Iron, brain and restless legs syndrome (original) (raw)

Iron in Restless Legs Syndrome

Movement Disorders Clinical Practice, 2014

A link between restless legs syndrome (RLS) and iron has been recognized for several decades. Yet, the precise role that iron or other components of iron metabolism play in bringing about RLS is still a matter of debate. During the last few years, many new pieces of evidence from genetics, pathology, imaging, and clinical studies have surfaced. However, the way this evidence fits into the larger picture of RLS as a disease is not always easily understood. To provide a better understanding of the complex interplay between iron metabolism and RLS and highlight areas that need further elucidation, we systematically and critically review the current literature on the role of iron in RLS pathophysiology and treatment with a special emphasis on genetics, neuropathology, cell and animal models, imaging studies, and therapy.

Multiregional brain iron deficiency in restless legs syndrome

Movement Disorders, 2008

Evidence for tissue iron deficiency in restless legs syndrome (RLS) is limited to the substantia nigra (SN). Using MRI, we assessed T2 values of various brain regions in 6 RLS patients and 19 controls and correlated them with sonographically assessed SN echogenicity. Both neuroimaging features are supposed to correlate with tissue iron content. Mean T2 values of all regions were higher in patients (2.9-7.8%), though significantly increased only in four regions; the mean T2 over all voxels was higher in patients (5.1%, P < 0.001) and correlated inversely with SN echogenicity (r = 20.61, P < 0.001). This indicates multiregional (global) brain iron deficiency in RLS and proposes SN echogenicity as a potential morphological marker for brain iron status.

Thy1 expression in the brain is affected by iron and is decreased in Restless Legs Syndrome

Journal of the Neurological Sciences, 2004

Thy-1 is a cell adhesion molecule that plays a regulatory role in the vesicular release of neurotransmitters. The objective of this study is to examine the relationship between iron status and Thy1 expression in neuronal systems of varying complexity. Pheochromocytoma cell (PC12) cells were used to explore whether there was a direct relation between cellular iron status and Thy1 expression. Iron chelation significantly decreased expression of Thy1 in PC12 cells in a dose and time dependent manner. Transferrin receptor expression was increased with iron chelation demonstrating that a global decrease in protein synthesis could not account for the Thy1 changes. We also examined brain homogenates from adult rats that were nursed by dams on an iron deficient (ID) diet and found a significant decrease in Thy1 compared to control rats. Finally, the substantia nigra from individuals with Restless Legs Syndrome reportedly has lower than normal amounts of iron. Therefore, we examined this brain region from individuals with the clinical diagnosis of primary Restless Legs syndrome (RLS) and found the concentration of Thy1 was less than half that of controls. The results of these studies support the novel concept that there is a relationship between Thy1 and iron and point to a novel mechanism by which iron deficiency can affect brain function. They also indicate a possible mechanism by which iron deficiency compromises dopaminergic transmission in RLS, providing a potentially important link between decreased brain iron and the responsiveness to levodopa and iron supplementation treatment in RLS. D

Altered Iron Metabolism in Lymphocytes from Subjects with Restless Legs Syndrome

Sleep, 2008

objective: Studies using cerebrospinal fluid, magnetic resonance imaging, and autopsy tissue have implicated a primary role for brain iron insufficiency in restless legs syndrome (RLS). If the abnormalities of brain iron regulation reflect a basic disturbance of iron metabolism, then this might be expressed at least partially in some peripheral systems. Thus the study aim was to determine whether patients with RLS and control subjects show differences in lymphocyte iron regulator proteins. methods: Fasting morning blood samples were used to obtain common serum measures of iron status and to determine lymphocyte iron management proteins. Twenty-four women with early-onset RLS and 25 control women without RLS symptoms were studied. Results: RLS and control subjects were matched for age, hemoglobin, and serum iron profile. However, transferrin receptor (TfR) and DMT1 (divalent metal transporter 1 protein) levels in lymphocytes were significantly higher for RLS patients than for controls. No significant differences in ferritin subtypes or transferrin levels were found. No significant correlations were found between lymphocyte and serum indices of iron status. Interpretation: RLS lymphocytes showed an increase in ferroportin, implying increased cellular iron excretion, in the face of increased iron need (increased TfR and DMT1). In the absence of changes in H-ferritin, the findings indicate a balance between input and output with no net iron change but probable overall increase in iron turnover. The lack of any significant correlation between serum and lymphocyte iron indices indicates that iron management proteins from lymphocytes are at a minimum an alternative and independent marker of cellular iron metabolism.

Iron deficiency anemia and restless legs syndrome: is there an electrophysiological abnormality?

Clinical Neurology and Neurosurgery, 2003

Objective: The pathogenesis of restless legs syndrome (RLS) is unknown. Although iron deficiency anemia (IDA) is related with RLS, the mechanism of this relationship is still unknown. Therefore, we decided to examine some neurophysiological parameters that reflect the function of brainstem, spinal cord and peripheral nervous system. Materials and methods: 34 patients diagnosed with IDA at the hematology department were questioned with a structured battery for RLS and additional symptoms. Of those, 14 patients had symptoms of RLS, while remaining 20 had no signs of this disorder. In both groups, electrophysiological examination including motor and sensory nerve conduction, F-responses, H-reflex, blink-reflex, and mixed nerve silent periods was performed. Results: Neurological examination of all patients was normal. The two groups were identical for age and sex, and the difference between both groups concerning motor and sensory nerve conduction, F-wave, H-reflex, blink-reflex, and mixed nerve silent periods was insignificant. Conclusion: Results suggest that IDA does not cause electrophysiological changes in the peripheral nerves, spinal cord and brainstem, and therefore, measurement of these parameters in IDA patients does not seem effective for the confirmation of RLS.

Neurodegenerative disease and iron storage in the brain

Current Opinion in Neurology, 2004

Iron is very important for normal regulation of various metabolic pathways. Neurons store iron in the form of ferrous ion or neuromelanin. In specific disorders the axonal transport of iron is impaired, leading to iron deposition which in the presence of reactive oxygen species results in neurodegeneration.