Susan Jeffrey

June 15, 2007

June 15, 2007 (Istanbul) — A new magnetic resonance imaging (MRI) study from German researchers shows a significant decrease in tissue iron content across all assessed brain regions in idiopathic restless legs syndrome (RLS) patients, implicating iron metabolism in the pathophysiology of this condition.

Jana Godau, MD, and colleagues from the University of Tübingen, Germany, reported results of a preliminary study here at the 11th International Congress of Parkinson's Disease and Movement Disorders.

"Finding the same abnormality in all regions we assessed, we see that this feature is specific and sensitive for restless legs," Dr. Godau told Medscape. "This suggests that iron deficiency is not only limited to the substantia nigra, a very small region within the brainstem, but that it is an effect comprising the whole brain, which may be of diagnostic importance."

Common Disorder

RLS is 1 of the most common neurological disorders, with a prevalence, for example, of up to 15% in Germany, she said. Pathophysiology is still unknown, but there is some evidence that some type of impairment in brain iron homeostasis may play a role. Histopathological and MRI studies have demonstrated decreased iron content in the substantia nigra, Dr. Godau noted, and most RLS patients show decreased echogenicity, most likely caused by iron deficiency, in this area of the brain on transcranial B-mode sonography.

However, electrophysiological and functional MRI studies suggest that the pathological process may also involve regions outside this brain area, Dr. Godau noted. "There's a lot of data suggesting that the substantia nigra is not the functionally relevant area for the symptoms of restless legs," she said. "Functional involvement seems to involve primarily other areas."

In this study, they used 1.5-tesla MRI and a turbo spin-echo sequence to study iron content in the brains of 19 control subjects and 7 patients with RLS. They studied 11 areas, including pallidum, putamen, substantia nigra, red nucleus, head of the caudate nucleus, thalamus (3x), frontal and temporal white matter, and hippocampus and calculated T2 values.

In all areas, T2 values were increased in patients compared with controls, indicating decreased iron levels. Differences showed highest significance for the thalamus and caudate nucleus ( P < .01) and somewhat less for the red nucleus, putamen, temporal white matter, and hippocampus ( P < .05).

Moreover, increased mean T2 over all regions had a sensitivity of 0.83 and a specificity of 0.84 for RLS, with a differentiation accuracy of 0.90 (receiver operating characteristics).

"The next thing we're going to do is to validate our data in a larger patient cohort," she said. They are already examining more patients and hope to have data on 100 patients and 100 controls by the end of this year.

The finding has also implications for the underlying disease mechanism in RLS, she noted, suggesting that any potential pathway would have to affect all brain areas. As RLS seems at least in part to be genetically determined, the most likely candidate gene would 1 related to iron metabolism.

Marcelo Merello, MD, from the Raul Carrea Institute for Neurological Research, in Buenos Aires, Argentina, selected Dr. Godau's abstract to be presented in a poster highlights session here. He told Medscape that although it is known that levels of iron in the brain are reduced in RLS, this study used a particular imaging methodology that resulted in high sensitivity and specificity.



The diagnosis for RLS is clinical, but this is a complementary analysis and gives a clue to etiology, he said. "Deficits of iron in the brain look to be quite related to the diagnosis of RLS."



11th International Congress of Parkinson's Disease and Movement Disorders: Poster 893. Presented June 7, 2007.

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