Jin Byungjoo, Wang Allan, Earley Christopher, Allen Richard
School of Arts and Sciences, Johns Hopkins University, USA.
Bloomberg School of Public Health, Johns Hopkins University, USA.
Sleep Med. 2020 Apr;68:89-95. doi: 10.1016/j.sleep.2019.09.005. Epub 2019 Oct 5.
Restless legs syndrome (RLS) patients have been found to have high rates of transitory increases in the activity of the sympathetic autonomic nervous system with increases in heart rate and blood pressure. These were identified by evaluating heart rate or blood pressure changes independent of any leg movement analyses. There has been an implicit assumption this high rate of sympathetic activations is abnormal, but there has been no direct comparison for similar measures with a healthy population free of RLS. Thus, it is not known if during sleep the rates of sympathetic nervous system activation are greater for RLS than for a healthy population. The objectives of this study were to determine if: (1) RLS patients compared to healthy controls have a greater frequency of sympathetic nervous system activation (significant heart rate increases) with a higher percentage of leg movements associated with these activations; (2) the sympathetic activation frequency and its relation to leg movements correlate significantly with RLS severity in RLS patients; and (3) there is some minimum threshold for RLS severity defining an RLS population where most (eg 85%) have abnormally high rates of sympathetic activation.
Sleep data on 32 RLS patients and 21 matched healthy controls were obtained from a prior study. All leg movements during sleep (LMS) and periodic leg movements in sleep (PLMS) were identified following the new WASM criteria; LMS that were not PLMS were considered isolated leg movements in sleep (ILMS). All episodes with significant heart rate increases were identified following procedures established by Cassel et al., (2016, see further on for citation) ie a slope of linear regression ≥2.5 beats per minute over five consecutive heartbeats. Severity of RLS was evaluated using the International Restless Legs Study Group Scale (IRLS).
RLS patients had significantly more heart rate increases than controls (67.88/hr vs. 9.87/hr). RLS patients had a significantly greater percentage of both LMS and PLMS occurring with heart rate increases than controls (44% vs. 30%; 48% vs. 18%, respectively). These measures correlated significantly with IRLS and also PLMS/hr. 85% of the RLS patients with IRLS scores >22 or PLMS >50/hr had rates of sympathetic activation that were >90th percentile for the healthy controls.
This is the first paper documenting that RLS patients showed clearly increased sympathetic activation when identified independent of PLMS. This, however, occurs for more severe RLS and not milder RLS. It has been proposed that the abnormally high rate of sympathetic activation for RLS patients relates to development of adverse cardiovascular health consequences observed in some studies. Thus, these data may provide a basic standard for possible use in epidemiological studies to identify the level of RLS severity more likely to have adverse health consequences (eg, cardiovascular disease). Since two-thirds of RLS patients have mild to even intermittent disease, including all RLS is likely to miss the potential health consequences of RLS.
研究发现,不宁腿综合征(RLS)患者交感自主神经系统活动短暂增加,心率和血压随之上升的发生率较高。这些情况是通过独立于任何腿部运动分析来评估心率或血压变化而确定的。一直以来都隐含着这样一种假设,即这种高发生率的交感神经激活是异常的,但尚未将类似指标与无RLS的健康人群进行直接比较。因此,尚不清楚在睡眠期间,RLS患者交感神经系统的激活率是否高于健康人群。本研究的目的是确定:(1)与健康对照组相比,RLS患者交感神经系统激活(显著心率增加)的频率是否更高,且与这些激活相关的腿部运动百分比更高;(2)RLS患者的交感神经激活频率及其与腿部运动的关系是否与RLS严重程度显著相关;(3)RLS严重程度是否存在某个最低阈值,以此界定一个RLS群体,其中大多数(如85%)的交感神经激活率异常高。
从先前的一项研究中获取了32例RLS患者和21例匹配的健康对照的睡眠数据。按照新的WASM标准识别睡眠期间的所有腿部运动(LMS)和睡眠期周期性腿部运动(PLMS);非PLMS的LMS被视为睡眠期孤立腿部运动(ILMS)。按照Cassel等人(2016年,引用见后文)制定的程序识别所有心率显著增加的发作,即连续五次心跳的线性回归斜率≥2.5次/分钟。使用国际不宁腿研究组量表(IRLS)评估RLS的严重程度。
RLS患者心率增加明显多于对照组(67.88次/小时 vs. 9.87次/小时)。RLS患者LMS和PLMS伴随心率增加出现的百分比均显著高于对照组(分别为44% vs. 30%;48% vs. 18%)。这些指标与IRLS以及PLMS/小时均显著相关。IRLS评分>22或PLMS>50次/小时的RLS患者中,85%的交感神经激活率高于健康对照组的第90百分位数。
本文首次记录了RLS患者在独立于PLMS进行识别时,交感神经激活明显增加。然而,这种情况发生在较严重的RLS患者中,而非较轻的RLS患者。有人提出,RLS患者异常高的交感神经激活率与一些研究中观察到的不良心血管健康后果的发生有关。因此,这些数据可能为流行病学研究提供一个基本标准,用于识别更可能产生不良健康后果(如心血管疾病)的RLS严重程度水平。由于三分之二的RLS患者患有轻度甚至间歇性疾病,纳入所有RLS患者可能会忽略RLS潜在的健康后果。