Explore Causes of Restless Legs Syndrome

By Brandon Peters, MD

Although many people with restless legs syndrome (RLS) may never be able to identify a cause to their disorder, often it results from other secondary causes. This thus results in two categories of the condition, the former being primary RLS (of unknown cause) and the latter deemed secondary RLS. There are many conditions that may independently lead to symptoms of RLS and these are described here.

1. Iron Deficiency

The relationship between iron deficiency and RLS symptoms has been extensively studied. In several research studies, low iron levels have been found in the blood and spinal fluid of individuals suffering from RLS. The lower the iron levels, the worse the symptoms. Magnetic resonance imaging (MRI) has shown that the iron content in an area of the brain called the substantia nigra is lower in those with RLS compared to normal individuals, which may contribute to the disorder. In addition, pathological studies have confirmed this change within the brain.

It is therefore recommended that you have your serum ferritin level (a marker of iron stores) checked if you have symptoms of RLS. If the ferritin level is low, generally at a value <75, a trial of oral iron replacement should be undertaken. Even if the levels are normal, some individuals respond to iron replacement.

2. End-stage Kidney Disease

RLS is very common among individuals suffering from end-stage kidney disease, especially those who are dependent upon dialysis. The incidence has been reported to range from 6 to 60 percent. It is unclear what may be contributing to RLS in this group. Anemia, iron deficiency, or even low parathyroid hormone levels may have a role based on various studies. In some cases, treating anemia with erythropoietin therapy or iron replacement has been effective.

3. Diabetes

In people with Type 2 or adult-onset diabetes, RLS may develop. If diabetes is left uncontrolled, nerve damage can result. This is thought to occur because of high levels of glucose within the blood. This can lead to damage of small blood vessels that supply the nerves called vaso nervorum. When these become clogged, the nerve itself will become damaged. Often this leads to a peripheral neuropathy, which consists of pain and a pins-and-needles sensation in the feet. This may progress up the legs and even involve the hands. Associated with these sensory changes, some people will also have symptoms of RLS. Therefore, it is thought that diabetes may be an independent risk factor for developing RLS. In people who have undergone pancreas and kidney transplants, their symptoms of RLS have improved.

4. Multiple Sclerosis

There is a growing body of evidence that multiple sclerosis seems to be associated with an increased risk of having RLS. Some of the studies are conflicting, however. In one of the larger studies that included 1500 subjects, the prevalence of RLS was 19 percent in people with MS compared to only 4 percent of those people without it.

5. Parkinson’s Disease

It is thought that RLS and Parkinson’s disease may be caused by a similar problem, namely disruptions in the neurotransmitter called dopamine. This is not fully understood, however. Regardless, RLS may be present in individuals who have Parkinson’s disease, with a prevalence ranging from 0 to 20.8 percent, based on the study. Parkinson’s disease often involves a sense of restlessness (called akathisia) that may also occur in RLS, which may make it difficult to discriminate between the disorders. When both conditions are present, RLS usually occurs after Parkinson’s disease has become apparent.

6. Pregnancy

Not all conditions that may lead to RLS are disorders. In fact, the state of being pregnant seems to increase not only the incidence but also the degree of RLS symptoms. In a study of 626 pregnant women, only 10 percent had symptoms of RLS prior to becoming pregnant but this increased to 27 percent during pregnancy. It seemed to worsen in the third trimester. The good news is that the symptoms rapidly improved after delivery. It is not clear what causes the increased frequency of RLS during pregnancy. It may be due to iron or folate deficiency or even because of hormonal changes associated with being pregnant.

7. Rheumatic Disease

There are many conditions such as rheumatoid arthritis, Sjogren’s syndrome, and fibromyalgia that may have an association with symptoms of RLS. This relationship is unclear. In one study, 25 percent of individuals with rheumatoid arthritis had RLS symptoms compared to only 4 percent of osteoarthritis. In another study, 42 of 135 patients with fibromyalgia had RLS. The exact reason for this association is not fully understood.

