Noninvasive neuromodulation reduces symptoms of restless legs syndrome

Abstract

Study objectives: Restless legs syndrome (RLS) is a common neurological disorder characterized by an uncontrollable nocturnal urge to move the legs and often associated with chronic sleep disturbances. The most common treatments for RLS are medications that can have debilitating side effects. Here, we evaluated a novel alternative modality of RLS treatment, noninvasive bilateral electrical stimulation of the common peroneal nerve.

Methods: To assess the impact of this noninvasive peripheral nerve stimulation (NPNS) approach to RLS symptomatology, we conducted a multisite randomized crossover study comparing NPNS to sham. RLS patients with moderate-to-severe RLS (n = 37) self-administered NPNS and sham nightly for 14 days per treatment in randomized order.

Results: NPNS resulted in a reduction in RLS severity of 6.81 points on the International RLS Rating Scale relative to 3.38 for sham (P < .01) and a 66% clinically significant responder rate on the Clinical Global Impressions-Improvement scale compared to 17% for sham (P < .01). Subgroup analysis indicated that medication-resistant and medication-naïve participants both exhibited similarly robust responses. There were no moderate or serious device-related adverse events.

Conclusions: These results suggest that NPNS could be a promising alternative to pharmacological therapies for RLS and could provide a solution for medication-resistant RLS patients and for medication-naïve RLS patients who are unwilling or unable to take medication.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome; URL: https://ichgcp.net/clinical-trials-registry/NCT04700683; Identifier: NCT04700683.

Citation: Buchfuhrer MJ, Baker FC, Haramandeep S, et al. Noninvasive neuromodulation reduces symptoms of restless legs syndrome. J Clin Sleep Med. 2021;17(8):1685-1694.

Keywords: bioelectronic; neurological disorder; neuromodulation; peripheral nerve stimulation; restless legs syndrome; sleep disorder.

© 2021 American Academy of Sleep Medicine.

Figures

Figure 1. Structural study design and participant disposition.

Flowchart indicating ordering and duration of interventions and disposition of participants. LOCF = last observation carried forward, mITT = modified intention-to-treat, NPNS = noninvasive peripheral nerve stimulation, RLS = restless legs syndrome.

Figure 2. NPNS device attached to body.

An electrode patch connected to the left leg and connected to (A) or disconnected from (B) a noninvasive peripheral nerve stimulation device. NPNS = noninvasive peripheral nerve stimulation.

Figure 3. Comparison of IRLS reduction before and after crossover.

The mean reduction in IRLS relative to baseline compared between NPNS (filled circles) and sham (open circles) and between the first intervention (before crossover, left) and the second intervention (after crossover, right). Error bars denote standard error of the mean. IRLS = International RLS Study Group rating scale, NPNS = noninvasive peripheral nerve stimulation.

Figure 4. RLS symptom severity and leg movement during the suggested immobilization test.

Participant ratings of RLS symptom severity on a 11-point numerical rating scale (NRS) during a 60-minute suggested immobilization test procedure. The mean ± SEM change in NRS relative to t = 0 (start of SIT) is shown for NPNS (blue), sham (gray), and baseline (black, no intervention). NPNS = noninvasive peripheral nerve stimulation, NRS = numerical rating scale, SEM = standard error of the mean, SIT = suggested immobilization test.