Gender differences in clinical,laboratory and polysomnographic features of restless legs syndrome

Restless legs syndrome is a common neurological disorder with a clear female predominance. This study aims to evaluate gender differences in clinical, laboratory and polysomnographic features in patients with restless legs syndrome. For this retrospective analysis, 42 women and 42 men from the Innsbruck RLS database matched by age and therapy were included. Demographic data as well as different severity scales (IRLS, RLS‐6 and CGI) were evaluated. Laboratory parameters included several indicators of serum iron status. In all patients, polysomnography was performed according to the AASM guidelines, and periodic leg movements during sleep were scored according to the AASM criteria. IRLS, RLS‐6 and CGI revealed more severe symptoms in women (IRLS median [range]: 17.5 [0–35] versus 13.5 [0–32], p = 0.028; RLS‐6 median [range]: 18 [0–39] versus 12 [1–42], p = 0.014). Women had lower serum ferritin levels than men (median [range] in μg L^?1: 74 [9–346] versus 167 [15–389], p < 0.001). Twenty‐two women and eight men (53.7% versus 22.2%, p = 0.003) had ferritin values below 75 μg L^?1. Periodic leg movements during sleep indices were significantly lower in women than in men (median [range] in number per hr: 11.4 [0–62.5] versus 40 [0–154], p = 0.004, and 12.6 [0–58.5] versus 40 [0.5–208], p = 0.002, for night I and night II, respectively). Restless legs syndrome severity as measured by validated scales was worse in women, while periodic leg movements during sleep indices were higher in men. These results suggest a possible gender difference in phenotypical presentation of restless legs syndrome, manifesting with predominantly sensory symptoms in women and predominantly motor symptoms in men.     

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.     

Defining the boundaries of the response of sleep leg movements to a single dose of dopamine agonist

STUDY OBJECTIVES: To define which leg movements (LM) associated with restless legs syndrome (RLS) respond to dopamine-agonist treatment and verify if they fall within current diagnostic criteria for periodic LM during sleep (PLMS). DESIGN: Single-blind placebo-controlled study. SETTINGS: Sleep laboratory. PATIENTS: 43 consecutive untreated patients with idiopathic restless legs syndrome. INTERVENTIONS: Patients underwent clinical and neurophysiological evaluation, hematological screening, and 2 consecutive full-night polysomnographic studies. Before the second polysomnographic study, all patients were randomized to receive 0.25 mg of pramipexole or placebo. MEASUREMENTS AND RESULTS: LM parameters such as duration, amplitude, interval, and periodicity were analyzed. Compared to placebo, pramipexole significantly (P < 0.01) reduced PLMS while increasing sleep efficiency. Specifically we observed a significant (P < 0.01) reduction in LM ranging 2-4 s in duration and with intermovement interval of 6-46 s and a significant decrease in the periodicity of motor events. No effect of pramipexole was observed on isolated LM. CONCLUSIONS: These results support a heterogeneous basis for LM in RLS patients; while isolated LM do not respond to pramipexole treatment, most, but not all, PLMS classified by means of the current criteria do. Further studies with different pramipexole doses or dopamine agonists with different receptor-binding preference are warranted to better define the borders of dopamine response of PLMS.     

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.     

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.     

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.     

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.     

Actigraphic assessment of periodic leg movements in patients with restless legs syndrome

