Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state

Abstract

a b s t r a c tBackground: Patients with chronic disorders of consciousness face a significant lack of treatment options. Objective: We aimed at investigating the feasibility and the behavioral effects of home-based transcranial direct current stimulation (tDCS), applied by relatives or caregivers, in chronic patients in minimally conscious state (MCS). Methods: Each participant received, in a randomized order, 20 sessions of active and 20 sessions of sham tDCS applied over the prefrontal cortex for 4 weeks; separated by 8 weeks of washout. Level of consciousness was assessed using the Coma Recovery Scale-Revised before the first stimulation (baseline), at the end of the 20 tDCS sessions (direct effects) and 8 weeks after the end of each stimulation period (long-term effects). Reported adverse events and data relative to the adherence (i.e., amount of sessions effectively received) were collected as well. Results: Twenty-seven patients completed the study and 22 patients received at least 80% of the stimulation sessions. All patients tolerated tDCS well, no severe adverse events were noticed after real stimulation and the overall adherence (i.e., total duration of stimulation) was good. A moderate effect size (0.47 and 0.53, for modified intention to treat and per protocol analysis, respectively) was observed at the end of the 4 weeks of tDCS in favor of the active treatment. Conclusions: We demonstrated that home-based tDCS can be used adequately outside a research facility or hospital by patients' relatives or caregivers. In addition, 4 weeks of tDCS moderately improved the recovery of signs of consciousness in chronic MCS patients.© 2018 Elsevier Inc. All rights reserved. IntroductionPatients who suffered from a severe brain injury and stay with a disorder of consciousness (DOC) represent a challenging population to treat since, by definition, these patients are unable to communicate, and therefore to participate in active rehabilitation programs. Currently, their treatment options are limited, especially in the chronic setting. Several drugs to improve the level of consciousness have been studied (e.g., zolpidem, levodopa or baclofen) [1]. However, so far, only amantadine showed significant clinical effects [2]. Recently, transcranial direct current stimulation (tDCS) showed promising results in patients in a minimally conscious state (MCS e i.e., showing fluctuating but reproducible signs of consciousness, such as response to command or visual pursuit for instance, while being unable to functionally communicate) while patients in unresponsive wakefulness syndrome (UWS e i.e., only showing cyclic eye-opening and reflexive behaviors) seem to be less responsive to that treatment. We demonstrated that a single session of tDCS, applied with the anode over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the contralateral supraorbital area, induced transient clinical improvement [4], as

Therapeutic interventions in patients with prolonged disorders of consciousness

“…Therefore, adapted therapeutic approaches that do not require patients' active participation need to be developed. Present findings suggest that some patients may benefit from rehabilitative interventions, 32,64,66 even years after the brain injury, 29,33,35 which highlights the importance of management of patients with prolonged DOC. To date, as highlighted in the American practice guidelines for DOC patients, 10 most studies are open-label studies and case-reports, in which results need to be taken with caution, and cannot yet be translated into clinical practice.…”

“…Finally, another RCT in 27 patients in MCS (10 months to 33 years post-injury) evaluated the effects of 20 sessions within 4 weeks of DLPFC tDCS applied by the patients' relatives or caregivers at home or in nursing homes. 35 While the overall compliance was good (i.e., 96% of sessions completed), the behavioral effect was not significant. However, when excluding the 5 patients who did not receive at least 80% of the tDCS sessions, a significant treatment effect was observed for the remaining 22 patients.…”

“…However, several RCTs are being published in the last 5 years ( 10 For neuromodulation, on the other hand, many studies and RCTs have been conducted in this patient cohort, showing the growing interest in this field, that may be partially explained by the low cost and absence of severe side-effects reported. TDCS applied over DLPFC has been shown to induce some clinical improvement in 5 RCTs, 4 class III 31,[33][34][35] and 1 class II, 29 in patients in MCS from TBI and non-TBI etiologies. Even if the sample sizes were relatively small (13 to 55 patients enrolled per study) and the field of non-invasive brain stimulation for patients with DOC is still at its infancy, tDCS seems a promising treatment approach for patients in MCS.…”

Exploring the neural, behavioural, and clinical effects of transcranial direct current stimulation in patients with a Prolonged Disorder of Consciousness; protocol for a double-blind randomised crossover feasibility study

“…Martens and colleagues delivered 20 sessions of 20 minutes 2mA tDCS to a group of 27 patients and reported no tDCS-related adverse effects other than mild skin redness or sleepiness in 1% of the sessions [46].…”

Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness

“…Encouraging results have been obtained on DoC patients with invasive electrical stimulation of the brain (16)(17)(18)(19) and recently, transcranial delivery of a low intensity electrical current over the scalp with tDCS (20)(21)(22). However, the efficacy of tDCS is debated (23)(24)(25), and its mechanisms have not been established yet.…”