaft für Neurotraumatologie und Klinische Neurorehabilitation (2001 to 2012);

    4. Deutsche Gesellschaft für Neurologie (2000 to 2012);

    5. Deutsche Gesellschaft für Neurorehabilitation (1999 to 2012); and

    6. 1st, 2nd and 3rd Asian Oceania Conference of Physical and Rehabilitation Medicine (2008, 2010 and 2012).

  2. Screened reference lists from relevant reviews, articles and textbooks.

  3. Contacted authors of identified trials and other researchers in the field.

  4. Used Science Citation Index Cited Reference Search for forward tracking of important articles.

  5. Contacted the following equipment manufacturers (April 2013):

    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); and

    10. Trans Cranial Technologies, Hong Kong (www.trans-cranial.com).

  6. 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:

  1. methods of random sequence generation;

  2. methods of allocation concealment;

  3. blinding of assessors;

  4. use of an intention-to-treat (ITT) analysis;

  5. adverse effects and dropouts;

  6. important differences in prognostic factors;

  7. participants (country, number of participants, age, gender, type of stroke, time from stroke onset to study entry and inclusion and exclusion criteria);

  8. comparison (details of interventions in treatment and control groups, duration of treatment and details of co-interventions in the groups);

  9. outcomes; and

  10. 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:

  1. 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);

  2. type of stimulation: cathodal versus anodal and position of electrodes/location of stimulation; and

  3. 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.

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.

Table 1. Patient characteristics
  1. 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
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 (%)
Boggio 2007a56 (11.14) years75 (NA) years33 (33.78) months39 months3 (100) male1 (100) male2 (67) left1 (100) leftMRC 4.2 (0.53)MRC 4.7 (NA)3 (100) ischaemic and subcortical1 (100) ischaemic and subcortical12 (100) right-handed
Bolognini 201142.57 (12.87) years50.86 (14.96) years

44.43 (31.31)

months

26.00 (18.36) months4 (57) female5 (71) female4 (57) left4 (57) leftBI 18.13 (2.42)BI 14.33 (5.46)2 (29) haemorrhagic, 5 (71) ischaemic7 (100) ischaemic14 (100) right-handed
Fregni 2005a53.67 (16.64) years27.08 (24.37) months2 (33) female3 (50) leftMRC 4.18 (0.37)Cause not clearly stated by the authors6 (100) right-handed
Fusco 201344.40 (15.90) years65.00 (22.26) years30.80 (13.48) days25.25 (4.99) days3 (60) female1 (25) female3 (60) left2 (50) leftGrasp force 17.83 (7.45) kg5 (100) ischaemic3 (75) ischaemic, 1 (25) haemorrhagic9 (100) right-handed
Geroin 201163.6 (6.7) years63.3 (6.4) years25.7 (6.0) months26.7 (5.1) months2 (20) female4 (40) femaleNot stated by the authorsNot stated by the authorsESS 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 201164.65 (9.55) years65.6 (10.3) years3.6 (1.61) weeks3.8 (1.5) weeks26 (41) female11 (34) female35 (55) left16 (50) leftBI 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) LACI32 (100) ischaemic; 13 (41) TACI, 13 (41) PACI, 6 (18) LACINot stated by the authors
Khedr 201359.00 (9.41) years57 (7.5) years13.08 (5.13) days12.6 (4.6) days9 (33) female5 (38) female12 (44) left6 (46) leftBI 32.76 (10.75)BI 31.1 (12.6)27 (100) ischaemic; 12 (44) cortical, 5 (19) corticosubcortical, 10 (37) subcortical13 (100) ischaemic; 6 (42) cortical, 3 (23) corticosubcortical, 4 (31) subcorticalNot stated by the authors
Kim 200962.80 (13.16) years6.40 (3.17) weeks7 (70) female8 (80) leftMRC between 3 and 5 for the all paretic finger flexors and extensors8 (80) infarction, 2 (20) haemorrhageNot stated by the authors
Kim 201054.33 (14.97) years62.9 (9.2) years27.36 (21.45) days22.9 (7.5) days2 (18) female3 (43) female7 (64) left2 (29) leftBI 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
Lindenberg 201061.7 (14.7) years55.8 (12.9) years30.5 (21.4) months40.3 (23.4) months2 (20) female3 (30) female6 (60) left7 (70) leftUE-FM 38.2 (13.3)UE-FM 39.8 (11.5)10 (100) ischaemic10 (100) ischaemic19 (95) right-handed, 1 (5) both-handed
Mahmoudi 201160.8 (14.11) years8.3 (5.45) months3 (33) female6 (60) left, 3 (30) right, 1 (10) brainstemJTHFT (without handwriting): 12.3 (7.3) s10 (100) ischemicNot stated by the authors
Nair 201161 (12) years56 (15) years33 (20) months28 (28) months2 (29) female3 (43) female3 (43) left5 (71) leftUE-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
Qu 200945 (11) years45 (14) years6 (range 3 to 36) months4 (range 3 to 12) months4 (16) female3 (12) female14 (56) left13 (52) leftBI 64 (17)BI 72 (22)10 (40) haemorrhagic, 15 (60) infarction10 (40) haemorrhagic, 15 (60) infarctionNot stated by the authors
Rossi 201366.1 (14.3) years70.3 (13.5) years2 days2 days13 (52) female11 (44) female18 (72) left16 (64) leftUE-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) subcorticalNot stated by the authors
Wu 201345.9 (11.2) years49.3 (12.6) years4.9 (3.0) months4.9 (2.9) months11 (24) female10 (22) female24 (53) left23 (51) leftBI 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) haemorrhagic26 (58) ischaemic, 19 haemorrhagic (42)Not stated by the authors
Table 2. Demographics of studies, including dropouts and adverse events
  1. 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.

Study
ID
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
Boggio 2007aA-tDCSSaline-soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere1 mA for 20 minutesA-tDCS, C-tDCS or S-tDCS 4 days once a dayNoneNoneNANANonePublished
C-tDCSSaline-soaked 35 cm² sponge electrodes over the M1 of the non-lesioned hemisphere
S-tDCSNot described by the authors1 mA for 30 seconds
Bolognini 2011A-tDCSSaline-soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere2 mA for 40 minutesBase treatment + A-tDCS or S-tDCS 5 days a week for 2 consecutive weeksCIMT up to 4 hours/d for 5 days a week for 2 consecutive weeks7 (33%)Frustration and tiredness during assessments (Bolognini 2013); these participants have been excluded from analysis and presentation of resultsNonePublished and unpublished
S-tDCS2 mA for 30 seconds
Fusco 2013A-tDCSSaline-soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere1.5 mA for 15 minutes1 active tDCS (A-tDCS, C-tDCS, dual-tDCS) and 1 S-tDCS session in 2 consecutive daysNoneNoneNANANonePublished and unpublished
C-tDCSSaline-soaked 35 cm² sponge electrodes over the M1 of the non-lesioned hemisphere1.5 mA for 15 minutes
Dual-tDCSSaline-soaked 35 cm² sponge electrodes with the anode over M1 of the lesioned hemisphere and the cathode over M1 of the non-lesioned hemisphere1.5 mA for 15 minutes
S-tDCSNot described by the authors
Fregni 2005aA-tDCSSaline-soaked 35 cm² sponge electrodes over the M1 of the lesioned hemisphere1 mA for 20 minutesEach participant underwent A-tDCS, C-tDCS and S-tDCS once, separated by at least 48 hours of restNoneNoneNANANonePublished
C-tDCSSaline-soaked 35 cm² sponge electrodes over the M1 of the non-lesioned hemisphere1 mA for 20 minutes
S-tDCSNot described by the authors1 mA for 30 seconds
Geroin 2011A-tDCSSaline-soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere1.5 mA for 7 minutesBase treatment + A-tDCS or S-tDCS 5 days a week for 2 consecutive weeks50-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 trainingNoneNANANonePublished
S-tDCS0 mA for 7 minutes
Hesse 2011A-tDCSSaline-soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere2 mA for 20 minutesBase treatment + A-tDCS, C-tDCS or S-tDCS 5 days a week for 6 consecutive weeks20 minutes of robot-assisted arm training 5 days a week for 6 consecutive weeks11 (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 enrolmentNonePublished
C-tDCSSaline-soaked 35 cm² sponge electrodes over M1 of the non-lesioned hemisphere2 mA for 20 minutes
S-tDCSAs in the A-tDCS or the C-tDCS group (changing consecutively)0 mA for 20 minutes
Khedr 2013A-tDCSSaline-soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere2 mA for 25 minutesBase treatment + A-tDCS, C-tDCS or S-tDCS for 6 consecutive days afterRehabilitation program within 1 hour after each tDCS session, starting with passive movement and range of motion exercise up to active resistive exerciseNoneNANANonePublished
C-tDCSSaline-soaked 35 cm² sponge electrodes, cathode over M1 of the non-lesioned hemisphere2 mA for 25 minutes
S-tDCSSaline-soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere2 mA for 2 minutes
Kim 2009A-tDCSSaline-soaked 25 cm² sponge electrodes, anode over M1 of the lesioned hemisphere1 mA for 20 minutesEach participant underwent A-tDCS and S-tDCS, separated by at least 24 hours of restNoneNoneNANANonePublished and unpublished
S-tDCS1 mA for 30 seconds
Kim 2010A-tDCSSaline-soaked 25 cm² sponge electrodes over M1 of the lesioned hemisphere (as confirmed by MEP)2 mA for 20 minutesBase treatment + A-tDCS, C-tDCS or S-tDCS 5 days a week for 2 consecutive weeks at the beginning of each therapy sessionOccupational therapy according to a standardised protocol aimed at improving paretic hand function for 30 minutes 5 days a week for 2 consecutive weeks2 of 201 participant discontinued treatment because of dizziness and another because of headacheNo dropouts2Published
C-tDCSSaline-soaked 25 cm² sponge electrodes over M1 of the non-lesioned hemisphere (confirmed by MEP)2 mA for 20 minutes
S-tDCSSaline-soaked 25 cm² sponge electrodes over M1 of the lesioned hemisphere (confirmed by MEP)2 mA for 1 minutes
Lindenberg 2010Dual-tDCSSaline-soaked 16.3 cm² sponge electrodes with the anode over M1 of the lesioned hemisphere and the cathode over M1 of the non-lesioned hemisphere1.5 mA for 30 minutesBase treatment + dual-tDCS or S-tDCS at 5 consecutive sessions on 5 consecutive daysPhysical and occupational therapy sessions at 5 consecutive sessions on 5 consecutive days for 60 minutes, including functional motor tasksNoneNANANonePublished
S-tDCS1.5 mA for 30 seconds
Mahmoudi 2011A-tDCS1Saline-soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere and cathode placed over the contralateral orbit1 mA for 20 minutesEach participant underwent A-tDCS1, A-tDCS2, C-tDCS, dual-tDCS and S-tDCS once with a washout period of at least 96 hoursNoneNoneNANANot clearly stated, most likely nonePublished
A-tDCS2Saline-soaked 35 cm² sponge electrodes, anode over M1 of the lesioned hemisphere and cathode placed on the contralateral deltoid muscle1 mA for 20 minutes
C-tDCSSaline-soaked 35 cm² sponge electrodes, cathode over M1 of the non-lesioned hemisphere1 mA for 20 minutes
Dual-tDCSSaline-soaked 35 cm² sponge electrodes with the anode over M1 of the lesioned hemisphere and the cathode over M1 of the non-lesioned hemisphere1 mA for 20 minutes
S-tDCSNot described by the authors1 mA for 30 seconds
Nair 2011C-tDCSSaline-soaked sponge electrodes with the cathode over M1 of the lesioned hemisphere1 mA for 30 minutesBase-treatment + C-tDCS or S-tDCS for 5 consecutive daily sessions, each at the beginning of the base treatment sessionsOccupational therapy (PNF; shoulder abduction, external rotation, elbow extension, forearm pronation) for 5 consecutive daily sessions (60 minutes each)NoneNANANonePublished
S-tDCSNot described by the authorsFor 30 minutes
Qu 2009C-tDCSSaline-soaked 18 cm² sponge electrodes over primary sensorimotor cortex of the lesioned hemisphere0.5 mA for 20 minutes, once a day for 5 consecutive days for 4 weeksNANoneNANANonePublished
PTNAPhysical therapy according to the Bobath, Brunnstrom and Rood approaches for 40 minutes twice a day for 5 consecutive days for 4 weeks
Rossi 2013A-tDCSSaline-soaked 35 cm² sponge electrodes over M1 of the lesioned hemisphere2 mA for 20 minutesOnce a day for 5 consecutive daysNot described by the authorsNoneNANANonePublished
S-tDCS2 mA for 30 seconds
Wu 2013C-tDCSSaline-soaked 24.75 cm² sponge electrodes over primary sensorimotor cortex of the lesioned hemisphere1.2 mA for 20 minutesOnce daily 5 days a week for 4 weeksQuote: "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"
NoneNANANonePublished
S-tDCS1.2 mA for 30 seconds

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.

