eMedicine Specialties > Neurology > Sleep-Related Diseases

Restless Legs Syndrome

Author: Ali M Bozorg, MD, Assistant Professor, Comprehensive Epilepsy Program, Department of Neurology, University of South Florida
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Updated: Aug 19, 2009

Introduction

Background

The term restless legs syndrome (RLS) was used initially in the mid-1940s by Swedish neurologist Karl A. Ekbom to describe a disorder characterized by sensory symptoms and motor disturbances of the limbs, mainly during rest. However, early descriptions date back to the 17th century. It is recognized now as a neurologic movement disorder of the limbs, often associated with a sleep complaint.¹ Patients with RLS have a characteristic difficulty in trying to depict their symptoms. They may report sensations such as an almost irresistible urge to move the legs, which are not painful but are distinctly bothersome. This can lead to significant physical and emotional disability. The sensations usually are worse during inactivity and often interfere with sleep, leading to walking discomfort, chronic sleep deprivation, and stress.² Once correctly diagnosed, RLS can usually be treated effectively and in some secondary cases, it can even be cured.

Pathophysiology

The pathogenesis of RLS is unclear.^3,4,5 Currently, the most widely accepted mechanism involves a genetic component along with abnormalities in the central, subcortical dopamine pathways and impaired iron homeostasis.^6,7 When centrally acting dopamine receptor antagonists are administered to patients with the syndrome, symptoms are reactivated. Results of single-photon emission computed tomography (SPECT) have suggested deficiency of dopamine D2 receptors. Abnormalities of iron homeostasis have also been implicated, based on CSF iron profile measures.

RLS also has a genetic component and tends to run to in families.⁸ Various chromosomes have been implicated so far, including 12q, 14q, 9p, 20p, 4q, and 17p, in both autosomal dominant and recessive fashion.⁶

Frequency

United States

RLS affects about 10-15% of the general population, with a female-to-male ratio of 2:1.⁹ The increased incidence of RLS in women is thought to be related to parity, and nulliparous women have the same risk of age-matched men.¹⁰ RLS is often unrecognized or misdiagnosed.^11,9 Many patients are not diagnosed until 10-20 years after symptom onset. RLS may begin at any age, even as early as infancy, but most patients who are affected severely are middle-aged or older. Symptoms progress over time in about two thirds of patients and, in some, may be severe enough to be disabling.

International

Although the exact prevalence is uncertain, limited studies have indicated that 2-15% of the population may experience symptoms of RLS.¹

Mortality/Morbidity

The severity of symptoms in patients with RLS ranges from mild to intolerable. Although patients experience the sensations in their legs, they also may occur in the arms or elsewhere. RLS symptoms are generally worse in the evening and night and less severe in the morning. While RLS may present early in adult life with mild symptoms, usually by age 50 it progresses to daily severe disruption of sleep leading to decreased daytime alertness. RLS is associated with reduced quality of life in cross-sectional analysis.^12,10

Race

RLS affects African Americans less commonly than white persons, even in secondary RLS caused by hemodialysis.

Sex

Women are affected more commonly than men at a ratio of almost 2:1. The increased risk of RLS in women is thought to be related to parity; nulliparous women have the same risk of developing RLS when compared to age-matched men.¹⁰

Age

Although the prevalence of RLS increases with age, it has a variable age of onset and can occur in children. In patients with severe RLS, 33-40% had their first symptom before the age of 20 years, although the precise diagnosis of RLS was made much later. It usually progresses slowly to daily symptoms and severe disruption of sleep after age 50 years. Individuals with familial RLS tend to have onset of symptoms before age 45 years.

Clinical

History

Diagnosis of restless legs syndrome (RLS) is based primarily on the clinical history. Often, patients do not bring RLS symptoms to the attention of the physician; therefore, including a few general sleep questions in the review of systems can be helpful. RLS patients typically report dysesthetic sensations described as "pins and needles," an "internal itch," or a "creeping or crawling" sensation.

