Differential Diagnosis for Restless Legs Syndrome

Primary Mimics That Must Be Excluded

The American Geriatrics Society recommends looking for visible varicosities, dependent edema, and skin changes consistent with chronic venous insufficiency to differentiate venous stasis from RLS 1
The American Academy of Sleep Medicine suggests that peripheral neuropathy can be distinguished from RLS by performing a thorough neurological examination to identify sensory deficits, diminished reflexes, or radiculopathy 1
Vascular disease (intermittent claudication) can be differentiated from RLS as claudication pain is exercise-induced and relieved by rest, whereas RLS symptoms worsen with rest 1
The American Academy of Sleep Medicine notes that arthritis pain is typically localized to joints rather than the diffuse leg discomfort of RLS 1, 2, 3, 4

The American Academy of Sleep Medicine states that leg cramps are sudden, painful muscle contractions that are distinct from the urge to move in RLS 2, 3, 4
Neuroleptic-induced akathisia involves a generalized urge to move the whole body, not just the legs, and lacks the uncomfortable leg sensations characteristic of RLS 1
The American Academy of Sleep Medicine recommends checking for diminished peripheral pulses and vascular bruits to differentiate vascular disease from RLS 1
Positional discomfort and muscle aches (myalgia) lack the circadian pattern of RLS and resolve with position change alone, not requiring sustained movement 1, 2, 3, 4
Leg edema presents with visible swelling and pitting on examination, and edema-related discomfort does not follow a circadian pattern 1, 2, 3, 4
Radiculopathy typically follows a dermatomal distribution with positive straight leg raise or other provocative maneuvers 1
Habitual foot tapping is a behavioral pattern without the uncomfortable sensations or urge to move that characterize RLS 1, 2, 3, 4

The American Academy of Sleep Medicine recommends confirming RLS by meeting all five essential criteria, including urge to move the legs, worsening with rest or inactivity, relief with movement, circadian pattern, and not solely accounted for by another medical or behavioral condition 2, 3, 4, 5

The American Academy of Sleep Medicine warns that without performing a proper differential diagnosis, 16% of subjects who do not have RLS will be misclassified as having RLS if you only ask about the four symptom criteria 2, 3, 4

The American Geriatrics Society recommends checking serum ferritin levels to investigate iron deficiency as a secondary cause of RLS, with levels <50 ng/mL suggesting secondary RLS 1, 5