Effects of restless legs syndrome (RLS) on sleep

Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move the legs, usually accompanied or caused by uncomfortable sensations in the legs. Symptoms are worse in the evening or at night than during the day and generally begin or worsen during periods of rest or inactivity. The chronic sleep disturbance often associated with RLS is likely due, at least in part, to the circadian nature of the symptoms. The relationship between disturbed sleep and reduced daytime functioning is well known and thus the accurate diagnosis and effective management of RLS is imperative.     

Restless legs syndrome

The restless legs syndrome (RLS) is a common neurological disorder to take possession of increasing attention. RLS is characterized by an urge to move the legs, usually accompanied by uncomfortable or unpleasant sensations, that occurs or worsen at rest and is relieved by activity. The symptoms of RLS have a major impact on nocturnal sleep and daytime functions. The clinical diagnostic criteria were established and published in 2003 by International Restless Legs Syndrome Study Group (IRLSSG). All four essential criteria must be met for a positive diagnosis. However, RLS encompassed an idiopathic form of genetic or unknown origin and secondary forms associated with many causes. Special awareness should be kept for differential diagnosis such as uremia, iron deficiency anemia, polyneuropathy, rheumatoid arthritis, and other neurodegenerative diseases. Polysomnography, actinography, L-dopa loading test, and suggested immobilization test (SIT) are helpful tools to reduce the diagnostic puzzle of false positive and false negative. Pathophysiological concepts of RLS are essentially based on the neuroimaging and neurophysiological data to assume a dysfunction of the dopaminergic system, possibly on the All neuron group localized in the hypothalamus. These neurons modulate spinal excitability and alter the sensory processing predominantly of leg afferents. Treatment may be closely linked to the dopaminergic system and iron metabolism. Dopaminergic stimulation with levodopa or dopamine agonists is the first choice in idiopathic restless legs syndrome, but the long-term adverse effect of augmentation should be carefully monitored.     

Preface

Four essential diagnostic criteria for restless legs syndrome (RLS) have been identified. Patients experience an urge to move the legs, which typically begins or worsens during periods of rest. The symptoms are at least partially relieved by movement, and are typically worse in the evening and night than in the day. All four criteria are necessary to confirm the diagnosis of RLS. In addition, a family history of RLS, the presence of periodic leg movements in sleep, and a positive response to dopaminergic therapy are useful supportive clinical features to confirm the diagnosis. Whilst many cases of RLS are idiopathic, secondary RLS is often observed in pregnant women, patients who have severe renal dysfunction, or in those with iron deficiency. Several other conditions have symptoms similar to those of RLS, but a detailed patient history is usually sufficient to identify these differential diagnoses. The accurate diagnosis and appropriate treatment of RLS should result in considerable improvements in patients’ quality of life.     

RLS patients: who are they?

Four essential diagnostic criteria for restless legs syndrome (RLS) have been identified. Patients experience an urge to move the legs, which typically begins or worsens during periods of rest. The symptoms are at least partially relieved by movement, and are typically worse in the evening and night than in the day. All four criteria are necessary to confirm the diagnosis of RLS. In addition, a family history of RLS, the presence of periodic leg movements in sleep, and a positive response to dopaminergic therapy are useful supportive clinical features to confirm the diagnosis. Whilst many cases of RLS are idiopathic, secondary RLS is often observed in pregnant women, patients who have severe renal dysfunction, or in those with iron deficiency. Several other conditions have symptoms similar to those of RLS, but a detailed patient history is usually sufficient to identify these differential diagnoses. The accurate diagnosis and appropriate treatment of RLS should result in considerable improvements in patients' quality of life.     

