Age-related changes in periodic leg movements during sleep in patients with restless legs syndrome

ObjectiveThe aim of this study was to evaluate and statistically describe the age-related changes in leg movements (LMs) during sleep in a large group of subjects with restless legs syndrome (RLS).Subjects and methodsOne hundred eight untreated patients affected by idiopathic RLS were included in this study (mean age 52.0 years, min 7.5, max 83.2 years). The time structure of their polysomnographically recorded LMs was analyzed using an approach particularly appropriate for assessing their quantity, periodicity, and distribution during the night.ResultsPeriodic LMs during sleep (PLMS) increased in number gradually in the age groups. Their typical interval was approximately 24–28 s before the age of 55 years but at approximately 14–16 s after the age of 65 years. PLMS index reached a plateau at 15–25 years of age and remained stable up to 65 years; after this age, it showed an important increase. Periodicity index (PI) increased progressively up to the age of 35 years and then remained stable up to the age of 85 years. No correlation was found between PLMS index and PI. The number of PLMS per hour of sleep declined through the night in subjects aged 15–75 years; after this age, PLMS tended to be equally distributed across the entire night.ConclusionsThe use of three main parameters derived from the analysis of leg motor activity during sleep in RLS patients (PLMS index, PI and PLMS time distribution) is capable of providing us with important information about the age-related changes of PLMS in this condition, which can be used in the evaluation of the sleep motor patterns in these subjects.     

Night-to-night variability in periodic leg movements in patients with restless legs syndrome

BACKGROUND AND PURPOSE: Although a night-to-night variability in periodic leg movements (PLM) occurrence has been described in patients with primary PLM disorder and sleep apnea syndrome, no study has apparently considered the inter-night effect on PLM index during wakefulness and sleep in patients with Restless Legs Syndrome (RLS). Moreover, no study has examined the night-to-night variability in PLM index according to sleep stage and time of night. We therefore examined changes in PLM index during wakefulness and sleep during two consecutive nights in a group of untreated RLS patients. PATIENTS AND METHODS: Twenty-eight drug-free RLS patients, aged 53.4+/-2.3 yr, with a mean International Restless Legs Syndrome Study Group (IRLSSG) severity score of 20.2+/-1.6, were studied during two consecutive nights. PLM duration and interval, PLM index during wakefulness (PLMWI), during total sleep time (PLMSI), as well as during each sleep stage were measured. Analysis was also extended to examine PLM occurrence during sleep cycles. RESULTS: In the group of patients as a whole, the PLMW and PLMS index, duration and interval did not show significant difference between nights, these measures being consistently similar for both nights. Comparison of PLMS index between different sleep stages did not reveal inter-night differences. Nocturnal variation in PLM number, duration and interval for total recording time and sleep period revealed a progressive decline across the night for PLM index (P相似文献   

Time course of arousal response during periodic leg movements in patients with periodic leg movements and restless legs syndrome.

OBJECTIVE: The temporal evolution of periodic leg movements (PLM) and the relationship of their arousing effect on sleep episode has not been extensively investigated. We studied the nocturnal evolution of PLM associated or not with microarousal (MA) and associated with slow wave activity (PLM with slow wave activity) in 23 patients with PLM and/or restless legs syndrome (RLS). METHODS: All subjects had PLM associated with MA or with slow wave activity as well as without MA and all slept for 4 sleep cycles. Spectral electroencephalogrpahic (EEG) analysis was done for the 4 sleep cycles to assess the nocturnal variation in slow wave activity (SWA). RESULTS: Sixty percent of PLM were associated with MA, 4% were associated with slow wave activity whereas 36% showed no EEG changes. There was a clear prevalence of PLM with MA in stages 1 and 2 while PLM without MA were prevalent in slow wave sleep. The night-time PLM index progressively declined from the first to the last sleep cycle (P<0.005), without differences between PLM types, or between PLM and RLS patients. The decline of PLM duplicated the temporal trend in SWA over consecutive sleep cycles. CONCLUSIONS: PLM showed a typical pattern of progressive decline throughout the night following the exponential decline in SWA. These over-time variations occurred independently of changes in the rate of PLM associated or not with MA or associated with slow wave activity, suggesting that variations in arousal threshold and sleep propensity did not affect the PLM arousing effect. The PLM-related arousal response might be affected by interaction of circadian and sleep stage influences with the addition of sleep oscillatory processes.     

