Restless Legs Syndrome

BASICS

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

Prevalence

Estimated 7.12% globally among adults 20 to 79 years old. Affects up to 10% of the elderly population in North American and Europe (1).Pregnancy Considerations

  • 10–30% prevalence; triggers/exacerbates RLS
  • Predictors: past history (Hx), family Hx, iron deficiency (ID), Hgb ≤11 g/dL (2)[C]
  • Peaks in 3rd trimester
  • Most symptoms are relieved by 1-month postpartum.

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).

Genetics

  • Susceptibility loci: 2p14, 2q, 6p21.2, 9p, 12q, 14q, 15q23, and 20p
  • Genes: MEIS1, BTBD9, PTPRD, TOX3, MAP2K5/LBXCOR1

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

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