Neurology Book


Restless Leg Syndrome

Aka: Restless Leg Syndrome, Restless Legs Syndrome, Ekboms Syndrome
  1. See Also
    1. Periodic Limb Movement
    2. Akathisia
    3. Leg Pain
    4. Movement Disorder
    5. Pediatric Restless Leg Syndrome
  2. Epidemiology
    1. Fourth leading cause of Insomnia
    2. Family History of restless legs in 50-60%
    3. Incidence in adults: 6-10% (only 2 to 3% seek treatment)
    4. Incidence in adults over age 65 years: 10-28%
    5. More common in women
    6. Onset before age 18 in one third of patients
  3. Risk Factors
    1. Family History of Restless Leg Syndrome (accounts for 50% of RLS patients)
    2. Iron Deficiency Anemia (especially if Serum Ferritin <50 ng/ml)
    3. Chronic Renal Failure (Chronic Kidney Disease)
    4. Antidepressant use (Akathisia)
    5. Pregnancy
    6. Neuropathy
  4. Pathophysiology: Possible etiologies
    1. Dopamine deficiency in Brainstem or spinal cord
    2. Endogenous Opiate deficiency
    3. Small fiber Peripheral Neuropathy
  5. Causes
    1. Idiopathic in most cases
    2. Iron Deficiency Anemia
    3. Renal Dialysis
    4. Pregnancy (as high as 19%)
    5. Hypothyroidism
    6. Diabetes Mellitus
    7. Electrolyte disturbance
      1. Decreased Serum Magnesium
      2. Decreased Serum Folate
    8. Leg varicosities
      1. May be relieved with sclerotherapy
    9. Drug-induced causes
      1. See Akathisia
      2. Selective Serotonin Reuptake Inhibitors (common)
      3. Antihistamines (e.g. Benadryl)
      4. Antipsychotics
      5. Antiemetics
        1. Phenergan
        2. Metoclopramide
        3. Prochlorperazine
      6. Lithium
      7. Tricyclic Antidepressants (e.g. Elavil)
        1. Treat with Propranolol 40 mg PO tid
      8. Substances
        1. Caffeine
        2. Tobacco use
  6. Symptoms
    1. Timing
      1. Symptoms worsen in the afternoon, evening and bedtime
      2. Contrast with Periodic Limb Movement which occurs during sleep
    2. Overall urge to move legs due to uncomfortable leg Sensations (Akathisia)
      1. Creeping or crawling restlessness
      2. Wormy or boring Sensation
      3. Tingling, pins and needles, or prickly Sensation
      4. Pulling or drawing Sensation
    3. Severity
      1. Symptoms can cause very significant morbidity (to point of Suicidal Ideation)
    4. Palliative
      1. Movement (e.g. walking) temporarily relieves Sensation until sitting or lying back down again
    5. Provocative
      1. Prolonged period of inactivity (e.g. car travel)
      2. Prolonged sitting (e.g. classes or meetings)
      3. Lying down or sleeping
  7. Signs
    1. Periodic flexions
      1. Occur every 20-40 seconds during non-REM Sleep
  8. Labs
    1. Serum Ferritin (<50 ng/ml associated with Restless Leg Syndrome)
    2. Serum Glucose
    3. Serum Creatinine
    4. Consider other lab testing to consider
      1. Thyroid Stimulating Hormone
      2. Serum Magnesium
      3. Serum Folate
  9. Differential Diagnosis
    1. See Akathisia
    2. Periodic Limb Movement
    3. Night Cramps (Leg Cramps)
    4. Peripheral Vascular Disease
    5. Anxiety Disorder
    6. Drug induced Akathisia
    7. Peripheral Neuropathy
    8. Tic Disorder
  10. Diagnosis: Essential Features (4 criteria)
    1. Intense urge to move legs (typically asssociated with uncomfortable creeping or aching leg Sensations) AND
    2. Symptoms begin or worsen with rest or inactivity AND
    3. Symptoms are at least in part relieved with walking or Stretching AND
    4. Worse or limited to evening and overnight
  11. Management: General measures
    1. Discontinue provocative habits
      1. Discontinue Caffeine usage
      2. Tobacco Cessation
      3. Alcohol cessation
    2. Encourage relaxing bedtime routine
      1. Avoid vigorous Exercise 2 hours before bedtime
      2. Avoid sexual activity 2 hours before bedtime
