Abstract Details

Title Evidence that Advanced Motor Cortex Pathology in Amyotrophic Lateral Sclerosis Causes Whole Brain Systemic Effects

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P1 - Poster Session 1 (12:00 PM-1:00 PM)

Poster/Presentation
Number 1-001

Objective

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).

Background

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.

Design/Methods ALS and age- and sex-matched normal MRI studies were identified in a preexisting database at our institution. WM integrity was estimated from fractional anisotropy (FA) values from DTI in 23 regions throughout the brain using Reproducible Objective Quantification Scheme. Iron deposition was measured on QSM using manual tracing on MRtrix3 software in all 23 regions and bilateral primary motor cortices. Control FA values were used to construct normal distributions per WM region and to compute Z-scores. Associations between FA Z-scores and corresponding iron concentrations were performed using non-parametric Spearman-Rho correlations.

Results

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).

Conclusions Iron accumulation outside the MC, decreased WM integrity in superior motor neurons, and increased integrity in frontal WM pathways may reflect previously unrecognized systemic effects of advanced ALS.

Authors/Disclosures
Anson Wang, MD (Massachusetts General Hospital) PRESENTER	Dr. Wang has nothing to disclose.
	No disclosure on file