Restless legs syndrome and other neurological disorders: A systematic-narrative hybrid literature review with...

Restless legs syndrome (RLS) is a sleep-related sensorimotor disorder affecting approximately 3% of adults worldwide. This review aims to synthesize current evidence on associations between RLS and major neurological conditions, provide an exploratory quantitative synthesis summarizing association patterns and heterogeneity, and identify priority mechanistic and clinical research gaps. Databases were searched from inception until August 2026. In our exploratory synthesis of 119 unique studies, RLS was significantly associated with Parkinson's disease (case-control OR 3.22, 95% CI 2.35-4.41; cohort RR 1.74, 95% CI 1.02-2.95), multiple sclerosis (OR 4.04, 95% CI 3.26-5.00), neuromyelitis optica spectrum disorder (OR 2.91, 95% CI 1.45-5.84), migraine or headache disorders (forward OR 2.72, 95% CI 2.19-3.38; reverse adjusted OR 1.53, 95% CI 1.36-1.73), peripheral neuropathy (OR 3.82, 95% CI 2.49-5.83), epilepsy (OR 2.11, 95% CI 1.58-2.82), and amyotrophic lateral sclerosis (OR 7.69, 95% CI 2.74-21.59). This work is an evidence-mapping review with exploratory pooling and is not intended as a definitive evidence synthesis. RLS is likely associated with neurodegenerative and other specific neurological conditions. Recognition of these associations may support earlier identification of comorbid conditions and targeted management strategies. However, the current evidence remains observational and heterogeneous.