Restless legs syndrome: An overview of pathophysiology, comorbidities and therapeutic approaches (Review)
- Authors:
- Andrei Vlasie
- Simona Corina Trifu
- Cristiana Lupuleac
- Bianca Kohn
- Mihai Bogdan Cristea
-
Affiliations: Department of Psychiatry, ‘Prof. Dr. Alexandru Obregia’ Clinical Hospital of Psychiatry, Bucharest 041914, Romania, Department of Clinical Neurosciences, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest 020021, Romania, Department of Morphological Sciences, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest 020021, Romania - Published online on: December 30, 2021 https://doi.org/10.3892/etm.2021.11108
- Article Number: 185
-
Copyright: © Vlasie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Varone F, Friello L, Di Blasi C, Sgalla G, Luigetti M, Iovene B, Richeldi L, Della Marca G and Brunetti V: Restless legs syndrome: A new comorbidity in idiopathic pulmonary fibrosis. Respir Med. 170(105982)2020.PubMed/NCBI View Article : Google Scholar | |
Tachibana N: Living with restless legs syndrome/willis-ekbom disease. Sleep Med Clin. 10:359–367, xv. 2015.PubMed/NCBI View Article : Google Scholar | |
Cotter PE and O'Keeffe ST: Restless leg syndrome: Is it a real problem? Ther Clin Risk Manag. 2:465–475. 2006.PubMed/NCBI View Article : Google Scholar | |
Allen RP, Picchietti DL, Auerbach M, Cho YW, Connor JR, Earley CJ, Garcia-Borreguero D, Kotagal S, Manconi M, Ondo W, et al: Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: An IRLSSG task force report. Sleep Med. 41:27–44. 2018.PubMed/NCBI View Article : Google Scholar | |
Buchfuhrer MJ: Strategies for the treatment of restless legs syndrome. Neurotherapeutics. 9:776–790. 2012.PubMed/NCBI View Article : Google Scholar | |
Allen RP: Restless leg syndrome/willis-ekbom disease pathophysiology. Sleep Med Clin. 10:207–214, xi. 2015.PubMed/NCBI View Article : Google Scholar | |
Schormair B, Kemlink D, Roeske D, Eckstein G, Xiong L, Lichtner P, Ripke S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, et al: PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome. Nat Genet. 40:946–948. 2008.PubMed/NCBI View Article : Google Scholar | |
Winkelmann J, Czamara D, Schormair B, Knauf F, Schulte EC, Trenkwalder C, Dauvilliers Y, Polo O, Högl B, Berger K, et al: Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1. PLoS Genet. 7(e1002171)2011.PubMed/NCBI View Article : Google Scholar | |
Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Pütz B, Eckstein G, Hauk S, et al: Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet. 39:1000–1006. 2007.PubMed/NCBI View Article : Google Scholar | |
Moore H IV, Winkelmann J, Lin L, Finn L, Peppard P and Mignot E: Periodic leg movements during sleep are associated with polymorphisms in BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD. Sleep. 37:1535–1542. 2014.PubMed/NCBI View Article : Google Scholar | |
Stefansson H, Rye DB, Hicks A, Petursson H, Ingason A, Thorgeirsson TE, Palsson S, Sigmundsson T, Sigurdsson AP, Eiriksdottir I, et al: A genetic risk factor for periodic limb movements in sleep. N Engl J Med. 357:639–647. 2007.PubMed/NCBI View Article : Google Scholar | |
Vilariño-Güell C, Soto AI, Young JE, Lin SC, Uitti RJ, Wszolek ZK and Farrer MJ: Susceptibility genes for restless legs syndrome are not associated with Parkinson disease. Neurology. 71:222–223. 2008.PubMed/NCBI View Article : Google Scholar | |
Allen RP, Auerbach S, Bahrain H, Auerbach M and Earley CJ: The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am J Hematol. 88:261–264. 2013.PubMed/NCBI View Article : Google Scholar | |
Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK and Allen RP: Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology. 54:1698–1700. 2000.PubMed/NCBI View Article : Google Scholar | |
