Acute Effects of Tonic Motor Activation (TOMAC) on Sleep in Adults with Medication-Refractory Restless Legs Syndrome

Study Objectives Tonic motor activation (TOMAC) delivers high-frequency electrical stimulation to the common peroneal nerve to reduce restless legs syndrome (RLS) symptoms and improve subjective sleep quality. This cross-sectional analysis provides the first objective evaluation of wake-sleep transition and exploration of sleep parameter and leg movement changes following mid-sleep TOMAC sessions during polysomnography (PSG). Methods Twenty participants with medication-refractory RLS completed two PSGs and activated 30-minute TOMAC sessions as needed when awakening mid-sleep with RLS symptoms. Objective sleep parameters including sleep re-initiation latency, architecture, and hourly indices of periodic leg movements during sleep (PLMS) and PLMS associated with arousal (PLMA) were compared between sleep periods before and after activating mid-sleep TOMAC sessions. Results Sleep re-initiation occurred during the 30-minute TOMAC session for 24 of 29 (82.8%) mid-sleep sessions, with median latency of 6.7 (range=0.9-45.9) minutes following TOMAC activation. The latency from TOMAC activation to sleep re-initiation was shorter in participants who activated TOMAC within 10-minutes of awakening compared to those who waited longer (p=0.016). There was a linear increase in the proportion of delta and decrease in alpha EEG frequency-band power after activating mid-sleep TOMAC (both p<0.001), indicating the transition towards deeper sleep. Comparing sleep intervals before and after activating mid-sleep TOMAC, PLMS/hour decreased by 47.9% (p=0.042) and PLMA/hour decreased by 70.8% (p=0.004). Conclusions TOMAC was compatible with sleep; rapid sleep re-initiation and transition to deeper sleep were observed during TOMAC stimulation. This data also provide proof-of-concept evidence that PLMS may decrease following activation of mid-sleep TOMAC. Clinical Trial Details This study was preregistered on January 31, 2022 ClinicalTrials.gov with name “Noninvasive Peripheral Nerve Stimulation for Medication-Naive and Medication-Refractory RLS” and number NCT05214963 at https://clinicaltrials.gov/study/NCT05214963.