Restless legs syndrome

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.

Description
RLS may be described as uncontrollable urges to move the limbs in order to stop uncomfortable, painful or odd sensations in the body, most commonly in the legs. Moving the affected body part eliminates the sensation, providing temporary relief. The sensations and need to move may return immediately after ceasing movement, or at a later time. RLS may start at any age, including early childhood, and is a progressive disease for a certain percentage of sufferers, although it has been known for the symptoms to disappear permanently in some sufferers.

Symptoms
The International Restless Legs Syndrome Study Group (IRLSSG) identified four criteria that must be present for an RLS diagnosis.

The sensations are unusual and unlike other common sensation and those with RLS have a hard time describing them. People use words such as: uncomfortable, electrical, creeping, painful, itching, pins and needles, pulling, creepy-crawly, ants inside the legs, and many others. The sensation and the urge can occur in any body part; the most cited location is legs, followed by arms. Some people have little or no sensation, yet still have a strong urge to move.
 * "An urge to move, usually due to uncomfortable sensations that occur primarily in the legs."


 * "Motor restlessness, expressed as activity, that relieves the urge to move."

Movement will usually bring immediate – however often temporary – relief. Walking is most common, however doing stretches, yoga, biking, or other physical activity may relieve the symptoms. Constant and fast up-and-down movement of the leg, coined "sewing machine legs" by at least one RLS sufferer, is often done to keep the sensations at bay without having to walk. Sometimes a specific type of movement will help a person more than another.


 * "Worsening of symptoms by relaxation."

Any type of inactivity involving sitting or lying – reading a book, a plane ride, watching TV or a movie, taking a nap - can trigger the sensations and urge to move. This depends on several factors: the severity of the person’s RLS, the degree of restfulness, the duration of the inactivity, etc.


 * "Variability over the course of the day-night cycle, with symptoms worse in the evening and early in the night."

While some people only experience RLS at bedtime and others experience it all day and all night, all sufferers notice that the RLS is worst in the evening and the least noticeable sometime in the early to mid morning.

Prevalence
Often sufferers think they are the only ones to be afflicted by this peculiar condition and are relieved when they find out that many others also suffer from it. The severity and frequency of the disorder vary tremendously. Many people only experience symptoms when they try to sleep, while other experience symptoms during the day. It is common to have symptoms on long car rides or during any long period of inactivity (like watching television or a movie, attending a musical or theatrical performance, etc.) Approximately 80-90% of people with RLS also have PLMD, Periodic Limb Movement Disorder, which causes slow "jerks" or flexions of the affected body part. These occur during sleep (PLMS = Periodic Limb Movement while Sleeping) or while awake (PLMW - Periodic Limb Movement while Waking).

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
RLS is either primary or secondary. Primary RLS is considered idiopathic, or with no known cause. However, there is a high incidence of familial cases, suggesting a genetic tendency in primary RLS. Primary RLS starts before age 40 or 45 (can occur as early as the first year of life). In primary RLS, the onset is often slow. The RLS may disappear for months, or even years, however it always returns. It is often progressive and gets worse as the person ages.

Secondary RLS often had a sudden onset and may be daily from the very beginning. It often occurs after the age of 40, however it can occur earlier. It is most associated with specific medical conditions or the use of certain drugs. The conditions include: pregnancy, iron deficiency, folate deficiency, uremia, diabetes, thyroid problems, peripheral neuropathy, and certain auto-immune disorders such as Sjogren's, Celiac Disease, and rheumatoid arthritis. Treatment of the underlying condition often eliminates the RLS.

Both primary and secondary RLS can be worsened by surgery of any kind, however back surgery or injury is often associated with causing RLS.

Certain medications may worsen RLS in those who already have it, or cause it secondarily. These include: anti-nausea drugs, certain antihistamines (often in over-the-counter cold medications), drugs used to treat depression (both older tricyclics and newer SSRIs), antipsychotic drugs, and certain medications used to control seizures.

Train drivers in South Africa operate a vigilance control by clicking a pedal with their right foot every thirty seconds. If it doesn't happen, a stimulus is emitted followed soon by emergency braking, it can contribute to restless legs syndrome which can keep the driver clicking the pedal while sleeping.

Treatment
An algorithm for treating RLS was created by leading RLS researchers at the Mayo Clinic and is endorsed by the Restless Legs Syndrome Foundation. This document provides guidance to both the treating physician and the patient, and includes both nonpharmacological and pharmacological treatments.

