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Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group.

A large International Restless Legs Syndrome (RLS) Study Group has been formed. As its first task, the group has taken upon itself the role of defining the clinical features of the RLS. As minimal criteria for diagnosis, the group proposes the following four features: (a) desire to move the extremities, often associated with paresthesias/dysesthesias; (b) motor restlessness; (c) worsening of symptoms at rest with at least temporary relief by activity, and (d) worsening of symptoms in the evening or night. Other features commonly seen in RLS include sleep disturbance, periodic limb movements in sleep and similar involuntary movements while awake, a normal neurological examination in the idiopathic form, a tendency for the symptoms to be worse in middle to older age, and, in some cases, a family history suggestive of an autosomal dominant mode of inheritance.

Age of Onset↗

Restless legs syndrome.

BACKGROUND: Restless legs syndrome is a common but not well-recognized central nervous system disorder that leads to insomnia and daytime distress. METHODS: A MEDLINE search of the recent English language literature was undertaken with review of appropriate articles and references. RESULTS: A growing body of work has added to an understanding of the epidemiology, diagnostic criteria, appropriate evaluation, and effective management of restless legs syndrome. CONCLUSIONS: Restless legs syndrome occurs in about 6% of the adult population, more so in the elderly. Affected patients experience uncomfortable sensations in the legs with inactivity, more pronounced late in the day and at bedtime, which are temporarily relieved by moving the limbs. Affected patients can suffer from insomnia, disrupted sleep, daytime fatigue, and difficulty with sedentary activities. Most cases are idiopathic, although secondary causes, such as iron deficiency, should be excluded. Dopaminergic agents are highly effective in treating restless legs syndrome, but side effects can be problematic. Alternative medications include benzodiazepines, opioids, gabapentin, and clonidine.

Humans↗

Cholesterol crystal microembolization: a cause of the restless leg syndrome.

The restless leg syndrome is characterized by unpleasant lower extremity nocturnal aching, muscle cramps, and restless shuffling. Although the cause remains unknown in the majority of cases, two instances are reported of the restless leg syndrome caused by peripheral cholesterol crystal microemboli. The syndrome caused by cholesterol microemboli and the syndromes of the restless leg are reviewed.

Aged↗

Dopamine agonists for the treatment of restless legs syndrome.

The restless legs syndrome is a neurological disorder characterised by the urge to move the extremities associated with paraesthesias, which are partially or totally relieved by movement, a worsening of symptoms at rest and in the evening or at night and, as a consequence, sleep disturbances. Restless legs syndrome is common and affects 1-10% of the population. The aetiology of restless legs syndrome is unknown, but, beside genetic factors, the dopaminergic system may play a crucial role. Current treatment strategies are not curative, but may nevertheless produce an effective and lasting relief of symptoms. Evidence-based and clinical guidelines identify dopamine agonists as a first-line treatment for daily restless legs symptoms, and such substances are in the process of registration for this indication. In May 2005, the first dopamine agonist, ropinirole, was approved by the FDA. This review discusses treatment studies of dopamine agonists in patients with restless legs syndrome and focuses on long-term treatment with dopamine agonists.

Dopamine Agonists↗

[Topiramate use as treatment in restless legs syndrome].

INTRODUCTION: Restless legs syndrome is an underdiagnosed disorder of unknown etiology, that generates severe sleep and life quality disturbances. In its therapeutic approach, drugs with very different action mechanisms and variable results have been used. METHODS: Nineteen outpatients diagnosed of restless legs syndrome were studied observationally. A semistructured interview was carried out and physical variables (weight, arterial pressure and heart rate), sensitive and motor symptoms, effective dose of topiramate, side effects and fulfillment of the treatment at 30, 60 and 90 days were studied. RESULTS: The patients studied, with an average age of 62.052 +/- 6.22 years, showed improvement in sensitive and motor symptoms, as well as non-significant reductions in cardiovascular parameters. The mean effective dose of topiramate was established at 42.1 +/- 18.7 mg. A significant reduction in weight stands out among the side effects. CONCLUSIONS: Topiramate is profiled as an effective treatment in restless legs syndrome, with good tolerability and minimal side effects.

Aged↗

[Restless legs syndrome].

The restless legs syndrome is restlessness of the extremities, particularly the legs. It occurs mainly during the hours before going to sleep or during the sleep and it frequently causes a refractory insomnia. The patients feel a typical, almost indefinable, particuliar crawling sensation reminiscent of the movement of worms. The intensity of this feeling may vary from time to time. From literature and our experience we concluded that this syndrome is not a disease of itself but an early symptom of an intoxication or auto-intoxication process.