PREFACE

Four essential diagnostic criteria for restless legs syndrome (RLS) have been identified. Patients experience an urge to move the legs, which typically begins or worsens during periods of rest. The symptoms are at least partially relieved by movement, and are typically worse in the evening and night than in the day. All four criteria are necessary to confirm the diagnosis of RLS. In addition, a family history of RLS, the presence of periodic leg movements in sleep, and a positive response to dopaminergic therapy are useful supportive clinical features to confirm the diagnosis. Whilst many cases of RLS are idiopathic, secondary RLS is often observed in pregnant women, patients who have severe renal dysfunction, or in those with iron deficiency. Several other conditions have symptoms similar to those of RLS, but a detailed patient history is usually sufficient to identify these differential diagnoses. The accurate diagnosis and appropriate treatment of RLS should result in considerable improvements in patients’ quality of life.     

Restless legs syndrome and its treatment by dopamine agonists

The restless legs syndrome (RLS) characteristically presents with an irresistible urge to move that is most often accompanied by creeping sensations deep in the limbs. Occasionally the upper limbs can also be affected. RLS symptoms occur at rest and are typically more intense at night and at bedtime. Some patients complain about involuntary leg movements, so-called periodic limb movements (PLM), while at rest or PLM have been observed by the bed partner. Often, patients have to get out of bed several times at night, to relieve themselves of their disagreeable sensations.The prevalence of RLS is estimated to be about 5%. Up to now only three classes of drugs have been systematically evaluated for treatment of RLS: benzodiazepines, opioids and dopaminergic agents.The most consistent results have been obtained with dopaminergic drugs. Several studies have shown that L-dopa given with a peripheral decarboxylase inhibitor at a 10:4 ratio is effective in treating RLS. Controlled studies using polysomnographic recordings in a double-blind design showed that L-dopa administered at night produces a significant reduction of RLS occurring at bedtime and of PLM, which are often associated with nocturnal arousals. In most cases, L-dopa 100mg, in conjunction with the decarboxylase inhibitor carbidopa or benserazide 25mg, suppresses RLS although a rebound of PLM may be observed in the last part of the night. The two major adverse effects frequently seen in patients treated with L-dopa are:Augmentation is one of the limiting factors of L-dopa therapy; thus, alternative treatment options are of major interest. In several open treatment trials performed with pergolide, patients reported a marked improvement of RLS symptoms including sleep problems. Mild symptoms of augmentation under pergolide treatment have been reported from single patients. In another 6-month open label trial, pergolide proved to be effective in patients who developed augmentation under L-dopa by relieving daytime symptoms after switching to pergolide.Most recently, the results of these open label trials have been replicated in a randomized, placebo-controlled, double-blind multicenter trial. Treatment with a single evening dose of 0.25-0.75mg pergolide resulted in a significant improvement of almost all subjective and objective parameters. Under pergolide, patients rated their RLS symptoms and sleep disturbances much less severe and polysomnographic recordings also revealed a significant improvement of all important sleep parameters. To prevent peripheral side-effects such as nausea or orthostatic hypotension, pergolide should be slowly up-titrated or domperidone should be added. Under these conditions, no major side-effects have been observed in treatment trials with pergolide in dosages up to 1.25mg.Pergolide with a half-life of 12-16h thus appears to be an appropriate drug in the therapy of RLS especially in those patients who developed augmentation under L-dopa therapy. Owing to the remarkable therapeutic effect of pergolide on RLS symptom control, other dopamine agonists are presently being tested for the treatment of RLS.     

The clinical neurophysiology of the restless legs syndrome and periodic limb movements. Part I: diagnosis, assessment, and characterization.

