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Sleep Medicine pp 249-254 | Cite as

History of Restless Legs Syndrome, Recently Named Willis–Ekbom Disease

Chapter

Abstract

After being recognized as a syndrome, Willis–Ekbom disease (WED) had been essentially ignored for three centuries until the excellent work of Ekbom in the mid-twentieth-century, carefully describing his case series. Shortly thereafter, attention to disorders disturbing sleep increased with advent of the discipline of sleep medicine. The discovery of periodic leg movements in sleep as a common feature of WED and then the serendipitous discovery of dopaminergic treatment both produced increased interest and attention to WED as a neurological disease. It was then appreciated that as Ekbom previously reported: This condition is so common that every physician is almost certain to see these patients in their practice. This has led to a rapid development of measurement instruments, diagnostic standards, approved treatments, and better understanding of the iron and genetic factors of WED. Much more could be considered about the history of assessments regarding social costs, quality of life, sleep, and multiple biological factors in the disease. Suffice it to note that this disease has rapidly progressed in the last half century from one unknown and untreatable to one with good treatment options and clear directions for biologically based improvements in the future.

Keywords

Wills-Ekbom disease Restless legs syndrome Serum ferritin Periodic limb movements in sleep and wakefulness International Restless Legs Syndrome Study Group RLS mimics 

