ALS Upper Motoneuron Involvement in DTI and VBM: a Longitudinal MRI Study

Extent and distribution of upper motoneuron (UMN) involvement in ALS has been described in post-mortem brains. Little is known about the development of UMN degeneration in vivo. Region of interest based analyses have suggested neuronal loss in central regions, and signal abnormalities were found in the corticospinal tract (CST) by computerized analyses in diffusion tensor imaging (DTI). Detection of cortical atrophy in the sensorimotor and frontal cortex and reduction of the anisotropy in the CST has been demonstrated using voxel-based morphometry (VBM) and DTI analyzed on a voxel-by-voxel basis. The aim of the present MRI study was to describe the development of UMN involvement in ALS patients over time. High-resolution anatomical MRI and DTI (15 directions) were performed in 21 patients with ALS at baseline and in 13 six month later, and 23 age matched controls on a 1.5 T GE-scanner. Images were analyzed on a voxel-by voxel basis using SPM2. Group comparisons of regional grey matter and FA and were made using ANCOVA with the global mean voxel value as confounding factor. Longitudinal assessments were done using paired t-tests. Compared with controls, ALS patients at baseline showed a relative decrease in GMV in the pre- and postcentral gyrus, inferior parietal lobe and the middle frontal gyrus. The CST showed redeuced FA bilaterally. After 6 months, the relative decrease in GMV had progressed to cingulate areas and the cerebellum.In DTI, FA had decreased in the genu of the internal capsule and CST descending into the brainstem bilaterally. The present study confirms our previous findings of largely central atrophy extending to frontal areas and FA reductions in the CST in a second cohort of patients. On follow up examination, the atrophy had spread to larger areas of the sensorimotor cortex and included cingulate and cerebellar structures which is in line with recent histopathological findings. Our results consistently show grey matter atrophy in sensorimotor, parietal and frontal regions which increases during the course of ALS. In groups of patients, voxel-based morphometry and DTI may be used as a monitoring tools in future clinical trials.