Mizuno S, Mihara T, Miyaoka T, Inagaki T and Horiguchi J: CSF iron, ferritin and transferrin levels in restless legs syndrome. J Sleep Res. 14:43–47. 2005.PubMed/NCBI View Article : Google Scholar | |
Rizzo G, Manners D, Testa C, Tonon C, Vetrugno R, Marconi S, Plazzi G, Pizza F, Provini F, Malucelli E, et al: Low brain iron content in idiopathic restless legs syndrome patients detected by phase imaging. Mov Disord. 28:1886–1890. 2013.PubMed/NCBI View Article : Google Scholar | |
Patton SM, Ponnuru P, Snyder AM, Podskalny GD and Connor JR: Hypoxia-inducible factor pathway activation in restless legs syndrome patients. Eur J Neurol. 18:1329–1335. 2011.PubMed/NCBI View Article : Google Scholar | |
Benediktsdottir B, Janson C, Lindberg E, Arnardóttir ES, Olafsson I, Cook E, Thorarinsdottir EH and Gislason T: Prevalence of restless legs syndrome among adults in Iceland and Sweden: Lung function, comorbidity, ferritin, biomarkers and quality of life. Sleep Med. 11:1043–1048. 2010.PubMed/NCBI View Article : Google Scholar | |
Connor JR, Ponnuru P, Lee BY, Podskalny GD, Alam S, Allen RP, Earley CJ and Yang QX: Postmortem and imaging based analyses reveal CNS decreased myelination in restless legs syndrome. Sleep Med. 12:614–619. 2011.PubMed/NCBI View Article : Google Scholar | |
Allen RP, Connor JR, Hyland K and Earley CJ: Abnormally increased CSF 3-Ortho-methyldopa (3-OMD) in untreated restless legs syndrome (RLS) patients indicates more severe disease and possibly abnormally increased dopamine synthesis. Sleep Med. 10:123–128. 2009.PubMed/NCBI View Article : Google Scholar | |
Stiasny-Kolster K, Möller JC, Zschocke J, Bandmann O, Cassel W, Oertel WH and Hoffmann GF: Normal dopaminergic and serotonergic metabolites in cerebrospinal fluid and blood of restless legs syndrome patients. Mov Disord. 19:192–196. 2004.PubMed/NCBI View Article : Google Scholar | |
Erikson KM, Jones BC, Hess EJ, Zhang Q and Beard JL: Iron deficiency decreases dopamine D1 and D2 receptors in rat brain. Pharmacol Biochem Behav. 69:409–418. 2001.PubMed/NCBI View Article : Google Scholar | |
Erikson KM, Jones BC and Beard JL: Iron deficiency alters dopamine transporter functioning in rat striatum. J Nutr. 130:2831–2837. 2000.PubMed/NCBI View Article : Google Scholar | |
Trifu SC, Tudor A and Radulescu I: Aggressive behavior in psychiatric patients in relation to hormonal imbalance (Review). Exp Ther Med. 20:3483–3487. 2020.PubMed/NCBI View Article : Google Scholar | |
Oertel W, Trenkwalder C, Beneš H, Ferini-Strambi L, Högl B, Poewe W, Stiasny-Kolster K, Fichtner A, Schollmayer E, Kohnen R, et al: Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: A 5-year open-label extension study. Lancet Neurol. 10:710–720. 2011.PubMed/NCBI View Article : Google Scholar | |
Desautels A, Turecki G, Montplaisir J, Xiong L, Walters AS, Ehrenberg BL, Brisebois K, Desautels AK, Gingras Y, Johnson WG, et al: Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity. Arch Neurol. 62:591–596. 2005.PubMed/NCBI View Article : Google Scholar | |
Yang Q, Li L, Chen Q, Foldvary-Schaefer N, Ondo WG and Wang QK: Association studies of variants in MEIS1, BTBD9, and MAP2K5/SKOR1 with restless legs syndrome in a US population. Sleep Med. 12:800–804. 2011.PubMed/NCBI View Article : Google Scholar | |
Ekbom K and Ulfberg J: Restless legs syndrome. J Intern Med. 266:419–431. 2009.PubMed/NCBI View Article : Google Scholar | |
Bassetti CL, Mauerhofer D, Gugger M, Mathis J and Hess CW: Restless legs syndrome: A clinical study of 55 patients. Eur Neurol. 45:67–74. 2001.PubMed/NCBI View Article : Google Scholar | |