The diagnosis of restless legs syndrome (RLS) relies upon diagnostic criteria which are based on history only, and dopaminergic treatment is not normally the first choice of treatment for all patients. It would be worthwhile to identify patients non‐responsive to dopaminergic treatment beforehand, because they may suffer from a restless legs‐like syndrome and may require alternative treatment. We included retrospectively 24 adult patients fulfilling the four essential criteria for restless legs and 12 age‐matched healthy controls. They were investigated by ambulatory actigraphy from both legs over three nights, and patients started treatment with dopamine agonists after this diagnostic work‐up. We examined 12 responders to dopaminergic treatment and 12 non‐responders and studied the association between response to dopaminergic treatment and the periodic limb movement index (PLMI) as assessed with actigraphy. Demographic characteristics, excessive daytime sleepiness and fatigue at baseline were similar in all three groups. Baseline RLS severity was similar between responders and non‐responders [International Restless Legs Severity Scale (IRLS): 25 ± 9 and 24 ± 8]. Group comparisons of PLMI before treatment initiation showed significant differences between the three groups. Post‐hoc pairwise comparisons revealed that healthy controls had significantly lower PLMI (4.9 ± 4.5) than responders (29.3 ± 22.7) and non‐responders (13.3 ± 11.2). Similarly, the PLMI in responders was lower than in non‐responders. PLMI day‐to‐day variability did not differ between responders and non‐responders and there was no correlation between treatment effect, as assessed by the decrease of the IRLS and baseline PLMI. Our retrospective study indicates that actigraphy to assess periodic limb movements may contribute to a better diagnosis of dopamine‐responsive restless legs syndrome.     

Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: an animal model of motor disorders in sleep

There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ-lesioned animals. In contrast, the sleep pattern was not significantly changed in the rostromedial and caudal VMPJ-lesioned animals. All three groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ-lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ-lesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra.     

Physiological time structure of the tibialis anterior motor activity during sleep in mice,rats and humans

The validation of rodent models for restless legs syndrome (Willis–Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild‐type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non‐rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter‐rater sensitivity of 92–95% and false‐positive rates of 13–19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non‐rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals <10 s mainly occurred in series of two‐three events, their occurrence rate in humans being lower than in mice and similar to that in rats. In conclusion, this study proposes reliable rules for scoring tibialis anterior electromyogram events during non‐rapid eye movement sleep in mice and rats, demonstrating that their physiological time structure is similar to that of healthy young human subjects. These results strengthen the basis for translational rodent models of periodic limb movements during sleep and restless legs syndrome/Willis–Ekbom disease.     

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.     

Estrogen therapy reduces nocturnal periodic limb movements

It is believed that periodic limb movement (PLM) and more specifically, restless leg syndrome (RLS), are a common cause of insomnia. And one study in the literature examined PLM when associated to the use of estrogens. Polo-Kantola et al. [Polo-Kantola P, Rauhala E, Erkkola R, Irjala K, Polo O. Estrogen replacement therapy and nocturnal periodic limb movements: a randomized controlled trial. Obstet Gynecol 2001;97(4):548-54] observed that estrogen therapy improved subjective sleep quality regardless of periodic limb movements or related arousals. Herein is a case of a symptomatic postmenopausal patient with high PLM index who complained of insomnia and leg pain. Given that the patient had hot flashes and a high Kupperman Menopausal Index (which evaluates climacteric symptoms), we decided to administer transdermal ESTRADOT 25 microg (Novartis, Brazil) twice-a-week. Our patient experienced a significant decrease in PLM as well as a great increase in REM and a slight increase in slow wave sleep (stages 3 and 4), as shown in the polysomnography. The patient reported an overall improvement in her condition.     

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.     

Interaction effect of obstructive sleep apnea and periodic limb movements during sleep on heart rate variability

