Abstract
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.
Highlights
Iron overload in the substantia nigra and its toxicity toward dopaminergic neurons has been suggested to play a key role in the pathogenesis of Parkinson’s disease (PD) [1]
Brain iron accumulation has been repeatedly documented in atypical parkinsonian syndromes (APS), mainly comprising multiple system atrophy (MSA), and progressive supranuclear palsy (PSP)
Pathological studies have shown that iron levels in the putamen, globus pallidus, and substantia nigra are higher in MSA patients than in PD and control patients, and resembles the levels found in PSP patients [2,3,4]
Summary
Iron overload in the substantia nigra and its toxicity toward dopaminergic neurons has been suggested to play a key role in the pathogenesis of Parkinson’s disease (PD) [1]. Significant increases in iron-related signals (SWI phase and QSM susceptibility) have been found in the midbrain and globus pallidus of patients with PSP, and in the putamen of patients with MSA (Figure 1) [34, 46]. In a recent study of correlations between R2∗ values and the degree of Unified Parkinson’s Disease Rating Scale scores in PSP, the burden of iron-related PSP pathologies in the lenticular nucleus was associated with the severity of rigidity, and nigrostriato-pallidal and dentate iron content were associated with the severity of tremors [62]. Other studies have failed to show a correlation of iron-sensitive MRI markers with clinical severity scale scores in MSA and PSP [34, 43, 49, 64], but have instead reported that diffusion tensor metrics, such as MD values, are TABLE 1 | Summary of studies using iron-sensitive MRI in atypical parkinsonian syndromes
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