Restless Legs Syndrome



  • Sensorimotor disorder consisting of a strong, nearly irresistible urge to move the limbs; legs are usually affected initially but may involve arms or other body parts.
  • The symptoms (Sx) begin or worsen during rest or inactivity and are relieved by movement or at least as long as the activity continues. If not current, previous relief by movement
  • Occur preferentially in the evening/night; if not currently, previously reported circadian aspect
  • Involuntary leg jerks reported during wake/sleep
  • Early onset phenotype: 40–92% familial, stable, slow progression of Sx
  • Late onset phenotype: more aggravating factors; rapid progression is common.
  • Synonym(s): Willis-Ekbom disease



  • 0.8–2.2% annually
  • Onset at any age
  • Parous females have twice the prevalence of males.
  • Temperature (cold weather, other environmental factors may increase incidence/trigger Sx)

Pregnancy Considerations

  • 10–30% prevalence; triggers/exacerbates RLS
  • Predictors: past history (Hx), family Hx, iron deficiency (ID), Hgb ≤11 g/dL (1)[C]
  • Peaks in 3rd trimester
  • Most are relieved by 1-month postpartum.

Etiology and Pathophysiology

  • Brain ID (BID), from either low serum iron or impaired transport of iron into the brain, leading to CNS dopamine (DA) dysregulation:
    • Higher than normal DA levels in the morning leading to DA D2 receptors downregulation
    • Lower than normal DA at night
    • Increased glutamate and decreased adenosine leading to hyperarousal and insomnia
  • Sensorimotor pathways abnormalities and increased motor excitability
  • Triggered by prolonged immobility, such ashospitalizations
  • Medication induced:
    • Most antidepressants (except bupropion)
    • DA-blocking antiemetics (e.g., metoclopramide, prochlorperazine)
    • Phenothiazine antipsychotics (risperidone, clozapine, olanzapine, quetiapine, etc.); possible exception: aripiprazole (partial D2 agonist)
    • PPIs, H2 blockers (increase risk)
    • Theophylline and other xanthines
    • Sedating α-histamines


  • Susceptibility loci: 2p14, 2q, 6p21.2, 9p, 12q, 14q, 15q23, and 20p

Risk Factors

  • ID; vitamin D deficiency
  • Family Hx
  • Chronic renal failure

General Prevention

  • Regular physical activity/exercise during the day, low-impact activity at night such as stretches and walks
  • Adequate sleep quality and quantity; delay wake time if possible.
  • Avoid caffeine, alcohol, and nicotine mainly in the evening.
  • Avoid use of meds that may trigger RLS (2)[C].

Commonly Associated Conditions

  • Insomnia, sleep walking, delayed sleep phase
  • ID, renal disease/uremia/dialysis, gastric surgery, IBS
  • Parkinson disease, multiple sclerosis, peripheral neuropathy, Machado-Joseph disease, migraine
  • Anxiety, depression, ADHD
  • Cardiovascular disease, coronary artery disease, and stroke
  • Venous insufficiency/peripheral vascular disease
  • Pulmonary hypertension, lung transplantation, chronic obstructive pulmonary disease (COPD)
  • Orthopedic problems, arthritis, fibromyalgia

There's more to see -- the rest of this topic is available only to subscribers.