Download PDF
Semin Neurol 2004; 24(3): 249-259
DOI: 10.1055/s-2004-835066
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Restless Legs Syndrome and Periodic Limb Movement Disorder: A Review of Management

Suzanne Lesage1 , Wayne A. Hening2
  • 1RLS Center, Department of Neurology, Johns Hopkins Medical School, Baltimore, Maryland
  • 2Department of Neurology, UMDNJ-RW Johnson Medical School, New Brunswick, New Jersey
Further Information

Publication History

Publication Date:
27 September 2004 (online)

    Permissions and Reprints

The restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are distinguishable but overlapping disorders. Both feature nocturnal involuntary limb movements (periodic limb movements) that can cause sleep disruption, but each has distinct clinical features that are relevant to the diagnosis and management of the patient. The diagnosis of RLS is made by meeting established clinical criteria, not from discovery of periodic limb movements of sleep (PLMS) on a sleep study. PLMD, however, does require the presence of PLMS on polysomnography as well as an associated sleep complaint. Moreover, PLMS are themselves nonspecific, occurring both with RLS and with other sleep disorders as well as in normal individuals. The diagnosis of PLMD, then, requires not merely finding a significant number of PLMS but also excluding other potential causes for the associated sleep complaint. Treatment of RLS is based on consideration of the pattern and severity of the disorder, with dopaminergic drugs generally favored for initial treatment. Anticonvulsants, opioids, and sedative/hypnotics also have a role. A treatment algorithm is provided to assist with the management of RLS. Treatment of PLMD relies on many of the same medications, but is generally more straightforward and places a greater reliance on levodopa compounds and sedative-hypnotics.

