Graph theory network analysis provides brain MRI evidence of a partial continuum of neurodegeneration in patients with UMN-predominant ALS and ALS-FTD

OBJECTIVE: Our routine clinical neuroimaging showed hyperintense signal along the corticospinal tract only in some but not all patients with upper motor neuron (UMN)-predominant ALS. ALS patients with CST hyperintensity (ALS-CST+) and those without CST hyperintensity (ALS-CST−) present with nearly identical clinical UMN-predominant symptoms. Some previous studies have suggested that ALS patients with frontotemporal dementia (FTD) are on a continuum with ALS patients without FTD, while others have not. We aimed to determine whether: (a) ALS-CST+, ALS-CST–, and ALS-FTD patients show differential sites of predominant neurodegeneration occurring primarily cortically in the perikaryon or subcortically in the white matter (WM), or (b) UMN-predominant ALS is on a continuum with ALS-FTD. METHODS: Exploratory whole brain grey matter (GM) voxel-based morphometry and WM network analysis using graph theory approach were performed. In this exploratory study, MRI data from 58 ALS patients (ALS-FTD, n = 15; ALS-CST+, n = 19; ALS-CST−, n = 24) and 14 neurological controls were obtained. RESULTS: Significant differences in degree measures (evaluating WM networks) were observed between ALS patients and controls in frontal, motor, extra-motor, subcortical, and cerebellar regions. GM atrophy was observed only in the ALS-FTD subgroup and not in the other ALS subgroups. CONCLUSION: Although WM network disruption by the ALS disease process showed different patterns between ALS-CST+, ALS-CST−, and ALS-FTD subgroups, there were some overlaps, particularly in prefrontal regions and between ALS-CST+ and ALS-FTD patients. Our preliminary findings suggest a partial continuum of, at least, WM degeneration between these subgroups with predominance of cortical pathology (“neuronopathy”) in ALS-FTD patients and subcortical WM pathology (“axonopathy”) in ALS-CST+ and ALS-CST− patients.