Restless Legs Syndrome (RLS) / Willis-Ekbom Disease

Restless Legs Syndrome (RLS) is a neurological sensorimotor disorder characterized by an irresistible urge to move the legs, usually due to uncomfortable sensations. Symptoms worsen at rest (especially in the evening/night) and improve with movement.

Diagnostic Criteria (International RLS Study Group)

A patient must meet all five of the following:

  1. Urge to move legs (usually with uncomfortable sensations like tingling, crawling, or aching).
  2. Symptoms begin/worsen during rest (sitting or lying down).
  3. Partial/temporary relief with movement (walking, stretching).
  4. Worse in the evening/night (circadian pattern).
  5. Not solely due to another condition (e.g., leg cramps, arthritis, positional discomfort).

Severity Levels:

  • Mild (occasional, minimal sleep disruption).
  • Moderate (symptoms 1-2x/week, delayed sleep onset).
  • Severe (daily, severely impacts sleep and quality of life).

Key Symptoms

  • Unpleasant sensations: Often described as:
    • “Bugs crawling under the skin”
    • “Electric shocks”
    • “Deep itching or throbbing”
  • Involuntary leg movements (Periodic Limb Movements of Sleep, PLMS):
    • ~80% of RLS patients also have PLMS (repetitive leg jerks during sleep).
  • Chronic sleep deprivation due to difficulty falling/staying asleep.

Causes & Risk Factors

Primary (Idiopathic) RLS

  • Strong genetic link (family history in ~50% of cases).
  • Brain iron dysregulation: Low ferritin (<50-75 µg/L) affects dopamine function.

Secondary RLS (Underlying Conditions)

  • Iron deficiency (most common reversible cause).
  • Pregnancy (usually resolves after delivery).
  • Chronic diseases:
    • Kidney failure (uremia).
    • Diabetes, peripheral neuropathy.
    • Parkinson’s disease, multiple sclerosis.
  • Medications:
    • Antidepressants (SSRIs, SNRIs).
    • Antihistamines (e.g., diphenhydramine).
    • Dopamine antagonists (anti-nausea drugs like metoclopramide).

Diagnosis

  1. Clinical history (meeting the 5 diagnostic criteria).
  2. Blood tests:
    • Serum ferritin (if <75 µg/L, consider iron supplementation).
    • Kidney function, glucose, magnesium.
  3. Polysomnography (sleep study):
    • Confirms Periodic Limb Movements of Sleep (PLMS) if suspected.

Treatment Options

1. Non-Pharmacological Therapies

  • Iron supplementation (if ferritin <75 µg/L):
    • Oral iron (ferrous sulfate 325 mg + vitamin C) – Take on empty stomach.
    • IV iron (for severe deficiency or malabsorption).
  • Lifestyle modifications:
    • Regular moderate exercise (avoid excessive or late-night workouts).
    • Leg massages, warm baths, compression socks.
    • Avoid caffeine, alcohol, nicotine (worsen symptoms).
  • Sleep hygiene: Cool, dark room; consistent sleep schedule.

2. Medications (For Moderate-Severe RLS)

First-Line (Dopamine Agonists)

  • Pramipexole (Mirapex), Ropinirole (Requip), Rotigotine (Neupro patch).
  • Side effects: Augmentation (worsening symptoms over time), nausea, impulse control disorders (gambling, shopping).

Second-Line (Alpha-2-Delta Ligands)

  • Gabapentin Enacarbil (Horizant), Pregabalin (Lyrica).
  • Best for patients with neuropathy or insomnia.

Third-Line (Opioids – Low Dose)

  • Oxycodone, Methadone (for refractory cases).
  • Risk of dependence (use cautiously).

Avoid These (Can Worsen RLS)

  • Antihistamines, SSRIs/SNRIs, dopamine blockers (e.g., antipsychotics).

Complications if Untreated

  • Chronic insomnia & daytime fatigue.
  • Depression/anxiety (due to sleep deprivation).
  • Augmentation (medication-induced worsening of symptoms).

When to See a Doctor

  • Symptoms disrupt sleep ≥3 nights/week.
  • Daytime fatigue or mood disturbances develop.
  • Suspected iron deficiency or secondary cause.

Prognosis

  • Primary RLS: Lifelong, but manageable with treatment.
  • Secondary RLS: May resolve with underlying condition (e.g., iron replenishment).