KEYWORDS

Restless legs - periodic limb movements - insomnia - diagnosis - treatment

REFERENCES

  • 1 Willis T. Two Discourses Concerning the Soul of Brutes. London; Dring, Harper, and Leigh 1683
    Google Scholar
  • 2 Ekbom K A. Restless legs: a clinical study.  Acta Med Scand Suppl. 1945;  158 1-122
    PubMedGoogle Scholar
  • 3 Ekbom K A. Restless legs syndrome.  Neurology. 1960;  10 868-873
    PubMedGoogle Scholar
  • 4 Allen R P, Picchietti D, Hening W A, Trenkwalder C, Walters A S, Montplaisi J. 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
    CrossrefPubMedGoogle Scholar
  • 5 Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lesperance P. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria.  Mov Disord. 1997;  12 61-65
    CrossrefPubMedGoogle Scholar
  • 6 Trenkwalder C, Hening W A, Walters A S, Campbell S S, Rahman K, Chokroverty S. Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome.  Mov Disord. 1999;  14 102-110
    CrossrefPubMedGoogle Scholar
  • 7 Allen R P, Earley C J. Restless legs syndrome: a review of clinical and pathophysiologic features.  J Clin Neurophysiol. 2001;  18 128-147
    PubMedGoogle Scholar
  • 8 Saletu M, Anderer P, Saletu B, Lindeck-Pozza L, Hauer C, Saletu-Zyhlarz G. EEG mapping in patients with restless legs syndrome as compared with normal controls.  Psychiatry Res. 2002;  115 49-61
    PubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 Rothdach A J, 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
    PubMedGoogle Scholar
  • 11 Tan E K, Seah A, See S J, Lim E, Wong M C, Koh K K. Restless legs syndrome in an Asian population: a study in Singapore.  Mov Disord. 2001;  16 577-579
    CrossrefPubMedGoogle Scholar
  • 12 Sevim S, Dogu O, Camdeviren H et al.. Unexpectedly low prevalence and unusual characteristics of RLS in Mersin, Turkey.  Neurology. 2003;  61 1562-1569
    PubMedGoogle Scholar
  • 13 Krishnan P R, Bhatia M, Behari M. Restless legs syndrome in Parkinson's disease: a case-controlled study.  Mov Disord. 2003;  18 181-185
    CrossrefPubMedGoogle Scholar
  • 14 Hening W A, Walters A S, Allen R P, 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
    CrossrefPubMedGoogle Scholar
  • 15 Hui D S, Wong T Y, Ko F W et al.. Prevalence of sleep disturbances in Chinese patients with end-stage renal failure on continuous ambulatory peritoneal dialysis.  Am J Kidney Dis. 2000;  36 783-788
    CrossrefPubMedGoogle Scholar
  • 16 Hui D, Wong T, Li T et al.. Prevalence of sleep disturbances in Chinese patients with end stage renal failure on maintenance hemodialysis.  Med Sci Monit. 2002;  8 CR331-CR336
    PubMedGoogle Scholar
  • 17 Collado-Seidel V, Kohnen R, Samtleben W, Hillebrand G F, Oertel W H, Trenkwalder C. Clinical and biochemical findings in uremic patients with and without restless legs syndrome.  Am J Kidney Dis. 1998;  31 324-328
    CrossrefPubMedGoogle Scholar
  • 18 Lee K A, Zaffke M E, Baratte-Beebe K. Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron.  J Womens Health Gend Based Med. 2001;  10 335-341
    CrossrefPubMedGoogle Scholar
  • 19 Suzuki K, Ohida T, Sone T et al.. The prevalence of restless legs syndrome among pregnant women in Japan and the relationship between restless legs syndrome and sleep problems.  Sleep. 2003;  26 673-677
    PubMedGoogle Scholar
  • 20 Winkelman J W, Chertow G M, Lazarus J M. Restless legs syndrome in end-stage renal disease.  Am J Kidney Dis. 1996;  28 372-378
    CrossrefPubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Benz R L, Pressman M R, Hovick E T, Peterson D D. A preliminary study of the effects of correction of anemia with recombinant human erythropoietin therapy on sleep, sleep disorders, and daytime sleepiness in hemodialysis patients (The SLEEPO study).  Am J Kidney Dis. 1999;  34 1089-1095
    PubMedGoogle Scholar
  • 23 Silber M H, Richardson J W. Multiple blood donations associated with iron deficiency in patients with restless legs syndrome.  Mayo Clin Proc. 2003;  78 52-54
    PubMedGoogle Scholar
  • 24 Polydefkis M, Allen R P, Hauer P, Earley C J, Griffin J W, McArthur J C. Subclinical sensory neuropathy in late-onset restless legs syndrome.  Neurology. 2000;  55 1115-1121
    PubMedGoogle Scholar
  • 25 Gemignani F, Marbini A, Di Giovanni G et al.. Cryoglobulinaemic neuropathy manifesting with restless legs syndrome.  J Neurol Sci. 1997;  152 218-223
    CrossrefPubMedGoogle Scholar
  • 26 Gemignani F, Marbini A, Di Giovanni G, Salih S, Terzano M G. Charcot-Marie-Tooth disease type 2 with restless legs syndrome.  Neurology. 1999;  52 1064-1066
    PubMedGoogle Scholar
  • 27 Abele M, Burk K, Laccone F, Dichgans J, Klockgether T. Restless legs syndrome in spinocerebellar ataxia types 1, 2, and 3.  J Neurol. 2001;  248 311-314
    CrossrefPubMedGoogle Scholar
