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Sleep Med. 2004 Jul;5(4):385-91.

Dopamine and iron in the pathophysiology of restless legs syndrome (RLS).

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  • 1Neurology and Sleep Medicine, Johns Hopkins Bayview Medical Center, Asthma and Allergy Bldg 1B46b, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.



The evaluation of the pathophysiology of restless legs syndrome (RLS) stems largely from recognition of the information provided by both pharmacological treatment of the disorder and the secondary forms of the disorder. This article examines the pathophysiological implications of each of these clinical aspects of RLS.


The article reviews the existing literature in relation to possible pathology suggested by the clinical data. It will then explore other data supporting each of the possible pathologies and examine the relationships between these pathologies.


The pharmacological treatment data strongly support a dopaminergic abnormality for RLS. Other pharmacological data and some imaging data also support this, although the data are not entirely consistent. The secondary forms of RLS strongly support an iron deficiency abnormality for RLS, further documented by several other studies. Some animal studies have shown a relation between iron deficiency and dopaminergic abnormalities that have some similarity to those seen in the RLS patient.


It is concluded that there may be an iron-dopamine connection central to the pathophysiology of RLS for at least some if not most patients with this disorder.

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