Cause of Restless Legs Syndrome

Restless Leg Syndrome
Causes of restless leg syndrome. brett lamb / Getty Images

Restless legs syndrome is an unusual affliction with an unknown cause. Studies may have now pinpointed a possible cause of restless legs syndrome.

What Is Restless Legs Syndrome?

Restless Leg Syndrome (RLS) may affect between 5 and 10 percent of the U.S. population, it is underdiagnosed. The main symptom is an irresistible urge to move the legs, often accompanied by "creepy-crawly" sensations in the legs.

Only movement of the legs relieves the sensations. For the millions who suffer from restless legs syndrome, the syndrome worsens at night after the sun sets, resulting in a pattern of sleeplessness.

A research team from Penn State College of Medicine and The Johns Hopkins University searched for answers regarding restless legs syndrome. Led by James Connor, Ph.D., professor and interim chair, Department of Neuroscience and Anatomy, Penn State College of Medicine, the team performed the first-ever autopsy analysis of the brains of people with restless legs syndrome. Their research which was presented at the Associated Professional Sleep Societies meeting in Chicago on June 5, 2003, revealed a possible cause of restless legs syndrome.

Study Findings

  • Though there are no unique pathological changes in the brains of patients with restless legs syndrome, it seems that cells in a portion of the mid-brain are not getting enough iron.
  • There was no evidence of neurodegeneration, lost or damaged brain cells, as is seen in Parkinson's disease and Alzheimer's disease.
  • The discovery of a physical cause of restless legs syndrome indicates that the problem is sensory-motor rather than psychological.
  • Since cells are not lost or damaged but are iron-deficient, there is hope for the development of treatments.

About the Study

  • Connor studied the brain tissue obtained from the Restless Legs Syndrome Foundation's brain collection at the Harvard Brain Bank.
  • Tissue from 7 people with restless legs syndrome was examined. 5 samples from people with no neurological conditions served as controls.
  • Cross-sectional slides of the substantia nigra, the portion of the middle brain thought to be associated with restless legs syndrome allowed the research team to examine cell structure and function.


  • Connor's study found that a specific receptor for iron transport is lacking in patients with restless legs syndrome. Enough iron gets into brain cells to keep them alive, but not enough to allow them to function optimally. It was suggested that the missing iron may cause a misfiring of neural signals to the legs causing the creepy-crawly sensation.
  • These conclusions do not suggest that a person has a dietary iron-deficiency and requires supplements. It does suggest that the receptors are not packaging and delivering an adequate amount of iron to the specific cells in the specified middle brain portion.​
  • Some patients have found temporary relief by taking iron supplements, but it is vitally important that any supplement therapy is managed by a physician.
  • Connor hopes to continue to detect other breakdowns in the iron packaging and transport system to this part of the brain, as well as focusing on the genes that regulate the iron transport proteins.
  • The hope is these discoveries will eventually result in a test that could diagnose restless legs syndrome and lead to treatments which would offer long-term relief to restless legs syndrome sufferers.

    This study was funded in part by grants from the National Institutes of Health and Restless Legs Syndrome Foundation.

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    Article Sources
    • Cause for Restless Legs Syndrome, NEWSWISE, June 6, 2003