Synonym: Ekbom's syndrome
The term restless legs syndrome (RLS) was first used in the mid-1940s by Swedish neurologist Karl Ekbom to describe a disorder characterised by sensory symptoms and motor disturbances of the limbs, mainly occurring during rest.
RLS is characterised by an urge to move, usually but not always affecting the legs. Abnormal sensations, including tingling, aching or burning, are usually present in association with restless legs. There may be associated pain, which can be severe. The abnormal sensations tend to be worse in the evenings and are temporarily or partially relieved by movement.
- Prevalence in the general population is between 1.9% and 15%.
- The prevalence increases with age. Symptoms begin after 40 years of age in most patients, but up to one third of patients develop symptoms before the age of 20 years.
- It occurs more frequently in women than in men.
RLS may be idiopathic or symptomatic of an underlying condition. 18.5-59.6% of patients with idiopathic RLS have a family history. Symptomatic forms are associated with:
- Renal failure.
- Iron deficiency, folate deficiency, B12 deficiency and magnesium deficiency.
- Endocrine: diabetes mellitus, hypothyroidism.
- Spinal disorders.
- Rheumatoid arthritis, Sjögren's syndrome.
- Drug causes include beta-blockers, neuroleptics, lithium, tricyclic antidepressants.
- Hereditary forms: three gene loci (located on chromosomes 12, 14, and 9) have been traced so far.
- Patients have characteristic difficulty in trying to depict their symptoms. Patients may describe creeping, crawling or other uncomfortable feelings in the legs and arms, relieved by rubbing or moving the affected limb.
- They may report sensations such as an almost irresistible urge to move the legs.
- Patients often complain of pain in their legs, which can be severe. Some patients describe a deep painful feeling in their legs.
- The sensations are usually worse during inactivity and often interfere with sleep, leading to chronic sleep deprivation and stress.
- It can lead to significant physical and emotional difficulties.
International Restless Legs Syndrome Study Group criteria. All four essential criteria must be met for a positive diagnosis.
- Essential criteria:
- An urge to move the legs, usually accompanied by uncomfortable or unpleasant sensations in the legs.
- Unpleasant sensations or the urge to move begin or worsen during periods of rest or inactivity such as lying or sitting.
- Unpleasant sensations or the urge to move are partly or totally relieved by movement such as walking, bending, stretching, etc, at least for as long as the activity continues.
- Unpleasant sensations or the urge to move are worse in the evening or at night than during the day, or only occur in the evening or night.
- Supportive criteria:
- Positive response to dopaminergic treatment.
- Periodic limb movements during wakefulness or sleep.
- Positive family history of RLS suggestive of an autosomal dominant mode of inheritance.
- Associated features:
- Natural clinical course of the disorder:
- It can begin at any age, but most patients seen in clinical practice are middle-aged or older.
- Most patients seen in the clinic have a progressive clinical course, but a static clinical course is sometimes seen. Remissions of a month or more are sometimes reported.
- Sleep disturbance:
- The leg discomfort and the need to move often result in insomnia.
- Medical investigation/neurological examination:
- Peripheral neuropathy or radiculopathy are sometimes present in the non-familial form of the syndrome.
- A low serum ferritin may be present
- Natural clinical course of the disorder:
- RLS may be triggered by peripheral neuropathy or radiculopathy, but a distinction should be made between these disorders. In pure peripheral neuropathy and radiculopathy, patients do not have the compelling need to move to relieve leg discomfort and the symptoms are not consistently worse at rest or at night.
- Neuroleptic-induced akathisia: motor restlessness induced by antipsychotic agents that block dopamine receptors. Patients feel compelled to move because of an inner sense of restlessness rather than a need to specifically move the legs.
- Positional discomfort: if the only movement needed is a small brief positional change to relieve pressure - eg, on an arthritic hip.
- Peripheral vascular disease: intermittent claudication.
- Nocturnal leg cramps.
- Venous insufficiency.
- Attention deficit hyperactivity disorder (ADHD) in children.
- Serum ferritin: RLS is frequently associated with iron deficiency.
- Renal function: RLS may be associated with renal failure.
- Other investigations for underlying possible cause include fasting blood glucose, magnesium, TSH, vitamin B12 and folate.
- If the neurological examination suggests an associated peripheral neuropathy or radiculopathy, electromyography and nerve conduction studies should be undertaken.
Periodic limb movement disorder (PLMD)
- PLMD is involuntary rhythmic limb movements, either while asleep or when awake.
- RLS disrupts sleep by delaying sleep; PLMD can disrupt sleep because of the constant limb movements.
- Most people who have RLS also have PLMD, but only some people with PLMD also have RLS.
- Give reassurance, advice on improving sleep (avoiding caffeine before bed, not getting too hot).
- Consider medications which may be aggravating the situation (CNS stimulants and tricyclic antidepressants, diuretics, calcium antagonists, phenytoin).
- Patients may be sensitive to, and therefore should avoid, caffeine, alcohol and nicotine. Patients may be sensitive to various other factors, and sensitivities (eg, sensitivity to salt) tend to vary from patient to patient.
