The Adjunct of Electric Neurostimulation to Rehabilitation Approaches in Upper Limb Stroke Rehabilitation: A Systematic Review With Network Meta-Analysis of Randomized Controlled Trials

Objective: This review analyzed the current evidence and the potential for the application of electric neurostimulation such as transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS) in upper limb stroke rehabilitation.Materials and Methods: We performed a systematic review of randomized controlled trials (RCTs) using network meta-analysis (NMA), searching the following data bases: PubMed, Web of Science, Cochrane, and Google Scholar, using specific keywords, from January 2010 to April 2021, and assessing the effects of "tDCS" or "VNS" combined with other therapies on upper limb motor function and activities of daily living (ADL) after stroke.Results: We included 38 RCTs with 1261 participants. Pairwise NMA showed transcutaneous VNS (tVNS) and anodal tDCS were effective in improving upper limb motor function (tVNS: mean difference [MD]: 5.50; 95% CI [0.67-11.67]; p < 0.05; anodal tDCS: MD: 5.23; 95% CI [2.45-8.01]; p < 0.05). tVNS and tDCS (anodal and cathodal) were also effective in improving ADL performance after stroke (tVNS: standard MD [SMD]: 0.96; 95% CI [0.15-2.06]; p < 0.05; anodal tDCS: SMD: 3.78; 95% CI [0.0-7.56]; p < 0.05; cathodal tDCS: SMD: 5.38; 95% CI [0.22-10.54]; p < 0.05). Surface under the cumulative ranking curve analysis revealed that tVNS is the best ranked treatment in improving upper limb motor function and performance in ADL after stroke. There was no difference in safety between VNS and its control interventions, measured by reported adverse events (VNS: risk ratio = 1.02 [95% CI = 0.48-2.17; I2 = 0; p = 0.96]).Conclusion: Moderate-to high-quality evidence suggests that tVNS and anodal tDCS were effective in improving upper limb motor function in both acute/subacute and chronic stroke. In addition to tVNS and anodal tDCS, cathodal tDCS is also effective in improving ADL performance after stroke.