Periodic leg movements during sleep in narcoleptic patients with or without restless legs syndrome

We compared periodic and non‐periodic leg movements during sleep and polysomnography in patients with narcolepsy with cataplexy (NC) with or without restless legs syndrome (RLS) with matched idiopathic RLS (iRLS) and control subjects. We enrolled 100 patients with NC: 17 having RLS were compared with 34 sex‐ and age‐matched patients without RLS and with 17 normal controls and 17 iRLS subjects. Periodic leg movements were highest in iRLS and lowest in controls, with those in NC with RLS very close to iRLS, but higher than those in NC without RLS. The periodicity indexes showed the highest value in iRLS followed by NC with or without RLS and, finally, by controls. The inter‐leg movement intervals peaked between 10 and 50 s in NC with RLS and in iRLS, the former did not display the nocturnal gradual decrease of periodic leg movements typical of iRLS. Periodic leg movements during sleep and polysomnography displayed specific features in RLS and NC, respectively, with NC with RLS showing an intermediate pattern. Even if RLS is only detected by targeted interview in NC, its frequency and impact on night‐time sleep architecture and continuity suggest that this condition should be routinely searched for in NC.     

Time structure analysis of leg movements during sleep in REM sleep behavior disorder

STUDY OBJECTIVES: To compare the time structure of leg movements (LM) during sleep of patients with rapid eye movement (REM) sleep behavior disorder (RBD) with that of patients with restless legs syndrome (RLS) or control subjects. DESIGN: The polysomnographically recorded tibialis anterior activity during sleep was analyzed by means of a new approach able to consider duration, intermovement interval, sleep stage and time of night distribution, and periodicity. PATIENTS AND PARTICIPANTS: Twenty patients with idiopathic RBD, 37 with idiopathic RLS and 14 age-matched control subjects were consecutively recruited. MEASUREMENTS AND RESULTS: Most patients with RBD (85%) presented periodic leg movements during sleep (PLMS). PLMS occurred more frequently during non-REM sleep in patients with RLS and during REM sleep in patients with RBD. PLMS were shorter in duration, less often bilateral, and with a higher intermovement interval in patients with RBD compared to those with RLS. The number of PLMS decreased across the night in patients with RBD and in those with RLS, but not in control subjects. In all subjects, LM periodicity clearly depended on sleep state, with higher values during non-REM than during REM sleep. Patients with RBD showed a lower LM periodicity, compared with patients with RLS, in each of the sleep states. CONCLUSIONS: Significant differences, together with some similarities in LM time structure, were observed between patients with RBD and those with RLS; for this reason, our approach seems to indicate that their phenotype might be dependent on 2 factors: disease and sleep stage.     

Peculiar lifespan changes of periodic leg movements during sleep in restless legs syndrome

The objective of this observational cohort study was to analyse the age‐related changes of periodic leg movements during sleep using the newest international scoring rules, to expand past analyses, including patients in the paediatric age range, and also to analyse the changes of short‐interval and isolated leg movements during sleep throughout the lifespan. One hundred and sixty‐five patients (84 women) with restless legs syndrome were recruited in the following age groups: 16 preschoolers (≤5 years of age), 29 school‐age children (6–12 years), 19 adolescents (13–17 years), 17 young adults (19–40 years), 47 adults (41–60 years) and 37 seniors (>60 years). Total, periodic, short‐interval and isolated leg movements during sleep and periodicity indexes were obtained by polysomnography. The total index showed (quartic polynomial interpolation) a decrease before 10 years, followed by a steady increase up to 30 years, a relatively stable period until 60 years, and a final increase up to 80 years. This course was almost entirely due to changes in periodic movements. Isolated movements did not change significantly and short‐interval movements showed only an increase in seniors. Our study indicates that, in restless legs syndrome, the total index shows a peculiar and unique course throughout the lifespan, mainly due to periodic movements. These age‐related changes may mirror developmental changes in network complexity known to occur in dopaminergic circuits. These data further confirm the need to better assess the periodicity of leg movements in sleep during the human development period, in order to obtain clinically useful information.     

