RESTLESS LEG SYNDROME (RLS)

The mean age of onset is the third and fourth decade of life. Typically there is a slow progression over years but onset can be more rapid. There is a higher risk of RLS in those who have first degree relatives who also suffer from it. It has also been linked to iron deficiency anaemia and kidney disease. RLS is common in pregnancy. Medication is not recommended in pregnancy or when breastfeeding and management should follow the behavioural and physical advice below. Sensory symptoms can occur on their own but are often accompanied by periodic repetitive, involuntary leg movements, usually while asleep.

Diagnostic criteria for restless leg syndrome (2012 revised IRLSSG)

(all 5 criteria must be met)

1. An urge to move the legs usually but not always accompanied by or felt to be caused by an uncomfortable and unpleasant sensation in the legs.
2. The urge to move the legs and any accompanying unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting.
3. The urge to move the legs and accompanying unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.
4. The urge to move the legs and accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night than during the day.
5. The occurrence of the above features is not solely accounted for by symptoms primary to another medical condition or behavioural condition (eg neuropathy, myalgia, venous stasis, leg oedema, arthritis, leg cramps, positional discomfort or habitual toe tapping).

Investigations

• full blood count
• transferrin
• ferritin - serum ferritin concentrations below 50ng/mL has been associated with RLS
• renal function, liver function, glucose, HbA1c, vitamin B12, folate and calcium levels.

Behavioural

• good sleeping pattern www.moodjuice.scot.nhs.uk/sleepproblems.asp
  • avoid alcohol, smoking, caffeine and hot baths in the evening
  • increase daytime activity but not too close to bed time
  • offer leaflet on RLS at http://www.patient.co.uk/pdf/pilsL764.pdf.
• Some medication can worsen symptoms - antihistamines, dopamine antagonists, anti-emetics, antidepressants, selective serotonin reuptake inhibitors, mirtazepine, neuroleptics, beta blockers, lithium and some antiepileptics. 
• Ensure ferritin concentration is above 50ng/mL and maintained between 50 to 75 ng/mL.

Medication to reduce symptoms

Patients should be aware that medication is to reduce the symptoms but that complete eradication is unlikely. Medical treatment should be deferred as long as possible with behavioural measures tried first.  Gabapentin and pregabalin can be used in patients with restless legs (advocated by NICE) but is off-label.  The choice of drug is also dependent on side-effect profile risk.

Avoid using more than one agent at the same time for restless legs. If one fails titrate off and use another rather than adding on treatment.

Choices

Gabapentin or pregabalin (off-label indication)

Useful in:

• patients who have sleep disturbance disproportionate to the RLS
• those with co-morbid insomnia, anxiety or pain
• patients in whom a dopamine agonist should be avoided, eg prior history of impulse control disorder.

Dopamine agonists - ropinirole, pramipexole and rotigotine skin patches

Patients must be made aware that dopamine agonists can cause an impulse control disorder.  This means that while taking the drug they are at risk of spending more time/money on things which give them pleasure but which can be harmful, eg gambling, alcohol and drug addiction, excessive shopping, hypersexuality.  Avoid dopamine agonists in those with a history of impulse control issues, eg alcohol misuse, substance misuse, gambling.

Impulse control disorders can emerge over time and patients on these medications for a long time should be asked about any emerging problems.

Repeat warnings on impulse control disorders at the time of any dose increases.

There is a risk of augmentation over time, ie that higher doses are needed to improve symptoms. Long-acting dopamine agonists increase the time to augmentation and should be used in preference to short-acting dopamine agonists.  Rotigotine patches may be useful if patient also has daytime symptoms, please note that they can cause application site reactions. Do not exceed the dose stated by the BNF for RLS as this will not improve symptoms and demonstrates augmentation.  Do not use in pregnancy.

Opiates

Weak opiates (codeines) may be useful in patients with severe augmentation.

Refer to BNF and SPCs for prescribing information (see also Highland Formulary section 4.7).

• Arrange regular follow-up and monitor side-effects
• Reinforce lifestyle changes
• Assess response after 3 months and reconsider need for treatment continuation.
• In prolonged treatment drug doses should be kept to the minimum required to ease symptoms as the higher the dose, the greater the risk of augmentation.

How can a neurology appointment help?

• If there is diagnostic doubt.
• Restless leg syndrome is more common in those with peripheral neuropathy, myelopathy or myelitis. If you suspect there is another condition which needs to be investigated please refer.