Restless Legs Syndrome
Abstract
Restless Legs Syndrome (RLS) is a common illness that aects approxima tely 10 percent of population. Of those affected with this condition, approximately one third have symptoms severe enough to require medical therapy. Patients express their symptoms as usually occurring during rest or inactivity such as lyingsitting or worsening urge to move the legs, uncomfortable sensations, and the pain. Restless Legs Syndrome causes sleep disturbances, is associated with anxiety and depression, and has a negative effect on quality of life. Restless Legs Syndrome may be a primary condition, or it may be secondary to any reason that causes local dopamine dysfunction. Although primary RLS has a familial component, the underlying mechanism is still not fully understoood. It may be secondary to iron deficiency, renal failure, pregnancy, or the use of certain medications for 25-30% of these situations. The diagnosisis clinical. With a focused history and physical examination, as well as with simple laboratory techniques, it is possible to make differential diagnosis or to reveal underlying causes of RLS. Because of its high prevalence and diagnostic facility, it is important for the discipline of family medicine. Goals in the treatment of RLS are to improve symptoms, and as a result of improvement to increase the quality of life for patients. Currently, there is little information regarding the effects of lifestyle changes on the symptoms of restless legs syndrome. Pharmacological treatment includes iron preparations, dopaminergic agents (levodopa), dopamine agonists, anticonvulsants, opioids and benzodiazepines. In addition, sleep hygiene, alcohol, caffeine and nicotine on avoidance provide improvement in symptoms.
References
- Ondo WG.Restless legs syndrome. Curr Neurol Neurosci Rep 2005;5:266-74.
- Zintzaras E, Kitsios G, Papathanasiou A, et al. Randomized trials of dopamine agonists in restless legs syndrome: A systematic review, quality assessment, and meta-analysis. Clin Thera 2010:32;2:221-37.
- Willis T. The London Practice of Physick. London: Thomas Basset and William Crook,1685.
- Mathis J. Update on restless legs. Swiss Med Wkly 2005:10;135:687-96.
- Mitchell UH. Nondrug-related aspect of treating Ekbom disease, formerly known as restless legs syndrome. Neuropsychiatr Dis Treat 2011;7:251-257.
- Yee B, Killick R, Wong K. Restless legs syndrome. Aust Fam Physician 2009;38:296-300.
- Tison F, Crochard A, Léger D, Bouée S, Lainey E, El Hasnaoui A. Epidemiology of restless legs syndrome in French adults: a nationwide survey: the INSTANT Study. Neurology 2005:26;65:239-46.
- Trenkwalder C, Paulus W, Walters AS. The restless legs syndrome. Lancet Neurol 2005;4:465-75.
- Cervenka S, Pålhagen SE, Comley RA, et al. Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain. 2006;129(Pt 8):2017-2028.
- Earley CJ, Connor JR, Beard JL, et al. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 2000:25;54:1698-700.
- Mizuno S, Mihara T, Miyaoka T, Inagaki T, Horiguchi J. CSF iron, ferritin and transferrin levels in restless legs syndrome. J Sleep Res 2005;14:43-47.
- Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ. MRI measurement of brain iron in patients with restless legs syndrome. Neurology 2001:23;56:263-265.
- Coleman RM, Pollak CP, Weitzman ED. Periodic movements in sleep (nocturnal myoclonus): relation to sleep disorders. Ann Neurol 1980;8:416-421.
- Desai AV, Cherkas LF, Spector TD, Williams AJ. Genetic influences in self-reported symptoms of obstructive sleep apnea and restless legs: a twin study. Twin Res 2004;7:589-595.
- Hanson M, Honour M, Singleton A, et al. Analysis of familial and sporadic restless legs syndrome in age of onset, gender and severity features. J Neurol 2004;251:1398-1401.
- Bayard M, Avonda T, Wadzinski J, et al. Restless legs syndrome. Am Fam Physician 2008;15:78(2):235-240.
- Walters AS. Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group. Mov Disord 1995;10:634-642.
- Allen RP, Picchietti D, Hening WA, et al. Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health; International Restless Legs Syndrome Study Group. 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. Sleep Med 2003;4:101-119.
- Walters AS, LeBrocq C, Dhar A, et al. International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 2003;4:121-132.
- Trenkwalder C, Seidel VC, Gasser T, Oertel WH. Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome. Mov Disord 1996;11:389-394.
- Lazzarini A, Walters AS, Hickey K, et al. Studies of penetrance and anticipation in five autosomal-dominant restless legs syndrome pedigrees. Mov Disord 1999;14:111-116.
- Allen RP, Earley CJ. Defining the phenotype of the restless legs syndrome (RLS) using age-of-symptom-onset. Sleep Med 2000;1:11-19.
- Nordlander Nb. Therapy in restless legs. Acta Med Scand 1953;145:453-457.
- O’Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing 1994;23:200-203.
- Manconi M, Govoni V, De Vito A, Economou NT, Cesnik E. Restless legs syndrome and pregnancy. Neurology 2004:28;63:1065-1069.
- Callaghan N. Restless legs syndrome in uremic neuropathy. Neurology 1966;16:359-361.
- Takaki J, Nishi T, Nangaku M, Shimoyama H, Inada T. Clinical and psychological aspects of restless legs syndrome in uremic patients on hemodialysis. Am J Kidney Dis 2003;41:833-839.
- Winkelmann J, Stautner A, Samtleben W, Trenkwalder C. Long-term course of restless legs syndrome in dialysis patients after kidney transplantation. Mov Disord 2002;17:1072-1076.
- Stehlik R, Arvidsson L, Ulfberg J. Restless legs syndrome is common among female patients with fibromyalgia. Eur Neurol 2009;61:107-111.
