Synonym: Ekbom's syndrome

The term restless legs syndrome 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.

Epidemiology

• Prevalence in the general population is between 3% and 9%.¹
• 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.
• Occurs more frequently in women than in men.²

Risk factors

Symptomatic forms are associated with:

• Pregnancy
• Renal failure
• Iron deficiency, folate deficiency, B₁₂ deficiency and magnesium deficiency
• Polyneuropathy
• Endocrine: diabetes mellitus, hypothyroidism
• Spinal disorders
• Rheumatoid arthritis, Sjogren's syndrome
• Amyloidosis
• Hereditary forms: three gene loci (located on chromosomes 12, 14, and 9) have been traced so far

Presentation

• 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.
• May report sensations such as an almost irresistible urge to move the legs, which are not painful but are very irritating.
• The sensations are usually worse during inactivity and often interfere with sleep, leading to chronic sleep deprivation and stress.
• Can lead to significant physical and emotional difficulties.

Diagnostic criteria

International Restless Legs Syndrome Study Group criteria.³ 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 the restless legs syndrome suggestive of an autosomal dominant mode of inheritance.
• Associated features:
  • Natural clinical course of the disorder:
    • 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

Differential diagnosis

• Restless legs syndrome 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 anti-psychotic 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 position change to relieve pressure, e.g. on an arthritic hip.
• Peripheral vascular disease: intermittent claudication
• Nocturnal leg cramps
• Parkinsonism
• Venous insufficiency
• Attention deficit hyperactivity disorder (ADHD) in children

Investigations

• Serum ferritin: the restless legs syndrome is frequently associated with iron deficiency.
• Renal function: restless legs syndrome 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.

Associated disorders

Periodic Limb Movement Disorder (PLMD)⁴

• 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.

Management

• 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 (a[centre]nd therefore should avoid) caffeine, alcohol and nicotine.
• 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.

Drugs

• Treatment is needed only in the moderate to severe forms of the disorder and mostly in elderly people.
• Dopaminergic treatment with levodopa and dopamine agonists (e.g. pergolide, ropinirole, cabergoline, rotigotine) is effective in idiopathic restless legs syndrome.⁵
• However cabergoline and pergolide may no longer be appropriate. The Medicines and Healthcare Products Regulatory Agency (MHRA) has advised that the ergot-derived dopamine receptor agonists bromocriptine, cabergoline and pergolide have been associated with pulmonary, retroperitoneal, and pericardial fibrotic reactions. It is recommended that cardiac valvulopathy should be excluded with echocardiography before starting treatment and it may also be appropriate to measure ESR and serum creatinine and to obtain a chest X-ray. Patients should be monitored during treatment, including echocardiography within 3-6 months of initiating treatment and at 6-12 month intervals.⁶
• 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 (100mg in evening or up to 600mg daily in divided doses) may be ideal for intermittent use, e.g. a few times a week.⁷
• Various other drugs provide alternative treatment possibilities, including:
  • Anticonvulsants are second line drugs (gabapentin, carbamazepine or sodium valproate).
  • Shorter acting benzodiazepine drugs such as clonazepam may be helpful, but longer acting forms should be avoided and possibility of dependence should be considered.
  • Opiates (eg oxycodone) may be useful in severe cases (but beware of tolerance and addiction).
  • Clonidine is probably effective in reducing symptoms in primary (idiopathic) RLS in the short term.⁵
  • Baclofen is occasionally helpful in severe PLMD to reduce the amplitude of the movements.
  • High-dose intravenous iron is a promising but still experimental approach.²
  • In extreme cases an overnight infusion of apomorphine can be very effective.

Complications

• Insomnia
• Significant negative effect on quality of life⁸