Restless legs syndrome in Parkinson's disease: epidemiology, pathogenetic overlaps, and clinical management

Abstract

Restless legs syndrome (RLS) and Parkinson's disease (PD) are both classified as neurological movement disorders, and they may be interconnected due to abnormalities in the dopaminergic system. The incidence of RLS in PD patients is higher than that in the general population. And PD patients with RLS exhibit a higher age of onset, more severe depression, worse nutritional status, lower quality of life, and a relatively lower frequency and severity of RLS symptom. The current research has unveiled several potential mechanisms underlying RLS in PD patients, such as iron deficiency, reduced function of the dopamine system in the A11 region, and decreased connectivity of related pathways and so on. By systematically summarizing the pathogenesis, clinical manifestations, diagnosis and treatment of PD with RLS, this paper not only provides ideas for the precise diagnosis and treatment of PD with RLS, but also lays a theoretical foundation for clarifying the intricate relationship between PD and RLS.

Keywords: Comorbidity; Dopamine; Parkinson's disease (PD); Restless legs syndrome (RLS).

Fig. 1

Studies evaluating the frequency of RLS in PD. From 1987 to 2024, studies on the incidence of RLS in PD have yielded incidence rates ranging from 0 to 52.3%

Fig. 2

Possible mechanisms of PD with RLS. Environmental factors and gene mutations lead to iron deficiency in the basal ganglia region, thereby causing the disease by affecting the function of the A11 region, dopamine synthesis, and DAT function. In addition, environmental toxins and PINK1 mutations increase the production of mitochondrial reactive oxygen species, thereby causing the degeneration and death of dopaminergic neurons

Fig. 3

Treatment of PD with RLS. Mild symptoms can be intervened first through diet, exercise, etc. Medications can be added when they are ineffective or the symptoms worsen. First-line medications include dopaminergic drugs and α-2-δ ligands, while second-line medications include opioids and iron supplements. When both lifestyle and drug interventions are ineffective, consider surgery on this basis