Central white matter degeneration in bulbar- and limb-onset amyotrophic lateral sclerosis

Previous studies using diffusion tensor imaging (DTI) have examined for differences between bulbar- and limb-onset amyotrophic lateral sclerosis (ALS). Findings between studies have been markedly inconsistent, though possibly as a consequence of poor matching for confounding variables. To address this problem, this study contrasted the DTI profiles of limb-onset (ALS-L) and bulbar-onset (ALS-B) in groups that were tightly matched for the potential confounding effects of power, age, cognitive impairment and motor dysfunction. 14 ALS-L and 14 ALS-B patients were selected from a large prospective study so as to be matched on clinical and demographic features. All subjects, including 29 controls, underwent neuropsychological and neurological assessment. Tract-based spatial statistics and region of interest techniques were used to analyse fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (λ1). Extensive bilateral FA and RD changes along the corticospinal tract were found in ALS-B compared to controls, p (corrected) <0.05; a similar distribution was seen for ALS-L at a less stringent statistical threshold. ROI analyses also showed more significant changes in ALS-B than ALS-L when each was compared to controls; for FA, MD and RD the changes reached statistical significance in the direct contrast between the two patient groups. With careful matching for confounding factors, the results suggest that ALS-B is associated with greater central white matter degeneration than ALS-L, possibly contributing to the known worse prognosis of ALS-B. The study, however, found no evidence that the spatial distribution of white matter degeneration differs between these groups.