Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis
Introduction
Stroke is a health concern worldwide and one of the main causes of disability (Kolominsky-Rabas et al., 2001, Albert and Kesselring, 2012). Motor impairment is the main cause of disability after stroke, leading to major health problems (Boggio et al., 2007, Clarke, 1999). In Europe, stroke costs around 64.1 billion euros and in the United Kingdom, around £8.9 billion per annum is spent on community care and rehabilitation of people with stroke (Saka et al., 2009, Gustavsson et al., 2011). At 6 months, 33–66% of people with upper extremity (UE) impairments do not present with functional upper limb function and only 5–20% achieve full recovery (Kwakkel et al., 2003, Kwakkel and Kollen, 2013). Thus a number of approaches are now being investigated in an attempt to increase the effectiveness of stroke rehabilitation techniques for the UE.
Non-invasive methods of brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are extensively researched and are beginning to be used clinically to modulate brain activity (Paulus, 2003, Pascual-Leone et al., 2000, Hummel et al., 2005). Although these two methods have very different modes of action (rTMS stimulates axons in the brain and initiates new action potentials; tDCS polarises the neurones, and modulates their ongoing firing pattern) both of them, when applied over the motor cortex, produce changes in cortical excitability which, in the case of tDCS can last up to 90 min (Nitsche and Paulus, 2000, Nitsche and Paulus, 2001, Fitzgerald et al., 2006). They also enhance motor performance and can change reaction times, movement accuracy and speed (Nitsche et al., 2003b, Kobayashi et al., 2004). More importantly, in the context of possible therapeutic application, they can improve motor skill learning (Reis and Fritsch, 2011, Teo et al., 2011) or adapt already learned skills to new conditions (Galea et al., 2011). There has therefore been considerable interest in examining the potential of these interventions to augment recovery of motor function after stroke.
Initial investigations with non-invasive brain stimulation concentrated on using methods of rTMS to improve recovery in acute and chronic stroke (Khedr et al., 2005, Kim et al., 2006). However in recent years there has been increased interest in using tDCS because of two main advantages: firstly it is far less expensive than rTMS, and secondly, stimulation can potentially be applied during rehabilitation whereas rTMS (because the equipment is bulky and the head needs to remain still), it can only be given before (or after) a training session (Brunoni et al., 2012). From a practical viewpoint, anodal tDCS is usually assumed to increase excitability whereas cathodal tDCS reduces excitability (Nitsche and Paulus, 2000). In stroke rehabilitation this means that researchers will employ anodal tDCS over the stroke hemisphere to improve the response of that hemisphere to training protocols (Hummel et al., 2005). Alternatively, employing the logic of inter-hemispheric imbalance, cathodal stimulation of the non-stroke hemisphere will inhibit that hemisphere to reduce its trans-hemispheric inhibition of the affected hemisphere or bihemispheric stimulation by simultaneously modulating the unaffected and affected motor cortex (Nitsche et al., 2003a, Lindenberg et al., 2010).
In healthy volunteers, the effects of tDCS on cortical excitability and performance are short-lasting and variable (Nitsche and Paulus, 2000, Lopez-Alonso et al., 2014, Wiethoff et al., 2014). However, it is usually assumed that multiple daily applications in stroke may lead to a build-up of effects that are larger and more persistent. The main evidence in favour of this comes from studies of rTMS to treat depression: a single session, or even 2 weeks daily treatment with rTMS has little effect on symptoms over and above placebo, whereas longer (>4 weeks) treatments can improve symptoms for several months (Dell’Osso et al., 2011, Galletly et al., 2012). Thus most recent clinical trials of tDCS have employed several days or weeks of repeated treatment with rehabilitation programmes in an attempt to maximise outcome (Lee and Chun, 2014, Viana et al., 2014). Interestingly it is still unclear whether repeated daily session of tDCS has cumulative effects in the healthy and stroke population (Alonzo et al., 2012, Monte-Silva et al., 2013).
