Arch. Gerontol. Geriatr., 7 (1988) 273-279 273 Elsevier

AGG 00226

Nightly variation of periodic leg movements in sleep in middle aged and elderly individuals

D o n a l d L. Bliwise a, M a r y A. C a r s k a d o n b a n d Wi l l i am C. D e m e n t a

a Sleep Disorders Center, Stanford University Medical School, Stanford, CA 94305, USA and b Department of Psychiatry and Human Behavior,

Brown University School of Medicine, East Providence, RI 02915, USA

(Received 29 June 1987; revised version received 8 December 1987; accepted 4 March 1988)

Summary

This study investigated night-to-night variation in periodic leg movements in sleep (PLMS). PLMS are common in the elderly, but their mechanism and significance are not understood. Forty-five aged individuals (.~ = 69.7 years) were studied polysomnographically for 2 or 3 nights with surface electrodes placed above the anterior tibialis. Results indicated that PLMS varied considerably from night to night within individuals, though there was not a significant difference between nights for the entire group. Some evidence indicated that individuals with less severe sleep complaints showed greater nightly variation. The nightly variation in PLMS was over four times as large as the nightly variation in breathing disturbance in sleep, another condition common in the sleep of the aged. These data suggest that studies relating PLMS to other key variables (e.g., symptoms of disturbed sleep) should rely on multiple nights of data or, if single night data are used, be particularly careful to replicate findings across samples.

Periodic leg movements; Nocturnal myoclonus; Sleep disorders

Introduction

Periodic leg movements in sleep (PLMS) are rhythmic, non-epileptiform move- ments of the lower limbs occurring during sleep (Coleman, 1982). They show a clear age-related prevalence (Coleman et al., 1980; Bixler et al., 1982, Roehrs et al., 1983). A recent study (Ancoli-Israel et al., 1985, 1986) reported that nearly 45% of a representative sample of individuals over 65 had over five movements per hour of sleep. The functional significance of PLMS is unknown (Bliwise et al., 1985); neither their mechanism nor their impact upon sleep disturbance and other health problems

Correspondence to Donald L. Bliwise, PhD, Sleep Disorders Center, Stanford University Medical School, Stanford, CA 94305, USA.

0167-4943/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)

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in the aged have been resolved. Some studies, for example, suggest that PLMS may play a role in geriatric insomnia (Roehrs et al., 1983; Saskin et al., 1985) whereas others do not (Kales et al., 1982). To the extent that PLMS vary within individuals from night to night, studies examining associations between PLMS and other conditions may face methodological problems. Because PLMS are highly prevalent in the elderly, it is of considerable importance to determine if we can rely upon a single night of data in their assessment. In addition, we will compare the nightly variation in PLMS to the nightly variation in sleep-related respiratory disturbance (Bliwise et al., 1983), which is another characteristic feature of sleep in older adults.

Materials and Methods

Subjects

Subjects in this study were 45 ambulatory, non-institutionalized elderly (X age = 69.7 years, SD = 8.24, range 49-87) individuals living in the Palo Alto area; 33 were females and 12 were males. Sleep Clinic patients were not included in the sample. Of the 45 subjects, 13 were recruited originally for studies of insomnia whereas the remaining 32 had no spontaneous sleep complaints. The recruitment of these two subgroups of individuals is described in greater detail elsewhere and correspondent to groups D and E, respectively, of that report (Bliwise et al., 1987).

None of these individuals showed significant sleep-related respiratory dis- turbance on any night of the study; respiratory disturbance index (RDI) values were less than 5.0 for all subjects. Seventeen of the 66 subjects in our earlier study of nightly variation in sleep-related respiratory disturbance (Bliwise et al., 1983) were included in this study.

Procedures

Subjects were studied for 2 or 3 nights in the laboratory. For 35 persons, recordings from nights 1 and 2 were used. For the remaining 10 individuals, inconsistencies in bilateral or unilateral recordings (see below) required our using nights 1 and 3. Electroencephalogram (EEG), electrooculogram (EOG), and surface mentalis electromyogram (EMG) were recorded and scored with standard tech- niques (Rechtschaffen and Kales, 1968) in 30-s epochs on Grass Model 7D Polysomnographs. Respiration during sleep was recorded with nasal/oral thermis- tors for airflow and strain gauges or single-channel, uncalibrated respiratory induc- tive plethysmography (Cohn, 1982; Bornstein, 1982). Periodic leg movements in sleep were recorded identically for each subject on both nights with bilateral or unilateral EMG electrodes on the skin surface above the anterior tibialis. Of the 45 subjects, 37 had bilateral recordings consisting of either separate left and right channels or left and right leads, simultaneously recorded on a single channel with a push-button selector panel. In the remaining eight subjects we recorded on a Grass 7D Polysomnograph with a dial selector panel allowing for only one side of anterior

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tibialis recording each night. Of these, five were left-sided recordings and three were right-sided recordings.