Figure 2.

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

See: Summary of findings for the main comparison Transcranial direct current stimulation (tDCS) for function and activities of daily living (ADLs) in patients after stroke

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.

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).

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).

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.

Table 3. Sensitivity analyses for primary outcome of ADL performance at the end of the intervention phase
  1. BI: Barthel Index.
    CI: confidence interval.
    MD: mean difference.

Sensitivity analysis Studies included in analysis Effect estimate
All studies with proper allocation concealment Hesse 2011; Khedr 2013; Kim 2010; Wu 2013(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 Hesse 2011; Khedr 2013; Kim 2010; Qu 2009; Wu 2013(MD 5.31; 95% CI -0.52 to 11.14; inverse variance method with random-effects model)
All studies with intention-to-treat analysis Hesse 2011; Khedr 2013; Qu 2009; Wu 2013(MD 4.92; 95% CI -1.31 to 11.15; inverse variance method with random-effects model)
Table 4. Sensitivity analyses for primary outcome of ADL performance at the end of follow-up at least 3 months after the end of the intervention phase
  1. BI: Barthel Index.
    CI: confidence interval.
    MD: mean difference.

Sensitivity analysis Studies included in analysis Effect estimate
All studies with proper allocation concealment Khedr 2013; Kim 2010(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 Khedr 2013; Kim 2010; Rossi 2013(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 Khedr 2013; Rossi 2013(MD 11.31 BI points; 95% CI -1.55 to 24.18; inverse variance method with random-effects model)

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 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.

  1. Most of the studies included participants with first-time ever stroke.

  2. 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 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.

Authors' conclusions

Implications for practice

Currently, evidence of very low to low quality suggests the effectiveness of tDCS (A-tDCS/C-tDCS/dual-tDCS) versus control (S-tDCS or any other approach or no intervention) for improving generic activities of daily living (ADLs) and function after stroke. However, evidence of high quality indicates that no effect regarding dropouts and adverse events can be seen between tDCS and control groups.

Implications for research

Further large-scale randomised controlled trials with a parallel-group design, broad inclusion criteria and sample size estimation in this area are needed to strengthen the evidence base, particularly regarding the effects of tDCS on lower limb function and the interaction of stimulation location (over the lesioned or the non-lesioned hemisphere) with types of tDCS administered (A-tDCS/C-tDCS/dual-tDCS). Methodological quality of future studies, particularly in relation to allocation concealment and intention-to-treat analysis, needs to be improved, along with dropout and adverse event reporting. Information on treatment order in randomised cross-over trials should be routinely presented in future publications.

Acknowledgements

We thank Brenda Thomas for assistance in developing the search strategy and Hazel Fraser for giving us helpful support.

Data and analyses

Download statistical data

Comparison 1. Primary outcome measure: tDCS for improvement of generic ADLs versus any type of placebo or control intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Generic ADLs at the end of the intervention phase, absolute values5286Mean Difference (IV, Random, 95% CI)5.31 [-0.52, 11.14]
2 Generic ADLs until the end of follow-up, absolute values399Mean Difference (IV, Random, 95% CI)11.16 [2.89, 19.43]
Analysis 1.1.

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.

Analysis 1.2.

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 or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Upper extremity function as measured by Fugl-Meyer Score (UE-FM) at the end of the intervention phase7302Mean Difference (IV, Random, 95% CI)3.45 [1.24, 5.67]
1.1 Change scores4144Mean Difference (IV, Random, 95% CI)3.51 [1.35, 5.68]
1.2 Absolute values3158Mean 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-up268Mean Difference (IV, Random, 95% CI)9.22 [-13.47, 31.90]
2.1 Change scores118Mean Difference (IV, Random, 95% CI)21.60 [8.50, 34.70]
2.2 Absolute values150Mean Difference (IV, Random, 95% CI)-1.60 [-7.28, 4.08]
3 Dropouts, adverse events and deaths during intervention phase11427Risk Difference (M-H, Random, 95% CI)0.00 [-0.02, 0.03]
Analysis 2.1.

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.

Analysis 2.2.

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.

Analysis 2.3.

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 or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Planned analysis: duration of illness—acute/subacute phase versus postacute phase for ADLs at the end of the intervention phase5 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)3146Mean Difference (IV, Random, 95% CI)5.23 [-3.74, 14.21]
1.2 Postacute phase (from the first to the sixth month after stroke)2140Mean 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 phase5 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 A-tDCS over the lesioned hemisphere3104Mean Difference (IV, Random, 95% CI)4.92 [-6.54, 16.39]
2.2 C-tDCS over the non-lesioned hemisphere3102Mean Difference (IV, Random, 95% CI)8.31 [1.11, 15.50]
2.3 C-tDCS over the lesioned hemisphere2140Mean Difference (IV, Random, 95% CI)10.78 [2.53, 19.02]
Analysis 3.1.

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.

Analysis 3.2.

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.

Appendices

Appendix 1. MEDLINE, EMBASE, AMED and INSPEC (Ovid SP) search strategies

1. cerebrovascular disorders/ or exp basal ganglia cerebrovascular disease/ or exp brain ischemia/ or exp carotid artery diseases/ or exp intracranial arterial diseases/ or exp "intracranial embolism and thrombosis"/ or exp intracranial haemorrhages/ or stroke/ or exp brain infarction/ or vertebral artery dissection/
2. (stroke or poststroke or post-stroke or cerebrovasc$ or brain vasc$ or cerebral vasc$ or cva$ or apoplex$ or SAH).tw.
3. ((brain$ or cerebr$ or cerebell$ or intracran$ or intracerebral) adj5 (isch?emi$ or infarct$ or thrombo$ or emboli$ or occlus$)).tw.
4. ((brain$ or cerebr$ or cerebell$ or intracerebral or intracranial or subarachnoid) adj5 (haemorrhage$ or haemorrhage$ or haematoma$ or hematoma$ or bleed$)).tw.
5. hemiplegia/ or exp paresis/
6. (hemipleg$ or hemipar$ or paresis or paretic).tw.
7. or/1-6
8. Electric Stimulation Therapy/
9. Electric Stimulation/
10. Electrodes/
11. (transcranial adj5 direct current adj5 stimulation).tw.
12. (transcranial adj5 DC adj5 stimulation).tw.
13. (transcranial adj5 electric$ adj5 stimulation).tw.
14. (tDCS or A-tDCS or C-tDCS or S-tDCS or electrode$ or anode or anodes or anodal or cathode or cathodes or cathodal).tw.
15. or/8-14
16. Randomized Controlled Trials as Topic/
17. random allocation/
18. Controlled Clinical Trials as Topic/
19. control groups/
20. clinical trials as topic/ or clinical trials, phase i as topic/ or clinical trials, phase ii as topic/ or clinical trials, phase iii as topic/ or clinical trials, phase iv as topic/
21. double-blind method/
22. single-blind method/
23. Placebos/
24. placebo effect/
25. cross-over studies/
26. Therapies, Investigational/
27. Research Design/
28. evaluation studies as topic/
29. randomized controlled trial.pt.
30. controlled clinical trial.pt.
31. (clinical trial or clinical trial phase i or clinical trial phase ii or clinical trial phase iii or clinical trial phase iv).pt.
32. (evaluation studies or comparative study).pt.
33. random$.tw.
34. (controlled adj5 (trial$ or stud$)).tw.
35. (clinical$ adj5 trial$).tw.
36. ((control or treatment or experiment$ or intervention) adj5 (group$ or subject$ or patient$)).tw.
37. (quasi-random$ or quasi random$ or pseudo-random$ or pseudo random$).tw.
38. ((multicenter or multicentre or therapeutic) adj5 (trial$ or stud$)).tw.
39. ((control or experiment$ or conservative) adj5 (treatment or therapy or procedure or manage$)).tw.
40. ((singl$ or doubl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).tw.
41. (coin adj5 (flip or flipped or toss$)).tw.
42. versus.tw.
43. (cross-over or cross over or crossover).tw.
44. placebo$.tw.
45. sham.tw.
46. (assign$ or alternate or allocat$ or counterbalance$ or multiple baseline).tw.
47. controls.tw.
48. or/16-47
49. 7 and 15 and 48
50. exp animals/ not humans.sh.
51. 49 not 50

Number of records retrieved:

  • MEDLINE: 1150

  • EMBASE: 1606

  • AMED: 100

  • INSPEC: 31

Appendix 2. CENTRAL search strategy

#1 MeSH descriptor Cerebrovascular Disorders, this term only
#2 MeSH descriptor Basal Ganglia Cerebrovascular Disease explode all trees
#3 MeSH descriptor Brain Ischemia explode all trees
#4 MeSH descriptor Carotid Artery Diseases explode all trees
#5 MeSH descriptor Intracranial Arterial Diseases explode all trees
#6 MeSH descriptor Intracranial Embolism and Thrombosis explode all trees
#7 MeSH descriptor Intracranial Hemorrhages explode all trees
#8 MeSH descriptor Stroke, this term only
#9 MeSH descriptor Brain Infarction explode all trees
#10 MeSH descriptor Vertebral Artery Dissection, this term only
#11 (stroke or poststroke or post-stroke or cerebrovasc* or brain vasc* or cerebral vasc* or cva* or apoplex* or SAH)
#12 ((brain* or cerebr* or cerebell* or intracran* or intracerebral) NEAR/5 (isch*emi* or infarct* or thrombo* or emboli* or occlus*))
#13 ((brain* or cerebr* or cerebell* or intracerebral or intracranial or subarachnoid) NEAR/5 (haemorrhage* or haemorrhage* or haematoma* or hematoma* or bleed*))
#14 MeSH descriptor Hemiplegia, this term only
#15 MeSH descriptor Paresis explode all trees
#16 (hemipleg* or hemipar* or paresis or paretic)
#17 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16)
#18 MeSH descriptor Electric Stimulation Therapy, this term only
#19 MeSH descriptor Electric Stimulation, this term only
#20 MeSH descriptor Electrodes, this term only
#21 (transcranial NEAR/5 direct current NEAR/5 stimulation)
#22 (transcranial NEAR/5 DC NEAR/5 stimulation)
#23 (transcranial NEAR/5 electric* NEAR/5 stimulation)
#24 (tDCS or A-tDCS or C-tDCS or S-tDCS or electrode* or anode or anodes or anodal or cathode or cathodes or cathodal)
#25 (#18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24)
#26 #17 AND #25

Number of records retrieved: 537

Appendix 3. CINAHL search strategy (EBSCO)