Diagnosis, Differential↗

[The use of ropinirol ++ as a treatment for restless leg syndrome].

INTRODUCTION: Restless legs is an unpleasant sensation in the calves that occurs when the individual is sitting or laying down, with an irresistible urge to move the legs. It has been know as a cause of insomnia. We have been using various drugs with a variety of effectiveness. Levodopa is now considered the drug of choice but drug tolerance is likely to develop the risk of drug dependence. Recently, a new drug was developed by Smithkline Beecham called ropinirol which principal indication is the treatment of initial phase of Parkinson's disease. PATIENTS AND METHODS: Base on the idea of the efficacy de la levodopa in patients with restless legs we administered 0.25 mg of ropinirol at bedtime to 15 of our patients diagnosed with restless legs syndrome. None of them had received positive results using the classic treatments during more than five years since they had developed this syndrome. Before the treatment was begun, we discontinued any medications relating to this illness. RESULTS: Beneficial effects were observed after the first administration and has continued until this time, 12 months after the initial treatment. Efficacy was measure by using sleep questionnaires (Spiegel). With only a pill (0.25 mg) at the moment of laying down at bedtime reports a clear improvement in the symptoms, including reducing the periodic leg movements. CONCLUSION: That improvements continue without any secondary side effects and without appearing to have built up any tolerance for the medication. Further research is needed to investigate the long term efficacy and side effects of this new treatment, but at this moment is a valuable and satisfactory tool to treat restless legs syndromes.

Adult↗

An item response analysis of the international restless legs syndrome study group rating scale for restless legs syndrome.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a common central nervous system disorder; however, there is currently a lack of well-validated and easily-administered measures of RLS severity available. The International Restless Legs Syndrome Study Group has recently developed a 10-item scale to meet this need. The International Restless Legs Severity Scale (IRLS) has been shown to have a high degree of reliability, validity, and internal consistency. In order to further demonstrate the validity of the IRLS, the present study examined the relationship between scores on individual IRLS items and overall RLS severity. PATIENTS AND METHODS: The 10-item IRLS was administered to 196 RLS patients. Option characteristic curves (the probability of scoring different options for a given item as a function of overall IRLS score) were generated in order to illustrate the scoring patterns for each item across the range of total RLS severity. Item characteristic curves (the expected score on an item as a function of overall IRLS score) were also generated to illustrate the relationship between scores on the individual items and total RLS severity. RESULTS: The IRLS items demonstrated excellent item response properties, with option and item characteristic curves closely approximating those of an ideal item. Item 3 (relief of arm or leg discomfort from moving around) was the most problematic item in that a 'floor' effect was evident; however, the item response characteristics for this item were still acceptable. CONCLUSIONS: Each IRLS item showed a good relationship between responses on that item and overall RLS severity, providing further evidence for the validity of the IRLS as a measure of RLS severity in RLS patients.

Adult↗

The restless legs syndrome.

The restless legs syndrome is a common disorder that encompasses an idiopathic form of genetic or unknown origin and symptomatic forms associated with many causes. Symptomatic forms occur during pregnancy and are coincident with uraemia, iron depletion, polyneuropathy, spinal disorders, and rheumatoid arthritis. For the hereditary forms, at least three gene loci, located on chromosomes 12, 14, and 9, have been traced so far. Prevalence in the general population is between 3% and 9%, increases with age, and is higher in women than in men. Treatment is needed only in the moderate to severe forms of the disorder and mostly in elderly people. Pathophysiology and treatment may be closely linked to the dopaminergic system and iron metabolism. Dopaminergic treatment with levodopa and dopamine agonists is the first choice in idiopathic restless legs syndrome, but augmentation and rebound should be monitored in long-term treatment. Various other drugs, such as opioids, gabapentin, and benzodiazepines, provide alternative treatment possibilities.

Adult↗

Clinical and biochemical findings in uremic patients with and without restless legs syndrome.

