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Restless Legs Syndrome

Restless legs syndrome is characterized by sensory symptoms and motor disturbance of the limbs, mainly during rest. Although the syndrome affects about 10% to 15% of the US population (2), it is often unrecognized.

Diagnostic criteria and common features

Criteria for diagnosing restless legs syndrome requires that four basic elements must be present to make the diagnosis: (1) a desire to move the limbs, often associated with paresthesia or dysesthesia, (2) symptoms exacerbated by rest and relieved by activity, (3) motor restlessness, and (4) nocturnal worsening of symptoms. These and several additional features commonly seen in restless legs syndrome are discussed.

  • Desire to move the limbs, paresthesia, dysesthesia. Patients often describe an unpleasant sensation in the calves and occasionally in the thighs, feet, or upper limbs.

  • Symptoms are similar to those described by patients with akathisia (which is usually caused by use of neuroleptic drugs). However, in contrast to patients with restless legs.

  • Symptoms exacerbated by rest, relieved by activity. The unpleasant limb sensations of restless legs syndrome are precipitated by rest or inactivity (eg, lying in bed at night, riding).

  • Motor restlessness. Patients describe a buildup of discomfort and involuntary limb jerking if they remain still. There is an urge to move the legs and relief after moving. Nocturnal worsening of symptoms. All patients notice worsening of symptoms at night (usually as they lie in bed before sleep or when they are awakened in the middle of the night) and improvement early in the morning.

  • Periodic limb movements of sleep. About 80% of patients with restless legs syndrome have unilateral or bilateral periodic limb movements of sleep, also called nocturnal myoclonus (1,3). These movements are stereotyped, repetitive, slow flexion.

  • Dyskinesias while awake. These motions, also called periodic limb movements while awake, are seen in 30% to 50% of patients with restless legs syndrome (3).

  • Sleep disturbance. Because of limb discomfort and jerking, most patients, restless leg syndrome.

Primary disease

In most cases, restless legs syndrome is idiopathic. Such idiopathic disease can be familial.

Secondary disease

Restless legs syndrome can develop as a result of certain conditions or factors (table 1), particularly iron deficiency and peripheral neuropathy (6-12). These two conditions should be ruled out on clinical grounds before restless legs syndrome is labeled primary (13).

Table 1. Factors and conditions that may contribute to secondary restless legs syndrome (in order of frequency)
Deficiency of iron, folate, or magnesium

Polyneuropathy caused by alcohol abuse, amyloidosis, diabetes mellitus, idiopathic polyneuropathy, lumbosacral radiculopathy, Lyme disease, monoclonal gammopathy of undetermined significance, rheumatoid arthritis, Sjögren's syndrome, uremia, or vitamin B12 deficiency



Parkinson's disease

Gastric surgery

Chronic obstructive pulmonary disease


Chronic venous insufficiency or varicose veins

Intake of certain substances or drugs: alcohol, caffeine, anticonvulsants (eg, methsuximide [Celontin Kapseals], phenytoin [Dilantin]), antidepressants (eg, amitriptyline HCl [Elavil], paroxetine HCl [Paxil]), beta blockers, histamine2 antagonists, lithium, neuroleptics

Withdrawal from vasodilators, sedatives, or imipramine HCl (Tofranil)

Cigarette smoking

Myelopathy or myelitis

Hypothyroidism or hyperthyroidism

Acute intermittent porphyria

Fibromyalgia syndrome

Arborizing telangiectasia of the lower limbs

Peripheral microemboli made of cholesterol

Restless legs syndrome can be the initial manifestation of iron deficiency (1,14). A low serum ferritin level may precede a drop in serum iron level. Depletion of iron stores.

About 5% of patients with sensory neuropathy (especially caused by uremia, rheumatoid arthritis, and diabetes) have restless legs syndrome (8). Treatment of the polyneuropathy may improve symptoms.


Diagnosis of restless legs syndrome is founded mainly on clinical history. If a secondary cause is suspected on the basis of history, abnormal findings on neurologic examination, or poor response to treatment, a laboratory workup should be done.

Needle electromyography and nerve-conduction studies should be considered if polyneuropathy is suspected on clinical grounds, even if results of neurologic examination are apparently normal.

Nonpharmacologic management

Patients with suspected restless legs syndrome who are sensitive to caffeine, alcohol, or nicotine should avoid these substances.

Supplementation to correct deficiencies in vitamins (eg, folate), electrolytes (eg, magnesium) (7), or iron may improve symptoms. Patients with prominent varicose veins in the legs.

Pharmacologic management

Drug therapy for primary restless legs syndrome is largely symptomatic, since cure is only possible in secondary disease. Medications should be initiated at a low dose and be taken an hour or two before bedtime to allow sufficient absorption and onset of action.

Levodopa with carbidopa

Levodopa with carbidopa (Sinemet) can improve sensory symptoms and periodic limb movements of sleep in primary restless legs syndrome and that associated with uremia (1-3,16). For symptoms that start before sleep, one 25/100-mg carbidopa/levodopa tablet can be taken 1 to 2 hours before bedtime. If symptoms occur during the night, one 25/100-mg controlled-release carbidopa/levodopa (Sinemet CR) tablet can be used. In patients who have symptoms both before sleep and during the night, a combination of short-acting.

Dopamine agonists

Dopamine agonists are less likely to produce augmentation or rebound and can be useful alone or along with levodopa in patients in whom one of these conditions develops.

Pergolide mesylate (Permax) is a potent, long-acting dopamine D1 and D2 receptor agonist that has been shown to be effective in restless legs syndrome.

Bromocriptine mesylate (Parlodel), a dopamine D2 receptor agonist.

Pramipexole (Mirapex), a dopamine D2 and D3 receptor agonist, and ropinirole hydrochloride (Requip), a dopamine D2 receptor agonist, were recently approved.


Benzodiazepines may be used as monotherapy in patients with mild or intermittent symptoms or as add-on therapy in severe cases. Clonazepam (Klonopin) has been shown to ease the sensory symptoms and periodic limb movements of sleep in restless legs syndrome.