S1 (MH "Cerebrovascular Disorders+")
S2 (MH "Basal Ganglia Cerebrovascular Disease+")
S3 (MH "Cerebral Ischemia+")
S4 (MH "Carotid Artery Diseases+")
S5 (MH "Intracranial Arterial Diseases+")
S6 (MH "Intracranial Embolism and Thrombosis+")
S7 (MH "Intracranial Hemorrhage+")
S8 (MM "Stroke")
S9 (MM "Hypoxia-Ischemia, Brain")
S10 (MM "Vertebral Artery Dissections")
S11 (S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10)
S12 TX (stroke or poststroke or post-stroke or cerebrovasc* or brain vasc* or cerebral vasc* or cva* or apoplex* or SAH)
S13 TX ((brain* or cerebr* or cerebell* or intracran* or intracerebral) N5 (isch#emi* or infarct* or thrombo* or emboli* or occlus*))
S14 TX ((brain* or cerebr* or cerebell* or intracerebral or intracranial or subarachnoid) N5 (haemorrhage* or haemorrhage* or haematoma* or hematoma* or bleed*))
S15 (MM "Hemiplegia")
S16 TX (hemipleg* or hemipar* or paresis or paretic)
S17 (S11 or S12 or S13 or S14 or S15 or S16)
S18 (MM "Electric Stimulation")
S19 (MM "Electrodes")
S20 TX (transcranial N5 direct current N5 stimulation)
S21 TX (transcranial N5 DC N5 stimulation)
S22 TX (transcranial N5 electric* N5 stimulation)
S23 TX (tDCS or A-tDCS or C-tDCS or S-tDCS or electrode* or anode or anodes or anodal or cathode or cathodes or cathodal)
S24 (S18 or S19 or S20 or S21 or S22 or S23)
S25 (MM "Randomized Controlled Trials")
S26 (MM "Random Assignment")
S27 (MM "Clinical Trials")
S28 (MM "Nonequivalent Control Group")
S29 (MM "Clinical Trials") OR (MM "Double-Blind Studies")
S30 (MM "Single-Blind Studies")
S31 (MM "Placebos") OR (MM "Placebo Effect")
S32 (MM "Crossover Design")
S33 (MM "Research, Occupational Therapy") OR (MM "Research, Physical Therapy") OR (MM "Therapeutic Exercise") OR (MM "Occupational Therapy Assessment") OR (MM "Occupational Therapy Practice,
Evidence-Based")
S34 (MM "Study Design")
S35 (MM "Evaluation Research")
S36 PT (randomized controlled trial)
S37 PT (clinical trial)
S38 PT (clinical trial or clinical trial phase i or clinical trial phase ii or clinical trial phase iii or clinical trial phase iv)
S39 TX random*
S40 TX (controlled N5 (trial* or stud*))
S41 TX (clinical* N5 trial*)
S42 TX ((control or treatment or experiment* or intervention) N5 (group* or subject* or patient*))
S43 TX (quasi-random* or quasi random* or pseudo-random* or pseudo random*)
S44 TX ((multicenter or multicentre or therapeutic) N5 (trial* or stud*))
S45 TX ((control or experiment* or conservative) N5 (treatment or therapy or procedure or manage*))
S46 TX ((singl* or doubl* or tripl* or trebl*) N5 (blind* or mask*))
S47 TX (coin N5 (flip or flipped or toss*))
S48 TX versus
S49 TX (cross-over or cross over or crossover)
S50 TX placebo*
S51 TX sham
S52 TX (assign* or alternate or allocat* or counterbalance* or multiple baseline)
S53 TX controls
S54 (S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32 or S33 or S34 or S35 or S36 or S37 or S38 or S39 or S40 or S41 or S42 or S43 or S44 or S45 or S46 or S47 or S48 or S49 or S50 or S51 or S52 or S53)
S55 (S17 and S24 and S54)
S56 (MM "Animals") OR (MM "Animals, Laboratory") OR (MM "Animal Population Groups")
S57 (S55 not S56)

Number of records retrieved: 319

Appendix 4. Web of Science search strategy

#1 TS=(cerebrovascular disorders or exp basal ganglia cerebrovascular disease or exp brain ischemia or exp carotid artery diseases or exp intracranial arterial diseases or exp "intracranial embolism and thrombosis" or exp intracranial haemorrhages or stroke or exp brain infarction or vertebral artery dissection)
#2 TS=(stroke or poststroke or post-stroke or cerebrovasc$ or brain vasc$ or cerebral vasc$ or cva$ or apoplex$ or SAH)
#3 TS=((brain* or cerebr* or cerebell* or intracran* or intracerebral) NEAR/5 (isch$emi* or infarct* or thrombo* or emboli* or occlus*))
#4 TS=((brain* or cerebr* or cerebell* or intracerebral or intracranial or subarachnoid) NEAR/5 (haemorrhage* or haemorrhage* or haematoma* or hematoma* or bleed*))
#5 TS=(hemiplegia or paresis)
#6 TS=(hemipleg* or hemipar* or paresis or paretic)
#7 #6 OR #5 OR #4 OR #3 OR #2 OR #1
#8 TS=(Electric Stimulation Therapy)
#9 TS=(Electric Stimulation)
#10 TS=(Electrodes)
#11 TS=(transcranial NEAR/5 "direct current" NEAR/5 stimulation)
#12 TS=(transcranial NEAR/5 DC NEAR/5 stimulation)
#13 TS=(transcranial NEAR/5 electric* NEAR/5 stimulation)
#14 TS=(tDCS or A-tDCS or C-tDCS or S-tDCS or electrode$ or anode or anodes or anodal or cathode or cathodes or cathodal)
#15 #14 OR #13 OR #12 OR #11 OR #10 OR #9 OR #8
#16 TS=(Randomized Controlled Trial)
#17 TS=(random allocation)
#18 TS=(Controlled Clinical Trial$)
#19 TS=control groups
#20 TS=(double-blind method)
#21 TS=(single-blind method)
#22 TS=(Placebos)
#23 TS=(placebo effect)
#24 TS=(cross-over studies)
#25 TS=(Investigational Therapies)
#26 TS=(Research Design)
#27 TS=(evaluation studies)
#28 TS=(Clinical Trial$)
#29 TS=(random*)
#30 TS=(controlled NEAR/5 (trial$ or stud$))
#31 TS=(clinical$ NEAR/5 trial$)
#32 TS=((control or treatment or experiment* or intervention) NEAR/5 (group* or subject* or patient*)).
#33 TS=(quasi-random* or quasi random* or pseudo-random* or pseudo random*)
#34 TS=((multicenter or multicentre or therapeutic) NEAR/5 (trial* or stud*))
#35 TS=((control or experiment* or conservative) NEAR/5 (treatment or therapy or procedure or manage*))
#36 TS=((singl* or doubl* or tripl* or trebl*) NEAR/5 (blind* or mask*))
#37 TS=(coin adj5 (flip or flipped or toss*))
#38 TS=(coin NEAR/5 (flip or flipped or toss*))
#39 TS=(versus)
#40 TS=(cross-over or cross over or crossover)
#41 TS=(sham)
#42 TS=(assign* or alternate or allocat* or counterbalance* or multiple baseline)
#43 TS=(controls)
#44 #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or#41 or #42 or #43
#45 #7 and #15 and #44

Number of records retrieved: 753

Appendix 5. PEDro search strategy

Abstract & Title: stroke
Therapy: electrotherapies, heat, cold
Subdiscipline: neurology
Method: clinical trial
(Search terms matched with AND)

Number of records retrieved: 186

Appendix 6. RehabDATA search strategy

Find results with all of the words: stroke
Where Abstract OR Title contains transcranial OR tDCS

Number of records retrieved: 76

Appendix 7. COMPENDEX search strategy (Dialog)

s1 s ((vertebral (w) artery (w) dissection?)) or brain or carotid or intracran?
s2 s stroke? or poststroke? or cerebr? or cva? or apoplex? or sah
s3 s cerebell? or intracerebral or subarachnoid
s4 s hemipleg? or hemipar? or paresis or paretic
s5 s s1-s4
s6 s ((electric (w) stimulation?)) or electrode?
s7 s transcranial (5n) direct (5n) current (5n) stimulation?
s8 s transcranial (5n) DC (5n) stimulation?
s9 s transcranial (5n) electric? (5n) stimulation?
s10 s tdcs or electrode? or anod? or cathod?
s11 s s6-s10
s12 s randomized (w) controlled (w) trial?
s13 s random (w) allocation
s14 s control (w) group?
s15 s clinical (w) trial?
s16 s blind (w) method?
s17 s placebo?
s18 s investigat? and therap???
s19 s research (5n) design
s20 s evaluation (w) stud???
s21 s ((evaluation (w) stud???)) or ((comparative (w) stud???))
s22 s random?
s23 s ((controlled (5n) trial?)) or ((controlled (5n) stud???))
s24 s (control or treatment or experiment? or intervention?) (5n) (group? or subject? or patient?)
s25 s (multicent??? or therapeutic) (5n) (trial? or stud???)
s26 s (control or experiment$ or conservative) (5n) (treatment or therap??? or procedure? or manage?)
s27 s (singl? or doubl? or tripl? or trebl?) (5n) (blind? or mask?)
s28 s (flip??? or toss?) (5n) coin
s29 s versus
s30 s ((cross (w) over)) or crossover)
s31 s sham
s31 s ((multiple (w) baseline)) or assign? or alternate or allocate? or counterbalance?
s33 s control? ?
s34 s s12-s33
s35 s s5 and s11 and s34

Number of records retrieved: 1024

Contributions of authors

All review authors contributed to the conception and design of the protocol and approved the final draft of the review.

All review authors participated in all stages of the review. BE was involved in screening titles and abstracts of publications identified by the searches; BE and JM extracted trial and outcome data from the selected trials and analysed outcome data. JM and MP were involved in assessing the methodological quality of the studies. All review authors participated in interpreting the results.

Declarations of interest

Two review authors (JM and MP) were involved in conducting and analysing the largest of the included trials (Hesse 2011).

Sources of support

Internal sources

  • Gesundheitswissenschaften/Public Health, Medizinische Fakultät Carl Gustav Carus der TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany.

  • Wissenschaftliches Institut, Private Europäische Medizinische Akademie der Klinik Bavaria in Kreischa GmbH, An der Wolfsschlucht 1-2, 01731 Kreischa, Germany.

  • Lehrstuhl Therapiewissenschaften, SRH Fachhochschule für Gesundheit Gera gGmbH, Hermann-Drechsler-Str. 2, 07548 Gera, Germany.

External sources

  • No sources of support supplied

Differences between protocol and review

We amended our planned subgroup analysis regarding type of control intervention (sham tDCS, conventional therapy or nothing) because all studies were sham-controlled, except Qu 2009, making statistical pooling impossible.

Two studies presented data regarding our secondary outcome measure of muscle strength (measured by grading of the Medical Research Council (MRC)). However, statistical pooling was not possible because of heterogeneity of examined muscle groups and the level of data aggregation.

We calculated risk differences (RDs) instead of risk ratios (RRs) for binary outcomes because of the low rates of dropouts and adverse events.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Boggio 2007a

Methods

Study design: randomised sham-controlled cross-over trial

Dropouts: none

Adverse effects: none

Deaths: none

ITT: yes

Country: Brazil

Duration: 16 weeks

Participants

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

InterventionsCharacteristics: four 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 S-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 JTHFT 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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskProcedure not described, quote: "The order of these conditions was counterbalanced and randomised across subjects"
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants were blinded; blinding of personnel was not described
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test"
Incomplete outcome data (attrition bias)
All outcomes
Low riskObjective outcome measures: 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)Low riskAll outcomes stated in the methods section were reported

Bolognini 2011

Methods

Study design: randomised sham-controlled double-blind multicenter cross-over trial

Dropouts: 7

Adverse effects: none

Deaths: not stated

ITT: no

Country: not stated

Participants

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: prestroke 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

  1. 14-day CIMT with shaping techniques + A-tDCS (2 mA, 40 minutes) over the lesioned primary motor cortex (M1)

  2. 14-day CIMT with shaping techniques + S-tDCS (40 minutes) over the lesioned primary motor cortex (M1)

Outcomes

Outcomes used:

Motor assessments: duration of JTHFT 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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated randomisation list (Bolognini 2013)
Allocation concealment (selection bias)Unclear riskThe principal investigator, who took no part in data collection, nor in participants' evaluations, nor in treatment, knew the randomisation list and performed allocation (Bolognini 20)
Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants were blinded; blinding of personnel was not described
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "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)
All outcomes
Unclear riskDropouts due to frustration and tiredness during assessments (Bolognini 20), 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)Low riskAll outcomes stated in the methods section were reported

Fregni 2005a

Methods

Study design: randomised double-blind sham-controlled cross-over trial

Dropouts: none

Adverse effects: none

Deaths: none

ITT: yes

Country: not clearly stated

Participants

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

  1. A-tDCS of the lesioned hemisphere's M1 (1 mA).

  2. C-tDCS of the non-lesioned hemisphere's M1 (1 mA).

  3. S-tDCS (electrode montage not stated by the authors).

Outcomes

Outcomes used: duration of JTHFT in seconds

Time point of measurement: at baseline after familiarisation session, during stimulation and directly after stimulation

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskParticipants were blinded; blinding of personnel was not described
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "A blinded neuropsychologist—instructed not to communicate with the patient during the task—evaluated patients’ performance"
Incomplete outcome data (attrition bias)
All outcomes
Low riskObjective outcome measures: 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)Low riskAll outcomes stated in the methods section were reported

Fusco 2013

Methods

Study design: double-blinded, sham-controlled, randomised cross-over study

Dropouts: none

Adverse effects: none

Deaths: none

ITT: yes

Country: Italy

Participants

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 (S-tDCS was obligatory)

