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PubMed2000

Restless legs syndrome: clinical features and treatment.

Restless legs syndrome (RLS), widely recognized as a definite clinical entity, has an estimated prevalence of 1 to 15% in different ethnic populations. However, it remains an underdiagnosed condition and its symptoms are frequently ascribed to stress and anxiety. Advancement in modern imaging techniques and clinical drug trials provide evidence of an impaired dopaminergic system in RLS. Management involves investigating and correcting treatable secondary causes, avoidance of aggravating factors, and pharmacologic therapy. Recent controlled trials have demonstrated the effectiveness of dopamine agonists such as pramipexole and pergolide. Additional research is needed to further elucidate the pathophysiology of RLS, through obtaining post-mortem specimens and refinement of neuroimaging and neurophysiologic techniques. Isolation of specific genetic loci in familial cases would enable better characterization of distinct clinical and genetic subsets of RLS and result in better understanding of this disease at the molecular level.

Adrenergic Agonists↗

PubMed2007

Current guidelines and standards of practice for restless legs syndrome.

Algorithms for treatment of restless legs syndrome (RLS) include both nonpharmacologic and pharmacologic therapy. Patients with RLS are divided into 3 groups: (1) those with intermittent RLS symptoms; (2) those with daily RLS symptoms; and (3) those whose symptoms are refractory to standard treatments. Many patients do not require medication, and symptoms often can be relieved with good sleep hygiene and avoidance of medications and factors that provoke symptoms. Recent large-scale clinical trials have proved the efficacy of therapy for RLS when it is required. Several classes of medications are helpful, but dopaminergic therapy appears to be most effective and relieves symptoms rapidly. The first step in managing RLS is to ensure that there is an adequate diagnosis; this involves discriminating RLS from other conditions that may share a number of features. Finally, it is important to tailor treatment to the needs of each individual patient.

Algorithms↗

PubMed1994

A clinical, serological and neurophysiological study of restless legs syndrome in rheumatoid arthritis.

The restless legs syndrome (RLS), defined by Gibb and Lees criteria, was investigated in patients with RA. RLS symptoms were more frequent in RA patients (25%) than in non-RA controls with OA or seronegative arthropathy (4%). RLS was significantly more common in females. Judged by a variety of clinical and laboratory indices, RA disease severity and current disease activity were greater in patients with RLS than in RA patients unaffected by RLS. In five out of 14 RLS patients undergoing neurophysiological study, delays in the P40 component of posterior tibial somatosensory evoked potentials (SSEPs) were observed suggesting the existence of myelopathy, whilst in another four RLS patients evidence of peripheral neuropathy was found. Though the higher frequency of neurophysiological abnormalities in RA patients with RLS was not statistically significant, possibly because of the small numbers of patients studied, these data suggest that RLS symptoms in RA may reflect the presence of neurological disorder.

Aged↗

PubMed2004

Mutational analysis of neurotensin in familial restless legs syndrome.

A susceptibility locus for restless legs syndrome (RLS) has been identified recently on chromosome 12q. This region contains several transcribed genes including neurotensin (NTS), which, as an important modulator of the dopaminergic transmission, represents a strong functional and positional candidate in the context of RLS. In this study, NTS was evaluated for mutational analysis. A panel of 19 individuals from 4 families supporting linkage to 12q was investigated using a combined denaturing high-performance liquid chromatography (dHPLC) and direct sequencing method. Analysis of the NTS genomic sequence revealed 2 intronic polymorphisms and 1 variant located in the 5' untranslated region (UTR). None of the observed variants co-segregated with RLS and no disease-associated polymorphisms were detected in any of the analyzed families. Based on these results, it is unlikely that NTS is the gene responsible for RLS in chromosome 12-linked families.

5' Untranslated Regions↗

PubMed2005

Cognitive deficits associated with restless legs syndrome (RLS).

