Quantitative susceptibility mapping reveals widespread brain iron abnormalities in sporadic patients with early-stage amyotrophic lateral sclerosis

In the present study, using the novel quantitative susceptibility mapping (QSM) technique, we aimed to systematically investigate brain iron alterations in a large group of sporadic early-stage amyotrophic lateral sclerosis (ALS-ES) patients and their correlation with clinical disability. In this study, ALS patients at King’s stage 1 were defined as ALS-ES patients, and 53 newly diagnosed ALS-ES patients and 50 healthy controls (HCs) were included. Voxel-based whole-brain QSM analysis was used to explore brain iron alterations. Voxel-based morphometry (VBM) analysis was also performed. Longitudinal follow-up was performed in ALS patients, and the follow-up progression rate (FPR) was calculated. We found that, compared with HCs, ALS-ES patients presented significantly increased susceptibility values, mainly in the motor cortex, prefrontal cortex, hippocampus, and cerebellar regions, while volumetric alterations were not detected. Moreover, motor and extra-motor cortex susceptibility values were significantly correlated with upper motor neuron (UMN) scores and FPR (r = 0.452-0.504, p < 0.01) in ALS-ES patients. We demonstrated a clear profile of early motor and extra-motor iron depositions and their important roles in early-stage ALS patients. We suggest that QSM is likely a promising neuroimaging approach for assessing early UMN damage and detecting early extra-motor alterations in ALS patients.