Restless legs syndrome

Background

Restless legs syndrome (RLS) is a disorder associated with a poorly defined feeling of discomfort in the legs and an often overwhelming urge to move.

Patients often find it very difficult to describe the feeling in the legs. Commonly used terms include:

  • Achy

  • Itchy on the inside

  • Crawling

  • Like the urge to yawn, but in the legs

Alongside these unpleasant sensations is a strong urge to move, shake or stretch the legs, which can give momentary relief from the sensation. These symptoms are most commonly felt in the legs, but may also occur in the arms.

The symptoms of RLS are commonly worse in the evenings and can interfere with the ability to sleep, hence its classification as a sleep disorder.

Epidemiology

The condition is common, affecting up 5-10% of the population. Prevalence increases with age and peak onset is between 30 and 40 years. Overall women are affected more than men, but part of this is due to the association with pregnancy. There is a positive family history in 50% of primary RLS.

Causes

Most cases of RLS have no underlying cause, in which case it is referred to as primary or idiopathic RLS, however there are a number of exacerbating factors including alcohol, nicotine, caffeine and lack of sleep.

In a minority of cases RLS is associated with an underlying condition, such as end stage chronic kidney disease, iron deficiency and multiple sclerosis, and can be a feature in a fifth of women during their third trimester of pregnancy. 

The underlying pathology of primary RLS is not well understood, though is thought to relate to reduced activity of the dopaminergic system. Reduced dopaminergic spinal inhibition may result in increased excitatory activity in the limbs, giving rise to the symptoms. Dopamine is released in a circadian fashion being low in the evenings and explains the predilection for nocturnal symptoms.

Association with Periodic Limb Movement Disorder – PLMD

In RLS, the motor urge to move the limbs can continue into sleep and manifest as recurrent repetitive movements of the legs, ankles, toes or hips, and occasionally the arms. These are called periodic limb movements during sleep (PLMS) and can wake the patient up. These sleep interruptions, called arousals can result in daytime sleepiness.

PLMS occur with a greater frequency in many sleep disorders including OSA, narcolepsy and REM sleep behaviour disorder, and the treatment is generally to treat the underlying sleep disorder, which is also the case when PLMS occur with RLS.

There is a similar condition called Period Limb Movement Disorder (PLMD), which is the repetitive movements of limbs during sleep, but which occurs in the absence of any other sleep disorder. It is uncommon to have PLMS in isolation (ie PLMD) and incidentally the treatment is similar to that of RLS. The practical value of this distinction is that if PLMS co-exist in a patient with untreated OSA, the treatment would be CPAP and monitor for resolution of the PLMS.

Both PLMS and PLMD are different to the sudden jolt and feeling of falling that can occur at the onset of sleep, known as a hypnic jerk, which is completely benign.

Assessment

Diagnosis is clinical and should be based on fulfilling all the following criteria set out by the International RLS study group (IRLSSG)

  1. The urge to move the legs, with or without an accompanying uncomfortable sensation

  2. The symptoms

    • Begin or worsen during periods of rest, such as sitting or lying down

    • Are partially or totally relieved by movement

    • Only occur, or are worse, in the evening or night

  3. The symptoms cannot be wholly attributed to another cause

The severity of RLS should be gauged using the IRLSSG rating scale which can be viewed here. This is very useful in attempting to quantify what can be quite a difficult condition to define and should be serially repeated in order to objectively track the response to treatment.

Attention should be given to identifying the underlying causes above, in particular iron deficiency. Iron is thought to facilitate dopamine uptake in the basal ganglia. Ferritin should be measured and iron supplements given to maintain a ferritin above 75mcg/L.

In addition to medical conditions, RLS may occur secondary to other sleep disorders including insomnia and obstructive sleep apnea, and appropriate attention should be given to ruling these out.

Treatment

Lifestyle Measures – these are grouped as preventative measures and alleviating measures.

Preventative

  • Smoking cessation

  • Reduce alcohol and caffeine – a practical approach is to stop these entirely for two weeks and assess response. If symptoms resolve, then the items can gradually be reintroduced in order to find the threshold which causes symptoms.

  • Sleep hygiene – symptoms are frequently worse when the patient is tired, so good sleep hygiene measures can resolve symptoms, or reduce them to a manageable level.

  • Regular moderate exercise and stretching – no real evidence base but often reported to improve symptoms.

    Alleviating

    Relaxation and distraction
    Walking and stretching
    Hot baths and leg massage

Pharmacological Treatment

  • Iron supplementation as above

  • Dopaminergic drugs – these can be effective at reducing symptoms, but are not without side effects, particularly impulse control disorders. While symptom control can be achieved, paradoxical worsening of symptoms can occur over time, leading to more severe symptoms, occurring earlier in the day and affecting previously unaffected body parts including the arms and trunk.

    Ropinirole at an initial dose of 250 micrograms or pramipexole at an initial dose of 88 micrograms pramipexole base given 1-2 hours before bed or the anticipated onset of symptoms is often used. Treatment is based on a ratio of risk to benefit, with lifestyle measures including sleep hygiene having been tried first.

  • Gabapentin and pregabalin – often used off label for RLS and can treat co-existing insomnia. These are less likely to cause an increase in symptoms. While off label, a common starting dose for gabapentin is 300mg if under 65 and for pregabalin 75mg if under 65.

  • Sleeping tablets – where RLS occurs exclusively, or is significantly worse, in response to sleep deprivation, then a short course of sleeping tablets can be used alongside sleep hygiene or CBT for insomnia treatment.