Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-25T11:03:07.895Z Has data issue: false hasContentIssue false
  • English
  • Français

Restless Legs Syndrome: A Review

Published online by Cambridge University Press:  07 November 2014

Lama M. Chahine  and
Zeina N. Chemali
Get access Rights & Permissions [Opens in a new window]

Abstract

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the limbs accompanied by uncomfortable sensations, leading to sleep disturbances. It is associated with psychiatric comorbidities and a decreased quality of life. RLS is common and most severe among females and the elderly. It may be primary or secondary to other conditions and may be familial. Linkage to several chromosomal loci have been demonstrated. The pathogenesis of RLS involves dopaminergic dysfunction, iron metabolism, and abnormalities in supraspinal inhibition. The mainstay of RLS therapy are dopamine agonists or levodopa.This article reviews the clinical characteristics, epidemiology, diagnosis, pathogenesis, and treatment of RLS.

Type
Review Articles
Information
CNS Spectrums , Volume 11 , Issue 7 , July 2006 , pp. 511 - 520
Copyright
Copyright © Cambridge University Press 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Ekbom, KA. Restless legs: clinical study of hitherto over-looked disease in legs characterized by peculiar paresthesia, pain, and weakness and occurring in two main forms, asthenia crurum paresthetica and asthenia crurum dolorosa. Acta Med Scand 1945;58(suppl l):1–123.Google Scholar
2.Gorman, CA, Dyck, PJ, Pearson, J.SSymptom of restless legs. Arch Intern Med. 1965;115:155–159.Google Scholar
3.Allen, RP, Earley, CJ. Restless legs syndrome: a review of clinical and pathophysiologic features. J Clin Neurophysiol. 2001:18:128–147.Google Scholar
4.Ondo, W, Jankovic, J. Restless legs syndrome: clinicoetiologic correlates. Neurology. 1996;47:1435–1441.CrossRefGoogle ScholarPubMed
5.Phillips, B. Movement disorders: a sleep specialist’s perspective. Neurology. 2004:62(5 suppl 2):S9–S16.CrossRefGoogle ScholarPubMed
6.Michaud, M, Chabli, A, Lavigne, G, Montplaisir, J. Arm restlessness in patients with restless legs syndrom. Mov Disord. 2000;115:289–293.3.0.CO;2-E>CrossRefGoogle Scholar
7.Lutz, EG. Restless legs, anxiety and caffeinism. J Clin Psychiatry. 1978:39:693–698.Google Scholar
8.Provini, F, Vetrugno, R, Meletti, S, et al.Motor pattern of periodic limb movements during sleep. Neurology. 2001:57:300–304.Google Scholar
9.Tan, Ek, Ondo, WG. Motor restlessness. IntJClin Pract. 2001:55:320–322.Google Scholar
10.Hening, W, Walters, AS, Allen, RP, Montplaisir, J, Myers, A, Ferini-Strambi, L. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med. 2004;5:237–246.CrossRefGoogle Scholar
11.Michaud, M, Dumont, M, Selmaoui, B, Paquet, J, Fantini, M, Montplaisir, J. Circadian rhythm of restless legs syndrome: relationship with biological markers. Ann Neurol. 2004;55:372–380.CrossRefGoogle ScholarPubMed
12.Trenkwalder, C, Hening, WA, Walters, AS, Campbell, SS, Rahman, K, Chokroverty, S. Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome. Mov Disord. 1999,14:102–110.Google Scholar
13.Hening, WA, Allen, RP. Restless legs syndrome (RLS): the continuing development of diagnostic standards and severity measures. Sleep Med. 2003;4:95–97.CrossRefGoogle ScholarPubMed
14.Allen, RP, Earley, CJ. Validation of the Johns Hopkins restless legs severity scale. Sleep Med. 2001;2:239–242.Google Scholar
