Restless legs syndrome

Last updated: November 23, 2023

Summarytoggle arrow icon

Restless legs syndrome (RLS; also referred to as Willis-Ekbom disease) is a common sleep-related movement disorder characterized by a strong urge to move the legs that is triggered and/or worsened with rest and is usually accompanied by uncomfortable sensations (e.g., pain, pins and needles, itching, tickling, crawling sensation). The urge to move the legs increases in the evenings and at night and is typically relieved by movement. Primary RLS is idiopathic but often associated with a positive family history. Secondary RLS is less common and results from a variety of underlying conditions (e.g., iron deficiency, uremia, Parkinson disease) and drugs (e.g., H1 antihistamines, antidepressants). Diagnostic studies (e.g., iron studies, polysomnography) can help exclude causes of secondary RLS and alternative diagnoses. Treatment depends on the duration and severity of symptoms and includes medications such as alpha-2-delta calcium channel ligands and treating underlying conditions (e.g., with iron supplementation).

Epidemiologytoggle arrow icon

  • 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.

Etiologytoggle arrow icon

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

  • Main features [9]
    • A recurrent urge to move the legs that is:
      • Typically relieved by movement
      • Triggered and/or worsened with rest
      • Worse in the evening and at night (may occur exclusively at night)
    • The urge to move the legs is often accompanied by uncomfortable sensations (e.g., pain, pins and needles, itching, tickling, or crawling sensations).
  • Other features

Diagnosticstoggle arrow icon

General principles [10]

Diagnostic criteria [9]

International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria [9][11]
Essential criteria
  • An urge to move the legs (or other body parts) which:
    • May be accompanied by uncomfortable sensations
    • Begins and/or increases with inactivity
    • Is wholly or partially relieved by movement (e.g., walking or stretching)
    • Only occurs at night or in the evening, or is worse than during the day
  • Symptoms cannot be solely accounted for by other medical or behavioral conditions (e.g., chronic venous disease, habitual foot tapping).
Supportive criteria
  • PLMS or PLMW that are more severe or frequent than expected for age or medical status
  • Initial (or longer lasting) reduction in symptoms with dopaminergic treatment
  • First-degree relative(s) with RLS
  • Lack of expected daytime sleepiness
If not all essential criteria are met but suspicion for RLS remains, supportive criteria can help diagnose RLS.

Diagnostic studies [10]

Laboratory studies

Advanced testing

30% of patients with iron deficiency have symptoms of RLS. [10]

Treatmenttoggle arrow icon

Treatment is mainly symptomatic. Pharmacotherapy is based on the severity and frequency of symptoms and the presence of comorbidities.

General principles [10][12]

  • Treat underlying and comorbid conditions.
  • Consider discontinuing or adjusting medications that may cause or aggravate RLS symptoms.
  • Encourage lifestyle modifications.
    • Consider a trial period of avoiding exacerbating factors, e.g., coffee and alcohol.
    • Sleep hygiene counseling
    • Regular physical activity
    • Activities to distract from symptoms, e.g., video games, crosswords
  • Consider stimulation techniques, e.g., vibrating pad, acupuncture, magnetic or electrical stimulation.
  • Consider pharmacotherapy in patients with inadequate response to iron supplementation and supportive care.

Iron supplementation [12]

  • Provide oral iron supplementation; e.g., ferrous sulfate with vitamin C for patients with serum ferritin ≤ 75 ng/L and transferrin saturation < 45% [10][12]
  • IV iron supplementation, e.g., ferric carboxymaltose , may be indicated for patients with: [13]
    • Moderate or severe chronic persistent RLS and either:
    • Intolerance or inadequate absorption of oral iron
    • Inadequate improvement after 3 months of oral iron supplementation
  • Monitor serum ferritin levels every 3–6 months.

Pharmacotherapy [10][12]

Intermittent RLS

Chronic persistent RLS [12]

Refractory RLS (or RLS associated with a severe pain disorder)

For pregnant patients, nonpharmacological interventions are the mainstay of treatment because most pharmacological agents are contraindicated. [10][12]

Close follow-up with risk mitigation for opioid prescribing is required for patients taking opioids. [10]

Referencestoggle arrow icon

  1. Ramar K, Olson EJ. Management of common sleep disorders. Am Fam Physician. 2013; 88 (4): p.231-238.
  2. Ohayon MM, O'Hara R, Vitiello MV. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev. 2012; 16 (4): p.283-95.doi: 10.1016/j.smrv.2011.05.002 . | Open in Read by QxMD
  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): p.617-22.doi: 10.1001/archneurol.2010.67 . | Open in Read by QxMD
  4. Weinstock LB, Bosworth BP, Scherl EJ, et al. Crohnʼs disease is associated with restless legs syndrome. Inflamm Bowel Dis. 2010; 16 (2): p.275-279.doi: 10.1002/ibd.20992 . | Open in Read by QxMD
  5. Weinstock LB, Walters AS, Mullin GE, Duntley SP. Celiac disease is associated with restless legs syndrome. Dig Dis Sci. 2009; 55 (6): p.1667-1673.doi: 10.1007/s10620-009-0943-9 . | Open in Read by QxMD
  6. Cotter PE, O'Keeffe ST. Restless leg syndrome: is it a real problem?. Therapeutics and clinical risk management. 2006; 2 (4): p.465-75.doi: 10.2147/tcrm.2006.2.4.465 . | Open in Read by QxMD
  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): p.335-341.doi: 10.1089/152460901750269652 . | Open in Read by QxMD
  8. Winkelman JW. Considering the causes of RLS. Eur J Neurol. 2006; 13 (s3): p.8-14.doi: 10.1111/j.1468-1331.2006.01586.x . | Open in Read by QxMD
  9. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria – history, rationale, description, and significance. Sleep Med. 2014; 15 (8): p.860-873.doi: 10.1016/j.sleep.2014.03.025 . | Open in Read by QxMD
  10. Manconi M, Garcia-Borreguero D, Schormair B, et al. Restless legs syndrome. Nat Rev Dis Primers. 2021; 7 (1).doi: 10.1038/s41572-021-00311-z . | Open in Read by QxMD
  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): p.184-93.doi: 10.12871/0003982920152343 . | Open in Read by QxMD
  12. Silber MH, Buchfuhrer MJ, Earley CJ, et al. The Management of Restless Legs Syndrome: An Updated Algorithm. Mayo Clin Proc. 2021; 96 (7): p.1921-1937.doi: 10.1016/j.mayocp.2020.12.026 . | Open in Read by QxMD
  13. Winkelman JW, Armstrong MJ, Allen RP, et al. Practice guideline summary: Treatment of restless legs syndrome in adults. Neurology. 2016; 87 (24): p.2585-2593.doi: 10.1212/wnl.0000000000003388 . | Open in Read by QxMD

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