Sleep stage measures included total sleep time (TST) and sleep efficiency (TST/ t ime in bed x 100). Respiratory disturbances were scored as absence (apnea) or diminution (hypopnea) of breathing for at least 10 s during sleep. Anterior tibialis scoring followed standard rules (Coleman, 1982). PLMS were defined as leg movements of at least half the amplitude of the EMG amplitude in a pre-sleep ankle dorsiflexion calibration. The movements were required to last between 0.5 and 4.0 s with an inter-event interval of greater than 4.0 but less than 90.0 s. In addition, movements had to occur in episodes of at least four movements meeting the above inter-movement criteria. The scoring of movements in an episode was terminated when the 90-s criterion expired, when an epoch of wakefulness or movement time occurred, or when over 15 consecutive s of EEG arousal occurred. PLMS were not scored if the movements occurred at termination of a respiratory event, even if the above criteria were met. We have previously shown inter-scorer reliability with these scoring criteria (Coleman et al., 1983). The number of movements was divided by TST (in min) and multiplied by 60 to yield a PLMS index per hour of sleep.

All but two subjects completed an abbreviated version of the Sleep Questionnaire and Assessment of Wakefulness (SQAW) (Miles, 1982). The SQAW generated data on the following specific sleep-related complaints: crawling in legs, twitching in legs, any physical pain in sleep, trouble falling asleep, night awakening, waking up too early in the morning, non-restorative sleep, daytime sleepiness, and daytime fatigue. We have reported previously on the relationship between these symptoms and PLMS (Bliwise et al., 1985).

Results

Thirty-eightland 43 subjects had over 300 min of sleep on the first and second lab nights, respectively. Table I shows the increase in total sleep time and sleep efficiency on the second lab night, as well as the low level of breathing disruption during the sleep of these subjects. There was no significant difference between lab nights on the PLMS index for the group as a whole, and there was substantial reliability for this measure within subjects. A graph of the PLMS index on the first and second lab nights (Fig. 1) however, shows substantial individual variability. Although subjects with relatively low values remained relatively low and those with high values remained relatively high, the magnitude of the nightly variation was frequently large. This is evidenced by the size of the standard deviations for this measure on each night (see Table I).

Are sleep complaints related to this nightly variation? We examined this in two ways: first, by comparing insomniac and non-insomniac subjects and second, by relating nightly variation to self-reported sleep complaints on the SQAW. Dif- ference scores (absolute values of the PLMS index) did not discriminate between the insomniac (.~ = 9.71) and non insomniac (X = 10.60) groups (t = 0.20, NS), nor did groups differ on the PLMS index on night 1 or night 2. Several SQAW-derived sleep

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complaints related to PLMS difference scores, however, including early morning awakening (rho = -0 .31 , p < 0.05), daytime fatigue (rho = - 0 . 2 9 , p < 0.06) and non-restorative sleep (rho = - 0 . 3 3 , p < 0.03). The direction of these results indi- cated that subjects with lower severity of symptoms were more likely to show nightly variation in PLMS.

It is of interest to compare this nightly variation in PLMS with the nightly variation known to occur in sleep-related respiratory disturbance. The means and

1 5 0 ~ L150

X Q~

. . .1 1 3 . .

v v

First night Second night Fig. 1. Marked nightly variation in periodic leg movements index on 2 lab. nights.

TABLE I

Sleep variables for lab nights

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Variable First lab night Second lab night Two-night Two-night (mean (SD) value) (mean (SD) value) paired reliability

comparison

Total sleep time a 382.12 411.26 t = 2.99 * * 0.61 * * * (79.45) (65.89)

Sleep efficiency a 76.85 79.85 t = 1.45 0.47 * * (14.65) (12.05)

Respiratory disturbance index a 0.86 1.35 t = 2.33 * 0.38 * (0.96) (1.41)

Periodic leg movements index b 20.62 19.14 z = 0.32 0.68 * * * (28.52) (20.47)

a Normally distributed variable; paired t tests used for paired comparisons; Pearson correlations for reliability.

b Non-normally distributed variable; Wilcoxon signed-rank tests used for paired comparisons; rank order correlations for reliability.

