see also insomnia; sleep hygiene

• effects 5-15% of population with varying severity and effect of ability to get to sleep
• can begin at any age
• early onset suggests hereditary form (50% have a family history)
• late onset suggests secondary cause

• hereditary (presumably autosomal dominant)

• iron deficiency
• pregnancy, especially 3rd TM
• uraemia
• peripheral neuropathies, esp. Charcot-Marie-Tooth type 2 & familial amyloid neuropathy
• diabetes mellitus
• rheumatoid arthritis
• vitamin B12/folate deficiency
• spinocerebellar ataxia, esp. type 3
• ? Parkinsons disease
• drugs:
  • anti-emetics eg. metoclopramide (Maxolon)
  • anticholinergic drugs
  • some anticonvulsants eg. phenytoin
  • anti-psychotic drugs eg. phenothiazines, haloperidol and lithium carbonate
  • occasionally antidepressant drugs eg. tricylics, SSRIs

• an urge to move the legs (and occasionally arms or other body parts), but not always, accompanied by uncomfortable or unpleasant sensations.
• symptoms begin or worsen during periods of rest or inactivity such as lying or sitting
• movement such as walking or stretching partially or totally relives the symptoms at least as long as the activity continues

a circadian pattern: symptoms worse or only present in the evening or at night, & this diurnal variation must have once been present if the symptoms are now so severe as to make diurnal variation unnoticeable

• family history
• response to dopaminergic Rx
• periodic limb movements during wakefulness or sleep

• over 90% have insomnia - usually trouble initiating or maintaining sleep
• neurologic examination usually normal unless secondary form and there is underlying neuropathy
• an association with cardiovascular disease

• IRLS (International Restless Legs Syndrome Study Group) rating scale

• limited utility unless suspect a secondary cause thus consider:
• iron studies
• urea level
• nerve conduction studies if suggestive of neuropathy
• sleep studies generally not warranted but may be considered if excessive daytime somnolence suggests significant sleep disruption

• most painful conditions such as peripheral arterial disease, arthritis, bursitis are not instantly ameliorated by activity
• must be distinguished from akathisia - a feeling of inner restlessness which makes the person unable to sit still and which are more likely to have repetitive stereotyped movements such as body rocking, and is often evident during examination rather than being precipitated by rest and sleep.
• Parkinsons disease - different neuro pathology
• nocturnal leg cramps
  • these can also interfere with sleep but are not a movement disorder but muscle cramps, often precipitated by cold peripheries
  • increased risk with potassium-sparing diuretics, thiazides, and inhaled long acting beta 2 adrenergic agonists (especially if used with corticosteroids, but not with statins or loop diuretics ¹⁾
  • daily dose of 180 μg vitamin K2 appears to significantly reduce nocturnal cramps ²⁾

• treat underlying causes (eg. iron deficiency, cease offending medications, etc)
• establish a good sleep hygiene
• sedatives, hypnotics and anxiolytics have a very limited role in Mx of occasional symptoms and should not be taken regularly as dependence and loss of effect are major issues
• dopamine agonists:
  • low dose dopamine agonists are largely replacing levodopa as 1st line Rx because of ease of Mx & better efficacy
    • pramipexole:
      • see NPS Radar review here
      • PBS listed for Rx of severe primary restless legs syndrome cases
      • pramipexole is associated with higher rates of nausea and other gastrointestinal adverse events, while levodopa with benserazide was associated with more nervous system adverse events but similar efficacy.
  • start low dose and gradually increase to minimise adverse effects
  • adverse effects:
    • common adverse effects, especially at starting Rx include:
      • nausea, postural hypotension
    • increasingly recognised adverse effects which may occur at low dose include:
      • impulse control disorders such as pathological gambling, hypersexuality
      • pathological daytime somnolence occurring as “sleep attacks” which may cause motor vehicle accidents
    • at 3-4 weeks, the phenomenon of augmentation may occur in up to 80% of pts Rx with levodopa in particular, whereby symptoms are shifted to an earlier time of day, may be more severe, more easily provoked and may spread to previously uninvolved limbs, and worsens with increasing dose
      • risk factors include taking dose well before symptom onset and doses of levodopa above 200mg/d.
      • if occurs, switch between dopamine agonists or add an opiate temporarily while dose is lowered
    • rebound:
      • symptoms reappear after drug has worn off and is related to the drug half life - usually early morning or late night

thus try long acting preparations, multiple dosing or switch to the long acting carbergoline

• ergot-derived dopamine agonists:
  • serious risk of restrictive cardiac valvulopathy, thus use low doses, consider bromocryptine which may reduce risk, and take care in prescribing these drugs.
  • cabergoline
    • has advantage of a very long half life & superior efficacy to levodopa
  • pergolide
• non-ergot dopamine agonists:
• newer class of drugs, largely still in trials (2008)
• ropinirole
• pramipexole

• Australian Prescriber vol 31 number 4, Aug 2008