  • 28 Schols L, Haan J, Riess O, Amoiridis G, Przuntek H. Sleep disturbance in spinocerebellar ataxias: is the SCA3 mutation a cause of restless legs syndrome?.  Neurology. 1998;  51 1603-1607
    PubMedGoogle Scholar
  • 29 Banno K, Delaive K, Walld R, Kryger M H. Restless legs syndrome in 218 patients: associated disorders.  Sleep Med. 2000;  1 221-229
    PubMedGoogle Scholar
  • 30 Salih A M, Gray R E, Mills K R, Webley M. A clinical, serological and neurophysiological study of restless legs syndrome in rheumatoid arthritis.  Br J Rheumatol. 1994;  33 60-63
    PubMedGoogle Scholar
  • 31 Ondo W, Tan E K, Mansoor J. Rheumatologic serologies in secondary restless legs syndrome.  Mov Disord. 2000;  15 321-323
    CrossrefPubMedGoogle Scholar
  • 32 Ondo W G, Vuong K D, Jankovic J. Exploring the relationship between Parkinson disease and restless legs syndrome.  Arch Neurol. 2002;  59 421-424
    CrossrefPubMedGoogle Scholar
  • 33 Allen R P, Earley C J. Augmentation of the restless legs syndrome with carbidopa/levodopa.  Sleep. 1996;  19 205-213
    PubMedGoogle Scholar
  • 34 Walters A S, LeBrocq C, Passi V et al.. A preliminary look at the percentage of patients with restless legs syndrome who also have Parkinson disease, essential tremor or tourette syndrome in a single practice.  J Sleep Res. 2003;  12 343-345
    PubMedGoogle Scholar
  • 35 Agargun M Y, Kara H, Ozbek H, Tombul T, Ozer O A. Restless legs syndrome induced by mirtazapine.  J Clin Psychiatry. 2002;  63 1179
    PubMedGoogle Scholar
  • 36 Bakshi R. Fluoxetine and restless legs syndrome.  J Neurol Sci. 1996;  142 151-152
    CrossrefPubMedGoogle Scholar
  • 37 Hargrave R, Beckley D J. Restless leg syndrome exacerbated by sertraline.  Psychosomatics. 1998;  39 177-178
    PubMedGoogle Scholar
  • 38 Sanz-Fuentenebro F J, Huidobro A, Tejadas-Rivas A. Restless legs syndrome and paroxetine.  Acta Psychiatr Scand. 1996;  94 482-484
    CrossrefPubMedGoogle Scholar
  • 39 Walters A S, Hening W, Rubinstein M, Chokroverty S. A clinical and polysomnographic comparison of neuroleptic-induced akathisia and the idiopathic restless legs syndrome.  Sleep. 1991;  14 339-345
    PubMedGoogle Scholar
  • 40 Chesson Jr A L, Ferber R A, Fry J M et al.. The indications for polysomnography and related procedures.  Sleep. 1997;  20 423-487
    PubMedGoogle Scholar
  • 41 Littner M, Hirshkowitz M, Kramer M et al.. Practice parameters for using polysomnography to evaluate insomnia: an update.  Sleep. 2003;  26 754-760
    PubMedGoogle Scholar
  • 42 Gorny S, Allen R, Krausman D, Earley C. Evaluation of the PAM-RL system for the detection of periodic leg movements during sleep in the lab and home environments.  Sleep. 1998;  21 183 , Abstract
    PubMedGoogle Scholar
  • 43 Allen R P. Ambulatory activity monitoring. In: Chokroverty S, Hening WA, Walters AS Sleep and Movement Disorders Philadelphia; Butterworth-Heinemann 2003: 144-152
    Google Scholar
  • 44 O'Keeffe S T, Gavin K, Lavan J N. Iron status and restless legs syndrome in the elderly.  Age Ageing. 1994;  23 200-203
    PubMedGoogle Scholar
  • 45 Sun E R, Chen C A, Ho G, Earley C J, Allen R P. Iron and the restless legs syndrome.  Sleep. 1998;  21 371-377
    PubMedGoogle Scholar
  • 46 Barton J C, Wooten V D, Acton R T. Hemochromatosis and iron therapy of restless legs syndrome.  Sleep Med. 2001;  2 249-251
    PubMedGoogle Scholar
  • 47 Earley C J. Hemochromatosis and iron therapy of restless legs syndrome.  Sleep Med. 2001;  2 181-183
    PubMedGoogle Scholar
  • 48 Hornyak M, Voderholzer U, Hohagen F, Berger M, Riemann D. Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study.  Sleep. 1998;  21 501-505
    PubMedGoogle Scholar
  • 49 Staedt J, Stoppe G, Kogler A et al.. Nightly myoclonus syndrome (NMS) and restless legs syndrome (RLS): review and case report [in German].  Fortschr Neurol Psychiatr. 1994;  62 88-93
    PubMedGoogle Scholar
  • 50 Eisensehr I, Wetter T C, Linke R et al.. Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome.  Neurology. 2001;  57 1307-1309
    PubMedGoogle Scholar
  • 51 Michaud M, Soucy J P, 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
    PubMedGoogle Scholar
  • 52 Ruottinen H M, Partinen M, Hublin C et al.. An FDOPA PET study in patients with periodic limb movement disorder and restless legs syndrome.  Neurology. 2000;  54 502-504
    PubMedGoogle Scholar
  • 53 Trenkwalder C, Walters A S, Hening W A et al.. Positron emission tomographic studies in restless legs syndrome.  Mov Disord. 1999;  14 141-145
    CrossrefPubMedGoogle Scholar
  • 54 Turjanski N, Lees A J, Brooks D J. Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies.  Neurology. 1999;  52 932-937
    CrossrefPubMedGoogle Scholar
  • 55 Connor J R, Boyer P J, Menzies S L, Dellinger B, Allen R P, Earley C J. Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome.  Neurology. 2003;  61 304-309
