Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (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.

• 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 performed 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, iron deficiency, hepatic function, and renal function).

• For RLS: 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 with low iron stores, iron supplementation is the first-line treatment; ferritin levels should be obtained, and if levels are low (< 50 mcg/L), supplementation with ferrous sulfate plus 100 to 200 mg of vitamin C at bedtime is warranted. Gabapentin enacarbil is the medication of choice to treat symptoms, but only if iron supplementation fails (1) or the patient is not iron deficient.

Gabapentin enacarbil, a prodrug of gabapentin, helps relieve RLS symptoms. It is taken once daily with food a few hours before sleep. Its most common adverse effects include somnolence and dizziness. It is much less likely to cause augmentation (increase in the severity of symptoms with increased medication dosage) than dopaminergic drugs (1, 2).

Gabapentin may help relieve RLS symptoms and is used when RLS is accompanied by pain.

Pregabalin, a nondopaminergic alpha-2-delta ligand, may also be useful for RLS accompanied by pain although use of this medication to treat RLS has not been extensively studied. Dizziness and somnolence are the most common adverse effects.

Dopaminergic drugs (pramipexole, ropinirole, rotigotine, and levodopa/carbidopa), although often effective, have several adverse effects, including 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 medication is stopped or after its effects dissipate), nausea, orthostatic hypotension, compulsive activity, and insomnia. While effective for treatment of symptoms, these medications are not recommended for long-term treatment of RLS (2).

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 can be used in patients with severe RLS and pain but are used cautiously because of tolerance, adverse effects, and abuse potential.

Adults with primary moderate to severe RLS who are refractory to medications can be treated with a device that provides tonic motor activation below the knee (3).

Patients should also implement good sleep hygiene.