Workup and Treatment for Restless Leg Syndrome
The initial workup for Restless Leg Syndrome (RLS) should include serum ferritin testing, complete blood count, basic metabolic panel, and liver function tests, followed by first-line treatment with alpha-2-delta ligands (pregabalin or gabapentin) for primary RLS or iron supplementation for patients with ferritin levels <50 ng/mL. 1
Diagnosis and Characterization
RLS is diagnosed based on four essential criteria:
- Uncomfortable urge to move the legs
- Symptoms begin or worsen during periods of rest
- Relief with movement
- Worsening of symptoms in the evening or night 1, 2
Differential Diagnosis
Several conditions can mimic RLS and must be ruled out:
- Leg cramps
- Venous stasis
- Positional discomfort
- Arthritis 1
Initial Workup
Laboratory Testing:
- Serum ferritin (primary test) - values <50 ng/mL suggest iron deficiency as a potential cause 1
- Complete blood count - to evaluate for anemia 1
- Basic metabolic panel - to assess electrolytes and kidney function 1
- Liver function tests - to rule out hepatic causes 1
- Thyroid function tests - to rule out thyroid disorders 1
- HbA1c and urine albumin:creatinine ratio - to screen for diabetes and kidney disease 1
- Pregnancy test when applicable 1
Additional Testing:
- Polysomnography - consider when sleep apnea is suspected, diagnosis is uncertain, or to confirm periodic limb movements during sleep 1
Treatment Algorithm
Step 1: Address Secondary Causes
Iron Deficiency (ferritin <50 ng/mL):
Other Secondary Causes:
Step 2: Non-pharmacological Approaches
- Regular aerobic and resistance exercise 1, 4
- Smoking cessation
- Alcohol avoidance
- Caffeine reduction or elimination 1
- For dialysis patients: consider cool dialysate 1
Step 3: Pharmacological Treatment
First-line Therapy:
- Alpha-2-delta ligands (preferred first-line due to favorable long-term safety profile) 1, 3
- Pregabalin or gabapentin
- Particularly indicated for patients with CKD or ESRD 1
Second-line Therapy:
Third-line Therapy:
- Low-dose opioids for moderate to severe RLS that has failed other therapies 1
Monitoring and Follow-up
- Regular monitoring for medication side effects, particularly augmentation with dopamine agonists 1, 6
- Augmentation warning signs: more intense symptoms, earlier symptom occurrence, and symptom spread to arms or other body regions 2
- Regular follow-up to assess symptom control and adjust treatment 1
- Periodic reassessment of iron status, especially with worsening symptoms 2
Special Considerations
Augmentation Management
Augmentation is characterized by paradoxical worsening of symptoms with dopamine agonist treatment 6, 7. If augmentation occurs:
- Consider switching to alpha-2-delta ligands 1, 3
- Evaluate iron status and supplement if needed 2
- Consider IV iron infusion for those intolerant to oral iron 3
Treatment-Resistant RLS
For patients with refractory RLS:
- Consider combination therapy 3
- High-potency opioids may be necessary for severe cases 1, 3
- Intravenous iron therapy may be beneficial 3
Pitfalls and Caveats
- Dopamine agonists, while effective, should be used cautiously due to high risk of augmentation with long-term use 1, 2, 7
- Starting with low doses of medications and titrating slowly helps minimize side effects 1, 5
- Regular monitoring of iron status is crucial, as iron deficiency can worsen symptoms and contribute to augmentation 1, 2
- Avoid medications that can exacerbate RLS symptoms (e.g., certain antidepressants, antihistamines, dopamine antagonists) 3