Abstract
Background
Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types.
Methods
We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. PROSPERO ID: CRD42016042055.
Results
We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events.
Conclusion
Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.
Background
An emerging approach for enhancing neural plasticity and hence rehabilitation outcomes after stroke is non-invasive brain stimulation (NIBS). Several stimulation procedures are available, such as repetitive transcranial magnetic stimulation (rTMS) [1], transcranial direct current stimulation (tDCS) [2, 3, 4], transcranial alternating current stimulation (tACS) [5], and transcranial pulsed ultrasound (TPU) [6]. In recent years a considerable evidence base for NIBS has emerged, especially for rTMS and tDCS.
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In anodal stimulation, the anodal electrode (+) usually is placed over the lesioned brain area and the reference electrode over the contralateral orbit [12]. This leads to subthreshold depolarization, hence promoting neural excitation [3].
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In cathodal stimulation, the cathode (−) usually is placed over the non-lesioned brain area and the reference electrode over the contralateral orbit [12], leading to subthreshold polarization and hence inhibiting neural activity [3].
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Dual tDCS means the simultaneous application of anodal and cathodal stimulation [13].
However, the literature does not provide clear guidelines, not only regarding the tDCS type, but also regarding the electrode configuration [14], the amount of current applied and the duration of tDCS, or the question if tDCS should be applied as a standalone therapy or in combination with other treatments, like robot-assisted therapy [15].
Rationale
There is so far conflicting evidence from systematic reviews of randomised controlled trials on the effectiveness of different tDCS approaches after stroke. For example, over the past two decades more than 30 randomised clinical trials have investigated the effects of different tDCS stimulation techniques for stroke, and there are 55 ongoing trials [16]. However, the resulting network of evidence from randomised controlled trials (RCTs) investigating different types of tDCS (i.e., anodal, cathodal or dual) as well as their comparators like sham tDCS, physical rehabilitation or pharmacological agents has not yet been analyzed in a systematic review so far.
A network meta-analysis (NMA), also known as multiple treatment comparison meta-analysis or mixed treatment comparison analysis, allows for a quantitative synthesis of the evidence network. This is made possible by combining direct evidence from head-to-head comparisons of three or more interventions within randomised trials with indirect evidence across randomised trials on the basis of a common comparator [17, 18, 19, 20]. Network meta-analysis has many advantages over traditional pairwise meta-analysis, such as visualizing and facilitating the interpretation of the wider picture of the evidence and improving understanding of the relative merits of these different types of neuromodulation when compared to sham tDCS and/or another comparator such as exercise therapy and/or pharmacological agents [21, 22]. By borrowing strength from indirect evidence to gain certainty about all treatment comparisons, network meta-analysis allows comparative effects that have not been investigated directly in randomised clinical trials to be estimated and ranked [22, 23].
Objective
The aim of our systematic review with NMA was to give an overview of the evidence network of randomised controlled trials of tDCS (anodal, cathodal, or dual) for improving capacity in activities of daily living (ADL) and upper limb function after stroke, as well as its safety, and to estimate and rank the relative effectiveness of the different stimulation types, while taking into account potentially important treatment effect modifiers.
Fig. 1 Study flow diagram
TBI Rehabilitation 