Restless Legs Syndrome (RLS): Definition, Symptom, Cause, and Treatment

Restless Legs Syndrome (RLS) is a neurological condition that causes an uncontrollable urge to move the legs, usually accompanied by uncomfortable sensations. These symptoms typically occur during periods of rest and worsen in the evening or at night, making RLS a leading cause of sleep disruption.

In medical terms, RLS stands for Restless Legs Syndrome, sometimes referred to as Willis-Ekbom disease. It affects an estimated 5–10% of adults, with women impacted more frequently than men. Research published in the Cochrane Library (Carlos et al., 2017) shows that over 80% of people with RLS also experience periodic limb movements during sleep (PLMS), which further impairs sleep quality and daytime functioning.

RLS is linked to dopamine imbalance, iron deficiency, and genetic factors, and may worsen during pregnancy or with chronic medical conditions such as kidney disease and diabetes. While RLS is not life-threatening, untreated symptoms can significantly affect mental health, concentration, and overall quality of life.

What Is Restless Legs Syndrome (RLS)?

Restless Legs Syndrome is a neurological disorder that causes an irresistible, intense compulsion, to move the legs. This condition is classified as a sleep disorder because it habitually interferes with sleep, leading to daytime fatigue and decreased quality of life. 

RLS acts on approximately 7-10% of the general population, with a higher prevalence in women, as discussed by Innes, Kim E., et al.’s (2011) scientific review “Prevalence of restless legs syndrome in North American and Western European populations: A systematic review.” The study further states that RLS is 1.5 to 2 times more common in women than in men, possibly due to hormonal factors and pregnancy-related changes.

According to the American Academy of Sleep Medicine (2009), in the article “Pregnancy-related Hormonal Changes Linked To Increased Risk Of Restless Legs Syndrome,” women are 1.5 to two times more likely than men to develop RLS. Additionally, AASM argues that 80 to 90 percent of individuals with RLS have a movement condition, periodic limb movements (PLMs) during sleep, attributed to involuntary jerking or twitching of the feet or legs. These movements mess with evening rest and instigate intense urges to move the legs.

The prevalence of Restless Legs Syndrome (RLS) is estimated to be between 5% and 15% in adults, as advanced by the research “Benzodiazepines for Restless Legs Syndrome” published in the Cochrane Library by Carlos, Karla, et al. (2017). The incidence of Restless Legs Syndrome (RLS) ranges from 2.2% to 7.9% when considering the frequency or severity of symptoms. Nevertheless, if the diagnosis is predicated solely on clinical interviews and differential diagnosis, the prevalence drops to between 1.9% and 4.6%. Individuals with RLS suffer tired sensations and movement conditions that further weigh heavily on their quality of life.

What Are the Symptoms of Restless Legs Syndrome (RLS)?

The primary symptoms of RLS involve uncomfortable leg sensations and an urge to move that worsens during rest and at night.

Common Symptoms of RLS:

• Strong urge to move the legs, especially when sitting or lying down
• Unpleasant sensations such as crawling, pulling, tingling, itching, or aching
• Symptoms worsen at night, disrupting sleep
• Temporary relief with movement, such as walking or stretching
• Periodic Limb Movements (PLMS) during sleep in over 80% of patients
• Difficulty sitting still, including during travel or long meetings
• Daytime fatigue, poor concentration, irritability, and mood changes

What Are the Causes of Restless Legs Syndrome (RLS)?

The main causes of Restless Legs Syndrome include genetic factors, iron deficiency, dopamine imbalance, and certain medical conditions. RLS has a strong genetic component, with studies indicating that 40-90% of individuals with RLS have at least one first-degree relative (biological parents, sibling, or child) with the ailment as discovered by Xiong, Lan, et al. (2010) in the “Family Study of Restless Legs Syndrome in Quebec, Canada Clinical Characterization of 671 Familial Cases.” The most common causes of Restless Legs Syndrome (RLS) are given below as explored by Sleep Foundation’s article by Dr. Wells, Audrey (2024) “Restless Legs Syndrome (RLS)- What it is, its causes and symptoms, and how it can be addressed to improve sleep”:

• Genetics: Genetics is the hereditary passing of traits from parents to offspring. RLS runs in families. A comprehensive study by Schormair, Barbara, et al. (2024), “Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology, and risk prediction,” published in Nature Genetics conducted meta-analyses of genome-wide association studies (GWAS) involving 116,647 cases and over 1.5 million controls. This research identified 161 risk loci for RLS, confirming known loci and adding 139 new ones, underpinning the genetic basis of RLS.
• Iron deficiency: Low brain iron levels impair dopamine function.
• Lower Dopamine: Impaired dopamine signaling in the brain contributes to RLS symptoms. A study by Bugnicourt, Jean-Marc (2024), “Dopamine Agonists in the Treatment of Restless Legs Syndrome: Too Much of a Good Thing?” published in theJournal of Sleep Medicinediscusses how patients with RLS show a marked response to dopaminergic agents, indicating a hypodopaminergic state in the brain. The findings suggest that impaired dopamine signaling contributes to RLS symptoms.
• Pregnancy: RLS is recurrent during pregnancy and as per a systematic review by Mislu, Esuyawkal, et al. (2023) published in Frontiers in Medicine, “Prevalence and factors associated with restless legs syndrome among pregnant women in middle-income countries: a systematic review and meta-analysis,” presented the pooled prevalence of RLS among pregnant women in middle-income countries to be 13.82%.
• Chronic diseases: Certain medical conditions, such as kidney disease, diabetes, and Parkinson’s disease, are associated with an elevated risk of developing RLS. A comprehensive assessment, “Restless Legs Syndrome in Chronic Kidney Disease- a Systematic Review”by Sarfapour, Yasaman, et al. (2023) disclosed that the prevalence of RLS among chronic kidney disease patients varies between 15% and 30%, with certain studies indicating rates as high as 68% in individuals with end-stage renal disease (ESRD).
• Antidepressants: Antidepressants, while primarily used to treat depression, exert RLS symptoms. Some medications in this category inflate or alleviate RLS, depending on their effects on neurotransmitter systems.

