Restless Legs Syndrome
Basics
Basics
Basics
Description
Description
Description
- 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 but recur with inactivity. If not current, previous relief by movement
- Occur preferentially in the evening/night. If not current, 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
Epidemiology
Epidemiology
Epidemiology
Incidence
- 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)
Prevalence
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
Etiology and Pathophysiology
Etiology and Pathophysiology
- Brain iron deficiency (BID), from either low serum iron or impaired transport of iron into the brain, leading to CNS dopamine dysregulation:
- Higher than normal dopamine (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)
- Theophylline and other xanthines
- Sedating antihistamines
Genetics
- Susceptibility loci: 2p14, 2q, 6p21.2, 9p, 12q, 14q, 15q23, and 20p
- Genes: MEIS1, MAP2K5/LBXCOR1, BTBD9, PRPRD, TOX3
Risk Factors
Risk Factors
Risk Factors
- ID
- Family Hx
- Chronic renal failure
- Sleep deprivation
- Alcohol, caffeine (limited data)
General Prevention
General Prevention
General Prevention
- Regular physical activity/exercise during the day, low-impact activity at night such as stretches, walks
- Adequate sleep; 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
Commonly Associated Conditions
Commonly Associated Conditions
- Insomnia, sleep walking, delayed sleep phase
- ID, renal disease/uremia/dialysis, gastric surgery, IBS, liver disease
- 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
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