Objective: To define the localization and extent of iron accumulation in multiple system atrophy (MSA).

Background: Elevated iron concentration in the basal ganglia has been reported in MSA, but only recently have non-invasive methods to quantify iron been developed. We used quantitative susceptibility mapping (QSM) to evaluate iron accumulation in MSA patients, Parkinson’s disease (PD), and age-matched healthy controls (HC).

Method: Seven MSA (Age=67±7; UMSARS=39.7±19.4), 5 of whom had motor symptoms for less than 3 years (early MSA), 17 PD (Age=63±6; UPDRS-III(Off)=26.9±10.1) and 12 HC participants (Age=63±7;) completed a neurologic examination and underwent 3T brain MRI. In early MSA patients, symptoms were considered mild to moderate in severity. Voxel-wise analyses were performed to assess differences between groups. Mean susceptibility values in the putamen, caudate, globus pallidus internus and externus (GPi/GPe), substantia nigra (SN) and red nucleus (RN) were obtained, and Wilcoxon tests were used to compared results between groups. Correlations between iron accumulation and UMSARS were evaluated using Spearman’s rho correlation coefficient.

Results: Voxel-wise evaluations revealed iron accumulation in MSA patients compared to both PD and HC in clusters located in the putamen, GPi, GPe, RN and thalamus. A cluster in the SN was also observed when compared to HC. The region-of-interest analysis showed increased iron concentration in MSA patients compared to PD and HC in the putamen (p=0.05 and 0.036), GPe (p=0.02 and 0.013) and GPi (p=0.05 and 0.028). In MSA patients, UMSARS total scores positively correlated with mean iron concentration in the GPe (rho=0.791, p=0.034), and voxel-wise evaluations also revealed a significant positive correlation between UMSARS and iron accumulation in clusters located in the SN and GPe.

Conclusion: Advanced quantitative MRI methods demonstrated pathological iron accumulation in the nigrostriatal, pallidal, and thalamic regions in early MSA. Iron concentration in the SN and GPe correlated with disease severity. QSM can improve patient selection in disease modifying trials in MSA and potentially serve as a biomarker of disease severity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/non-invasive-imaging-markers-of-iron-accumulation-in-multiple-system-atrophy/