  1. A-tDCS for 15 minutes at 1.5 mA over M1 of the lesioned hemisphere

  2. C-tDCS for 15 minutes at 1.5 mA over M1 of the non-lesioned hemisphere

  3. 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

  4. S-tDCS (dosage and application not clearly stated, probably as in the other groups)

Outcomes

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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "For the random sequence generation, we used the RAND function in Matlab" (Fusco 2013)
Allocation concealment (selection bias)Low riskQuote: "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" (Fusco 2013)
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "Patients were blinded while physicians and assessors knew the treatment (real or sham)" (Fusco 2013)
Blinding of outcome assessment (detection bias)
All outcomes
High riskQuote: "Patients were blinded while physicians and assessors knew the treatment (real or sham)" (Fusco 2013)
Incomplete outcome data (attrition bias)
All outcomes
Low riskObjective and subjective outcome measures: 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)Low riskAll outcomes stated in the methods section were reported

Geroin 2011

Methods

Study design: pilot randomised controlled trial

Dropouts: none

Adverse effects: none

Deaths: none

ITT: yes

Country: Italy

Participants

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

  1. Robot-assisted gait training + A-tDCS of the lesioned hemisphere over the presumed leg area (1.5 mA for 7 minutes)

  2. Robot-assisted gait training + S-tDCS of the lesioned hemisphere over the presumed leg area (for 7 minutes)

  3. Overground walking exercises according to the Bobath approach

Outcomes

Primary outcomes: six-minute walking test, 10-m 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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "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 riskQuote: "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)
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "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)
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "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)
All outcomes
Low riskObjective outcome measures: 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 riskAll outcomes stated in the methods section were reported, except muscle tone as measured by MAS

Hesse 2011

Methods

Study design: double-blind randomised sham-controlled multicenter 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%)

Country: Germany/Italy

Participants

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; S-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:

  1. A-tDCS (2 mA) with the anode positioned over the presumed hand area of the lesioned hemisphere

  2. C-tDCS (2 mA) with the cathode positioned over the presumed hand area of the non-lesioned hemisphere

  3. S-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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "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 riskQuote: "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)
All outcomes
Low riskParticipants and personnel were blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "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)
All outcomes
Low risk1 dropout occurred during the study phase as the result of pneumonia, and 10 after the end of the intervention phase 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 riskAll outcomes stated in the methods section were reported

Khedr 2013

Methods

Study design: randomised controlled trial (parallel assignment)

Dropouts: none

Adverse effects: none

Deaths: none

ITT: yes, all participants completed the study

Country: Egypt

Participants

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 tranquillizer, inability to give informed consent, no MEP recorded from FDI muscle of the affected hand

Interventions

3 arms:

  1. 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)

  2. 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)

  3. S-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 phase 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 phase 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 phase 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 phase, 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 phase, at 1, 2 and 3-month follow-up (with greater intensity indicating a higher threshold)

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Each patient was given a serial number from a computer-generated randomisation table [...]"
Allocation concealment (selection bias)Low riskQuote: "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)
All outcomes
Low riskParticipants were blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessor was blinded
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo loss to follow-up
Selective reporting (reporting bias)Low riskAll outcomes stated in the study protocol and listed in the methods section of the publication have been reported

Kim 2009

Methods

Study design: single-blinded, sham-controlled, randomised cross-over study

Dropouts: none

Adverse effects: none

Deaths: none

ITT: yes

Country: South Korea

Participants

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

  1. A-tDCS (1 mA) over the primary motor cortex of the first dorsal interossei muscle of the lesioned hemisphere

  2. S-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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskQuote: "A doctor who works in tDCS's room, he randomised patients on his own sequence" (Kim 2013)
Allocation concealment (selection bias)Unclear riskQuote: "A doctor who works in tDCS's room, he randomised patients on his own sequence" (Kim 2013)
Blinding of participants and personnel (performance bias)
All outcomes
Low riskBoth participants and personnel were blinded (Kim 2013)
Blinding of outcome assessment (detection bias)
All outcomes
High riskNo 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"
Incomplete outcome data (attrition bias)
All outcomes
Low riskObjective outcome measures: 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)Low riskAll outcomes stated in the methods section were reported

Kim 2010

Methods

Study design: double-blind sham-controlled multicenter 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

Country: South Korea

Participants

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; S-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:

  1. A-tDCS over the primary motor cortex (M1) of the contralateral FDI muscle of the lesioned hemisphere (2 mA for 20 minutes)

  2. C-tDCS over the M1 of the ipsilateral FDI of the non-lesioned hemisphere (2 mA for 20 minutes)

  3. S-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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "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 riskQuote: "Sealed opaque envelopes were used for randomisation"
Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants and personnel were blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Two independent raters blinded to the type of intervention performed outcome measurements"
Incomplete outcome data (attrition bias)
All outcomes
High risk1 participant of each interventional arm (14% each) discontinued intervention; we excluded these participants from analysis
Selective reporting (reporting bias)Low riskAll outcomes stated in the methods section were reported

Lindenberg 2010

Methods

Study design: sham-controlled double-blinded randomised trial

Dropouts: not stated

Adverse effects: none

Deaths: not stated, likely none

ITT: not stated

Country: USA

Participants

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:

  1. 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)

  2. S-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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Patients were randomly assigned to one of two groups [...] using a block randomisation with 3 strata of impairment [...]"
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants and personnel were blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "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)
All outcomes
Low riskObjective outcome measures: 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)Low riskAll outcomes stated in the methods section were reported

Mahmoudi 2011

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

Country: Iran

Participants

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 JTHFT

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:

  1. A-tDCS of lesioned M1 (with the cathodal electrode positioned at the contralateral supraorbital area, 1 mA for 20 minutes)

  2. A-tDCS of lesioned M1 (with the cathodal electrode positioned at the contralateral deltoid muscle, 1 mA for 20 minutes)

  3. C-tDCS of lesioned M1 (with the anodal electrode positioned at the contralateral supraorbital area, 1 mA for 20 minutes)

  4. Dual-tDCS: A-tDCS of lesioned M1 + C-tDCS of non-lesioned M1

  5. S-tDCS (20 minutes)

Outcomes

Outcomes used: JTHFT (with familiarisation sessions)

Time points of measurement: at baseline and after stimulation

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskQuote: "The order of these conditions was counterbalanced and randomised across patients"
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskParticipants 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)
All outcomes
Low riskQuote: "A blinded physiatrist—instructed not to communicate with the patients during the task—evaluated patients' performance"
Incomplete outcome data (attrition bias)
All outcomes
Low riskObjective outcome measures: 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)Low riskAll outcomes stated in the methods section were reported

Nair 2011

Methods

Study design: randomised double-blind sham-controlled trial

Dropouts: none

Adverse effects: none

Deaths: none

ITT: yes

Country: USA

Participants

Number of participants: 14 right-handed

Age: (mean) 55.8, range of 40 to 76 years

Gender: 5 female (36%)

Type of stroke: first-ever unihemispheric stroke, 6 (43%) had right-hemispheric stroke, 9 (64%) had predominantly cortical stroke, 5 (36%) had predominantly subcortical stroke

Time poststroke: (mean ± SD)

Severity: moderate to severe upper extremity impairment, UE-FM (mean ± SD) 30.1 ± 10.4

Inclusion criteria: not clearly stated

Exclusion criteria: previous history of stroke, bilateral infarcts, haemorrhage, arthritis, chronic pain, other neurological diseases

Interventions

Number of arms: 2 participants underwent occupational therapy + 1 of the following conditions:

  1. C-tDCS over M1 of the non-lesioned hemisphere (1 mA for 30 minutes)

  2. S-tDCS over M1 of the non-lesioned hemisphere (for 30 minutes)

Outcomes

Primary outcomes: mean ROM for shoulder abduction, elbow extension and wrist extension (3J-ROM; calculated as active ROM∗100/passive ROM for each joint, 0 to 100, with higher values indicating better function) and proportional change in UE-FM (0 to 66, with higher scores indicating better motor performance)

Time point of measurement: at baseline, after the intervention and at 1-week follow-up

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described, quote: "Patients were randomised to either the cathodal group or the sham group"
Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants and personnel were blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The 3J-ROM and the FM assessments were done by an investigator who was blind with regard to whether real tDCS or sham tDCS was applied"
Incomplete outcome data (attrition bias)
All outcomes
Low riskObjective outcome measures: 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)High riskResults of Wolf Motor Function Test, Modified Ashworth Scale and Motor Activity Log Rating Scale were not reported, as intended by the protocol (http://ClinicalTrials.gov/show/NCT00792428)

Qu 2009

Methods

Study design: RCT

Dropouts: none

Adverse effects: not reported

Deaths: none

ITT: yes

Country: China

Duration: 1 month

Participants

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:

  1. 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)

  2. 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 phase

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskQuote: "Subjects were randomly assigned using a computer-generated randomisation list by a single investigator" (Wu 2013)
Allocation concealment (selection bias)Unclear riskQuote: "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 2013)
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "All other investigators, subjects, and outcome assessors remained blinded to group allocation until the completion of the final statistical analyses" (Wu 2013)
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskSee "Blinding of participants and personnel"
Incomplete outcome data (attrition bias)
All outcomes
Low riskObjective outcome measures: 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)Low riskAll outcomes from the methods section were reported

Rossi 2013

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

Country: Italy

Participants

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: prestroke 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:

  1. 5 daily sessions of A-tDCS to M1 of the lesioned hemisphere (2 mA for 20 minutes)

  2. 5 daily sessions of S-tDCS (for 20 minutes)

OutcomesPrimary 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
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomisation scheme was generated by a computer program (Koch 2013)
Allocation concealment (selection bias)Unclear riskAllocation was performed by a third person via telephone (Koch 2013)
Blinding of participants and personnel (performance bias)
All outcomes
Low riskPersonnel were blinded to the type of treatment (Koch 2013)
Blinding of outcome assessment (detection bias)
All outcomes
Low riskEvaluators were blinded (Koch 2013)
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts were stated
Selective reporting (reporting bias)Low riskAll outcomes were stated as mentioned in preceding conference papers

Wu 2013

  1. a

    A-tDCS: anodal transcranial direct current stimulation
    AMT: active motor threshold
    ASS: Ashworth Spasticity Score
    AT: arm robotic training
    BI: Barthel Index
    C-tDCS: cathodal transcranial direct current stimulation
    CIMT: constraint-induced movement therapy
    EEG: electroencephalography
    ESS: European Stroke Scale
    FAC: Functional Ambulation Category
    FDI: first dorsal interosseous muscle
    FMA: Fugl-Meyer Assessment
    ITT: intention-to-treat analysis
    JTHFT: Jebsen Taylor Hand Function Test
    M1: primary motor cortex
    MAL: Motor Activity Log Rating Scale
    MAS: Modified Ashworth Scale
    MBI: Modified Barthel Index
    MCA: middle cerebral artery
    MEP: motor-evoked response
    MI: Motricity Index
    MMSE: Mini Mental State Examination
    MRC: Medical Research Council
    MRI: magnetic resonance imaging
    NIHSS: National Institute of Health Stroke Scale
    NMDA: N-methyl-D-aspartate
    OMCASS: Orgogozo MCA scale
    RCT: randomised controlled trial
    ROM: range of motion
    RMI: Rivermead Mobility Index
    RMT: resting motor threshold
    SD: standard deviation
    S-tDCS: sham transcranial direct current stimulation
    tDCS: transcranial direct current stimulation
    UE-FM: Upper Extremity Fugl-Meyer Score
    WMFT: Wolf Motor Function Test

Methods

Study design: RCT with parallel-group design

Dropouts: none

Adverse effects: none

Deaths: none

ITT: yes

Country: China

Duration: 1 month

Participants

Number of participants: 90

Age: mean (SD) C-tDCS: 45.9 (11.2), S-tDCS 49.3 (12.6) years

Gender: C-tDCS: 34 (76%) male, S-tDCS: 35 (78%) male

Type of stroke: C-tDCS: 27 (60%) ischaemic, S-tDCS: 26 (58%) ischaemic

Time poststroke in months: mean (SD) C-tDCS: 4.9 (3.0); S-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 S-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 arms:

  1. 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)

  2. Physical therapy twice daily for 30 minutes each, S-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 phase and at 4-week follow-up

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Subjects were randomly assigned using a computer-generated randomisation list by a single investigator"
Allocation concealment (selection bias)Low riskQuote: "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)
All outcomes
Low riskQuote: "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)
All outcomes
Low riskQuote: "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)
All outcomes
Low riskObjective outcome measures: 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)Low riskAll outcomes from the methods section were reported

