Periodic limb movements in Parkinson’s disease: a critical review of pathophysiology and a framework for clinical management

Periodic limb movements (PLM) refer to periodic episodes of repetitive and stereotypical limb movements, predominantly affecting the lower extremities. The prevalence of PLM is estimated at 17.6% to 86.7% in patients with Parkinson's disease (PD), which is much higher than 4% to 11% in the general population. PD is a chronic neurodegenerative movement disorder characterized by both motor and non-motor symptoms (NMS), and PLM represents one of the common non-motor manifestations. PLM in PD has garnered increasing attention due to its high prevalence, association with reduced sleep quality, elevated risk of comorbidities, unclear pathophysiology, and limited treatment options. This review outlines the epidemiology and risk factors for PLM in PD patients. We explore several underlying mechanisms including iron deficiency, dopaminergic dysregulation, and sympathetic nervous activity. Treatment strategies for PLM comorbid with PD are broadly categorized into non-pharmacological and pharmacological therapies where dopamine agonists can alleviate symptoms of both PD and PLM. Clarifying the relationship between PLM and PD is essential, as it may lead to expanded novel treatment approaches and improved quality of life for affected patients.