EEG arousals and awakenings in relation with periodic leg movements during sleep

It is known that periodic leg movements are frequently accompanied by full awakenings or by signs of EEG arousals. The time relationship of these EEG arousals with leg movements varies from patient to patient. They may precede or follow leg movements or occur simultaneously. It is not clear whether these arousals trigger leg movements or, alternatively, whether both EEG arousals and leg movements are separate expressions of a common pathophysiological mechanism. We investigated the temporal relationship of five EEG arousals, such as alpha activity, K-complexes, spindles, K-alpha, K-spindle activities and awakenings, with leg movements in 10 periodic leg movement patients. These EEG arousals were considered to be associated with leg movements if they occurred 10 s before/after or simultaneously with the onset of right or left tibialis muscle EMG potentials. It was found that 49.19% of EEG arousals occurred before leg movements, 30.61% occurred simultaneously and 23.18% occurred just after leg movements. The number of EEG arousals was significantly higher in the 10 s preceding leg movement than simultaneously or in the 10 s following. Alpha activity was the phenomenon associated most frequently with leg movements, irrespective of its temporal organization and was significantly higher during the 10 s preceding movement. Spindle and K-spindle activities were significantly higher before leg movement, whereas K-complex activity was significantly more frequent during leg movements. The number of awakenings was significantly higher after leg movements than simultaneously. These results indicated that leg movements are not primary, but rather are a phenomenon associated with an underlying arousal disorder.     

Sleep/wake abnormalities in patients with periodic leg movements during sleep: Factor analysis on data from 24-h ambulatory polygraphy

Periodic Leg Movements (PLM) in sleep occur in a wide variety of sleep/wake disorders but their relationship with sleep disturbance, and notably with the concomitant existence of a 'restless legs' syndrome (RLS) remains unclear. We performed 24-h ambulatory polygraphy in a population of 54 consecutive, unselected patients with PLMs (Coleman's index greater than 5/h) who complained of different sleep disorders. A Principal Component Analysis (PCA) was conducted on seven variables from the sample, namely PLM index, patient's age, sleep stage changes per hour, sleep depth index (SWS+PS/TST), diurnal sleep time, number of awakenings exceeding 2 min and presence of a RLS. PCA yielded four independent factors. The PLM index and the changes of sleep stage clustered in a single factor, linking therefore sleep fragmentation to the frequency of PLMs. The second factor appeared to reflect a circadian sleep/wake disorder, combining diurnal sleep time with the number of long night awakenings. The third factor was mainly loaded by the patients' age and the sleep depth index, thus reflecting a well known relationship. Finally, the variable reflecting the existence of a RLS appeared isolated in a single factor, independent from the three previously described. These results confirm and extend the link between PLMs and sleep fragmentation, as well as the recently described dissociation between PLMs and diurnal somnolence. On the other hand, our analysis suggests that in PLM patients the concomitant existence of a RLS is not related to the frequency of occurrence of PLMs, at least when these latter are quantified independently of their arousal index.     

Local sweating responses during recovery sleep after sleep deprivation in humans

Changes in the central control of sweating were investigated in five sleep-deprived subjects (kept awake for 40 h) during their recovery sleep under warm ambient conditions [operative temperature (T _o) was either 35 or 38° C]. Oesophageal (T _oes) and mean skin (T _sk) temperatures, chest sweat rate (m _sw,ch), and concomitant electro-encephalographic data were recorded. Throughout the night at 35 or 38° C T _o, m _sw,ch changes were measured at a constant local chest skin temperature (T _ch) of 35.5° C. The results showed that body temperatures (T _oes and T _sk) of sleep-deprived subjects were influenced by thermal and hypnogogic conditions. The m _sw,ch levels correlated positively with T _oes in the subjects studied during sleep stage 1–2 (light sleep: LS), sleep stage 3–4 (slow wave sleep: SWS) and rapid eye movement (REM) sleep. Contrary to what has been reported in normal sleep, firstly, the T _oes threshold for sweating onset differed between REM sleep and both LS and SWS, and, secondly, the slopes of the m _sw,ch versus T _oes relationships were unchanged between REM and non-REM (i.e. LS or SWS) sleep. The changes observed after sleep deprivation were hypothesized to be due to alterations in the functioning of the central nervous system controller.     

