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May 2008: Exercise beneficial for restless legs syndrome

How common is restless legs syndrome?

What are the diagnostic symptoms of restless legs?

What drug treatments are effective?

How common is restless legs syndrome?

What are the diagnostic symptoms of restless legs?

What drug treatments are effective?

Restless legs syndrome, or Ekbom syndrome, is a common movement disorder, which remains underdiagnosed and undertreated.1 Recognition and management within primary care are feasible and important, as symptoms are often distressing but usually respond well to treatment.

Restless legs syndrome has an estimated prevalence of 10-15% in the general population;2 this equates to around nine million affected adults in the UK. It is equally common in men and women,3 although it is associated with pregnancy, which increases lifetime prevalence in women. There is an age-related increase in prevalence, so it is more often seen in middle-aged and elderly patients.1 It may affect children and adolescents,4 although formal recognition may take years as in many patients the symptoms are mild and vague. Patients with early-onset restless legs syndrome often have a family history of the condition.5

There is no known anatomical pathology associated with restless legs syndrome. Neurophysiological studies indicate changes in excitability of the motor cortex, making it relatively disinhibited,6 and positron emission tomography has shown mildly reduced uptake of 18F-deoxyphenylalanine, with some reduction of D2 receptor binding in the striatum, suggesting postsynaptic dopaminergic dysfunction.7

Diagnosis

Clinical features

The key feature of restless legs syndrome is akathisia: an uncontrollable urge to move the legs.8 This occurs in almost all patients, although in some cases the upper limbs and shoulder girdle may be involved.

Akathisia may be accompanied by deep pain, which may be perceived as throbbing, bubbling, a ‘creepy crawly' sensation, or an itch, with no evidence of a rash or other skin disorder, that is relieved by scratching.

Symptoms are worse at rest, particularly in bed, and relieved by movement. The International Restless Legs Syndrome Study Group has suggested four diagnostic criteria:9

• U – Urge to move
• R – Rest brings it on
• G – ‘Get up and go' helps
• E – Evenings are worse.

41190522Sleep quality is often poor, and restless legs syndrome is commonly associated with jerking limb movements when asleep and even when awake.10 This inevitably affects partners, who may be the ones who seek help for the patient. See table 1,left, for differential diagnoses.

Patients with more severe symptoms may try drastic self-help measures, such as soaking their legs in hot or cold water, which may cause tissue damage.

About 40% of patients with restless legs syndrome have a positive family history. Hereditary restless legs syndrome is an autosomal dominant disorder, although it has widely variable penetrance and clinical expressivity.5 It becomes symptomatic earlier but progression is slower and more painful. The pathology is the same.

Restless legs syndrome is associated with iron deficiency in around 25% of patients. It is particularly common in older patients, irrespective of whether anaemia is present.11 Other clinical associations include renal failure (20-60% of patients undergoing dialysis have restless legs syndrome),12 pregnancy (20% of pregnant women have the condition),13 diabetes and rheumatoid arthritis.3

CNS stimulants, such as caffeine and nicotine, may aggravate restless legs syndrome. Excessive alcohol consumption may also exacerbate the condition, and alcohol withdrawal has a paradoxical excitatory effect.

41190523Several classes of drugs may aggravate restless legs syndrome; the major catecholamines (adrenaline, noradrenaline, serotonin and dopamine) all have some overlap in action and drugs that nominally inhibit the activity of one may have some effect on others.14 See table 2, left.

Investigations

Diagnosis is essentially clinical and investigations have a limited role. However, patients should have a full blood count and ferritin level, as well as urea and electrolytes, because of the association with iron deficiency and renal failure.

If there is suspicion of diabetic neuropathy, which is a differential diagnosis when pain is prominent in restless legs syndrome, glucose estimation should also be undertaken.

Management

Self-help

Several non-pharmacological measures can help patients with restless legs syndrome.

Exercise should be recommended as it ameliorates symptoms. Ideally, this should be frequent and vigorous, but if this is not feasible then walking and stretching exercises may help.

Rubbing the legs may be useful. A perception of heat is improved by cold bathing and vice versa.

Complementary therapies, such as massage, acupuncture and transcutaneous electrical nerve stimulation, have been reported to help some patients, although there is a lack of evidence that these treatments are effective.3

Drug therapy

If a patient has a low or borderline ferritin level, a trial of iron should be given as there is often a good clinical response.9

Drug therapy is required in only 20-25% of cases. Dopamine agonists are the mainstay of treatment and show benefit in nearly all patients.15 Pramipexole (0.125mg daily for 4-7 days increased as necessary to 0.75mg daily) and ropinirole (0.25mg daily increased to a maximum of 4mg daily) are licensed for restless legs syndrome in the UK. These doses are much lower than those used to treat Parkinson's disease, and side-effects are less troublesome. However, nausea, dizziness, sedation and insomnia may occur. Ergot dopamine agonists (such as cabergoline) may be used but the risk of fibrotic reactions makes them less popular.

For patients with milder or intermittent symptoms, other classes of drugs may be helpful. Hypnotics may be useful for fragmented sleep3 and drug choice should be based on the patient's symptoms. If proximal insomnia is dominant, a short-acting agent (for example zolpidem 3.25mg nightly) should be used, while an intermediate-acting agent (such as temazepam 10 mg nightly) is more suitable for distal insomnia.

Gabapentin is well established in the management of peripheral neuropathies, irrespective of cause. It is particularly useful in painful restless legs syndrome and in patients with restless legs syndrome and chronic renal failure.

Restless legs syndrome in pregnancy should not be treated because of the lack of safety data on all classes of drugs. Patients can be reassured that symptoms will resolve after delivery and that they are not at greater risk of restless legs syndrome in later life.

Conclusion

Restless legs syndrome is a common movement disorder that affects up to 15% of patients – mainly, but not exclusively, patients who are middle-aged or elderly. Its symptoms cause considerable morbidity but quality of life can be markedly improved by early recognition in primary care. There is a fairly strong association with iron deficiency.

For most patients, management consists of treating any underlying disorder, lifestyle modification and non-pharmacological therapies. Drug therapy is indicated for more resistant cases; dopamine agonists are the first-choice agents, although some patients may benefit from hypnotics or gabapentin.

Author

Dr Edin Lakasing
MB ChB MRCS MRCGP
GP, Chorleywood, Hertfordshire and
GP tutor to University College Hospital and Imperial College, London

Tab1legs Tab2_legs Key points Restless legs syndrome

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