Dopamine agonists restore cortical plasticity in patients with idiopathic restless legs syndrome

In the present work, we aimed at assessing whether patients with idiopathic restless legs syndrome (RLS) showed alterations of sensory-motor plasticity, an indirect probe for motor learning, within the motor cortex (M1). Previous findings suggest that learning in human M1 occurs through LTP-like mechanisms. To test our hypothesis, we employed the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in the motor cortex of normal subjects. Twelve patients with idiopathic RLS and 10 age- and sex-matched control subjects were recruited. PAS protocol consisted of 0.05 Hz electrical median nerve stimulation (90 stimuli), paired with 0.05 Hz TMS (90 stimuli) over the hot spot for stimulating the abductor pollicis brevis (APB) muscle given 25 milliseconds after the onset of the electrical stimulus. Corticospinal excitability recorded in APB muscle, as indexed by MEP obtained after single stimulus, was tested before and up to 30 minutes after PAS protocol. Eight of 12 patients were studied before and after 4 weeks of dopaminergic treatment. PAS protocol increased significantly corticospinal excitability as long as 30 minutes in healthy subjects. On the contrary, PAS protocol did not change the amplitude of MEPs in patients with idiopathic RLS without treatment. PAS associative plasticity was restored after 4 weeks of dopaminergic treatment. Our data demonstrated that associative sensory-motor plasticity, an indirect probe for motor learning, is impaired in idiopathic RLS patients but may be reverted to normal after dopaminergic treatment.