Inter-rater reliability for scoring periodic leg movements in sleep

This study investigated inter-rater reliability for scoring periodic leg movements in sleep (PLMS) and related phenomena. Five highly experienced polysomnographic technologists each scored 24 nocturnal polysomnograms, the majority of which contained an appreciable number of PLMS. Results indicated high inter-rater reliability for some variables but more modest reliability for others. We discuss these findings in terms of efforts of standardization in polysomnographic scoring of sleep disorders.     

Peripheral vasoconstriction in patients with sleep related periodic leg movements

Two patients complaining of insomnia had sleep-related periodic leg movements (nocturnal myoclonus) on polysomnographic evaluation. Both also complained of cold feet and had abnormal peripheral pulse examinations. Treatment with phenoxybenzamine, alpha-adrenergic blocker, normalized the peripheral pulse responses, reduced the complaint of insomnia, and reduced the sleep related leg movements but resulted in only mild sleep improvements. Peripheral pulse examinations of ten other patients with sleep-related periodic leg movements revealed abnormal responses in four. From these and other results, it is hypothesized that the sympathetic nervous system may mediate the periodicity of sleep related periodic leg movements.     

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.     

Morbidity cut-offs for sleep apnea and periodic leg movements in predicting subjective complaints in seniors

Despite its widespread use, the validity of the 5/h morbidity cut-off for the Respiratory Disturbance Index (RDI) or the Movement Index (MI) in determining presence of sleep apnea (SA) or sleep-related periodic leg movements (PLMs), respectively, has not been determined for any aged population. One hundred community resident seniors 60 years of age or older underwent three consecutive nights of polysomnography and also completed conventional measures of subjective sleep-wake complaints (written sleep questionnaire, sleep log, sleep interview) and mood disturbances (Zung Self-Rating Depression and Anxiety Scales, Profile of Mood States, Beck Depression Inventory). Based on the 5/h cut-off, 34% had SA and 58% had PLMs. Despite this, the frequency of subjective sleep-wake and mood disturbance was low across methods of assessment. Groups formed by the 5/h cut-off for RDI or MI failed to differ significantly in responses on all subjective sleep-wake and mood measures. Higher cut-offs also were examined and proved weak or ineffective in predicting subjective sleep-wake and mood disturbance. Preliminary investigations suggested that alternative measures of severity of SA (means oxygen desaturation and means duration of apneas or hypopneas) may be better predictors of subjective disturbance than RDI in this population. These findings both (a) demonstrate that the polygraphically identified SA and PLMs which are widespread in seniors tend not to be manifested in self-reported sleep-wake or mood disturbance, and (b) illustrate the need for validated morbidity cut-offs for SA and PLMs.     

Night-to-night variability in sleep apnea and sleep-related periodic leg movements in the elderly

The amount of night-to-night variability in sleep apnea (SA) and sleep-related periodic leg movements (PLMs) is largely unknown but, despite this, clinical decisions are based on single-night studies in many clinical sleep laboratories. We examined variability in SA and PLMs over three nights in 46 community-resident seniors. No evidence was found for either a first-night effect or a directional trend across nights in either the Respiratory Disturbance Index (RDI) or the Movement Index (MI), despite a prominent first-night effect on pattern of sleep. Duration of apneas/hypopneas and degree of associated heart rate change and oxygen desaturation in subjects with SA and intermovement interval in subjects with PLMs also failed to show systematic change across nights. However, if a cut-off score of 5/h for RDI and MI was used, the classification recorded on the first night did differ from the classification given on at least one of the other nights in 43% of the subjects. The magnitude of fluctuation in RDI or MI from night to night was large enough in some subjects that, in a clinical situation, decisions based on one night would have been entirely different had the subject been studied on a different night. Night-to-night variability in RDI and MI within subjects also was associated with significant alterations in the sleep pattern. We conclude that caution should be taken in drawing conclusions from single-night studies, especially in individuals with relatively mild forms of SA and PLMs where nightly variations could easily place them above or below an arbitrary cut-off score.     

Short‐interval leg movements during sleep entail greater cardiac activation than periodic leg movements during sleep in restless legs syndrome patients

Periodic leg movements during sleep (PLMS) are sequences of ≥4 motor events with intermovement intervals (IMI) of 10–90 s. PLMS are a supportive diagnostic criterion for restless legs syndrome (RLS) and entail cardiac activation, particularly when associated with arousal. RLS patients also over‐express short‐interval leg movements during sleep (SILMS), which have IMI <10 s and are organized mainly in sequences of two movements (doublets). We tested whether the cardiac activation associated with SILMS doublets differs from that associated with PLMS in a sample of 25 RLS patients. We analysed time–series of R–R intervals synchronized to the onset of SILMS doublets or PLMS that entailed an arousal during non‐rapid eye movement (NREM) sleep. We assessed cardiac activation based on the R–R interval decrease with respect to baseline during NREM sleep without leg movements. We found that the duration of the R–R interval decrease with SILMS doublets was significantly longer than that with PLMS, whereas the maximal decrease in R–R interval was similar. Scoring SILMS in RLS patients may therefore be relevant from a cardiac autonomic perspective.     