References

  1. 1.
    Willis T. The London practice of physick. London: Bassett and Crooke; 1685.Google Scholar
  2. 2.
    Allen RP, Stillman P, Myers AJ. Physician-diagnosed restless legs syndrome in a large sample of primary medical care patients in western Europe: prevalence and characteristics. Sleep Med. 2010;11:31–7.Google Scholar
  3. 3.
    Allen RP, Bharmal M, Calloway M. Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord. 2011;26:114–20.Google Scholar
  4. 4.
    Willis T. De Animae Brutorum. London: Wells and Scott; 1672.Google Scholar
  5. 5.
    Wittmaack T. Pathologie und Therapie der Sensibilitäts neurosen. Liepzig: Schäfer; 1861.Google Scholar
  6. 6.
    Beard G. A practical treatis on nervous exhaustion. New York: William Wood; 1880.Google Scholar
  7. 7.
    Ekbom KA. Asthenia crurum paraesthetica (“irritable legs”). Acta Medica Scandinavica. 1944;118(1–3):197–209.Google Scholar
  8. 8.
    Ekbom KA. Restless legs. Stockholm: Ivar Haeggströms; 1945.Google Scholar
  9. 9.
    Mussio-Fournier JC, Rawak F. Familiäres Auftreten von Pruritus, Utikaria und parästhetischer Hyperkinese der unteren Extremitäten. Confinia Neurol. 1940;3:110–4.Google Scholar
  10. 10.
    Allison FG. Obscure pains in the chest, back or limbs. Can Med Assoc J. 1943;48:36–9.Google Scholar
  11. 11.
    Symonds CP. Nocturnal myoclonus. J Neurol Neurosurg Psychiatr. 1953;16:166.Google Scholar
  12. 12.
    Lugaresi E, Coccagna G, Berti Ceroni G, Ambrosetto C. Restless legs syndrome and nocturnal myoclonus. In: Gastaut H, Lugaresi E, Berti Ceroni G, editors. The abnormalites of sleep in man. Bologna: Aulo Gaggi Editore; 1968. 285–94.Google Scholar
  13. 13.
    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;12:61–5.Google Scholar
  14. 14.
    Montplaisir J, Michaud M, Denesle R, Gosselin A. Periodic leg movements are not more prevalent in insomnia or hypersomnia but are specifically associated with sleep disorders involving a dopaminergic impairment. Sleep Med. 2000;1:163–7.Google Scholar
  15. 15.
    Pennestri MH, Whittom S, Adam B, Petit D, Carrier J, Montplaisir J. PLMS and PLMW in healthy subjects as a function of age: prevalence and interval distribution. Sleep. 2006;29:1183–7.Google Scholar
  16. 16.
    ASDA. International classification of sleep disorders, revised: Diagnostic and coding manual. Rochester, Minnesota: American Sleep Disorders Association; 1997.Google Scholar
  17. 17.
    Allen RP, Barker PB, Horska A, Earley CJ. Thalamic glutamate/glutamine in restless legs syndrome: increased and related to disturbed sleep. Neurology. 2013;80:2028–34.Google Scholar
  18. 18.
    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 syndrome. Acta Neurol Scand. 1988;77:418–21.Google Scholar
  19. 19.
    Walters AS, Aldrich MA, Allen RP, Ancoli-Israel S, Buchholz D, Chockroverty S, et al. Toward a better definition of the restless legs syndrome. Mov Disord. 1995;10:634–42.Google Scholar
  20. 20.
    Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir 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;4:101–19.Google Scholar
  21. 21.
    Hening WA, Allen RP, Washburn M, Lesage S, Earley C. The four diagnostic criteria for the restless legs syndrome are unable to exclude confounding conditions (“mimics”). Sleep Med. 2009;10:976–81.Google Scholar
  22. 21a.
    Cho, Y.W., et al., Prevalence and clinical characteristics of restless legs syndrome in diabetic peripheral neuropathy: comparison with chronic osteoarthritis. Sleep Med, 2013; 14: 1387–92Google Scholar
  23. 21b.
    Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walter 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 signifi cance. Sleep Med, 2014;15:860–73.Google Scholar
  24. 22.
    Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003;4:121–32.Google Scholar
  25. 23.
    Abetz L, Arbuckle R, Allen RP, Garcia-Borreguero D, Hening W, Walters AS, et al. The reliability, validity and responsiveness of the International Restless Legs Syndrome Study Group rating scale and subscales in a clinical-trial setting. Sleep Med. 2006;7:340–9.Google Scholar
  26. 24.
    Lavigne GJ, Montplaisir JY. Restless legs syndrome and sleep bruxism: prevalence and association among Canadians. Sleep. 1994;17:739–43.Google Scholar
  27. 25.
    Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med. 2005;165:1286–92.Google Scholar
  28. 26.
    Allen RP, Burchell BJ, MacDonald B, Hening WA, Earley CJ. Validation of the self-completed Cambridge-Hopkins questionnaire (CH-RLSq) for ascertainment of restless legs syndrome (RLS) in a population survey. Sleep Med. 2009;10:1097–100.Google Scholar
  29. 27.
    O’Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing. 1994;23:200–3.Google Scholar
  30. 28.
    O’Keeffe ST, Noel J, Lavan JN. Restless legs syndrome in the elderly. Postgrad Med J. 1993;69:701–3.Google Scholar
  31. 29.
    Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ. MRI measurement of brain iron in patients with restless legs syndrome. Neurology. 2001;56:263–5.Google Scholar
  32. 30.