- Taylor-Gjevre RM, Gjevre JA, Skomro R, Nair B. Restless legs syndrome in a rheumatoid arthritis patient cohort. J Clin Rheumatol 2009;15:12-15.
- Ondo WG. Restless legs syndrome. Neurol Clin 2009;27:779-99.
- Boehm G, Wetter TC, Trenkwalder C. Periodic leg movements in RLS patients as compared to controls: Are there differences beyond the PLM index? Sleep Med 2009;10:566-571.
- Earley CJ, Allen RP, Hening W. Restless legs syndrome and periodic leg movements in sleep. Handb Clin Neurol 2011;99:913-948.
- Lavigne GL, Lobbezoo F, Rompré PH, et al. Cigarette smoking as a risk factor or an exacerbating factor for restless legs syndrome and sleep bruxism. Sleep 1997;20:290-293.
- Oksenberg A. Alleviation of severe restless legs syndrome (RLS) symptoms by cigarette smoking. J Clin Sleep Med 2010:15;6:489-490.
- Ondo WG, Lai D. Association between restless legs syndrome and essential tremor. Mov Disord 2006;21:515-518.
- Picchietti D, Winkelman JW.Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep 2005:1;28:891-898.
- Hornyak M, Kopasz M, Berger M, et al. Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome. J Clin Psychiatry 2005;66:1139-1145.
- Pearson VE, Allen RP, Dean T, et al. Cognitive deficits associated with restless legs syndrome (RLS). Sleep Med 2006;7:25-30.
- Happe S, Reese JP, Stiasny-Kolster K, et al. Assessing health-related quality of life in patients with restless legs syndrome. Sleep Med. 2009;10:295-305
- Broman JE, Mallon L, Hetta J. Restless legs syndrome and its relationship with insomnia symptoms and daytime distress: epidemiological survey in Sweden. Psychiatry Clin Neurosci 2008;62:472-475.
- d’Onofrio F, Bussone G, Cologno D, et al. Restless legs syndrome and primary headaches: a clinical study. Neurol Sci 2008;29 Suppl 1:S169-72.
- Pennestri MH, Montplaisir J, Colombo R, et al. Nocturnal blood pressure changes in patients with restless legs syndrome. Neurology 2007:10;68:1213-1218.
- Krieger J, Schroeder C. Iron, brain and restless legs syndrome. Sleep Med Rev 2001;5:277-286.
- Oertel WH, Trenkwalder C, Zucconi M, et al. State of the art in restless legs syndrome therapy: practice recommendations for treating restless legs syndrome. Mov Disord 2007;22 Suppl 18:S466-75.
- Restless legs syndrome: detection and management in primary care. National Heart, Lung, and Blood Institute Working Group on Restless Legs Syndrome. Am Fam Physician 2000:1;62(1):108-114.
- Tunç T, Karadağ YS, Doğulu F, Inan LE. Predisposing factors of restless legs syndrome in pregnancy. Mov Disord 2007:15;22:627-631.
- Patrick LR. Restless legs syndrome: pathophysiology and the role of iron and folate. Altern Med Rev 2007;12:101-112.
- Akpinar S. Treatment of restless legs syndrome with levodopa plus benserazide. Arch Neurol 1982;39:739.
- von Scheele C. Levodopa in restless legs. Lancet 1986:23;2:426-427.
- Conti CF, de Oliveira MM, Andriolo RB, et al. Levodopa for idiopathic restless legs syndrome: evidence-based review. Mov Disord 2007:15;22:1943-51.
- Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996;19:205-213.
- Trenkwalder C, Högl B, Benes H, Kohnen R. Augmentation in restless legs syndrome is associated with low ferritin. Sleep Med 2008;9:572-574.
- Brindani F, Vitetta F, Gemignani F. Restless legs syndrome: differential diagnosis and management with pramipexole. Clin Interv Aging 2009;4:305-313.
- Inoue Y, Hirata K, Kuroda K, et al. Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized, double-blind, placebo-controlled study. Sleep Med 2010;11:11-16.
- Erichsen D, Ferri R, Gozal D. Ropinirole in restless legs syndrome and periodic limb movement disorder. Ther Clin Risk Manag 2010:15;6:173-182.
- Hansen RA, Song L, Moore CG, et al. Effect of ropinirole on sleep outcomes in patients with restless legs syndrome: meta-analysis of pooled individual patient data from randomized controlled trials. Pharmacotherapy 2009;29:255-262.
- Oertel WH, Benes H, Garcia-Borreguero D, et al. Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: a randomized, placebocontrolled polysomnographic study. Sleep Med 2010;11:848-856.
- Trenkwalder C, Benes H, Poewe W, et al. SP790 Study Group. Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2008;7:595-604.
- Happe S, Trenkwalder C. Role of dopamine receptor agonists in the treatment of restless legs syndrome. CNS Drugs 2004;18:27-36.
- Walters AS, Winkelmann J, Trenkwalder C, et al. Long-term follow-up on restless legs syndrome patients treated with opioids. Mov Disord 2001;16:1105-1109.
- Saletu M, Anderer P, Saletu-Zyhlarz G, et al. Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol 2001;11:153-161.
- Happe S, Sauter C, Klösch G, Saletu B, Zeitlhofer J. Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome. Neuropsychobiology 2003;48:82-86.
- Garcia-Borreguero D, Larrosa O, de la Llave Y, et al. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology 2002:26;59:1573-1579.
- Sloand JA, Shelly MA, Feigin A, Bernstein P, Monk RD. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 2004;43:663-670.
- Grote L, Leissner L, Hedner J, Ulfberg J. A randomized, double-blind, placebo controlled, multi-center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome. Mov Disord. 2009:30;24:1445-52.
