Controlled clinical trial of repeated left prefrontal transcranial direct current stimulation in patients with chronic minimally conscious state

Thibaut A., Bruno MA., Wannez S., Donneau AF., Martial C., Chatelle C., Laureys S.
Background: A recent study showed that single-session anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (LDLPF) transiently improves consciousness in 43% of patients in minimally conscious state (MCS) (1). We here test the potential effects and safety of repeated tDCS in severely brain-damaged patients with MCS.

Methods: In this double-blind cross-over sham-controlled experimental design, we delivered two sessions of repeated (5 days of stimulation) tDCS, either anodal or sham in a randomized order. We stimulated the LDLPF cortex (Figure 1) during twenty minutes in 20 MCS patients (12 men, aged 48±16 years, time since onset 78±95 months, 12 post-traumatic). Consciousness was assessed by the French adaptation of the Coma Recovery Scale Revised (CRS-R; 2) before and after each stimulation (Figure 2).

Results: A treatment effect was observed for the comparison between CRS-R total scores at baseline and after 5 days of real tDCS (p<0.01). Behaviorally, 10/20 patients showed a tDCS- related improvement; 5 patients responded after the first stimulation and 5 other patients responded after 2, 3 or 4 days of stimulation (Figure 3). No side effect (e.g. epilepsy, sign of pain, drowsiness) was reported.

Conclusion: Our results demonstrate that repeated (5 days) anodal LDLPF tDCS is safe and might improve signs of consciousness in about half of patients in MCS. It is important to note that the first session is not predictive for a future positive effect of the efficacy of the non-invasive electrical stimulation.

References:
1. Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014 Apr 1;82(13): p. 1112-8.
2. Schnakers C, Majerus S, Giacino J, Vanhandenhuyse A, Bruno MA, Boly M, Moonen G, Damas P,
Lambermont B, Lamy M, Damas F, Ventura M, Laureys S. A French validation study of the Coma Recovery Scale-Revised (CRS-R). Brain Injury. 2008 Sep ;22(10): p. 786-92.