Sequence analysis of leg movements during sleep with different intervals (<10, 10–90 and >90 s) in restless legs syndrome

The aim of this study was to define the time structure of leg movements during sleep occurring with an intermovement interval (onset‐to‐onset) shorter than 10 s in patients with restless legs syndrome and controls, and to compare it to the structure of movements with intervals of 10–90 s or >90 s. Polysomnographic recordings of 141 untreated patients and 68 age‐matched normal controls were analysed. All movements were detected and classified into three categories, separated by intervals of <10, 10–90 or >90 s. The number of movements included in each category was significantly higher in patients than in controls. The movements with an interval of >90 s occurred steadily during the night, whereas the hourly distribution of movements with intervals of <10 or 10–90 s was decreasing or bell‐shaped in patients or controls, respectively. Movements with an interval of <10 s tended to have a shorter duration and constituted shorter sequences than movements with intervals of 10–90 or >90 s. The time structure features of the three categories of movements considered in this study were found to be clearly different. This, together with previous observations on the differential effects of dopamine agonists on movements with different intervals, suggests that movements with intervals of <10 and >90 s are regulated by neurotransmitter mechanisms different from those modulating movements with an interval of 10–90 s.     

Spectral analysis of all-night human sleep EEG in narcoleptic patients and normal subjects

To investigate the pathophysiology of narcoleptic patients' sleep in detail, we analysed and compared the whole-night polysomnograms of narcoleptic patients and normal human subjects. Eight drug-naive narcoleptic patients and eight age-matched normal volunteers underwent polysomnography (PSG) on two consecutive nights. In addition to conventional visual scoring of the polysomnograms, rapid eye movement (REM)-density and electroencephalograph (EEG) power spectra analyses were also performed. Sleep onset REM periods and fragmented nocturnal sleep were observed as expected in our narcoleptic patients. In the narcoleptic patients, REM period duration across the night did not show the significant increasing trend that is usually observed in normal subjects. In all narcoleptic patient REM periods, eye movement densities were significantly increased. The power spectra of narcoleptic REM sleep significantly increased between 0.3 and 0.9 Hz and decreased between 1.0 and 5.4 Hz. Further analysis revealed that non-rapid eye movement (NREM) period duration and the declining trend of delta power density in the narcoleptic patients were not significantly different from the normal subjects. Compared with normal subjects, the power spectra of narcoleptic NREM sleep increased in the 1.0-1.4 Hz and 11.0-11.9 Hz frequency bands, and decreased in a 24.0-26.9 Hz frequency band. Thus, increased EEG delta and decreased beta power densities were commonly observed in both the NREM and REM sleep of the narcoleptic patients, although the decrease in beta power during REM sleep was not statistically significant. Our visual analysis revealed fragmented nocturnal sleep and increased phasic REM components in the narcoleptic patients, which suggest the disturbance of sleep maintenance mechanism(s) and excessive effects of the mechanism(s) underlying eye movement activities during REM sleep in narcolepsy. Spectral analysis revealed significant increases in delta components and decreases in beta components, which suggest decreased activity in central arousal mechanisms. These characteristics lead us to hypothesize that two countervailing mechanisms underlie narcoleptic sleep pathology.     

Pontine reticular formation (PnO) administration of hypocretin-1 increases PnO GABA levels and wakefulness

