Restless Legs Syndrome (RLS) – Diagnosis, Symptoms and Treatment

What is Restless Legs Syndrome?

Restless legs syndrome (RLS) is a movement disorder characterized by an uncomfortable urge to move the legs during periods of inactivity such as evenings and sleep. Symptoms tend to improve temporarily with leg movement. The cause is unknown but may be related to abnormalities in the central and peripheral nervous system.

This medical condition is often associated with iron deficiency, and therefore, individuals with the disease should typically have iron studies checked. Other potential contributing factors include kidney disease, spinal cord disease, and peripheral neuropathy. Studies show that restless legs syndrome could be an early sign of Parkinson's disease.

What Causes Restless Legs Syndrome?

The exact cause of restless legs syndrome is unclear. There appears to be a genetic basis as family members of affected patients frequently have the disease. Furthermore, studies in twins demonstrate high concordance rates.

The disease may be related to central and peripheral nervous system abnormalities. Studies suggest that restless legs are associated with low iron stores in the brain. There may also be neurotransmitter abnormalities involving dopamine, glutamate, and GABA (gamma-aminobutyric acid). Individuals can demonstrate peripheral nerve abnormalities, such as increased pain to pinprick testing.

Conditions that often coexist in patients with restless legs syndrome include iron deficiency, kidney disease (uremia), central or peripheral nervous system disease and pregnancy. Studies also show that restless legs syndrome may be an early sign of Parkinson's disease.

Certain medications can exacerbate the disease, as well. These typically include sedating antihistamines such as Benadryl (diphenhydramine), dopamine antagonists such as Haldol (haloperidol), and certain antidepressants, including Remeron (mirtazapine).

How Common is Restless Legs Syndrome?

RLS is a common disorder that has a prevalence of approximately 5%-15% in Caucasians. Its overall prevalence is about 2%-3%. The condition appears to have a higher prevalence in Northern European countries.

Atypical or advanced cases of the condition often require referral to a neurology specialist, especially if first-line and conservative measures are unsuccessful.

Signs and Symptoms

Symptoms often include an unpleasant urge to move the legs during periods of inactivity. Individuals frequently describe a need to move or a crawling/tingling sensation. Symptoms are most noticeable and bothersome in the evening. The discomfort is typically located between the knees and ankles, and leg movement often provides temporary relief. Occasionally, symptoms will also involve the upper limbs.

Diagnosis

The diagnosis is based on a history of an urge to move the legs when lying in bed in the evenings. Additional testing usually includes iron studies (e.g., iron, ferritin, total iron-binding capacity, iron saturation) and a comprehensive metabolic panel to check kidney and liver function. Patients are occasionally evaluated with a sleep study (polysomnography) to evaluate for periodic limb movements at night.

If you have coexisting conditions such as peripheral neuropathy, spinal cord disease, or pregnancy, your doctor may obtain additional tests.

Restless Legs Syndrome Treatment

Restless legs syndrome is treated with oral iron, behavioral techniques, and pharmacologic therapy. A trial of oral iron therapy is typically indicated in patients with borderline or low iron levels. Behavioral and physical techniques include avoiding aggravating substances (e.g., caffeine), exercise, leg massage, and applied heat. Patients with uremia due to chronic kidney disease may benefit from dialysis.

Patients that do not adequately respond to the treatments above often benefit from pharmacologic therapy with one of the following agents:

•         Dopamine agonists
•       Mirapex (Pramipexole)
•       Requip (Ropinirole)
•       Neupro (Rotigotine)
•         Alpha-2-delta calcium channel ligands
•         Horizant (gabapentin enacarbil)
•         Neurontin (gabapentin)
•         Lyrica (pregabalin)

If one drug class or agent is ineffective, treatment with another class or agent can be attempted. Alpha-2-delta ligands should be used cautiously in the elderly as these patients have a higher likelihood of developing side effects such as sedation, which may increase fall risk. Patients with occasional symptoms that do not occur daily can benefit from an as-needed dopamine agonist.

References:

1. Yeh P, Walters AS, Tsuang JW. Restless legs syndrome: a comprehensive overview on its epidemiology, risk factors, and treatment. Sleep Breath 2012; 16:987. - https://www.ncbi.nlm.nih.gov/pubmed/22038683
2. Trotti LM, Bhadriraju S, Becker LA. Iron for restless legs syndrome. Cochrane Database Syst Rev 2012; :CD007834. - https://www.ncbi.nlm.nih.gov/pubmed/22592724
3. Scholz H, Trenkwalder C, Kohnen R, et al. Dopamine agonists for restless legs syndrome. Cochrane Database Syst Rev 2011; :CD006009. - https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006009.pub2/full