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PubMed2006

Genetic aspects of restless legs syndrome.

Restless legs syndrome (RLS), also known as Ekbom syndrome, is a common movement disorder with sensorimotor symptoms occurring during sleep and quiet wakefulness. The underlying cause for RLS is unknown but genetic influences play a strong part in the pathogenesis of RLS, particularly when the condition starts at a young age. This review explores the genetic basis of RLS and related phenotypic variations. Recently, three loci showing vulnerability to RLS have been described in French-Canadian and Italian families in chromosomes 12q, 14q and 9q, emphasising on an autosomal dominant mode of inheritance. These have been labelled RLS1, RLS2 and RLS3, respectively. However, specific causative mutations remain elusive and no linkage analysis has been identified so far in the candidate genes investigated in RLS.

Chromosome Mapping↗
PubMedDate not supplied

Restless legs syndrome--relevant aspects for internal medicine specialists.

Restless legs syndrome (RLS), also known as Ekbom's syndrome, is a fairly common complaint which is not widely recognised by medical professionals, although it seems to affect 1-10% of the population. Despite recent attempts to better characterize RLS, this neurologic disorder remains poorly understood. Idiopathic RLS frequently follows an autosomal dominant inheritance with a variable clinical expressivity of symptoms. Secondary RLS is usually associated with neuropathy of chronic disorders (uremia, cryoglobulinemia, diabetes mellitus, infections, etc). RLS gives the sufferer an unpleasant sensation in the legs at rest, causing an irresistible desire to move which alleviates the discomfort. Other features that characterize RLS include sleep disturbance, involuntary movements in sleep or wakefulness, a normal neurologic examination, a chronic clinical course (waxing and waning over the time), and, in some cases, a positive family history. Periodic limb movements during sleep, which also may occur as an isolated finding, may or may not cause frequent arousals or awakenings. Clinical diagnosis of idiopathic or symptomatic forms of RLS can be supported with polysomnography. Full understanding of the features of RLS will provide the clinician with the strongest tool for recognizing the disorder. Many different treatments have been tried for RLS. Since the cause is unclear, therapy of RLS and PLMS remains symptomatic except for some secondary forms. Treatment of first choice consists of dopaminergic drugs or dopamine agonist, opioids and benzodiazepines.

Aged↗
PubMed1999

Circadian rhythm of motor restlessness and sensory symptoms in the idiopathic restless legs syndrome.

STUDY OBJECTIVES: To determine if motor restlessness in the Restless Legs Syndrome (RLS) shows a circadian rhythm with maximum at night, as previously found for subjective discomfort and periodic limb movements (PLMs), and to correlate RLS peak intensity with the core temperature cycle. DESIGN: Subjects underwent two days of normally timed wakefulness and sleep followed by a night and subsequent day of sleep deprivation. Activity was standardized through modified suggested immobilization tests (mSITs). SETTING: The study was conducted in a laboratory environment with a bedroom equipped for polysomnography during sleep and the mSITs. PATIENTS: Nine patients (mean age 59.8+/-11.3 years [range: 33-72]; 4 males, 5 females) with clinically severe idiopathic RLS. INTERVENTIONS: Patients were monitored with continuous ambulatory activity and core temperature recording. The mSITs were performed every three hours while subjects were awake. During the mSITs, subjective discomfort was measured every 15 minutes while motor restlessness was assessed through activity monitoring. MEASUREMENTS AND RESULTS: Subjective discomfort and motor restlessness increased from a trough in the morning to a maximum at night in the hours following midnight. Peak intensity was found on the falling phase of the core temperature cycle, whose circadian rhythm appeared to be within the normal range for age. CONCLUSIONS: An independent circadian factor modulates the intensity of RLS, which seems to peak on the falling phase of the core temperature cycle. Therefore, the diagnostic criteria that RLS occurs with rest and during the night have independent bases. Furthermore, RLS may be partially controlled by some process or substance whose level varies with the normal circadian rhythm.

Adult↗
PubMed2006

The reliability, validity and responsiveness of the International Restless Legs Syndrome Study Group rating scale and subscales in a clinical-trial setting.