STUDY OBJECTIVES: GABAergic transmission in the oral part of the pontine reticular formation (PnO) increases wakefulness. The hypothalamic peptide hypocretin-1 (orexin A) promotes wakefulness, and the PnO receives hypocretinergic input. The present study tested the hypothesis that PnO administration of hypocretin-1 increases PnO GABA levels and increases wakefulness. This study also tested the hypothesis that wakefulness is either increased or decreased, respectively, by PnO administration of drugs known to selectively increase or decrease GABA levels. DESIGN: Awithin-subjects design was used for microdialysis and microinjection experiments. SETTING: University of Michigan. PATIENTS OR PARTICIPANTS: Experiments were performed using adult male Crl:CD (SD)IGS BR (Sprague-Dawley) rats (n=46). INTERVENTIONS: PnO administration of hypocretin-1, nipecotic acid (a GABA uptake inhibitor that increases extracellular GABA levels), 3-mercaptopropionic acid (a GABA synthesis inhibitor that decreases extracellular GABA levels; 3-MPA), and Ringer solution (vehicle control). MEASUREMENTS AND RESULTS: Dialysis administration of hypocretin-1 to the PnO caused a statistically significant, concentration-dependent increase in PnO GABA levels. PnO microinjection of hypocretin-1 or nipecotic acid caused a significant increase in wakefulness and a significant decrease in non-rapid eye movement (NREM) sleep and REM sleep. Microinjecting 3-MPA into the PnO caused a significant increase in NREM sleep and REM sleep and a significant decrease in wakefulness. CONCLUSIONS: An increase or a decrease in PnO GABA levels causes an increase or decrease, respectively, in wakefulness. Hypocretin-1 may promote wakefulness, at least in part, by increasing GABAergic transmission in the PnO.     

Hypocretin/orexin and narcolepsy: new basic and clinical insights

Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain–Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ‘narcolepsy with cataplexy’ and ‘narcolepsy due to medical condition’). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress.     

The effect of dream report collection and dream incorporation on memory consolidation during sleep

Collecting dream reports typically requires waking subjects up from their sleep—a method that has been used to study the relationship between dreams and memory consolidation. However, it is unclear whether these awakenings influence sleep‐associated memory consolidation processes. Furthermore, it is unclear how the incorporation of the learning task into dreams is related to memory consolidation. In this study we compared memory performance in a word–picture association learning task after a night with and without awakenings in 22 young and healthy participants. We then examined if the stimuli from the learning task are successfully incorporated into dreams, and if this incorporation is related to the task performance the next morning. We show that while the awakenings impaired both subjective and objective sleep quality, they did not affect sleep‐associated memory consolidation. When dreams were collected during the night by awakenings, memories of the learning task were successfully incorporated into dreams. When dreams were collected in the morning, no incorporations were detected. Task incorporation into non‐rapid eye movement sleep dreams, but not rapid eye movement sleep dreams positively predicted memory performance the next morning. We conclude that the method of awakenings to collect dream reports is suitable and necessary for dream and memory studies. Furthermore, our study suggests that dreams in non‐rapid eye movement rather than rapid eye movement sleep might be related to processes of memory consolidation during sleep.     

Control of hypoglossal motoneurones during naturally occurring sleep and wakefulness in the intact,unanaesthetized cat: a field potential study

The present electrophysiological study was designed to determine the discharge threshold of hypoglossal motoneurones during naturally occurring states of sleep and wakefulness in the intact, unanaesthetized cat. The antidromic field potential, which reflects the net level of membrane excitability of motoneurones and therefore their discharge threshold, was recorded in the hypoglossal nucleus following stimulation of the hypoglossal nerve. The amplitude of the antidromic field potential was larger during wakefulness and non‐rapid eye movement (NREM) sleep compared with REM sleep. There was no significant difference in the amplitude of the field potential when wakefulness was compared with NREM sleep (P = 0.103, df = 3, t = 2.324). However, there was a 46% reduction in amplitude during REM sleep compared with NREM sleep (P < 0.001, df = 10, t = 6.421) or wakefulness (P < 0.01, df = 4, t = ?4.598). These findings indicate that whereas the excitability of motoneurones that comprise the hypoglossal motor pool is relatively constant during wakefulness and NREM sleep, their excitability is significantly reduced during REM sleep. This state‐dependent pattern of control of hypoglossal motoneurones during REM sleep is similar to that reported for motoneurones in other motor nuclei at all levels of the neuraxis. The decrease in the evoked response of hypoglossal motoneurones, which reflects a significant increase in the discharge threshold of individual motoneurones, results in atonia of the lingual and related muscles during REM sleep.     