Recent meta-analyses have explored the effect of tDCS in addition to rehabilitation on UE activity in stroke (Bastani and Jaberzadeh, 2012, Adeyemo et al., 2012, Butler et al., 2013, Elsner et al., 2013). Adeyemo et al. (2012) demonstrated a significant effect size (0.58) of non-invasive brain stimulation on motor function. Bastani and Jaberzadeh, 2012 showed that anodal tDCS had a small non-significant effect size of 0.39 on hand function in stroke, but a moderate significant effect size of 0.59 on motor evoked potential amplitude. Butler et al. (2013) also demonstrated a significant small effect size of 0.40 of anodal tDCS on UE motor recovery. A Cochrane review showed that tDCS has a small effect on UE motor impairments but not on activities of daily living at post-intervention (Elsner et al., 2013). However, at follow-up they showed an effect of tDCS on activities of daily living but not on UE motor impairments. No effect of tDCS in sub-groups involving people with acute, sub-acute and chronic stroke was found. The analyses in these reviews combined studies including one or multiple sessions of tDCS, and the pooled effects of only multiple tDCS sessions plus therapy remains uninvestigated.
The aim of the current study was to systematically review the methodology adopted in various studies of tDCS. In particular treatment options, outcomes reported, and the effect of multiple sessions of tDCS with rehabilitation programmes for UE recovery post stroke. We included trials in which anodal, cathodal or bi-hemispheric tDCS was applied in conjunction with UE rehabilitation programmes at any stage post stroke.
Section snippets
Search
A systematic search was conducted for articles written in English and published between 1990 and July 2014. Full text articles in electronic databases MEDLINE, EMBASE (Excerpta Medica Database), CINAHL (Cumulated Index of Nursing and Allied Health Literature), AMED (Allied and Complementary Medicine Database), PubMed, PEDro (Physiotherapy Evidence Database) were systematically searched by the first author (LTT). Combination of key words with the use of ‘AND’ and ‘OR’ were used for the searches (
Search results
The PRISMA flow chart (Fig. 1) shows the search and selection results. Nine papers scored 16 points or above using the Downs and Black scoring were included in the qualitative analysis and eight were (Eng et al., 2007) (Table 2).
Main characteristics of the RCT’s
In total, 371 participants with stroke (243 males) meeting the eligibility criteria for our review study were included in the nine selected studies. All participants had a single stroke apart from the ones in the study by Viana et al. (2014). Limited detail was reported
Discussion
Driven by the positive benefits of repeated sessions of rTMS to treat depression, many current trials apply the same logic when using tDCS to improve recovery of arm function after stroke. This is the first review to explore the effect of just multiple sessions of tDCS and UE rehabilitation programmes on outcome measures based on the ICF; impairment and activity. Therefore, it examines the potential clinical use of tDCS. We performed a meta-analysis of the data, in which this approach was used
Conclusions
Systematic reviews and meta-analyses have been a popular method of exploring the effect of tDCS on UE recovery in stroke. The results from this review showed that multiple sessions of tDCS regimes combined with UE rehabilitation had a small and non-significant effect on upper limb impairments and activities of daily living post-intervention. However, from this review there is wide variation in tDCS parameters adopted in the constituent trials and different UE therapy. Factors such as selection
Acknowledgments
We would to thank the Faculty of Health Sciences of the 502 University of Southampton and also the Strategic Educational Pathways Scholarship Scheme (Malta) – The scholarship is part-financed by the European Union – European Social Fund.
Conflicts of interest statement: None of the authors have potential conflicts of interest to be disclosed.
References (56)
- et al.
Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation
Brain Stimul
(2012) - et al.
Does anodal transcranial direct current stimulation enhance excitability of the motor cortex and motor function in healthy individuals and subjects with stroke: a systematic review and meta-analysis
Clin Neurophysiol
(2012) - et al.
Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions
Brain Stimul
(2012) - et al.
A meta-analysis of the efficacy of anodal transcranial direct current stimulation for upper limb motor recovery in stroke survivors
J Hand Ther
(2013) - et al.
Rasch analysis of a new stroke-specific outcome scale: the stroke impact scale
Arch Phys Med Rehabil
(2003) - et al.
A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition
Clin Neurophysiol
(2006) - et al.
Cost of disorders of the brain in Europe 2010
Eur Neuropsychopharmacol
(2011) - et al.
Combination transcranial direct current stimulation and virtual reality therapy for upper extremity training in patients with subacute stroke
Arch Phys Med Rehabil
(2014) - et al.
Inter-individual variability in response to non-invasive brain stimulation paradigms
Brain Stimul
(2014) - et al.
Obot-assisted movement training compared with conventional therapy techniques for the rehabilitation of upper-limb motor function after stroke
Arch Phys Med Rehabil
(2002)