Impaired short-term plasticity in Restless Legs Syndrome: a pilot rTMS study

Background: Previous studies showed an impairment of the LTP-like plasticity to TMS in restless legs syndrome (RLS). Clinically, repetitive TMS (rTMS) was effective in alleviating the sensory-motor complaints of patients, although the effects induced by low-frequency (inhibitory) rTMS have not yet been investigated. An impaired LTD-like mechanism of cortical plasticity has been hypothesized, which we have directly assessed in this pilot study. Methods: Motor evoked potentials (MEPs) from the right first dorsal interosseus muscle were recorded at the stimulus intensity of 110% of the resting motor threshold (rMT) from 13 right-handed patients and ten age-matched right-handed healthy controls. Median peak-to-peak amplitudes were calculated in all participants at baseline (T0), after the first train of a single evening session of low-frequency (1 Hz) rTMS over the left primary motor cortex (T1), and after the whole rTMS procedure (T2), which consists of 20 trains with 50 stimuli per train and intertrain interval of 30 s (1000 stimuli in total). Results: No differences were found for rMT and MEPs size between the two groups at T0. Smaller MEPs amplitudes at both T1 and T2 were observed in all subjects, although this was significantly more pronounced in controls than in patients. Conclusions: Compared to normal individuals, patients exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus adding support to the involvement of GABA in RLS pathophysiology. Although future studies with a larger population are needed, TMS is confirmed to be effective in noninvasive probing of the neurophysiology and neurochemistry of RLS.