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.

Most cited references 96

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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.

Richard Allen, Daniel Picchietti, Wayne Hening … (2003)

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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Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.

Florian Holsboer, Claudia Trenkwalder, Bertram Müller-Myhsok … (2007)

Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.

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A genetic risk factor for periodic limb movements in sleep.

Hreinn Stefansson, David B. Rye, Andrew Hicks … (2007)

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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Author and article information

Journal

Journal ID (nlm-ta): Ther Clin Risk Manag

Journal ID (publisher-id): Therapeutics and Clinical Risk Management

Title: Therapeutics and Clinical Risk Management

Publisher: Dove Medical Press

ISSN (Print): 1176-6336

ISSN (Electronic): 1178-203X

Publication date Collection: 2010

Publication date (Print): 2010

Publication date (Electronic): 15 April 2010

Volume: 6

Pages: 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

Publisher ID: tcrm-6-173

PMC ID: 2857615

PubMed ID: 20421915

SO-VID: f1e7ae5f-61de-40e9-b0db-a88aa4e7d285

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

History

Date received : 13 April 2010

Ropinirole in restless legs syndrome and periodic limb movement disorder

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Abstract

Most cited references 96

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.

Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.

A genetic risk factor for periodic limb movements in sleep.

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