We aimed at assessing cardiac autonomic function by heart rate variability during sleep in patients with obstructive sleep apnea and periodic limb movements during sleep, and to compare it with that of patients with obstructive sleep apnea only, periodic limb movements during sleep only, and controls. We also aimed at investigating the interaction effect between apnea–hypopnea index and periodic limb movement index on heart rate variability. Four groups of patients (n = 42 each, total = 168) were identified based on the presence/absence of obstructive sleep apnea and periodic limb movements during sleep: + obstructive sleep apnea/? periodic limb movements during sleep (5 ≤ apnea–hypopnea index < 30 events per hr), ? obstructive sleep apnea/+ periodic limb movements during sleep (periodic limb movement index > 15 events per hr), + obstructive sleep apnea/+ periodic limb movements during sleep, ? obstructive sleep apnea/? periodic limb movements during sleep (controls). All groups were matched for age, sex and body mass index. Time‐ and frequency‐domain heart rate variability measures were calculated over 5‐min periods of stable stage 2 non‐rapid eye movement sleep. In patients with both obstructive sleep apnea and periodic limb movements during sleep, LFnu and LF/HF ratio were higher than in those with obstructive sleep apnea only, periodic limb movements during sleep only, and controls, while HFnu was the lowest among the four groups. LFnu, HFnu and LF/HF ratio were significantly and independently associated with minimal oxygen saturation in the + obstructive sleep apnea/+ periodic limb movements during sleep group. There was a significant interaction effect between apnea–hypopnea index and periodic limb movement index on LF/HF ratio (p = 0.038) in patients with obstructive sleep apnea. Patients with elevated apnea–hypopnea index and elevated periodic limb movement index exhibited higher sympathovagal balance compared with those with high apnea–hypopnea index and low periodic limb movement index, and compared with those with low apnea–hypopnea index (regardless of periodic limb movement index). Increased sympathetic activation and decreased parasympathetic control appear to be related to the severity of oxygen desaturation. Apnea–hypopnea index and periodic limb movement index had interactive effects on increased sympathovagal balance in patients with obstructive sleep apnea.     

Cardiovascular Variability During Periodic Leg Movements in Sleep in Children

Study Objectives:

Periodic leg movements in sleep (PLMS) are episodes of repetitive and stereotypic leg movements occurring during sleep. In adults, research indicates that PLMS affects sleep quality and duration and are associated with a shift to relatively greater sympathetic influence over cardiovascular variables. However, little research has been performed to investigate the effect of PLMS episodes on cardiac autonomic control in children. This study aimed to quantify the effect of PLMS episodes during NREM2 sleep on heart rate variability (HRV) measures of sympathovagal balance in children.

Participants:

Overnight polysomnography data from 20 children (7–12 y) referred for assessment of sleep disordered breathing (SDB) were analyzed retrospectively. Ten children with episodes of PLMS were matched for age and SDB severity with a control group of 10 children without PLMS episodes.

Results:

The LF/HF ratio was significantly higher in the PLM+ compared with both the PLM− periods from PLMS subjects (P < 0.001) and the periods from the control group (P < 0.001). However, this effect could not be parsimoniously interpreted due to the likelihood that leg movements had a direct effect on the lower frequencies. Analysis of the ratio PLM+ to PLM+ plus PLM− indicated parasympathetic inhibition during periods of periodic leg movement and the onset of individual leg movements were associated with cardiac acceleration followed by a return to pre-movement levels.

Conclusion:

This study identified vagal inhibition in association with episodes of PLMS in children. Rapid cardiac acceleration occurring concurrently with the onset of individual leg movements also suggested decreased vagal activity associated with the movements.

Citation:

Walter LM; Foster AM; Patterson RR; Anderson V; Davey MJ; Nixon GM; Trinder J; Walker AM; Horne RSC. Cardiovascular variability during periodic leg movements in sleep in children. SLEEP 2009;32(8):1093-1099.     

Are serum ferritin and transferrin saturation risk markers for restless legs syndrome in young adults? Longitudinal and cross‐sectional data from the Western Australian Pregnancy Cohort (Raine) Study

Restless legs syndrome has been associated with serum iron deficiency in clinical studies. However, studies investigating this relationship have had inconsistent results and there are no studies in young adults. Therefore, we investigated the relationship between serum measures of iron stores and restless legs syndrome in young adults in the community. Participants in the Western Australian Pregnancy Cohort (Raine) Study answered questions on restless legs syndrome (n = 1,100, 54% female) at age 22 years, and provided serum measures of iron stores (ferritin and transferrin saturation) at ages 17 and 22 years. Restless legs syndrome was diagnosed when four International RLS Study Group criteria were met (urge to move, dysaesthesia, relief by movement, worsening during evening/night) and these symptoms occurred ≥5 times per month. Logistic regression was used to assess associations between serum iron stores and restless legs syndrome, adjusting for potential confounders. The prevalence of restless legs syndrome at age 22 years was 3.0% (n = 33, 70% female). Among those who provided restless legs syndrome and iron data at age 22 years (n = 865), the median (interquartile range) ferritin was not different between the restless legs syndrome (55 [29.5–103.5] µg L^?1) and the non‐restless legs syndrome group (65.0 [35.0–103.3] µg L^?1, p = 0.2), nor were there differences in iron deficiency prevalence (p = 0.36). There was no association between restless legs syndrome (22 years) and iron stores (17, 22 years) before or after adjustment for potential confounders. There was no association between restless legs syndrome at 22 years and iron stores at 17 or 22 years in this cohort. Serum iron stores may not be a useful indicator of restless legs syndrome risk in young adults in the community.     

