Effects of the modulation of sensory or motor cortical excitability by rTMS in RLS

Introduction: An electrocortical “disinhibition” to transcranial magnetic stimulation (TMS)was reported in restless legs syndrome (RLS), resulting in a hyperexcitability state; the aim of this study was to explore the role of inhibitory low-frequency repetitive TMS (rTMS) over the primary motor and sensory cortices in de novo patients with idiopathic RLS. Materials and methods: Twenty right-handed participants (10 RLS patients and 10 age-matched controls) were enrolled and EEG was performed to rule out predisposition to seizure. Measures of corticospinal excitability, including resting motor threshold (rMT), motor evoked potentials (MEPs) and cortical silent period (CSP), were assessed by means of single-pulse TMS using a figure-of-eight coil and recording from the right first dorsal interosseus (FDI) muscle. Patients were randomly assigned to a stimulation sequence including, in differing order, real (motor and sensory) and sham stimulations. By using a stimulus intensity of 110% of the rMT, a session of low-frequency rTMS over the primary motor (M1) and primary somatosensory (S1) cortices were performed in two different days, at the same time (late afternoon) and experimental conditions. In each session, 20 rTMS trains were delivered, with 50 stimuli at 1 Hz for each train and an intertrain interval of 30 s (1000 stimuli in total). Clinical, and TMS parameters (rMT, MEPs, CSP) were assessed before and after every stimulation procedure. The statistical analysis was focused on the pre- vs. post-treatment finding comparison by means of tests for paired datasets. Results: Preliminary data analysis confirmed the pattern of cortical excitability to TMS previously described in patients with idiopathic RLS (normal rMT and MEPs latency, shorter CSP duration, smaller MEPs amplitude). In addition, we found a beneficial, and possibly long-lasting, effect of the inhibitory real rTMS significantly higher than that of sham stimulation (simulated), as subjectively reported using an ad hoc visual analog scales to practically detect changes in patients sleep quality before and after each stimulation procedure. In particular, compared with sham stimulation, patients generally reported an overall improvement of sleep only after the M1 rTMS, with only part of them reporting more easy falling asleep after both M1 and S1 stimulation; the overall quality of sleep did not change significantly. The single-pulse TMS assessment, repeated after each session, showed a more prolonged CSP after M1 stimulation compared with baseline and a trend toward an higher rMT value, whereas MEPs amplitude remained basically unchanged; conversely, S1 and sham stimulations did not produce any variation. No clinical or neurophysiological effect was observed in healthy controls. Conclusion: The distinctive profile to TMS related to motor and somatosensory complaints we found in RLS patients might be considered a target of specific repetitive paradigms of stimulation. If this study provides valuable information at the individual level, TMS might prompt a design of an instrument for an innovative nonpharmacological approach.