Restless Legs Syndrome and Neurological Comorbidities: A Narrative Review

Restless legs syndrome (RLS) is a common yet underrecognized neurological disorder characterized by uncomfortable sensations and an irresistible urge to move he legs, typically following a circadian pattern. RLS frequently co-occurs with various other neurological diseases, raising questions about shared mechanisms and clinical consequences. This review synthesizes evidence on the prevalence, outcomes, and pathophysiology of RLS in various neurological disorders, including Parkinson’s disease, multiple sclerosis, migraine, dementia, stroke, epilepsy, and peripheral neuropathy. In Parkinson’s disease, RLS is linked to disease progression and dopaminergic therapy. In stroke and multiple sclerosis, RLS is associated with structural lesions at specific locations, such as the pons or spinal cord. In epilepsy, RLS is associated with refractory or nocturnal seizures. In neuropathies, disruption of small sensory fibers may contribute to RLS symptoms. In dementia, RLS adds diagnostic complexity. Overlapping mechanisms between RLS and its neurological comorbidities include altered sensorimotor processing, brainstem and spinal circuitry, and sleep/arousal regulation. RLS in neurological conditions often worsens sleep quality, mood, and fatigue, and contributes to reduced quality of life and worse outcomes. Future research should prioritize longitudinal designs, standardized diagnostic approaches, and mechanistically driven studies to clarify relationships between RLS and these neurological comorbidities.