Transcranial direct current stimulation for gait recovery following stroke: A systematic review of current literature and beyond

Abstract

BackgroundOver the last decade, transcranial direct current stimulation (tDCS) has set promise contributing to post-stroke gait rehabilitation. Even so, results are still inconsistent due to low sample size, heterogeneity of samples, and tDCS design differences preventing comparability. Nonetheless, updated knowledge in post-stroke neurophysiology and stimulation technologies opens up opportunities to massively improve treatments.ObjectiveThe current systematic review aims to summarize the current state-of-the-art on the effects of tDCS applied to stroke subjects for gait rehabilitation, discuss tDCS strategies factoring individual subject profiles, and highlight new promising strategies.MethodsMEDLINE, SCOPUS, CENTRAL, and CINAHL were searched for stroke randomized clinical trials using tDCS for the recovery of gait before 7 February 2022. In order to provide statistical support to the current review, we analyzed the achieved effect sizes and performed statistical comparisons.ResultsA total of 24 records were finally included in our review, totaling n = 651 subjects. Detailed analyses revealed n = 4 (17%) studies with large effect sizes (≥0.8), n = 6 (25%) studies with medium ones (≥0.5), and n = 6 (25%) studies yielding low effects sizes (≤ 0.2). Statistically significant negative correlations (rho = −0.65, p = 0.04) and differences (p = 0.03) argued in favor of tDCS interventions in the sub-acute phase. Finally, significant differences (p = 0.03) were argued in favor of a bifocal stimulation montage (anodal M1 ipsilesional and cathodal M1 contralesional) with respect to anodal ipsilesional M1.ConclusionOur systematic review highlights the potential of tDCS to contribute to gait recovery following stroke, although also the urgent need to improve current stimulation strategies and subject-customized interventions considering stroke severity, type or time-course, and the use of network-based multifocal stimulation approaches guided by computational biophysical modeling.Systematic review registrationPROSPERO: CRD42021256347.

Transcranial Direct Current Stimulation in the Treatment of Gait Disturbance in Post-Stroke Patients: An Overview of Systematic Reviews

“…While 7 studies were rated with "Critically Low" confidence [4,14,18,[20][21][22]29], the remaining 5 studies were classified with "Low" confidence. [13,15,19,23,24].…”

“…Studies were screened by title and abstract to check that they met the previously established inclusion criteria. Finally, 13 reviews were included [4,[12][13][14][15][18][19][20][21][22][23][24]29] for a total of 195 randomised controlled trials (RCT). The selection process is shown in the flow chart (Figure 1) with a list of excluded studies, reasons, and funding (Table S1).…”

“…Several reviews have attempted to answer the evidence of tDCS application for gait recovery in stroke patients [4,[12][13][14][15][16][17][18][19][20][21][22][23][24]. However, the variability of the protocols and the heterogeneity of the outcome measures make it difficult to interpret the results.…”

High-density transcranial direct current stimulation to improve upper limb motor function following stroke: study protocol for a double-blind randomized clinical trial targeting prefrontal and/or cerebellar cognitive contributions to voluntary motion

“…Transcranial DCS has been used as a therapeutic intervention to boost cognitive and motor recovery following stroke in diverse settings and evaluated to improve voluntary upper limb function (12)(13)(14)(15)(16). Despite its success in small samples of selected participants, the effects reported by accumulative tDCS interventions in stroke are often inconsistent when applied to larger cohorts of patients (17). Additionally, tDCS outcomes have been found to be highly influenced by variables such as post-stroke-to-treatment-onset time-lag, lesion location, extent, a large variety of stimulation parameters (electrode location, current intensity, density, regime periodicity, etc.…”

“…stroke motor dysfunctions have based their interventions on (i) the up-regulation (with anodal tDCS, highfrequency rTMS or iTBS patterns) of ipsilesional M1/premotor systems, (ii) the down-regulation (with cathodal tDCS, low-frequency rTMS or cTBS patterns) of spared contralesional M1/premotor systems by virtue of the trans-callosal rivalrous interactions, remapping, reorganization or normalization of abnormal excitability of lesional/perilesional areas (66) or (iii) the up-regulation of motor regulation systems such as the supplementary motor area (SMA) or the cerebellum. Unfortunately, initial enthusiasm for many of these approaches based on small clinical trials has dwindled by the lack of consistent effects when tested in larger populations of patients, and efficacy remains debated(67). For this reason, it is paramount to explore and provide proof-of-concept for new treatments based on the manipulation of cortical sites, with the ability to drive improvements by acting on spared non-purely motor regions indirectly contributing to the recovery of voluntary motion via associated cognitive processes and network-synchronization mechanisms.In the cognitive domain, anodal tDCS over the ipsilesional DLPFC and/or cathodal stimulation of the contralesional DLPFC have shown efficacy in the rehabilitation of prefrontal functions such as sustained attention…”