PATIENTS AND METHODS: To assess the reliability, validity, and responsiveness of the International Restless Legs Syndrome Study Group's rating scale (the International Restless Legs Scale (IRLS)) (V2.0), using pooled data from two matching, placebo-controlled studies of ropinirole for treating Restless Legs Syndrome (RLS). RESULTS: Pooled patient samples comprised 550 patients in the baseline (validation) sample and 439 patients in the week 12 longitudinal (responsiveness) sample. Factor analysis revealed acceptability of the IRLS total score (accounting for 40% of the variance) and that nine of the 10 IRLS items could also be assigned to two distinct subscales, the symptoms or symptoms impact subscales. The IRLS total score, symptoms and symptoms impact subscales had acceptable construct validity, internal consistency reliability (alpha=0.81, 0.80, and 0.76, respectively), and concurrent validity (r=-0.68, -0.52, -0.70, respectively, with the Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) overall life impact score). IRLS scores differed significantly between different levels of sleep problems and Clinical Global Impression (CGI) of health status (P<0.0001), indicating known groups and clinical validity, respectively. Changes in scores differed significantly among CGI 'global improvement' levels (P<0.0001), providing evidence of responsiveness. CONCLUSIONS: The IRLS total score, symptoms, and symptoms impact subscales are reliable, valid, and responsive in a clinical trial setting.

Adult↗
PubMed2006

Time to REST: epidemiology and burden.

Restless legs syndrome (RLS) is a neurological disorder characterized by a compelling urge to move, accompanied by disturbing sensations within the legs. It is now recognized that RLS is a common condition that has a substantial impact on sleep, daily activities and quality of life. Recent data from the REST (RLS Epidemiology, Symptoms, and Treatment) general population study show that symptoms of RLS are present in approximately 7% of the general population, and that 2-3% experience moderate or severe symptoms at least twice a week. Amongst this RLS cohort, approximately 88% reported sensory disturbances and 76% reported sleep-related symptoms. These symptoms had a marked effect on everyday life, with up to 50% of the RLS cohort reporting disruption of everyday activities or personal relationships. Sleep disturbances in turn lead to impaired daytime functioning. RLS is associated with a significant impairment of quality of life, comparable with that seen in chronic medical conditions such as diabetes or depression. Given the significant burden of morbidity associated with RLS, there is a strong case for treatment in patients with troublesome symptoms.

Cognition↗
PubMed2003

Managing patients with restless legs.

Estimates suggest that around 10-15% of adults have restless legs, or Ekbom syndrome. This condition is characterised by a range of uncomfortable and sometimes distressing motor and sensory symptoms during quiet wakefulness and/or sleep, such as feelings of burning, tickling or crawling, pain, cramping, numbness or weakness in the lower limbs, and, sometimes, also in the trunk and arms. The problem can seriously affect quality of life, yet is frequently dismissed as trivial. Often, it is unrecognised, incorrectly regarded as a neurosis, or managed poorly or not at all. Here we review how people with restless legs can best be helped.

Diagnosis, Differential↗
PubMed2005

Nonmotor complications in Parkinson's disease.

Parkinson's disease (PD) is most often considered a disorder of movement. Whereas bradykinesia, rigidity, tremor, and postural instability result in disability, nonmotor complications in PD may be of equal or greater significance in some patients. This review will discuss many of the nonmotor complications in PD, including cognitive, autonomic, sleep, and sensory difficulties that may occur.

Antidepressive Agents↗
PubMed2005

Different levels of work-related stress and the effects on sleep, fatigue and cortisol.

OBJECTIVES: The aim of the study was to relate different levels of work stress to measures of sleep and the diurnal pattern of salivary cortisol and subjective sleepiness. METHODS: Thirty-four white-collar workers participated under two different conditions. One workweek with a relatively high stress level (H) and one with a lower stress level (L) as measured through self-rated stress during workdays. The workers wore activity monitors, filled out a sleep diary, gave saliva samples (for cortisol), and rated their sleepiness and stress during one workday and one free day. RESULTS: During the week with stress the number of workhours increased and total sleep time decreased. Sleepiness showed a significant interaction between weeks and time of day, with particularly high levels towards the evenings of the stress week. Cortisol also showed a significant interaction, with a more flattened pattern, probably due to increased evening levels during the stress week. Stress (restlessness) at bedtime was significantly increased during the stress week. CONCLUSIONS: The results demonstrate that a workweek with a high workload and much stress increases sleepiness and workhours, impairs sleep, and affects the pattern of diurnal cortisol secretion.

