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Abstract
Restless Legs Syndrome (RLS), or Willis-Ekbom disease, is a common neurological disorder that impairs sleep, mood, and increases cardiovascular risk. RLS is defined by an urge to move the legs in the evening when at rest. The pathophysiology is still unclear but involves genetic susceptibility, brain iron deficiency, and dopamine deregulation.
The diagnosis is based on the five essential criteria and a normal neurological examination. Periodic leg movements during
sleep are found in 60-80% of RLS cases. Serum ferritin level is mandatory, and iron supplementation is provided if ferritin levels are < 50-75µg/l.
On-demand treatment with opiates can be proposed for moderate and intermittent symptoms. Daily treatment is required in severe cases only and is initiated with small doses of dopamine agonists, alpha-2 delta ligands, and opiates alone or in combination. Augmentation syndrome is a serious complication in treated RLS, related to high doses of dopamine agonists and/or low ferritin levels, and is characterized by an increase in symptom severity that begins earlier and spreads to other parts of the body.
References
Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, et al. Restless Legs Syndrome Prevalence and Impact: REST General Population Study. Archives of Internal Medicine. 2005 Jun 13;165(11):1286–92.
Manconi M, Garcia-Borreguero D, Schormair B, Videnovic A, Berger K, Ferri R, et al. Restless legs syndrome. Nat Rev Dis Primers. 2021 Nov 3;7(1):80.
Leclair-Visionneau L, Vecchierini MF, Schröder C, Charley Monaca C. French Consensus: How to diagnose restless legs syndrome. Revue Neurologique. 2018 Sep 1;174(7):508–14.
Limousin N, Flamand M, Schröder C, Charley Monaca C. French consensus: Treatment of newly diagnosed restless legs syndrome. Revue Neurologique. 2018 Sep 1;174(7):515–21.
Leu-Semenescu S, Petiau C, Charley Monaca C, Dauvilliers Y. French consensus: Augmentation syndrome in restless legs S. Cheninisyndrome. Revue Neurologique. 2018 Sep 1;174(7):532–9.
Chenini S, Arnulf I, Monaca CC, Ghorayeb I. French consensus:Pharmacoresistantrestless legs syndrome. Revue Neurologique. 2018 Sep 1;174(7):522–31.
Allen RP, Picchietti DL, GarciaBorreguero D, Ondo WG, Walters AS, Winkelman JW, et al. Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group [IRLSSG] consensus criteria – history, rationale, description, and significance. Sleep Medicine. 2014 Aug 1;15(8):860–73.
Ohayon MM, Bagai K, Roberts LW, Walters AS, Milesi C. Refining duration and frequency thresholds of restless legs syndrome diagnosis criteria. Neurology. 2016 Dec 13;87(24):2546–53.
Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lespérance P. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: A study of 133 patients diagnosed with new standard criteria. Movement Disorders. 1997;12(1):61–5.
Tison F, Crochard A, Léger D, Bouée S, Lainey E, Hasnaoui AE. Epidemiology of restless legs syndrome in French adults: A nationwide survey: The INSTANT Study. Neurology. 2005 Jul 26;65(2):239–46.
Haba-Rubio J, Marti-Soler H, MarquesVidal P, Tobback N, Andries D, Preisig M, et al. Prevalence and determinants of periodic limb movements in the general population. Annals of Neurology. 2016;79(3):464–74.
Xiong L, Jang K, Montplaisir J, Levchenko A, Thibodeau P, Gaspar C, et al. Canadian Restless Legs Syndrome Twin Study. Neurology. 2007 May 8;68(19):1631–3.
Schormair B, Zhao C, Bell S, Tilch E, Salminen AV, Pütz B, et al. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a metaanalysis. The Lancet Neurology. 2017 Nov 1;16(11):898–907.
Allen RP, Earley CJ. The role of iron in restless legs syndrome. Movement Disorders. 2007;22(S18):S440–8.
Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of Mammalian iron metabolism. Cell. 2010 Jul 9;142(1):24–38.
Dauvilliers Y, Chenini S, Vialaret J, Delaby C, Guiraud L, Gabelle A, et al. Association between serum hepcidin level and restless legs syndrome. Movement Disorders. 2018;33(4):618–27.
Chenini S, Delaby C, Rassu AL, Barateau L, Vialaret J, Hirtz C, et al. Hepcidin and ferritin levels in restless legs syndrome: a case-control study. Sci Rep. 2020 Jul 17;10(1):11914.
Akpinar S. Treatment of restless legs syndrome with levodopa plus benserazide. Arch Neurol. 1982 Nov;39(11):739.
Allen RP, Earley CJ, Jones BC, Unger EL. Iron-deficiency and dopaminergic treatment effects on RLS-Like behaviors of an animal model with the brain iron deficiency pattern of the restless legs syndrome. SleepMedicine. 2020 Jul1;71:141–8.