* p < 0.05; * *p < 0.01; * * *p < 0.005.

standard deviations for the PLMS index across the 2 nights are certainly higher in these cases than for the respiratory disturbance index (RDI) in our previous report (Bliwise et al., 1983), and higher than RDI in the current data as well. The mean difference in the PLMS index across the 2 lab nights in the present study was 10.35 (SD = 13.17). In our previous report, the mean RDI difference across nights 1 and 2 for the 66 subjects was 1.16 (SD = 3.65). These data suggest that the PLMS index varies from night to night much more than the RDI. Because 17 subjects (of the 66) in that initial study (Bliwise et al., 1983) were in the current study, we also computed the nightly difference in RDI on the remaining 49 individuals (.~ = 2.54, SD = 3.53). A t test for independent samples using the latter RDI data showed a significant difference in the nightly variation in PLMS relative to RDI (t = 3.87, p < 0.001), confirming the approximately 4-fold nightly difference in PLMS relative to breathing disturbance in sleep.

Discussion

These data confirm that PLMS vary considerably from night to night in the sleep laboratory in an elderly non-clinic sample. In fact, the variation observed here for PLMS was greater than for sleep-related respiratory disturbance, though the varia- tion was not as systematic. That is, breathing disturbance in sleep was consistently higher on the second of 2 lab nights in our earlier report (Bliwise et al., 1983), and only in one of 66 subjects the breathing disruption in sleep decreased appreciably on the second night. PLMS showed no such pattern, with variation occurring somewhat randomly (Fig. 1). The larger difference scores and higher means and standard deviations for the PLMS index relative to the RDI suggest that reported relation-

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ships between PLMS and other variables (e.g., clinical symptoms, factors relating to their mechanism) using single night data may be particularly susceptible to Type I error. Either multiple lab nights of polysomnography should be employed or a greater emphasis should be placed on confirming findings across studies. Results based on a single night of data could well be spurious unless replicated. It may also be difficult to define a pathological criterion for PLMS because the movements vary so much within individuals.

Although our insomniac and non-insomniac groups did not differ significantly in nightly variation of PLMS, several specific sleep complaints were related to the night-to-night variability. Specifically, subjects experiencing more trouble with daytime fatigue, non-restorative sleep, and early morning awakening were less likely to show nightly PLMS variation. Such findings may be important clinically. For many elderly persons with insomnia, a single night of diagnostic polysonmography demonstrating PLMS may represent a purely incidental finding. Our results suggest that, in such cases, the presence of PLMS on 2 nights would increase confidence that at least some sleep complaints may be related to those movements.

The significance of PLMS during sleep in the elderly has yet to be resolved. The condition occurs in a wide range of sleep pathologies such as narcolepsy (Coleman et al., 1980), and, as mentioned above, it is now clear that the movements may be a completely asymptomatic, incidental finding (Bixler et al., 1982; Ancoli-Israel et al., 1985). Some preliminary evidence using single night data suggests that they may be related to a decline in kidney function in elderly females (Bliwise et al., 1985), but a more precise mechanism, particularly in explaining the stereotypical, periodic qual- ity of the jerks, is yet to be elucidated. At some level, higher central nervous system involvement is implicated, inasmuch as successful treatment with L-dopa has been reported recently (Montplaisir et al., 1986). Still, a more purely vascular mechanism may be involved; the rhythmic aspects of the movements could correspond to the 30-s so-called Mayer waves in systemic blood pressure (Coccagna et al., 1971). Finally, spinal influences must also be involved because the reduction of PLMS activity in REM sleep probably reflects hyperpolarization of spinal cord motor neurons during that state (Chandler et al., 1980). Whatever the mechanism of PLMS in the aged, it is clear that the considerable variation of the movements across nights will make their mechanisms and significance, if any, considerably more difficult to discover.

A c k n o w l e d g e m e n t s

This study was supported by NIA AG02504, NIA AG 04558 and NIMH 05804.

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