Phenotypes of Restless Legs Syndrome (RLS) in Neurological Disorders

Restless Legs Syndrome is a highly prevalent sensorimotor disorder characterized by an irresistible urge to move the limbs, typically worsening during rest and at night. While classically studied as an idiopathic condition, Restless Legs Syndrome frequently manifests alongside a wide range of neurological disorders, including neurodegenerative, neuromuscular, and neuroinflammatory diseases. In these comorbid contexts, the presentation of Restless Legs Syndrome often diverges significantly from the idiopathic phenotype, exhibiting unique patterns of periodic limb movements during sleep, severe sleep fragmentation, and distinct sensory comorbidities such as neuropathic pain, headache, and chronic insomnia. This clinical intersection complicates the diagnostic process, as these sensory and motor manifestations can easily overlap with or be masked by the symptoms of the primary neurological condition, highlighting the critical need for a deeper understanding of these diverse clinical phenotypes.The primary goal of this Research Topic is to address the clinical challenge of phenotypic heterogeneity in Restless Legs Syndrome, particularly when it occurs in the presence of comorbid neurological conditions. Standard therapeutic approaches, primarily focused on dopamine agonists, often face long-term limitations such as dopaminergic dysfunction and the development of augmentation, which significantly worsens symptoms. Recent clinical and translational advances have underscored the necessity of moving beyond a one-size-fits-all approach toward precision medicine. To achieve this, researchers are exploring non-dopaminergic pathways, including the roles of iron deficiency and the endogenous opioid system, which may offer safer, more targeted therapeutic alternatives. By consolidating recent discoveries in clinical phenotyping, genetics, neuroimaging, and pharmacological interventions, this collection aims to establish clearer diagnostic boundaries and personalized management strategies. Ultimately, this Research Topic seeks to bridge the gap between basic neurobiological research and clinical practice, providing clinicians with the tools necessary to identify specific Restless Legs Syndrome phenotypes and select the most effective, individualized treatment regimens for complex patient populations.The scope of this research includes exploring the diverse clinical and physiological presentations of Restless Legs Syndrome (RLS) in both adult and pediatric populations with comorbid neurological disorders. We welcome articles addressing, but not limited to, the following themes:o Characterization of painful versus painless Restless Legs Syndrome phenotypeso The role of subcortical structural and functional changes using neuroimagingo The impact of dopaminergic and non-dopaminergic pharmacological agents on sleep architectureo Management of complications such as augmentationo Genetic risk variants and clinical biomarkerso Clinical overlap with other sleep-related movement disorders, parasomnias, and chronic pain syndromesConflict of Interest: Topic Editor, Elias Georges Karroum, receives consulting fees from Noctrix Health Inc. All other Topic Editors declare no competing interests with regards to the Research Topic subject. Topic editors: Maria Paola Mogavero, ELIAS G KARROUM Source: https://www.frontiersin.org/research-topics/81947/phenotypes-of-restless-legs-syndrome-rls-in-neurological-disorders