Periodic limb movements during sleep: a narrative review

Area of Science:

• Neurology
• Sleep Medicine
• Genetics

Background:

• Periodic limb movement disorder (PLMD) affects 5-8% of children and 4-11% of adults, causing sleep disruption and potential long-term health risks like dementia.
• PLMD is linked to functional impairments including hyperactivity, developmental delays, poor concentration, and increased risk of depression and anxiety.
• Despite extensive research, the underlying pathophysiology and proposed phenotypes of PLMD remain debated, with variations influenced by scoring methods, age, and comorbidities.

Purpose of the Study:

• To evaluate evidence for separable pathophysiological mechanisms underlying distinct periodic limb movement (PLM) motor patterns and phenotypes.
• To identify potential new treatment modalities by elucidating divergent biological pathways of PLMs.

Main Methods:

• A narrative review was conducted to examine the evidence linking PLM motor patterns and phenotypes with hypothesized underlying pathophysiological mechanisms.
• Key proposed mechanisms include spinal cord motor control, iron deficiency, dopamine system dysfunction, thalamic hyperactivity, and cortical-subcortical interactions.

Main Results:

• Evidence suggests distinct pathophysiological mechanisms may underlie different PLM phenotypes.
• PLM rhythmicity appears connected to sleep microarchitecture, similar to events in obstructive sleep apnea (OSA).

Conclusions:

• Further investigation into divergent biological pathways is recommended.
• Prospective, multimodal imaging studies are needed to differentiate treatment responses in conditions like restless legs syndrome (RLS) with and without PLMS.
• Delineating these pathways could lead to novel therapeutic strategies for PLMD and related disorders.