What leg pain characteristics differentiate restless‑legs syndrome from other causes (e.g., muscle cramp, neuropathy, claudication, osteoarthritis, deep‑vein thrombosis) in middle‑aged to older adults, especially women?

Distinguishing RLS from Other Causes of Leg Pain

Restless legs syndrome is diagnosed when leg discomfort meets four essential criteria—urge to move that worsens with rest, improves with movement, and follows a circadian pattern (worse at night)—and critically, when symptoms cannot be explained by another medical condition such as muscle cramps, neuropathy, claudication, arthritis, or deep vein thrombosis. 1

Core Diagnostic Features of RLS

The diagnosis requires all five of the following criteria 1:

• An urge to move the legs usually accompanied by uncomfortable sensations described as creepy-crawly, burning, itching, or aching 1
• Symptoms begin or worsen during rest or inactivity such as sitting or lying down 1
• Relief occurs with movement (walking, stretching, rubbing) and persists as long as the activity continues 1
• Circadian pattern with symptoms worse in the evening or night than during the day 1
• Symptoms not solely accounted for by another condition—this fifth criterion is critical to avoid misdiagnosis 1

RLS Mimics: What Likely Isn't RLS

Muscle Cramps

• Sudden, painful muscle contractions rather than an urge to move 1
• Pain is localized and sharp, not the diffuse discomfort of RLS 1
• No relief with gentle movement; cramps resolve spontaneously or with stretching after they occur 1
• No consistent circadian pattern 1

Peripheral Neuropathy

• Numbness and tingling are prominent, often described as "pins and needles" rather than an urge to move 1
• Symptoms are constant rather than fluctuating with rest/activity 1
• No circadian variation—present throughout the day 1
• Abnormal neurologic examination with reduced sensation, absent reflexes, or weakness 1
• Associated with diabetes, renal disease, or other systemic conditions 1

Intermittent Claudication (Vascular Disease)

• Pain is exercise-induced and worsens with walking, opposite of RLS 1
• Relief occurs with rest, not movement 1
• Pain is typically cramping or aching in the calf during exertion 1
• No circadian pattern 1
• May have diminished pulses or vascular bruits on examination 1

Osteoarthritis

• Pain is localized to specific joints (knee, hip) rather than diffuse leg discomfort 1, 2
• Worsens with activity and improves with rest—opposite of RLS 2
• No circadian pattern characteristic of RLS 2
• Physical examination reveals joint abnormalities (crepitus, limited range of motion, tenderness) 2
• Morning stiffness that improves throughout the day 2

Deep Vein Thrombosis (DVT)

• Unilateral leg swelling, warmth, and tenderness 1
• Pain is constant, not relieved by movement 1
• Positive Homan's sign or palpable cord 1
• No circadian variation 1
• RLS typically affects both legs bilaterally, even if asymmetric 3, 2

Positional Discomfort

• Discomfort immediately relieved by position change alone, without need for continued movement 1
• No urge to move once comfortable position is found 1
• No circadian pattern 1

Leg Edema/Venous Stasis

• Visible swelling that worsens throughout the day 1
• Discomfort is aching or heaviness, not an urge to move 1
• Improves with leg elevation, not necessarily movement 1
• Physical examination shows pitting edema, varicosities 1

Critical Diagnostic Pitfall

Without proper differential diagnosis, 16% of patients without RLS will be misclassified as having RLS if only the four symptom criteria are assessed without excluding mimics. 1 This emphasizes the importance of the fifth diagnostic criterion.

Key Distinguishing Algorithm

When evaluating leg discomfort, ask these questions in sequence 1:

1. Is there an urge to move? If no → consider neuropathy, arthritis, DVT, cramps
2. Do symptoms worsen with rest? If no → consider claudication, arthritis
3. Does movement provide relief? If no → consider DVT, neuropathy, cramps
4. Are symptoms worse at night? If no → consider other diagnoses
5. Is the physical examination normal? If no → consider secondary causes (neuropathy, arthritis, vascular disease) 1

Additional RLS Characteristics

• Bilateral involvement is typical, though severity may be asymmetric 3, 2
• Sensations are described as deep inside the legs, not superficial 1
• Sleep disruption is common, leading to insomnia and daytime sleepiness 1
• Symptoms may involve arms or trunk in severe cases 1
• Physical examination is typically unremarkable in primary RLS 1

When to Suspect Secondary RLS

Consider secondary causes when 1, 2:

• Serum ferritin <50 ng/mL (check in all RLS patients) 1
• End-stage renal disease present 1
• Pregnancy (especially third trimester) 1
• Medications: SSRIs, tricyclic antidepressants, dopamine antagonists, antihistamines 1
• Abnormal neurologic examination suggesting peripheral neuropathy 1