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PubMed1999

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.

Adult↗
PubMed1999

Studies of penetrance and anticipation in five autosomal-dominant restless legs syndrome pedigrees.

Restless legs syndrome (RLS) can occur with an autosomal-dominant mode of inheritance. To determine if there are distinguishing features of RLS pedigrees which might clarify molecular mechanisms of pathogenesis, five pedigrees with 81 affected members were analyzed for age of onset, sex ratio, and transmission pattern. One-factor analysis of variance of ages of onset between generations was carried out, and segregation ratios were calculated for each generation. These kindreds showed an autosomal-dominant mode of inheritance and a male:female ratio of 1:1.4 (p = 0.15). One of the five analyzed pedigrees shows some evidence of reduced penetrance. In two of the five analyzed pedigrees, there is statistical support for anticipation (p<0.05). These variations in penetrance and anticipation suggest possible genetic heterogeneity.

Adolescent↗
PubMed2005

The restless legs syndrome.

The restless legs syndrome (RLS) is one of the commonest neurological sensorimotor disorders at least in the Western countries and is often associated with periodic limb movements (PLM) during sleep leading to severe insomnia. However, it remains largely underdiagnosed and its underlying pathogenesis is presently unknown. Women are more affected than men and early-onset disease is associated with familial cases. A genetic origin has been suggested but the mode of inheritance is unknown. Secondary causes of RLS may share a common underlying pathophysiology implicating iron deficiency or misuse. The excellent response to dopaminegic drugs points to a central role of dopamine in the pathophysiology of RLS. Iron may also represent a primary factor in the development of RLS, as suggested by recent pathological and brain imaging studies. However, the way dopamine and iron, and probably other compounds, interact to generate the circadian pattern in the occurrence of RLS and PLM symptoms remains unknown. The same is also the case for the level of interaction of the two compounds within the central nervous system (CNS). Recent electrophysiological and animals studies suggest that complex spinal mechanisms are involved in the generation of RLS and PLM symptomatology. Dopamine modulation of spinal reflexes through dopamine D3 receptors was recently highlighted in animal models. The present review suggests that RLS is a complex disorder that may result from a complex dysfunction of interacting neuronal networks at one or several levels of the CNS and involving numerous neurotransmitter systems.

Animals↗
PubMed2002

Exploring the relationship between Parkinson disease and restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) and Parkinson disease (PD) are common neurological conditions that respond to dopaminergic therapy. To our knowledge, the relationship between the two has not been thoroughly explored. METHODS: We consecutively queried 303 patients with PD seen in our clinic for the presence of RLS symptoms, and evaluated their condition with the Epworth Sleepiness Scale and other demographic and sleep measures. We then looked for predictors of RLS in these patients with PD. We also compared a larger group of patients with PD/RLS with a group of patients with RLS alone. RESULTS: Of 303 patients with PD, 63 (20.8%) had symptoms of RLS. Neither PD patient demographics nor PD treatments could reliably predict the development of RLS symptoms; however, lower serum ferritin levels were associated with RLS symptoms in our patients with PD (P =.01). In 54 (68%) of the 79 total patients with PD/RLS (including additional patients with PD/RLS seen in the clinic) with reliable age-at-onset data, the PD symptoms preceded the RLS symptoms (chi(2) test, P<.001). Compared with patients with idiopathic RLS (N = 146), patients with PD/RLS (N = 109) were older at RLS onset (P<.001), were less likely to have a family history of RLS (P<.001), and had lower serum ferritin levels (P =.01). CONCLUSIONS: Symptoms of RLS are common in patients with PD; however, except in patients with a family history of RLS, they seem to reflect a secondary phenomenon, perhaps in relation with lower ferritin levels. There is no evidence that RLS symptoms early in life predispose to the subsequent development of PD.

Aged↗
PubMed2005

Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome.