Karroum EG, Golmard JL, LeuSemenescu S, Arnulf I. Sensations in restless legs syndrome. Sleep Medicine. 2012 Apr 1;13(4):402–8.
Hammerschlag AR, Stringer S, de Leeuw CA, Sniekers S, Taskesen E, Watanabe K, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Nov;49(11):1584–92.
Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al. Validation of the International Restless Legs S. Chenini Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003 Mar;4(2):121–32.
Trenkwalder C, Allen R, Högl B, Paulus W, Winkelmann J. Restless legs syndrome associated with major diseases. Neurology. 2016 Apr 5;86(14):1336–43.
Fulda S, Wetter TC. Is daytime sleepiness a neglected problem in patients with restless legs syndrome? Movement Disorders. 2007;22(S18):S409–13.
Lopez R, Micoulaud Franchi JA, Chenini S, Gachet M, Jaussent I, Dauvilliers Y. Restless legs syndrome and iron deficiency in adults with attentiondeficit/hyperactivity disorder. Sleep. 2019 May 1;42(5):zsz027.
Chenini S, Barateau L, Rassu AL, Lopez R, Guiraud L, Cavaillès C, et al. Systematic assessment of autonomic symptoms in restless legs syndrome. Sleep Medicine. 2021 Apr1;80:30–8.
Trenkwalder C, Tinelli M, Sakkas GK, Dauvilliers Y, Ferri R, Rijsman R, et al. Socioeconomic impact of restless legs syndrome and inadequate restless legs syndrome management across European settings. European Journal of Neurology. 2021;28(2):691–706.
Chenini S, Barateau L, Guiraud L, Denis C, Rassu AL, Lopez R, et al. Depressive Symptoms and Suicidal Thoughts in Restless Legs Syndrome. Movement Disorders. 2022;37(4):812–25.
Li Y, Wang W, Winkelman JW, Malhotra A, Ma J, Gao X. Prospective study of restless legs syndrome and mortality among men. Neurology. 2013 Jul 2;81(1):52–9.
Li Y, Li Y, Winkelman JW, Walters AS, Han J, Hu FB, et al. Prospective study of restless legs syndrome and total and cardiovascular mortality among women. Neurology. 2018 Jan 9;90(2):e135–41.
Cholley-Roulleau M, Chenini S, Béziat S, Guiraud L, Jaussent I, Dauvilliers Y. Restless legs syndrome and cardiovascular diseases: A case-control study. PLoS One. 2017;12(4):e0176552.
Chenini S, Rassu AL, Guiraud L, Evangelista E, Barateau L, Lopez R, et al. Blood pressure profile and endothelial function in restlesslegs syndrome. Sci Rep. 2019 Nov 4;9(1):15933.
Yano Y, Kario K. Nocturnal blood pressure and cardiovascular disease: a review of recent advances. Hypertens Res. 2012 Jul;35(7):695–701.
Gao X, Ba DM, Bagai K, Liu G, Ma C, Walters AS. Treating Restless Legs Syndrome Was Associated With Low Risk of Cardiovascular Disease: A Cohort Study With 3.4 Years of Follow‐Up. Journal of the American Heart Association. 2021 Feb 16;10 (4):e018674.
Chenini S, Rassu AL, Barateau L, Lopez R, Carlander B, Guiraud L, et al. Increased Blood Pressure Dipping in Restless Legs Syndrome WithRotigotine: A Randomized Trial. MovementDisorders. 2020;35 (12):2164–73.
Song ML, Park KM, Motamedi GK, Cho YW. Cognitive behavioral therapy for insomnia in restless legs syndrome patients. Sleep Medicine. 2020 Oct 1;74:227–34.
Garcia-Borreguero D, Silber MH, Winkelman JW, Högl B, Bainbridge J, Buchfuhrer M, et al. Guidelines for the first line treatment of restless legs syndrome/Willis–Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLSfoundation. Sleep Medicine. 2016 May 1;21:1–11.
Allen RP, Chen C, Garcia-Borreguero D, Polo O, DuBrava S, Miceli J, et al. Comparison of Pregabalin with Pramipexole for Restless Legs Syndrome. N Engl J Med. 2014 Feb 13;370 (7):621–31.
Yasmine C, Aicha D. Pregabalin addiction caracteristics at oran: A cohort S. Chenini study. EuropeanPsychiatry. 2021 Apr;64 (S1):S559–S559.
Trenkwalder C, Beneš H, Grote L, García-Borreguero D, Högl B, Hopp M, et al. Prolonged release oxycodone–naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebocontrolled trial with an open-label extension. The Lancet Neurology. 2013 Dec1;12 (12):1141–50.
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