Employment↗
PubMed2006

Controlled withdrawal of pramipexole after 6 months of open-label treatment in patients with restless legs syndrome.

Although dopamine agonists are becoming first-line therapy for restless legs syndrome (RLS), few reports describe treatment periods exceeding 12 weeks. Here, 150 RLS patients who had responded to pramipexole during a 6-month run-in period (mean dose, 0.50 mg) were randomly assigned to receive placebo or continue receiving pramipexole at an individually optimized dose of 0.125 to 0.75 mg/day for a further 3 months. Patients switched to placebo reached the primary endpoint (a predefined worsening on both the Clinical Global Impressions-Global Improvement scale and the International RLS Study Group Rating Scale) significantly more often than patients who continued to receive pramipexole (85.5% vs. 20.5%; P < 0.0001). They also reached the primary endpoint faster, in 5 versus 42 days to a Kaplan-Meier survival estimate of 0.85 and 7 versus > 84 days to an estimate of 0.5. Over the total 9 months, clinician and patient ratings of symptoms, sleep, and quality of life identified no decline in pramipexole's benefit or tolerability. The great majority of adverse events (AEs) were mild or moderate, and of expected types. Augmentation was considered an AE, but in this population of responders it did not occur.

Adult↗
PubMed2005

On the pharmacotherapy of sleep bruxism: placebo-controlled polysomnographic and psychometric studies with clonazepam.

OBJECTIVES: Sleep bruxism (SB) is a parasomnia defined as a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep. Pathophysiologically, SB is the result of biological and psychosocial influences. Treatment comprises behavioral, orthodontic and pharmacological interventions. While benzodiazepines and muscle relaxants have been reported by clinicians to reduce bruxism-related motor activity, placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate the acute effects of clonazepam (Rivotril) as compared with placebo, utilizing polysomnography and psychometry. METHOD: Ten drug-free outpatients (6 females, 4 males), aged 46.5 +/- 13.1 years, suffering from SB (ICD-10: F45.8; ICSD: 306.8) and having been treated by bite splints were included in the trial. Comorbidity was high: 7 patients presented nonorganic insomnia related to adjustment or anxiety disorders (5 patients) or depression (2 patients); all patients had a concomitant movement disorder (6 restless legs syndrome, 4 periodic leg movement disorder). After one adaptation night, patients received placebo and 1 mg clonazepam 1/2 hour before lights out in a single-blind, nonrandomized study design. Objective sleep quality was determined by polysomnography, subjective sleep and awakening quality by rating scales, objective awakening quality by psychometric tests. Clinical evaluation was based on the Pittsburgh Sleep Quality Index (PSQI), the Zung Depression (SDS) and Anxiety (SAS) Scales, the Quality of Life Index, the Epworth Sleepiness Scale and the International Restless Legs Syndrome Study Group (IRLSSG) Scale. RESULTS: On admission, SB patients exhibited deteriorated PSQI, SAS, SDS and IRLSSG measures. As compared with placebo, 1 mg clonazepam significantly improved the mean bruxism index from 9.3 to 6.3/h of sleep. Furthermore, it significantly improved the total sleep period, total sleep time, sleep efficiency, sleep latency and time awake during the total sleep period, and increased stage 2 sleep and movement time. Periodic leg movements decreased significantly, while the apnea index and apnea-hypopnea index increased marginally, but remained within normal limits. Subjective sleep quality improved as well, while in mood, performance and psychophysiology no changes were observed. CONCLUSION: Acute clonazepam therapy significantly improved not only the bruxism index but also objective and subjective sleep quality, with unchanged mood, performance and psychophysiological measures upon awakening, suggesting good tolerability of the drug.

Adult↗
PubMed2002

Endocrine rhythms in patients with restless legs syndrome.

