Facts on Restless Legs Syndrome

Please note that the RLS pages are currently under review and update. Please also refer to our RLS Factsheet

On this page:
What is RLS?
Causes of RLS
Symptoms of RLS
Diagnosis of RLS

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What Is RLS?

Restless Legs Syndrome (RLS) is a neurological condition in which you have an uncontrollable urge to move your legs, usually due to leg discomfort. It is often described as tingling, creeping, crawling, jumpy, cramping and sore feeling. Some liken the sensation to shooting darts of electricity, or even squirming insects inside the legs. It typically happens in the evenings or nights while you're sitting or lying down, but can also happen at any time of the day. Moving your legs eases the unpleasant feeling, temporarily. The sensations usually occur deep inside the leg, between the knee and ankle; or 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, or they can sometimes alternate between sides.

Restless legs syndrome, now known as Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED), can begin at any age and generally worsens the older you get. It disrupts sleep which can make you drowsy the next day. Extended travel can also be an issue as sitting still is nearly impossible.

It is estimated that between 7%-10% of the general population have symptoms of this disorder, according to US sources. There are no such statistics available here in Australia.

Genetic Factors. Studies show that approximately 50% of sufferers have a family history of the disorder. Clinical surveys of large groups of RLS patients, have demonstrated that the prevalence of developing RLS symptoms for those with a family history, is three to five times greater than in the population without RLS in the family.

Onset of Symptoms. Although occurring in very young children, the onset of RLS is more typical in the 50+ age group. Usually, at this age, symptoms continue and often increase in severity. For some however, RLS can be intermittent, with symptoms decreasing significantly or even disappearing for a period of time. People with a milder form of RLS may experience their symptoms fairly consistently in later life, but for limited periods. However, for those who begin symptoms in young adult life, or as a child, the condition can become chronic and increase in frequency and severity as they grow older. For those with associated conditions the onset may be more sudden, but the symptoms may also remit when, or if, the condition is resolved. Such conditions include: iron deficiency anaemia, diabetes, alcoholism, rheumatoid arthritis, kidney failure and Parkinson's Disease.

Timing of RLS symptoms. In the majority of cases, the urge to move the legs as well as the unpleasant sensations, appear to be worse in the evening or night than during the day. For many, the symptoms only occur at night. This tendency is associated with our body’s biological clock, the circadian rhythm (from the Latin circa diem, meaning about a day). Diminishing light causes a rise in the hormone melatonin, which triggers the process of lulling our bodies to sleep. Researchers do not fully understand why the symptoms are so linked with the circadian rhythm but they have revealed a peak of RLS restlessness between the hours immediately after midnight and a decrease in the late morning, around 10am to 11am. For some people mid to late afternoon is also a concern.

What Can You Do? As you can see from this information RLS can be different for everyone. No one thing will always work the same way for everyone. It is important to find a specialist to diagnose the condition and try to find the treatment that best suits the individual. Many GP’s are unaware of the condition which is why you should ask to be referred to a Sleep Disorder specialist. Ferritin iron levels should be taken and an overnight sleep study will help make the diagnosis possible. Please refer to the Medical Information section for a list of RLS specialists in your state.)

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Causes of RLS

Although no clear cause is understood for RLS, research has been conducted over the past 20 years into trying to understand the causes of RLS. From this research there appears to be three main factors relating to the disease: brain concentrations of iron; brain dopamine concentrations; and genes.

Role of Iron in RLS (see *1 below)
The single most consistent finding and the strongest environmental risk factor associated with RLS is iron insufficiency. Professor Nordlander first recognized the association between iron deficiency and RLS, and reported that treatment of the iron deficiency markedly improved, if not eliminated, the RLS symptoms.

Despite this strong association between serum iron insufficiency and RLS, only about 15% of the RLS clinical population appears to have peripheral iron deficiency (serum ferritin < 50 mcg/l). To account for this, Professor Nordlander stated in proposing his hypothesis, “It is possible…that there can exist an iron deficiency in the tissues in spite of normal serum iron.” This hypothesis has led investigators to examine whether the brain could be deficient in iron in the face of otherwise normal serum iron measures.

