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      Ropinirole in restless legs syndrome and periodic limb movement disorder

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          Abstract

          Restless legs syndrome and periodic limb movement disorder of sleep are now recognized as prevalent, distinct, yet overlapping disorders affecting all age groups. Although delineation of the mechanisms underlying these disorders continues to be the focus of very intense research efforts, it has become apparent that there is a prominent role for dopaminergic agents in the clinical management of these patients. Among the various dopaminergic drugs, ropinirole has undergone relatively intense and critical scrutiny, and appears to provide a safe and efficacious treatment option for patients with these two conditions. The more recent development of a controlled formulation for this drug is likely to yield additional benefits such as improved adherence and reduced fluctuations in daytime and nighttime symptoms. However, there is not enough evidence at this time to support such assumption.

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          Most cited references 67

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          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.

          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. The restless legs syndrome diagnostic criteria and epidemiology workshop at the National Institutes of Health. Members of the International Restless Legs Syndrome Study Group and authorities on epidemiology and the design of questionnaires and scales. 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. 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.
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            A genetic risk factor for periodic limb movements in sleep.

            The restless legs syndrome (RLS) is a common neurologic disorder characterized by an irresistible urge to move the legs. It is a major cause of sleep disruption. Periodic limb movements in sleep are detectable in most patients with RLS and represent an objective physiological metric. To search for sequence variants contributing to RLS, we performed a genomewide association study and two replication studies. To minimize phenotypic heterogeneity, we focused on patients with RLS who had objectively documented periodic limb movements in sleep. We measured serum ferritin levels, since iron depletion has been associated with the pathogenesis of RLS. In an Icelandic discovery sample of patients with RLS and periodic limb movements in sleep, we observed a genomewide significant association with a common variant in an intron of BTBD9 on chromosome 6p21.2 (odds ratio, 1.8; P=2x10(-9)). This association was replicated in a second Icelandic sample (odds ratio, 1.8; P=4x10(-4)) and a U.S. sample (odds ratio, 1.5; P=4x10(-3)). With this variant, the population attributable risk of RLS with periodic limb movements was approximately 50%. An association between the variant and periodic limb movements in sleep without RLS (and the absence of such an association for RLS without periodic limb movements) suggests that we have identified a genetic determinant of periodic limb movements in sleep (odds ratio, 1.9; P=1x10(-17)). Serum ferritin levels were decreased by 13% per allele of the at-risk variant (95% confidence interval, 5 to 20; P=0.002). We have discovered a variant associated with susceptibility to periodic limb movements in sleep. The inverse correlation of the variant with iron stores is consistent with the suspected involvement of iron depletion in the pathogenesis of the disease. Copyright 2007 Massachusetts Medical Society.
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              Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke.

              Evidence is reviewed documenting an intimate relationship among restless legs syndrome (RLS) / periodic limb movements in sleep (PLMS) and hypertension and cardiovascular and cerebrovascular disease. Sympathetic overactivity is associated with RLS/PLMS, as manifested by increased pulse rate and blood pressure coincident with PLMS. Causality is far from definitive. Mechanisms are explored as to how RLS/PLMS may lead to high blood pressure, heart disease, and stroke: (a) the sympathetic hyperactivity associated with RLS/PLMS may lead to daytime hypertension that in turn leads to heart disease and stroke; (b) in the absence of daytime hypertension, this sympathetic hyperactivity may predispose to heart disease and stroke either directly or indirectly via atherosclerotic plaque formation and rupture; and (c) comorbidities associated with RLS/PLMS, such as renal failure, diabetes, iron deficiency, and insomnia, may predispose to heart disease and stroke. One theoretical cause for sympathetic hyperactivity is insufficient All diencephalospinal dopaminergic neuron inhibition of sympathetic preganglionic neurons residing in the intermediolateral cell columns of the spinal cord. We cannot exclude the possibility that peripheral vascular, cardiovascular, and cerebrovascular disease may also contribute to RLS/PLMS, and mechanisms for these possibilities are also discussed.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2010
                2010
                15 April 2010
                : 6
                : 173-182
                Affiliations
                [1 ]Department of Pediatrics, University of Chicago, Chicago, IL, USA;
                [2 ]Department of Neurology, Oasi Institute IRCCS, Troina, Italy
                Author notes
                Correspondence: David Gozal, Department of Pediatrics, University of Chicago, 5721 S. Maryland Avenue, MC 8000, Suite K-160 Chicago, IL 60637, USA, Tel +1 (773) 702 6205, Fax +1 (773) 702 4523, Email dgozal@ 123456uchicago.edu
                Article
                tcrm-6-173
                2857615
                20421915
                © 2010 Erichsen et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Categories
                Review

                Medicine

                restless legs syndrome, dopaminergic drugs, period limb movement disorder, ropinirole

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