Recent data suggest mechanistic links among perturbed iron homeostasis, oxidative stress, and misfolded protein aggregation in neurodegenerative diseases. Iron overload and toxicity toward dopaminergic neurons have been established as playing a role in the pathogenesis of Parkinson's disease (PD). Brain iron accumulation has also been documented in atypical parkinsonian syndromes (APS), mainly comprising multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Iron-sensitive magnetic resonance imaging (MRI) has been applied to identify iron-related signal changes for the diagnosis and differentiation of these disorders. Topographic patterns of widespread iron deposition in deep brain nuclei have been described as differing between patients with MSA and PSP and those with PD. A disease-specific increase of iron occurs in the brain regions mainly affected by underlying disease pathologies. However, whether iron changes are a primary pathogenic factor or an epiphenomenon of neuronal degeneration has not been fully elucidated. Moreover, the clinical implications of iron-related pathology in APS remain unclear. In this review study, we collected data from qualitative and quantitative MRI studies on brain iron accumulation in APS to identify disease-related patterns and the potential role of iron-sensitive MRI.

Susceptibility-weighted imaging (SWI) has been shown to be superior in its ability to demonstrate brain mineralization than other conventional MR imaging. The goal of our study was therefore to assess the frequency and extent of putaminal hypointensity in parkinsonian variant MSA using SWI. 11 patients with multiple system atrophy-parkinsonian type (MSA-p), 30 patients with Parkinson's disease (PD), and age matched 30 controls were investigated using 3 Tesla MRI. The pattern of putaminal hypointensity was measured using a visual grading scale and scored from 0 to 3. Hemi- or bilateral putaminal hypointensity (a score of ≥ 2) and hyperintense rim were recognized in 81.8% and 54.5% of 11 MSA-p, respectively. The scores of putaminal hypointensity of MSA-p were significantly higher than other groups (p < 0.001), a score of ≥ 2 differentiated MSA-p from other groups. And all five patients with early disease stage also showed these characteristic findings. SWI appears to be useful for depicting putaminal hypointensity even in early stage of MSA-p. This finding suggests that iron deposition associated putaminal degeneration can occur early in the disease process.