- Some patients may be helped by a variety of methods that may be worth trying: mild exercise, hot or cold baths, whirlpool baths, limb massage or vibratory or electrical stimulation of the feet and toes before bedtime.
- Treatment of any underlying cause, including supplementation to correct vitamin, electrolyte or iron deficiency.
- Treatment is needed only in the moderate to severe forms of the disorder and mostly in elderly people.
- Dopaminergic treatment with levodopa (L-dopa) and dopamine agonists (eg, pergolide, ropinirole, cabergoline, rotigotine) is effective in idiopathic RLS.L-dopa has been shown to be effective for the short-term treatment of RLS. A recent Cochrane review found that dopamine agonists were effective. Cabergoline and pramipexole showed greater efficacy compared with L-dopa in some but not all outcomes.
- NB: bromocriptine, cabergoline and pergolide have been associated with pulmonary, retroperitoneal, and pericardial fibrotic reactions. Cardiac valvulopathy should be excluded with echocardiography before starting treatment. It may also be appropriate to measure the ESR and serum creatinine, and refer for a chest X-ray. Patients should be monitored for dyspnoea, persistent cough, chest pain, cardiac failure, and abdominal pain or tenderness. For long-term treatment, lung function tests may also be helpful. Patients taking cabergoline or pergolide should be regularly monitored for cardiac fibrosis by echocardiography (within 3-6 months of initiating treatment and then at 6- to 12-month intervals).
- Augmentation of symptoms can occur (usually symptoms occurring earlier in the day). This happens frequently with L-dopa itself (which is not recommended as continuous treatment because of this). However, L-dopa (100 mg in the evening or up to 600 mg daily in divided doses) may be ideal for intermittent use - eg, a few times a week.
- Various other drugs provide alternative treatment possibilities, including:
- Anticonvulsants, which are second-line drugs (gabapentin, carbamazepine or sodium valproate).
- Recent studies have shown gabapentin and pregabalin to be effective treatment options.
- Shorter-acting benzodiazepine drugs such as clonazepam, which may be helpful, but longer-acting forms should be avoided and possibility of dependence should be considered.
- Opiates (eg, oxycodone), which may be useful in severe cases (but beware of tolerance and addiction).
- Clonidine, which is probably effective in reducing symptoms in primary (idiopathic) RLS in the short term.
- Baclofen, which is occasionally helpful in severe PLMD, to reduce the amplitude of the movements.
- High-dose intravenous iron, which is a promising but still experimental approach.
- In extreme cases an overnight infusion of apomorphine, which can be very effective.
Refer to a neurologist or sleep specialist if:
- There is insufficient initial response despite adequate duration and dose of treatment.
- Response to treatment becomes insufficient despite an increased dose.
- Side-effects are intolerable.
- The maximum recommended dosage is no longer effective
- Augmentation develops (onset of symptoms earlier in the day, increased severity of symptoms, or the spread of symptoms to different parts of the body, such as the arms, trunk or face).
Children with RLS should not be treated in primary care.
- Significant negative effect on quality of life.
- RLS is usually a chronic disorder that worsens with time, but does fluctuate.
- Periods of remission are common, especially in younger adults.
- Daily symptoms often don't develop until the age range of 40-60 years.
Further reading & references
- Restless legs syndrome, Prodigy (December 2009)
- Aurora RN, Kristo DA, Bista SR, et al; The treatment of restless legs syndrome and periodic limb movement disorder in adults-an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an american academy of sleep medicine clinical practice guideline. Sleep. 2012 Aug 1;35(8):1039-62.
- Leschziner G, Gringras P; Restless legs syndrome. BMJ. 2012 May 23;344:e3056. doi: 10.1136/bmj.e3056.
- Satija P, Ondo WG; Restless legs syndrome: pathophysiology, diagnosis and treatment. CNS Drugs. 2008;22(6):497-518.
- Allen RP, Picchietti D, Hening WA, et al; Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003 Mar;4(2):101-19.
- Anderson WE, Periodic Limb Movement Disorder, Medscape, May 2010
- Bozorg AM; Restless Legs Syndrome, Medscape, Apr 2012
- Scholz H, Trenkwalder C, Kohnen R, et al; Levodopa for restless legs syndrome. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD005504.
- Scholz H, Trenkwalder C, Kohnen R, et al; Dopamine agonists for restless legs syndrome. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD006009.
- British National Formulary; 63rd Edition (Mar 2012) British Medical Association and Royal Pharmaceutical Society of Great Britain, London
- Earley CJ; Clinical practice. Restless legs syndrome. N Engl J Med. 2003 May 22;348(21):2103-9.
- Abetz L, Allen R, Follet A, et al; Evaluating the quality of life of patients with restless legs syndrome. Clin Ther. 2004 Jun;26(6):925-35.
|Original Author: Dr Colin Tidy||Current Version: Dr Colin Tidy||Peer Reviewer: Prof Cathy Jackson|
|Last Checked: 11/10/2012||Document ID: 2090 Version: 22||© EMIS|
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