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    A-tDCS: anodal transcranial direct current stimulation
    ADLs: activities of daily living
    C-tDCS: cathodal transcranial direct current stimulation
    RCT: randomised controlled trial
    rTMS: repetitive transcranial magnetic stimulation
    tDCS: transcranial direct current stimulation

Boggio 2007bNot an RCT
Byblow 2011Not an RCT
Celnik 2009Outcome number of correct key presses clinically not relevant
Edwards 2009Not an RCT
Gandiga 2006Not an RCT
Gurchin 1988Irrelevant intervention: transcranial alternating current stimulation
Hummel 2005aNot an RCT
Hummel 2005bNot an RCT
Jayaram 2009Outcome 'motor evoked potentials (MEP)' clinically not relevant
Kasashima 2012Outcome 'event-related desynchronization' clinically not relevant
Kharchenko 2001Irrelevant Intervention: transcranial alternating current stimulation
Kitisomprayoonkul 2012Irrelevant outcome 'sensation'
Kumar 2011Irrelevant intervention: study did not evaluate impact of tDCS on upper limb/lower limb function and/or ADLs
Kwon 2012Not an RCT
Lefebvre 2013Not a randomised controlled cross-over trial
Madhavan 2011Outcome accuracy index clinically not relevant
Manganotti 2011Not an RCT
Ochi 2013Irrelevant comparison: A-tDCS versus C-tDCS with no control group
Paquette 2011Intervention tDCS was contaminated with rTMS at each stimulation session
Sheliakin 2006Not an RCT
Stagg 2012aOutcome response time clinically not relevant
Takeuchi 2012Outcome 'bimanual co-ordination', as measured by tapping task, clinically not relevant
Zimerman 2012Not a randomised controlled cross-over trial because of pseudo-randomisation

Characteristics of studies awaiting assessment [ordered by study ID]

Brem 2010

MethodsNot clearly stated by the study authors
Participants3 right-handed participants with acute stroke (< 5 weeks)
InterventionsA-tDCS at 1 mA for 20 minutes twice a day on 5 consecutive days
OutcomesUE-FM, NHPT
Notes 

Danzl 2012

MethodsRandomised sham-controlled double-blind trial (stratified randomisation)
Participants10 people with chronic stroke in an outpatient setting
Interventions

2 arms:

  1. tDCS (2 mA for 20 minutes) for 12 sessions over 1 month

  2. S-tDCS

Application of tDCS/S-tDCS was followed by robotic-assisted locomotor training

Outcomes

Primary outcome measure: 10 MWT

Secondary outcome measures: FAC, TUG, BBS, SIS, cortical excitability (as measured by TMS)

Notes 

Tahtis 2012

  1. a

    10 MWT: 10-Metre Walk Test
    A-tDCS: anodal transcranial direct current stimulation
    BBS: Berg Balance Scale
    Dual-tDCS: dual transcranial direct current stimulation
    FAC: Functional Ambulation Category
    M1: primary motor cortex
    NHPT: Nine-Hole Peg Test
    S-tDCS: sham transcranial direct current stimulation
    SIS: Stroke Impact Scale-16
    TMS: transcranial magnetic stimulation
    TUG: Timed Up and Go
    UE-FM: Upper Extremity Fugl-Meyer Assessment

MethodsStudy design: randomised sham-controlled, double-blind trial
Participants10 subacute stroke patients (2 to 8 weeks after stroke)
Interventions

2 arms:

  1. Dual-tDCS with the anode placed over M1 of the lesioned hemisphere and the cathode placed over M1 of the non-lesioned hemisphere

  2. S-tDCS with the anode placed over M1 of the lesioned hemisphere and the cathode placed over M1 of the non-lesioned hemisphere

Outcomes

TUG at baseline and at the end of the intervention phase

Tinnetti Balance and Gait Index at baseline and at the end of the intervention phase

Notes 

Characteristics of ongoing studies [ordered by study ID]

ACTRN12613000109707

Trial name or titleA pilot investigation of the effect of cathodal transcranial direct current stimulation (ctDCS) plus standard upper limb rehabilitation to augment motor recovery post acute stroke
Methods

RCT with blinded outcome assessor

ITT analysis: yes

Participants

37 to 40 people between 18 and 80 years of age with acute first-ever ischaemic stroke (in the first week) and moderate to severe hemiparesis (UE-FM < 52) with MEPs detectable by TMS, stable blood pressure parameters and MMSE > 24

Exclusion criteria: preexisting upper limb impairment causing functional limitation, hemiplegic shoulder pain, metallic implants (pacemaker or artificial cochlea), history of seizure or another unstable medical condition, pregnancy, severe language disturbance, English as a second language, severe neglect (score < 44 out of 54 points on the Star Cancellation test), history of depression, alcohol or drug abuse, coexistent neurological or psychiatric disease, current treatment with antidepressants, antipsychotics or benzodiazepines or current treatment with Na+ or Ca2+ Channel blockers or NMDA receptor antagonists

Interventions

10 rehabilitation sessions (30 minutes each) to the affected arm over a period of 2 weeks (i.e. 5 days of treatment, 2 days rest, 5 days of treatment) + 1 of the following interventions:

  1. Experimental: C-tDCS to the non-lesioned hemisphere

  2. Sham comparator: S-tDCS to the non-lesioned hemisphere

Outcomes

All assessments are to be completed at baseline and at 1 day, 2 weeks and 3 months after the end of the intervention

Primary outcome measure: UE-FM change scores

Secondary outcome measures: MEP as measured by TMS, NIHSS, Tardieu Spasticity Assessment, FIM, Post- Stroke Depression Scale

Starting date4 February 2013
Contact informationMs Jimena Garcia-Vega, jimena.garcia-vega@health.wa.gov.au
Notes 

Ang 2012

Trial name or titleTranscranial direct current stimulation and EEG-based motor imagery BCI for upper limb stroke rehabilitation
MethodsRandomised sham-controlled trial
ParticipantsStroke participants, estimated enrolment not stated by the authors
Interventions

2 arms:

  1. A-tDCS over M1 of the lesioned hemisphere (with the cathode placed over M1 of the non-lesioned hemisphere) at 1 mA for 20 minutes

  2. S-tDCS over M1 of the lesioned hemisphere (with the cathode placed over M1 of the non-lesioned hemisphere) at 1 mA for 30 seconds

Each participant undergoes 10 sessions of tDCS/S-tDCS for 2 weeks, 5 times a week followed by 8 minutes of evaluation and 60 minutes of MI-BCI with robotic feedback

OutcomesFBCSP algorithm calculated from EEG data
Starting dateNot stated
Contact information kkang@i2r.a-star.edu.sg
Notes 

Chelette 2012

Trial name or titleNot stated by the authors
MethodsRandomised sham-controlled double-blind trial
ParticipantsEstimated enrolment: 44 participants with severe upper extremity motor deficit due to chronic stroke
Interventions

Every participant is randomly assigned to 1 of 4 arms, consisting of 10 tDCS-treatment sessions, followed by 3 hours of OT:

  1. A-tDCS to excite ipsilesional hemisphere

  2. C-tDCS to inhibit contralesional hemisphere

  3. Dual-tDCS as a simultaneous combination of anodal and cathodal tDCS

  4. S-tDCS

Outcomes

UE-FM at baseline and postintervention

ARAT

SIS

Starting dateNot stated by the study authors
Contact informationNone known
Notes 

ChiCTR-TRC-11001398

Trial name or titleEffect of transcranial direct current stimulation on recovery of upper limb function after stroke
Methods

Randomised controlled pilot trial in parallel-group design

Random sequence generation: computer software

Blinding: participants, study staff and outcome assessors are blinded

Participants120 people with first-time ever stroke and upper limb hemiplegia in the first 3 months after stroke, spasticity at the wrist and elbow (MAS < 1) and no history of spasmolytics
Interventions

Experimental 1: physical therapy + active tDCS

Sham comparator: physical therapy + sham tDCS

OutcomesBrunnstrom stages, FMA, BI, MAS, ARAT
Starting date1 July 2011
Contact informationDongyu Wu, wudongyu73@yahoo.com.cn
Notes 

ChiCTR-TRC-11001490

Trial name or titleUsing transcranial direct current stimulation to treat ataxia and balance impairment after stroke
Methods

Randomised controlled pilot trial in parallel-group design

Random sequence generation: computer software

Blinding: participants, study staff and outcome assessors are blinded

Participants

40 people with first-time ever stroke and upper limb hemiplegia in the first 3 months after stroke and lesions involving the cerebellum without obvious cerebral edema

Exclusion criteria: unstable vital signs; depression after stroke; severe aphasia; obvious cognition dysfunction (MMSE < 24); serious vision or vision correction anomalies; or history of vertigo attack; hearing impairment or otitis media

Interventions

Experimental 1: balance and intervention training + active tDCS

Sham comparator: balance and intervention training + sham tDCS

OutcomesBiodex Balance System, International Cooperative Ataxia Rating Scale, BBS, BI
Starting date1 August 2011
Contact informationDongyu Wu, wudongyu73@yahoo.com.cn
Notes 

NCT00542256

Trial name or titleEffects of transcranial DC stimulation coupled with constraint-induced movement therapy on motor function in stroke patients
MethodsDouble-blind RCT
Participants

50 people 18 to 80 years of age with radiologically confirmed first-time ever ischaemic or haemorrhagic stroke; at least 6 months prior to study enrolment, demonstrating adequate balance with the non-lesioned arm restraint and the ability to stand up from sitting and to stand without help of the upper extremity 

Exclusion criteria: significant prestroke disability, neuropsychological impairments that hinder motor testing, considerable joint pain in the paretic extremity, life expectancy less than 1 year because of terminal medical diagnosis, advanced disease of viscera, considerable neurological or psychiatric disease, history of substance abuse, use of neuropsychotropic drugs, inability to enrol in another study targeting stroke recovery, prior admittance of CIMT or tDCS

Interventions

Experimental group: 40 minutes of tDCS over M1 at the beginning of 10 of 14 consecutive up to 6 hours lasting CIMT training sessions

Control group: 30 seconds of tDCS over M1 at the beginning of 10 of 14 consecutive up to 6 hours lasting CIMT training sessions

Outcomes

Primary outcome measures: Jebsen Taylor Hand Function Test at baseline, training days 1, 5, and 10 and follow-up; Motor Activity Log Rating Scale at baseline, training days 1, 5, and 10 and follow-up; Beck Depression Inventory at baseline, training days 1, 5, and 10 and follow-up; Visual Analogue Scale for Anxiety at baseline, training days 1, 5, and 10 and follow-up

Secondary outcome measures: Fugl-Meyer Assessment of Motor Recovery at baseline; Barthel Index Score at baseline; Modified Ashworth Scale at baseline

Starting dateSeptember 2007
Contact information

Julie A Williams, MSc

617-667-5261

jawillia@bidmc.harvard.edu

NotesLast updated: 9 May 9 2008

NCT00783913

Trial name or titleEnhancing the beneficial effects of upper extremity visuomotor training with tDCS
MethodsDouble-blind RCT in a parallel-group design
Participants

18 people 18 to 85 years of age with ability to sit and be active for an hour on a chair/wheelchair without cardiac, respiratory and/or pain disturbances as assessed during the screening visit; willingness to commit to participate in the long-term follow-up study (up to 3 months); willingness to give written informed consent; diagnosis of a first clinically apparent unilateral cortical or subcortical stroke at least 3 months before study entry

Exclusion criteria: history of severe neurological illness, severe cognitive impairment (MMSE < 23); MRI contraindications; history of alcohol or drug abuse; active depression with psychoactive medication changes in the last 2 months, active psychosis, disruptive or violent behavior, poor motivational capacity; aphasia or language disturbances that would interfere with performance of study tasks; uncontrolled medical problems; increased intracranial pressure; severe neglect or ataxia that would interfere with completion of study tasks; history of more than one stroke or a stroke that affects both sides of the brain, the brainstem or the cerebellum; inflammation of the tissue, severe rheumatoid arthritis or abnormal function of the joints due to arthritis in the affected arm used most often; pregnancy

Interventions

Baseline intervention: 1-hour computerised movement training and tDCS sessions twice a day, 5 days a week, for 3 weeks. Participants will sit in front of a computer screen that shows a target (round dots) and a cursor (a line). Participants will be instructed to move the cursor to various targets on the computer screen as fast and as accurately as possible, while controlling the position of the cursor by moving their arm, which will rest on a mechanical device

