Feasibility, safety and efficacy of transauricular vagus nerve stimulation in a cohort of patients with disorders of consciousness

Disorders of consciousness (DOC) are one of many neurological diseases for which there is still no curative treatment. The majority of therapeutic options performed in these patients have focused on accelerating clinical recovery through pharmacological interventions, environmental stimulation or, more recently, using neuromodulatory brain stimulation techniques, among others [1]. Vagus nerve stimulation (VNS), has recently been used in neurorehabilitation based on its effects on cortical plasticity [2]. Two recent case reports using VNS have shown promising results for increasing the level of consciousness in two patients in Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS) after severe traumatic brain injury [3,4]. However the role of VNS in DOC has not been systematically studied. We prospectively enrolled chronic adult patients with DOC who weremore than six months post injury, and were receiving rehabilitation in our facility between May 2018 and January 2019. We included only patients with no changes in at least five Coma Recovery Scale-Revised (CRS-R) scores performed weekly in the four weeks before inclusion. The experimental intervention consisted of forty, 30-minute transauricular (left tragus) VNS (Parasym® CE) sessions administered twice a day (five days per week). Stimulation parameters (sinusoidal waveform; pulse width: 250 us; frequency: 20 Hz; amplitude: 1.5 mA) were chosen according to previous studies [4]. All patients included in the study were assessed with the CRS-R at baseline (T0), week 1 (T1), week 2 (T2), week 3 (T3), and week 4 (T4: end of treatment) with a further follow-up 4 weeks after the termination of stimulation. Each subject’s heart rate (HR) and blood pressure (BP) were monitored during all treatment sessions. Additionally, during the first VNS session, subjects were monitored by a multimodal monitor that included continuous ECG. Our primary outcome measure was the number of subjects presenting any improvement in at least one item in the CRS-R evaluation at one time point. We also recorded the type and number of