Prevalence and clinical profile of patients with restless legs syndrome in Parkinson's ' s disease: A meta-analysis

Introduction: Restless legs syndrome (RLS) is a sensorimotor disorder of sleep/wake regulation characterized by an urge to move the legs accompanied by a wide range of sensory symptoms, mainly affecting the lower limbs. An increased incidence of RLS has been demonstrated in Parkinson's disease (PD) and has been associated with severe motor and non-motor manifestations. We aimed to provide a reliable estimate of RLS prevalence and the clinical features associated with its occurrence in PD (PD-RLS). Methods: We performed a systematic literature search up to January 2024 using PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with or without RLS, and these proportions were used to estimate the prevalence of PD-RLS. Clinical profile associated with PD-RLS was explored by comparing the clinical characteristics of PD patients with and without RLS. Results: Forty-six studies were included in the meta-analysis. Pooled RLS prevalence was 20% of a total sample of 6990 PD patients and was associated with female sex, mixed motor phenotype, worse motor disturbances and functional disability, and a wide range of non-motor symptoms such as sleep disorders, cognitive and autonomic dysfunctions, and more severe neuropsychiatric manifestations. Sensitivity analyses indicated significant associations of PD-RLS with variables related to dopaminergic therapy. No association was found with serum ferritin, serum iron and hemoglobin levels. Conclusions: The prevalence of PD-RLS exceeds that reported in the general population, suggesting the existence of a relationship between the two disorders. Dopaminergic treatment seems to play an ambivalent role relieving, worsening or "mimicking" RLS manifestations. However, the clinical profile of PD-RLS patients, characterized by a greater severity of non-motor symptoms, also suggests that neurotransmitter systems other than the dopaminergic one are involved in PD-RLS etiology.