Winkelmann J, Wetter TC, Collado-Seidel V, Gasser T, Dichgans M, Yassouridis A and Trenkwalder C: Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients. Sleep. 23:597–602. 2000.PubMed/NCBI | |
Holmes R, Tluk S, Metta V, Patel P, Rao R, Williams A and Chaudhuri KR: Nature and variants of idiopathic restless legs syndrome: observations from 152 patients referred to secondary care in the UK. J Neural Transm (Vienna). 114:929–934. 2007.PubMed/NCBI View Article : Google Scholar | |
Michaud M, Chabli A, Lavigne G and Montplaisir J: Arm restlessness in patients with restless legs syndrome. Mov Disord. 15:289–293. 2000.PubMed/NCBI View Article : Google Scholar | |
Karroum EG, Leu-Semenescu S and Arnulf I: Topography of the sensations in primary restless legs syndrome. J Neurol Sci. 320:26–31. 2012.PubMed/NCBI View Article : Google Scholar | |
Buchfuhrer MJ: Restless legs syndrome (RLS) with expansion of symptoms to the face. Sleep Med. 9:188–190. 2008.PubMed/NCBI View Article : Google Scholar | |
Ruppert E, Cretin B, Meyer C, Kilic-Huck U and Bourgin P: Characterization of periodic upper limb movement disorder in a patient with restless arms syndrome. Mov Disord. 27:1459–1461. 2012.PubMed/NCBI View Article : Google Scholar | |
Horvath J, Landis T and Burkhard PR: Restless arms. Lancet. 371(530)2008.PubMed/NCBI View Article : Google Scholar | |
Michaud M, Lavigne G, Desautels A, Poirier G and Montplaisir J: Effects of immobility on sensory and motor symptoms of restless legs syndrome. Mov Disord. 17:112–115. 2002.PubMed/NCBI View Article : Google Scholar | |
Duffy JF, Lowe AS, Silva EJ and Winkelman JW: Periodic limb movements in sleep exhibit a circadian rhythm that is maximal in the late evening/early night. Sleep Med. 12:83–88. 2011.PubMed/NCBI View Article : Google Scholar | |
Hening WA, Walters AS, Wagner M, Rosen R, Chen V, Kim S, Shah M and Thai O: Circadian rhythm of motor restlessness and sensory symptoms in the idiopathic restless legs syndrome. Sleep. 22:901–912. 1999.PubMed/NCBI View Article : Google Scholar | |
Trenkwalder C, Winkelmann J, Inoue Y and Paulus W: Restless legs syndrome-current therapies and management of augmentation. Nat Rev Neurol. 11:434–445. 2015.PubMed/NCBI View Article : Google Scholar | |
Trenkwalder C, Hening WA, Walters AS, Campbell SS, Rahman K and Chokroverty S: Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome. Mov Disord. 14:102–110. 1999.PubMed/NCBI View Article : Google Scholar | |
Möller C, Wetter TC, Köster J and Stiasny-Kolster K: Differential diagnosis of unpleasant sensations in the legs: Prevalence of restless legs syndrome in a primary care population. Sleep Med. 11:161–166. 2010.PubMed/NCBI View Article : Google Scholar | |
Hening WA, Allen RP, Washburn M, Lesage S and Earley CJ: Validation of the Hopkins telephone diagnostic interview for restless legs syndrome. Sleep Med. 9:283–289. 2008.PubMed/NCBI View Article : Google Scholar | |
Benes H and Kohnen R: Validation of an algorithm for the diagnosis of restless legs syndrome: The restless legs syndrome-diagnostic index (RLS-DI). Sleep Med. 10:515–523. 2009.PubMed/NCBI View Article : Google Scholar | |
Hening WA, Allen RP, Washburn M, Lesage SR and Earley CJ: The four diagnostic criteria for restless legs syndrome are unable to exclude confounding conditions (‘mimics’). Sleep Med. 10:976–981. 2009.PubMed/NCBI View Article : Google Scholar | |
Trifu S, Carp EG and Nadoleanu A: Alcohol as a substitute, mask of depression and ‘antidote’ of narcissism. Eur Proc Soc Behav Sci. 31:986–994. 2017. | |
Richeldi L, Collard HR and Jones MG: Idiopathic pulmonary fibrosis. Lancet. 389:1941–1952. 2017.PubMed/NCBI View Article : Google Scholar | |
