Sleep Disorders Causes & Risk Factors Print Restless Leg Syndrome or Willis-Ekbom Disease Causes By Brandon Peters, MD Updated December 31, 2018 Medically reviewed by a board-certified physician More in Sleep Disorders Causes & Risk Factors Symptoms Diagnosis Treatment Living With Sleep Apnea Insomnia & More Disorders Healthy Sleep Habits Although many people with restless legs syndrome (RLS) may never be able to identify a cause of their disorder, often it results from other secondary causes. This results in two categories of the condition, primary RLS (of unknown cause and often familial) and secondary RLS. There are many conditions that may independently lead to symptoms of RLS. 1 Iron Deficiency LWA/Getty Images The first condition that may lead to symptoms of RLS is 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. In addition, a trial of oral iron replacement if the levels are low should be undertaken. Even some individuals with normal levels respond positively to iron replacement. 2 End-stage Kidney Disease Getty Images 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 Getty Images 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 to 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 Tetra Images/Getty Images There is a growing body of evidence that multiple sclerosis seems to be associated with an increased risk of RLS. Some of the studies are conflicting, however. In one of the larger studies that included 1,500 subjects, the prevalence of RLS was 19 percent in people with MS compared to only 4 percent of those people without it. This may contribute to fatigue, which responds well to amantadine use. 5 Parkinson's Disease Jose Luis Pelaez Inc/Blend Images/Getty Images It is thought that RLS and Parkinson’s disease may be caused by a similar problem, namely disruptions in the neurotransmitter 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, varying based on the study. Parkinson’s disease often involves a sense of restlessness (called akathisia) that overlap with RLS, which may make it difficult to differentiate between the disorders. When both conditions are present, RLS usually occurs after Parkinson’s disease has become apparent. 6 Pregnancy Squaredpixels/Getty Images Not all conditions that may lead to RLS are disorders. In fact, 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 EMS-FORSTER-PRODUCTIONS/Getty Images 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 those with 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 Getty Images 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 varicose veins are often engorged and blue in color and may be a sign of venous insufficiency. In a study of 1,397 patients with varicose veins, 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 Malcolm MacGregor/Moment Open/Getty Images Beyond the conditions described above, there are many other disorders that seem to be associated with RLS symptoms. These include: ObesityHypothyroidismHigh blood pressureHeart diseasePeripheral neuropathiesVitamin deficienciesExcessive caffeine intakeLow blood sugarLumbosacral radiculopathySpinal stenosisUse of mianserin (an antidepressant medication) If you have restless legs symptoms, fortunately, there are effective medications that are used in treatment. Was this page helpful? Thanks for your feedback! Tossing and turning night over night can have a big impact on your quality of life. Our free guide can help you get the rest you need. Sign up for our newsletter and get it free. Email Address Sign Up There was an error. Please try again. Thank you, , for signing up. What are your concerns? Other Inaccurate Hard to Understand Submit Article Sources Allen, RP et al. “MRI Measurement of Brain Iron in Patients With Restless Legs Syndrome.” Neurology 2001; 56:263. Connor, JR et al. “Neuropathological Examination Suggests Impaired Brain Iron Acquisition in Restless Legs Syndrome.” Neurology 2003; 61:304. Earley, CJ et al. “Abnormalities in CSF Concentrations of Ferritin and Transferrin in Restless Legs Syndrome.” Neurology 2000; 54:1698. Kavanagh, D et al. “Restless Legs Syndrome in Patients on Dialysis.” Am J Kidney Dis 2004; 43:763. Lee, JE et al. “Factors Contributing to the Development of Restless Legs Syndrome in Patients With Parkinson Disease.” Mov Disord 2009; 24:579. 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