Causes of Willis-Ekbom disease, or RLS & PLMD

The causes of Willis-Ekbom disease (WED), or restless legs syndrome (RLS), and periodic limb movement disorder (PLMD) are unknown. Most cases occur independently of other disease processes. It is certain that these conditions often cause insomnia, and some research shows that they might also be caused by other sleep disturbances. This is not likely, however, as PLMD and WED/RLS have not been found to a significant degree in most cases of sleep apnea, which seems to precipitate many secondary consequences of sleep disturbance.

There are many conditions that have been associated with Willis-Ekbom disease and PLMD, including:

  • Chronic kidney (renal) failure
  • Myelopathies (conditions of the spinal cord)
  • Peripheral neuropathies
  • Amyloidosis (metabolic disorder of organs and tissues)
  • Diabetes
  • Anemia and related hemoglobin deficiencies
  • Iron deficiency
  • Vitamin B12 deficiency
  • Uremia (kidney-related toxicity)
  • Chronic lung disease
  • Leukemia
  • Rheumatoid arthritis (RA)
  • Fibromyalgia
  • Stiff-person syndrome (SPS)
  • Isaac's syndrome (neuromyotonia)
  • Huntington's chorea
  • Amyotrophic lateral sclerosis (ALS)

Certain medications may also induce WED (RLS) and PLMD, including lithium and antidepressants. Withdrawal from other medications, including anticonvulsants, benzodiazepines, and barbiturates may also induce Willis-Ekbom disease (or restless legs syndrome) and PLMD.

Publication Review By: the Editorial Staff at

Published: 30 Nov 2000

Last Modified: 02 Oct 2015