Periodic limb movements in sleep exhibit a circadian rhythm that is maximal in the late evening/early night

Abstract

Objective: Periodic limb movements in sleep (PLMS) show a time-of-night pattern, with most movements at the beginning of the night. Our study aimed to determine whether this pattern is due to an endogenous circadian rhythm, like that in the related movement disorder Restless Legs Syndrome (RLS).

Methods: Four healthy older adults with a screening PLMI>20 were studied in an inpatient forced desynchrony protocol with an imposed sleep-wake cycle of 20 h for 12 "nights," allowing separation of circadian and sleep homeostatic influences on leg movements. We recorded sleep polysomnographically throughout each scheduled episode, including left and right anterior tibialis EMG.

Results: PLMS in Stage 2 showed both a significant time-within-sleep pattern and a significant circadian rhythm. The circadian rhythm in PLMS peaked at the circadian phases when usual sleep onset occurs, preceding the evening rise in melatonin secretion.

Conclusions: In our subjects, the circadian pattern of PLMs expression was very similar to that previously reported in patients with RLS. This evidence for a circadian rhythm in PLMS has implications for treatment and provides direction for future studies of the pathophysiology of this movement disorder.

Figure 1

Raster plot of study protocol. The x-axis shows time of day and is 24 hours in length. The y-axis shows the day of the experiment, with each day shown beneath the previous day. Black bars indicate scheduled sleep episodes. The first three 24-hour baseline days (8 hours scheduled bedrest) were scheduled at the subjects’ habitual times. Following this was the forced desynchrony segment, during which the subjects were scheduled to live on a 20-hour rest-activity cycle for 30 cycles (26 calendar days), with one-third (6.67 hours) of each “day” spent lying in bed in the dark attempting to sleep. The final three 24-hour recovery days were scheduled at the same times as the baseline. Non-shaded areas on the plot indicate those study segments that were included in our analysis.

Figure 2

Pattern of periodic limb movements of sleep (PLMS) across the night during baseline nights (upper panel) when sleep was scheduled for 8 hours at habitual times, and during forced desynchrony (lower panel) when sleep was scheduled for 6.67 hours at many circadian phases. Mean ± standard deviation PLMS per hour of stage 2 sleep are plotted with respect to elapsed time since lights out. Data were binned per subject and then averaged across subjects.

Figure 3

Pattern of endogenous melatonin secretion (upper panel) and periodic limb movements of sleep (lower panel) with respect to circadian phase during forced desynchrony. Upper panel: Plasma melatonin data from each subject were averaged per 60° circadian phase bin (~4 hours), and then averaged across the four subjects. Mean ± standard deviation are double-plotted with respect to the center of the bin. Lower panel: PLMS counts per hour of stage 2 sleep from each subject were averaged per 60° circadian phase bin, and then averaged across the four subjects. Mean ± standard deviation are double-plotted with respect to the center of the bin. The upper x-axis indicates corresponding time of day under entrained conditions. The shaded area indicates where the nightly sleep episode would occur, on average, during entrained conditions.