15.Garcia-Borreguero, D, Odin, P, Serrano, C. Restless legs syndrome and PD: a review of the evidence for a possible association. Neurology. 2003:61(6 suppl 3):S49–S55.Google Scholar
16.Saletu, B, Anderer, P, Saletu, M, Hauer, C, Lindeck-Pozza, L, Saletu-Zyhlarz, G. EEG mapping, psychometric, and polysomnographic studies in restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) patients as compared with normal controls. Sleep Med. 2002;(3 suppl):S35–S42.CrossRefGoogle ScholarPubMed
17. Recording and scoring leg movements. The Atlas Task Force. Sleep. 1993;16:748–759.Google Scholar
18.Allen, RP, Picchietti, D, Hening, WA, et al.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.Google Scholar
19.Bastuji, H, Garcia-Larrea, L. Sleep/wake abnormalities in patients with periodic leg movements during sleep: factor analysis on data from 24-h ambulatory polygraphy. J Sleep Res. 1999;8:217–223.CrossRefGoogle ScholarPubMed
20.Vandeputte, M, de Weerd, A. Sleep disorders and depressive feelings: a global survey with the Beck depression scale. Sleep Med. 2003;4:343–345.Google Scholar
21.Young, JR, Humphries, AW, DeWolfe, VG. Restless leg syndrome. Geriatrics. 1969;24:167–171.Google Scholar
22.Ulfberg, J, Nystrom, B, Carter, N, Edling, C. Prevalence of restless legs syndrome among men aged 18 to 64 years: an association with somatic disease and neuropsychiatrie symptoms. Mov Disord. 2001;16:1159–1163.Google Scholar
23.Mosko, S, Zetin, M, Glen, S, et al.Self-reported depressive symptomatology, mood ratings, and treatment outcome in sleep disorders patients. J Clin Psychol. 1989;45:51–61.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
24.Banno, K, Delaive, K, Walld, R, Kryger, MH. Restless legs syndrome in 218 patients: associated disorders. Sleep Med. 2000;1:221–229.Google Scholar
25.Abetz, L, Allen, R, Follet, A, et al.Evaluating the quality of life of patients with restless legs syndrome. Clin Ther. 2004;26:925–935.Google Scholar
26.Walter, AS. Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group. Mov Disord. 1995;10:634–642.Google Scholar
27.Rothdach, AJ, Trenkwalder, C, Haberstock, J, Keil, U, Berger, K. Prevalence and risk factors of RLS in an elderly population: the MEMO study. Memory and Morbidity in Augsburg Elderly. Neurology. 2000;54:1064–1068.Google Scholar
28.Phillips, B, Young, T, Finn, L, Asher, K, Hening, WA, Purvis, C. Epidemiology of restless legs symptoms in adults. Arch Intern Med. 2000;160:2137–2141.Google Scholar
29.Tan, EK, Seah, A, See, SJ, Lim, E, Wong, MC, Koh, KK. Restless legs syndrome in an Asian population: A study in Singapore. Mov Disord. 2001;16 577–579.Google Scholar
30.Inoue, Y, Ishizuka, T, Arai, H. Surveillance on epidemiology and treatment of restless legs syndrome in Japan. J New Rem Clin. 2000:49:244–254.Google Scholar
31.Bhowmik, D, Bhatia, M, Gupta, S, Agarwal, SK, Tiwari, SC, Dash, SC. Restless legs syndrome in hemodialysis patients in India: a case controlled study. Sleep Med. 2003;4:143–146.Google Scholar
32.Ohayon, MM, Roth, T. Prevalence of restless legs syndrome and periodic limb movement disorder in the general population. J Psychosom Res. 2002;53:547–554.CrossRefGoogle ScholarPubMed
33.Berger, K, Luedemann, J, Trenkwalder, C, John, U, Kessler, C. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med. 2004;164:196–202.Google Scholar
34.Ondo, WG, Vuong, KD, Jankovic, J. Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol. 2002;59:421–424.Google Scholar
35.Walters, AS. Is there a subpopulation of children with growing pains who really have Restless Legs Syndrome? A review of the literature. Sleep Med. 2002;3:93–98.Google Scholar