Development of restless legs syndrome after dopaminergic treatment in a patient with periodic leg movements in sleep

Periodic leg movements in sleep (PLMS) unrelated to restless legs syndrome (RLS) are a polysomnographic finding with a controversial clinical value. We describe a patient with isolated periodic leg movements in sleep (without any awake or sleep complaints), who developed severe diurnal RLS symptoms a few months after starting dopaminergic treatment, a phenomenon mimicking augmentation. The diurnal RLS symptoms disappeared after withdrawal of the dopaminergic drugs. Serum ferritin levels were relatively low (31-61 mcg/l; normal: 30-400 mcg/l). Since low levels of ferritin have been implicated in the genesis of RLS, and augmentation is a phenomenon associated with RLS, our findings here suggest that asymptomatic PLMS may have pathogenic mechanisms similar to RLS. Isolated PLMS and RLS could be, at least in some cases, different clinical forms of the same disorder. The conjunction of dopaminergic treatment with low ferritin levels may expose a patient with isolated PLMS to the development of RLS. Discontinuation of dopaminergic drugs in patients with isolated PLMS who develop RLS during the course of the treatment would be a reasonable recommendation.     

Leg movements during wakefulness in restless legs syndrome: time structure and relationships with periodic leg movements during sleep

Background and objectiveApproximately one third of patients with restless legs syndrome (RLS) also show periodic leg movements (PLM) during relaxed wake fulness (PLMW). In contrast with the large amount of data published on periodic leg movements during sleep (PLMS), PLMW have received less attention from the scientific community. The objective of this study was to evaluate the correlations/differences of time–structure and response to a dopamine-agonist between PLMW and PLMS in patients with RLS.MethodsNinety idiopathic RLS patients and 28 controls were recruited. Subjects underwent clinical and neurophysiological evaluation, hematological screening, and one or two consecutive full-night polysomnographic studies. A subset of patients received 0.25 mg of pramipexole or placebo before the second recording. Polysomnographic recordings were scored and LM activity was analyzed during sleep and during the epochs of wakefulness occurring during the first recording hour.ResultsRLS patients had higher LM activity during wakefulness than controls, but with a similar periodicity. Even if correlated, the ability of the PLMW index to predict the PLMS index decreased with increasing LM activity. Intermovement intervals during wakefulness showed one peak only at approximately 4 s, gradually decreasing with increasing interval in both patients and controls. The effect of pramipexole was very limited and involved the small periodic portion of LM activity during wakefulness.ConclusionsPLMW index and PLMS index were correlated; however, the magnitude of this correlation was not sufficient to suggest that PLMW can be good predictors of PLMS. Short-interval LM activity during wakefulness and sleep might be linked to the severity of sleep disruption in RLS patients and the differences between their features obtained during wakefulness or sleep might be relevant for the diagnosis of sleep disturbances in RLS.     

Evaluation of periodic leg movements and associated transcranial magnetic stimulation parameters in restless legs syndrome

Restless legs syndrome (RLS), a sensorimotor disorder characterized by unpleasant sensations commonly localized in the legs, is frequently associated with periodic limb movements (PLMs) during sleep. We investigated the role of transcranial magnetic stimulation (TMS) and cortical silent period (CSP) duration as diagnostic and monitoring tools in 20 patients with primary RLS before and after 1 month of treatment and also studied 15 normal age- and gender-matched subjects. Polysomnographic assessment was undertaken and the PLM index determined in 17 of the 20 patients. We also studied the correlation between sleep efficiency index and CSP duration because of the increasing severity of the sleep disturbance and PLMs in patients with RLS. Our results demonstrate that the duration of the CSP was reduced in patients with RLS, and that dopaminergic treatment normalized this duration. There was no correlation between the PLM index and CSP duration. It may be speculated that PLMs and the CSP are due to different inhibitory mechanisms and they may be used separately as diagnostic and monitoring tools in patients with primary RLS.     

Age and gender effects on heart rate activation associated with periodic leg movements in patients with restless legs syndrome.

OBJECTIVE: Periodic leg movements during sleep (PLMS) are often associated with electroencephalographic (EEG) changes, such as microarousals (MA), and with heart rate (HR) variations. The aim of the present study was to evaluate the effects of age and gender on HR changes associated with PLMS in restless legs syndrome (RLS) patients. METHODS: Forty-two RLS patients underwent one night of polysomnographic recordings. They were divided into 3 groups of 14 subjects (7 women and 7 men) according to age, i.e. young (25-40 years), middle-aged (41-55 years) and elderly (56-71 years) patients. The RR interval was calculated for 5 intervals before and 15 intervals after the onset of 50 PLMS in each patient. RESULTS: PLMS were associated with HR changes characterized by a tachycardia followed by a bradycardia. However, a reduction in the tachycardia and the bradycardia was observed with age. Moreover, women showed a higher amplitude in the bradycardia than men. No age or gender difference was found for MA index and duration. CONCLUSIONS: This study showed age and gender differences in the magnitude of the HR changes associated with PLMS. The knowledge of HR variations during sleep, including rapid HR changes associated with sleep events such as PLMS or MA, may be helpful in understanding the potential mechanisms involved in the increased cardiac risk observed in elderly.     

SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep

Restless legs syndrome (RLS) is a common sleep-related disorder principally characterised by leg paresthesia associated with an irresistible urge to move. A majority of RLS patients experience periodic leg movements during sleep (PLMS) and wakefulness. Pharmacological evidence suggests that RLS-PLMS may be caused by a central nervous system dopaminergic (DA) dysfunction. The aim of the present study was to evaluate the striatal pre- and postsynaptic DA status in patients suffering from both RLS and PLMS, by means of [123I] beta-CIT and [123I]IBZM SPECT respectively. Ten drug-na?ve patients and ten age-matched controls participated in this study. All participants were recorded for at least one night of polysomnography before the SPECT studies. No difference was seen in DA transporter ([123I] beta-CIT) binding between RLS-PLMS patients (MD=4.89) and controls (MD=4.81; p=0.81). The study of the striatal D2-receptor binding ([123I]IBZM) revealed a significantly lower binding in patients (MD= 1.72) compared with controls (MD=1.85; p=0.006). These results support the hypothesis that a central DA dysfunction is involved in the physiopathology of RLS-PLMS. Several mechanisms may be responsible for the decrease of the D2-receptor binding. However, since [123I] beta-CIT binding is normal, a decreased number of D2-receptors or a decreased affinity of D2-receptors for [123I]IBZM is more likely than an increased level of synaptic DA with attendant downregulation of D2-receptors.     

First night efficacy of pramipexole in restless legs syndrome and periodic leg movements

OBJECTIVE: Restless legs syndrome (RLS) seems to improve immediately after a single dose of dopamine-agonists (DA). The aim of the present study was to investigate the acute effects of a low standard dose of pramipexole in RLS drug-na?ve patients. METHODS: A single-blind placebo-controlled study in 32 consecutive idiopathic RLS de-novo patients was carried out. Patients who met the standard criteria for RLS, with a PLMS index greater than 10 as well as an RLS rating scale score greater than 20 underwent clinical and neurophysiological evaluation, hematological screening and two consecutive full-night polysomnographies. On the second night, all patients received 0.25mg of pramipexole or placebo at 9:00 p.m. Acute symptom response was assessed by a visual analogical scale (VAS). RESULTS: Eighteen patients received pramipexole and 14 patients received placebo. Compared to placebo, the single low dose (0.25mg) of pramipexole significantly improved RLS symptoms (VAS: from 7.4+/-1.68 to 1.3+/-1.62, p<0.00001) and strongly reduced PLMS index (from 45.8+/-33.56 to 9.4+/-11.40, p<0.0002). A significant increase in the percentage of stage 2 non-rapid eye movement (NREM) sleep was also observed in the pramipexole group (from 38.7+/-10.50 to 50.6+/-12.13, p<0.02). CONCLUSIONS: A low dose of pramipexole was effective in treatment-na?ve patients with RLS from the first night of administration. These results support a direct involvement of the dopaminergic system in RLS pathogenesis and might have important implications for a possible future pramipexole administration on-demand, as well as for a pharmacological test to confirm diagnosis in clinically complex cases.     

Opioid treatment of periodic movements in sleep in patients without restless legs

Opioids may be a useful treatment for some patients with Periodic Movements of Sleep (PMS) and sleep disturbances. Four patients who had only idiopathic PMS and sleep disturbances but not Restless Legs Syndrome (RLS) were treated with various opioids. Two of the patients responded with a more than 98% decrease in the number of PMS per night of sleep and a doubling of the percentage of sleep period time spent in deep (Stages 3 and 4) sleep.     

Management of restless legs and periodic movements of sleep

INTRODUCTION: Restless legs syndrome and periodic leg movements in sleep are frequently observed, often in association. Misdiagnosis of these two conditions is common. STATE OF ART: Physical examination can provide the diagnosis of restless legs syndrome but polysomnography recording must be performed to confirm the presence of periodic leg movements. Dopaminergic pathways are implicated in the pathophysiology of these two syndromes and the same treatment is given: dopaminergic agents, benzodiazepines, opioids and/or antiepileptic drugs. PERSPECTIVES AND CONCLUSION: Treatment provides an improvement in quality-of-life for these patients.     

