Connecting clinical aspects to corticomotor excitability in restless legs syndrome: a TMS study

We assessed corticomotor excitability in the primary motor cortex (M1) of participants with moderate-to-severe restless legs syndrome (RLS) symptoms using transcranial magnetic stimulation (TMS) in relation to the clinical and sleep aspects of the disease. Thirty-five participants (20 F; mean age: 59.23 ± 1.66 years; range: 42-78 years) affected by primary RLS (off medications) and 31 age-matched controls (19 F; mean age: 57.90 ± 1.50 years; range: 43-79 years) underwent TMS following two nights of polysomnography (PSG). Paired-pulse TMS measures [short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF)] of the dominant M1_hand and M1_leg muscles were collected and analyzed in relation to clinical features of RLS and PSG. We found decreased corticomotor excitability in M1_hand, whereas it was increased in M1_leg, which was greater in patients with more severe RLS. Participants with RLS with a history of dopamine-agonist-induced symptom augmentation showed decreased LICI (reduced inhibition) compared to nonaugmented participants with RLS for M1_leg. None of the TMS measures (M1_hand or M1_leg) correlated with the PSG parameters. This study shows hyperexcitability in M1_leg, and this appears related to RLS disease severity and decreased excitability in M1_hand. The results provide new insight into the complex neurobiology of RLS, particularly in more advanced stages of the disease.