BACKGROUND AND PURPOSE: Restless legs syndrome produces significant chronic sleep loss, which despite not causing expected profound sleepiness, might nonetheless produce cognitive deficits similar to those seen with acute sleep deprivation, i.e. involving mostly pre-frontal cortical (PFC) functioning. PATIENTS AND METHODS: Sixteen patients off RLS treatment for at least 2 weeks and 15 age- and gender-matched control subjects had polysomnograms (PSGs) on two consecutive nights. Cognitive tests were given in the morning after the second night. Six cognitive tests were used: two Verbal Fluency tests and the Trail Making tests were selected to be particularly sensitive to PFC function and sleep loss. Porteus Mazes and the Stroop Test were selected to reflect more general frontal and executive function. The Colored Progressive Matrices were used to assess general cognitive skills. RESULTS: RLS patients compared to controls showed significant (P<0.05) and sizeable (20-40%) deficits on two of the three PFC tests and marginally non-significant deficit (P<0.1) on the third. The other three tests showed no significant differences. CONCLUSIONS: The results indicate that RLS patients show cognitive deficits similar to that reported for one night of sleep loss.

Aged↗

PubMed1999

How to help patients with restless legs syndrome. Discerning the indescribable and relaxing the restless.

Restless legs syndrome is a common, potentially disabling condition that affects about 10% to 15% of the general population and yet is often unrecognized and misdiagnosed. It is mainly diagnosed clinically and only rarely requires polysomnography. The condition is usually primary and treatable. First, however, secondary causes should be sought, especially iron deficiency and peripheral neuropathy, because when the source is an accompanying factor or condition, the syndrome may be curable. The most effective drugs are dopaminergic agents, clonazepam, opioids, gabapentin, and clonidine. Additional agents are available that may be beneficial as add-on or alternative therapy.

Anti-Anxiety Agents↗

PubMed1986

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.

Drug Evaluation↗

PubMed2004

Childhood-onset restless legs syndrome.

The clinical characteristics of childhood-onset restless legs syndrome are described. Thirty-two of 538 subjects (5.9%) examined in our sleep disorders center received diagnoses of restless legs syndrome. They were classified based on published criteria into probable (n = 9/32 or 28%) and definite (n = 23/32 or 78%) categories. Apart from an earlier age of diagnosis of the probable group, no differences were found between the two categories. Sleep onset or sleep maintenance insomnia was the most common symptoms, being present in 28 of 32 subjects (87.5%). Inattentiveness was seen in 8 of 32 subjects (25%). Serum ferritin levels were measured in 24 of 32 subjects and were below 50 microg/L in 20 of 24 subjects (83%). A family history of restless legs syndrome was present in 23 of 32 (72%) subjects, with mothers almost three times more likely to be affected than fathers (p = 0.02). We conclude that iron deficiency and a strong family history are characteristic of childhood-onset restless legs syndrome.

Adolescent↗

PubMed2003

Analysis of CAG repeat expansions in restless legs syndrome.

STUDY OBJECTIVES: A relatively high prevalence of restless legs syndrome symptoms has been recently reported in a substantial proportion of patients affected with spinocerebellar ataxia type 3. Our aim was to investigate whether there is a common genetic etiology between restless legs syndrome and spinocerebellar ataxia type 3. DESIGN: Systematic differences in the number of spinocerebellar ataxia type 3 trinucleotide repeat were investigated by means of an association study. The relationship between the size of the expanded alleles and several clinical features was also considered. PARTICIPANTS AND SETTING: 125 extensively characterized restless legs syndrome patients compared with 188 healthy controls matched for ethnic background. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: No CAG repeat expansions in the pathologic or intermediate range were detected in any of the examined subjects, including patients and controls. A similar allelic distribution was observed in both groups (Mann-Whitney U test = 78406; P = 0.99). Moreover, stratification analyses of the patients' samples according to different clinical and polysomnographic variables disclosed no significant differences. CONCLUSIONS: These results do not provide evidence toward an involvement of large CAG trinucleotide expansions at the spinocerebellar ataxia type 3 locus in idiopathic restless legs syndrome.

Female↗

PubMed1998

Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder.

