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 (λ ₁). 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.