DESCRIPTION

• Sensorimotor disorder consisting of a strong urge to move the limbs; legs are commonly affected initially but may involve arms/other body parts.
• Symptoms (Sx) begin/worsen during rest or inactivity; current or previous relief of symptoms by movement
• Occurs often in the evening; 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 and rapid progression.
• Synonym(s): Willis-Ekbom disease

EPIDEMIOLOGY

ETIOLOGY AND PATHOPHYSIOLOGY

• Brain iron deficiency (BID), from 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 as hospitalizations
• 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 antihistamines
  • Melatonin may exacerbate symptoms (3).

RISK FACTORS

• ID; vitamin D deficiency
• Family Hx
• Chronic renal failure
• Temperature (cold weather, other environmental factors may increase incidence/trigger Sx) (4)

GENERAL PREVENTION

• Regular physical activity during the day, low-impact activity at night such as stretches, walks
• Adequate sleep quality/quantity; delay wake time if possible.
• Avoid caffeine, alcohol, and nicotine mainly in the evening.
• Avoid meds that may trigger RLS (5)[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, migraines
• Anxiety, depression, ADHD
• Cardiovascular disease, diabetes mellitus, pulmonary hypertension, COPD