Neurostimulation for restless legs syndrome: A systematic review and meta-analysis

Neurostimulation may reduce restless legs syndrome (RLS) symptoms by modulating sensorimotor network excitability, providing a non-pharmacological option when drugs are ineffective or poorly tolerated. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review of clinical studies of neurostimulation for RLS, appraised quality with the Downs and Black checklist, and performed random-effects meta-analyses when outcomes were comparable. Primary outcomes were change in the International RLS Study Group Rating Scale (IRLS) and global improvement. Twenty-three studies were included, with marked heterogeneity across techniques and frequent small, short-term designs. The most consistent sham-controlled evidence supported tonic motor activation therapy delivered by noninvasive peroneal nerve stimulation: across three trials it improved IRLS versus sham (pooled mean difference -3.66 points) and increased Patient Global Impression of Improvement responders (pooled risk ratio 3.11). Small trials of repetitive transcranial magnetic stimulation suggested benefit but were highly heterogenous. Current evidence most strongly supports noninvasive peroneal nerve stimulation, yielding modest but reproducible improvement. Other modalities remain preliminary and warrant adequately powered, well-blinded trials with standardized sleep and symptom outcomes.