Experimental: A-tDCS stimulation during the first 20 minutes of each training session; electrode sponges soaked in tap water are placed on the scalp and forehead

Control: S-tDCS

Outcomes

Primary outcome measures: accuracy (defined as the difference between the straight line connecting the origin and the target and the line followed by the participant) during reaching. 1 of the additional outcomes is the time to complete a reaching task

Secondary outcome measures: UE-FM

Starting dateOctober 2008
Contact informationNational Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, USA
Notes 

NCT00853866

Trial name or titleEnhancement of motor function with reboxetine and transcranial direct current stimulation (STIMBOX)
MethodsRandomised sham-controlled double-blind cross-over trial
Participants

12 people with stroke between 18 and 86 years of age, able to give informed consent, with first-ever ischaemic stroke at least 6 months before study enrolment and paresis of arm/hand muscles above 3 on MRC scale 

Exclusion criteria: multiple cerebral lesions with associated residual deficits, severe head trauma, seizures, ferromagnetic implants in the head/neck region, pacemaker, other psychiatric or neurological diseases, substance abuse, inability to give informed consent, contraindications for reboxetine (seizures, glaucoma, prostate hyperplasia with urinary retention, cardiac arrhythmias, potential interactions with co-medication), pregnancy and breast-feeding

Interventions

Experimental group 1: reboxetine + active tDCS: single dose of reboxetine/edrona × 4 mg 80 minutes before assessment of JTHFT + 20 minutes of 1 mA tDCS during JTFHT assessment with the active electrode over M1 of the lesioned hemisphere 

Experimental group 2: reboxetine + sham tDCS: single dose of reboxetine/edrona × 4 mg 80 minutes before assessment of JTHFT + 30 seconds of 1 mA tDCS during JTFHT assessment with the active electrode over M1 of the lesioned hemisphere

Experimental group 3: placebo drug + active tDCS: placebo 80 minutes before assessment of JTHFT + 20 minutes of 1 mA tDCS during JTFHT assessment with the active electrode over M1 of the lesioned hemisphere

Experimental group 4: placebo drug + sham tDCS: placebo 80 minutes before assessment of JTHFT + 30 s of 1 mA tDCS during JTFHT assessment with the active electrode over M1of the lesioned hemisphere

Outcomes

Primary outcome measures: Jebsen Taylor test at 4 different sessions with 4 different interventions

Secondary outcome measures: maximum grip force at 4 different sessions with 4 different interventions; Nine-Hole Peg Test at 4 different sessions with 4 different interventions

Starting dateJanuary 2009
Contact information

Contact: GianpieroLiuzzi, MD

+49 40 7410 ext 59278

g.liuzzi@uke.de

Contact: Christian Gerloff, MD

+ 49 40 7410 ext 53770

gerloff@uke.de

NotesLast updated: 1 December 2010

NCT00909714

Trial name or titleNeuroregeneration enhanced by tDCS in stroke
MethodsDouble-blind RCT (parallel assignment)
Participants

250 people aged 18 years and older with subacute stroke (5 to 21 days after stroke), ischaemic subcortical or cortical first-ever strokes and moderate to moderately severe upper extremity hemiparesis (UE-FM between 28 and 50)

Exclusion criteria: more than 1 stroke; progressive stroke; completely lesioned hand knob area of M1 affected, cerebellar lesions, history of severe alcohol or drug abuse, psychiatric illnesses such as severe depression, poor motivational capacity or severe language disturbances, or with serious cognitive deficits; severe uncontrolled medical problems; rheumatological or traumatic diseases affecting the upper extremities; other neurological diseases; severe microangiopathy, polyneuropathy, ischaemic peripheral disease; pregnancy; contraindication for MRI or TMS

Interventions

Baseline intervention: standardised upper extremity rehabilitative training; A-tDCS (20 minutes) or S-tDCS will be applied once a day in combination with standardised upper extremity rehabilitative training

Experimental: tDCS once a day for 20 minutes + baseline (polarity and dosage not stated)

Control: S-tDCS + baseline

Outcomes

Primary outcome measures: UE-FM at 12 months after the end of the intervention phase

Secondary outcome measures: JTHFT, ARAT, 9-HPT, SIS, UE-FM at days 11, 40, 100 and 190 after the end of intervention phase and at 12 months after the end of the intervention phase

Starting dateJuly 2009
Contact information

Friedhelm Hummel, Dr

f.hummel@uke.uni-hamburg.de

Christian Gerloff, Prof Dr

gerloff@uke.uni-hamburg.de

Notes 

NCT01007136

Trial name or titleTDCS-enhanced stroke recovery and cortical reorganization
MethodsDouble-blind randomised controlled trial in parallel-group design
Participants

150 people with single ischaemic stroke between 18 and 80 years of age with arm weakness between 5 and 15 days poststroke and no other neurological or psychiatric diseases

Exclusion criteria: patients with bilateral motor impairment, with poor motivational capacity or history of severe alcohol or drug abuse, patients with severe aphasia, MMSE Score < 23; patients with severe uncontrolled medical problems (e.g. seizures, progressive stroke syndromes, severe rheumatoid arthritis, active joint deformity of arthritic origin, active cancer or renal disease, end-stage pulmonary or cardiovascular disease, a deteriorated condition due to age or others); patients with unstable thyroid disease; patients with increased intracranial pressure; patients with unstable cardiac arrhythmia; patients with contraindication to TMS or tDCS stimulation (pacemaker, an implanted medication pump, a metal plate in the skull, or metal objects inside the eye or skull, patients who had a craniotomy, skin lesions at the site of stimulation); patients who are not available for follow-up at 3 and 12 months; pregnancy; patients with contraindication to MRI will not participate in MRI

Interventions

Experimental: tDCS and occupational therapy: 1 mA electrical current will be delivered over M1 of the lesioned hemisphere for the first 20 minutes during the 1-hour physical therapy 

Sham comparator: sham and occupational therapy: electrical current will be ramped up and down over M1 of the lesioned hemisphere for the first seconds during the 1 hour physical therapy

Outcomes

Primary outcome measures: UE-FM at 2 weeks, 3 months and 1 year after stroke

Secondary outcome measures: JTHFT at 2 weeks, 3 months and 1 year after stroke; WMFT at 2 weeks, 3 months and 1 year after stroke; MRC grading scale at 2 weeks, 3 months and 1 year after stroke; BI at 2 weeks, 3 months and 1 year after stroke; Abilhand questionnaire at 2 weeks, 3 months and 1 year after stroke; Ashworth Spasticity Scale at 2 weeks, 3 months and 1 year after stroke; Beck Depression Inventory at 2 weeks, 3 months and 1 year after stroke; Visual Analog Pain Scale at 2 weeks, 3 months and 1 year after stroke; Mini Mental Status Scale at 2 weeks, 3 months and 1 year after stroke; NIHSS at 2 weeks, 3 months and 1 year after stroke; Motor Activity Log at 2 weeks, 3 months and 1 year after stroke; fMRI overactivation in motor cortex: voxel count and intensity at 2 weeks, 3 months and 1 year after stroke 

Starting dateMarch 2009
Contact information

Timea Hodics, MD Timea.Hodics@UTSouthwestern.edu

Charlotte Bentley Charlotte.Bentley@UTSouthwestern.edu

Notes 

NCT01014897

Trial name or titletDCS in chronic stroke recovery—pilot
MethodsDouble-blind randomised sham-controlled cross-over trial
Participants

45 people between 18 and 80 years of age with single symptomatic stroke more than 3 months ago with hand/arm weakness and ability to perform required tests and provide consent; Modified Ashworth scale < 3; ROM functional at shoulder, elbow, wrist and hand

Exclusion criteria: more than 1 symptomatic stroke in MCA territory or bilateral involvement; severe medical or psychiatric conditions, drug abuse, seizure disorder; pregnancy/breast feeding; SAH, lobar haemorrhage; patients who cannot have tDCS (prior head surgery, pacemakers, metallic implants in the head, etc); patients taking antiadrenergic medications

Interventions

Experimental: subcortical: subcortical stroke participants will receive tDCS stimulation and sham in random order; tDCS and sham will be applied in random order during standardised occupational therapy

Experimental: cortical: participants will receive active and sham tDCS in random order; tDCS and sham will be applied in random order during standardised occupational therapy

Outcomes

Primary outcome measures: WMFT at baseline and after the end of the intervention period; UE-FM at baseline and after the end of the intervention period

Secondary outcome measures: adverse events during the intervention phase

Starting dateApril 2009
Contact informationTimea Hodics, MD Timea.Hodics@UTSouthwestern.edu
Notes 

NCT01127789

Trial name or titleUse of transcranial direct current stimulation (tDCS) to study implicit motor learning on patients with brain injury 
MethodsDouble-blind RCT (parallel assignment)
Participants

Enrolment: 0

People 18 to 65 years of age with TBI or stroke participants with partially preserved fine motor function

Exclusion criteria: with metal clips in head or device (e.g. pacemaker); active CNS drugs

InterventionsExperimental: non-invasive brain stimulation (both anodal and cathodal tDCS will be used)
Outcomes

Primary outcome measures: reaction time (millisecond) of a serial reaction time task at 24 hours post intervention

Secondary outcome measures: error rate (percentage) of a serial reaction time task at 24 hours post intervention

Starting dateMarch 2010
Contact information

Wen-Shiang Chen, MD, PhD

Department of Physical Medicine and Rehabilitation, NTUH, Taipei, Taiwan, 100

Notes 

NCT01143649

Trial name or titleEffects of transcranial DC stimulation coupled with constraint induced movement therapy on motor function in stroke patients
MethodsDouble-blind RCT (parallel-group design)
Participants

120 people between 18 and 90 years of age: 40 of whom have first-time ever clinical ischaemic or haemorrhagic cerebrovascular accident confirmed by a radiological or physician's report, with weakness less than 55 (out of 66) on the UE-FM scale; stroke onset > 6 months before study enrolment. The remaining 80 people are healthy volunteers

Exclusion criteria: significant prestroke disability, major depression; any substantial decrease in alertness, language reception, or attention that might interfere with understanding instructions for motor testing; excessive pain in any joint of the paretic extremity (not applicable to severe stroke patients), contraindications to single pulse transcranial magnetic stimulation (TMS) (TMS will be used to measure cortical excitability); contraindications to tDCS, advanced liver, kidney, cardiac or pulmonary disease; terminal medical diagnosis consistent with survival < 1 year; coexistent major neurological or psychiatric disease; history of significant alcohol or drug abuse in the prior 6 months; use of carbamazepine and amitriptyline; patients may not be actively enrolled in a separate intervention study targeting stroke recovery and prior CIMT and/or tDCS treatment for stroke; history of epilepsy before stroke; patients with global aphasia and deficits of comprehension; pregnancy

Interventions

Experimental 1: tDCS + CIMT in stroke participants (40 people), tDCS over M1; intensity 1 mA, for the first 40 minutes of 10 consecutive sessions of CIMT (Monday to Friday)

Experimental 2: tDCS + motor training in healthy participants (40 people); 1 day of treatment (when the order in which they receive sham or active tDCS stimulation will be randomly assigned). Each stimulation day will include up to 6 hours of training termed "shaping" in the non-dominant hand, while the dominant hand is restrained in a resting hand splint and is secured in a sling. At the start of this training, participants will undergo 40 minutes of real tDCS at 1 mA or sham tDCS

Active comparator: tACS 40 healthy participants, 1 day of treatment (when the order in which they receive sham or active transcranial alternating current stimulation (tACS) stimulation will be randomly assigned), stimulated at 1 mA for 40 minutes

Outcomes

Primary outcome measures: motor function as measured by JTHFT, MAS, UE-FM, BI at 2 weeks after the end of the intervention phase

Secondary outcome measures: cortical excitability measured by MEP and the resting motor threshold, intracortical excitability by paired-pulse and also transcallosal inhibition to measure interhemispheric differences

Starting dateApril 2010
Contact information

Location: Spaulding Rehabilitation Hospital, Boston, Massachusetts, 02114, USA

Investigator: Felipe Fregni, PhD

Notes 

NCT01201629

Trial name or titleDoes transcranial direct current stimulation (tDCS) improve functional motor recovery in the affected arm-hand in patients after an acute ischemic stroke? Pilot study
MethodsDouble-blind RCT (parallel-group design)
Participants

50 people 19 to 90 years of age with unilateral, first-time ever acute ischaemic stroke within 4 weeks of admission to an inpatient rehabilitation facility and severe upper limb weakness (MRC < 2), medically stable from a cardiorespiratory standpoint so that they can participate in daily therapies, with ability to give informed consent