OBJECTIVE: The restless legs syndrome is a common sensorimotor disorder impacting on sleep which has been known for centuries, but only recently become recognized as a significant clinical and pathophysiological problem. The definition of RLS has evolved until certain key clinical features have been defined as diagnostic, while others are strongly associated: the urge to move is seen as primary. Epidemiology suggests ethnic variation with highest frequency in populations of European origin; family and genetic studies support a genetic basis to many idiopathic cases while links to secondary disorders usually involving low iron stores are also known. Abnormalities of brain iron transport and consequent dysfunction of the dopamine system are suspected sources of the disorder. METHODS: The literature was searched for all references relating clinical neurophysiologic investigations to the diagnosis, assessment, and characterization of RLS. RESULTS: RLS is defined clinically and diagnosed by medical history while its frequent concomitant, periodic limb movements (PLM), must be diagnosed by polysomnography or movement recording. Severity of RLS is generally assessed by subjective measures, but sleep recording and measurement of PLM frequency and association with sleep disruption are also used to measure severity. A provocative test, the suggested immobilization test, can also be used with both subjective and movement recording. RLS and PLM in RLS are both associated with the circadian cycle and are maximal early in the sleep period. PLM appear to be associated both with unstable EEG phases involving the cyclic alternating pattern and cyclical autonomic changes whose initiation may precede the muscle activity. CONCLUSIONS: While RLS remains a subjective disorder, neurophysiologic measures have been important, especially for assessment. Ambulatory methodologies may offer the most accurate and economical means of assessing motor activity as a key marker of RLS and of accurately measuring PLM from night to night. As the pathophysiology of RLS is better understood, more focused techniques may be developed to measure its presence and severity in individual patients.     

Épidémiologie du syndrome des jambes sans repos

IntroductionRestless legs syndrome (RLS) is a chronic sensorimotor disorder where patients complain of an almost irresistible urge to move their legs. This urge can often be accompanied by pain or other unpleasant sensations, it either occurs or worsens with rest particularly at night, and improves with activity. The International Restless Legs Syndrome Study Group has established four essential criteria for clinical diagnosis of RLS.State of artAffecting an estimated 7.2 to 11.5% of the adult population, the symptoms of RLS may be associated with significant sleep disturbance and may have a negative impact on quality of life. The prevalence of RLS increases with age, and women are more frequently affected than men. In France, the estimated prevalence is 8.5%. Among sufferers, 4.4% complain of very severe symptoms. Although RLS is mainly idiopathic, several clinical conditions have been associated with it, especially iron deficiency with or without anemia, end-stage renal disease and pregnancy. These conditions may share a common pathophysiological mechanism involving a disorder of iron metabolism. By contrast, controversy persists as to whether polyneuropathy, particularly when associated with diabetes, is to be considered as an important cause of secondary RLS. This association is difficult to demonstrate as conventional electromyography is not adequate to detect small fiber neuropathy often associated with diabetes.Conclusion and perspectivesRLS is often underdiagnosed and few subjects receive recommended RLS drug treatment. There is a clear need for complementary education to improve the accurate diagnosis of RLS. Indeed, better knowledge of this syndrome is a prerequisite to prompt an appropriate therapeutic management.     

Restless legs syndrome and periodic limb movements in sleep: clinical features,epidemiology, diagnosis

In this review article we summarise the clinical features, epidemiology and differential diagnosis of the Restless Legs Syndrome (RLS) and Periodic Limb Movements in Sleep (PLMS). RLS and PLMS belong to the most common causes which disturb sleep, and the RLS prevalence in the general population is estimated to range from 5 to 15%. The RLS is encountered in 10-20% of patients presenting with a problem of initiating and maintaining sleep, and in over 10% of patients with excessive daytime sleepiness. The RLS is characterised by unpleasant sensations felt deep in the legs, usually between the ankle and knee, but occasionally involving also the upper limbs or the trunk, and occurring at rest, especially at bedtime. The paresthesias are accompanied by motor restlessness and by an urge to move the limb, which results in a temporary relief of the symptoms. In virtually all of the sleeping RLS patients PLMS are observed. These are stereotyped, periodic jerking movements of a non-epileptic origin consisting in an extension of the big toe and dorsiflexion of the ankle with an occasional flexion of the knee and hip. PLMS are accompanied by usually short awakenings or transient arousals as demonstrated by sleep LEG resulting in sleep disruption. In establishing the diagnosis of RLS/PLMS idiopathic and secondary forms should be distinguished, and in particular, a number of other conditions (e.g. uremia or iron-deficiency) need to be ruled out. The clinical diagnosis of the RLS is based on the criteria of The International Restless Legs Syndrome Study Group, and the most useful laboratory support is gained from all-night polysomnography and high-resolution actography.     

