Abstract
INTRODUCTION: Kennedy's disease (KD) is a progressive degenerative disorder affecting lower motor neurons. We investigated the correlation between disease severity and whole brain white matter microstructure, including upper motor neuron tracts, by using diffusion-tensor imaging (DTI) in eight patients with KD in whom disease severity was evaluated using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS). METHODS: From DTI acquisitions we obtained maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1) and radial diffusivities (L2, L3). We then employed tract-based spatial statistics (TBSS) to investigate within-patient correlations of DTI invariants with ALSFRS and disease duration (DD). RESULTS: We found a significant correlation between low ALSFRS and 1) low FA values in association commissural and projection fibers, and 2) high L3 values in commissural tracts and fronto-parietal white matter. Additionally, we found a significant association between longer DD and 1) low FA in the genu and body of corpus callosum, association fibers and midbrain and 2) high L1 in projection and association tracts. CONCLUSIONS: The associations between clinical variables and white matter microstructural changes in areas thought to be spared by the disease process support the hypothesis of a multisystem involvement in the complex pathogenic mechanisms responsible for the clinical disability of these patients.