We examined iron accumulation and white matter (WM) microstructural integrity throughout the entire brain to determine if oxidative stress causes WM pathology outside the motor cortex (MC) and motor neurons in amyotrophic lateral sclerosis (ALS). 

Recent studies have demonstrated that excessive oxidative stress in motor neurons due to iron accumulation in the MC results in loss of WM microstructural integrity along the motor pathway in ALS. Measuring WM integrity and iron accumulation using advanced MRI techniques such as diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM) respectively may provide insights into ALS pathophysiology.

40 ALS (mean age 63±9, 16 F) and 35 controls were obtained. Increasing pathologic MC iron deposition was significantly associated with increased iron deposition in 20 regions after controlling for multiple comparisons (p<0.002, all 23 regions p<0.005). In the centrum semiovale, decreased WM integrity was associated with iron concentration (right p=0.124 R=0.434, left p=0.007 R=0.520). Additionally, increased FA in the presence of increased iron deposition was identified in frontal WM pathways implicated in higher cognitive functions (right uncinate fasciculus p=0.009, R=0.407, genu of corpus callosum, p=0.008, R=0.412).