    Earley CJ, Barker PB, Horska A, Allen RP. MRI-determined regional brain iron concentrations in early- and late-onset restless legs syndrome. Sleep Med. 2006;7:459–61.Google Scholar
  33. 31.
    Schmidauer C, Sojer M, Seppi K, Stockner H, Hogl B, Biedermann B, et al. Transcranial ultrasound shows nigral hypoechogenicity in restless legs syndrome. Ann Neurol. 2005;58:630–4.Google Scholar
  34. 32.
    Godau J, Klose U, Di Santo A, Schweitzer K, Berg D. Multiregional brain iron deficiency in restless legs syndrome. Mov Disord. 2008;23:1184–7.Google Scholar
  35. 33.
    Godau J, Manz A, Wevers AK, Gaenslen A, Berg D. Sonographic substantia nigra hypoechogenicity in polyneuropathy and restless legs syndrome. Mov Disord. 2009;24:133–7.Google Scholar
  36. 34.
    Godau J, Schweitzer KJ, Liepelt I, Gerloff C, Berg D. Substantia nigra hypoechogenicity: definition and findings in restless legs syndrome. Mov Disord. 2007;22:187–92.Google Scholar
  37. 35.
    Connor JR, Boyer PJ, Menzies SL, Dellinger B, Allen RP, Earley CJ. Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology. 2003;61:304–9.Google Scholar
  38. 35a.
    Stefansson H1, Rye DB, Hicks A, et al. A genetic risk factor for periodic limb movements in sleep. N Engl J Med. 2007 Aug 16;357(7):639-47.Google Scholar
  39. 36.
    Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet. 2007;39:1000–6.Google Scholar
  40. 37.
    Hening WA, Walters A, Kavey N, Gidro-Frank S, Cote L, Fahn S. Dyskinesias while awake and periodic movements in sleep in restless legs syndrome: treatment with opioids. Neurology. 1986;36:1363–6.Google Scholar
  41. 38.
    Mitler MM, Browman CP, Menn SJ, Gujavarty K, Timms RM. Nocturnal myoclonus: Treatment efficacy of clonazepam and temazepam. Sleep. 1986;9:385–92.Google Scholar
  42. 39.
    Boghen D, Lamothe L, Elie R, Godbout R, Montplaisir J. The treatment of the restless legs syndrome with clonazepam: a prospective controlled study. Can J Neurol Sci. 1986;13:245–7.Google Scholar
  43. 40.
    Akpinar S. Treatment of restless legs syndrome with levodopa plus benserazide [letter]. Arch Neurol. 1982;39:739.Google Scholar
  44. 41.
    Kaplan PW, Allen RP, Buchholz DW, Walters JK. A double-blind, placebo-controlled study of the treatment of periodic limb movements in sleep using carbidopa/levodopa and propoxyphene. Sleep. 1993;16:717–23.Google Scholar
  45. 42.
    Allen RP, Kaplan PW, Buchholz DW, Earley CJ, Walters JK. Double-blinded, placebo controlled comparison of high dose propoxyphene and moderate dose carbidopa/levodopa for treatment of periodic limb movements in sleep. Sleep Res. 1992;21:166.Google Scholar
  46. 43.
    Allen R, Early CJ, Hening WA, Walters AS, Wagner MI, Yaffee JB. Double-blind, placebo-controlled, multi-center evaluation of the restless legs syndrome treatment with pergolide (abstract). Sleep. 1998;21:142.Google Scholar
  47. 44.
    Montplaisir J, Nicolas A, Denesle R, Gomez-Mancilla B. Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology. 1999;52:938–43.Google Scholar
  48. 45.
    Freeman A, Rye D, Bliwise DL, Chakravorty S, Krulewicz S, Watts R. Ropinirole fo restless legs syndrome (RLS): an open-label and double-blind placebo-controlled study. Neurology. 2001;56:A5.Google Scholar
  49. 46.
    Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep. 1996;19:205–13.Google Scholar
  50. 47.
    Silber MH, Girish M, Izurieta R. Pramipexole in the management of restless legs syndrome: an extended study. Sleep. 2003;26:819–21.Google Scholar
  51. 48.
    Winkelman JW, Johnston L. Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med. 2004;5:9–14.Google Scholar
  52. 49.
    Inoue Y, Uchimura N, Kuroda K, Hirata K, Hattori N. Long-term efficacy and safety of gabapentin enacarbil in Japanese restless legs syndrome patients. Prog Neuropsychopharmacol Biol Psychiatry. 2012;36:251–7.Google Scholar
  53. 50.
    Lee DO, Ziman RB, Perkins AT, Poceta JS, Walters AS, Barrett RW, et al. A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome. J Clin Sleep Med. 2011;7:282–92.Google Scholar
  54. 51.
    Walters AS, Ondo WG, Kushida CA, Becker PM, Ellenbogen AL, Canafax DM, et al. Gabapentin Enacarbil in Restless Legs Syndrome: A Phase 2b, 2-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Clin Neuropharmacol. 2009; 6:311-20.Google Scholar
  55. 52.
    Ondo WG. Methadone for refractory restless legs syndrome. Mov Disord. 2005;20:345–8.Google Scholar
  56. 53.
    Earley CJ, Connors JR, Allen RP. RLS patients have abnormally reduced CSF ferritin compared to normal controls. Neurology. 1999;52 (suppl 2):A111–A2.Google Scholar
  57. 54.
    Nordlander NB. Therapy in restless legs. Acta Med Scand. 1953;145:453–7.Google Scholar
  58. 55.
    Nordlander NB. Restless legs. Brit J Phys Med. 1954;17:160–2.Google Scholar
  59. 56.
    Unger EL, Earley CJ, Thomsen LL, Jones BC, Allen RP. Effects of IV iron isomaltoside-1000 treatment on regional brain iron status in an iron-deficient animal. Neuroscience. 2013;246:179–85.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2015

Authors and Affiliations

  1. 1.Department of NeurologyJohns Hopkins UniversityBaltimoreUSA

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