OBJECTIVE: Restless legs syndrome (RLS) is a distressing sensorimotor disorder with a 5% to 10% prevalence in the United States and Western Europe. The nocturnal occurrence of symptoms often leads to severe sleep disturbances. RLS has been reported to be associated with depression and anxiety. The aim of the present study was to investigate the relationship between RLS symptom severity, sleep disturbances, and depressive symptoms. METHOD: Questionnaire data from 100 consecutive patients with idiopathic RLS who had been investigated in our Sleep Disorders Unit from April 1999 to December 2004 were evaluated. Patients were untreated regarding RLS, depression, or sleep disturbances. Severity of RLS was assessed with the International RLS Study Group rating scale (IRLS). Depressive symptoms and subjective sleep quality were determined using the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI), respectively. RESULTS: IRLS scores indicated moderate-to-severe RLS symptoms in the population studied (mean +/- SD IRLS score = 23.6 +/- 6.7). The mean +/- SD BDI score was 9.3 +/- 5.6, with highest values on the "reduced sleep," "loss of energy," and "work difficulties" items, indicating predominating somatic symptoms of depression. Fourteen patients had a BDI score of 15 to 20 ("mild depression"), and 3 patients had a BDI score of 20 to 30 ("mild to moderate depression"). Overall, patients estimated their sleep quality as moderately impaired (mean +/- SD PSQI score = 10.9 +/- 3.7). Severity of RLS correlated with the impairment of subjective sleep quality (r = 0.281, p = .007) but not with self-rated depressive symptoms (r = 0.119, p = .237). CONCLUSION: RLS patients scored high on the somatic items of the BDI, particularly on those related to sleep disturbance, but not on the other items that mostly address cognitive symptoms. Our results indicate that RLS might be associated with some features of depression but not with the full spectrum of a depressive disorder. The relationship between the 2 disorders should be investigated in further studies.

Comorbidity↗
PubMed2004

A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common disorder in patients with end-stage renal disease (ESRD) that causes motor agitation and insomnia. Because RLS has been associated with iron deficiency, we sought to investigate the effects of intravenous (IV) iron dextran on symptoms of RLS in a double-blind placebo-controlled trial. METHODS: Patients determined to have RLS by International RLS Study Group criteria were administered either iron dextran, 1,000 mg, or normal saline IV in a blinded fashion. Patient demographic data were collected, and blood chemistry tests, liver function studies, serum iron levels, ferritin levels, and total iron-binding capacity were obtained at baseline and 1, 2, and 4 weeks postinfusion. Side effects or adverse events to interventions were monitored, and RLS symptoms were assessed by a rating scale at the same intervals. RESULTS: Eleven patients were randomly assigned to the administration of iron dextran, and 14 patients to the administration of saline. RLS severity scores were slightly higher in the placebo group at baseline, but hemoglobin levels, iron stores, and other biochemical parameters did not differ. Although no change in symptoms were seen in the placebo-treated group, significant improvement in RLS symptom scores in response to iron dextran was seen 1 week after infusion (-2; interquartile range [IQR], -6 to -1; P = 0.03, Wilcoxon's rank sums), but was greatest at 2 weeks (-3; IQR, -5 to -2 compared with -1 to 0; P = 0.01). Salutary effects of iron persisted at 4 weeks, but were no longer statistically significant. The significant increase in serum ferritin levels and iron saturation observed in the iron dextran-treated group was not seen in the placebo-treated group. No differences in adverse events were noted between groups. CONCLUSION: High-dose iron dextran infusion is associated with a significant, but transient, reduction in symptoms of RLS in patients with ESRD.

Adult↗
PubMedDate not supplied

Diagnosis and management of sleep apnea syndrome and restless legs syndrome in dialysis patients.

Sleep complaints are very common in patients with end-stage renal disease (ESRD) and contribute to their impaired quality of life. Both obstructive and central sleep apnea syndromes are reported more often in patients on dialysis than in the general population. Impaired daytime functioning, sleepiness, and fatigue, as well as cognitive problems, are well known in patients with sleep apnea. Increasing evidence supports the pathophysiological role of sleep apnea in cardiovascular disorders, which are the leading cause of death in ESRD patients. Uremic factors may be involved in the pathogenesis of sleep apnea in this patient population and optimal dialysis may reduce disease severity. Furthermore, treatment with continuous positive airway pressure may improve quality of life and may help to manage hypertension in these patients. Secondary restless legs syndrome is highly prevalent in patients on maintenance dialysis. The pathophysiology of the disorder may also involve uremia-related factors, iron deficiency, and anemia, but genetic and lifestyle factors might also play a role. The treatment of restless legs syndrome involves various pharmacologic approaches and might be challenging in severe cases. In this article we review the diagnosis and treatment of sleep apnea and restless legs syndrome, with a focus on dialysis patients. We also briefly review current data regarding sleep problems after transplantation, since these studies may indirectly shed light on the possible pathophysiological role of uremia or dialysis in the etiology of sleep disorders. Considering the importance of sleep disorders, more awareness among professionals involved in the care of patients on dialysis is necessary. Appropriate management of sleep disorders could improve the quality of life and possibly even impact upon survival of renal patients.

Humans↗
PubMed2003

Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome.