36.Picchietti, DL, England, SJ, Walters, AS, Willis, K, Verrico, T. Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder. J Child Neurol. 1998;13:588–594.CrossRefGoogle ScholarPubMed
37.Walters, AS, Hickey, K, Maltzman, J, et al.A questionnaire study of 138 patients with restless legs syndrome: the ‘Night-Walkers’ survey. Neurology. 1996;46:92–95.Google Scholar
38.Winklemann, J, Muller-Myhsok, B, Wittchen, HU, et al.Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families. Ann Neurol. 2002;52:297–302.Google Scholar
39.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.Google Scholar
40.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.Google Scholar
41.Bonati, MXFerini-Strambi, L, Aridon, ROldani, A, Zucconi, M, Casari, G. Autosomal dominant restless legs syndrome maps on chromosome 14q. Brain. 2003;126(pt 6)1485–1492.Google Scholar
42.Ondo, WG, Vuong, KD, Wang, Q. Restless legs syndrome in monozygotic twins: clinical correlates. Neurology. 2000;55:1404–1406.Google Scholar
43.Desautels, A, Turecki, G, Montplaisir, J, Sequeira, A, Verner, A, Rouleau, GA. Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. Am J Hum Genet. 2001;69:1266–1270.CrossRefGoogle Scholar
44.Ferini-Strambi, L, Bonati, MT, Oldani, A, Aridon, P, Zucconi, M, Casari, G. Genetics in restless legs syndrome. Sleep Med. 2004;5:301–304.Google Scholar
45.Levchenko, A, Montplaisir, JYDube, MP, et al.The 14q restless legs syndrome locus in the French Canadian population. Ann Neurol. 2004;55:887–891.Google Scholar
46.Chen, S, Ondo, WG, Rao, S, Li, L, Chen, Q, Wang, Q. Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p. Am J Hum Genet. 2004;74:876–885.CrossRefGoogle ScholarPubMed
47.Desautels, A, Turecki, G, Montplaisir, J, et al.Evidence for a genetic association between monoamine oxidase A and restless legs syndrome. Neurology. 2002;59:215–219.CrossRefGoogle ScholarPubMed
48.Desautels, A, Turecki, G, Montplaisir, J, et al.Dopaminergic neurotransmission and restless legs syndrome: a genetic association analysis. Neurology. 2001;57:1304–1306.Google Scholar
49.Hening, WA. Subjective and objective criteria in the diagnosis of the restless legs syndrome. Sleep Med. 2004;5:285–292.CrossRefGoogle ScholarPubMed
50.Montplaisir, J, Boucher, S, Nicolas, A, et al.Ilmmobilization tests and periodic leg movements in sleep for the diagnosis of restless leg syndrome. Mov Disord 1998;13:324–329.CrossRefGoogle ScholarPubMed
51.O’Keeffe, ST. Restless legs syndrome. A review. Arch Intern Med. 1996;156:243–248.Google Scholar
52.Walters, AS, Hening, WA, Chokroverty, S. Frequent occurrence of myoclonus while awake and at rest, body rocking and marching In place in a subpopulation of patients with restless legs syndrom. Acta Neurol Scand. 1988;77:418–421.CrossRefGoogle Scholar
53.Allen, R. Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). Sleep Med. 2004;5:385–391.Google Scholar
54.Earley, C. Restless Legs Syndrome. N Engl J Med. 2003;348:2103–2109.Google Scholar
55.Manconl, M, Govoni, V, De Vito, A, Economou, NT, Cesnik, E, Mollica, G, Granieri, E. Pregnancy as a risk factor for restless legs syndrome. Sleep Med. 2004;5:305–308.CrossRefGoogle Scholar
56.Patel, S. Restless legs syndrome and periodic limb movements of sleep: fact, fad, and fiction. Curr Opin Pulm Med. 2002;8:498–501.Google Scholar
57.O’Keeffe, ST, Gavin, K, Lavan, JN. Iron status and restless legs syndrome in the elderly. Age Ageing. 1994;23:200–203.Google Scholar
