Multiple system atrophy (MSA) is a progressive neurodegenerative disease for which, to date, no causal therapy is available, symptomatic treatment therefore playing a pivotal role in patient care (Fanciulli \& Wenning, 2015). Unfortunately, there are very limited effective symptomatic treatments, especially for the cerebellar variant of MSA (MSA-C) which calls for the urgent need of developing alternative strategies to improve patients' disability and quality of life (QoL). An emergent approach to cerebellar disorders of various etiologies stands in the use of non-invasive brain stimulation (NIBS) techniques (Erro R et al., 2017), namely in the use of trans-cranial direct current stimulation (tDCS), to modulates neuronal excitability in a polarity-specific manner by delivering prolonged (up to 20-30 min) but weak (1-2 mA) currents to brain tissues via electrodes placed on the scalp (Stagg \& Nitsche, 2011).
This project has been designed as a double-blinded, sham-controlled, cross-over trial with two independent arms to assess the feasibility and compare the efficacy of two different tDCS protocols. Sample size calculation has been calculated on preliminary unpublished results of our own research using tDCS in other atypical parkinsonisms (i.e., PSP) and we will accordingly recruit 15 patients for each arm of the study. Patients will be randomly assigned to one of the two arms and all will receive a sham-stimulation for 5 consecutive days/week (i.e.,Monday to Friday) and an active stimulation for 5 consecutive days/week (i.e., Monday to Friday). The order of the sham- vs active-stimulation will be also randomized within each arm. The active stimulation will consist of an anodal stimulation over the cerebellum area (2 cm under the inion, using a 7 × 5 cm sponge electrode), with the cathode being applied either to the right deltoid muscle (arm 1: cerebellar stimulation) or over the spinal lumbar enlargement (2 cm under T11; arm 2: cerebellar-spinal stimulation) using a sponge electrode of the same size as the anode. During anodal stimulation, a constant current of 2 mA will be applied for 20 minutes, as suggested by recently published consensus recommendations (Grimaldi et al, 2014). For the sham condition, the electrode placement will be the same as for the active stimulation, but the electric current will be ramped down 5 seconds after the beginning of the stimulation to make this condition indistinguishable from the experimental stimulation.
Before (T0), soon after the first week of the protocol (T1) and soon after the second week of the protocol (T2) all patients will be evaluated using 1) validated clinical scales for cerebellar disorders (SARA, ICARS) and 2) through the 8-m walking test (8MW); defined as the time needed to walk 8 m as quickly as possible but safely with any device but without the help of another person or wall. During the 8MW wearable sensors (OPAL) will be further used to collect objective measures of gait and balance. Finally, PROs will be collected by means of 1) the clinical global improvement measure (CGI-I) ranging from 1 (very much improved) to 7 (very much worse), with patients being asked to report their perceived improvement at T1 and T2; and 2) by two instruments for depicting change in QoL, namely the EuroQoL-5Dimensions, 3Levels (EQ-5D-3L) and the MSA-QoL (Schrag, Mov Disord 2007), both of which will be performed at T0, T1 and T2. Patients will be further asked whether they thought they were receiving real or sham stimulation at the end of the 2-week treatment.