BACKGROUND: There is a need for an easily administered instrument which can be applied to all patients with restless legs syndrome (RLS) to measure disease severity for clinical assessment, research, or therapeutic trials. The pathophysiology of RLS is not clear and no objective measure so far devised can apply to all patients or accurately reflect severity. Moreover, RLS is primarily a subjective disorder. Therefore, a subjective scale is at present the optimal instrument to meet this need. METHODS: Twenty centers from six countries participated in an initial reliability and validation study of a rating scale for the severity of RLS designed by the International RLS study group (IRLSSG). A ten-question scale was developed on the basis of repeated expert evaluation of potential items. This scale, the IRLSSG rating scale (IRLS), was administered to 196 RLS patients, most on some medication, and 209 control subjects. RESULTS: The IRLS was found to have high levels of internal consistency, inter-examiner reliability, test-retest reliability over a 2-4 week period, and convergent validity. It also demonstrated criterion validity when tested against the current criterion of a clinical global impression and readily discriminated patient from control groups. The scale was dominated by a single severity factor that explained at least 59% of the pooled item variance. CONCLUSIONS: This scale meets performance criteria for a brief, patient completed instrument that can be used to assess RLS severity for purposes of clinical assessment, research, or therapeutic trials. It supports a finding that RLS is a relatively uniform disorder in which the severity of the basic symptoms is strongly related to their impact on the patient's life. In future studies, the IRLS should be tested against objective measures of RLS severity and its sensitivity should be studied as RLS severity is systematically manipulated by therapeutic interventions.

Adult↗
PubMed2003

Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health.

BACKGROUND: Restless legs syndrome is a common yet frequently undiagnosed sensorimotor disorder. In 1995, the International Restless Legs Syndrome Study Group developed standardized criteria for the diagnosis of restless legs syndrome. Since that time, additional scientific scrutiny and clinical experience have led to a better understanding of the condition. Modification of the criteria is now necessary to better reflect that increased body of knowledge, as well as to clarify slight confusion with the wording of the original criteria. SETTING: The restless legs syndrome diagnostic criteria and epidemiology workshop at the National Institutes of Health. PARTICIPANTS: Members of the International Restless Legs Syndrome Study Group and authorities on epidemiology and the design of questionnaires and scales. OBJECTIVE: To modify the current criteria for the diagnosis of restless legs syndrome, to develop new criteria for the diagnosis of restless legs syndrome in the cognitively impaired elderly and in children, to create standardized criteria for the identification of augmentation, and to establish consistent questions for use in epidemiology studies. RESULTS: The essential diagnostic criteria for restless legs syndrome were developed and approved by workshop participants and the executive committee of the International Restless Legs Syndrome Study Group. Criteria were also developed and approved for the additional aforementioned groups.

Age Factors↗
PubMed1986

Restless legs syndrome.

Patients with restless legs syndrome often have difficulty describing their symptoms. Three features characterize the classic syndrome: an unusual, almost indescribable sensation in the lower extremities; an irresistible urge to move the legs, and the exclusive occurrence of the symptoms at rest, with their relief by movement. Restless legs syndrome may cause severe insomnia. Variants of the syndrome, as well as numerous associated conditions, have been described. The etiology is unknown. Clonazepam and carbamazepine are reported to be effective in treating this syndrome.

Adolescent↗
PubMed1996

Restless legs syndrome. A review.

Restless legs syndrome is characterized by unpleasant, deep-seated paresthesias in the legs and sometimes the arms. These sensations occur at rest and are relieved by movement. Sleep disturbance is common. Many patients also have periodic movements of sleep. Mild symptoms of restless legs occur in up to 5% of the population. Restless legs syndrome is idiopathic in most patients, but it may be the presenting feature of iron deficiency and is also common in uremia, pregnancy, diabetes mellitus, rheumatoid arthritis, and polyneuropathy. Treatment of the underlying cause, when possible, usually relieves the symptoms. For patients with severe symptoms, levodopa, bromocriptine mesylate, opioids, carbamazepine, clonazepam, and clonidine hydrochloride have proved to be effective.

Diagnosis, Differential↗
PubMed1996

Restless legs syndrome and paroxetine.

Restless legs syndrome is a frequent dyssomnia with well-known clinical features but uncertain origin and treatment. This paper describes a case of restless legs syndrome worsened by paroxetine. A possible pathogenic hypothesis related to the attributed neurochemical properties of the drug is proposed.

Adjustment Disorders↗
PubMed1983

The restless legs syndrome (Ekbom's syndrome).