      3. Adjust schedule to allow awakening later
    3. Correct Iron Deficiency Anemia
      1. Screen with Serum Ferritin in most if not all patients with Restless Leg Syndrome
      2. Consider Iron Supplementation for Serum Ferritin <75 mcg/L
    4. Local massage (leg massage)
    5. Moderate intensity Exercise (e.g. brisk walking) may also decrease symptoms longterm
    6. Cold compress application
    7. Consider adaptive changes at work or school
      1. Work at high desk with stool
      2. Sit in aisle seat on trips or meetings
    8. Consider sleep clinic referral for refractory symptoms
  12. Management: GABA Agents (preferred first line)
    1. First-line option for persistent restless legs
      1. Delayed onset of relief while starting and titrating medication
      2. Better tolerated longterm than the Dopaminergic agents (listed above)
      3. Similar efficacy to the Dopaminergic agents (50% symptom reduction with NNT 5)
    2. Gabapentin (Neurontin)
      1. Start: 300 mg orally at bedtime
      2. Increase: every 3-4 nights until symptoms controlled or at a maximum of 1800 mg
      3. Effective in RCT at 1800 mg/day (600 mg tid)
        1. Garcia-Borreguero (2002) Neurology 59:1573-9 [PubMed]
    3. Pregabalin (Lyrica)
      1. Start 300 mg orally at bedtime
  13. Management: Non-Ergotamine Dopamine Agonists (preferred second line)
    1. Preferred for frequent or nightly restless legs symptoms
      1. Quick onset of improved symptoms
      2. Risk of sedation, Nausea, Hallucinations and Compulsive Gambling and other behaviors
      3. Augmentation (worsening symptoms) occurs in 6-7% of patient per year
        1. Switch to GABA Agent (Gabapentin or Pregabalin) - see below
    2. Pramipexole (Mirapex)
      1. Initial dose: 0.125 mg one tablet orally at bedtime
      2. Subsequent: Increase dose every third night until symptoms controlled or at a maximum of 4 tablets at bedtime
      3. See Mirapex for dosing strategy
    3. Ropinirole (Requip)
      1. Initial dose: 0.25 mg orally at bedtime
      2. Subsequent: Increase dose every third night until symptoms controlled or at a maximum of 4 tablets at bedtime
      3. See Requip for dosing strategy
    4. Rotigotine (Neupro) Transdermal
      1. Dopamine Agonist transdermal patch
      2. Indicated for moderate to severe symptoms refractory to Pramipexole or Ropinirole
      3. Dosing
        1. One patch applied daily to a new site
        2. Do not repeat the same site for 14 days
        3. Start at 1 mg/24 hours
        4. May increase weekly to a maximum of 3 mg/24 hours
  14. Management: Other agents
    1. Analgesics at bedtime
      1. Acetaminophen (Tylenol)
      2. NSAIDS (e.g. Ibuprofen)
      3. Nighttime Opioid Analgesics (e.g. Oxycodone 5-10 mg at bedtime) may also be effective
    2. Dopamine Agonists
      1. Consider for occsional symptoms
      2. Carbidopa and Levodopa
        1. Sinemet 12.5/50 mg PO qhs prn
        2. Sinemet CR 25/100 mg PO qhs prn
    3. Ergotamine Dopamine Agonists
      1. Pergolide (Permax) 0.05 to 1 mg
        1. First dose at dinner
        2. Second dose one hour before bed
      2. Cabergoline (Dostinex)
        1. Initial dose: 0.5 mg PO at bedtime
    4. Benzodiazepines
      1. Not recommended
    5. Alpha Adrenergic Agonists
      1. Clonidine 0.1 mg PO qhs
  15. Course
    1. Symptoms progress with age
  16. Resources
    1. Restless Legs Syndrome Foundation
  17. References
    1. (2017) Presc Lett 24(4):20-1
    2. (2000) Am Fam Physician 62:108-14 [PubMed]
    3. Bayard (2008) Am Fam Physician 78(2): 235-43 [PubMed]
    4. Clark (2001) J Am Board Fam Pract 14:368-74 [PubMed]
    5. Henning (1999) Sleep 22:970-99 [PubMed]
    6. Holder (2022) Am Fam Physician 105(4): 397-405 [PubMed]
    7. Paulson (2000) Geriatrics 55:35-48 [PubMed]
    8. Ramar (2013) Am Fam Physician 88(4): 231-8 [PubMed]

