An Evidence-based Analysis of the Association between Periodic Leg Movements during Sleep and Arousals in Restless Legs Syndrome

Abstract

Study objectives: To analyze statistically the association between periodic leg movements during sleep (PLMS) and arousals, in order to eventually support or challenge the current scoring rules and to further understand their reciprocal influence.

Setting: Sleep research center.

Patients: Twenty untreated consecutive patients with restless legs syndrome (RLS) (13 women and 7 males, mean age 60.9 y).

Methods: In each recording, we selected all PLMS/arousal pairs that met the following inclusion criteria: (a) PLMS events that were separated from another PLMS event (preceding or following) by at least 10 s of EMG inactivity; (b) arousal events separated from another arousal event (preceding or following) by at least 10 s of stable EEG baseline activity; (c) PLMS/arousal pairs were then selected among events identified according to the previous two criteria, when PLMS and arousals were separated (offset-to-onset) by no more than 10 s, regardless of which was first.

Measurements and results: We selected a mean of 46.1 (SD 25.55) PLMS/arousal pairs per subject; in these pairs, average PLMS duration was 3.2 s (0.65) and average arousal duration was 6.5 s (0.92). Within these event pairs, the great majority (on average 98.4%, SD 3.88) was separated by less than 0.5 s (i.e., between the end of one event and the onset of the other, regardless of which was first). Arousal onsets preceded PLMS onset in 41.2% of pairs, while the opposite was true for the remaining 58.8% of pairs. A significant correlation between PLMS duration and arousal duration was also found (r = 0.447, P < 0.000001).

Conclusion: The results of this study support the current rule for the definition of the association between periodic leg movements during sleep (PLMS) and arousals. The tight time relationship between PLMS and arousals and their correlated durations seem to indicate that both events might be regulated by a complex mechanism, rather than being connected by a simple reciprocal cause/effect relationship.

Keywords: PLMS; arousals; periodic leg movements during sleep; restless legs syndrome; sleep scoring.

Figure 1

(A) Offset-to-onset distance in each pair of events (bottom graph) and their statistical distribution (upper graph). (B) Bottom graph – Time relationship between all pairs of PLMS/arousal events; the vertical line indicates the PLMS onset while the “sigmoid” curve over the right side of the figure represents the end of each PLMS event; the horizontal lines represent the extent of the arousal accompanying each PLMS in the pairs. Upper graph – statistical distribution of the time relationship between the two events in the pairs. (C) Onset-to-onset distance in each pair of events (bottom graph) and their statistical distribution (upper graph); negative values indicate arousals preceding PLMS, positive values indicate the opposite combination.

Figure 2

Analysis of the percentage of event pairs (PLMS/arousal) separated by different time lags. Data are shown as mean (filled circles) and standard error (whiskers). Dotted lines represent the regression lines obtained for lags from 0 to 0.5 s and from 0.6 to > 2 s.

Figure 3

Analysis of the correlation between PLMS duration and arousal duration in all event pairs used in this study. The regression line is drawn as a continuous black line. Dotted lines represent the 95% confidence intervals of the regression line.