Exclusion criteria: haemorrhagic stroke, patients with an episode of poststroke seizure or history of epilepsy; medically unstable, demented, or terminally ill patients; spasmolytics and medications known to enhance motor recovery such as d-amphetamine, implanted pacemakers and defibrillators and refusal to provide informed consent

Interventions

Experimental: tDCS + OT, 1 mA of tDCS will be delivered through surface electrodes (25 to 35 cm2) to the unaffected motor cortex for 30 minutes before a participant's scheduled OT

Sham comparator: tDCS + OT, stimulation for 30 seconds only

Outcomes

Primary outcome measures: total Functional Independence Measure (TFIM) after 4 weeks of therapy

Secondary outcome measures: Action Research Arm Test (ARAT) after 4 weeks of therapy

Starting dateJanuary 2009
Contact information

Meheroz H Rabadi, MD, MRCPI

rabadimh@gmail.com

Notes 

NCT01207336

Trial name or titleEffect of combined anodal tDCS and peripheral nerve stimulation on motor recovery in acute stroke
MethodsDouble-blind RCT (parallel assignment)
Participants

20 people 35 to 85 years of age with first-ever ischaemic stroke within 5 to 30 days; paresis of the arm/hand with NIHSS < 15

Exclusion criteria: pregnancy, psychiatric history, history of substance abuse or severe depression, severe language disturbances,  patients with increased intracranial pressure or serious cardiac disease, patients with contraindication to TMS

Interventions

Experimental: 1 session of A-tDCS (1.2 mA for 13 minutes) to the ipsilesional primary motor cortex (M1) combined with peripheral radial nerve electrical stimulation (rEPNS) to the paretic hand repeated on 5 successive days, rEPNS (at radial nerve 5 Hz), 0.7* motor threshold (MT)

Sham: the same rEPNS regimen as in the experimental group but combined with sham tDCS

Outcomes

Primary outcome measures: Jebsen Taylor test at 5, 15 and 30 days

Secondary outcome measures: grip and wrist force at 5, 15 and 30 days; Nine-Hole Peg Test at 5, 15 and 30 days; cortical excitability of ipsilesional M1 (as measured by TMS) at 5, 15 and 30 days

Starting dateSeptember 2010
Contact information

Marion Simonetta-Moreau, MD, PhD

simonetta.m@chu-toulouse.fr

Notes 

NCT01356654

Trial name or titleThe use of transcranial direct current stimulation in the recovery of postural control in stroke
MethodsDouble-blind randomised controlled cross-over trial
Participants

34 people 18 to 75 years of age, suffering from a stroke in the MCA region, during subacute phase (4 to 24 weeks after onset), hospitalised in rehabilitation Hospital Hof Ter Schelde, Antwerp, Belgium, capable of understanding and giving informed consent

Exclusion criteria: cerebellum or brainstem lesions, recent multiple lesions and older lesions manifested clinically, history of severe substance abuse (alcohol, drugs, benzodiazepines), cardiac diseases that in the opinion of the clinician preclude participation in the trial (e.g. severe dyspnoea in rest, severe rhythm disturbances), history of epileptic insults not caused by the stroke, severe organic comorbidity, history of psychiatric disorders, pacemaker/internal defibrillator, pregnancy

Interventions

Experimental: tDCS, 20 minutes, 4 times a week for 4 weeks

Sham comparator: sham TDCS, 20 minutes, 4 times a week for 4 weeks

OutcomesPrimary outcome measures (at baseline, after one month and after two months): Trunk Impairment Scale (change score); RMAB; Tinetti test
Starting dateMarch 2010
Contact informationWim Saeys, MSc, wim.saeys@hotmail.com
Notes 

NCT01405378

Trial name or titleCombining transcranial direct current stimulation (tDCS) with robot therapy for the impaired upper limb in early stroke rehabilitation
MethodsDouble-blind RCT in parallel-group design
Participants

50 people between 18 and 80 years of age with first-ever or recurrent ischaemic or haemorrhagic, cortical and subcortical stroke, radiologically confirmed, and upper limb impairment

Exclusion criteria: history of epilepsy, MMSE < 24, metal implants in the head, neurological condition other than stroke, current involvement in other TMS/tDCS studies

Interventions

Experimental group: arm robot training (device: Armeo) with high-intensity, repetitive, task-oriented movements directed by video screens + A-tDCS (device: Newronika Italy) applied by 35 cm² electrodes

Control group: arm robot training (device: Armeo) with high-intensity, repetitive, task-oriented movements directed by video screens + S-tDCS (device: Newronika Italy) applied by 35 cm² electrodes

Outcomes

Primary outcome measure: change in UE-FM from baseline to the end of the intervention phase (at 8 weeks) and at 3 months of follow-up

Secondary outcome measure: change in cortical excitability from baseline to the end of the intervention phase (at 8 weeks) and at 3 months of follow-up, as measured by MEP

Starting dateOctober 2011
Contact information

Jane Burridge, PhD, Restorative Neuroscience, jhb1@soton.ac.uk

Lisa Tedesco Triccas, MSc, Health and Rehabilitation, ltt1g09@soton.ac.uk

Notes 

NCT01414582

Trial name or titleTranscranial direct current stimulation (tDCS) as a potential adjunct intervention in stroke rehabilitation
MethodsDouble-blind RCT (parallel assignment)
Participants

80 people 18 to 80 years of age who are willing and able to give informed consent for participation in the study and who should be at least 6 months post first symptomatic stroke affecting motor function of the hand

Exclusion criteria: no adequate understanding of verbal and written information in English, sufficient to complete any of the safety screening forms, previous history of epilepsy, history of drug abuse or a previous history of a neurological or psychiatric illness, or a history of neurosurgical procedure; prescription of medications such as antidepressants, took or taking of antimalarial treatment in the last 72 hours, pregnancy, metallic implant in the neck, head, or eye; any implanted electrical devices, claustrophobia, more than one stroke, limited communication in the form of aphasia or a history of dementia

Interventions

Baseline intervention: standardised motor training intervention for the upper paretic limb

Experimental group: baseline Intervention and A-tDCS over the M1 of the ipsilesional hemisphere, stimulation intensity of 1 mA for the first 20 minutes of motor training (9 consecutive sessions from Monday to Friday)

Sham comparator: baseline Intervention and S-tDCS over M1 of the ipsilesional hemisphere for the first 20 minutes of motor training (9 consecutive sessions from Monday to Friday)

Outcomes

Primary outcome measures: UE-FM, WMFT, ARAT, Nine-Hole Peg Test

Secondary outcome measures: Reaction Time Test, SIS

All assessed at 2 separate baseline sessions (at least 1 week apart), and then again immediately after the end of the intervention phase (day 10), 1 week, 1 month and 3 months after the end of the intervention phase

Starting dateJanuary 2011
Contact informationHeidi Johansen-Berg, Prof, heidi@fmrib.ox.ac.uk
Notes 

NCT01500564

Trial name or titleFunctional Interest of non invasive brain stimulation during physiotherapy at a subacute phase post stroke (anodal protocol)
MethodsDouble-blind RCT (parallel-group design)
Participants

20 people 18 to 80 years of age; participants volunteer to participate in the study, with written informed consent, affiliation with a national health insurance program, first-time ever clinical ischaemic or haemorrhagic cerebrovascular accident as evidenced by a radiological (or physician's) report, contralesional motor deficit with a lesion sparing M1, stroke onset > 1 month and < 6 months before study enrolment

Exclusion criteria: coexistent major neurological or psychiatric disease, history of epilepsy before stroke, substantial decrease in alertness, language reception, or attention that might interfere with understanding instructions for motor testing; patients with global aphasia and deficits of comprehension, excessive pain in any joint of the paretic extremity (VAS > 4), contraindications to tDCS such as metal in the head, implanted brain medical devices, history of significant substance abuse in the prior 6 months, antimalarial treatment in the last 72 hours, no prior CIMT/tDCS treatment for stroke; pregnancy

Interventions

Baseline intervention: 20 minutes of motor training during physiotherapy in 10 consecutive sessions (Monday to Friday) during 2 weeks

Experimental: baseline intervention + A-tDCS over M1 of the ipsilesional hemisphere; stimulation intensity of 1 mA

Sham comparator: baseline intervention + S-tDCS over the M1 of the ipsilesional hemisphere

Outcomes

Primary outcome measures: UE-FM (change score from baseline to 2 weeks after the end of the intervention phase)

Secondary outcome measures (change score from baseline to 2 weeks after the end of the intervention phase, 2 weeks, 1 month, 3 months and 6 months later): FIM, MAL, JTHFT, BBT, MAS, muscle strength as measured by MRC

Starting dateDecember 2011
Contact informationSophie Jacquin-Courtois, MD, sophie.courtois@chu-lyon.fr
Notes 

NCT01503073

Trial name or titleNoninvasive brain stimulation for stroke improvement
MethodsDouble-blind RCT cross-over trial
Participants

200 persons 18 to 90 years of age with acute or chronic stroke (and with a slight deficit at least)

Exclusion criteria: epilepsy, contraindication to tDCS and/or to fMRI, inability to understand/complete behavioural tasks, history of substance abuse, major health condition, presence of pacemaker, pregnancy

Interventions

Active comparator: tDCS

Sham comparator: S-tDCS

Outcomes

Primary outcome measures: change in function before/after tDCS, any brain function impaired by stroke

Secondary outcome measures: change in neuroimaging and neurophysiological outcome measures before/after tDCS: (1) noninvasive neuroimaging: brain activity studied by means of fMRI, (2) noninvasive neurophysiological measure: TMS, EEG, evoked potentials, EMG

Time points of their measurement: before intervention, immediately after intervention, 10, 20, 30, 40, 50, 60 minutes after intervention; long-term after intervention: 1, 2, 3 and 4 weeks and 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 months after the end of the intervention phase

Starting dateJanuary 2008
Contact informationYves Vandermeeren, MD, PhD, yves.vandermeeren@uclouvain.be
Notes 

NCT01519843

Trial name or titlePost-stroke procedural learning: from neural substrates to therapeutic modulation by non-invasive brain stimulation
MethodsDouble-blind randomised controlled cross-over trial
Participants

200 people 18 to 95 years of age with chronic stroke with an at least slight deficit

Exclusion criteria: epilepsy, contraindication to tDCS and/or to fMRI, inability to understand/complete behavioural tasks, history of substance abuse, major health condition, presence of pacemaker, pregnancy

Interventions

Active comparator: tDCS

Placebo comparator: S-tDCS

Outcomes

Primary outcome measures: motor learning improvement with tDCS from baseline to 4 weeks after the end of the intervention phase as measured by a motor skill learning task and by Purdue Pegboard, hand dynamometer, pinch dynamometer, 9-HPT

Secondary outcome measures: neuroimaging before motor learning task, during motor learning and after (immediately, 30 minutes, 60 minutes) motor learning; neurophysiological outcome measure (of brain excitability and connectivity with TMS (single and paired pulse)) 5 minutes before motor learning, just at the end of motor learning, after 30 minutes of motor learning, after 60 minutes of motor learning and at 1, 2, 3, and 4 weeks after the day of intervention

Starting dateSeptember 2010
Contact informationYves Vandermeeren, MD, PhD, yves.vandermeeren@uclouvain.be
Notes 

NCT01539096

Trial name or titleBrain stimulation-aided stroke rehabilitation: neural mechanisms of recovery
MethodsDouble-blind RCT (parallel-group design)
Participants

30 people 21 years of age and older diagnosed with a stroke that occurred at least 6 months ago

Exclusion criteria: pregnancy, ongoing use of CNS-activating medications, presence of an electrically, magnetically or mechanically activated implant, including cardiac pacemaker or cochlear implants, metal in the head, history of medication-resistant epilepsy in the family, history of seizures or unexplained spells of loss of consciousness

Interventions

Baseline intervention: CIMT for 3 days a week for 5 weeks for 1 hour each day. Participants will also be asked to use their affected hand in daily activities at home for 5 hours a day while wearing a mitt on the unaffected hand

Experimental: baseline intervention + tDCS to areas of the brain responsible for movement of the affected hand

Sham comparator: baseline intervention + S-tDCS with a similar setup to that for the active tDCS

Outcomes

Primary outcome measures: change in upper limb function at baseline during intervention (on average 2.5 weeks from baseline) and at 5 weeks at the end of the intervention phase

