Noctrix Health, Inc., Pleasanton, California.
Sleep Medicine Specialists of California, San Ramon, California.
J Clin Sleep Med. 2023 Jul 1;19(7):1199-1209. doi: 10.5664/jcsm.10536.
Restless legs syndrome (RLS) is a prevalent sleep disorder with limited treatment options. Bilateral high-frequency noninvasive peroneal nerve stimulation (NPNS) reduces RLS symptoms. Here, we sought to characterize the mechanism of action for NPNS and identify predictors of treatment response. We hypothesized that, similar to voluntary leg movements, NPNS reduces RLS symptoms by activating leg muscles.
For 20 adults with moderate-severe RLS, we tested this hypothesis by recording surface electromyography (EMG) from the tibialis anterior leg muscle while administering NPNS at varying amplitudes to determine the minimum NPNS amplitude that evoked EMG activity (motor threshold) and maximal NPNS amplitude that was not distracting (therapeutic intensity level). Afterwards, participants self-administered NPNS (at the therapeutic intensity level) and sham control for 14 days, each in randomized order. Efficacy was defined as International RLS Study Group Rating Scale (IRLS) score difference for NPNS compared with sham.
NPNS consistently activated leg muscles; NPNS evoked EMG activity at the therapeutic intensity level for 19 of 20 participants (mean TIL: 26.6 mA, mean MT: 18.3 mA). Evoked EMG activity was tonic (not phasic) and sustained over time. Evoked EMG activity predicted efficacy; participants with lower motor thresholds had greater IRLS improvement ( = .45, = .046). NPNS treatment did not interfere with self-reported sleep onset (NPNS: 16% of nights; sham: 11%; = .629) and frequently improved self-reported sleep onset (NPNS: 52% of nights; sham: 15%; = .002).
These results demonstrate that NPNS reduces RLS symptoms by activating afferent pathways, thereby generating tonic and sustained leg muscle activity without interfering with sleep.
Registry: ClinicalTrials.gov; Name: Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT04700683; Identifier: NCT04700683.
Charlesworth JD, Adlou B, Singh H, Buchfuhrer MJ. Bilateral high-frequency noninvasive peroneal nerve stimulation evokes tonic leg muscle activation for sleep-compatible reduction of restless legs syndrome symptoms. . 2023;19(7):1199-1209.
不宁腿综合征（RLS）是一种常见的睡眠障碍，治疗选择有限。双侧高频非侵入性腓肠神经刺激（NPNS）可减轻 RLS 症状。在这里，我们试图描述 NPNS 的作用机制，并确定治疗反应的预测因素。我们假设，与自愿腿部运动类似，NPNS 通过激活腿部肌肉来减轻 RLS 症状。
对于 20 名中度至重度 RLS 成人，我们通过记录胫骨前肌的表面肌电图（EMG）来测试这一假设，同时以不同的幅度给予 NPNS，以确定诱发 EMG 活动的最小 NPNS 幅度（运动阈值）和不分散注意力的最大 NPNS 幅度（治疗强度水平）。之后，参与者以随机顺序在 14 天内分别接受 NPNS（治疗强度水平）和假刺激治疗。疗效定义为 NPNS 与假刺激相比的国际 RLS 研究组评分量表（IRLS）评分差异。
NPNS 始终激活腿部肌肉；NPNS 在 20 名参与者中的 19 名（平均 TIL：26.6mA，平均 MT：18.3mA）达到治疗强度水平时诱发 EMG 活动。诱发的 EMG 活动是紧张的（非阶段性的），并随时间持续。诱发的 EMG 活动可预测疗效；运动阈值较低的参与者 IRLS 改善更大（ =.45， =.046）。NPNS 治疗不会干扰自我报告的入睡（NPNS：16%的夜晚；假刺激：11%； =.629），并经常改善自我报告的入睡（NPNS：52%的夜晚；假刺激：15%； =.002）。
这些结果表明，NPNS 通过激活传入通路来减轻 RLS 症状，从而产生紧张和持续的腿部肌肉活动，而不干扰睡眠。
注册处：ClinicalTrials.gov；名称：非侵入性周围神经刺激治疗不宁腿综合征；网址：https://clinicaltrials.gov/ct2/show/NCT04700683；标识符：NCT04700683。
Charlesworth JD, Adlou B, Singh H, Buchfuhrer MJ. 双侧高频非侵入性腓肠神经刺激引起紧张性腿部肌肉激活，用于睡眠兼容的不宁腿综合征症状缓解。 2023；19(7)：1199-1209。
