ABSTRACT
BACKGROUND AND PURPOSE: Extension and characteristics of WM involvement other than the brain stem remain inadequately investigated in ARSACS. The aim of this study was to investigate whole-brain WM alterations in patients with ARSACS. MATERIALS AND METHODS: Nine Turkish unrelated patients with ARSACS and 9 sex- and age-matched healthy control participants underwent neurologic examination, molecular studies, electrophysiologic studies, and DTI of the brain. TBSS was used for whole-brain voxelwise analysis of FA, AD, RD, mean diffusivity of WM. Tractographies for the CST and TPF were also computed. RESULTS: Molecular studies revealed 8 novel mutations (3 nonsense, 4 missense, and 1 frameshift insertion) and a missense variation in the SACS gene. Thick TPF displaced and compressed the CST in the pons. The TPF had increased FA, decreased RD, and increased AD, which may be attributed to hypertrophy and/or hypermyelination. Widespread decreased FA and increased RD, suggesting demyelination, was found in the limbic, commissural, and projection fibers. In addition to demyelination, CST coursing cranial and caudal to the pons also showed a marked decrease in AD, suggesting axonal degeneration. Electrophysiologic studies revealed findings that concur with demyelination and axonal involvement. CONCLUSIONS: In addition to developmental changes of the TPF and their effects on the CST in the brain stem, axonal degeneration mainly along the pyramidal tracts and widespread demyelination in WM also occur in patients with ARSACS. Widespread tissue damage may be associated with extensive loss of sacsin protein in the brain and may explain a wide range of progressive neurologic abnormalities in patients with ARSACS.
Subject(s)
Diffusion Tensor Imaging/methods , Heat-Shock Proteins/genetics , Muscle Spasticity/genetics , Muscle Spasticity/pathology , Pyramidal Tracts/pathology , Spinocerebellar Ataxias/congenital , Adolescent , Adult , Anisotropy , Child , Child, Preschool , Codon, Nonsense , Evoked Potentials, Motor , Evoked Potentials, Somatosensory , Female , Frameshift Mutation , Genes, Recessive , Humans , Leukoencephalopathies/genetics , Leukoencephalopathies/pathology , Leukoencephalopathies/physiopathology , Male , Muscle Spasticity/physiopathology , Mutation, Missense , Nerve Fibers, Myelinated/pathology , Pons/pathology , Pons/physiology , Pyramidal Tracts/physiology , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/pathology , Spinocerebellar Ataxias/physiopathology , Young AdultABSTRACT
We investigated limits on the human visual system's ability to discount directional variation in complex lights field when estimating Lambertian surface color. Directional variation in the light field was represented in the frequency domain using spherical harmonics. The bidirectional reflectance distribution function of a Lambertian surface acts as a low-pass filter on directional variation in the light field. Consequently, the visual system needs to discount only the low-pass component of the incident light corresponding to the first nine terms of a spherical harmonics expansion [Basri, R., Jacobs, D. (2001). Lambertian reflectance and linear subspaces. In: International Conference on Computer Vision II, pp. 383-390; Ramamoorthi, R., Hanrahan, P., (2001). An efficient representation for irradiance environment maps. SIGGRAPH 01. New York: ACM Press, pp. 497-500] to accurately estimate surface color. We test experimentally whether the visual system discounts directional variation in the light field up to this physical limit. Our results are consistent with the claim that the visual system can compensate for all of the complexity in the light field that affects the appearance of Lambertian surfaces.
