Restless legs syndrome

• Family History of restless legs in 50-60%
• Incidence in adults: 6-10% (only 2 to 3% seek treatment)
• Incidence in adults over age 65 years: 10-28%
• More common in women
• Onset before age 18 in one third of patients

Primary and Secondary Forms

• RLS has both primary and secondary forms.
• 40-60% of patients with primary RLS report a family history.
• Secondary Causes
  • iron deficiency
  • pregnancy
  • renal failure
  • peripheral neuropathy
  • diabetes mellitus
  • thyroid disorders
  • fibromyalgia
  • rheumatoid arthritis.

• Risk factors
  • Iron deficiency
    • restless leg syndrome can be a symptom of iron deficiency
    • A ferritin level less than 50 ng (even in the absence of anemia) is associated with restless legs syndrome
  • Chronic Renal Failure
  • Antidepressant use
  • Pregnancy
  • Neuropathy
  • decreased Mg
  • decreased Folate

four essential features:

• (1) Akathisia – the intense urge to move the legs, usually accompanied or caused by uncomfortable sensations (e.g., “creepy crawly,” aching, tingling pins and needles, prickly sensation, pulling or drawing sensation) in the legs
• (2) symptoms that begin or worsen during periods of rest or inactivity
• (3) symptoms that are partially or totally relieved by movements such as walking or stretching
• (4) Periodic limb movements during sleep
  • characterized by periodic episodes of repetitive, stereotypic movements that predominantly occur in the lower extremities.
  • Patients’ bed partners may notice these movements.

• Differentiation needed from
  • paraesthesia
  • peripheral neuropathy
  • arthritis pain
  • muscle cramps.
• History should include
  • symptom impact on sleep
  • presence of periodic limb movements.
• Physical examination
  • can identify secondary causes like peripheral neuropathy or anaemia.

Investigations

• Fe Studies
• Mg
• Folate
• TSH, TFT if needed
• eGFR/Cr
• Polysomnography and Other Tests
  • Not routinely required, but helpful in assessing sleep quality and concurrent sleep disorders.
  • Periodic limb movements during non-REM sleep identifiable in sleep studies.
  • Questionnaire symptom scales and immobilisation tests used mainly in research for treatment monitoring.

Management

• General measures
  • Discontinue provocative habits
    1. Discontinue Caffeine usage
    2. Tobacco Cessation
    3. Alcohol cessation
  • 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
  • Correct Iron Deficiency Anemia
  • Local massage
  • Moderate intensity Exercise (e.g. brisk walking) may also decrease symptoms longterm
  • Cold compress application

Medications

Mild and infrequent, use:

• levodopa+carbidopa 100+25 to 200+50 mg orally, before bedtime PRN -OR-
• levodopa+benserazide 100+25 to 200+50 mg orally, before bedtime PRN  

More severe symptoms:

• Dopaminergic agonists
  • first-line therapy for patients with nightly, persistent symptoms.
  • Common adverse effects of dopaminergic agonists include
    • insomnia
    • nasal congestion
    • swelling of the extremities
    • daytime sleepiness
    • increased tendency toward compulsive behaviors, such as gambling
  • Pramipexole 0.125 mg orally, once daily 2 to 3 hours before bedtime
    • If needed, after 4 to 7 days increase dose to 0.25 mg at night, then increase daily dose by 0.25 mg every 4 to 7 days as tolerated and according to response, up to 0.75 mg daily      
  • Ropinirole 0.25 mg orally, once daily 1 to 3 hours before bedtime.
    • If initial dose is tolerated, after 2 days increase dose to 0.5 mg once daily for 5 days, then increase daily dose by 0.5 mg every 7 days according to response, up to 4 mg daily (usual daily dose is 2 mg)    
  • Rotigotine 1 mg transdermally, once daily applied for 24 hours.
    • If needed, increase dose as tolerated and according to response, up to 3 mg daily

• alpha 2 delta ligands:
  • Gabapentin 100 to 300 mg orally, once daily at night.
    • Gradually increase dose every 3 to 7 days as tolerated and according to response, up to 2400 mg daily.
    • If the daily dose is more than 1200 mg, give one-third in the evening and two-thirds at bedtime      
  • pregabalin 75 mg orally, once daily at night.
    • If needed, gradually increase dose every 3 to 7 days as tolerated and according to response, up to 450 mg daily

Augmentation is when the symptoms of restless legs and periodic limb movements of sleep/wakefulness get worse after treatment—the symptoms may shift to an earlier time in the day, have greater intensity and involve new limb areas. Augmentation is mainly a problem with dopaminergic drugs, particularly levodopa, and may occur as early as 3 to 4 weeks after starting treatment.

Risk factors for augmentation are taking more than 200 mg levodopa daily, and taking levodopa early in the day.

Strategies to reduce or stop augmentation include having a drug holiday, stopping the drug or using an alternative drug

Rebound restless leg symptoms occur when drug treatment has worn off, similar to ‘wearing off’ in Parkinson disease. These symptoms often occur late at night or early in the morning, and are treated by using long-acting preparations (eg transdermal rotigotine) or divided levodopa doses.

Refer patients with augmentation or rebound to an expert.

In patients with iron deficiency, iron supplementation may improve or resolve symptoms of restless legs syndrome.