How Is Restless Legs Syndrome Diagnosed?

RLS is diagnosed through clinical evaluation using criteria established by the International Restless Legs Syndrome Study Group.

Diagnostic Criteria Include:

1. Urge to move the legs with uncomfortable sensations
2. Symptoms worsen during rest or inactivity
3. Relief with movement
4. Symptoms worsen in the evening or at night

Additional evaluations include:

• Blood tests to assess iron levels
• Neurological examination
• Sleep studies (polysomnography) if PLMS or other sleep disorders are suspected

What Are the Treatments of Restless Legs Syndrome?

The main treatments for Restless Legs Syndrome are lifestyle changes, medications, and physical therapies.

Lifestyle Changes

• Improving sleep hygiene
• Moderate, regular exercise
• Leg massage before bed
• Warm baths 60–90 minutes before sleep
• Reducing caffeine, nicotine, and alcohol

Medications

• Dopamine agonists (ropinirole, pramipexole)
• Iron supplements for low ferritin levels
• Alpha-2-delta ligands (gabapentin, pregabalin)
• Benzodiazepines (used cautiously to improve sleep)

Physical Treatments

Physical treatments for Restless Legs Syndrome (RLS) include pneumatic compression devices and transcutaneous electrical nerve stimulation (TENS).

Pneumatic compression devices use rhythmic pressure from inflatable cuffs to enhance blood flow and reduce muscle tension, alleviating discomfort and promoting better sleep.

Transcutaneous Electrical Nerve Stimulation (TENS) applies low-voltage electrical currents through electrodes on the skin, modulating nerve activity to relieve the sensations associated with RLS. This non-invasive method can help reduce symptoms in some individuals.

What Age Group Does Restless Legs Syndrome Affect?

Restless legs syndrome affects children aged 8-11, adolescents aged 12-17, and ages 10, 20, and 45 in adults. A population-based study, “Restless legs syndrome: prevalence and impact in children and adolescents–the Peds REST study” published in the journal Sleep Medicine by Picchietti, Daniel, et al. (2007) spotlights RLS being incident in approximately 1.9% of children aged 8-11 years, 2.0% of adolescents aged 12-17, and 25% of adults with RLS between the ages of 10 and 20. The early-onset form of RLS begins in childhood and the signs and symptoms worsen slowly over time. The late-onset form starts after age 45 and tends to progress more rapidly.

What Opioids Are Used for Restless Leg Syndrome?

Opioids used for Restless Leg Syndrome treatment are methadone, oxycodone formulations, hydrocodone, and tramadol. A randomized controlled trial, “Opioids for restless legs syndrome” by Osório de Oliveira, César, et al. (2016) demonstrated the efficacy of combining oxycodone and naloxone for treating refractory RLS patients. After 12 weeks of treatment, 42% of the oxycodone/naloxone group were symptom-free.

How Much Oxycodone for Restless Legs Syndrome (RLS)?

To know how much oxycodone for Restless Legs Syndrome to take, stick to the recommended starting maximum daily dose for an opioid-naïve patient which is 10 mg/5 mg of oxycodone hydrochloride/naloxone hydrochloride taken every 12-hour intervals. As referenced by Lv, Qing, et al. (2021) in the research paper “Pharmacologic Treatment of Restless Legs Syndrome,” a 12-week double-blind and 40-week open-label trial with 306 patients with severe RLS demonstrated that 5.0 mg oxycodone and 2.5 mg naloxone administered twice daily—up titrated to a maximum of 40 mg and 20 mg twice daily, respectively—proved effective in patients with severe RLS who did not respond to dopaminergic drugs. This dosing is aligned with the pain indication for managing severe RLS.

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Can Sleep Disorder Cause Restless Leg Syndrome?

Yes, sleep disorders can cause Restless Legs Syndrome (RLS), the common sleep disorders being obstructive sleep apnea, periodic limb movement, and insomnia. Polysomnographic (PSG) studies, as deliberated about in the research paper “Effects of restless legs syndrome (RLS) on sleep” by Bogan, Richard K. (2006) have shown that patients with Restless Legs Syndrome (RLS) experience major sleep disruptions. On average, they had less total sleep time (326.3 minutes) compared to those without RLS (383.3 minutes), lower sleep efficiency (73.2% versus 86.6%), and more frequent awakenings (12.2 times versus 7.4 times). Moreover, they recounted lower sleep quality and effectiveness, as measured by the Pittsburgh Sleep Quality Index, relative to people without RLS.