Restless Legs Syndrome
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Basics
Description
- Sensorimotor disorder consisting of a strong, nearly irresistible urge to move the limbs (1)[A]
- The urge usually affects the legs at least initially but may involve arms or other body parts (2)[C].
- The urge might be accompanied by uncomfortable and unpleasant sensations.
- The symptoms (Sx):
- Begin or worsen during rest or inactivity
- Are relieved by movement but recur with inactivity. If not present, previous relief by movement
- Occur preferentially in the evening/night. If not present, previously reported circadian aspect
- Involuntary leg jerks reported during wake/sleep (1)[A].
- System(s) affected: nervous; musculoskeletal
- Early <45 years versus late >45 years onset (1)[A]
- 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
- Predominant sex: male = female (nulliparous)
- Parous females have twice the prevalence of males
- Temperature (cold weather, other environmental factors may increase incidence/trigger Sx.
Prevalence
- 4–15% in Caucasian adults, underdiagnosed
- 2–3% are clinically significant.
- 1–3% in children and adolescents
- Increases with age up to 70s
- 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, ID and associated conditions
- BID leads to central nervous system dopamine dysregulation:
- Higher than normal dopamine levels in the morning and lower than normal dopamine at night leading to downregulation of dopamine D2 receptors
- Decreased dopamine transporter
- BID results in increased glutamate and decreased adenosine leading to hyperarousal and insomnia.
- Changes in substantia nigra, striatum, putamen: reduced iron, less myelin, fewer D2 receptors
- Sensorimotor pathways: abnormalities and increased motor excitability
- Increased endogenous opioids, possibly
- Triggering and exacerbating factors:
- Prolonged immobility, such hospitalizations
- Medications (meds):
- Most antidepressants (except bupropion)
- Dopamine-blocking antiemetics (e.g., metoclopramide, prochlorperazine)
- Phenothiazine antipsychotics (e.g., risperidone, clozapine, olanzapine quetiapine). Possible exception: aripiprazole (partial D2 agonist)
- Cognition-enhancing meds: memantine
- Theophylline and other xanthines
- Sedating antihistamines, OTC cold preparations
Genetics
Heterogeneous:
- 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 Tsat<16
- Family Gx
- Increased with every pregnancy
- Chronic renal failure: 11–58% affects dialysis compliance
- Sleep deprivation (including untreated OSA)
- 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 (dis)
- Parkinson dis, multiple sclerosis, peripheral neuropathy, Machado-Joseph dis, migraine
- Anxiety, depression, ADHD
- Cardiovascular dis, coronary artery dis and stroke
- Venous insufficiency/peripheral vascular dis
- Pulmonary hypertension, lung transplantation, chronic obstructive pulmonary dis (COPD)
- Orthopedic problems, arthritis, fibromyalgia
-- To view the remaining sections of this topic, please log in or purchase a subscription --
Basics
Description
- Sensorimotor disorder consisting of a strong, nearly irresistible urge to move the limbs (1)[A]
- The urge usually affects the legs at least initially but may involve arms or other body parts (2)[C].
- The urge might be accompanied by uncomfortable and unpleasant sensations.
- The symptoms (Sx):
- Begin or worsen during rest or inactivity
- Are relieved by movement but recur with inactivity. If not present, previous relief by movement
- Occur preferentially in the evening/night. If not present, previously reported circadian aspect
- Involuntary leg jerks reported during wake/sleep (1)[A].
- System(s) affected: nervous; musculoskeletal
- Early <45 years versus late >45 years onset (1)[A]
- 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
- Predominant sex: male = female (nulliparous)
- Parous females have twice the prevalence of males
- Temperature (cold weather, other environmental factors may increase incidence/trigger Sx.
Prevalence
- 4–15% in Caucasian adults, underdiagnosed
- 2–3% are clinically significant.
- 1–3% in children and adolescents
- Increases with age up to 70s
- 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, ID and associated conditions
- BID leads to central nervous system dopamine dysregulation:
- Higher than normal dopamine levels in the morning and lower than normal dopamine at night leading to downregulation of dopamine D2 receptors
- Decreased dopamine transporter
- BID results in increased glutamate and decreased adenosine leading to hyperarousal and insomnia.
- Changes in substantia nigra, striatum, putamen: reduced iron, less myelin, fewer D2 receptors
- Sensorimotor pathways: abnormalities and increased motor excitability
- Increased endogenous opioids, possibly
- Triggering and exacerbating factors:
- Prolonged immobility, such hospitalizations
- Medications (meds):
- Most antidepressants (except bupropion)
- Dopamine-blocking antiemetics (e.g., metoclopramide, prochlorperazine)
- Phenothiazine antipsychotics (e.g., risperidone, clozapine, olanzapine quetiapine). Possible exception: aripiprazole (partial D2 agonist)
- Cognition-enhancing meds: memantine
- Theophylline and other xanthines
- Sedating antihistamines, OTC cold preparations
Genetics
Heterogeneous:
- 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 Tsat<16
- Family Gx
- Increased with every pregnancy
- Chronic renal failure: 11–58% affects dialysis compliance
- Sleep deprivation (including untreated OSA)
- 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 (dis)
- Parkinson dis, multiple sclerosis, peripheral neuropathy, Machado-Joseph dis, migraine
- Anxiety, depression, ADHD
- Cardiovascular dis, coronary artery dis and stroke
- Venous insufficiency/peripheral vascular dis
- Pulmonary hypertension, lung transplantation, chronic obstructive pulmonary dis (COPD)
- Orthopedic problems, arthritis, fibromyalgia
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