BOSTON—Researchers have found no clear evidence that periodic leg movements (PLM) in sleep should be treated in patients without restless legs syndrome, according to a study reported at the 26th Annual Meeting of the Associated Professional Sleep Societies. “We have no evidence that the suppression of PLM per se may improve sleep quality and somnolence,” said Mauro Manconi, MD, PhD, Head of the Sleep and Epilepsy Center of the Neurocenter of Southern Switzerland in Lugano.
“It might be that PLM has no sure or absolute pathologic role,” said Dr. Manconi. If, as evidence suggests, PLM does not cause cortical arousals or autonomic activation, then the condition might not need to be a target of therapy, he added. However, the contribution of PLM in increasing the amplitude of cortical and heart-rate oscillations remains to be clarified.
Identifying the Mechanism of Dopamine Therapy for PLM
After reviewing observational analyses of the relationship between periodic leg movements, cortical arousal, and autonomic activation, Dr. Manconi and his colleagues used an interventional approach to study the relationship. In a placebo-controlled trial, the investigators found that 0.25 mg of pramipexole, a dopamine agonist, strongly suppressed PLM and periodicity of leg movement.
In a study published in 2008, Dr. Manconi found that pramipexole did not suppress all leg movements that occur during sleep, but only those that occur with a specific periodicity around 10 to 30 seconds (ie, the second peak of the intermovement interval distribution curve). The results indicated that the leg movements in the second peak are under dopaminergic control and that the earlier movements might be triggered by a different system or neurotransmitter, according to Dr. Manconi. A subsequent trial using ropinerole, another dopamine agonist, confirmed the original results.
To determine which dopamine receptor is the target for this PLM suppression, the investigators compared the efficacy of pramipexole, which acts preferentially on the D3 receptor, to that of bromocriptine, a preferential D2 agonist. The group compared equivalent doses (ie, 0.25 mg of pramipexole and 2.5 mg of bromocriptine) of the two drugs. Pramipexole was much more effective at reducing PLM than bromocriptine, which suggested that D3 receptors are the target of dopamine agonist treatment, and not D2 receptors.