Peripheral hypoxia in restless legs syndrome (Willis-Ekbom disease)

Neurology. 2014 May 27;82(21):1856-61. doi: 10.1212/WNL.0000000000000454. Epub 2014 Apr 30.


Objective: A case-control study to measure oxygen and carbon dioxide partial pressures in the legs in order to assess the involvement of peripheral hypoxia or hypercapnia in the pathogenesis of restless legs syndrome (RLS).

Methods: RLS severity was assessed with a standard questionnaire. Suggested immobilization tests were performed twice in 15 patients with RLS and 14 healthy controls. Patients with RLS participated in the tests with and without pramipexole medication. During the tests, peripheral oxygen and carbon dioxide partial pressures were measured noninvasively on the skin of the legs and the chest.

Results: During immobilization, the patients with RLS had lower partial pressure of oxygen in their legs (5.54 vs 7.19 kPa, p < 0.01) but not on the chest (8.75 vs 8.20 kPa, p = 0.355). More severe RLS correlated with high chest-to-foot oxygen gradient (ρ = 0.692, p < 0.01). Carbon dioxide levels did not differ between the groups. Pramipexole corrected the peripheral hypoxia toward the levels observed in the controls (from 5.54 to 6.65 kPa, p < 0.05).

Conclusions: Peripheral hypoxia is associated with the appearance of RLS symptoms. Strong correlation with RLS severity suggests a close pathophysiologic link between peripheral hypoxia and the symptoms of RLS. This is further supported by the simultaneous reversal of hypoxia and discomfort by dopaminergic treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Female
  • Humans
  • Hypoxia / physiopathology*
  • Leg / physiopathology
  • Male
  • Middle Aged
  • Restless Legs Syndrome / physiopathology*