There is increased evidence that the dopaminergic system plays a major role in the pathophysiology of the restless legs syndrome (RLS). Dopamine is the major inhibitory factor of prolactin release and also influences growth hormone (hGH) secretion. The aim of this study was to measure the endocrine activity of RLS patients, to compare it with that of normal subjects and to detect possibly altered patterns of hormonal secretion in RLS patients. Prolactin, hGH and cortisol plasma levels were measured every 20 min for 24 hours in 10 male never-medicated RLS patients (aged 56 +/- 6 years) who have had mild to moderate symptoms for 15 +/- 10 years and in 8 age-matched male controls (aged 57 +/- 5 years). The blood samples taken during the night were paralleled by polysomnographic recordings including the assessment of periodic leg movements (PLM). Plasma levels as well as frequency and amplitude of the pulses of prolactin, hGH and cortisol were not different between RLS patients and controls. Both groups showed the same rhythms during the night- and daytime for all hormones. Cross correlations resulted in high correlation coefficients for each hormone at lag 0 (0.964,0.943 and 0.971 for mean locations of cortisol, hGH and prolactin, respectively). Concerning sleep parameters, there were no significant differences between the two groups apart from a higher PLMS arousal index in RLS patients (25.9 +/- 17.1) compared with the controls (12.0 +/- 9.2; p < 0.05). It is suggested that a possible dysfunction of the dopaminergic system in RLS does not affect the release of prolactin and hGH from the pituitary gland.

Chronobiology Disorders↗
PubMed1991

Sleep and cardiac rhythm in healthy men.

Cardiac rhythm during sleep was analysed in 168 healthy men aged 19 to 30 (mean 21.8) years using continuous nocturnal ECG recordings. Thirty five of the subjects were endurance athletes; 99 were recorded at home and 69 at a garrison during military service. The number of short term (less than one min) accelerations of heart rate of more than ten beats per minute ranged from 1.3 to 14.3 per hour; the number or accelerations (greater than one min) of more than 25 beats per minute typical of nocturnal restlessness ranged from zero to 6.1 per hour. The accelerations indicating nocturnal restlessness were more common during recordings done at the garrison than at home (2.2 per hour vs 1.3 per hour, P less than 0.01), whereas the short term accelerations were not (5.8 per hour vs 5.1 per hour, NS). Sinus pauses exceeding 2.00 sec occurred in 17 men (13 in athletes), occasional second degree atrioventricular block in 19 (eight in athletes) and ventricular premature beats in 37. Eighty-two per cent of sinus pauses, 83% of second degree atrioventricular blocks, and 81% of ventricular premature beats (when less than ten in the same subject) were associated with short term changes in heart rate. In conclusion, rapid changes in heart rate, presumably as a results of autonomic activation, are closely associated with most arrhythmias in healthy men during sleep, whereas changes in heart rate typical of nocturnal restlessness have little arrhythmogenic effect.

Adult↗
PubMed2006

Prevalence and clinical characteristics of restless legs syndrome in Japanese patients with Parkinson's disease.

To explore the clinical significance of restless legs syndrome (RLS) in Parkinson's disease (PD) and the causal relationship between these two disorders, we made a comparison of both the prevalence of RLS and the severity of sleep disturbance manifested on the Pittsburg Sleep Quality Index (PSQI) between patients with PD (n=165) and age- and sex-matched control subjects (n=131). The prevalence of RLS diagnosed by clinical interview was significantly higher in PD patients than in control subjects (12% vs. 2.3%). PSQI score was significantly higher in PD patients with RLS than in both patients without RLS and controls. However, PSQI score was not statistically different between the latter two groups. Among the PD patients with RLS, only 2 had a positive family history of RLS. Only 3 PD patients had requested treatment for the disorder. Our results emphasize the etiological link between RLS and PD in a Japanese cohort, and the existence of RLS is thought to be one of the most important factors aggravating sleep disturbance in PD, despite the low RLS severity.

Aged↗
PubMed2002

Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study.