    PubMedGoogle Scholar
  • 56 Tergau F, Wischer S, Paulus W. Motor system excitability in patients with restless legs syndrome.  Neurology. 1999;  52 1060-1063
    PubMedGoogle Scholar
  • 57 Quatrale R, Manconi M, Gastaldo E et al.. Neurophysiological study of corticomotor pathways in restless legs syndrome.  Clin Neurophysiol. 2003;  114 1638-1645
    CrossrefPubMedGoogle Scholar
  • 58 Earley C J, Allen R P, Beard J L, Connor J R. Insight into the pathophysiology of restless legs syndrome.  J Neurosci Res. 2000;  62 623-628
    CrossrefPubMedGoogle Scholar
  • 59 Allen R P, Barker P B, Wehrl F, Song H K, Earley C J. MRI measurement of brain iron in patients with restless legs syndrome.  Neurology. 2001;  56 263-265
    PubMedGoogle Scholar
  • 60 Earley C J, Connors J R, Allen R P. RLS patients have abnormally reduced CSF ferritin compared to normal controls.  Neurology. 1999;  52(suppl 2) A111-A112
    PubMedGoogle Scholar
  • 61 Akpinar S. Treatment of restless legs syndrome with levodopa plus benserazide.  Arch Neurol. 1982;  39 739
    PubMedGoogle Scholar
  • 62 Montplaisir J, Godbout R, Poirier G, Bédard M A. Restless legs syndrome and periodic movements in sleep: physiopathology and treatment with L-dopa.  Clin Neuropharmacol. 1986;  9 456-463
    PubMedGoogle Scholar
  • 63 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
    PubMedGoogle Scholar
  • 64 Hening W A, Allen R P, Earley C J, Picchietti D L, Silber M. An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder: An American Academy of Sleep Medicine interim review.  Sleep. 2004;  27 560-583
    PubMedGoogle Scholar
  • 65 Silber M H, Girish M, Izurieta R. Pramipexole in the management of restless legs syndrome: an extended study.  Sleep. 2003;  26 819-821
    PubMedGoogle Scholar
  • 66 Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study.  Neurology. 2002;  59 1573-1579
    CrossrefPubMedGoogle Scholar
  • 67 Walters A S, Wagner M L, Hening W A et al.. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo.  Sleep. 1993;  16 327-332
    PubMedGoogle Scholar
  • 68 The Atlas Task Force . Recording and scoring leg movements.  Sleep. 1993;  16 748-759
    PubMedGoogle Scholar
  • 69 Michaud M, Poirier G, Lavigne G, Montplaisir J. Restless legs syndrome: scoring criteria for leg movements recorded during the suggested immobilization test.  Sleep Med. 2001;  2 317-321
    PubMedGoogle Scholar
  • 70 Diagnostic Classification Steering Committee of the American Sleep Disorders Association (M. J. Thorpy-Chairperson) .The International Classification of Sleep Disorders: Diagnostic and Coding Manual. Rochester, MN; American Sleep Disorders Association 1997
    Google Scholar
  • 71 Wetter T C, Pollmacher T. Restless legs and periodic leg movements in sleep syndromes.  J Neurol. 1997;  244 S37-S45
    CrossrefPubMedGoogle Scholar
  • 72 Fantini M L, Michaud M, Gosselin N, Lavigne G, Montplaisir J. Periodic leg movements in REM sleep behavior disorder and related autonomic and EEG activation.  Neurology. 2002;  59 1889-1894
    PubMedGoogle Scholar
  • 73 Smith R C. Relationship of periodic movements in sleep (nocturnal myoclonus) and the Babinski sign.  Sleep. 1985;  8 239-243
    PubMedGoogle Scholar
  • 74 Bara-Jimenez W, Aksu M, Graham B, Sato S, Hallett M. Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex.  Neurology. 2000;  54 1609-1616
    PubMedGoogle Scholar
  • 75 Trenkwalder C, Bucher S F, Oertel W H. Electrophysiological pattern of involuntary limb movements in the restless legs syndrome.  Muscle Nerve. 1996;  19 155-162
    PubMedGoogle Scholar
  • 76 Provini F, Vetrugno R, Meletti S et al.. Motor pattern of periodic limb movements during sleep.  Neurology. 2001;  57 300-304
    PubMedGoogle Scholar
  • 77 de Weerd A W, Rijsman R M, Brinkley A. Activity patterns of leg muscles in periodic limb movement disorder.  J Neurol Neurosurg Psychiatry. 2004;  75 317-319
    PubMedGoogle Scholar
  • 78 Simakajornboon N, Gozal D, Vlasic V, Mack C, Sharon D, McGinley B M. Periodic limb movements in sleep and iron status in children.  Sleep. 2003;  26 735-738
    PubMedGoogle Scholar
  • 79 Ancoli-Israel S, Kripke D F, Mason W, Kaplan O J. Sleep apnea and periodic movements in an aging sample.  J Gerontol. 1985;  40 419-425
    PubMedGoogle Scholar
  • 80 Nicolas A, Lespérance P, Montplaisir J. Is excessive daytime sleepiness with periodic leg movements during sleep a specific diagnostic category?.  Eur Neurol. 1998;  40 22-26
    CrossrefPubMedGoogle Scholar
  • 81 Eisensehr I, Ehrenberg B L, Noachtar S. Different sleep characteristics in restless legs syndrome and periodic limb movement disorder.  Sleep Med. 2003;  4 147-152
    CrossrefPubMedGoogle Scholar

Suzanne LesageM.D. 

RLS Center, Asthma and Allergy, 1B76, Johns Hopkins Bayview Medical Center

5501 Hopkins Bayview Circle, Baltimore, MD 21224