Revisiting brain iron deficiency in restless legs syndrome using magnetic resonance imaging

STUDY OBJECTIVES: Studies on brain iron content in restless legs syndrome (RLS) using magnetic resonance imaging (MRI) are heterogeneous. In this study, we sought to leverage the availability of a large dataset including a range of iron-sensitive MRI techniques to reassess the association between brain iron content and RLS with added statistical power and to compare these results to previous studies. METHODS: The relaxation rates R(2), R(2)′, and R(2)* and quantitative susceptibility are MRI parameters strongly correlated to iron content. In general, these parameters are sensitive to magnetic field variations caused by iron particles. These parameters were quantified within iron-rich brain regions using a fully automatized approach in a cohort of 72 RLS patients and individually age and gender-matched healthy controls identified from an existing dataset acquired at the Sleep Laboratory of the Department of Neurology, Medical University of Innsbruck. 3 T-MRI measures were corrected for age and volume of the segmented brain nuclei and results were compared with previous findings in a meta-analysis. RESULTS: In our cohort, RLS patients had increased R(2)* signal in the caudate and increased quantitative susceptibility signal in the putamen and the red nucleus compared to controls, suggesting increased iron content in these areas. The meta-analysis revealed no significant pooled effect across all brain regions. Furthermore, potential publication bias was identified for the substantia nigra. CONCLUSIONS: Normal and increased iron content of subcortical brain areas detected in this study is not in line with the hypothesis of reduced brain iron storage, but favors CSF investigations and post mortem studies indicating alteration of brain iron mobilization and homeostasis in RLS.