Restless Legs Syndrome and Periodic Limb Movements

By | March 12, 2015

Patients with restless legs syndrome describe subjective discomfort of the lower extremities that worsens at night. Patients can have an irresistible need to move their legs in bed or during prolonged periods of sedentary activity, such as airplane flights. This condition was first described by Ekblom in 1945. As a result of these distressing symptoms, patients can experience insomnia or have unre-freshing sleep.


Restless legs syndrome is often unrecognized but is far from rare. For years, all data about this condition were collected in clinical settings and the prevalence in community samples was essentially unknown. A community-based survey showed a prevalence of restless legs syndrome of 3% in respondents ages 18-29 years, 10% in those ages 30-79 years, and 19% in those age 80 years and older. The overall prevalence was 10% with equal rates for male and female respondents. In the study, risk factors for restless legs syndrome were identified as greater age and high body mass index as well as nicotine dependence, diabetes mellitus, and lack of exercise. Another survey of community-dwelling adults in five European countries had slightly different findings. The prevalence of restless legs syndrome according to the criteria of the International Classification of Sleep Disorders was 5.5% and associated with older age, female sex, musculoskeletal disease, hypertension, use of an SSRI, and engaging in physical activities close to bedtime.

Restless legs syndrome sometimes occurs in association with anemia and iron deficiency. The condition can develop during the third trimester of pregnancy, likely because of the presence of functional anemia. Case reports have shown that patients with restless legs syndrome who donate blood may have an exacerbation of the condition, which warrants more medication. Patients with restless legs syndrome should care-fully consider the condition a risk of donating blood.

Restless legs syndrome is known to be secondary to diabetes, peripheral neuropathy, and uremia; 20%-30% of patients with renal failure experience restless legs syndrome. Familial occurrence of restless legs syndrome has been described. In several large families, an autosomal dominant mode of inheritance has been observed. In a large French Canadian kindred, restless legs syndrome was mapped to chromosome 12q. In familial restless legs syndrome, the disorder can have a childhood onset.

Clinical Features

Periodic limb movement disorder is a condition that frequently overlaps with restless legs syndrome. Approximately 80% of patients with restless legs syndrome have intermittent muscle twitches called periodic limb movements. These movements are involuntary leg jerks that occur at night. They can cause insomnia and, as a result, excessive daytime sleepiness. Almost all patients with restless legs syndrome have periodic limb movements, but many patients with periodic limb movements have no symptoms. The periodic limb movements can affect a variety of muscles in the legs or arms. Periodic limb movements in the absence of subjective symptoms of restlessness are of uncertain clinical significance.

Periodic limb movements must be differentiated from nocturnal leg cramps, which are extremely painful sustained muscle contractions, particularly involving the gastrocnemius and soleus muscles. Predisposing factors include pregnancy, diabetes mellitus, electrolyte disturbances, and prior vigorous exercise. Nocturnal leg cramps are not periodic and usually occur, at most, several times a night. The differential diagnosis of restless legs syndrome and periodic limb movement disorder includes neuropathic pain, arthritis, restless insomnia, and drug-induced akathisia.


Patients with restless legs syndrome experience irritability, depressed mood, or cognitive disturbance due to disturbed sleep; headache, especially on awakening; depressed mood; social isolation; and reduced libido.

Pathophysiological Mechanism

Restless legs syndrome is believed to be a condition associated with decreased dopamine levels. Treatment with dopamine antagonists aggravates the symptoms, and this syndrome occurs with increased frequency in Parkinson’s disease. Positron emission tomographic studies of restless legs syndrome have shown decreased dopaminergic functioning in the caudate and putamen regions of the brain. Treatment with dopaminergic agonists, even low doses, leads to marked improvement. Restless legs syndrome has been strongly associated with anemia. Deficient iron stores appear to play a role in the pathophysiological mechanism because iron is hypothesized to be a cofactor for tyrosine hydroxylase, the enzyme for the rate-limiting step in the synthesis of dopamine.

Diagnostic Testing

A rating scale for restless legs syndrome has facilitated diagnosis. Attempts to develop a self-administered screening survey for restless legs syndrome in dialysis populations have been less successful because of low specificity and a high false-positive rate.

An overnight sleep study is not essential, because the diagnosis of restless legs syndrome can be based on the patient’s history. Polysomnography is valuable when a patient may have a coexisting sleep disorder, such as obstructive sleep apnea, or if the patient does not respond to treatment of restless legs syndrome diagnosed on the basis of history alone. Useful laboratory tests include complete blood count to assess for anemia and ferritin, especially when levels are less than 50 mg/L.

Treatment of restless legs syndrome

Treatment of restless legs syndrome is primarily with dopaminergic medications. Direct dopamine receptor agonists, such as pramipexole, have become first-line agents. These drugs have replaced low-dose, controlled-release carbidopa and levodopa because of a lower incidence of side effects and improved efficacy. There have been encouraging reports about the benefits of gabapentin. Long-acting benzodiazepines, such as clonazepam, and opioids, including codeine and methadone, also have been used. Medications that can lead to physical dependence require careful monitoring for tolerance. As a result, these drugs are not preferred treatment choices. Most clinicians use drug treatment of restless legs syndrome. Nonpharmaco-logical options include physical therapy.


Selections from the book: “Textbook of Psychosomatic Medicine”, 2005.