Sleep disruption can lead to symptoms of attention-deficit hyperactivity disorder (ADHD) in children. Since periodic limb movement disorder and/or restless legs syndrome can cause sleep disruption, we assessed whether these two specific sleep disorders are likely to occur in children with ADHD. We asked a series of 69 consecutive parents of children with ADHD questions about the symptoms of periodic limb movement disorder. Based on a positive response to these periodic limb movement disorder queries, 27 children underwent all-night polysomnography. Eighteen children (aged 2 to 15 years) of the 27 (26% of the 69 children with ADHD) had 5 or more periodic leg movements in sleep per hour of sleep and had complaints of sleep disruption, thus fulfilling the criteria for periodic limb movement disorder. A comparably age- and sex-matched group of children referred to a sleep laboratory for sleep complaints but without ADHD showed only a 5% prevalence (2 of 38 subjects) of periodic leg movements in sleep (P=.017). Eight of the 18 children with ADHD and periodic limb movement disorder and one of the two control patients with periodic limb movement disorder had both a personal and parental history of restless legs syndrome symptomatology. This study further documents the occurrence of periodic limb movement disorder and restless legs syndrome in children and is the first large-scale study establishing a possible comorbidity between ADHD and periodic limb movement disorder. We propose that the sleep disruption associated with periodic limb movement disorder and restless legs syndrome and the motor restlessness of restless legs syndrome while awake could contribute to the inattention and hyperactivity seen in a subgroup of ADHD-diagnosed children.

Adolescent↗

PubMed2002

Restless legs syndrome and periodic limb movement disorder.

Restless leg syndrome and PLMD are nocturnal movement disorders associated with significant adverse effects on the health and well-being of patients and their families [66]. Although the pathophysiological basis remains to be fully described, current research points to abnormalities in CNS function and neurotransmitter systems. The accurate diagnosis of RLS and PMD requires a thorough history, physical examination, diagnostic tests, and often, a referral to a sleep disorders specialist. Considering the prevalence of these conditions and their negative impact, nurses should be well-versed in the assessment and management of these problems as well as in the appropriate education of patients and their families. Nursing research is greatly needed, particularly with regard to the development and testing of biobehavioral interventions designed to decrease associated symptoms and improve clinical outcomes. Finally, because of the complexity of the clinical presentation of RLS and PLMD, this population of patients presents nurse clinicians and researchers alike with an extraordinary opportunity for interdisciplinary collaboration.

Diagnosis, Differential↗

PubMed2004

[Six months treatment of restless legs syndrome with levodopa/benserazide in domiciliary practice].

Restless legs syndrome is a common neurological condition with 2-10% prevalence in the general population. Patients suffer from uncomfortable or unpleasant sensations in legs or arms and motor restlessness with a compelling desire to move the extremities. The symptoms worsen at rest with at least temporary relief by activity but also later in the day and in the evening. Dopaminergic drugs are considered to be the first choice in therapy, however, only levodopa/benserazide is approved until now. In this six months observational study, eighty patients with diagnosed RLS were treated with levodopa/ benserazide. The RLS symptoms improved in 90%, 77.5% of the patients continued with the treatment after the end of the study. Levodopa/Benserazide proved to be efficacious independently of severity of RLS and was well tolerated in long-term therapy.

Adult↗

PubMed1993

Restless legs syndrome in the elderly.

The prevalence and significance of restless legs syndrome was assessed in 307 patients presenting to an acute-care geriatric medical service. Fifteen patients (5%) had restless legs syndrome; 13 (87%) of these patients had insomnia and 10 (67%) reported troublesome or frequent leg symptoms. Of 147 patients with current insomnia, iron deficiency (serum ferritin < 18 ng/ml) was present in 4/13 (31%) patients with restless legs and 8/134 (6%) patients without restless legs (P < 0.025). Improvement in symptoms of restless legs was noted with iron repletion. These findings suggest that restless legs syndrome is relatively common in the elderly and causes significant discomfort and sleep disturbance. Iron deficiency is a common and treatable cause.

Aged↗

PubMed2006

Restless legs syndrome triggered by heart surgery.

This report presents the case of a 9-year-old child with a familial history of restless legs syndrome who began to complain of restless legs syndrome symptoms after heart surgery. Hypotheses on the potential interactions between genetic and environmental factors in the development of her restless legs syndrome are discussed. Increasing evidence supports reduced brain iron in the pathophysiology of idiopathic restless legs syndrome. It is possible that the child inherited a compromised brain and peripheral iron regulation, which predisposed her to restless legs syndrome. The interaction between her dysfunctional iron management and her intraoperatory blood loss may have led to a significant decrease in brain iron, triggering restless legs syndrome symptoms. Other factors, such as immobilization and sleep deprivation after surgery, may have contributed to trigger the restless legs syndrome symptoms. If confirmed by further evidence, this patient suggests the need to carefully monitor for restless legs syndrome symptoms in young surgical patients who present with a familial history of restless legs syndrome.

