Restless Legs Syndrome
Content of This Page
1- Introduction
2- Causes
3- Symptoms
4- Investigations & Lab Results
5- Complications
6- Treatment
Introduction
Restless Legs Syndrome (RLS), also known as Willis-Ekbom Disease, is a neurological sensorimotor disorder characterized by an unpleasant urge to move the legs, usually accompanied by uncomfortable sensations. These symptoms typically occur or worsen during periods of rest or inactivity, especially in the evening or at night, and are relieved by movement such as walking or stretching.
RLS can significantly affect sleep quality and overall quality of life. It may occur as a primary (idiopathic) condition or secondary to other medical conditions like iron deficiency, pregnancy, or renal failure. The exact cause is not fully understood but is thought to involve dysfunction in the dopaminergic system and iron metabolism in the central nervous system.

Causes
1. Primary (Idiopathic) RLS
Often familial, suggesting a genetic component
Usually begins in middle age or earlier
Exact cause unknown but thought to involve:
Dysfunction in dopaminergic pathways in the brain
Abnormal iron metabolism in the central nervous system
No identifiable underlying medical condition
2. Secondary Causes of RLS
RLS may develop as a result of or be associated with other medical conditions or factors:
Iron deficiency anemia (most common secondary cause)
Chronic kidney disease / End-stage renal disease
Pregnancy, especially in the third trimester
Peripheral neuropathy
Diabetes mellitus
Parkinson’s disease
Rheumatoid arthritis
Certain medications (e.g., antidepressants, antipsychotics, lithium, antihistamines)
Vitamin B12 deficiency
3. Triggers / Exacerbating Factors
Caffeine, nicotine, and alcohol
Sleep deprivation or irregular sleep schedules
Stress or anxiety

Symptoms
-Core Symptoms
Urge to move the legs, often accompanied by unpleasant sensations described as:
Crawling, tingling, itching, burning, or aching
Symptoms worsen during periods of rest or inactivity, such as sitting or lying down
Symptoms are most severe in the evening or at night, leading to difficulty falling asleep or staying asleep
Movement relieves the discomfort temporarily, such as walking, stretching, or shaking the legs
-Additional Features
Symptoms may also affect the arms or other body parts (less common)
Severity can vary from mild to debilitating
Often associated with sleep disturbances and resulting daytime fatigue or irritability
Some patients may experience periodic limb movements during sleep (PLMS) — involuntary jerking or twitching of the legs
-Important Points
Symptoms typically have a daily pattern, worsening at night
The sensations are unpleasant and difficult to describe but are distinct from pain
The condition can lead to significant impairment of quality of life if untreated
Investigations & Lab Results
1. Clinical Diagnosis
RLS is primarily diagnosed based on patient history and symptom criteria.
Diagnostic criteria include:
Urge to move the legs usually accompanied by uncomfortable sensations
Symptoms worsen during rest and in the evening or night
Relief with movement
Symptoms not explained by another condition
2. Laboratory Tests
Used to identify secondary causes of RLS:
Complete blood count (CBC)
To check for iron deficiency anemia
Serum ferritin
Low ferritin (<50 ng/mL) is often associated with RLS even if hemoglobin is normal
Serum iron, total iron-binding capacity (TIBC), transferrin saturation
To assess iron status in detail
Renal function tests
To rule out chronic kidney disease
Blood glucose and HbA1c
To screen for diabetes mellitus
Vitamin B12 and folate levels
To detect deficiencies that may contribute to symptoms
3. Polysomnography (Sleep Study)
Not routinely required but can be useful if diagnosis is uncertain
Detects periodic limb movements during sleep (PLMS), which often coexist with RLS
4. Neurophysiological Tests
Occasionally used to exclude other neurological disorders, such as peripheral neuropathy
Complications
1. Sleep Disturbances
Difficulty falling asleep and frequent awakenings
Poor sleep quality and reduced total sleep time
Leads to chronic insomnia
2. Daytime Fatigue and Sleepiness
Excessive daytime tiredness
Impaired concentration and attention
Reduced productivity at work or school
3. Mood Disorders
Increased risk of depression and anxiety due to chronic sleep deprivation and discomfort
Irritability and emotional distress
4. Impaired Quality of Life
Social withdrawal and reduced participation in activities
Difficulties in relationships due to sleep problems and mood changes
5. Secondary Effects
In severe cases, may increase risk of accidents due to daytime sleepiness
Possible exacerbation of coexisting medical conditions due to poor rest
Treatment
1. Address Underlying Causes
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Correct iron deficiency if present (iron supplements)
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Manage associated conditions such as renal failure, diabetes, or vitamin deficiencies
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Review and stop medications that may worsen symptoms if possible (e.g., certain antidepressants, antihistamines)
2. Lifestyle Modifications
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Regular moderate exercise
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Avoid caffeine, nicotine, and alcohol, especially in the evening
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Maintain a regular sleep schedule
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Leg massages, warm baths, or applying heat/cold may provide relief
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Stress reduction techniques
3. Pharmacological Treatment
First-line Medications:
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Dopamine agonists (e.g., pramipexole, ropinirole)
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Effective in reducing symptoms
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Side effects: nausea, dizziness, impulse control disorders
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Alpha-2-delta calcium channel ligands (e.g., gabapentin, pregabalin)
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Useful especially if pain or sensory symptoms are prominent
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Alternative or Adjunctive Medications:
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Iron supplementation if ferritin is low
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Benzodiazepines (e.g., clonazepam) for sleep improvement, used cautiously
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Opioids reserved for severe refractory cases
4. Monitoring and Follow-up
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Regular assessment of symptom control and side effects
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Adjust treatment as needed for efficacy and tolerability