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.