OBJECTIVE: To assess the effects of gabapentin on sensory and motor symptoms in patients with restless legs syndrome (RLS). METHODS: Patients with RLS (22 idiopathic, 2 secondary to iron deficiency) were randomized and treated for 6 weeks with either gabapentin or placebo. After a 1-week washout they crossed over to the alternative treatment for 6 weeks. Patients were rated at baseline and at scheduled intervals by the RLS Rating Scale, Clinical Global Impression, pain analogue scale, and Pittsburgh Sleep Quality Index. At the end of each treatment period, all-night polysomnography was performed. RESULTS: Compared to placebo, gabapentin was associated with reduced symptoms on all rating scales. In addition, sleep studies showed a significantly reduced periodic leg movements during sleep (PLMS) index and improved sleep architecture (increased total sleep time, sleep efficiency, and slow wave sleep, and decreased stage 1 sleep). Patients whose symptoms included pain benefited most from gabapentin. The mean effective dosage at the end of the 6-week treatment period was 1,855 mg, although therapeutic effects were already observed at the end of week 4 (1,391 mg). CONCLUSIONS: Gabapentin improves sensory and motor symptoms in RLS and also improves sleep architecture and PLMS.

Acetates↗
PubMed1997

Nocturnal respiratory failure as an indication of noninvasive ventilation in the patient with neuromuscular disease.

Patients with neuromuscular disease may suffer from nocturnal respiratory failure despite normal daytime respiratory function. The physiological reduction in muscle tone during sleep may be life-threatening in a patient with impaired muscle strength. Nocturnal respiratory failure may occur in patients with the postpolio syndrome, amyotrophic lateral sclerosis, myasthenia gravis, myotonic dystrophy, and muscular dystrophy. Diagnosis of obstructive, central and mixed apneas, hypopneas, and hypoventilation is best made using polysomnography. Therapeutic options include noninvasive ventilation such as continuous positive airway pressure, bilevel positive airway pressure, intermittent positive pressure ventilation and, rarely, tracheostomy, oxygen, or protriptyline. Evaluation by a sleep specialist should be initiated in any neuromuscular patient with nocturnal symptoms such as air hunger, intermittent snoring or breathing, orthopnea, cyanosis, restlessness, and insomnia. Daytime symptoms may include morning drowsiness, headaches and excessive daytime sleepiness. Polycythemia, hypertension, and signs of heart failure may also be seen. Effective treatment is available, and may improve the quality of life, and possibly increase survival.

Adrenergic Uptake Inhibitors↗
PubMed2000

Periodic arm movements in patients with the restless legs syndrome.

A high proportion of patients with restless legs syndrome (RLS) also complain of arm paresthesia but the presence of periodic arm movements (PAM) has never been documented in a sleep laboratory in these patients. We investigated the prevalence of PAM during nocturnal sleep and awakenings in 22 RLS patients. Fifteen patients had a PAM index >5 movements per hour during wakefulness and among them only 3 had a PAM index >5 during sleep. Twenty patients had a periodic leg movement (PLM) index >5 during wakefulness and 17 had a PLM index >5 during sleep. In 42.8% of cases, PAM showed temporal relationship with PLM during wakefulness. These results show that PAM is frequent in RLS and suggest that the basic neurological dysfunction responsible for RLS is probably not located exclusively at the level of the lumbar spinal cord but involves neuronal systems located at upper levels.

Adult↗
PubMedDate not supplied

Effect of nonnutritive sucking on behavioral state in preterm infants before feeding.

To describe the effect of nonnutritive sucking (NNS) on behavioral state (BSt) in preterm infants before feedings 24 preterm infants were randomly assigned and studied before each of their first 16 bottle feedings. Twelve received NNS by pacifier for 5 minutes; 12 did not receive a pacifier. BSt was measured with a 12-category scale for 30 seconds before the 5-minute period (BSt1) and for 30 seconds after (BSt2). Sleep states decreased for both groups. BSts considered more optimal for feeding increased more during NNS (86 vs. 46). Restless states were three times less frequent after NNS (23 vs. 68). Differences between groups were nonsignificant at BSt1, but were significant at BSt2, p less than .001. In the absence of self-regulatory feeding policies based on early hunger cues, NNS for 5 minutes prefeeding is simple, brief, and suitable for implementation in busy neonatal intensive care units. Nonnutritive sucking was an effective modulator of behavioral state for this sample.

Child Behavior↗