The treatment of the restless leg syndrome with or without periodic leg movements in sleep.

There are presently three main treatments for restless leg syndrome-periodic leg movements in sleep (RLS-PLMS). The benzodiazepines (especially clonazepam) are considered by most clinicians to be the treatment of choice in mild cases, especially in young subjects. In our experience, however, L-dopa and bromocriptine are more effective treatments, although no controlled studies have ever been conducted to compare their therapeutic benefits and the side effects of benzodiazepines and dopaminergic drugs. The use of opioids should be restricted to patients who have severe symptoms and who fail to respond to benzodiazepines or L-dopa. Propoxyphene was found less effective than L-dopa in decreasing PLMS, but some patients resistant to L-dopa may exhibit a masked therapeutic response to opioids. However, there is currently no method to predict the response to any treatment modality.     

The evoked heart rate response to periodic leg movements of sleep.

STUDY OBJECTIVES: Periodic leg movements of sleep are currently subdivided based upon whether or not they are associated with EEG arousal. "Autonomic" arousals, characterized by elevations in heart rate and blood pressure without AASM-defined EEG changes, have been associated with daytime somnolence in experimental protocols. In this study, we will describe the heart rate response to periodic leg movements of sleep, both with and without associated arousals. DESIGN: Heart rate was averaged for each of the ten cardiac cycles before, and after, the onset of individual periodic leg movements occurring in non-REM sleep for eight patients with Periodic Limb Movement Disorder (PLMD). Records were blindly scored (without EKG data) to determine if AASM-defined EEG arousals occurred within two seconds of leg movement onset. Leg movements during wakefulness were performed by four non-patient controls as a control condition. SETTING: Sleep Disorders Center INTERVENTIONS: None MEASUREMENTS AND RESULTS: A significant rise in heart rate was observed following the onset of individual leg movements of sleep (N = 796), which was also significantly larger than that seen after waking leg movements (N = 275). Although heart rate elevation was 10%-40% higher when leg movements were associated with AASM-defined arousal, these differences did not reach statistical significance. CONCLUSIONS: Periodic leg movements of sleep are associated with cardiac acceleration, even in the absence of AASM-defined arousal. It appears premature to conclude that periodic leg movements of sleep not associated with visible EEG arousal are clinically insignificant.     

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.     

Contactless detection of periodic leg movements during sleep: A 3D video pilot study

In clinical practice, the quality of polysomnographic recordings in children and patients with neurodegenerative diseases may be affected by sensor displacement and diminished total sleep time due to stress during the recording. In the present study, we investigated if contactless three‐dimensional (3D) detection of periodic leg movements during sleep was comparable to polysomnography. We prospectively studied a sleep laboratory cohort from two Austrian sleep laboratories. Periodic leg movements during sleep were classified according to the standards of the World Association of Sleep Medicine and served as ground truth. Leg movements including respiratory‐related events (A1) and excluding respiratory‐related events (A2 and A3) were presented as A1, A2 and A3. Three‐dimensional movement analysis was carried out using an algorithm developed by the Austrian Institute of Technology. Fifty‐two patients (22 female, mean age 52.2 ± 15.1 years) were included. Periodic leg movement during sleep indexes were significantly higher with 3D detection compared to polysomnography (33.3 [8.1–97.2] vs. 30.7 [2.9–91.9]: +9.1%, p = .0055/27.8 [4.5–86.2] vs. 24.2 [0.00–88.7]: +8.2%, p = .0154/31.8 [8.1–89.5] vs. 29.6 [2.4–91.1]: +8.9%, p = .0129). Contactless automatic 3D analysis has the potential to detect restlessness mirrored by periodic leg movements during sleep reliably and may especially be suited for children and the elderly.     

Computer-assisted detection of nocturnal leg motor activity in patients with restless legs syndrome and periodic leg movements during sleep

STUDY OBJECTIVES: To assess the performance of a new method for automatic detection of periodic leg movements during sleep. METHODS: Leg movements during sleep were visually detected in the tibialis anterior muscles recordings of 15 patients with restless legs syndrome and 15 normal controls. Leg movements were detected automatically by means of a new computer method with which electromyogram signals are first digitally band-pass filtered and then rectified; subsequently, the detection of leg movements is performed by using 2 thresholds: one for the starting point and another to detect the end point of each leg movement. Sensitivity and false-positive rate were obtained; the American Sleep Disorders Association parameters were also computed, and the results analyzed by means of the Kendall W coefficient, the linear correlation coefficient and the Bland-Altman plots. SETTING: N/A. PARTICIPANTS: Fifteen patients with restless legs syndrome and periodic leg movements and 15 controls. MEASUREMENTS AND RESULTS: High values of the Kendall W coefficient of concordance between automatic and visual analysis were found with values close to 1 and the linear correlation coefficient for leg movements index and total leg movements index was > 0.950 (p < .000001). The Bland-Altman plots provided the limits of agreement between visual and computer detection, which were -9.01 and +9.89 for the periodic leg movement index. None of the normal controls was found to have periodic leg movement indexes >5 after automatic analysis. CONCLUSIONS: Our method can be applied to the clinical evaluation of periodic leg movements during sleep, with some caution in patients with a low periodic leg movement indexes. Large-scale research application is possible and can be considered as reliable.     

Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome

STUDY OBJECTIVES: Polysomnographic study evaluating the efficacy of ropinirole for the treatment of patients with restless legs syndrome (RLS) suffering from periodic leg movements in sleep (PLMS). DESIGN: Double-blinded, placebo-controlled, parallel-group study. SETTING: 15 tertiary referral centers in the USA. Participants: 65 patients with RLS and PLMS. INTERVENTIONS: Ropinirole (0.25-4.0 mg per day) or placebo for 12 weeks. MEASUREMENTS AND RESULTS: Data from 59 patients were included in the primary endpoint analysis. PLMS per hour decreased more with ropinirole (48.5 to 11.8), compared with placebo (35.7 to 34.2; adjusted treatment difference: -27.2; 95% confidence interval [CI]: -39.1, -15.4; P < .0001). Periodic limb movements with arousal per hour decreased from 7.0 to 2.5 with ropinirole but increased from 4.2 to 6.0 with placebo (adjusted treatment difference: -4.3, 95% CI: -7.6, -1.1; P = .0096). Periodic limb movements while awake per hour decreased from 56.5 to 23.6 with ropinirole but increased from 46.6 to 56.1 with placebo (adjusted treatment difference: -39.5; 95% CI: -56.9, -22.1; P < .0001). Ropinirole treatment significantly improved patients' ability to initiate sleep (P < .05) and the amount of Stage 2 sleep compared with placebo (P < .001). There were also non-significant trends toward increases in total sleep time and sleep efficiency. Sleep adequacy (measured on the subjective Medical Outcomes Study sleep scale) was significantly improved with ropinirole treatment (adjusted treatment difference: 12.1; 95% CI: 1.1, 23.1; P = .0316). In contrast, the placebo group showed a greater increase in Stage 3/4 sleep (P < .01). No serious adverse events occurred in either group. CONCLUSIONS: Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS.     

New approaches to the study of periodic leg movements during sleep in restless legs syndrome

STUDY OBJECTIVES: To describe a new approach for the analysis of quantity, type, and periodicity of the leg motor activity during sleep in patients with restless legs syndrome (RLS) and periodic leg movements (PLM). METHODS: The following parameters were taken into account for LM: duration, amplitude, area under the curve, sleep stage, side, interval, and bilaterality. The analysis of inter-LM intervals was carried out by drawing their distribution graphs. A new index evaluated their periodicity and was validated by means of a Markovian analysis. The differences in inter-LM intervals, LM duration, and area under the curve between normal controls and patients and between the 3 patient subgroups identified on the basis of their periodicity were statistically analyzed. SETTING: N/A. PARTICIPANTS: Sixty-five patients with RLS and periodic LM and 22 young healthy controls. MEASUREMENTS AND RESULTS: The RLS patients' inter-LM interval distribution graph showed a wide peak with a maximum located at around 15 to 30 seconds and extending from 10 to 90 seconds, not present in controls, and another peak for intervals less than 8 seconds, higher than that of controls. Three patient subgroups were identified with different proportions of these 2 peaks, periodicity, and Markovian parameters. Periodicity was not dependent on the periodic leg movement index. Patients showing the peak mainly at around 15 to 30 seconds tended to show slightly longer and higher area under the curve LM than did the other 2 subgroups. CONCLUSIONS: Our new approach seems to be useful in a new qualitative differentiation among patients with PLM, which is not possible by using the simple PLM index.     

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

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.     

Body position changes and periodic movements in sleep

What triggers episodes of periodic movements in sleep (PMS) remains unknown. Despite the uncertainties, there is no doubt of the widespread prevalence of PMS, particularly in elderly populations. This study explored possible consistent temporal relationships between body position and PMS episodes. Eleven subjects, monitored by polygraph and videotape, averaged 299 leg jerks in nine episodes, and 13 body position changes of greater than or equal to 90 degrees. Leg jerk episodes had a significant tendency to terminate soon before body position changes, and likewise there was a trend for leg jerk episodes to begin soon after position changes. It is hypothesized that adverse body positioning, via an influence upon the spinal cord or peripheral tissue perfusion, triggers PMS episodes, which persist until the adverse positions are changed. In this small sample, "adverse" positions could not be elucidated.