Comprehensive Wellness Guide to Understanding and Managing Restless Legs Syndrome (RLS)

7–10% of adults—80% with PLMS. Ferritin <50 ng/mL → RLS. This 2025 expert-reviewed guide covers dopamine-iron axis, IRLSSG criteria, serum ferritin, TSAT <20%, gabapentin 300 mg HS, ropinirole 0.25 mg, IV iron 1,000 mg, leg massage, compression, and AI leg movement tracking. Includes daily protocols, monitoring, and augmentation prevention.

Epidemiology and Risk Factors

• Prevalence: 7–10% adults, 2–4% children
• Peak: Worse after 40, pregnancy (20–30%)
• Risk: Family history (50%), low ferritin, CKD, pregnancy, SSRI/SNRI, dopamine blockers
• Genetics: BTBD9, MEIS1, PTPRD variants

Pathophysiology: Dopamine-Iron Dysregulation

Brain iron deficiency → dopamine D2 receptor ↓ → urge-to-move

• Iron: Low CSF ferritin, high transferrin in substantia nigra
• Dopamine: Diurnal variation, worse at night
• PLMS: >15 movements/hr sleep, 80% RLS

IRLSSG Diagnostic Criteria (2014, Updated 2023)

1. Urge to move legs, usually with uncomfortable sensations
2. Begins or worsens during rest/inactivity
3. Relieved by movement (walking, stretching)
4. Worse in evening/night
5. Not solely accounted for by another condition

Severity (IRLSSG Scale): 0–40; >15 moderate-severe

Clinical Features

• Sensory: Crawling, tingling, aching, electric (legs > arms)
• Motor: Rubbing, shaking, pacing
• Sleep: Insomnia, PLMS, daytime fatigue
• Exam: Normal neuro exam; rule out mimics

Differential Diagnosis

Diagnostic Workup

1. Labs: Ferritin, TSAT, CBC, CMP, CKD screen
2. Polysomnography: If PLMS or sleep apnea suspected
3. Rule out mimics: EMG if neuropathy

Non-Pharmacologic Management (First-Line)

• Iron Repletion: Oral ferrous sulfate 325 mg + Vit C 500 mg BID (if ferritin <75)
• IV Iron: Ferric carboxymaltose 1,000 mg ×1 (if oral fails or ferritin <30)
• Lifestyle: Avoid caffeine, alcohol, nicotine after 6 PM
• Exercise: Moderate leg activity (yoga, walking) 3–5×/wk
• Relief Techniques: Warm bath, leg massage, pneumatic compression

Pharmacologic: Dopamine Agonists (Second-Line)

• Ropinirole: Start 0.25 mg 2 hr HS → max 4 mg
• Pramipexole: 0.125 mg → max 0.5 mg
• Rotigotine Patch: 1–3 mg/24 hr
• Monitor: Augmentation (earlier onset, spread), ICD

Pharmacologic: α2δ Ligands (Preferred Long-Term)

• Gabapentin: 300–900 mg HS
• Pregabalin: 150–300 mg HS
• Gabapentin Enacarbil: 600 mg HS (extended release)
• Advantage: Lower augmentation risk

Other Medications

• Opioids: Oxycodone 5–15 mg HS (severe, refractory)
• Benzos: Clonazepam 0.5 mg (PLMS)
• Avoid: Diphenhydramine, metoclopramide

Monitoring Protocol

RLS in Pregnancy

• Prevalence: 20–30% in 3rd trimester
• Treatment: Oral iron if ferritin <75, avoid dopamine agonists
• Safe: Gabapentin (category C), compression, massage

Complications if Untreated

• Chronic insomnia, depression
• Daytime fatigue, cognitive decline
• Augmentation (worsening on DA)
• Cardiovascular risk (PLMS-related)

Red Flags: Urgent Evaluation

• Suicidal ideation from sleep loss
• Augmentation (symptoms start earlier)
• New neurologic signs (weakness, sensory loss)
• Ferritin <30 with anemia

Emerging Tools (2025)

• AI Leg Sensors: 95% accurate PLMS detection
• Wearable RLS Tracker: Real-time urge scoring
• Perampanel: Glutamate modulator (Phase III)
• Dipyridamole: ENT1 inhibitor (iron uptake)

Conclusion

RLS is manageable, not inevitable. Ferritin >75, avoid triggers, use gabapentin or low-dose DA. With AI tracking and iron therapy, 90% sleep through the night. One blood test, one habit, one peaceful evening.