Restless Legs Syndrome
Basics
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
- 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 (<45 years) versus late (>45 years) onset
- 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
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
- 1–3% of Caucasians (likely underdiagnosed)
- Increases with age
- Lower in non-Caucasians (except Koreans)
Pregnancy Considerations
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 and lower than normal DA at night leading to downregulation of DA D2 receptors
- Increased glutamate and decreased adenosine leading to hyperarousal and insomnia
- Sensorimotor pathways abnormalities and increased motor excitability
- Triggered by prolonged immobility, such 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)
- Cognition-enhancing meds: memantine
- Theophylline and other xanthines
- Sedating antihistamines, OTC cold preparations
Genetics
- Susceptibility loci: 2p14, 2q, 6p21.2, 9p, 12q, 14q, 15q23, and 20p
- Genes: MEIS1, MAP2K5/LBXCOR1, BTBD9, PRPRD, TOX3
Risk Factors
- ID: ferritin <75 ng/mL or transferrin saturation (TSAT) <16
- Family history
- Chronic renal failure
- Sleep deprivation
- Alcohol, caffeine (limited data)
General Prevention
Commonly Associated Conditions
- Insomnia, sleep walking, delayed sleep phase
- Iron deficiency, 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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Citation
Domino, Frank J., et al., editors. "Restless Legs Syndrome." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2020. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116907/all/Restless_Legs_Syndrome.
Restless Legs Syndrome. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2020. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116907/all/Restless_Legs_Syndrome. Accessed June 3, 2023.
Restless Legs Syndrome. (2020). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (27th ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116907/all/Restless_Legs_Syndrome
Restless Legs Syndrome [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2020. [cited 2023 June 03]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116907/all/Restless_Legs_Syndrome.
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