Periodic leg movements in RLS patients as compared to controls: Are there differences beyond the PLM index?

ObjectiveTo characterize periodic leg movements (PLM) and their association with sleep disturbances in drug-free patients with restless legs syndrome (RLS) and healthy subjects without sleep complaints.MethodsPolysomnographic recordings of 95 patients with idiopathic RLS and 31 age-matched controls were compared, and correlation analysis between sleep efficiency and PLM variables was performed. All patients and controls were free of medication for 10 days prior to polysomnography.ResultsPLM measures revealed a significantly longer mean duration of single PLM during wakefulness and non rapid eye movement (NREM) sleep in RLS patients as compared to controls. PLM indices were higher in RLS patients than in controls during all sleep stages, but not during wakefulness and slow wave sleep. A significantly higher number of PLM sequences was found in RLS patients than in controls. In RLS patients decreased sleep efficiency was associated with a higher number and a shorter duration of PLM sequences.ConclusionsThe mean duration of single PLM might be an appropriate parameter to discriminate between healthy subjects with PLM and patients with RLS. High numbers of PLM sequences of short duration might be an indicator for the decreased sleep quality in RLS patients.     

Restless legs syndrome and periodic limb movement disorder in the elderly

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an urge to move the extremities, mostly the legs, caused or accompanied by unpleasant sensations in the affected limbs. Symptoms appear or increase in the evening or during the night and at rest. Sleep disturbances are the most frequent reason why patients seek medical aid. The diagnosis of periodic limb movement disorder (PLMD) requires polysomnographic confirmation and relies on the exclusion of other causes of sleep disturbances. The diagnosis of RLS is a clinical one and usually based on the patient's history. Diagnosis criteria should be applied in a modified form in the cognitively impaired elderly. The newly revised criteria emphasize behavioral indicators and supportive features in diagnosing RLS in this special population. Prevalence of both disorders increases strongly with age. Epidemiological studies revealed a 9% to 20% prevalence of RLS and an estimated 4% to 11% prevalence of PLMD in the elderly. Recent studies indicate RLS occurring approximately twice as often in older women than in older men. Treatment with dopaminergic drugs, opioids, anticonvulsants or hypnotics are usually well tolerated in the elderly. However, interaction with other medications and the possibility of severe sedation due to slower metabolism in the elderly should be considered.     

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.     

Epidemiology and clinical findings of restless legs syndrome

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.     

不宁腿综合征

不宁腿综合征为临床常见中枢神经系统感觉运动障碍性疾病,发病机制尚不明确,与遗传因素或多巴胺能系统功能失调有关。发病原因与缺铁性贫血、妊娠、免疫系统疾病、肾衰竭、糖尿病、周围神经病等有关。临床主要表现为感觉障碍、运动症状,并于休息时、傍晚或夜间出现或加重。以铁离子、多巴胺制剂、多巴胺受体激动药、抗癫痂药及阿片类药物为主要治疗药物,     

Sensory symptoms in restless legs syndrome: the enigma of pain

Restless legs syndrome (RLS) is a common sensorimotor condition characterized by an urge to move the legs, worsening of symptoms at rest and during the evening/night, and improvement of symptoms with movement. Our review explores the role and impact of sensory symptoms in RLS. The phenomenology of RLS is discussed, highlighting the difficulty patients have in describing their sensations and in differentiating between sensory and motor symptoms. Sensory symptoms have a significant impact on quality of life but remain much less well understood than motor symptoms and sleep disturbances in RLS. Although RLS symptoms usually are not described as painful, sensory manifestations in RLS do share some similarities with chronic pain sensations, and RLS frequently occurs in chronic pain and neuropathic conditions. Peripheral neuropathies may account for some of the sensory disturbances in secondary RLS, while alterations in central somatosensory processing may be a more viable explanation for the sensory disturbances in primary RLS. The effectiveness of analgesics in treating RLS supports the concept of abnormal sensory modulation in RLS and suggests an overlap between pain modulatory pathways and sensory disturbances. Future studies are needed to better understand the experiential and biologic aspects of altered sensory experiences in RLS.     