Raghu G, Amatto VC, Behr J and Stowasser S: Comorbidities in idiopathic pulmonary fibrosis patients: A systematic literature review. Eur Respir J. 46:1113–1130. 2015.PubMed/NCBI View Article : Google Scholar | |
Mucsi I, Molnar MZ, Ambrus C, Szeifert L, Kovacs AZ, Zoller R, Barótfi S, Remport A and Novak M: Restless legs syndrome, insomnia and quality of life in patients on maintenance dialysis. Nephrol Dial Transplant. 20:571–577. 2005.PubMed/NCBI View Article : Google Scholar | |
Tuncel D, Orhan FO, Sayarlioglu H, Isık IO, Utku U and Dinc A: Restless legs syndrome in hemodialysis patients: Association with depression and quality of life. Sleep Breath. 15:311–315. 2011.PubMed/NCBI View Article : Google Scholar | |
Takaki J, Nishi T, Nangaku M, Shimoyama H, Inada T, Matsuyama N, Kumano H and Kuboki T: Clinical and psychological aspects of restless legs syndrome in uremic patients on hemodialysis. Am J Kidney Dis. 41:833–839. 2003.PubMed/NCBI View Article : Google Scholar | |
Ohayon MM, O'Hara R and Vitiello MV: Epidemiology of restless legs syndrome: A synthesis of the literature. Sleep Med Rev. 16:283–295. 2012.PubMed/NCBI View Article : Google Scholar | |
Stefanidis I, Vainas A, Dardiotis E, Giannaki CD, Gourli P, Papadopoulou D, Vakianis P, Patsidis E, Eleftheriadis T, Liakopoulos V, et al: Restless legs syndrome in hemodialysis patients: An epidemiologic survey in Greece. Sleep Med. 14:1381–1386. 2013.PubMed/NCBI View Article : Google Scholar | |
Turk AC, Ozkurt S, Turgal E and Sahin F: The association between the prevalence of restless leg syndrome, fatigue, and sleep quality in patients undergoing hemodialysis. Saudi Med J. 39:792–798. 2018.PubMed/NCBI View Article : Google Scholar | |
Zadeh Saraji N, Hami M, Boostani R and Mojahedi MJ: Restless leg syndrome in chronic hemodialysis patients in Mashhad hemodialysis centers. J Renal Inj Prev. 6:137–141. 2016.PubMed/NCBI View Article : Google Scholar | |
Azar SA, Hatefi R and Talebi M: Evaluation of effect of renal transplantation in treatment of restless legs syndrome. Transplant Proc. 39:1132–1133. 2007.PubMed/NCBI View Article : Google Scholar | |
Pizza F, Persici E, La Manna G, Campieri C, Plazzi G, Carretta E, Cappuccilli ML, Ferri B, Stefoni S and Montagna P: Family recurrence and oligo-anuria predict uremic restless legs syndrome. Acta Neurol Scand. 125:403–409. 2012.PubMed/NCBI View Article : Google Scholar | |
Micozkadioglu H, Ozdemir FN, Kut A, Sezer S, Saatci U and Haberal M: Gabapentin versus levodopa for the treatment of restless legs syndrome in hemodialysis patients: An open-label study. Ren Fail. 26:393–397. 2004.PubMed/NCBI View Article : Google Scholar | |
Razazian N, Azimi H, Heidarnejadian J, Afshari D and Ghadami MR: Gabapentin versus levodopa-c for the treatment of restless legs syndrome in hemodialysis patients: A randomized clinical trial. Saudi J Kidney Dis Transpl. 26:271–278. 2015.PubMed/NCBI View Article : Google Scholar | |
Sagheb MM, Dormanesh B, Fallahzadeh MK, Akbari H, Sohrabi Nazari S, Heydari ST and Behzadi S: Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: A randomized, double-blind, placebo-controlled trial. Sleep Med. 13:542–545. 2012.PubMed/NCBI View Article : Google Scholar | |
Cikrikcioglu MA, Hursitoglu M, Erkal H, Kınas BE, Sztajzel J, Cakirca M, Arslan AG, Erek A, Halac G and Tukek T: Oxidative stress and autonomic nervous system functions in restless legs syndrome. Eur J Clin Invest. 41:734–742. 2011.PubMed/NCBI View Article : Google Scholar | |
Giannaki CD, Hadjigeorgiou GM, Karatzaferi C, Maridaki MD, Koutedakis Y, Founta P, Tsianas N, Stefanidis I and Sakkas GK: A single-blind randomized controlled trial to evaluate the effect of 6 months of progressive aerobic exercise training in patients with uraemic restless legs syndrome. Nephrol Dial Transplant. 28:2834–2840. 2013.PubMed/NCBI View Article : Google Scholar | |
