Restless Legs Syndrome (RLS)

Symptoms

People describe the sensations as:

• crawling, creeping or "bugs under the skin"
• pulling, tugging or throbbing
• aching or itching deep in the legs
• electric or fizzy feelings

The sensations are usually in the calves but can affect the thighs, feet and, in more severe cases, the arms. They lead to:

• an irresistible need to move, stretch, walk or rub the legs
• trouble falling asleep and frequent waking
• daytime tiredness, low mood and poor concentration

Diagnostic criteria

RLS is diagnosed when all five are present:

1. an urge to move the legs, usually with uncomfortable sensations
2. the urge begins or worsens during rest or inactivity, such as sitting or lying down
3. it is partly or fully relieved by movement, at least while moving
4. it is worse in the evening or night than during the day
5. it is not solely explained by another condition, such as leg cramps, positional discomfort, arthritis or swelling

Periodic limb movements

Most people with RLS also have periodic limb movements of sleep: repetitive jerking or kicking movements of the legs every 20 to 40 seconds during sleep, which can disturb sleep for the person and their bed partner. When these occur without RLS, the condition is periodic limb movement disorder.

Causes and risk factors

Primary RLS

Often runs in families, starting before age 45, and slowly progresses. Several genes have been identified. It is linked to low iron in the brain and changes in dopamine signaling.

Secondary RLS

• iron deficiency, even without anemia; see iron-deficiency anemia
• pregnancy, especially the third trimester, usually resolving after delivery
• chronic kidney disease and dialysis
• peripheral neuropathy, including from diabetes
• medicines: many antidepressants (SSRIs, SNRIs, mirtazapine), sedating antihistamines (diphenhydramine), anti-nausea medicines (metoclopramide, prochlorperazine) and antipsychotics
• alcohol, caffeine and nicotine
• sleep deprivation
• spinal cord conditions, multiple sclerosis and Parkinson's disease

RLS vs conditions that mimic it

Diagnosis

A doctor diagnoses RLS from the history. Tests look for causes:

• ferritin, iron and transferrin saturation: iron treatment is recommended if ferritin is 75 ng/mL or below, or transferrin saturation is below 20 percent, even if blood count is normal
• kidney function, blood sugar, vitamin B12 and thyroid tests
• sleep study in some cases, to measure limb movements or rule out sleep apnea
• nerve tests if neuropathy is suspected

Treatment

Lifestyle and home measures

• regular moderate exercise, but not intense exercise close to bedtime
• consistent sleep schedule
• cut back on caffeine, alcohol and nicotine, especially in the evening
• leg stretches, massage, and warm or cool baths before bed
• mentally engaging activities when sitting, such as puzzles
• compression devices or a vibrating pad may help some people
• review medicines with your doctor; switching an antidepressant or antihistamine can help

Iron replacement

Iron tablets, taken with vitamin C on an empty stomach and often every other day, or intravenous iron, improve symptoms when iron stores are low or borderline. Ferritin is rechecked after a few months.

Medicines

• Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) are now preferred first-line medicines for most people
• Dopamine agonists (pramipexole, ropinirole, rotigotine patch) work well at first but can cause augmentation, where symptoms become worse, start earlier and spread over time. Current guidelines advise against their routine use and recommend low doses when used
• Low-dose opioids for severe, refractory RLS under specialist care
• Bilateral high-frequency peroneal nerve stimulation is an approved device for some people

Pregnancy

Non-drug measures and iron are first-line. Most RLS in pregnancy resolves within weeks of delivery.

Outlook

Secondary RLS often improves when the cause is treated, such as correcting iron or after pregnancy. Primary RLS is usually lifelong but manageable, with periods of remission. Good sleep and treatment of symptoms greatly improve quality of life.

Frequently asked questions

What causes restless legs syndrome?

Often it runs in families. Other causes include low iron, pregnancy, kidney failure, peripheral neuropathy and some medicines such as antidepressants and sedating antihistamines. Caffeine, alcohol and sleep loss can worsen symptoms.

Why are restless legs worse at night?

RLS follows a daily rhythm linked to dopamine and iron levels in the brain, which dip in the evening. Being still in bed also triggers symptoms, since rest is a key provoking factor.

Does iron help restless legs?

Yes, if iron stores are low or borderline. Doctors recommend treatment when ferritin is 75 ng/mL or below or transferrin saturation is below 20 percent. Oral or intravenous iron can reduce symptoms significantly.

What is the best medicine for restless legs?

Current guidelines favor gabapentin, gabapentin enacarbil or pregabalin as first-line medicines, along with iron when stores are low. Dopamine agonists can help but carry a risk of augmentation with long-term use.

Can restless legs be cured?

Secondary RLS can resolve if the cause is fixed, for example after correcting iron deficiency or after pregnancy. Primary RLS is usually a long-term condition, but symptoms can be well controlled with lifestyle measures and treatment.