Levodopa for idiopathic restless legs syndrome: evidence-based review.

Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. The prevalence of RLS is estimated at 2.7 to 5% of adults and it is more common in women. The treatment of RLS with levodopa has been reported thus a systematic synthesis of evidence is necessary to evaluate the effectiveness and safety of levodopa for RLS. Systematic review of randomized or quasi-randomized, double blind trials on levodopa. Relief of restless legs symptoms marked on a validated scale, subjective sleep quality, sleep quality measured by night polysomnography and actigraphy, quality of life measured by subjective measures, adverse events associated with the treatments. Nine eligible clinical trials were included. The subjective analyses of these studies showed contradictory results, although the objective analyses showed that treatment group had a statistically significant improvement of periodic leg movement (PLM) index, favoring the treatment group. The most commonly adverse event seen was gastrointestinal symptoms. The short-term treatment with levodopa was demonstrated effective and safety for PLM, but there was only few trials assessing long-term treatment and the augmentation phenomenon in RLS. Further long-term randomized controlled trials using standard follow-up measurements as the International RLS Study Group Rating Scale are necessary.     

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.

     

Alterations of Functional Connectivity in Patients With Restless Legs Syndrome

Restless legs syndrome (RLS) is a common neurological illness marked by a strong desire to move one’s legs, usually in association with uncomfortable sensations. Recent studies have investigated brain networks and connectivity in RLS. The advent of network analysis has greatly improved our understanding of the brain and various neurological disorders. A few studies have investigated alterations in functional connectivity in patients with RLS. This article reviews functional connectivity studies of patients with RLS, which have identified significant alterations relative to healthy controls in several brain networks including thalamic, salience, default-mode, and small-world networks. In addition, network changes related to RLS treatment have been found, including to repetitive transcranial magnetic stimulation, transcutaneous spinal cord direct-current stimulation, and dopaminergic drugs. These findings suggest that the underlying pathogenesis of RLS includes alterations in the functional connectivity in the brain and that RLS is a network disorder.     

Restless legs syndrome

Restless legs syndrome (RLS), first described in 1672 and given its name in 1945, is one of the most common sleep and movement disorders. Modern population-based studies demonstrate a prevalence between 5% and 15% in adult white populations. According to the diagnostic criteria, RLS is defined as an irresistable desire to move limbs, usually associated with paresthesias/dysesthesias and motor restlessness. The symptoms start or worsen at rest and improve with activity. Additionally, the symptoms worsen in the evenings and/or nights, which often results in disturbance of sleep with daytime tiredness. There is often a family history of RLS. Initially, the disease course is usually fluctuating and later may become continuous or chronic-progressive. The diagnosis is based on the patient history and is supported by a normal neurological examination. RLS is confirmed by the finding of periodic limb movements (PLM) in polysomnographic investigations and by a response to dopaminergic medication. A large number of studies have confirmed the effect of levodopa (L-dopa) in the treatment of RLS. A majority of the patients treated over a longer period of time with L-dopa, however, develop problems with an effect called augmentation, where the RLS symptoms begin appearing earlier during the day and involve new parts of the body with increasing severity. A large number of studies have now confirmed that dopamine agonists can also be effective in RLS therapy, and that this treatment seems to involve less risk for augmentation. This paper provides a general review of RLS with a focus on current treatment options.