• Clinical science

Restless legs syndrome (Willis-Ekbom disease)


Restless legs syndrome (RLS), also referred to as Willis-Ekbom disease (WED), is a relatively common, neurological sleep disorder characterized by unpleasant sensations in the legs and a strong urge to move them. The urge increases during periods of rest, especially in the evenings, and may diminish with movement. Primary RLS is idiopathic and is often associated with a positive family history. Secondary RLS is less common and can result from a variety of underlying conditions, including iron deficiency, attention deficit hyperactivity disorder (ADHD), uremia, and Parkinson disease. Diagnostic tests are used to exclude secondary causes of RLS. Tests include ferritin levels, vitamin levels, autoantibody assays, thyroid profile, etc. Treatment for primary RLS includes dopamine agonists, while secondary RLS is managed by treating the underlying cause. If left untreated, RLS can cause significant social and functional impairment.


  • RLS affects up to 15% of the general US population [1]
  • Sex: >
  • Peak incidence: 30–40 years of age (often misdiagnosed as growing pains in childhood) [2]

Epidemiological data refers to the US, unless otherwise specified.



  • The pathophysiology of RLS remains unclear.
  • Studies suggest that abnormal dopamine pathways in the brain and impaired iron homeostasis (leading to iron deficiency in the substantia nigra) are the most prominent pathophysiological mechanisms involved. [8]

Clinical features

  • Main clinical features [9]
    • A recurrent urge to move the legs that is:
      • Typically relieved by movement
      • Begins and/or worsened with rest
    • Symptoms are worse in the evening and at night (may occur exclusively at night)
    • Can be accompanied by dysesthesias (e.g., pain, pins and needles, itching, tickling, or crawling sensations).
  • Other features


RLS is mainly a clinical diagnosis but additional testing may be indicated to rule out an underlying disease, including conducting laboratory tests, nerve conduction studies, polysomnogram, and needle electromyogram.

  • Clinical diagnosis (according to DSM V) [11]
    • See “Clinical features” above
    • Symptoms occur at least 3 times per week and persist for at least 3 months
    • Symptoms cause significant distress or impairment in social, occupational, educational, academic, behavioral, or other areas of functioning
    • Symptoms cannot be attributed to another medical condition (e.g., leg edema, arthritis, leg cramps) or behavioral condition (e.g. positional discomfort, habitual foot tapping)
    • Symptoms cannot be explained by drug/medication abuse
  • Laboratory tests
  • Polysomnogram: quantification of periodic limb movements of sleep (PLMS)
  • Needle electromyogram and nerve conduction studies: if a polyneuropathy or radiculopathy is suspected [12]


Treatment for primary RLS is largely symptomatic. Treatment of secondary RLS depends on the underlying cause. Intermittent treatment may be necessary for recurrent cases with spontaneous remission.

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  • 2. Ohayon MM, O'Hara R, Vitiello MV. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev. 2012; 16(4): pp. 283–95. doi: 10.1016/j.smrv.2011.05.002.
  • 3. Xiong L, Montplaisir J, Desautels A, et al. Family study of restless legs syndrome in Quebec, Canada: clinical characterization of 671 familial cases. Arch Neurol. 2010; 67(5): pp. 617–22. doi: 10.1001/archneurol.2010.67.
  • 4. Weinstock LB, Bosworth BP, Scherl EJ, et al. Crohnʼs disease is associated with restless legs syndrome. Inflamm Bowel Dis. 2010; 16(2): pp. 275–279. doi: 10.1002/ibd.20992.
  • 5. Weinstock LB, Walters AS, Mullin GE, Duntley SP. Celiac disease is associated with restless legs syndrome. Dig Dis Sci. 2009; 55(6): pp. 1667–1673. doi: 10.1007/s10620-009-0943-9.
  • 6. Cotter PE, O'Keeffe ST. Restless leg syndrome: is it a real problem?. Therapeutics and clinical risk management. 2006; 2(4): pp. 465–75. doi: 10.2147/tcrm.2006.2.4.465.
  • 7. Lee KA, Zaffke ME, 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(4): pp. 335–341. doi: 10.1089/152460901750269652.
  • 8. Winkelman JW. Considering the causes of RLS. Eur J Neurol. 2006; 13(s3): pp. 8–14. doi: 10.1111/j.1468-1331.2006.01586.x.
  • 9. International Restless Legs Syndrome Study Group. 2012 Revised IRLSSG Diagnostic Criteria for RLS. http://irlssg.org/diagnostic-criteria/. Updated March 31, 2017. Accessed March 31, 2017.
  • 10. Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lespérance P. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord. 1997; 12(1): pp. 61–65. doi: 10.1002/mds.870120111.
  • 11. Marelli S, Galbiati A, Rinaldi F, et al. Restless legs syndrome/Willis Ekbom disease: new diagnostic criteria according to different nosology. Arch Ital Biol. ; 153(2-3): pp. 184–93. doi: 10.12871/0003982920152343.
  • 12. Happe S, Paulus W. [Neurophysiological and neuroimaging studies for restless legs syndrome and periodic leg movement disorder]. Nervenarzt. 2006; 77(6): pp. 652, 654–6, 659–62. doi: 10.1007/s00115-005-2025-3.
  • 13. Silber MH, Ehrenberg BL, Allen RP, et al. An algorithm for the management of restless legs syndrome. Mayo Clin Proc. 2004; 79(7): pp. 916–922. doi: 10.1016/S0025-6196(11)62160-5.
  • 14. Garcia-Borreguero D, Kohnen R, Silber MH, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med. 2013; 14(7): pp. 675–684. doi: 10.1016/j.sleep.2013.05.016..
last updated 11/23/2020
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