Acute Dopamine-Agonist Treatment in Restless Legs Syndrome: Effects on Sleep Architecture and NREM Sleep Instability

Study Objectives:

To analyze cyclic alternating pattern (CAP) in restless legs syndrome (RLS) and the eventual changes induced by the acute administration of pramipexole.

Setting:

Sleep clinic in a scientific research institute.

Interventions:

Placebo or pramipexole 0.25 mg.

Methods:

Thirty-four patients were included: 19 patients received 0.25 mg of pramipexole and 15 were given placebo. The control group included 13 normal subjects. Nocturnal polysomnography was carried out in all subjects, and a second night was recorded after pramipexole or placebo was administered to patients with RLS. Sleep stages, CAP, and leg movement activity were scored following standard criteria.

Measurements and Results:

At baseline, rapid eye movement sleep latency was significantly longer in patients with RLS than in normal control subjects, and the periodic leg movement during sleep index (PLMS) was also significantly higher. On the contrary, many CAP parameters appeared to be significantly different, with a general increase in CAP rate in patients with RLS. Acute administration of pramipexole induced moderate changes in sleep architecture (increased number of stage shifts/h, sleep efficiency, and percentage of stage 2 sleep; decreased wakefulness after sleep onset; and a lower PLMS index. No effects of treatment on CAP were observed.

Conclusion:

Patients with RLS show significant abnormalities in sleep microstructure, represented by an excessive sleep instability/discontinuity. Acute pramipexole administration seems to exert no action on these abnormalities; the moderate effects seen on sleep architecture might be interpreted as the beneficial consequence of the removal of presleep RLS symptoms and PLMS.

Citation:

Ferri R; Manconi M; Aricò D; Sagrada C; Zucconi M; Bruni O; Oldani A; Ferini-Strambi L. Acute dopamine-agonist treatment in restless legs syndrome: effects on sleep architecture and NREM sleep instability. SLEEP 2010;33(6):793-800.     

Different periodicity and time structure of leg movements during sleep in narcolepsy/cataplexy and restless legs syndrome

STUDY OBJECTIVES: To analyze periodic leg movements (PLM) during sleep in patients with narcolepsy and compare the results with those obtained in normal controls and subjects with restless legs syndrome (RLS). METHODS: We recruited 40 HLA DQB1*0602-positive patients with narcolepsy/cataplexy, 22 with RLS, and 22 controls. The time structure of their polysomnographically recorded LMs was analyzed by means of an approach particularly able to consider their periodicity. MEASUREMENTS AND RESULTS: Nineteen patients with narcolepsy had a PLM index greater than 15. The distribution of inter-LM intervals was clearly bimodal in RLS and narcoleptics, with 1 peak at 2 to 4 seconds and another at around 22 to 26 seconds; in the range 22 to 40 seconds, patients with RLS had values significantly higher than patients with narcolepsy. All periodicity parameters were significantly lower in the narcolepsy group. Finally, the distribution of the number of PLM per hour of sleep was bell shaped in normal controls and patients with narcolepsy, whereas patients with RLS showed a progressive decrease throughout the night. CONCLUSION: Most narcoleptic patients show a high number of LMs that are significantly less periodic than those of patients with RLS. PLM are in functional interrelationship with the cyclic alternating pattern, which is reduced in patients with narcolepsy; decreased arousal fluctuations during sleep may be one of the factors influencing the reduction in periodicity of LMs during sleep in narcolepsy.