Behavioral Effects in Disorders of Consciousness Following Transcranial Direct Current Stimulation: A Systematic Review and Individual Patient Data Meta-analysis of Randomized Clinical Trials

Background In patients with Disorders of Consciousness (DoC), transcranial direct current stimulation (tDCS) was a promising intervention for it. However, uncertainties remain about the treatment effect and the optimal treatment strategy of the tDCS in the DoC. Objective In this meta-analysis of individual patient data (IPD), we assess whether utilizing tDCS as a treatment in DoC could improve patients’ behavioral performance and whether patient characteristics or tDCS protocol could modify the treatment effect. Methods We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials through April 7, 2022, using the terms “persistent vegetative state,” “minimally conscious state,” “disorder of consciousness,” or “unresponsive wakefulness syndrome,” and “transcranial direct current stimulation” to identify Randomized Controlled Trials (RCTs) in English-language publication. Studies were eligible for inclusion if they reported pre- and post-tDCS Coma Recovery Scale-Revised (CRS-R) scores. From the included studies, any patients who had incomplete data were excluded. We performed a meta-analysis to assess the treatment effect of the tDCS compared with sham control. Additionally, a subgroup analysis was performed to determine whether patients’ baseline characteristics could modify the treatment effect and the optimal tDCS protocol. Results We identified 145 papers, eight trials (including 181 patients) were finally included in the analysis, and one individual data were excluded because of incompletion. Our meta-analysis demonstrated a mean difference change in the CRS-R score of 0.89 (95% CI, 0.17-1.61) between tDCS and sham-control, favoring tDCS. The subgroup analysis showed that patients who were male or in minimally conscious state (MCS) were associated with a greater improvement in CRS-R score and that adopting 5 or more sessions of tDCS protocol might have a better treatment effect than just one session. Conclusion tDCS can improve the behavioral performance of DoC patients. However, heterogeneity existed within the patients’ baseline condition and the stimulation protocol. There should be more exploration of the optimal tDCS protocol and the most beneficial patient group based on the mechanism of tDCS in the future.