Measuring the progression of upper motor neuron disease using diffusion MRI and its correlation with Clinical phenotype

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor and extra-motor systems. Diffusion tensor imaging (DTI) can be used to assess white matter (WM) tracts and has potential to be a marker of disease progression. Aims: This study aims to assess the abnormalities in brain white and gray matter in patients with amyotrophic lateral sclerosis (ALS) using MRI. It focuses on the white matter changes associated with cognitive change and serial studies in patients with ALS. Methods: MRI data were acquired in a total of 30 patients and 19 healthy controls. Patients were scanned up to three times with 6–month intervals on a 3T MRI. ALSFRS-R and cognitive testing were administered at each clinical visit. The MRI included a T1-weighted image and diffusion weighted MRI along 64 directions. MRI data were analyzed using voxel-based morphometry (VBM), and tract-based spatial statistics (TBSS) for all DTI metrics, sub-grouping ALS patients based on their cognitive performance. For the serial studies, TBSS and region-of-interest (ROI) methods were applied to the longitudinal datasets. In the 6–month follow-up study, total number of ALS subjects was 23, FA and MD were measured for the motor and extra-motor pathways and correlated with the revised ALS functional rating scale (ALSFRS–R) and disease duration. TBSS and ROI methods, both manual and atlas-based approaches, were used for the 12–month follow-up study which included only 15 subjects. Results for both ROI approaches were compared. Results: There was variability in clinical presentation among patients, with a mixture of site of onset and presence/absence of cognitive changes. At the first time-point study, all DTI measures and GM volume differed significantly between ALS subjects and controls in motor and extra-motor regions. Comparing each ALS subgroup to controls, greater DTI changes were present in ALS with cognitive impairment (ALScog) than ALS subjects without cognitive impairment (ALSnon-cog) subjects. In ALS compared to controls, there were changes on the right side and in a small region in the left middle frontal gyrus. Comparing ALS sub-groups, GM results showed reduction in the caudate nucleus volume in ALScog subjects. In the serial scans, when comparing all ALS time-points, the TBSS showed no significant changes between the first two scans or at three time-points. Using ROI method for 6-month follow-up, the average changes in FA and MD in the selected ROIs were small and not significant after correcting for multiple com parisons. The FA correlated with ALSFRS-R in the genu of corpus callosum (gCC) and bilaterally in the forceps minor and inferior longitudinal fasciculus (ILF) at first scan but not at the second scan. The MD in the hippocampus WM tracts (Hpc), the association fibers and anterior limb of internal capsule (ALIC), gCC and corona radiata (CR) correlated with disease duration and ALSFRS-R. Over 12-month follow-up, when TBSS group comparison were performed for each time-point compared to controls, the changes in serial three time-points were mainly along the cortico-spinal tract (CST) and the whole corpus callosum (CC). ROI methods showed no significant differences in the average FA in the posterior limb of internal capsule (PLIC) or CST at the pons between time-point. There was a significant correlation of the values for the rate of loss in the left PLIC with survival and the correlation approached significance for the right PLIC. Linear regression analysis showed a significant relationship between the manual and atlas based methods for the PLIC but not the pons. However, this study found that manual ROI (mROI) is correlated with the atlas-based ROI (aROI). Conclusion: The combined DTI and VBM study at the first time point showed changes in motor and extra-motor regions in patients with ALS compared to controls. The DTI changes were more extensive in ALS with cognitive impairment than pure ALS subjects. It is likely that the inclusion of ALS subjects with cognitive impairment in previous studies resulted in extra-motor WM abnormalities being reported in ALS subjects. Our study finds that there was little change in the DTI over time in patients with ALS. However, there was variability in clinical features among patients. For individuals there is some correlation with disease progression, measured by ALSFRS-R and survival. Our results would suggest that better results are obtained from the PLIC than the CST in the pons

Dynamic and diverse ways of knowing in mental health occupational therapy

This study focused on evidence based practice in mental health occupational therapy. It investigated the theoretical, evidentiary and practical knowledge that occupational therapists use to support consumers and understand the relationship between occupation and health