Child↗

PubMedDate not supplied

[Restless leg syndrome. Diagnosis and treatment].

INTRODUCTION: The restless legs syndrome is characterized by an unpleasant sensation in the legs which causes an imperative need to move the legs and is therefore considered to be a disorder of movement. When it appears before going to sleep, it may interfere with falling asleep and lead to a sleep-deficit. DEVELOPMENT AND CONCLUSIONS: It is a clinical condition with a satisfactory treatment, and improvement of the associated sleep disorder. The etiology is unknown, sometimes it is familial. The syndrome is increasingly often diagnosed, particularly in association with iron deficiency, during pregnancy, in chronic renal failure and in patients with peripheral neuropathy. Polysomnography is not necessary, unless one suspects an associated disorder of periodic leg movements. Treatment is by dopaminergic, opiate, benzodiazepine, anticonvulsant drugs or clonidine.

Anticonvulsants↗

PubMed2002

Clinical symptomatology and treatment of restless legs syndrome and periodic limb movement disorder.

Patients with restless legs syndrome (RLS) suffer from sensory and motor symptoms evoked in the limbs at rest. Symptoms increase in the evening and during the night. The circadian rhythm and the presence of involuntary periodic limb movement in sleep (PLMS) which are frequently associated with arousals probably cause the leading symptom of sleep disturbances in RLS. Patients who do not have typical RLS symptoms but whose polysomnography shows PLMS that either impact on sleep continuity or daytime functioning are diagnosed as having the periodic limb movement disorder (PLMD). Dopaminergic agents such as levodopa/dopa decarboxylase inhibitor (DDI) and dopamine agonists are considered the treatment of choice for RLS and PLMS. This article gives an overview of the epidemiology, pathophysiology, clinical symptomatology and diagnosis of RLS and PLMD and focuses on treatment strategies in both disorders.

Corpus Striatum↗

PubMed2001

[Restless legs syndrome. Therapy according to plan].

The restless legs syndrome is characterised by an imperative desire to move lower legs because of paraesthesias or dysesthesias sometimes associated with pain witch occur at rest. The symptoms temporary relief by activity. Worsening of symptoms in the evening or at night are typical. Therefore patients with RLS often have problems with initiating and maintaining sleep. In polysomnographic investigation typical periodic limb movements in sleep (PLMS) can be found. The treatment of choice for RLS is levodopa. In case of augmentation or time shifting transfer to dopamine agonists should be considered. Alternative medications are opioids, benzodiazepines or some antiepileptic drugs (carbamazepine or gabapentin).

Central Nervous System Agents↗

PubMed2006

[Neurophysiological and neuroimaging studies for restless legs syndrome and periodic leg movement disorder].

The restless legs syndrome (RLS) is a clinical diagnosis based on the four essential criteria defined by the International Restless Legs Syndrome Study Group (IRLSSG). An idiopathic form can be separated from a symptomatic form. Neurophysiological studies have investigated the pathophysiology of the idiopathic RLS or have been used to exclude a symptomatic cause, in particular polyneuropathy. So far cortical excitability changes, corticomotor, somatosensory and auditory pathways, spinal cord excitability, B-wave rhythm and cycling alternating pattern, as well as reflex mechanisms have been investigated by electroencephalography, evoked potentials, Bereitschaftspotentials, nerve conduction and thermal threshold measurements, electromyography, transcranial Doppler sonography, measurements of the spinal flexor reflex as well as neuroimaging techniques. The etiology of the RLS cannot be revealed by these methods, neurophysiological studies in RLS are, however, useful for a better understanding of the pathophysiology and for exclusion of a polyneuropathy or other symptomatic causes. In addition to neurophysiological investigations, small fiber neuropathy, which seems to be a more common finding in RLS patients than expected to date, may need biopsy for confirmation. This review will focus on investigations of the different systems involved with diverse neurophysiological methods.

Brain↗