The significance of the sympathetic nervous system in the pathophysiology of periodic leg movements in sleep

Abstract

Study objectives: Periodic leg movements in sleep (PLMS) are frequently accompanied by arousals and autonomic activation, but the pathophysiologic significance of these manifestations is unclear.

Design: Changes in heart rate variability (HRV), HRV spectra, and electroencephalogram (EEG) spectra associated with idiopathic PLMS were compared with changes associated with isolated leg movements and respiratory-related leg movements during sleep. Furthermore, correlations between electromyographic activity, HRV changes, and EEG changes were assessed.

Setting: Sleep laboratory.

Patients: Whole-night polysomnographic studies of 24 subjects fulfilling the criteria of either periodic leg movements disorder (n = 8), obstructive sleep apnea syndrome (n = 7), or normal polysomnography (n = 9) were used.

Measurements and results: Spectral HRV changes started before all EEG changes and up to 6 seconds before the onset of all types of leg movements. An initial weak autonomic activation was followed by a sympathetic activation, an increase of EEG delta activity, and finally a progression to increased higher-frequency EEG rhythms. After movement onset, HRV indicated a vagal activation, and, the EEG, a decrease in spindle activity. Sympathetic activation, as measured by HRV spectra, was greater for PLMS than for all other movement types. In EEG, gamma synchronization began 1 to 2 seconds earlier for isolated leg movements and respiratory-related leg movements than for PLMS. Significant correlations were found between autonomic activations and electromyographic activity, as well as between autonomic activations and EEG delta activity, but not between higher-frequency EEG rhythms and EMG activity or HRV changes.

Conclusions: These results suggest a primary role of the sympathetic nervous system in the generation of PLMS.

Figure 1

The time courses of heart-rate variability (HRV) and electroencephalogram (EEG) changes are shown relative to onset of periodic limb movements of sleep (PLMS) at 0 seconds. A. Mean HRV ± 95% confidence interval of all subjects with periodic limb movement disorder (PLMD). B. Time-frequency decomposition of HRV with a continuous wavelet transform event related to leg-movement onset. The grand average of power changes from baseline (−10 to −7 s) of all PLMS is shown with nonsignificant changes set to 0. The frequencies are plotted with a pseudologarithmic scale. Three different processes could be distinguished, as indicated in the graph. As explained in the text, process 1 was interpreted as a general weak autonomic activation, process 2 as sympathetic activation, and process 3 as vagal activation. C. Time-frequency decomposition of EEG channel C3-M2 with a sinusoidal wavelet transform. The mean power spectrum over time is shown in black and white. Significant power changes to baseline (−10 to −7 s) are overlaid in color. EEG changes began clearly after the first spectral HRV changes shown in B.

Figure 2

Comparison of spectral heart-rate variability (HRV) and electroencephalogram (EEG) changes of all 3 leg-movement types in sleep. In contrast to Figure 1, nonsignificant power changes are not masked to 0. Note the stronger intensities of HRV processes in association with periodic limb movements of sleep than during other types of leg movements in sleep and the different time course of EEG changes for different leg-movement types. PLMS refers to periodic limb movements of sleep; ILMS, isolated leg movements in sleep; RRLMS, respiratory-related leg movements in sleep.

Figure 3

The time course of heart-rate variability (HRV) changes are shown in relation to the onset of the 3 different movement types analyzed. Analysis was performed in the time domain (HRV) as well as in the time-frequency plane using a continuous wavelet transform (low frequency [LF], high frequency [HF], and LF/HF). Thick lines show mean ± SEM values. Stair plots below each graph indicate the statistical probability that HRV changes are equal for all 3 movement types at the given time point. Note the 2 distinctive peaks of LF and HF power changes as well as of LF/HF ratio changes, occurring similarly for all examined movement types. LF-power- and LF/HF-ratio changes before and immediately after movement onset (indicating sympathetic activations, process 2) were significantly different between movement types. Furthermore, LF-power changes 4 seconds after movements (indicating vagal activations, process 3) were significantly different. PLMS refers to periodic limb movements of sleep; ILMS, isolated leg movements in sleep; RRLMS, respiratory-related leg movements in sleep.

Figure 4

Comparison of the time course of electroencephalogram (EEG) changes during sleep stage 2 of electrode C3-M2 between the different leg-movement types. Thick lines show mean ± SEM values. Stair plots below each graph indicate the statistical probability that EEG changes are equal for all 3 movement types at the given time point. Note that the spectral EEG changes were similar for all examined movement types. However, delta and alpha synchronization were significantly smaller for isolated leg movements in sleep (ILMS) than for periodic limb movements of sleep (PLMS). Furthermore, an increase in gamma activity occurred later for PLMS than for the other movement types. RRLMS refers to respiratory-related leg movements in sleep.

Figure 5

Scatter plots illustrating the correlations between sympathetic activation during process 2 and motor activity in sleep stage 2. Significant correlations were found between LF/HF change during process 2 and movement duration (r=0.53, P=0.008), inter-movement interval (r=−0.70, P<0.001), and PLMS-index (r=0.58, P=0.003).”