The restless legs syndrome (RLS) is one of the most common and unpleasant complaints of uremic patients. The pathophysiology of the RLS is still unclear. Various factors, including anemia and iron deficiency, are proposed to play a major role. We determined the prevalence of RLS in all stable hemodialysis patients under long-term treatment in two dialysis centers (n = 136) and compared the clinical and biochemical findings of patients with RLS and without RLS. Twenty-three percent of all patients investigated fulfilled the diagnostic criteria of RLS according to the International Restless Legs Syndrome Study Group. There were no statistical differences between the two groups regarding age, duration of uremia and need for dialysis, time on dialysis per week, hemoglobin, hematocrit, erythrocytes, s-ferritin, s-transferrin, s-iron, calcium, and standard biochemical indices, except for intact parathyroid hormone (iPTH) levels. Uremic patients with RLS showed significantly lower iPTH (P < 0.01) concentrations. In addition, the RLS group received a significantly higher number and dosage of psychopharmacological drugs, (ie, L-DOPA), than patients without RLS. These biochemical findings suggest that neither the severity of anemia nor that of iron deficiency has to be considered a major pathophysiological factor in established RLS. The significantly lower iPTH secretion in uremic patients with RLS, however, is a new finding, and further investigations will be necessary to determine whether this result is of any clinical significance to this group of patients. The significantly higher number of psychopharmacological drugs prescribed to uremic patients with RLS may be related to the symptoms of RLS.

Adult↗

Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a sensory-movement disorder affecting 5 to 10% of the population. Its etiology is unknown, but MRI analyses and immunohistochemical studies on autopsy tissue suggest the substantia nigra (SN) of patients with RLS has subnormal amounts of iron. METHODS: Neuromelanin cells from the SN of four RLS and four control brains were isolated by laser capture microdissection, and a profile of iron-management protein expression was obtained by immunoblot analysis. Binding assays for iron regulatory protein activity were performed on cell homogenates. RESULTS: Ferritin, divalent metal transporter 1, ferroportin, and transferrin receptor (TfR) were decreased in RLS neuromelanin cells compared with control. Transferrin was increased in RLS neuromelanin cells. This protein profile in RLS neuromelanin cells is consistent with iron deficiency with the exception that TfR expression was decreased rather than increased. The concentration and activity of the iron regulatory proteins (IRP1 and IRP2) were analyzed to determine whether there was a functional deficit in the post-transcriptional regulatory mechanism for TfR expression. Total IRP activity, IRP1 activity, and IRP1 protein levels were decreased in RLS, but total IRP2 protein levels were not decreased in RLS. CONCLUSION: Restless legs syndrome may result from a defect in iron regulatory protein 1 in neuromelanin cells that promotes destabilization of the transferrin receptor mRNA, leading to cellular iron deficiency.

Aged↗

Restless legs syndrome: an unusual cause for a perplexing syndrome.

Restless legs syndrome (RLS) is a well-defined symptom complex, occurring either as idiopathic RLS or in association with many other disorders. Although no definite etiology is known for this condition, several pathophysiological mechanisms have been proposed. There is supportive evidence that RLS is a central nervous system (CNS) dysfunction, suggesting involvement of the descending dopaminergic (DA) pathways, but it can also occur with spinal disorders. We present a patient suffering from RLS who eventually was diagnosed with a foramen magnum tumor. Based on the available evidence, we attempt to correlate the location of the tumor with the patient's symptoms of RLS.

Adult↗

Restless legs syndrome: detection and management in primary care. National Heart, Lung, and Blood Institute Working Group on Restless Legs Syndrome.

Restless legs syndrome (RLS) is a neurologic movement disorder that is often associated with a sleep complaint. Patients with RLS have an irresistible urge to move their legs, which is usually due to disagreeable sensations that are worse during periods of inactivity and often interfere with sleep. It is estimated that between 2 and 15 percent of the population may experience symptoms of RLS. Primary RLS likely has a genetic origin. Secondary causes of RLS include iron deficiency, neurologic lesions, pregnancy and uremia. RLS also may occur secondarily to the use of certain medications. The diagnosis of RLS is based primarily on the patient's history. A list of questions that may be used as a basis to assess the likelihood of RLS is included in this article. Pharmacologic treatment of RLS includes dopaminergic agents, opioids, benzodiazepines and anticonvulsants. The primary care physician plays a central role in the diagnosis and management of RLS.

Anticonvulsants↗

Sensory and motor components of the restless legs syndrome.

The restless legs syndrome (RLS) is characterized by two major manifestations: dysesthesias in the legs and irresistible leg movements. We developed a procedure to quantify these manifestations, and we studied their temporal interrelationships. We found that many dysesthesias may either closely precede or follow occurrences of EMG-defined leg activity, or both manifestations may occur independently. These results suggest that the sensory and motor components of RLS may represent two distinct manifestations of a common basic neurologic defect.

