Defining the boundaries of the response of sleep leg movements to a single dose of dopamine agonist (original) (raw)
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2010
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/discontinu-abnormalities in sleep microstructure, represented by an excessive sleep instability/discontinu-in sleep microstructure, represented by an excessive sleep instability/discontinu-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.
European Neurology, 1991
Restless legs syndrome is a frequent neurological disorder with potentially serious and highly distressing treatment complications. The role and potential implications of periodic leg movements during sleep range from being a genetic risk marker for restless legs syndrome to being a cardiovascular risk factor. The diagnosis of restless legs syndrome in patients with daytime movement disorders is challenging and restless legs syndrome needs to be differentiated from other sleep-related movement disorders. This article provides an update on the diagnosis of restless legs syndrome as an independent disorder and the role of periodic leg movements and reviews the association of restless legs syndrome with Parkinson's disease and other movement disorders. V
Sleep Medicine, 2003
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. q
Neuropsychobiology, 2000
The restless legs syndrome (RLS) is a common sensorimotor disorder which leads to severe sleep disturbances and showed a prevalence of 7.9% in our sleep laboratory. The aim of this study was to investigate periodic leg movements (PLM), arousal and respiratory variables in 12 untreated RLS patients and to measure the acute effects of 0.5 mg ropinirole, a nonergoline dopamine agonist, as compared with placebo. In the target variable PLM/h of total sleep time (PLM/h TST), RLS patients showed an increased value of 40/h (normal 0–5/h). Further, we found an increased number of PLM (368), PLM/h of time in bed (49/h), PLM/h of REM sleep (11), PLM/h of non-REM sleep (46) and PLM/h awake (61). The arousal index was also increased (32/h; normal 0–25/h), as were arousals due to PLM. In the confirmatory part of our descriptive data analysis, ropinirole 0.5 mg significantly improved, as compared with placebo, the index PLM/h TST by 75%. In the descriptive part, all the other PLM variables were im...
Sleep Medicine, 2009
Objective: To evaluate, both polysomnographically and by subjective scales, the efficacy and safety profile of pramipexole for restless legs syndrome (RLS) via a 3-week, double-blind, placebo-controlled, parallelgroup, dose-ranging study. Methods: At baseline and after 3 weeks, periodic limb movements (PLM) and sleep parameters were assessed by polysomnography, and patients self-assessed their sleep disturbance and overall RLS severity using the international RLS study group rating scale (IRLS). Four pramipexole doses were evaluated: 0.125, 0.25, 0.50, and 0.75 mg/d. Data from 107 patients were included in the intent-to-treat (ITT) analysis. Results: For pramipexole recipients, the primary outcome measure, PLM per hour in bed asleep or awake (the PLM index, or PLMI), decreased by a median of À26.55 to À52.70 depending on dosage group, vs. À3.00 for placebo (p < 0.01 or 60.001 for each group vs. placebo; Wilcoxon-Mann-Whitney test). Improvements in the secondary endpoints of PLM while asleep and while awake were also significantly superior for pramipexole. At 3 weeks, all pramipexole doses reduced the median for PLM while asleep to levels considered normal (<5 PLM/h). Except for delta-sleep time and awakenings/arousals, sleep parameters remained unchanged or favored pramipexole. Median sleep latency was reduced by À5.00 to À11.75 min in the pramipexole groups, vs. À2.00 for placebo (p < 0.05 for all groups except 0.25 mg/d). Median total sleep time increased by 25.75-66.75 min, vs. 25.50 (p < 0.05 for 0.50 mg/d), and median time in stages 2-4/rapid eye movement (REM) sleep increased by 37.00-68.00 min, vs. 26.75 (p < 0.05 for 0.50 mg/d). By subjective IRLS ratings, all pramipexole doses were significantly superior to placebo. Safety analysis demonstrated no dose-dependent increase in adverse events, and no drug-related increase in daytime somnolence was observed. Conclusions: Pramipexole is effective and well tolerated in RLS, most notably among objective measures, for reducing PLM and decreasing sleep latency. Although other sleep parameters showed lesser, usually insignificant change, patients' subjective ratings of RLS severity and sleep disturbance were significantly improved (p 6 0.0023).