58.Aul, EA, Davis, BJ, Rodnitzky, RL. The importance of formal serum iron studies in the assessment of restless legs syndrome. Neurology. 1998:51:912–913.Google Scholar
59.Goodman, JD, Brodie, C, Ayida, GA. Restless leg syndrome in pregnancy. BMJ. 1988;297:1101–1102.CrossRefGoogle ScholarPubMed
60.Winkleman, JW, Chertow, GM, Lazarus, JM. Restless legs syndrome in end-stage renal disease. Am J Kidney Dis. 1996;28:372–378.CrossRefGoogle Scholar
61.Tan, EK, Ho, SC, Eng, P, et al.Restless legs symptoms in thyroid disorders. Parkinsonism Relat Disord. 2004;10:149–151.Google Scholar
62.Reynolds, G, Blake, DR, Pall, HS, Williams, A. Restless leg syndrome and rheumatoid arthritis. Br Med J (Clin Res Ed). 1986;292:659–660.CrossRefGoogle ScholarPubMed
63.Salih, AM, Gray, RE, Mills, KR, Webley, M. A clinical, serological and neurophysiological study of restless legs syndrome in rheumatoid arthritis. Br J Rheumatol. 1994;33:60–63.CrossRefGoogle ScholarPubMed
64.Rutkove, SB, Matheson, JK, Logigian, EL. Restless legs syndrome in patients with polyneuropathy. Muscle Nerve. 1996;19:670–672.Google Scholar
65.Krishnan, PR, Bhatia, M, Behari, M. Restless legs syndrome in Parkinson’s disease: a case-controlled study. Mov Disord. 2003;18:181–185.Google Scholar
66.Poewe, W, Hogl, B. Akathisia, restless legs and periodic limb movements in sleep in Parkinson’s disease. Neurology. 2004:63(8 suppl 3):S12–S16.Google Scholar
67.Allen, RP, Barker, PB, Wehrl, F, Song, HK, Earley, CJ. MRI measurement of brain iron in patients with restless legs syndrome. Neurology. 2001;56:263–265.Google Scholar
68.Hogl, B, Frauscher, B, Seppi, K, Ulmer, H, Poewe, W. Transient restless legs syndrome after spinal anesthesia: a prospective study. Neurology. 2002;59:1705–1707.Google Scholar
69.LaRochelle, JS, Karp, BI. Restless legs syndrome due to interferon-alpha. Mov Disord. 2004;19:730–731.Google Scholar
70.Akyol, A, Kiylioglu, N, Kadikoylu, G, Bolaman, AZ, Ozgel, N. Iron deficiency anemia and restless legs syndrome: is there an electrophysiological abnormality? Clin Neurol Neurosurg. 2003;106:23–27.CrossRefGoogle ScholarPubMed
71.Sevim, S, Dogu, O, Kaleagasi, H, Aral, M, Metin, O, Camdeviren, H. Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey. J Neurol Neurosurg Psychiatry. 2004;75:226–230.Google Scholar
72.Takaki, J, Nishi, T, Nangaku, M, et al.Clinical and psychological aspects of restless legs syndrome In uremic patients on hemodialysis. Am J Kidney Dis. 2003;41:833–839.Google Scholar
73.Mountifield, JA. Restless leg syndrome relieved by cessation of smoking. CMAJ. 1985;133:426–427.Google Scholar
74.Bucher, SF, Seelos, KC, Oertel, WH, Reiser, M, Trenkwalder, C. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol. 1997;41:639–645.Google Scholar
75.Bucher, SF, Trenkwalder, C, Oertel, WH. Reflex studies and MRI in the restless legs syndrome. Acta Neurol Scand. 1996;94:145–150.Google Scholar
76.Etgen, T, Draganski, B, Ilg, C, et al.Bilateral thalamic gray matter changes in patients with restless legs syndrome. Neuroimage. 2005;24:1242–1247.Google Scholar
77.Eisensehr, I, Wetter, TC, Linke, R, et al.Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome. Neurology. 2001;57:1307–1309.Google Scholar
78.Trenkwalder, C, Walters, AS, Hening, WA, et ak.Positron emission tomographic studies in restless legs syndrome. Mov Disord. 1999;14:141–145.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
79.Turjanksi, N, Lees, AJ, Brooks, DJ. Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11 C-raclopride PET studies. Neurology. 1999;52:932–937.Google Scholar