Saha L: Irritable bowel syndrome: Pathogenesis, diagnosis, treatment, and evidence-based medicine. World J Gastroenterol. 20:6759–6773. 2014.PubMed/NCBI View Article : Google Scholar | |
Wajszilber D, Santiseban JA and Gruber R: Sleep disorders in patients with ADHD: Impact and management challenges. Nat Sci Sleep. 10:453–480. 2018.PubMed/NCBI View Article : Google Scholar | |
Thomas R, Sanders S, Doust J, Beller E and Glasziou P: Prevalence of attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. Pediatrics. 135:e994–e1001. 2015.PubMed/NCBI View Article : Google Scholar | |
Chervin RD, Archbold KH, Dillon JE, Pituch KJ, Panahi P, Dahl RE and Guilleminault C: Associations between symptoms of inattention, hyperactivity, restless legs, and periodic leg movements. Sleep. 25:213–218. 2002.PubMed/NCBI | |
Chaiard J and Weaver TE: Update on research and practices in major sleep disorders: Part II-Insomnia, Willis-Ekbom disease (Restless Leg Syndrome), and narcolepsy. J Nurs Scholarsh. 51:624–633. 2019.PubMed/NCBI View Article : Google Scholar | |
Didato G, Di Giacomo R, Rosa GJ, Dominese A, de Curtis M and Lanteri P: Restless legs syndrome across the lifespan: Symptoms, pathophysiology, management and daily life impact of the different patterns of disease presentation. Int J Environ Res Public Health. 17(3658)2020.PubMed/NCBI View Article : Google Scholar | |
Anguelova GV, Vlak MHM, Kurvers AGY and Rijsman RM: Pharmacologic and nonpharmacologic treatment of restless legs Syndrome. Sleep Med Clin. 13:219–230. 2018.PubMed/NCBI View Article : Google Scholar | |
Garcia-Borreguero D, Silber MH, Winkelman JW, Högl B, Bainbridge J, Buchfuhrer M, Hadjigeorgiou G, Inoue Y, Manconi M, Oertel W, 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 RLS-foundation. Sleep Med. 21:1–11. 2016.PubMed/NCBI View Article : Google Scholar | |
Trenkwalder C, Winkelmann J, Oertel W, Virgin G, Roubert B and Mezzacasa A: FCM-RLS Study Investigators. Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial. Mov Disord. 32:1478–1482. 2017.PubMed/NCBI View Article : Google Scholar | |
Trenkwalder C, Allen R, Högl B, Clemens S, Patton S, Schormair B and Winkelmann J: Comorbidities, treatment, and pathophysiology in restless legs syndrome. Lancet Neurol. 17:994–1005. 2018.PubMed/NCBI View Article : Google Scholar | |
Avni T, Reich S, Lev N and Gafter-Gvili A: Iron supplementation for restless legs syndrome-A systematic review and meta-analysis. Eur J Intern Med. 63:34–41. 2019.PubMed/NCBI View Article : Google Scholar | |
Akpinar S: Treatment of restless legs syndrome with levodopa plus benserazide. Arch Neurol. 39(739)1982.PubMed/NCBI View Article : Google Scholar | |
Benes H, Kurella B, Kummer J, Kazenwadel J, Selzer R and Kohnen R: Rapid onset of action of levodopa in restless legs syndrome: A double-blind, randomized, multicenter, crossover trial. Sleep. 22:1073–1081. 1999.PubMed/NCBI View Article : Google Scholar | |
Trenkwalder C, Garcia-Borreguero D, Montagna P, Lainey E, de Weerd AW, Tidswell P, Saletu-Zyhlarz G, Telstad W and Ferini-Strambi L: Therapy with Ropiunirole; Efficacy and Tolerability in RLS 1 Study Group. Efficacy and Tolerability in RLS 1 Study Group. Ropinirole in the treatment of restless legs syndrome: Results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry. 75:92–97. 2004.PubMed/NCBI | |
Collado-Seidel V, Kazenwadel J, Wetter TC, Kohnen R, Winkelmann J, Selzer R, Oertel WH and Trenkwalder C: A controlled study of additional sr-L-dopa in L-dopa-responsive restless legs syndrome with late-night symptoms. Neurology. 52:285–290. 1999.PubMed/NCBI View Article : Google Scholar | |