First night efficacy of pramipexole in restless legs syndrome and periodic leg movements
Sleep Medicine, 2007
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-naïve 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 0.25 mg 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 (0.25 mg) 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-naïve 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.
Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD)
European Neuropsychopharmacology, 2001
Restless legs syndrome (RLS)-a common sensorimotor disorder-and periodic limb movement disorder (PLMD) are currently treated with substances of four classes: dopaminergic agents, which are considered the drugs of choice, benzodiazepines, opioids and anticonvulsants. As their effects on sleep variables differ considerably, the aim of the present placebo-controlled sleep laboratory study was to measure the acute effects of 1 mg clonazepam on objective and subjective sleep and awakening quality in ten RLS and 16 PLMD patients, utilizing polysomnography (PSG) and psychometry. Descriptive data analysis demonstrated at the confirmatory level concerning three target variables that-as compared with placebo-clonazepam significantly improved objective sleep efficiency and subjective sleep quality in both patient groups, but failed to reduce the index PLM / h of sleep. At the descriptive level, in PLMD clonazepam improved PLM during time in bed, REM and wakefulness and showed more significant changes in various sleep and awakening measures than in RLS patients, though there were no significant inter-group differences. In conclusion, in both PLMD and RLS clonazepam exhibited acute therapeutic efficacy regarding insomnia, which is quite different from the mode of action of dopamine agonists.
Sleep, 2005
Periodic leg movements in sleep (PLMS) are a frequent phenomenon in various sleep disorders. The pathophysiology of PLMS is still not understood, but recent studies indicate a hypoactivity of the dopaminergic system in subjects with PLMS. In the present study, we investigated the intrasubject variance of PLMS from one night to the other because a fluctuation in the number of PLMS may influence the outcome of pharmacologic and pathophysiologic studies. Retrospective observational study. Data collection occurred in the sleep disorders unit. Sleep electroencephalogram and PLMS data of 115 patients with PLMS monitoring over 2 consecutive nights were evaluated retrospectively. Patients were grouped into the following diagnostic categories: restless legs syndrome, insomnia secondary to a psychiatric disorder, primary insomnia, sleep apnea syndrome, and narcolepsy or idiopathic hypersomnia. N/A. In 27% of the entire patient population, we found a considerable variability of the PLMS index ...
Epidemiology and clinical findings of restless legs syndrome
Sleep Medicine, 2004
Restless legs syndrome (RLS) is a sensory-motor disorder characterized by discomfort of and urge to move the legs, primarily during rest or inactivity, partial or total relief with movement, with presence or worsening exclusively in the evening. It is a relatively common but frequently unrecognized disorder, with a prevalence ranging from 2.5 to 15% of the general population, increasing with age and with a female preponderance. The diagnosis is clinical but polysomnography is useful to determine its profound impact on sleep (difficulties in sleep onset, maintaining sleep during the night, and sleep fragmentation) and for the evidence of periodic legs movements during sleep and wake. RLS is generally idiopathic, with familial association in 40 -60% of the cases, but may also be symptomatic of such associated conditions (secondary forms) as peripheral neuropathies, uremia, iron deficiency (with or without anemia), diabetes, Parkinson's disease and pregnancy. Response to dopaminergic drugs indicates that dopamine receptors are implicated, and although much progress has been made in diagnosis and treatment in the last decade, more is needed for complete elucidation of the etiology and pathophysiology of RLS. q
Sleep Medicine, 2007
Objectives: Augmentation of symptom severity is the main complication of dopaminergic treatment of restless legs syndrome (RLS). The current article reports on the considerations of augmentation that were made during a European Restless Legs Syndrome Study Group (EURLSSG)-sponsored Consensus Conference in April 2006 at the Max Planck Institute (MPI) in Munich, Germany, the conclusions of which were endorsed by the International RLS Study Group (IRLSSG) and the World Association of Sleep Medicine (WASM). The Consensus Conference sought to develop a better understanding of augmentation and generate a better operational definition for its clinical identification. Design and methods: Current concepts of the pathophysiology, clinical features, and therapy of RLS augmentation were evaluated by subgroups who presented a summary of their findings for general consideration and discussion. Recent data indicating sensitivity and specificity of augmentation features for identification of augmentation were also evaluated. The diagnostic criteria of augmentation developed at the National Institutes of Health (NIH) conference in 2002 were reviewed in light of current data and theoretical