Interleukin-8 promotes non-rapid eye movement sleep in rabbits and rats

Interleukin-8 (IL-8) is a cytokine found in the brain. In this study, the ability of IL-8 to induce sleep in rabbits and rats was investigated. Twenty-seven Sprague-Dawley rats and 16 male New Zealand White rabbits were provided electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly (i.c.v.) with pyrogen-free saline and, one of the following doses of IL-8 on a separate day: 1.25 or 12.5 ng in rabbits and 10, 50, or 100 ng in rats. EEG, brain temperature, and motor activity were recorded for 23 h after the i.c.v. injections. IL-8 increased time spent in non-rapid eye movement sleep (NREMS) without affecting rapid eye movement sleep (REMS). In rabbits, both doses of IL-8 promoted NREMS. In rats, the 10 and 50 ng doses of IL-8 failed to affect sleep, but the 100 ng dose of IL-8 enhanced NREMS. EEG slow-wave activity during NREMS was increased after the high dose of IL-8 in rabbits. IL-8 also induced fever in rabbits but not rats. Heat inactivated IL-8 did not alter any of the parameters measured. Current results support the notion that the brain cytokine network plays a role in sleep regulation.     

Periodic limb movement disorder of sleep in children

To characterize periodic limb movement disorder (PLMD) in a cohort of prepubertal children we examined sleep-related identifiable differences between children with PLMD and attention-deficit/hyperactivity disorder (ADHD), PLMD alone, and age-matched controls. Children were selected from a chart review of all children referred to a pediatric sleep medicine center and from a community survey of 5-7-year-old-children. Polysomnography (PSG) and parental report data from all children identified as having periodic limb movement index (PLMI) >5 were reviewed and compared with a cohort of age-matched controls. A total of 8.4% of children in the clinic-referred sample, and 11.9% of the children recruited from the community had PLMI >5. Of those, 44.4% were identified as having ADHD. Children with PLMD had significantly lower percentage of rapid eye movement (REM) than control children (P < 0.001). Children in the PLMD/ADHD group had a significantly greater number of arousals associated with PLM (PLMa) than children with PLMD only (P < 0.05). While a relationship between ADHD and PLMD was observed, it was weaker than previous reports (Chervin, R. D. et al. Sleep, 2002; 25: 213; Chervin, R. D. and Archbold, K. H. Sleep, 2001; 24: 313; Picchietti et al. J. Child Neurol., 1999; 13: 588; Picchietti et al. Mov. Disord., 1999; 14: 1000; Picchietti and Walters Sleep, 1999; 22: 297). Children in the PLMD/ADHD group were more likely to have PLMas than were children with PLMD only. We postulate that rather than a direct relationship between ADHD and PLMD, this link may be mediated by the presence of reduced REM sleep and more importantly by the sleep fragmentation associated with PLM-induced arousals.     

Periodic limb movements in sleep are associated with stroke and cardiovascular risk factors in patients with renal failure

Periodic limb movements in sleep (PLMS) is prevalent among dialysed patients and is associated with increased risk of mortality. Our study aimed to determine the prevalence of this disease in a sample of transplanted and waiting-list haemodialysed patients. One hundred transplanted and 50 waiting-list patients underwent polysomnography. Moderate and severe diseases were defined as periodic limb movements in sleep index (PLMSI) higher than 15 and 25 events h(-1), respectively. The 10-year coronary heart disease risk was estimated for all patients using the Framingham Score. Moreover, the 10-year estimated risk of stroke was calculated according to the modified version of the Framingham Stroke Risk Profile. PLMS was present in 27% of the transplanted and 42% of the waiting-list group (P = 0.094); the proportion of severe disease was twice as high in waiting-list versus transplanted patients (32 versus 16%, P = 0.024). Patients with severe disease had a higher 10-year estimated risk of stroke in the transplanted group [10 (7-17) versus 5 (4-10); P = 0.002] and a higher 10-year coronary heart disease risk in both the transplanted [18 (8-22) versus 7 (4-14); P = 0.002], and the waiting-list groups [11 (5-18) versus 4 (1-9); P = 0.032]. In multivariable linear regression models the PLMSI was associated independently with the Framingham cardiovascular and cerebrovascular scores after adjusting for important covariables. Higher PLMSI is an independent predictor of higher cardiovascular and cerebrovascular risk score in patients with chronic kidney disease. Severe PLMS is less frequent in kidney transplant recipients compared to waiting-list dialysis patients.     

