Bilateral high-frequency noninvasive peroneal nerve stimulation evokes tonic leg muscle activation for sleep-compatible reduction of restless legs syndrome symptoms
Bilateral high-frequency noninvasive peroneal nerve stimulation evokes tonic leg muscle activation for sleep-compatible reduction of restless legs syndrome symptoms
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DOI：
10.5664/jcsm.10536
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发表时间：
2023-07-01
影响因子：
4.3
通讯作者：
Buchfuhrer, Mark J.
中科院分区：
文献类型：
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作者：
Charlesworth, Jonathan D.;Adlou, Bahman;Buchfuhrer, Mark J.
研究目的：不宁腿综合征（RLS）是一种常见的睡眠障碍，治疗选择有限。双侧高频无创腓神经刺激（NPNS）可减轻不宁腿综合征症状。在此，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，与自主腿部运动类似，NPNS通过激活腿部肌肉来减轻不宁腿综合征症状。
方法：对于20名患有中重度不宁腿综合征的成年人，我们通过记录胫骨前肌的表面肌电图（EMG）来验证这一假设，同时给予不同幅度的NPNS，以确定诱发EMG活动的最小NPNS幅度（运动阈值）以及不会造成干扰的最大NPNS幅度（治疗强度水平）。之后，参与者自行给予NPNS（按治疗强度水平）和假刺激对照，为期14天，顺序随机。疗效定义为NPNS与假刺激相比的国际不宁腿综合征研究小组评分量表（IRLS）得分差异。
结果：NPNS持续激活腿部肌肉；在20名参与者中的19名，NPNS在治疗强度水平诱发了EMG活动（平均治疗强度水平：26.6毫安，平均运动阈值：18.3毫安）。诱发的EMG活动是强直性的（非阶段性的）且随时间持续。诱发的EMG活动可预测疗效；运动阈值较低的参与者IRLS改善更明显（r = 0.45，P = 0.046）。NPNS治疗不干扰自我报告的入睡情况（NPNS：16%的夜晚；假刺激：11%；P = 0.629），且经常改善自我报告的入睡情况（NPNS：52%的夜晚；假刺激：15%；P = 0.002）。
结论：这些结果表明，NPNS通过激活传入通路减轻不宁腿综合征症状，从而产生强直性且持续的腿部肌肉活动，且不干扰睡眠。
临床试验注册：注册机构：ClinicalTrials.gov；名称：不宁腿综合征的无创外周神经刺激；网址：https://clinicaltrials.gov/ct2/show/NCT04700683；标识符：NCT04700683
Study Objectives: 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. Methods: 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. Results: 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 (r = .45, P = .046). NPNS treatment did not interfere with self-reported sleep onset (NPNS: 16% of nights; sham: 11%; P = .629) and frequently improved self-reported sleep onset (NPNS: 52% of nights; sham: 15%; P = .002). Conclusions: These results demonstrate that NPNS reduces RLS symptoms by activating afferent pathways, thereby generating tonic and sustained leg muscle activity without interfering with sleep. Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome; URL: https://clinicaltrials. gov/ct2/show/NCT04700683; Identifier: NCT04700683.