Progressive and widespread brain damage in ALS: MRI voxel-based morphometry and diffusion tensor imaging study

Abstract

We investigated 17 patients with sporadic amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) and voxel-based analysis of diffusion tensor images (DTI) at baseline and after a six-month follow-up. Compared with 17 healthy controls, ALS patients at baseline showed only minimal white matter volume decreases in the inferior frontal gyrus but marked decreases in the gray matter of several regions, especially in the bilateral paracentral lobule of the premotor cortex. DTI revealed reduced fractional anisotropy in the bilateral corticospinal tracts, insula, ventrolateral premotor cortex, and parietal cortex. Increased mean diffusivity was noted bilaterally in the motor cortex, ventrolateral premotor cortex, insula, hippocampal formation, and temporal gyrus. At the six-month follow-up, ALS patients showed widespread volume decreases in gray matter, and DTI abnormalities extended mainly into the bilateral frontal lobes, while volume changes in the white matter remained minimal but more distinct. Our combined VBM and DTI techniques revealed extra-corticospinal tract neuronal degeneration mainly in the frontotemporal lobe of ALS patients. In particular, follow-up examinations in these patients showed that whole-brain DTI changes occurred predominantly in the regions of brain atrophy. These objective analyses can be used to assess the disease condition of the ALS brain.

Behavioral changes in early ALS correlate with voxel-based morphometry and diffusion tensor imaging

“…The spatial distribution of brain atrophy in ALS patients in this study was consistent with those observed in previous studies [31,35]. In the white matter, atrophy was shown only in the midbrain corresponding to the pyramidal tract.…”

“…These FA and MD images were normalized to MNI space using the transformation matrix obtained when the EPI was normalized to the T2-weighted template image by a 12-parameter affine model, using the SPM5 module [27]. Finally, these normalized FA and MD maps were smoothed with an 8-mm isotropic Gaussian kernel [31].…”

Widespread Microstructural White Matter Involvement in Amyotrophic Lateral Sclerosis: A Whole-Brain DTI Study

“…Moreover, this is not the first study in which ALS effects were manifest as lateralized in the motor system. 4,10,15,20,37,43,44 Our findings are also in agreement with the descriptions of asymmetry in ALS pathology of the CSTs, 45 though a correspondence between the side of greater MR imaging differences and the side of greater muscle strength deficit of the limbs was not found, 10 probably because the muscle-strength score is a result of the upper and lower motor neuron involvement, whereas MR imaging detects only the UMN damage.…”

“…35 According to previous neuropathologic findings, 27,34,36 ALS degenerative changes in the cerebral cortex mainly involve motor areas, though recent whole-brain voxel-based morphometry analyses have largely reported GM abnormalities even in extramotor regions. 12,14,15,20,31,37 Thereby, the trends of MD and RD changes, which largely overlapped in our patients in both the genu and splenium of the CC, may represent an increase in the extracellular volume secondary to axonal loss associated with injury to the myelin sheaths, as previously reported in human and animal models of demyelination and axonal degeneration. 2,38,39 Thus, our results also suggest that in advanced stages of ALS, FA changes in the middle body of the CC reflect the degenerative process of axonal damage, inducing loss of motor function, whereas the increase in RD and MD in both the genu and splenium of the CC reflect more subtle axonal damage that could affect fine motor or extramotor skills.…”

“…Most of these studies reported changes of FA and MD mainly in the CSTs, but also in the CC 6,8,15,[17][18][19] and the frontal and temporal lobes. 8,9,15,17,20 Here we used TBSS and VOI DTI analyses to evaluate FA, MD, RD, and AD in whole-brain WM of a heterogeneous group of patients with ALS. These 2 quantitative methods are quite different; TBSS performs statistical analysis on the socalled "FA skeleton" derived from mean FA maps, whereas VOI analysis is based on the Johns Hopkins University WM tractography atlas maps 21,22 obtained from the direct fiber tracking.…”