Restless Legs Syndrome (C0035258)

Definition (MSH) A disorder characterized by aching or burning sensations in the lower and rarely the upper extremities that occur prior to sleep or may awaken the patient from sleep.
Definition (MEDLINEPLUS)

Restless legs syndrome (RLS) causes a powerful urge to move your legs. Your legs become uncomfortable when you are lying down or sitting. Some people describe it as a creeping, crawling, tingling, or burning sensation. Moving makes your legs feel better, but not for long. RLS can make it hard to fall asleep and stay asleep.

In most cases, there is no known cause for RLS. In other cases, RLS is caused by a disease or condition, such as anemia or pregnancy. Some medicines can also cause temporary RLS. Caffeine, tobacco, and alcohol may make symptoms worse.

Lifestyle changes, such as regular sleep habits, relaxation techniques, and moderate exercise during the day can help. If those don't work, medicines may reduce the symptoms of RLS.

Most people with RLS also have a condition called periodic limb movement disorder (PLMD). PLMD is a condition in which a person's legs twitch or jerk uncontrollably, usually during sleep. PLMD and RLS can also affect the arms.

NIH: National Heart, Lung, and Blood Institute

Definition (NCI_NCI-GLOSS) A condition in which a person has a strong urge to move his or her legs in order to stop uncomfortable sensations. These include burning, itching, creeping, tugging, crawling, or pain. These feelings usually happen when a person is lying or sitting down, and are worse at night. They can also occur in other parts of the body.
Definition (NCI) A condition that occurs while resting or lying in bed; it is characterized by an irresistible urgency to move the legs to obtain relief from a strange and uncomfortable sensation in the legs.
Definition (CSP) neurological disorder characterized by unpleasant sensations of the legs and an urge to move them for relief; usually occurs during or just prior to sleep, causing difficulty falling asleep or staying asleep.
Concepts Disease or Syndrome (T047)
MSH D012148
ICD9 333.94
ICD10 G25.81
SnomedCT 393579008, 32914008
English Restless Legs, RESTLESS LEGS, Restless leg syndrome, Restless Legs Syndrome, Restless legs syndrome (RLS), restless leg syndrome (diagnosis), restless leg syndrome, restless legs syndrome, Legs restless, Syndrome restless legs, Restless Legs Syndrome [Disease/Finding], restless leg, restless leg disorder, ekbom's syndrome, restless leg syndrome (RLS), Wittmaack-Ekbom Syndrome, Willis Ekbom Syndrome, Willis Ekbom Disease, Wittmaack Ekbom Syndrome, Willis-Ekbom Disease, Syndrome, Willis Ekbom, Disease, Willis Ekbom, Syndrome, Willis-Ekbom, Disease, Willis-Ekbom, Syndrome, Wittmaack Ekbom, Restless Leg Syndrome, Syndrome, Wittmaack-Ekbom, Syndrome, Restless Leg, Willis-Ekbom Syndrome, RLS, Restless legs syndrome, Ekbom syndrome, Restless legs, Restless legs (disorder), restless legs, Ekbom, restless legs; syndrome, syndrome; restless legs, ekbom syndrome
Spanish PIERNAS INQUIETAS, Síndrome de piernas inquietas, Piernas inquietas, piernas inquietas (trastorno), piernas inquietas, síndrome de piernas inquietas, Síndrome de la pierna inquieta, Síndrome de las Piernas Inquietas
Dutch restless legs, trekbenen, restless leg syndroom, syndroom restless legs, Restless legs, restless legs; syndroom, syndroom; restless legs, restless legs-syndroom, Ekbom-syndroom, Restless-legssyndroom, Syndroom, restless-legs-
German Beine unruhig, Restless leg Syndrom, unruhige Beine, RESTLESS LEGS, Syndrom der ruhelosen Beine, Syndrom der unruhigen Beine, Wittmaack-Ekbom-Syndrom, Restless-legs-Syndrom
Italian Gambe senza riposo, Sindrome di Ekbom, Sindrome delle gambe senza riposo
Portuguese Pernas irrequietas, Síndrome das pernas irrequietas, Síndrome de pernas irrequietas, SINDROME DAS PERNAS INQUIETAS, Síndrome das Pernas sem Repouso, Síndroma da perna inquieta, Síndrome das Pernas Inquietas
Japanese 下肢静止不能, 下肢静止不能症候群, カシセイシフノウショウコウグン, カシセイシフノウ, Ekbom症候群, Restless Legs症候群, エクボム症候群, エクボン症候群, レストレスレッグ症候群, 下肢不穏状態, 不穏下肢, 脚不穏, 脚不穏症候群, エクボーム症候群
Swedish Rastlösa ben-syndrom
Czech syndrom neklidných nohou, nohy neklidné, Syndrom neklidné nohy, Neklidné nohy, Syndrom neklidných nohou
Finnish Levottomat jalat -oireyhtymä
French SYNDROME DES JAMBES SANS REPOS, SJSR, Syndrome de Wittmaack-Ekbom, Impatience des membres inférieurs, Syndrome des jambes sans repos, IMI (Impatience des Membres Inférieurs), Impatiences des membres inférieurs, Impatiences, Jambes sans repos, Syndrome d'impatience des membres inférieurs
Polish Zespół niespokojnych nóg, Zespół Ekboma
Hungarian Nyugtalan-lábak, Nyugtalan lábak, Nyugtalan-lábak syndroma, Nyugtalan láb syndroma
Norwegian Urolige bein, Restless legs syndrome, Rastløse bein, Ekboms syndrom, Urolige ben, Rastløse ben
Derived from the NIH UMLS (Unified Medical Language System)

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