Restless Legs Syndrome

Definition and diagnostic criteria (IRLSSG — all five essential; mnemonic URGE). (i) Urge to move the legs, usually with unpleasant crawling or creeping sensations; (ii) begins or worsens at Rest; (iii) partially or completely Relieved by movement; (iv) worse in the Evening or night; (v) not solely explained by another condition (leg cramps, positional discomfort, neuropathy, akathisia, arthritis).

Classification and mechanism. Primary — idiopathic, often familial (BTBD9, MEIS1), earlier onset. Secondary — iron deficiency, chronic kidney disease and dialysis, diabetes and peripheral neuropathy, Parkinson’s disease, rheumatoid arthritis and pregnancy. The core pathophysiology is brain iron deficiency with dopaminergic dysfunction.

Aggravating drugs — a high-yield geriatric point. Antihistamines (including sedating antiemetics), metoclopramide and prochlorperazine, antipsychotics, SSRIs, SNRIs, mirtazapine and tricyclics, and lithium; plus caffeine, alcohol and nicotine. Always review the drug chart before starting new treatment.

Consequences in the elderly. Sleep-onset insomnia and non-restorative sleep, daytime fatigue, depression, and nocturnal wandering with falls and confusion. It is commonly misdiagnosed as anxiety, akathisia, nocturnal cramps or agitation in dementia, and it worsens the burden of coexisting cardiovascular disease.

Investigations. The diagnosis is clinical. Measure serum ferritin and transferrin saturation (morning, fasting sample), renal function, blood glucose and TSH. Periodic limb movements of sleep accompany RLS in about 80% of patients; polysomnography is needed only if the diagnosis is uncertain or obstructive sleep apnoea is suspected.

Treatment. Treat the cause and withdraw offending drugs. Non-pharmacological: sleep hygiene, moderate regular exercise, leg massage, avoidance of caffeine, alcohol and nicotine. Iron replacement if iron stores are low. Drugs: alpha-2-delta ligands — gabapentin, gabapentin enacarbil, pregabalin (sedation, dizziness, ataxia, ankle oedema; reduce dose in renal impairment); dopamine agonists (pramipexole, ropinirole) which cause augmentation, rebound and impulse-control disorders; and low-dose opioids for refractory disease.

AASM Clinical Practice Guideline, J Clin Sleep Med 2025 — a paradigm shift. Dopamine agonists are no longer recommended as first-line therapy because long-term harm from augmentation outweighs short-term benefit. Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) and iron therapy (oral ferrous sulfate or intravenous iron) are now first line, targeting serum ferritin >100 ng/mL and transferrin saturation >20%. Extended-release oxycodone/opioids and bilateral high-frequency peroneal nerve stimulation are conditionally recommended additional options.