The restless legs syndrome is a condition of unknown aetiology characterized by nocturnal paraesthesiae in the lower limbs, an irreversible tendency to move the limbs, pain in the distribution of the paraesthesiae, and psychiatric disturbances. The syndrome may occur at any age and in either sex and usually runs a course over many years with spontaneous improvements and exacerbations. An association with iron deficiency has been suggested but in most cases no apparent cause has been found, and treatment at present is symptomatic with analgesics and sedatives. The differential diagnosis includes phenothiazine-induced akathisia and meralgia paraesthetica.

Diagnosis, Differential↗
PubMed2006

Epidemiology of familial and sporadic restless legs syndrome in Iran.

Restless legs syndrome is one of the most common sleep and movement disorders. For lack of sufficient information on this syndrome in Iran, this study was conducted at Alzahra Hospital, Isfahan, Central Iran, to determine the epidemiology of idiopathic, familial and sporadic forms of the syndrome. From September 1999 to April 2003, 61 patients in two groups were selected. A questionnaire with emphasis on sleep history and neurological history was completed and a thorough physical examination was performed for each patient. Familial and sporadic groups had mean +/- SD ages of 22 +/- 2.1 and 41 +/- 3.2 years, respectively (P < 0.05). Female to male ratio was 2:1. The mean +/- SD ages for women and men were 31 +/- 5.3 and 42 +/- 6.1 years (P < 0.05), respectively. Our findings support the current opinion that restless legs syndrome should be divided into the early-onset disease with a clear genetic component and the late-onset disease with an unclear etiology.

Adult↗
PubMed2003

Factor analysis of the International Restless Legs Syndrome Study Group's scale for restless legs severity.

OBJECTIVE: The International Restless Legs Syndrome Study Group has developed and validated a ten-item scale for assessing the severity of the restless legs syndrome. This International Restless Legs Severity Scale (IRLS) is reported to have a high degree of internal consistency and it has generally been used as a single scale. This study uses a factor analytic approach to evaluate the IRLS for possibly useful subscales. METHODS: A large convenience sample (n=516) of self-identified restless leg syndrome patients completed the IRLS over the Internet. Data were analyzed using principal component analyses. RESULTS: Two primary factors were identified, one with six items related to symptom severity and a second with three items related to impact of the symptoms on life. These accounted for 41.8 and 22.5% of the variance, respectively. CONCLUSIONS: The IRLS can be evaluated using separate subscale scores: one for symptoms and the other symptom impact. The relative merits of these subscale scores versus the score for the entire test need to be evaluated in different situations in further studies, in especially the ones involving assessing responsiveness to treatment effects.

Factor Analysis, Statistical↗
PubMed1998

Encouraging initial response of restless legs syndrome to pramipexole.

Restless legs syndrome (RLS) is a common condition that results in uncomfortable sensations and an urge to move the limbs. Two centers tested a new dopamine agonist, pramipexole, in 23 patients with RLS in a time-limited, open-label, clinical trial. After 4 weeks or more, 19 patients reported significant improvement as assessed by the short International Restless Legs Syndrome Study Group questionnaire (p < 0.0001). These encouraging preliminary results justify larger, controlled trials for pramipexole in patients with RLS.

Adult↗
PubMed1998

Immobilization tests and periodic leg movements in sleep for the diagnosis of restless leg syndrome.

Patients with restless leg syndrome (RLS) complain of motor restlessness, usually occurring while they rest in the evening. Two immobilization tests have been described to assess leg restlessness in these patients. In the first test, the patient sits in bed with his or her legs outstretched while electromyograms are recorded from right and left anterior tibialis muscles for an hour (Suggested Immobilization Test [SIT]); in the second test, the legs are immobilized in a stretcher (Forced Immobilization Test [FIT]). In the current study, the SIT and the FIT were compared in patients with RLS and normal control subjects matched for age and sex. More leg movements were seen in patients than in controls during immobilization tests, especially the SIT. These movements were periodic, occurring at a frequency of approximately one every 12 seconds. The SIT (index > 40) was found to discriminate between RLS and control subjects better than the FIT (index > 25). Patients were also recorded during two consecutive nights to measure periodic leg movements in sleep (PLMS). A SIT index greater than 40 and a PLMS index greater than 11 (highest PLMS index of 2 consecutive nights) were found to discriminate patients with RLS from control subjects with similar power. With each of these two measures, the clinical diagnosis was correctly predicted in 81% of patients and 81% of the control subjects. The SIT has several advantages over the measure of the PLMS index; it does not require an all-night polygraphic recording and can be administered several times a day to measure circadian fluctuation of motor restlessness.

Adult↗