Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are characterized by abnormal motions of and sometimes sensations in the lower or upper extremities, which may interfere with sleep.

PLMD and RLS are more common during middle and older age; > 80% of patients with RLS also have PLMD.

The mechanism is unclear but may involve abnormalities in dopamineSome Trade Names
INTROPIN
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neurotransmission in the CNS. The disorders can occur in isolation or during drug withdrawal, with use of stimulants or certain antidepressants, during pregnancy, or in patients with chronic renal or hepatic failure, iron deficiency, anemia, or other disorders. In primary RLS, heredity may be involved; more than one third of patients with primary RLS have a family history of it. Risk factors may include a sedentary lifestyle, smoking, and obesity.

Symptoms and Signs

PLMD is characterized by repetitive (usually every 20 to 40 sec) twitching or kicking of the lower or upper extremities during sleep. Patients usually complain of interrupted nocturnal sleep or excessive daytime sleepiness. They are typically unaware of the movements and brief arousals that follow and have no abnormal sensations in the extremities.

RLS is a sensorimotor disorder characterized by an irresistible urge to move the legs, arms, or, less commonly, other body parts, usually accompanied by paresthesias (eg, creeping or crawling sensations) and sometimes pain in the upper or lower extremities; symptoms are more prominent when patients are inactive or recline and peak in severity around bedtime. To relieve symptoms, patients move the affected extremity by stretching, kicking, or walking. As a result, they have difficulty falling asleep, repeated nocturnal awakenings, or both.

Diagnosis

• For RLS, history alone
• For PLMD, history and polysomnography

Diagnosis may be suggested by the patient's or bed partner's history. For example, patients with PLMD typically have insomnia, EDS, and/or excessive twitching just before sleep onset or during sleep.

Polysomnography is necessary to confirm the diagnosis of PLMD, which is usually apparent as repetitive bursts of electromyographic activity. Polysomnography may be also done after RLS is diagnosed to determine whether patients also have PLMD, but polysomnography is not necessary for diagnosis of RLS itself.

Patients with either disorder should be evaluated medically for disorders that can contribute (eg, with blood tests for anemia and iron deficiency and with hepatic and renal function tests).

Treatment

• For RLS: PramipexoleSome Trade Names
  MIRAPEX
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  , ropiniroleSome Trade Names
  REQUIP
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  , a rotigotineSome Trade Names
  NEUPRO
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  patch, or gabapentinSome Trade Names
  NEURONTIN
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  enacarbil, plus iron supplements if ferritin is < 50 ng/mL
• For PLMD: Usually the same treatments as for RLS

For RLS, numerous drugs (eg, dopaminergic drugs, benzodiazepines, anticonvulsants, vitamins and minerals) are used.

Dopaminergic drugs, although often effective, may have adverse effects such as augmentation (RLS symptoms that worsen before the next drug dose is given and that affect other body parts such as the arms), rebound (symptoms that worsen after the drug is stopped or after the effects of the drug dissipate), nausea, orthostatic hypotension, and insomnia. Three dopamineSome Trade Names
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agonists, pramipexoleSome Trade Names
MIRAPEX
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, ropiniroleSome Trade Names
REQUIP
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, and rotigotineSome Trade Names
NEUPRO
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(used as a patch), are effective and have few serious adverse effects:

• PramipexoleSome Trade Names
  MIRAPEX
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  0.125 mg po is given 2 h before onset of moderate to severe symptoms and is increased, as needed, by 0.125 mg po q 2 nights until symptoms are relieved (maximum dose 0.5 mg).
• RopiniroleSome Trade Names
  REQUIP
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  0.25 mg po is given 1 to 3 h before onset of symptoms and is increased, as needed, by 0.25 mg nightly (maximum dose 4 mg).
• The rotigotineSome Trade Names
  NEUPRO
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  patch (1 mg/24 h) is initially applied any time during the day; dosage is increased as needed by 1 mg/24 h at weekly intervals, up to 3 mg/24 h.

Gabapentin enacarbil may help relieve RLS symptoms. It is a prodrug of gabapentinSome Trade Names
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; its mechanism in RLS is unknown. The recommended dose is 600 mg once/day taken with food at about 5 pm. Its most common side effects include somnolence and dizziness.

Benzodiazepines may improve sleep continuity but do not reduce limb movements; they should be used cautiously to avoid tolerance and daytime sleepiness. GabapentinSome Trade Names
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beginning with 300 mg at bedtime can help when RLS is accompanied by pain. Dose is increased by 300 mg weekly (maximum dose 2700 mg). Opioids may also work but are used as a last resort because of tolerance, adverse effects, and abuse potential.

Ferritin levels should be obtained and, if low (< 50 μg/L), supplementation with ferrous sulfateSome Trade Names
FEOSOL
FER-GEN-SOL
FER-IN-SOL
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325 mg plus 100 to 200 mg of vitamin C at bedtime is warranted. Patients should exercise good sleep hygiene.

For PLMD, there are no specific treatments, but the treatments for RLS are usually used and often help.

Key Points

• PLMD is repetitive twitching or kicking of the lower or upper extremities during sleep, often interrupting nocturnal sleep and causing excessive daytime sleepiness.
• RLS is characterized by an irresistible urge to move the legs, arms, or, less commonly, other body parts, usually accompanied by paresthesias, often causing difficulty falling asleep and/or repeated nocturnal awakenings.
• Diagnose RLS clinically, but if PLMD is suspected, consider polysomnography.
• PMLD has no specific treatments, but those used for RLS often help.
• For RLS, try dopaminergic drugs or gabapentinSome Trade Names
  NEURONTIN
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  enacarbil, which are often effective.

Last full review/revision November 2012 by Karl Doghramji, MD

Content last modified January 2013