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By Carol Rados
Restless Legs Syndrome (RLS) is a medical condition characterized by unpleasant sensations in the legs, including burning, tugging, and tightening, and feels "like insects crawling inside the legs," according to the National Institute of Neurological Disorders and Stroke (NINDS).
Although experts have known about RLS for years, a broader lack of awareness appears to have severely limited diagnosis of the condition. A survey conducted by the Restless Legs Syndrome Foundation (RLSF) not only found that more than half of those who responded had never heard of RLS, but also found that many did not fully understand the impact that the condition can have on daily life.
"RLS is sometimes described as 'the most common condition you've never heard of,'" says Georgianna Bell, executive director of the RLSF.
The abnormal sensations (paresthesias) or unpleasant abnormal sensations (dysesthesias) often range from uncomfortable to irritating and painful.
The NINDS says that some researchers estimate that RLS affects as many as 12 million people in the United States. However, others estimate a much higher occurrence because RLS is thought to be underdiagnosed, and, in some cases, misdiagnosed. There are a number of people who don't seek medical attention, because they believe that their concerns will not be taken seriously, their symptoms are too mild, or their condition is not treatable.
In May 2005, the Food and Drug Administration approved the first drug treatment for RLS for which the cause is unknown (idiopathic). Called Requip (ropinirole), the drug is specifically labeled for the treatment of moderate-to-severe symptoms of the condition. According to the RLSF, the FDA's approval of Requip represents a significant step forward in patient care. "It is our hope that the millions of people suffering from RLS will benefit from this increased awareness and will more easily find the help they need," says Bell.
People with RLS feel uncomfortable sensations in their legs, especially when sitting or lying down, accompanied by an irresistible urge to move about. The NINDS says that these sensations usually occur deep inside the leg, between the knee and ankle. More rarely, they occur in the feet, thighs, arms, and hands. Although the sensations can occur on just one side of the body, they most often affect both sides.
Because moving the legs, or other affected parts of the body, temporarily relieves the discomfort, people with RLS often keep their legs in motion to minimize or prevent the sensations. They may pace the floor, constantly move their legs while sitting, and toss and turn in bed.
The most distinctive or unusual aspect of RLS is that lying down and trying to relax actually activates the symptoms. As a result, most people with RLS have difficulty falling asleep and staying asleep. The NINDS says that left untreated, the condition causes exhaustion and daytime fatigue. Many people with RLS report that their jobs, personal relations, and daily activities are affected as a result of their lack of sleep. They are often unable to concentrate, have impaired memory, or fail to accomplish daily tasks.
The cause of RLS, in most cases, is unknown. A family history of the condition is seen in about half of these cases, the NINDS says, suggesting a genetic basis for the disorder. In some cases, RLS appears to be related to chronic medical conditions, including low iron levels, severe kidney disease, and peripheral nerve diseases--referred to as "secondary forms of RLS." These secondary forms can also be associated with pregnancy and the use of certain medications.
Researchers also have found that caffeine, alcohol, and tobacco may aggravate or trigger symptoms in people who are predisposed to the development of RLS. The reduction or complete elimination of such substances may relieve symptoms, but the NINDS says that it remains unclear whether either can prevent RLS symptoms entirely.
NINDS researchers are investigating the possible role of dopamine function in RLS. Dopamine is a chemical messenger that carries nerve cell signals in the brain that control body movement. When the dopamine system does not function properly, it may upset the normal communication of these signals. Researchers suspect that impaired transmission of dopamine signals may play a role in RLS.
RLS was first fully described in a paper published in 1945 by a Swedish neurologist. Although he did not call the disorder RLS, the neurologist characterized the condition as having sensory symptoms and motor disturbances of the limbs, mainly during rest.
Men and women experience RLS, but the incidence may be slightly higher in women, the NINDS says. The syndrome may begin at any age, even in infancy, but most people who are severely affected are middle-aged or older. In most cases, the severity of the disorder increases with age, but there are exceptions, like that of Benjamin Brown.
The 34-year-old Bethesda, Md., resident experienced much worse symptoms of RLS through high school and as an avid athlete in college. "Restless is the best word to describe the feelings," Brown says. "It felt like a tingling or tightening in my legs, like I needed to stretch or exercise them." Brown says that the sensations came on usually during sedentary periods in the evening, when he was watching TV or studying for school. "It may have made it more difficult for me to fall asleep," he says, but only occasionally. Brown says that although a long walk would help alleviate the sensation, he remembers that "it wasn't easy to get rid of."
As he got older, the condition got better, to the point where "it just didn't seem like it was at the level where you'd see a health professional." Despite not seeking treatment for the disorder, Brown says the feelings gradually went away. In fact, he says he hasn't felt the leg sensations for more than seven years.
If such improvements do occur, the NINDS says it is usually during the early stages of the disorder. In general, however, symptoms become more severe over time.
Older patients experience symptoms more frequently and for longer periods of time.