Treatment for RLS is based on how disruptive the symptoms are. All people should review their lifestyle and see what changes could be made to reduce or eliminate their RLS symptoms. These include: finding the right level of exercise (too much worsens it, too little may trigger it); eliminating caffeine, smoking, and alcohol; changing the diet to eliminate foods that trigger RLS (different for each person, but may include eliminating sugar, triglycerides, gluten, sugar substitutes, following a low-fat diet, etc.); keeping good sleep hygiene; treating conditions that may cause secondary RLS; avoiding or stopping OTC or prescription drugs that trigger RLS; adding supplements such as magnesium, B-12, folate, vitamin E, and calcium. Some of these changes, such as diet and adding supplements are based on anecdotal evidence from RLS sufferers, as few studies have been done on these alternatives.

All people with RLS should have their ferritin levels tested; ferritin levels should be at least 50 mcg for those with RLS. Oral iron supplements, taken under a doctor's care, can increase ferritin levels. For some people, increasing ferritin will eliminate or reduce RLS symptoms. At least 40% of people will not notice any improvement, however. IV iron is being tested at the US Mayo Clinic as a method of treating RLS. It is dangerous to take iron supplements without first having ferritin levels tested, as many people with RLS do not have low ferritin and excess iron in the body can cause hemochromatosis, a very dangerous condition.

For those who experience RLS infrequently and do not need or want to try medication, in addition to lifestyle changes they can try:
 * some form of exercise for several minutes such as walking, stretching, yoga, etc. at bedtime
 * heat or cold, such as a hot or cold bath, a heating pad, or a fan
 * engrossing the mind into a game, the computer, or figuring something out
 * wearing compression stockings, tight pantyhose, or wrapping the legs in ace bandages

For those whose RLS disrupts or prevents sleep or regular daily activities, medication is often required. Doctors currently use, and the Mayo Clinic Algorithm includes, medication from four categories:


 * Dopamine agonists such as ropinirole, pramipexole, carbidopa/levodopa or pergolide
 * Opioids such as propoxyphene, oxycodone, or methadone
 * Benzodiazepines, which often assist in staying asleep and reducing awakenings from the movements
 * Anticonvulsants, which often help people who experience the RLS sensations as painful, such as gabapentin

There is also strong anecdotal evidence that medical marijuana alleviates RLS, although studies are lacking because of governmental restrictions.

In 2005, The Food and Drug Administration approved ropinirole to treat moderate to severe Restless Legs Syndrome (RLS). The drug was first approved for Parkinson's disease in 1997. In February 2006, the EU Scientific Committee issued a positive recommendation for approving pramipexole (Sifrol, Mirapexen in the EU) for the treatment of RLS in the EU. US FDA approval is expected sometime in 2006. Another dopamine agonist, rotigitine delivered via a transdermal patch, is currently in process for US FDA and EU approval for RLS.

Dopamine agonists may cause augmentation. This is a medical condition where the drug itself causes symptoms to increase in severity and/or occur earlier in the day. Dopamine agonists may also may cause rebound, when symptoms increase as the drug wears off.

Theories regarding RLS
No one knows the exact cause of RLS at present. Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra (study published in Neurology, 2003). Iron is involved in the formation of dopamine. An Icelandic study in 2005 confirmed the presence of an RLS susceptibility gene also found previously in a smaller French-Canadian population in 2003.

The continual-activation theory of restless legs syndrome proposed by Jie Zhang hypothesizes that RLS occurs when a brain mechanism which is evolved for safeguard brain from "brain death" during sleep, is wrongly turned on during waking time. The theory is developed through a series of hypotheses. Zhang believes that human brain can be divided into two subsidiary systems: the conscious brain and the non-conscious brain. The conscious subsidiary system of brain is evolved to process conscious related human information like declarative memory for instance, while the non-conscious subsidiary system is evolved to process non-conscious related information such as procedural memory and motor skills. In order to maintain brain proper functioning, Zhang proposes that both systems have to be continually activated through their life times. To carry out this task, Zhang suggests that human brain has a continual-activation mechanism in each subsidiary system. When the level of activation in any subsidiary system descends to a given threshold, the corresponding continual-activation mechanism will be triggered to generate a pulse-like activation signal. According to this theory, the continual-activation mechanism in the non-conscious part of brain is supposed to be turned on during NREM sleep; while the continual-activation mechanism in the conscious part of brain is supposed to be switched on during REM sleep. RLS occurs when the continual-activation mechanism in the non-conscious subsidiary system of brain is wrongly triggered during waking, due to the malfunction of continual-activation thresholds. The theory also predicts that a close related illness - PLMD (periodic limb movement disorder) is sprung from the same mechanism, but with different cause. PLMD occurs when the lowered muscle tone is lacking while this mechanism is activated during NREM sleep. (Zhang, 2005a & 2005b).