Adult↗

[The restless leg syndrome].

The restless legs syndrome (RLS) is characterized by unusual sensations in the lower legs which are difficult to describe. These sensations are experienced in the muscles and bones. They always occur at rest, most frequently at night, and disappear normally on movement. The etiology and pathogenesis are still unknown. The incidence is stated to be 5%. RLS is the fourth most frequent cause of insomnia. Treatment has been empirical. In recent single controlled investigations clonazepam (Rivotril), carbamazepine (Tegretol) and levodopa plus benserazide (Madopar) have all proved to be superior to a placebo and these drugs are, therefore, recommended. Local treatment should, however, be tried initially in all patients.

Humans↗

Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome.

Idiopathic restless legs syndrome (RLS) frequently follows an autosomal dominant inheritance with a variable clinical expressivity of symptoms. We describe the largest German kindred of familial RLS with 20 affected and investigated members in four generations with a variety of clinical symptoms. Patients were examined clinically, and polysomnography was performed in selected cases. The diagnosis was set according to the diagnostic criteria of the International RLS Study Group. All patients showed sensory symptoms of their legs and a worsening of symptoms with increasing age. Older patients, who needed treatment, responded well to opioids. Segregation ratios were close to 0.5, confirming a virtually complete penetrance. The mean age of onset fell from 51.5 years in the second generation to 19.8 years in the fourth generation (ANOVA, p = 0.025). The identification of presymptomatic carriers in the fourth generation in the following years, however, may prejudice this result. This large family showed the variety of clinical RLS symptoms with decreasing age of onset in generations II-IV, suggesting at least the possibility of anticipation.

Adolescent↗

Role of dopamine receptor agonists in the treatment of restless legs syndrome.

The restless legs syndrome (RLS) is defined by four essential criteria obligatory for clinical diagnosis which were established, and recently revised, by the International RLS Study Group. These are (i) the urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs, which are (ii) worse during rest/inactivity, (iii) partially or totally relieved by movement and (iv) worse at night/in the evening. Treatment with levodopa leads to symptom relief, but augmentation (occurrence of symptoms before levodopa administration in the evening) may occur, limiting the long-term use of this drug. This article gives an overview of the treatment in general and the role of dopamine receptor agonists in the therapy of RLS and periodic limb movements (PLMs). Dopamine receptor agonists are widely used as an effective treatment for RLS and PLMs, presumably because of their longer half-lives, lower likelihood of augmentation and good tolerability compared with levodopa. It was shown that, for example, pergolide, ropinirole, pramipexole and cabergoline alleviated RLS symptoms in 70-90% of patients. A new non-oral (transdermal) formulation of one dopamine receptor agonist, rotigotine, has recently been developed and shown to be efficacious in RLS. Further research should focus on long-term observations and comparisons of different dopamine receptor agonists in RLS.

Dopamine Agonists↗

The effect of sclerotherapy on restless legs syndrome.

BACKGROUND: Restless Legs syndrome (RLS) is a disorder of unknown etiology characterized by relentless leg discomfort when stationary, which compels voluntary leg movement to obtain temporary relief. We have received anecdotal reports of coincidental relief from symptoms of RLS in patients following sclerotherapy for varicose vein disease. OBJECTIVE: To prospectively evaluate the concomitant occurrence of RLS and varicose veins in a population seeking treatment for varicose veins, and to assess the therapeutic response of RLS to sclerotherapy. METHODS: One thousand three hundred and ninety-seven patients were screened for RLS symptoms by questionnaire and interview, and for saphenous vein disease by clinical examination, including continuous-wave Doppler. Sclerotherapy with sodium tetradecyl sulphate was performed on 113 RLS patients. RESULTS: RLS symptoms were present in 22% (312/1,397), with a Doppler-negative to Doppler-positive ratio of 3:2. One hundred and eleven of the 113 treated patients (98%) reported initial relief from RLS symptoms. Follow-up thus far shows a recurrence rate of 8% and 28% at 1 and 2 years, respectively. CONCLUSIONS: RLS is common in patients with both saphenous and nontruncal varicose vein disease, and can respond frequently and rapidly to sclerotherapy. This subpopulation of RLS sufferers should be considered for phlebological evaluation and possible treatment before being consigned to chronic drug therapy.

Adult↗