Format

Send to

Choose Destination
Sleep Med. 2017 Mar;31:61-70. doi: 10.1016/j.sleep.2016.07.028. Epub 2016 Nov 10.

Iron and restless legs syndrome: treatment, genetics and pathophysiology.

Author information

1
Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, USA. Electronic address: jconnor@psu.edu.
2
Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, USA.
3
Institut für Humangenetik, Technische Universität, Munich, Germany.
4
The Johns Hopkins University, Dep of neuroloy, Baltimore, MD USA.

Abstract

In this article, we review the original findings from MRI and autopsy studies that demonstrated brain iron status is insufficient in individuals with restless legs syndrome (RLS). The concept of deficient brain iron status is supported by proteomic studies from cerebrospinal fluid (CSF) and from the clinical findings where intervention with iron, either dietary or intravenous, can improve RLS symptoms. Therefore, we include a section on peripheral iron status and how peripheral status may influence both the RLS symptoms and treatment strategy. Given the impact of iron in RLS, we have evaluated genetic data to determine if genes are directly involved in iron regulatory pathways. The result was negative. In fact, even the HFE mutation C282Y could not be shown to have a protective effect. Lastly, a consistent finding in conditions of low iron is increased expression of proteins in the hypoxia pathway. Although there is lack of clinical data that RLS patients are hypoxic, there are intriguing observations that environmental hypoxic conditions worsen RLS symptoms; in this chapter we review very compelling data for activation of hypoxic pathways in the brain in RLS patients. In general, the data in RLS point to a pathophysiology that involves decreased acquisition of iron by cells in the brain. Whether the decreased ability is genetically driven, activation of pathways (eg, hypoxia) that are designed to limit cellular uptake is unknown at this time; however, the data strongly support a functional rather than structural defect in RLS, suggesting that an effective treatment is possible.

KEYWORDS:

Blood-brain barrier; Dopamine; Genetics; Hypoxia; Iron; RLS

PMID:
28057495
PMCID:
PMC5334282
DOI:
10.1016/j.sleep.2016.07.028
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center