Allen RP and Earley CJ: Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep. 19:205–213. 1996.PubMed/NCBI View Article : Google Scholar | |
Wijemanne S and Ondo W: Restless Legs Syndrome: Clinical features, diagnosis and a practical approach to management. Pract Neurol. 17:444–452. 2017.PubMed/NCBI View Article : Google Scholar | |
Picchietti DL, Hensley JG, Bainbridge JL, Lee KA, Manconi M, McGregor JA, Silver RM, Trenkwalder C and Walters AS: International Restless Legs Syndrome Study Group (IRLSSG). Consensus clinical practice guidelines for the diagnosis and treatment of restless legs syndrome/Willis-Ekbom disease during pregnancy and lactation. Sleep Med Rev. 22:64–77. 2015.PubMed/NCBI View Article : Google Scholar | |
Beneš H, García-Borreguero D, Ferini-Strambi L, Schollmayer E, Fichtner A and Kohnen R: Augmentation in the treatment of restless legs syndrome with transdermal rotigotine. Sleep Med. 13:589–597. 2012.PubMed/NCBI View Article : Google Scholar | |
Garcia-Borreguero D, Cano-Pumarega I and Marulanda R: Management of treatment failure in restless legs syndrome (Willis-Ekbom disease). Sleep Med Rev. 41:50–60. 2018.PubMed/NCBI View Article : Google Scholar | |
Comella CL: Treatment of restless legs syndrome. Neurotherapeutics. 11:177–187. 2014.PubMed/NCBI View Article : Google Scholar | |
Prosperetti C and Manconi M: Restless legs syndrome/willis-ekbom disease and pregnancy. Sleep Med Clin. 10:323–329, xiv. 2015.PubMed/NCBI View Article : Google Scholar | |
Telstad W, Sørensen O, Larsen S, Lillevold PE, Stensrud P and Nyberg-Hansen R: Treatment of the restless legs syndrome with carbamazepine: A double blind study. Br Med J (Clin Res Ed). 288:444–446. 1984.PubMed/NCBI View Article : Google Scholar | |
Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X and Hernandez G: Treatment of restless legs syndrome with gabapentin: A double-blind, cross-over study. Neurology. 59:1573–1579. 2002.PubMed/NCBI View Article : Google Scholar | |
Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E and Agúndez JAG: Treatment options for idiopathic restless legs Syndrome. Eur Neurol Rev. 10:45–55. 2015. | |
Walters AS, Wagner ML, Hening WA, Grasing K, Mills R, Chokroverty S and Kavey N: Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep. 16:327–332. 1993.PubMed/NCBI View Article : Google Scholar | |
Walters AS, Winkelmann J, Trenkwalder C, Fry JM, Kataria V, Wagner M, Sharma R, Hening W and Li L: Long-term follow-up on restless legs syndrome patients treated with opioids. Mov Disord. 16:1105–1109. 2001.PubMed/NCBI View Article : Google Scholar | |
Montagna P, Sassoli de Bianchi L, Zucconi M, Cirignotta F and Lugaresi E: Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand. 69:428–430. 1984.PubMed/NCBI View Article : Google Scholar | |
Saletu M, Anderer P, Saletu-Zyhlarz G, Prause W, Semler B, Zoghlami A, Gruber G, Hauer C and Saletu B: Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): Acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol. 11:153–161. 2001.PubMed/NCBI View Article : Google Scholar | |
Xu XM, Liu Y, Jia SY, Dong MX, Cao D and Wei YD: Complementary and alternative therapies for restless legs syndrome: An evidence-based systematic review. Sleep Med Rev. 38:158–167. 2018.PubMed/NCBI View Article : Google Scholar | |
Einollahi B and Izadianmehr N: Restless leg syndrome: A neglected diagnosis. Nephrourol Mon. 6(e22009)2014.PubMed/NCBI View Article : Google Scholar | |
Harrison EG, Keating JL and Morgan PE: Non-pharmacological interventions for restless legs syndrome: A systematic review of randomised controlled trials. Disabil Rehabil. 41:2006–2014. 2019.PubMed/NCBI View Article : Google Scholar |