• Highlights
• Introduction
• Causes
• Risk Factors
• Complications
• Diagnosis
• Treatment
• Medications
• Resources
• References

Restless legs syndrome and related disorders

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of RLS.

Alternative Names

Ekbom's syndrome; Nocturnal leg cramps; Periodic limb movement disorder

Causes

The primary cause of restless legs syndrome is not known. Researchers are investigating neurologic problems that may arise either in the spinal cord or the brain. One current theory on the cause of restless legs syndrome involves a deficiency in a brain chemical called dopamine. RLS probably has a genetic basis in many cases, particularly those that develop before age 40. When the onset of the condition occurs in older adults, it most likely due to some neurologic problem.

Genetic Factors

People with restless legs syndrome often have a family history of the disorder. Researchers have detected specific genetic locations or factors that might be responsible for this condition. Much of the research is based on studies of families with a strong history of RLS-related conditions. In 2005, researchers confirmed that a location on chromosome 12 is definitely linked to RLS. They named this genetic marker RLS1. Locations on chromosomes 14 and 9 may also be associated with hereditary forms of RLS.

Neurologic Abnormalities

Dopamine and Neurologic Abnormalities in the Brain. Other research suggests that neurologic abnormalities involved with RLS and PLMD originate in the brain. A variety of studies support the hypothesis that an imbalance in neurotransmitters (chemical messengers in the brain), notably dopamine and serotonin, may play a part in RLS. Dopamine and serotonin unleash an array of nerve impulses that affect muscle movement. A similar effect is seen in Parkinson's disease, and indeed, drugs that increase dopamine are used for both disorders. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on.

Neurologic Abnormalities in the Spine. Some research suggests that restless legs syndrome may be due to nerve impairment in the spinal cord. It had been thought that such abnormalities were likely to originate from nerve pathways in the lower spine. However, some patients with RLS commonly have symptoms in the arms suggesting that the upper spine may be involved as well. One 2001 study suggested that in patients with RLS and PLMD there is an abnormal overexcitable response along the entire spinal cord, which is triggered by sleep-related factors.

Neuropathy. Some experts suggest that RLS, particularly if it occurs in older adults, may be a form of neuropathy, which is an abnormality in the nervous system outside the spine and brain. Nevertheless, there is no evidence of a causal relationship.

Deficiencies in Iron Metabolism

Iron deficiency, even at a level too mild to cause anemia, has been linked to RLS in some people. Studies suggest, in fact, that RLS in some people may be due to impaired iron acquisition in cells that regulate dopamine in the brain. (Dopamine abnormalities are known to play a role in RLS.) Some studies have reported RLS in 25 - 30% of people with low iron levels. (In fact, the common connection between RLS and Parkinson's disease may derive from iron deficiencies in these patients.)

Causes of Periodic Limb Movement Disorder (PLMD)

The cause or causes of PLMD are not clear. Some research suggests that it may be due to abnormalities in the autonomic nervous system, which regulates the involuntary actions of the smooth muscles, heart, and glands.

• Review Date: 10/18/2006
• Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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