The Basics - Restless legs syndrome

This condition remains under-diagnosed and under-treated, says Dr Louise Newson

Polysomnography in a patient with RLS: Symptoms are worse during rest, in the evening and at night
Polysomnography in a patient with RLS: Symptoms are worse during rest, in the evening and at night

Restless legs syndrome (RLS), also known as Ekbom’s syndrome, is a neurologic movement disorder characterised by an irresistible urge to move the limbs, usually the legs, accompanied by uncomfortable sensations. Symptoms are worse during rest, in the evening, and at night and improve with movement.

RLS affects 3-9% of the population and prevalence increases with age. Although most people are over 40 years of age when they present with symptoms, up to one third of patients develop symptoms before 20 years of age.

It is more common in women than men, however, it is still an under-diagnosed and under-treated condition

1. Causes of RLS
The underlying cause of RLS is not fully understood, although it is likely that there is involvement of the dopaminergic system and depletion of iron stores (thought to be due to a defect in iron transport or storage). The majority of patients have no underlying cause for their condition although up to half of patients have a family history of RLS.1

The box below outlines the causes of secondary RLS.

Causes of secondary RLS
  • Pregnancy (occurs in around one in five pregnant women, usually in the third trimester)
  • Iron deficiency
  • Chronic kidney disease stage 5
  • Parkinson’s disease
  • Peripheral neuropathy
  • Rheumatoid arthritis
  • Diabetes
  • Hypothyroidism
  • Fibromyalgia
  • Drugs (tricyclic antidepressants, SSRIs, neuroleptics, lithium, calcium channel blockers)

Other factors possibly associated with RLS include smoking, caffeine or alcohol intake, obesity, sedentary lifestyle and lower socioeconomic status. However, the evidence to support this is limited. 2

2. Diagnosis
RLS is clinically diagnosed according to four main criteria: 3

  • An urge to move the legs, usually associated with unpleasant leg sensations.
  • Induction or exacerbation of symptoms by rest.
  • Symptom relief on activity.
  • Diurnal fluctuations in symptoms with worsening in the evening and at night.

For most patients, symptoms are progressive. Many complain of insomnia as their sleep is disturbed by their symptoms.

Clinical examination is usually unremarkable. However, some patients may have a peripheral neuropathy or radiculopathy.

3. Investigations
Investigations are usually performed to exclude an underlying cause of RLS. Typical investigations include serum ferritin, U&Es, fasting blood glucose, magnesium, TSH, vitamin B12 and folate. 

If a patient has a peripheral neuropathy or radiculopathy then they should be referred for electromyography and nerve conduction studies.

4. Treatment
For mild cases, reassurance may be sufficient. Drug treatment is usually only necessary for those patients with moderate to severe forms of the disorder and mostly in elderly people.

Patients should be advised on general measures to improve sleep and on smoking, alcohol and caffeine intake as well as ways of improving their lifestyle, if appropriate. Any medication they are taking needs to be reviewed in case they are taking drugs that may be causing their symptoms.

If any underlying cause for their symptoms is found following investigations, then this obviously needs to be treated.

Some patients find mild exercise, hot or cold baths, whirlpool baths, limb massage or vibratory or electrical stimulation of the feet and toes before bedtime beneficial.

Dopamine agonists are recommended as first-line treatment for RLS. A recent meta-analysis investigated the efficacy and safety of dopamine agonist treatment compared to placebo or to other treatments for RLS. 4 The results showed that dopamine agonists lead to a larger improvement in symptoms, quality of sleep and quality of life compared to placebo.

However, patients were more likely to discontinue dopamine agonist treatment and experienced more adverse events when compared to placebo. Cabergoline and pergolide have potentially serious side-effects such as cardiac valve fibrosis so are not usually recommended first line.

Levodopa may be efficacious for short-term treatment of RLS.5 However, augmentation of symptoms can occur (usually symptoms occurring earlier in the day) so levodopa is not recommended as continuous treatment.

Alternative, second-line treatments include anticonvulsants (such as gabapentin, carbamazepine or sodium valproate). Shorter-acting benzodiazepine drugs such as clonazepam may be helpful, but these should not be used in the long term due to the possibility of dependence.

Opiates such as oxycodone are sometimes given to patients with severe symptoms. Clonidine may be effective in reducing symptoms in primary (idiopathic) RLS in the short term.

Key points
  • Symptoms are usually worse at night.
  • RLS is still under-diagnosed.
  • This condition can be familial in around half of cases.
  • Iron deficiency can be a cause of RLS.
  • Lifestyle advice should be given to patients.
  • Drug treatment is usually reserved for more severe cases.

5. Outlook
The severity and frequency of symptoms usually worsen over time. In older patients symptoms usually progress more rapidly. In those with secondary RLS, symptoms typically resolve after treatment of the underlying condition. Pregnant women usually have resolution of their symptoms within a few weeks of delivery.

  • Dr Newson is  GP in the West Midlands

References
1. Kushida CA. Clinical presentation, diagnosis, and quality of life issues in restless legs syndrome. Am J Med 2007;120(1 Suppl 1): S4-S12.

2. Chahine LM, Chemali ZN. Restless legs syndrome: a review. CNS Spectr2006;11(7): 511-20.

3. Trenkwalder C, Paulus W. Restless legs syndrome: pathophysiology, clinical presentation and management. Nat Rev Neurol 2010; 6(6): 337-46.

4. Scholz H, Trenkwalder C, Kohnen R et al. Dopamine agonists for restless legs syndrome. Cochrane Database Syst Rev 2011; (3): CD006009.

5. Scholz H, Trenkwalder C, Kohnen R et al. Levodopa for restless legs syndrome. Cochrane Database Syst Rev 2011; (2): CD005504.


 

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