All studies to date support the concept of diminished brain iron in patients with RLS, even when blood tests indicate that their iron stores are normal. Cerebrospinal fluid obtained by lumbar puncture has shown that the iron storage protein ferritin is low in RLS patients, despite these patients having normal serum levels of iron.

Studies using MRI have shown decreased iron concentrations in the substantia nigra, one of the primary brain regions where dopamine-producing cells reside. One study using MRI found a strong relation between iron concentrations in the substantia nigra and the severity of the RLS symptoms.

Through the generous efforts of RLS Foundation in the SA, a Brain Bank has been set for RLS patients who posthumously donate their brains for study. Studies on these tissues have shown markedly diminished iron and iron storage protein in the substantia nigra, consistent with iron insufficiency in the dopamine cells. Overall the studies support the concept of iron dysregulation in brains of patients with RLS, particularly in dopamine-producing cells.

Gaps in our knowledge. Despite the substantial body of research on peripheral iron regulation, we still know very little about how iron is regulated by the blood-brain barrier or by the different cells within the brain. Also there is a relative lack of research on the effects of having iron insufficiency and on exactly how a brain region can be low in iron yet other organs in the body have normal levels?

Role of Dopamine in RLS (see *1 below)
Marked improvement in RLS symptoms seen with drugs that stimulate the dopamine system, and RLS-like symptoms produced with drugs that block the dopamine system, implicate the dopamine system in the pathogenesis of RLS. Although CerebroSpinal Fluid (CSF) is a crude method for assessing the dopamine system in the brain, data from CSF indicate a possible increase in brain dopamine production. Imaging studies using special radioactive chemicals have found reduced receptor and transporter function in the brain of more severely affected RLS patients.

Tissues from the Brain Bank have shown that the dopamine cells are normal in appearance and number, with no indication of damage. However, these studies also found that the dopamine receptors were decreased and the proteins associated with producing dopamine (tyrosine hydroxylase) were increased. The composite results suggest the presence of increased production and release of dopamine might be a malfunction of the receptors that bind the dopamine and transmit the dopamine signal to other cells. The increase in dopamine may be the brain cells' response to the poor signal. When you cannot hear the voices clearly on the TV, you turn up the volume. Cells interact with each other in a similar manner: if a cell cannot “hear” the dopamine message from another cell, it "tells" the other cell to "turn up" the dopamine. Thus despite the increase in dopamine, the end result may be a decrease in the effect that dopamine has on certain brain cells at certain times of the day, leading to the development of RLS symptoms.

Future Exploration. Exactly how iron influences dopamine function is still unclear. Iron deficiency affects other systems in the brain, which potentially could affect the dopamine systems. Recent work done at Johns Hopkins suggests another chemical in the brain, glutamate, may be equally important in causing some of the symptoms experienced by RLS patients. Brain cells in culture and brains from animals show similar changes in the dopamine activity when the iron levels are lowered. These models of disease can be used to examine the connections between iron and dopamine or glutamate, which may reveal what is happening in the human brain and specifically what is happening in RLS.

Role of Genes in RLS. (see *1 below)
Understanding how genes can affect our lives is quite complex. When a specific gene is damaged, for example, an abnormal protein or lack of protein can cause disease such as hemophilia or sickle cell disease. Other problems such as high blood pressure, heart disease and Alzheimer’s disease may result from not just one damaged gene but an interaction of several genes under certain environmental conditions. For instance, most of us are born with normal hearts but over time, because of the interaction between environmental factors (aging, high cholesterol, smoking, increased blood pressure, diabetes, etc.) and genes, some people will progress to having a bad heart.

RLS is also related to environmental factors and genes. The single largest known environmental factor is low iron levels, which may occur before birth, during infancy or childhood, during pregnancy or later in adult life. The low iron may resolve long before one even develops RLS symptoms, but the condition may set into motion certain conditions that eventually lead to RLS. Subtle variations in several genes (BTBD9, MEIS1, MAP2K5/LBXCOR1, PTPRD, TOX3,) are associated with an increased risk of developing RLS.

For example, the change in the BTBD9 gene associated with increased risk of developing RLS is present in about 75% of patients who have RLS but also present in about 65% of patients who never had RLS. We know from studies that there is some point of interaction between several of the genes and iron regulation, thus supporting the concept of an interaction between your iron levels at some point in your life and several genes that may trigger the onset of RLS.

