Restless Legs Syndrome (Willis-Ekbom Disease)

Restless legs syndrome is a chronic sensorimotor disorder characterized by an irresistible urge to move the legs, usually accompanied by uncomfortable sensations that worsen during periods of rest and in the evening.

Key Points

• Neurological sensorimotor disorder
• Circadian pattern with evening/night predominance
• Can begin at any age, including childhood
• Both primary (genetic) and secondary forms exist
• Significant impact on sleep and quality of life

Epidemiology & Risk Factors

Prevalence

• General Population:
  • Adults: 5-10%
  • Children: 2-4%
  • Higher in females (2:1 ratio)
• High-Risk Groups:
  • Pregnant women: 20-30%
  • Iron deficiency: 25-35%
  • End-stage renal disease: 20-40%
  • Parkinson's disease: 20%

Risk Factors

• Primary Risk Factors:
  • Family history (40-60% cases)
  • Female gender
  • Advancing age
  • Northern European descent
• Secondary Risk Factors:
  • Iron deficiency
  • Pregnancy
  • Chronic kidney disease
  • Diabetes mellitus
  • Peripheral neuropathy
  • Multiple sclerosis
  • Certain medications

Pathophysiology

Neurobiological Basis

• Dopaminergic System:
  • Dysfunction in D2 receptors
  • Altered dopamine transport
  • Circadian fluctuation in dopamine levels
• Iron Metabolism:
  • Decreased brain iron storage
  • Impaired iron transport across blood-brain barrier
  • Role of iron in dopamine synthesis
• Genetic Factors:
  • BTBD9 gene variants
  • MEIS1 gene mutations
  • MAP2K5/SKOR1 variants
  • PTPRD gene variations

Pathophysiological Mechanisms

• Central Nervous System:
  • Altered sensorimotor integration
  • Spinal cord involvement
  • Thalamic dysfunction
  • Altered pain processing
• Peripheral Mechanisms:
  • Small fiber neuropathy
  • Peripheral hypoxia
  • Vascular dysfunction

Clinical Features

Essential Diagnostic Criteria (IRLSSG)

• 1. Urge to move legs ± uncomfortable sensations
• 2. Symptoms worse with rest/inactivity
• 3. Partial/total relief with movement
• 4. Symptoms worse in evening/night
• 5. Not solely explained by another condition

Sensory Symptoms

• Character of Sensations:
  • Crawling
  • Creeping
  • Pulling
  • Tingling
  • Electric sensations
  • Pain
• Distribution:
  • Primarily legs (calves)
  • Can involve arms (15-20%)
  • Bilateral but asymmetric
  • Deep rather than superficial

Motor Symptoms

• Voluntary Movements:
  • Walking
  • Stretching
  • Rubbing legs
  • Position changes
• Involuntary Movements:
  • Periodic limb movements during sleep (PLMS)
  • Present in 80-90% of RLS patients
  • May occur during wakefulness

Diagnosis & Assessment

Clinical Assessment

• Detailed History:
  • Age of onset
  • Family history
  • Pattern of symptoms
  • Impact on sleep/quality of life
  • Aggravating/relieving factors
• Severity Assessment:
  • International RLS Rating Scale (IRLS)
  • RLS Quality of Life Instrument
  • Clinical Global Impression

Laboratory Testing

• Essential Tests:
  • Complete blood count
  • Ferritin levels
  • Iron studies (TIBC, transferrin saturation)
  • Renal function tests
  • Blood glucose
• Additional Tests (as indicated):
  • Vitamin B12 levels
  • Folate
  • Thyroid function
  • Magnesium levels

Sleep Studies

• Indications:
  • Diagnostic uncertainty
  • Sleep apnea suspicion
  • Treatment resistance
• Parameters Assessed:
  • Periodic limb movements
  • Sleep architecture
  • Sleep efficiency
  • Arousal index

Management Strategies

Non-Pharmacological Approaches

• Sleep Hygiene:
  • Regular sleep schedule
  • Optimal sleep environment
  • Avoid caffeine/alcohol
  • Exercise timing optimization
• Lifestyle Modifications:
  • Regular exercise
  • Stress reduction
  • Evening activity modification
  • Counter-stimulus activities

Pharmacological Treatment

• First-Line Medications:
  • Dopaminergic agents:
    • Pramipexole (0.125-0.5 mg/day)
    • Ropinirole (0.25-4 mg/day)
    • Rotigotine patch (1-3 mg/24h)
  • α2δ ligands:
    • Gabapentin (300-2400 mg/day)
    • Pregabalin (75-300 mg/day)
• Second-Line Treatments:
  • Opioids:
    • Oxycodone
    • Methadone
    • Tramadol
  • Benzodiazepines:
    • Clonazepam
    • Used primarily for sleep

Iron Supplementation

• Indications:
  • Ferritin <75 μg/L
  • Symptomatic patients
• Administration:
  • Oral iron: 325 mg ferrous sulfate BID
  • IV iron: iron sucrose or ferric carboxymaltose
  • Monitor response every 3 months

Special Populations

Pediatric RLS

• Diagnostic Challenges:
  • Different symptom description
  • Growing pains confusion
  • ADHD overlap
• Management Considerations:
  • Iron supplementation priority
  • Sleep hygiene emphasis
  • Cautious medication use

Pregnancy

• Clinical Course:
  • Often worsens during pregnancy
  • Peak in third trimester
  • Usually improves post-partum
• Management:
  • Iron supplementation
  • Non-pharmacological approaches
  • Careful medication selection

Complications & Impact

Sleep-Related Complications

• Direct Effects:
  • Sleep onset insomnia
  • Sleep maintenance problems
  • Reduced total sleep time
  • Poor sleep quality
• Secondary Effects:
  • Daytime sleepiness
  • Cognitive impairment
  • Mood disturbances

Quality of Life Impact

• Psychosocial Effects:
  • Depression risk increased
  • Anxiety
  • Social isolation
  • Relationship strain
• Functional Impact:
  • Work performance
  • Academic achievement
  • Driving safety
  • Daily activities