Update on Restless Legs Syndrome: from Mechanisms to Treatment

  • Paulina Gonzalez-Latapi
  • Roneil Malkani
Movement Disorders (T. Simuni, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Movement Disorders


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.

Recent Findings

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.


Restless 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.

Supplementary material

11910_2019_965_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 15 kb)


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Paulina Gonzalez-Latapi
    • 1
  • Roneil Malkani
    • 1
    • 2
  1. 1.Department of Neurology Feinberg School of MedicineChicagoUSA
  2. 2.Center for Circadian and Sleep MedicineNorthwestern UniversityChicagoUSA

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