The symptoms of the condition vary in severity and duration from person to person. Mild RLS generally occurs episodically, with only mild disruption of sleep, and causes little distress. In severe cases, the symptoms of RLS occur more than twice a week and result in burdensome interruption of sleep and impairment of daytime function.
More than 80 percent of people with RLS also experience a more common condition known as periodic limb movement disorder (PLMD), according to the NINDS. PLMD is characterized by involuntary leg twitching or jerking movements during sleep that typically occur every 10 to 60 seconds, sometimes throughout the night. The symptoms can cause repeated awakening and severely disrupted sleep.
The difference between the two disorders is that PLMD occurs while people are sleeping and has no symptoms, while RLS keeps people awake because of the symptoms. Although many patients with RLS also develop PLMD, the NINDS says that most people with PLMD do not experience RLS. And like RLS, the cause of PLMD is unknown.
There is no single diagnostic test for RLS. It is diagnosed clinically by evaluating a person's symptoms and medical history. In 1995, the International Restless Legs Syndrome Study Group identified four basic criteria for diagnosing RLS: a desire to move the limbs, symptoms that are worse or present only during rest and are partially or temporarily relieved by activity, motor restlessness, and worsening of such symptoms at night. The NINDS says that most people with RLS have sleep disturbances, largely because of the limb discomfort and jerking.
Despite established standard criteria, the clinical diagnosis of RLS is often difficult to make. Doctors must rely on patients' descriptions of the symptoms and information from their medical history, including past medical problems, family history, and current medications. The NINDS says that blood tests to rule out anemia--a reduction in the number of red blood cells--as well as decreased iron stores, diabetes, and renal dysfunction, should be performed. Other tests that measure electrical activity in muscles and nerves also are recommended.
Other tests are important to determine whether the RLS is secondary to another disorder that requires treatment. The treatment of that disorder may, on it own, relieve the symptoms of RLS.
Most people find the symptoms to be less noticeable during the day and more pronounced in the evening or at night. For many, the symptoms disappear by early morning. Other triggering situations are periods of inactivity, such as long car trips, watching a movie, long-distance airplane flights, or relaxation exercises.
Movement of the legs generally brings about temporary relief from RLS. And sometimes treating associated medical conditions, such as diabetes or Parkinson's disease, will often alleviate many symptoms.
While central nervous system depressants, anticonvulsants, dopaminergic agents--largely used to treat Parkinson's disease--and opiods have been commonly used by doctors to treat RLS, there have been no clinical studies conducted to support their safety and effectiveness in treating the condition. Finally, Requip was approved for RLS, based on scientific evidence from clinical trials.
First approved for Parkinson's disease in 1997, Requip is a dopamine agonist--it directly stimulates dopamine receptors in the brain. The drug was specifically approved to treat moderate-to-severe RLS last year, after it was found to be effective in three studies in adults. The studies measured effectiveness of the drug using a patient-rated scale that measures different aspects of RLS, including severity of muscle movement and discomfort, sleep disturbance, mood, and overall effect on quality of life, as well as an investigator-rated scale that scores improvement of symptoms after treatment. All three studies demonstrated a difference between the treatment group receiving Requip and the group receiving an inactive pill (placebo).
There has been a clinical impression that "drugs that help Parkinson's disease seem to also help RLS," says Norman Hershkowitz, M.D., the primary clinical reviewer for RLS in the FDA's Center for Drug Evaluation and Research. But Hershkowitz says that the physiological mechanism--or what's actually happening in the body when RLS occurs--isn't well understood.
Requip works to prevent the symptoms of RLS, so patients take the drug at the same time every day, rather than on an as-needed basis. Common side effects include nausea, headache, and vomiting. The drug's label also includes a caution that Requip has been associated with sedating effects, including sleepiness, and the possibility of falling asleep while engaged in activities of daily living. Fainting or low blood pressure also may occur, particularly during initial treatment or dosing.
The RLSF reports that some medicines can make RLS worse and that people need to make their doctors aware of all drugs they are taking, including herbal remedies and over-the-counter medicines.
Although there is no cure for RLS, treatment with Requip can control the disorder, thereby minimizing symptoms and increasing periods of restful sleep. In most cases, RLS can be effectively diagnosed and treated by a primary care physician--in the more difficult cases, by a sleep specialist or a neurologist.
As distressing a condition as it is, some patients like Brown do experience remissions, or periods in which symptoms decrease or disappear. And the NINDS says that a diagnosis of RLS does not indicate the onset of another neurological disorder.
Currently, another medication for treating the symptoms of the condition is under FDA consideration. Additional research should provide a scientific understanding of how RLS occurs, which is likely to lead to more effective treatments and even prevention of the disorder.
The National Institute of Neurological Disorders and Stroke
www.ninds.nih.gov
(800) 352-9424
Restless Legs Syndrome Foundation
www.rls.org
National Sleep Foundation
www.sleepfoundation.org