Clinical-electrophysiological impact of low-frequency rTMS over the sensory-motor cortex in Restless Legs Syndrome

Objective: Transcranial Magnetic Stimulation (TMS) showed hyperexcitability and disinhibition in Restless Legs Syndrome (RLS). We first explored low-frequency (inhibitory) repetitive TMS (rTMS) over primary (M1) and somatosensory cortices (S1) of RLS subjects. Methods: 13 right-handed drug-free patients and 10 age-matched controls were studied by clinical scales and TMS, including resting motor threshold (rMT), motor evoked potentials (MEPs), cortical silent period (CSP), central conduction time. A single evening 1 Hz-rTMS session over left M1, left S1, and sham (simulated) was administered. Results: at baseline, patients exhibited shorter CSP. Patients perceived a clinical improvement of both initiating and maintain sleep the night after real stimulation, although S1-rTMS produced a higher benefit. CSP remained persistently shorter in patients. Patients showed a decrease of rMT after S1-rTMS only, but with a smaller effect than in controls. MEPs amplitude decreased after M1-rTMS, although the difference was more evident in controls. Sham did not produce variations. Conclusions: rTMS on S1-M1 connectivity may alleviate the sensory-motor complaints of RLS patients, who exhibit only partial GABA-mediated short-term cortical plasticity. TMS changes points also at an involvement of glutamatergic excitatory intracortical and cortical-spinal circuitries. The rTMS-induced activation of ipsilateral dorsal striatum, with the consequent increase of dopamine release, may contribute to the clinical response.