Description

• Sensorimotor disorder consisting of a strong urge to move the limbs; legs commonly affected initially but may involve arms/other body parts
• Symptoms begin/worsen during rest or inactivity; relief of symptoms with movement
• Often occurs in the evening
• Involuntary leg jerks reported during wake/sleep
• Early-onset phenotype: 40–60% familial, stable, slow progression of symptoms
• 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 dysregulation:
  • Higher than normal dopamine agonists (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: mirtazapine, TCAs, SSRIs, SNRIs
  • 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
• End-stage renal disease
• Temperature (cold weather, other environmental factors may increase incidence/trigger symptoms) (4)
• Pregnancy

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, nicotine mainly in the evening.
• Avoid meds that may trigger RLS (5)[C].

Commonly Associated Conditions

• Insomnia, 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