• The criteria for diagnosis of RLS are based on those developed by the International RLS Study Group in 1995; 4 basic elements must be present to make the diagnosis.^11,10,13 They are as follows:¹⁴
  • A compelling urge to move the limbs, usually associated with paresthesias/dysesthesias
  • Motor restlessness, as seen in activities such as floor pacing, tossing and turning in bed, and rubbing the legs
  • Symptoms worse or exclusively present at rest (ie, lying, sitting) with variable and temporary relief on activity
  • Circadian variation of symptoms that are present in the evening and at night (Often, symptoms are relieved after 5:00 am. In more severe cases, symptoms can be present throughout the day without circadian variation.)
• A positive response to dopaminergic therapy supports the diagnosis of RLS.
• Approximately 85% of patients with RLS have periodic leg movements of sleep (PLMS), usually involving the legs.³ PLMS is characterized by involuntary forceful dorsiflexion of the foot lasting 0.5-5 seconds and occurring every 20-40 seconds throughout sleep.
• A large majority of patients (85%) with RLS report difficulty falling asleep at night because of RLS, and they may experience excessive daytime somnolence because of poor sleep quality due to multiple PLMS-induced arousals. PLMS noted on polysomnography alone do not warrant treatment. Clinicians should consider treating PLMS if they are causing frequent arousals.
• Other features commonly associated with RLS but not required for diagnosis include sleep disturbances, daytime fatigue, and involuntary, repetitive, periodic, jerking limb movements either during sleep or while awake and at rest. A positive family history also aids in the diagnosis, especially in children.

RLS in children

• RLS can be difficult to diagnose in children, especially younger children.¹⁵ In order to make the diagnosis of definite RLS, patients must endorse the 4 criteria of RLS and be able to describe leg symptoms in their own language.
• Alternatively, they must have the 4 essential criteria and have sleep disturbances, a sibling or parent with RLS, and a PLMS index >5 on polysomnography.¹⁵ For a possible diagnosis of RLS, a PLMS index >5 on polysomnography and a first-degree family member with RLS are required.
• These strict criteria are intended to prevent overdiagnosis of RLS in children.

Physical

The physical examination is usually normal in patients with RLS; it is performed to identify secondary causes and to exclude other disorders. In particular, the patient should be evaluated for neuropathy, radiculopathy, and parkinsonism.

Causes

RLS can be primary or secondary.

• Primary RLS
  • In most cases, RLS is an idiopathic CNS disorder. Such idiopathic disease can be familial in 25-75% of cases. In the familial cases, it appears to follow a pattern of autosomal dominant or recessive inheritance (see Pathophysiology).
  • Progressive decrease in age at onset with subsequent generations (ie, genetic anticipation) has been described in some families. Patients with familial RLS tend to have an earlier age at onset (<45 y) and slower progression.
  • Psychiatric factors, stress, and fatigue can exacerbate symptoms of RLS.
• Secondary RLS¹
  • RLS can develop as a result of certain conditions or factors, particularly iron deficiency and peripheral neuropathy.⁹ These 2 conditions should be excluded before RLS is labeled as primary.⁹ Because of the prevalence of these conditions in the general population, their association with RLS needs to be interpreted with caution.
  • Other causes are folate or magnesium deficiency, amyloidosis, diabetes mellitus, lumbosacral radiculopathy, Lyme disease, monoclonal gammopathy of undetermined significance, rheumatoid arthritis, Sjögren syndrome, uremia, or vitamin B-12 deficiency.
  • Women can be affected by RLS during pregnancy, and the syndrome usually subsides within a few weeks after delivery. It affects 25-40% of pregnant women.
  • RLS also occurs in as many as 25-50% of patients who have end-stage renal disease and find their symptoms particularly bothersome during hemodialysis. One study found that hyperphosphatemia, anxiety, and a great degree of emotion-oriented coping with stress were independently related to the presence of RLS in patients with uremia who were taking hemodialysis therapy.⁴
  • Certain medications can also cause RLS. Antidopaminergic medications (such as neuroleptics), diphenhydramine, selective serotonin reuptake inhibitors (SSRIs), alcohol, caffeine, lithium, and beta-blockers have been known to cause or exacerbate the symptoms of RLS.
• The pathogenesis of RLS seems to involve more than one mechanism, which leads to restless legs as the final common pathway.

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