Restless legs syndrome (RLS, or Wittmaack-Ekbom's syndrome, which is not to be confused with Ekbom's syndrome) is a poorly understood and often misdiagnosed neurological disorder characterized by unpleasant or painful sensations in the body's extremities and an overwhelming urge to move them. Moving the limbs provides temporary relief for this chronic condition. Symptoms are often discernable in early childhood, and may become disabling in later life, particularly due to sleep deprivation.

Symptoms

The key symptoms of RLS are:

an urge to move the legs and sometimes arms, which can be irresistible when severe; this is usually associated with an abnormal sensation such as a "creepy" or "crawly" feeling, a tickle, an ache, or a discomfort that may be very difficult to put into words. These sensations generally occur inside the legs or arms (along the axis) in the calf or forearm area.
involuntary muscle movements (spasms or 'twitching')
excessive movement of the legs or arms when at rest,
aggravation of the discomfort during rest and at least temporary relief by movement,
a circadian rhythm of severity with symptoms being worse at the patient's usual bedtime.

Prevalence

Most sufferers think they are the only ones to be afflicted by this peculiar condition. Many people only have this problem when they try to sleep, but some people show symptoms during the day and pace or 'bounce' their legs. Some people get the symptoms on long car rides or during any long period of inactivity (like watching movies, attending dinners, etc.) The limbs may also start to twitch involuntarily, sometimes causing large limb excursions (flailing) especially during sleep. This is sometimes defined as a related syndrome, called Periodic limb movement disorder. It is not unknown for some people to be thrown out of bed by violent leg movements.

About 10 percent of adults in North America and Europe may experience RLS symptoms, according to the National Sleep Foundation, which reports that "lower prevalence has been found in India, Japan and Singapore," indicating that ethnic factors, including diet, may play a role in the prevalence of this syndrome.

Causes

There is a high incidence of familial cases, suggesting a genetic tendency. Secondary causes of RLS include antipsychotics, antidepressants, antihistamines (particularly those that cause drowsiness), serotonin reuptake inhibitors, and antinausea agents. As there seems to be a link between dopamine and RLS, drugs that interact with dopamine may also cause secondary RLS.

Treatment

Common medications include dopamine agonists (dopaminergic agents) such as levodopa, ropinirole, sinemet or pergolide, opioids such as propoxyphene or oxycodone, benzodiazepines (which improve quality of sleep), or anticonvulsants (patients who report pain may benefit most) such as gabapentin. In 2005, The Food and Drug Administration approved Requip (ropinirole) to treat moderate to severe Restless Legs Syndrome (RLS). The drug was first approved for Parkinson’s disease in 1997.

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Iron for restless legs syndrome
From Townsend Letter for Doctors and Patients, 12/1/04 by Alan R. Gaby

Twenty-five patients with end-stage renal disease who had symptoms of restless legs syndrome (RLS) were randomly assigned to receive, in double-blind fashion, a single intravenous infusion of iron dextran (1,000 mg) or placebo. Prior to treatment, none of the patients had evidence of iron deficiency (serum levels of ferritin and percent iron saturation were normal). Compared with baseline, the median RLS symptom score improved by approximately 43% in the active-treatment group after one and two weeks and by 28% after four weeks. The improvement was significant relative to placebo after one and two weeks, but not after four weeks.

Comment: RLS is a common problem, particularly among elderly people. Because the condition responds to dopaminergic drugs, it has been suggested that reduced dopaminergic activity in the brain may play a role in its pathogenesis. Iron is required for the conversion of tyrosine to levodopa, so a deficiency of iron in the brain may lead to reduced dopaminergic activity. Iron supplementation is known to relieve symptoms of RLS in patients with documented iron deficiency. The present study suggests that iron therapy may also be beneficial for some patients whose standard laboratory tests for iron status are normal. Recent studies suggest that patients with RLS have impaired uptake of iron into some portions of the brain. Consequently, a deficiency of iron could exist in the brain, despite normal iron levels in the periphery.

Other interventions that may be beneficial for RLS include cessation of cigarette smoking and supplementation with vitamin E, folic acid, and magnesium. When these treatments do not work, a trial of iron therapy may be considered for non-iron-deficient patients, as long as they have been screened to rule out hemochromatosis.

Sloand JA, et al. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 2004;43:663-670.

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