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Periodic Limb Movement Disorder and Restless Legs Syndrome

by Karl Doghramji, MD

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 dopamine neurotransmission in the CNS. The disorders can occur

  • In isolation

  • During drug withdrawal

  • With use of stimulants, certain antidepressants, or dopamine antagonists

  • During pregnancy

  • In patients with chronic renal or hepatic failure, iron deficiency, anemia, diabetes mellitus, a neurologic disorder (eg, multiple sclerosis, Parkinson disease), 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.

Periodic leg movement disorder is common among people with narcolepsy and REM behavior disorder.

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 of disturbed sleep or EDS 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: Pramipexole, ropinirole, a rotigotine patch, or gabapentin 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 dopamine agonists, pramipexole, ropinirole, and rotigotine (used as a patch), are effective and have few serious adverse effects other than augmentation:

  • Pramipexole 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).

  • Ropinirole 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 rotigotine 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.

Levodopa/carbidopa may be used, but other drugs, which are less likely to cause augmentation and rebound symptoms, are usually preferred.

Gabapentin may help relieve RLS symptoms and is used when RLS is accompanied by pain. Dosing begins with 300 mg at bedtime and can be increased by 300 mg weekly (maximum dose 900 mg po tid). However, this drug is not approved for the treatment of RLS.

Gabapentin enacarbil , a prodrug of gabapentin, may help relieve RLS symptoms and is approved for this indication. The recommended dose is 600 mg once/day taken with food at about 5 pm . Its most common adverse effects include somnolence and dizziness.

Pregabalin , a nondopaminergic α2δ ligand, may help relieve RLS symptoms; augmentation is less likely to occur than with pramipexole. Pregabalin may also be useful for RLS accompanied by pain. For RLS, a dose of 300 mg once/day has been used. Dizziness and somnolence are the most common adverse effects. However, use of this drug to treat RLS has not been extensively studied.

Benzodiazepines may improve sleep continuity but do not reduce limb movements; they should be used cautiously to avoid tolerance and daytime sleepiness.

Opioids may also work for patients with RLS and pain but are used as a last resort because of tolerance, adverse effects, and abuse potential.

Ferritin levels should be obtained, and if levels are low (< 50 μg/L), supplementation with ferrous sulfate 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. However, treatments require further study.

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 gabapentin enacarbil, which are often effective.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • No US brand name
  • NEURONTIN
  • NEUPRO
  • REQUIP
  • LODOSYN
  • LYRICA
  • MIRAPEX

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