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MRI-determined regional brain iron concentrations in early- and late-onset restless legs syndrome
Christopher J Earley1, Peter B Barker, Alena Horská
1Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA. cearley@jhmi.edu
Objective:
Cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and autopsy studies have suggested that brain iron may be reduced in restless legs syndrome (RLS). Further analysis of the data also suggests that diminished brain iron may selectively be for early-onset RLS. This study was designed to replicate and extend our previous findings, specifically with regard to early-onset RLS. In this study our primary hypothesis was that substantia nigra (SN) iron index would be decreased in early-onset RLS compared to controls.
Methods:
The iron concentration or 'iron index' in 10 brain regions was determined using MRI in 39 controls and in 22 early-onset and 19 late-onset RLS subjects. The Johns Hopkins RLS severity (JHRLSS) scale was used to define disease severity.
Results:
The mean iron index from the SN was significantly lower in the early-onset RLS compared to controls (t=2.5, P=0.016), while late-onset RLS and controls did not differ. There was a significant negative Spearman rank correlation between SN iron index and JHRLSS scale for the control-early-onset-RLS cohort (rho=-0.32, P=0.016).
Conclusions:
The current MRI results in combination with previous autopsy data support the role of low brain iron in the SN in at least those with early-onset RLS symptoms.
Insights
Early-onset restless legs syndrome (RLS) is linked to lower iron levels in the substantia nigra (SN), a key brain region. This finding supports the role of iron deficiency in early RLS development.
Area of Science:
- Neuroscience
- Neurology
- Medical Imaging
Background:
- Previous studies suggest reduced brain iron in restless legs syndrome (RLS).
- Diminished iron may be specific to early-onset RLS.
- Substantia nigra (SN) iron levels are of particular interest.
Purpose of the Study:
- To investigate and confirm reduced iron concentration in the SN of early-onset RLS patients.
- To compare SN iron index between early-onset RLS, late-onset RLS, and control groups.
- To explore the relationship between SN iron index and RLS severity.
Main Methods:
- Magnetic resonance imaging (MRI) was used to measure the iron index in 10 brain regions.
- Participants included 39 controls, 22 early-onset RLS, and 19 late-onset RLS subjects.
- The Johns Hopkins RLS severity (JHRLSS) scale assessed disease severity.
Main Results:
- The SN iron index was significantly lower in early-onset RLS compared to controls (P=0.016).
- No significant difference in SN iron index was found between late-onset RLS and controls.
- A negative correlation was observed between SN iron index and JHRLSS in the control-early-onset RLS cohort (rho=-0.32, P=0.016).
Conclusions:
- MRI findings support a role for low substantia nigra iron in early-onset RLS.
- Combined with autopsy data, this suggests iron deficiency in the SN is a factor in early RLS.
- Further research into brain iron metabolism in RLS is warranted.
