Restless legs syndrome
Exam Tips
- Use the IRLSSG 5-point diagnostic framework in OSCEs: urge, rest worse, movement relief, evening/night worse, not explained by mimics.
- A normal neurological exam does not exclude RLS; it supports idiopathic RLS after excluding secondary causes.
- Always mention fasting iron studies even if FBC is normal; anaemia is not required for iron-related RLS.
- State symptom pattern language clearly: 'worse at rest, better with movement, worse in evening/night'.
- In viva, distinguish RLS from akathisia and nocturnal cramps by circadian pattern and movement-responsive relief.
Definition
Restless legs syndrome (RLS, Willis-Ekbom disease) is a neurological sensorimotor disorder defined clinically by an urge to move the legs, usually with unpleasant paraesthesia-like sensations, that begin or worsen during rest and improve with movement. Symptoms follow a circadian pattern (typically worse in the evening/night), commonly disrupt sleep, and must not be better explained by another medical or behavioural condition.
Pathophysiology
RLS is thought to arise from interacting abnormalities in central dopaminergic signalling and iron handling rather than a single lesion. Brain iron insufficiency (which may occur even without overt anaemia) can impair dopamine metabolism in subcortical pathways and increase spinal excitability, helping explain sensory discomfort, motor restlessness, and evening predominance (dopamine activity has circadian variation). Genetic susceptibility is important (often autosomal dominant patterns in familial disease, with multiple risk loci), and secondary forms are linked to pregnancy, iron deficiency, and end-stage kidney disease. See Figure: dopaminergic-iron interaction model in standard neurology sleep-disorder diagrams.
Risk Factors
- Family history of RLS (present in up to half of cases)
- Female sex after age 35 years
- Pregnancy, especially third trimester
- Iron deficiency (with or without anaemia)
- Stage 5 chronic kidney disease/dialysis
- Comorbid neurological disease (for example parkinsonism, polyneuropathy, multiple sclerosis, spinal pathology)
- Diabetes mellitus, hypothyroidism, rheumatoid arthritis, obesity
- Anxiety, depression, ADHD (epidemiological association)
- Drugs/substances: SSRIs, SNRIs, tricyclics, antipsychotics, lithium, dopamine antagonists (metoclopramide, prochlorperazine), sedating antihistamines, beta-blockers, excess alcohol/caffeine/chocolate
Clinical Features
Symptoms
- Irresistible urge to move the legs (sometimes without sensory symptoms)
- Unpleasant deep leg sensations: creeping/crawling, tingling, burning, throbbing, itching, cramping, aching, or 'fizzy' feelings
- Symptoms start or worsen at rest (sitting/lying) and improve with walking/stretching while movement continues
- Evening or night predominance; severe cases may lose obvious diurnal contrast
- Sleep-onset and sleep-maintenance insomnia, non-restorative sleep, daytime fatigue
- Painful symptoms in a substantial minority; severe disease may spread to arms
Signs
- Neurological and vascular examination is usually normal in idiopathic RLS
- Look for signs of secondary causes: pallor (iron deficiency), peripheral neuropathy signs, uraemic stigmata, thyroid disease features, venous stasis/oedema
Investigations
Management
Lifestyle Modifications
- Explain diagnosis and chronic fluctuating course; screen for triggers and offending medicines
- Sleep hygiene: regular sleep schedule, reduce evening screen time, optimise bedroom environment
- Reduce/avoid caffeine, alcohol, nicotine, and sedating antihistamines where possible
- Daily moderate exercise and leg stretching/massage; avoid prolonged immobility
- Correct reversible causes (iron deficiency, renal/metabolic contributors) and review psychiatric comorbidity
Pharmacological Treatment
Iron replacement (if iron deficiency or low iron stores)
- Ferrous sulfate 200 mg oral tablet once daily (about 65 mg elemental iron), increase to twice daily if needed/tolerated
- Alternative oral iron salts at equivalent elemental iron dosing when adverse effects occur
Take on an empty stomach if tolerated; consider vitamin C co-administration to aid absorption. Counsel on constipation, nausea, dark stools, and interactions (separate from levothyroxine, tetracyclines, quinolones). Recheck iron indices after treatment.
Dopamine agonists (moderate-severe persistent idiopathic RLS)
- Pramipexole 88 micrograms base once daily 2-3 hours before bedtime; titrate every 4-7 days; usual maximum 540 micrograms base daily
- Ropinirole 250 micrograms once daily 1-3 hours before bedtime; increase weekly according to response; maximum 4 mg daily
- Rotigotine transdermal patch 1 mg/24 h, increase by 1 mg/24 h at weekly intervals; maximum 3 mg/24 h
Warn about augmentation (earlier/daytime spread of symptoms), impulse-control disorders, hallucinations, orthostatic hypotension, nausea, and sudden sleep attacks (driving risk). Avoid abrupt withdrawal (dopamine agonist withdrawal syndrome risk). Adjust pramipexole in renal impairment; check interactions (for example CYP1A2 inhibitors with ropinirole). Avoid in pregnancy unless specialist advice.
Alpha-2-delta ligands (specialist-led, often when pain/insomnia prominent or dopamine agonists unsuitable)
- Gabapentin 300 mg at night initially (lower, e. g. 100 mg, in frailty/renal impairment), titrate to effect
- Pregabalin 75 mg at night initially, titrate (commonly 150-300 mg nightly)
Use caution with sedation, dizziness, falls, peripheral oedema, and respiratory depression (especially with opioids or severe respiratory disease). Dose-adjust in renal impairment; misuse/dependence potential with pregabalin.
Refractory severe disease (specialist only)
- Low-dose opioid strategies may be considered in specialist sleep/neurology services
Reserve for refractory cases because of dependence, constipation, endocrine effects, overdose risk, and driving/occupation safety implications.
Complications
- Chronic insomnia and fragmented sleep
- Reduced daytime functioning, concentration, and quality of life
- Anxiety and depressive symptoms/comorbidity
- Potential augmentation from dopaminergic treatment
- Possible increase in all-cause mortality signal in epidemiological studies (causality uncertain)
Prognosis
Course is variable: many patients have gradual progression, especially with younger-onset disease, and around 70% may develop moderate-severe symptoms over time. Remission or stability can occur (including in familial cohorts), while secondary RLS may improve substantially if the precipitating condition is corrected. Pregnancy-related RLS usually resolves after delivery but predicts higher future risk of idiopathic RLS.
Sources & References
🏥BMJ Best Practice(4)
✅NICE Guidelines(1)
- Restless legs syndrome[overview]