Investigation of white matter pathology in ALS and PLS using tract-based spatial statistics

Abstract

Objective: We aimed to investigate differences in fractional anisotropy (FA) between primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) and the relationship between FA and disease progression using tract-based spatial statistics (TBSS).

Methods: Two scanners at two different sites were used. Differences in FA between ALS patients and controls scanned in London were investigated. From the results of this analysis, brain regions were selected to test for (i) differences in FA between controls, patients with ALS and patients with PLS scanned in Oxford and (ii) the relationship between FA and disease progression rate in the Oxford patient groups.

Results: London ALS patients showed a lower FA than controls in several brain regions. Oxford patients with PLS showed a lower FA than ALS patients and than controls in the body of the corpus callosum and in the white matter adjacent to the right primary motor cortex (PMC), while ALS patients showed reduced FA compared with PLS patients in the white matter adjacent to the superior frontal gyrus. Significant correlations were found between disease progression rate and (i) FA in the white matter adjacent to the PMC in PLS, and (ii) FA along the cortico-spinal tract and in the body of the corpus callosum in ALS.

Conclusions: We described significant FA changes between PLS and ALS, suggesting that these two presentations of motor neuron disease show different features. The significant correlation between FA and disease progression rate in PLS suggests the tissue damage reflected in FA changes contributes to the disease progression rate.

Figure 1

Red voxels show the regions within and outside the CST where the FA was significantly reduced in patients with ALS when compared to controls scanned in London (all P values < 0.05, corrected at cluster level). These regions are: the cerebral peduncles (a), the anterior and posterior limb of the internal capsule, the external capsule, the white matter adjacent to the bilateral inferior frontal gyrus (b), the corona radiata, the white matter adjacent to the bilateral pre‐central gyrus (or primary motor cortex), the right superior frontal gyrus, the bilateral pre‐motor cortex and the post‐central gyrus (or primary sensory cortex) (c), and the corpus callosum (d). The background image is the mean FA and the coordinates are in MNI152 space.

Figure 2

Red voxels show the regions where there is a significant difference in FA between patients with PLS and patients with ALS scanned in Oxford (P < 0.05, corrected at cluster level within regions of interest). Patients with PLS showed lower FA than ALS patients in the white matter adjacent to the right primary motor cortex (P = 0.029) (a) and the body of the corpus callosum (P = 0.036) (b). Patients with ALS showed reduced FA than PLS patients in the white matter adjacent to the right superior frontal gyrus (P = 0.014) (c). The background image is the mean FA and the coordinates are in MNI152 space. Left = L and Right = R.

Figure 3

Voxels in red showed the white matter adjacent to the right primary motor cortex in which FA correlates with the disease progression rate in patients with PLS scanned in Oxford. The background image is the mean FA and the coordinate is in MNI152 space. The plot of the FA of this region versus the rate of disease progression (units/month) in 6 patients with PLS is displayed on the right side of the figure.

Figure 4

Voxels in blue showed the left cerebral peduncle where FA correlates with disease progression rate in patients with ALS scanned in Oxford. The background image is the mean FA and the coordinate is in MNI152 space. The plot of the FA of this region versus the rate of disease progression (units/month) in 13 patients with ALS is displayed on the right side of the figure.