What is restless legs syndrome?

Causes and Symptoms

Patients with restless legs
syndrome complain about unpleasant sensations, especially in the evening or at night, that drive them to move their limbs in order to alleviate the discomfort. Sufferers typically describe an inability to tolerate sitting, lying, or remaining still for even short periods of time, accompanied by an intense urge to walk, run, or move about.

The specific etiology of restless legs syndrome remains to be determined, although a number of theories have been proposed. Several of these include central nervous system (CNS) iron deficiency (especially in the brain’s substantia nigra) leading to dopamine defects, CNS hypersensitivity and arousal, disrupted circadian rhythm, and genetic predisposition. Given the complexities of the human brain, more than one process is probably implicated in restless legs syndrome.

As for secondary causes, medications that can produce similar symptoms include caffeine, theophylline, antidepressants (with their anticholinergic effects), dopamine antagonists that cross the blood-brain barrier (the majority of antipsychotic medications), and metoclopramide, as well as withdrawal from any of a number of drugs.

The condition appears to be relatively common, with an estimated prevalence in the general population of up to 10 percent. Further, a greater prevalence appears to exist among first-degree relatives of patients than in those without the condition, suggesting at least some heritability. In fact, evidence initially points to a genetic locus mapped for restless legs syndrome on chromosome 12q.

Although excessive leg movements can be demonstrated during a sleep study test (nocturnal polysomnography), restless legs syndrome is diagnosed by history only. Four essential criteria are used in this process. First, the patient experiences a compelling urge to move the legs (or affected body parts) as a result of unpleasant sensations. Second, the unpleasant sensations and urge to move the legs worsen during the evening or at night and can significantly interfere with relaxation and sleep. Third, the unpleasant sensations and urge to move the legs worsen during periods of inactivity or rest, including sitting in a chair or lying in bed. Fourth, the unpleasant sensations and urge to move the legs are partially or completely relieved by activity, including stretching or walking, but only as long as the activity continues. In addition, patients reporting symptoms of restless legs syndrome should undergo toxicology studies, as well as have their iron, electrolyte, and medication levels checked. Comorbid psychiatric disorders must also be identified.

The symptoms and sensations of restless legs syndrome are typically depicted in negative terms—“fidgety,” “creepy crawlies,” “insect crawlies,” “painful,” and “electric,” among other descriptors. Most report that these sensations can become so intense that they must “jiggle” or “shake,” before ultimately resorting to getting up and walking. Spouses may also complain that patients move their limbs while asleep, thus disturbing the quality of sleep for both partners.

Restless legs syndrome is not limited to the evening hours, bedtime, or sleeping, nor is it necessarily limited to the lower extremities. It can involve an inability to tolerate confinement or immobility—at any time of the day—on airplanes, buses, and cars, as well as in meetings, in movie theaters, and during medical testing, such as magnetic resonance imaging (MRI) or computed tomography (CT) scanning. It can also involve, in more severe cases, other areas of the body, including the hips, upper back, shoulders, and arms. Patients report that it is difficult or impossible to ignore the negative sensations, which adversely affect not only sleep but also daily activities.

Treatment and Therapy

Difficulties arise when attempting to treat restless legs syndrome, as the disorder appears to involve multiple brain processes. The mainstay of medical therapy today consists of daily low-dose dopamine agonists (dopaminergics), the most popular of which are ropinirole and pramipexole, the only medications approved for “idiopathic” restless legs syndrome. Doses of these medications are slowly titrated until therapeutic results are attained. For example, pramipexole is started at 0.125 milligrams taken two hours prior to bedtime for five days and then increased to the usual evening dose of 0.25 milligrams.

The side effects of ropinirole and pramipexole are representative of the dopamine agonists as a class: headaches, nausea, insomnia, “sleep attacks,” and problems related to impulse control (gambling, drinking, shopping, hypersexuality). Anticonvulsants, opioids, and sedative-hypnotics have also been used to treat restless legs syndrome, all with varying success depending on individual patient profiles.

Additionally, sufferers should be instructed to stay away from caffeine, tea, chocolate, alcohol, or tobacco in the evening (after 5 p.m.). They should also be taught to engage in good sleep hygiene (obtain sufficient hours of rest, have a regular time to retire and awaken), to avoid exercising too close to bedtime, to avoid aggravating medications, and to take ferrous sulfate supplements if iron studies show this to be warranted.

Perspective and Prospects

Restless legs syndrome is an underappreciated disorder that causes millions of people a great deal of distress and misery. While many may think of the condition as a new disease, it has been described for centuries. Yet, only since the 1980s has this complex neurological disorder captured the attention of medical scientists and researchers. Such interest has led to the development of medical therapies tailored to relieve the symptoms of restless legs syndrome. Much remains to be done. Primary care physicians, neurologists, psychiatrists, rheumatologists, and other health care professionals are beginning to take this problem seriously as a disorder with a significant morbidity resulting from chronic interruption of sleep and daily activities. Further, future directions in pharmacology will hopefully take into account the need for longer-acting medications and nondopaminergic options.

Bibliography

Allen, Richard P., and Merrill M. Mitler. "Restless Legs Syndrome (RLS) and Sleep." National Sleep Foundation, 2011.

Badash, Michelle, and Michael Woods. "Restless Legs Syndrome." Health Library, Mar. 15, 2013.

Buchfuhrer, Mark J., Wayne Hening, and Clete Kushida. Restless Legs Syndrome: Coping with Your Sleepless Nights. New York: Demos, 2007.

Maheswaran, Murali, and Clete A. Kushida. “Restless Legs Syndrome in Children.” Medscape General Medicine 8, no. 2 (June 20, 2006): 79.

"Restless Legs." MedlinePlus, Mar. 5, 2013.

"Restless Legs Syndrome Fact Sheet." National Institute of Neurological Disorders and Stroke, Nov. 25, 2011.