80.Michaud, M, Soucy, JP, Chabli, A, Lavigne, G, Montplaisir, J. SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep. J Neurol. 2002;249:164–170.CrossRefGoogle ScholarPubMed
81.Ruottinen, HM, Partineri, M, Hublin, C, et al.An FDOPA PET study in patients with periodic limb movement disorder and restless legs syndrome. Neurology. 2000;54:502–507.Google Scholar
82.Trenkwalder, C, Walters, AS, Hening, W. Periodic limb movements and restless legs syndrome. Neurol Clin. 1996;14:629–649.Google Scholar
83.von Spiczak, S, Whone, AL, Hammers, A, et al.The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study. Brain. 2005;128:906–917.Google Scholar
84.Rau, C, Hummel, F, Gerloff, C. Cortical involvement in the generation of “involuntary” movements in restless legs syndrome. Neurology. 2004;62:998–1000.Google Scholar
85.Entezari-Taher, M, Singleton, JR, Jones, CR, Meekins, G, Petajan, JH, Smith, AG. Changes in excitability of motor cortical circuitry in primary restless legs syndrome. Neurology. 1999;53:1201–1205.Google Scholar
86.Tergau, F, Wischer, S, Paulus, W. Motor system excitability in patients with restless legs syndrome. Neurology. 1999:52:1060–1063.Google Scholar
87.Stiasny-Kolster, K, Magerl, W, Oertel, WH, Moller, JC, Treede, RD. Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome. Brain. 2004;127(pt4):773–782Google Scholar
88.Polydefkis, M, Allen, RRHauer, CJ, Griffin, JW, McArthur, JC. Subclinical sensory neuropathy in late-onset restless legs syndrome. Neurology. 2000;55:1115–1121.Google Scholar
89.Schattschneider, J, Bode, A, Wasner, G, Binder, A, Deuschl, G, Baron, R. Idiopathic restless legs syndrome: abnormalities in central somatosensory processing. J Neurol. 2004;251:977–982.Google Scholar
90.Beard, JL, Connor, JR. Iron status and neural functioning. Annu Rev Nutr. 2003:23:41–58.Google Scholar
91.Connor, JR, Boyer, PJ, Menzies, SL, et al.Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology. 2003;61:304–309.Google Scholar
92.Sowers, JR, Vlachakis, N. Circadian variation in plasma dopamine levels in man. J Endocrinol Invest 1984;7:341–345.Google Scholar
93.Wang, X, Wiesinger, J, Beard, J, et al.Thy1 expression in the brain is affected by iron and is decreased in Restless Legs Syndrome. J Neurol Sci. 2004;220:59–66.Google Scholar
94.Earley, CJ, Connor, JR, Beard, JL, Malecki, EA, Epstein, DK, Allen, RP. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology. 2000;54:1698–1700.Google Scholar
95.Hening, W, Allen, R, Earley, C, Kushida, C, Picchietti, D, Silber, M. The treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Review.Sleep. 1999;22:970–999.Google Scholar
96.Littner, MR, Kushida, C, Anderson, WM, et al.Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep. 2004;27:557–559.Google Scholar
97.Hening, W, Allen, R, Earley, C, Picchietti, D, Silber, M. An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep. 2004;27:560–583.Google Scholar
98.Trenkwalder, C, Garcia-Borreguera, D, Montagna, P, et al.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. 2004;75:92–97.Google Scholar
99.Walters, AS, Ondo, WG, Dreykluft, T, et al.Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study. Mov Disord. 2004;19:1414–1423.Google Scholar
100.Garcia-Borreguero, D, Odin, P, Schwarz, C. Restless legs syndrome: an overview of the current understanding and management. Acta Neurol Scand. 2004;109:303–317.Google Scholar
101.Garcia-Borreguero, D. Augmentation: understanding a key feature of RLS. Sleep Med. 2004;5:5–6.Google Scholar