8. Varicose Veins

In some instances, poor blood flow in the legs has been associated with RLS. In particular, weak veins that distend and become uncomfortable have been blamed. These so-called varicose veins are often engorged and blue in color and may be a sign of venous insufficiency. In a study of 1397 patients, 312 people complained of symptoms of RLS.

Treatment of varicose veins has proven to be effective in alleviating some of the symptoms of RLS. Sclerotherapy led to initial improvement in 98 percent of people, with relief maintained at two years in 72 percent. Medication treatment, including hyrdoxyethylrutoside, has also been shown to be modestly effective.

9. Other Conditions

Beyond the conditions described above, there are many other disorders that seem to be associated with RLS symptoms. These include:

• Obesity

• Obstructive sleep apnea

• Hypothyroidism

• High blood pressure

• Heart disease

• Peripheral neuropathies

• Vitamin deficiencies

• Excessive caffeine intake

• Low blood sugar

• Lumbosacral radiculopathy

• Spinal stenosis

• Use of mianserin (an antidepressant medication)

Sources:

Earley, CJ et al. “Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome.” Neurology 2000; 54:1698.

Allen, RP et al. “MRI measurement of brain iron in patients with restless legs syndrome.” Neurology 2001; 56:263.

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Manconi, M et al. “Multicenter case-control study on restless legs syndrome in multiple sclerosis: the REMS study.” Sleep 2008; 31:944.

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What Is Restless Legs Syndrome (RLS)?

By Brandon Peters, MD

Restless legs syndrome (RLS) is one of those conditions that sounds a little too strange to be true, but if you have ever laid down to fall asleep and felt an uncomfortable sensation of bugs crawling under your skin, you may be all too familiar with what RLS is. This condition may leave you kicking your legs as you fall asleep, but a better understanding of the disorder and its causes may lead to the treatment and rest that you need.

What is RLS?

RLS is a movement disorder that is characterized by unpleasant feelings in the legs associated with a need to move. The sensations (called paresthesias) may include aches, pulling, itching, or even the feeling of bugs crawling under the skin. The symptoms typically come on during periods of rest, especially at night, and are relieved by movement. They may make it hard to fall or stay asleep, resulting in insomnia.

There are four features that are used to diagnose RLS and these include:

1. An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs.

2. The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting.

3. The sensations are relieved by movement, such as walking or stretching, as long as the activity continues.

4. The sensations are worse during the evening or night.

Symptoms typically come on within 15 to 30 minutes of resting. In very severe cases, the problems may occur with any seated activity during the day, such as sitting in meetings or in a movie theater. This may lead to fidgeting, constant movement, or the need to kick or massage the legs to relieve the symptoms. Some people are so bothered by the symptoms at night that they will get out of bed.

Individuals with RLS may experience periodic limb movements of sleep (PLMS), which consist of sudden jerking leg movements involuntarily during sleep.

How Common is RLS?

Mild symptoms associated with RLS occur in 5 to 15 percent of the population. It seems to increase as we get older and occurs more commonly in women.

There are two types of RLS. The first, called primary (or idiopathic) RLS, has no clear cause and tends to run in families. The other type, called secondary RLS, occurs as the result of separate conditions, including iron deficiency, diabetes, pregnancy, and more.

Diagnosis and Treatment of RLS

RLS is diagnosed using the four criteria described above. A sleep study called a polysomnogram is not necessary but it may be helpful if the condition is resistant to treatment. It is important to identify any contributing causes so that these can be addressed appropriately. The treatment of RLS may include iron replacement, a combination of medications (including those that enhance GABA or dopamine), exercises, and other therapies.

Sources:

Allen, RP et al. "Restless legs syndrome prevalence and impact: REST general population study." Arch Intern Med. 2003; 163:2323.

American Academy of Sleep Medicine. "International classification of sleep disorders: Diagnostic and coding manual." 3rd ed Text Revision. 2014.

Hogl, B et al. "Restless legs syndrome: a community-based study of prevalence, severity, and risk factors." Neurology. 2005; 64:1920.