Update on Restless Legs Syndrome: from Mechanisms to Treatment
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Purpose of Review
To provide an overview of the molecular pathways and recent genetic risk loci associated with restless legs syndrome/Willis-Ekbom disease (RLS/WED) and describe the most recent treatment guidelines.
Diagnostic criteria for RLS/WED now include a fifth criterion to differentiate from RLS/WED mimics. Our understanding of disease pathophysiology has improved, specifically regarding iron regulation in the brain and the role of other pathways such as opioid signaling and brain and spinal cord circuitry may play. Finally, several genetic risk loci have been described, including MEIS1 which is currently considered to be the strongest genetic risk factor for RLS/WED. Treatment guidelines now suggest α2δ ligands such as gabapentin enacarbil should be used as first-line treatment.
The current literature focuses on disease pathways as well as the development of animal models based on genetic risk factors for RLS/WED. Updated treatment guidelines expand on first-line treatment options.
KeywordsRestless legs syndrome Willis-Ekbom disease Augmentation Iron Dopamine
Compliance with Ethical Standards
Conflict of Interest
Roneil Malkani reports grant support from the Alzheimer’s Association, Illinois Department of Public Health, National Institutes of Health, and Northwestern University Parkinson’s Disease Advisory Council, and speaking honoraria for Advocate Healthcare and for American Academy of Neurology. Paulina Gonzalez-Latapi declares no potential conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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