(*1) Excerpt from HopkinsMedicine, Neurology and Neurosurgery as reported by Dr Christopher Early "What is the evidence for the Iron Dopamine hypothesis?"
http://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/restless-legs-syndrome/what-is-rls/causes.html

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Symptoms of RLS

The compelling desire to move is what gives restless legs syndrome its name. Common characteristics of RLS include:

~ An uncomfortable sensation in the legs with a clear need or urge to move the legs. The sensation may be described in many different ways and can also be painful, not just uncomfortable. In the end, all sufferers can clearly identify a need or urge to move the legs as a driving force behind their complaint. These sensations usually occur in the calf area, but may be felt anywhere from the thigh to the ankle. One or both legs may be affected. For some people, the sensations are also felt in the arms. People with RLS have an irresistible urge to move the affected limb when the sensations occur.

~ The symptoms are worse at night. Symptoms may present only at bedtime or they may start in the afternoon or early evening when trying to sit for any period of time. Sleep problems are common with RLS because of the difficulty it causes in getting to sleep. Some individuals may have symptoms throughout the day, but these symptoms will always be worse at night and better sometime in the morning.

~ The symptoms come on with rest. Whether trying to lie quiet at bedtime or sitting through a long plane flight during the day, the sensations can often strike. Whether trying to sit through a movie or quietly reading a book, the symptoms will make what used to be an enjoyable event a most unbearable one. You cannot rest; you cannot relax; you cannot sleep without the tingling and urge to move your legs, or the affected part of your body.

~ The symptoms are relieved with movement. Getting up and walking will immediately relieve the symptoms of Restless Legs Syndrome. However, as soon as the individual settles back into a restful state, the symptoms will usually return. Any movement of the legs will usually bring about some immediate, although temporary relief. If the legs are not moved, they may jump on their own. In some individuals, there may be semi-involuntary movements of the legs preceded by only a very brief sensation. Most individuals with restless legs syndrome will have rhythmic or semi-rhythmic movements of their legs while they are asleep. RLS may also be associated with another, more common condition called Periodic Limb Movement of Sleep (PLMS), which causes the legs to twitch and kick, possibly throughout the night, while they sleep. Although they may not be aware of their movements, usually their bed partner is. It is this movement of the legs, this constant walking to ward off the sensation that gives the the perception of the sufferer being restless, thus the term "Restless Legs Syndrome".

People typically describe restless legs syndrome symptoms as abnormal, unpleasant sensations in their legs or feet, usually on both sides of the body but can also alternate between the two. Less commonly, the sensations can affect the arms and hands. The sensations, which generally occur inside the limb rather than on the skin, are described as:

  • Crawling
  • Creeping
  • Pulling
  • Throbbing
  • Aching
  • Itching
  • Sometimes the sensations are described as “Ants crawling under the skin” and sometimes the sensations seem to defy description. The symptoms are not usually described as muscle cramps or numbness. They are, however, consistently described as the desire to move the legs.

    It's common for symptoms to fluctuate in severity. In some cases, symptoms disappear for periods of time, then recur.

    If you think you may have RLS/WED, contact your doctor.


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    Diagnosis of RLS

    Your doctor may conduct a physical and a neurological exam. Blood tests, particularly for iron deficiency, may be ordered to exclude other possible causes for your symptoms. In addition, your doctor may refer you to a sleep specialist. This may involve an overnight stay at a sleep clinic, where doctors can study your sleep if another sleep disorder such as sleep apnea is suspected. However, a diagnosis of RLS/WED usually doesn't require a sleep study.

    A diagnosis of RLS/WED is based on the following criteria, established by the International Restless Legs Syndrome Study Group:

    ~ You have a strong, often irresistible urge to move your legs, usually accompanied by uncomfortable sensations typically described as crawling, creeping, cramping, tingling or pulling.

    ~ Your symptoms start or get worse when you're resting, such as sitting or lying down.

    ~ Your symptoms are partially or temporarily relieved by activity, such as walking or stretching.

    ~ Your symptoms are worse at night.

    ~ Symptoms can't be explained solely by another medical or behavioural condition.


    Please note that the RLS pages are currently under review and update.