Restless legs and periodic leg movements in sleep syndromes

Restless legs syndrome (RLS) is a common sensorimotor disorder with an estimated prevalence of between 1% and 5%. The symptomatology is characterized by unpleasant sensations experienced predominantly in the legs and rerely in the arms. The symptoms occur only at rest and become more pronounced in the evening or at night. In addition, the patients suffer from a strong urge to move the limbs, typically manifest as walking around, which leads to complete but only temporary relief of the symptoms. Most of the patients with RLS have periodic leg movements (PLMS) during sleep and relaxed wakefulness that are characterized by repetitive flexions of the extremities. PLMS can occur as an isolated phenomenon, but often they occur together with other sleep disorders including RLS, narcolepsy, sleep apnoea syndrome or REM sleep behaviour disorder. In all these disorders, PLMS contribute considerably to disturbed sleep, as the movements may lead to brief arousals or repeated full awakenings. The aetiology of RLS and PLMS is unknown. It is hypothesized that periodic leg movements result from a suprasegmental disinhibition of descending inhibitory pathways. Based on the efficacy of the drugs listed below, the dopaminergic, adrenergic and opiate systems are thought to play a major role in the pathogenesis of RLS/PLMS. Since the cause is unclear, therapy of RLS and PLMS remains symptomatic except for some secondary forms. Studies on the pharmacological treatment of RLS have shown the efficacy of levodopa, dopamine agonists, benzodiazepines, opioids, clonidine and carbamazepine. With regard to the drug treatment of PLMS in other sleep disorders including their isolated occurrence, indications and efficacy have been poorly defined until now.

     

Dyskinesias while awake and periodic movements in sleep in restless legs syndrome: treatment with opioids

In five unrelated patients with the restless legs syndrome, opioid drugs relieved restlessness, dysesthesias, dyskinesias while awake, periodic movements of sleep, and sleep disturbances. When naloxone was given parenterally to two treated patients, the signs and symptoms of the restless legs syndrome reappeared. Naloxone placebo had no effect. Opioid medications may offer a useful therapy for the restless legs syndrome. The endogenous opiate system may be involved in the pathogenesis of the syndrome.     

The influence of sex, age and sleep/wake state on characteristics of periodic leg movements in restless legs syndrome patients.

Restless legs syndrome (RLS) patients experience periodic stereotyped leg movements while awake and during sleep. The aim of the present study was to measure the effects of sex, age and the sleep/wake state on several characteristics (frequency, duration and periodicity) of these periodic leg movements (PLM). One hundred unrelated patients diagnosed with primary RLS were studied. During wakefulness, frequency of PLM increased and the mean inter-movement interval decreased with advancing age. The modal value of inter-movement interval distribution was also altered suggesting that aging influences rhythm-generation mechanisms. Sleep/wake states had a profound effect on leg movement characteristics. Movements of longer duration were seen during wakefulness, while REM sleep was characterized by the shorter duration and the lowest frequency of PLM, due most likely to the inhibition of spinal motoneurons that prevails in REM sleep. States of vigilance also modulated the periodicity of PLM. Intervals were shorter during wakefulness and increased progressively from stage 1 to stage 2 sleep, and to slow wave sleep (SWS). During REM, the duration of sleep intervals returned to values obtained in stage 1 sleep; these two stages sharing similar patterns of EEG activity. These results indicate that a single state dependent mechanism may be responsible for the periodicity of PLM noted both during sleep and wakefulness.     

Restless legs syndrome and central nervous system gamma-aminobutyric acid: preliminary associations with periodic limb movements in sleep and restless leg syndrome symptom severity

Background

Previous research has demonstrated abnormalities in glutamate and N-acetyl aspartate (NAA) in the thalamus in individuals with restless legs syndrome (RLS) compared with healthy matched controls. However, levels of these transmitters in other RLS-related brain areas and levels of the most common inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have not been assessed.

Methods

This study examined GABA, glutamate, and NAA levels in the dorsal anterior cingulate cortex (ACC), thalamus and cerebellum with the use of proton magnetic resonance spectroscopy (¹H-MRS) at 4 tesla (4 T) and Megapress difference-editing in 18 subjects with RLS and a matched control group without RLS. Actigraphy was performed on the nights before scans to assess periodic limb movements of sleep (PLMS).

Results

Levels of GABA, glutamate, and NAA were no different between RLS and control subjects in any of the three voxels of interest. However, GABA levels were positively correlated with both PLM indices and RLS severity in the thalamus and negatively with both of these measures in the cerebellum in RLS subjects. In addition, NAA levels were higher in the ACC in RLS than in controls.

Conclusion

Our preliminary data suggest that known cerebellar–thalamic interactions may modulate the intensity of RLS sensory and motor symptoms. In addition, anterior cingulate cortex may be associated with the affective components of the painful symptoms in this disorder.