Restless legs syndrome: a review of clinical and pathophysiologic features

J Clin Neurophysiol. 2001 Mar;18(2):128-47. doi: 10.1097/00004691-200103000-00004.


Restless legs syndrome (RLS), although long ignored and still much underdiagnosed, disrupts the life and sleep considerably of those who have it. Recent clinical and basic research provides for better definition and pathophysiologic understanding of the disorder. The body of knowledge about this disorder has been expanding rapidly during the past decade and it has altered our concepts of this disorder. This review of RLS covers history, diagnosis, morbidity of sleep disturbance, relation to periodic limb movements in both sleep and waking, secondary causes, severity assessment methods, phenotypes for possible genetic patterns, epidemiology, pathophysiology, and medical treatment considerations. The emphasis on pathophysiology includes consideration of central nervous system localization, neurotransmitter and other systems involved, and the role of iron metabolism. Studies to date support the authors' recently advanced iron-dopamine model of RLS.

Publication types

  • Review

MeSH terms

  • Anemia, Iron-Deficiency / complications
  • Anemia, Iron-Deficiency / diagnosis
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain / physiopathology
  • Diagnosis, Differential
  • Dopamine / metabolism
  • Ferritins / blood
  • Humans
  • Iron / cerebrospinal fluid
  • Iron / metabolism
  • Iron / therapeutic use
  • Iron Deficiencies
  • Magnetic Resonance Imaging
  • Nocturnal Myoclonus Syndrome / diagnosis
  • Nocturnal Myoclonus Syndrome / physiopathology
  • Phenotype
  • Radiculopathy / complications
  • Radiculopathy / diagnosis
  • Restless Legs Syndrome / diagnosis*
  • Restless Legs Syndrome / drug therapy
  • Restless Legs Syndrome / physiopathology*
  • Severity of Illness Index
  • Tomography, Emission-Computed
  • Tomography, Emission-Computed, Single-Photon


  • Ferritins
  • Iron
  • Dopamine