Secondary outcome measures: study of change in neural mechanisms that underlie the complementary association of cortical stimulation and CIMT

Starting dateJuly 2011
Contact information

Ela B Plow, PhD, PT, plowe2@ccf.org

Alexandria Wyant, wyanta@ccf.org

Notes 

NCT01544699

Trial name or titleImpact of non-invasive brain stimulation on motor recuperation
MethodsDouble-blind randomised controlled cross-over trial
Participants

200 people 18 to 90 years of age with chronic stroke (> 6 months after stroke) and at least a slight deficit in upper or lower limb

Exclusion criteria: epilepsy, contraindication to tDCS and/or to fMRI, inability to understand/complete behavioural tasks, history of substance abuse, major health condition, presence of pacemaker, pregnancy

Interventions

Active comparator: tDCS

Sham comparator: S-tDCS

OutcomesPrimary outcome measures: change in motor function of upper/lower limb before/after tDCS from baseline to immediately after intervention (30 minutes of tDCS) to 10, 20, 30, 40, 50, 60 minutes after intervention and long-term after intervention: 1, 2, 3, and 4 weeks
Starting dateJanuary 2012
Contact informationYves Vandermeeren, MD, PhD, yves.vandermeeren@uclouvain.be    
Notes 

NCT01574989

Trial name or titleEffects of repetitive transcranial magnetic stimulation and transcranial DC stimulation on motor function in stroke patients
MethodsDouble-blind randomised controlled cross-over trial
Participants

26 people 18 to 90 years of age

Additional inclusion criteria for stroke participants: first-time ever clinical ischaemic or haemorrhagic cerebrovascular events as evidenced by a radiological (or physician's) report; weakness, defined as score of less than 55 (out of 66) on UE-FM scale; stroke onset > 6 months before study enrolment

Exclusion criteria: history of major depression, BDI > 30, any substantial decrease in alertness, language comprehension, or attention that might interfere with understanding instructions for motor testing; contraindications to TMS/tDCS; advanced liver, kidney, cardiac or pulmonary disease; terminal medical diagnosis consistent with survival < 1 year; coexistent major neurological or psychiatric disease, history of significant substance abuse in the prior 6 months, patients may not be actively enrolled in a separate intervention study targeting stroke recovery and any other clinical trials, patients with global aphasia and deficits of comprehension, pregnancy, neuropsychotropic medication (healthy people only)

Additional exclusion criteria for stroke patients: patients may not have already received TMS and/or tDCS stimulation for stroke, history of epilepsy before stroke or episodes of seizures within the last 6 months

Interventions

Participants will receive 5 sessions of stimulation. They will undergo (1) active low-frequency rTMS (1 Hz continuous), (2) active high-frequency rTMS (10 Hz, 2-second trains with intertrain interval of 28 seconds) or (3) sham rTMS (using a sham coil). Each session will last 20 minutes and will be conducted at 100% of the motor threshold. Each tDCS session will last 20 minutes and will be conducted using 1 mA with 35 cm² electrodes

Experimental 1: single session of active low-frequency rTMS/sham tDCS on the scalp during the 20-minute session

Experimental 2: single session of active high-frequency rTMS/sham tDCS on the scalp during the 20-minute session

Experimental 3: single session of sham rTMS/active anodal tDCS on the scalp during the 20-minute session

Experimental 4: single session of sham rTMS/active cathodal tDCS on the scalp during the 20-minute session

Sham comparator: single session of sham rTMS/sham tDCS on the scalp during the 20-minute session

Outcomes

Primary outcome measures: changes in cortical excitability measures using single- and paired-pulse TMS before and after each single stimulation session

Secondary outcome measures: changes in motor function as measured by behavioural tasks (e.g. Purdue pegboard, JTHFT, ROM) both before and after the stimulation sessions

Time frame: measured for approximately 6 weeks

Starting dateMay 2011
Contact information

Felipe Fregni, MD, PhD, MPH, ffregni@partners.org

Kayleen M Weaver, BA, kmweaver@partners.org

Notes 

NCT01644929

Trial name or titleRehabilitation combined with bihemispheric transcranial direct current stimulation in subacute ischemic stroke to increase upper limb motor recovery: a randomised, controlled, double-blind study (RECOMBINE)
MethodsDouble-blind randomised controlled cross-over trial (multicentre)
Participants

36 people 18 years of age or older with subcortical or subcortical/cortical ischaemic lesions in the territory of MCA, as confirmed by neuroimaging in the subacute phase (2 to 4 weeks after stroke) with persistent hemiparesis (score of 1 to 3 on the motor arm item of the NIH Stroke Scale (NIHSS) but wrist and finger movement is not required) and no upper extremity injury or conditions that limited its use before the stroke; subscription of informed consent

Exclusion criteria: history of epilepsy, brain tumour, major head trauma, learning disorder, severe cognitive impairment, drug or alcohol abuse, major psychiatric illness. Use of medications that may lower seizure threshold (e.g. metronidazole, fluoroquinolones), severe pain in the affected upper limb (≥ 8 on the shoulder item of the "joint pain during passive motion" of the UE-FM); recurrent stroke or other significant medical complications during the study; evidence of severe leucoencephalopathy (grade IV according to Fazeka's scale); significant aphasia that would impair understanding and performance on assessment scales

Interventions

Each participant receives standardised physical/occupational treatment according to the Impairment-Oriented Training, plus 1 of the following treatment schemes:

  1. Experimental 1: A-tDCS of the ipsilesional motor cortex and C-tDCS of the contralesional motor cortex (1.5 mA, 30 minutes) for 15 days during 3 weeks, then sham stimulation for 30 seconds on 15 days during 3 weeks

  2. Experimental 2: S-tDCS for 30 seconds on 15 days during 3 weeks, then A-tDCS of the ipsilesional motor cortex and C-tDCS of the contralesional motor cortex (1.5 mA, 30 minutes) for 15 days during 3 weeks

  3. Sham comparator: treatment for 6 weeks daily with S-tDCS for 30 seconds on 15 days during 6 weeks

Outcomes

Primary outcome measures: UE-FM at the end of the intervention phase

Secondary outcome measures: UE-FM at 3 weeks and at 6 months; BI at 3 weeks, at 6 weeks and at 6 months; Ashworth scale at 3 weeks, at 6 weeks and at 6 months; Test of Upper Limb Apraxia (TULIA) at 6 weeks and at 6 months; grip strength at 3 weeks, at 6 weeks and at 6 months; Hamilton Depression Rating Scale at 6 weeks and at 6 months

Starting dateSeptember 2012
Contact information

Carlo Cereda, MD, Carlo.Cereda@eoc.ch

René Müri, MD, rene.mueri@insel.ch

Notes 

NCT01726673

Trial name or titleEffects of transcranial direct current stimulation paired with robotic arm therapy on recovery of upper extremity motor function in stroke patients
MethodsDouble-blind RCT (parallel assignment)
Participants

66 people 18 years of age or older with first single focal unilateral lesion as verified by brain imaging at least 6 months after stroke, with cognitive function sufficient to understand experiments and follow instructions; FMA of 7 to 58 out of 66 (neither hemiplegic nor fully recovered motor function in the muscles of the shoulder, elbow and wrist)

Exclusion criteria: Botox treatment within 6 weeks of enrolment, fixed contraction of the affected limb, complete flaccid paralysis of the affected limb, history of haemorrhagic stroke, ongoing use of CNS active or psychoactive medications, presence of additional potential tDCS/TMS risk factors, including damaged skin at the site of stimulation, presence of a magnetically/mechanically active implant, metal in the head, family history of epilepsy and personal history of seizures

Interventions

Experimental arm: tDCS + robotic arm therapy, 2 mA for 20 minutes over M1 in the lesioned hemisphere, followed by robotic arm therapy for 60 minutes, 3 times per week for 12 weeks

Placebo comparator arm: S-tDCS + robotic arm therapy (0 mA) for 20 minutes over M1 in the lesioned hemisphere, followed by robotic arm therapy for 60 minutes, 3 times per week for 12 weeks

Outcomes

Primary outcome measures: change from baseline in UE-FM at the end of the intervention phase and at 6 months of follow-up

Secondary outcome measures: change from baseline in kinematic data (upper extremity mobility as measured by Interactive Motion Technologies planar (shoulder/elbow) robot and wrist (wrist flexion/extension and pronation/supination) robots during therapy and evaluations) at the end of the intervention phase and at 6 months of follow-up; change from baseline in WMFT at the end of the intervention phase and at 6 months of follow-up; change from baseline Motor Power Manual Muscle Test at the end of the intervention phase and at 6 months of follow-up; change from baseline NIH stroke scale at the end of the intervention phase and at 6 months of follow-up; change from baseline SIS at the end of the intervention phase and at 6 months of follow-up

Starting dateSeptember 2012
Contact information

Bruce T Volpe, MD, bvolpe1@nshs.edu

Johanna Chang, MS, jchang14@nshs.edu

Notes 

NTR3315

Trial name or titleThe effect of noninvasive brain stimulation on lower limb motor skill acquisition
MethodsRandomised controlled double-blind trial with parallel assignment
Participants

60 participants 18 years of age or older with hemiparesis due to a first-time ever ischaemic subcortical stroke at least 6 months before study enrolment, good vision on 2 m distance, being able to stand and to make stepping movements for 42 minutes, independent walkers with clear walking impairment

Exclusion criteria: metallic implants in the brain, presence of severe or frequent headache, other neurological disorders or orthopaedic problems, history of cardiac conditions that interfere with physical load

Interventions

3 training sessions with 3 different interventions of tDCS during the first 10 minutes of each training session:

  1. Experimental 1: A-tDCS of M1

  2. Experimental 2: A-tDCS of cerebellum

  3. Sham comparator: S-tDCS

Outcomes

Primary outcome measure: relative change in motor skill between the first and last training blocks (total learning)

Secondary outcome measure: change in motor skill during motor skill training (online learning); change in motor skill between 2 consecutive motor skill training sessions (offline learning)

Starting date1 March 2012
Contact informationEdwin van Asseldonk, e.h.f.vanasseldonk@utwente.nl
Notes 

Sattler 2012

  1. a

    9-HPT: Nine-Hole Peg Test
    A-tDCS: anodal transcranial direct current stimulation
    ARAT: Action Research Arm Test
    BBS: Berg Balance Scale
    BBT: Box and Block Test
    BDI: Beck Depression Inventory
    BI: Barthel Index
    C-tDCS: cathodal transcranial direct current stimulation
    CIMT: constraint-induced movement therapy
    CNS: central nervous system
    EEG: electroencephalography
    EMG: electromyography
    FBCSP: Filter Bank Common Spatial Pattern
    FIM: Functional Independence Measure
    FMA: Fugl-Meyer Assessment
    fMRI: functional magnetic resonance imaging
    JTHFT: Jebsen Taylor Hand Function Test
    M1: primary motor cortex
    MEP: motor-evoked potentials
    MAL: Motor Activity Log
    MAS: Motor Assessment Scale
    MCA: middle cerebral artery
    MI-BCI: motor imagery brain-computer interface
    MMSE: Mini Mental State Examination
    MRC: Medical Research Council
    NIHSS: National Institutes of Health Stroke Scale
    NMDA: N-methyl-D-aspartate
    OT: occupational therapy
    RCT: randomised controlled trial
    ROM: range of motion
    RMAB: Rivermead Motor Assessment Battery
    rEPNS: repetitive peripheral nerve stimulation
    S-tDCS: sham transcranial direct current stimulation
    SAH: subarachnoidal haemorrhage
    SIS: Stroke Impact Scale
    TBI: traumatic brain injury
    tDCS: transcranial direct current stimulation
    TMS: transcranial magnetic stimulation
    UE-FM: Upper Extremity Fugl-Meyer
    VAS: Visual Analogue Scale
    WMFT: Wolf Motor Function Test

Trial name or titleNot stated by the authors
MethodsStudy design: randomised double-blind sham-controlled trial (parallel-group design)
ParticipantsEstimated enrolment: 20 patients within the first month of a cortical or subcortical stroke
Interventions

2 arms:

  1. A-tDCS + rEPNS of the radial nerve of the paretic side at 5 consecutive daily sessions

  2. S-tDCS + rEPNS of the radial nerve of the paretic side at 5 consecutive daily sessions

Outcomes

Motor performance as measured by JTHFT at baseline, after the intervention phase and at 5, 15 and 30 days of follow-up

Cortical excitability at baseline

Starting dateNot stated by the authors
Contact informationNone known
Notes 

Ancillary