Periodic limb movements during sleep are associated with cardiovascular diseases: A systematic review and meta‐analysis

Periodic limb movements during sleep present with repetitive movements, typically in the lower limbs, during sleep. Periodic limb movements during sleep have been proposed to be associated with increased risk of heart diseases. The aim of this study was to examine the co‐morbidity rates of heart disease, including acute myocardial infarction, coronary artery disease and cardiovascular disease, in subjects with or without periodic limb movements during sleep through a meta‐analysis. An electronic review of PubMed, Embase, ScienceDirect, Cochrane Library, ProQuest, Web of Science, ClinicalKey and ClinicalTrials.gov was performed. Clinical studies, case‐controlled trials and cohort studies were all included in the search. Case reports or series, and non‐clinical studies were excluded. A meta‐analysis of the results of six studies comparing the prevalence of coronary artery disease/acute myocardial infarction/cardiovascular disease in subjects with/without periodic limb movements during sleep was performed. There were significantly higher co‐morbidity rates of coronary artery disease (odds ratio = 1.568, 95% confidence interval: 1.187–2.073, p = 0.002) and cardiovascular disease (odds ratio = 1.279, 95% confidence interval: 1.095–1.494, p = 0.002), but not acute myocardial infarction (odds ratio = 1.272, 95% confidence interval = 0.942–1.718, p = 0.117), in the periodic limb movements during sleep group than in the non‐periodic limb movements during sleep group. This meta‐analysis highlights the importance of a significantly high prevalence of coronary artery disease and cardiovascular disease in subjects with periodic limb movements during sleep. Further studies should be focused on the potential pathophysiology, and whether treatment for periodic limb movements during sleep can improve the outcome of heart disease.     

Periodic limb movements and obstructive sleep apneas before and after continuous positive airway pressure treatment

Periodic limb movements during sleep (PLMS) and obstructive sleep apnea syndrome (OSAS) are two common sleep disorders. The similarity in periodicity of periodic limb movements (PLMs) and obstructive sleep apneas (OSAs) led us to hypothesize the existence of a common central generator responsible for the periodicity of both OSAs and PLMs. In order to test this hypothesis, we compared apnea periodicity before continuous positive airway pressure (CPAP) treatment with PLMs periodicity during CPAP treatment in 26 OSA patients, consecutively recorded and treated in our sleep laboratory. The investigation on CPAP was performed twice, once during the initial evaluation and once during a follow-up evaluation after 3 months of home treatment with CPAP. Our results showed that, in this sample, 16 patients out of 26 had an association of OSAS and PLMS, defined as the occurrence of at least 5 PLMs per hour of sleep. The mean apnea interval - measured as the time between the beginning of two successive apneas - was 43.1 s (+/-15.2, SD) and the mean PLM interval - calculated in the same way - was 29.6 s (+/-15.2) during the baseline night, 28.5 s (+/-15.7) during the first CPAP night, and 29.8 s (+/-14.8) during the second CPAP night. Thus, the periodicity of the two phenomena (apneas and PLMs) was different, both before and after CPAP treatment (P< 0.05). When considering the interval between the end of an event (apnea or PLM) and the beginning of the next one the mean apnea interval was 19.5 s (+/-11. 6), and the mean PLM interval was 28.1 s (+/-15.3) during the untreated night, 26.6 s (+/-16) during the first CPAP night and 27.9 s (+/-15) during the second CPAP night. The shortening of apnea intervals with this method of measuring intervals reflects the longer duration of apneas as compared to PLMs. Again the intervals between PLMs were not different between each other but the intervals between apneas were different from the intervals between PLMs (P< 0. 05) These results show that the periodicity of PLMs is different from that of OSAs, suggesting that sleep apneas and PLMs are not generated by a common central generator.