Periodic limb movement during sleep (PLMS) is repetitive and stereotyped limb movements that occur during sleep. Though this phenomenon, commonly observed in polysomnography, has significant associations with various sleep and physical disorders, its etiology has not been clearly identified. In fact, PLMS, which is not entirely stereotyped, might include similar movements ac-tually caused by different mechanisms. According to attempts to classify the phenotypes of PLMS, genuine PLMS is character-ized by a periodicity of 10-90 seconds, predominantly appearing in the first half of sleep, and gradually decreasing over time. The MEIS1 and BTBD9 genes are associated with iron and dopamine metabolism, and these genetic variants are associated with an increase of PLMS. Brain iron deficiency could be the reason of dopamine and glutamate dysfunctions. Pre-synaptic hy-perdopaminergic state leads to down-regulation of post-synaptic dopamine 2 receptor, which result in a nocturnal dopaminergic deficit. It could induce spinal hyperactivity via the A11 dopamine-inhibitory spinal descending pathway. Due to a hyperactivity of spinal cord, the central pattern generators in the spinal cord might be activated, possibly forming synchronous patterns of PLMS. The periodicity of PLMS could be regulated by the cyclic alternating pattern, one of the microstructures of sleep, which means the modulation of cortical-subcortical regions. To date, definitive research on the etiology and pathophysiology of PLMS is lack-ing. Future research will require a precise definition of PLMS, use of parameters with less inter-night variability with analyzing the microstructure of sleep.
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