Restless Leg Syndrome and Complex Regional Pain Syndrome

Pathophysiology and Diagnosis

The American Geriatrics Society notes that RLS pathophysiology involves dopaminergic dysfunction in the substantia nigra with reduced intracellular iron transport, creating a compelling urge to move the legs that worsens at rest and improves with movement, following a circadian pattern with evening/nighttime predominance 1, 2
RLS has four essential diagnostic criteria: (1) urge to move legs with uncomfortable sensations, (2) symptoms begin or worsen with rest/inactivity, (3) symptoms relieved by movement, and (4) symptoms worse in evening/night 2

Iron deficiency states (ferritin <50 ng/mL) are the primary secondary cause of RLS, including iron-deficiency anemia, end-stage renal disease, and pregnancy 1
Medications that exacerbate RLS include tricyclic antidepressants, SSRIs, lithium, dopamine antagonists (antipsychotics), and antihistamines—many of which might be prescribed for CRPS pain management 1, 3

The American Geriatrics Society recommends checking morning fasting serum ferritin and transferrin saturation in any patient with suspected RLS, targeting ferritin ≤75 ng/mL or transferrin saturation <20% for supplementation 4, 5
A thorough neurologic examination should be performed to distinguish RLS from peripheral neuropathy, radiculopathy, vascular disease, or arthritides 2
Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) are first-line pharmacological treatment for RLS, which also helps neuropathic pain from CRPS 4, 5
Correct iron deficiency with oral ferrous sulfate or IV ferric carboxymaltose if ferritin ≤75 ng/mL or transferrin saturation <20% 4, 5