Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are characterized by abnormal motions of and, for RLS, usually sensations in the lower or upper extremities, which may interfere with sleep.
(See also Approach to the Patient With a Sleep or Wakefulness Disorder.)
PLMD is 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 central nervous system (CNS). PLMD and RLS 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 rapid eye movement (REM) sleep behavior disorder.
Symptoms and Signs of PLMD and RLS
Periodic limb movement disorder is characterized by repetitive (usually every 20 to 40 seconds) 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. Bed partners may complain about being kicked.
Restless legs syndrome 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. Symptoms may be worsened by stress. Episodes may occur occasionally, causing few problems, or daily.
Diagnosis of PLMD and RLS
For RLS, history alone
For PLMD, polysomnography
Diagnosis of RLS or PLMD 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 of PLMD and RLS
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 restless legs syndrome and periodic limb movement disorder, numerous drugs (eg, dopaminergic drugs, benzodiazepines, antiseizure drugs, 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, compulsive activity, 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 is given orally 2 hours before onset of moderate to severe symptoms and is increased, as needed, by 0.125 mg orally every 2 nights until symptoms are relieved (maximum dose 0.5 mg).
Ropinirole 0.25 mg is given orally 1 to 3 hours before onset of symptoms and is increased, as needed, by 0.25 mg nightly (maximum dose 4 mg).
The rotigotine patch (1 mg/24 hours) is initially applied any time during the day; dosage is increased as needed by 1 mg/24 hours at weekly intervals, up to 3 mg/24 hours.
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 orally 3 times a day). However, gabapentin is not approved for the treatment of RLS.
Gabapentin enacarbil, a prodrug of gabapentin, may help relieve RLS symptoms; it is approved for the treatment of RLS. The recommended dose is 600 mg once a day taken with food at about 5 pm. Its most common adverse effects include somnolence and dizziness. It is less likely to cause augmentation than the dopaminergic drugs.
Pregabalin, a nondopaminergic alpha-2-delta 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 a 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, exacerbation of sleep apnea (if present), and daytime sleepiness.
Opioids are also indicated for patients with severe RLS and pain but are used cautiously because of tolerance, adverse effects, and abuse potential.
Ferritin levels should be obtained, and if levels are low (< 50 mcg/L), supplementation with ferrous sulfate 325 mg plus 100 to 200 mg of vitamin C at bedtime is warranted.
Patients should implement good sleep hygiene.
Ключові моменти
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.
For RLS or PMLD, use dopaminergic drugs or gabapentin enacarbil, both of which are effective.