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
BACKGROUND AND PURPOSE: Studies shows ictal behavior and symptoms are affected by patient sex in temporal lobe epilepsy. The purpose of our study was to determine whether alterations in the WM as assessed by DTI display different patterns in male and female patients with unilateral HS. MATERIALS AND METHODS: Patients with unilateral HS were categorized as women with right HS (n=12), men with right HS (n=10), women with left HS (n=12), and men with left HS (n=10). DTI of the brain along 64 noncollinear directions was obtained from 44 patients and 37 sex-matched control participants. We used TBSS to analyze whole-brain WM. Regions with significant changes of FA and MD, and their mean FA, MD, total number of significant voxels, and asymmetry indices were determined for each group. RESULTS: All groups showed bilateral and extensive reductions of FA and elevated MD in the WM, more prominent ipsilateral to the affected hippocampus. The total number of voxels with decreased FA in patients compared with that of control participants was higher in women with right HS (24,727 vs 5,459) and in men with left HS (27,332 vs 14,013) than in their counterparts. Changes in MD associated with right HS were more extensive in both men and women (right vs left HS, women: 16,926 vs 5,458; men: 5,389 vs 4,764) than in those with left HS. In patients with right HS, the ipsilateral cingulum, uncinate fasciculus, internal and external capsules, and right acoustic radiation were involved extensively in women. CONCLUSIONS: Women and men showed different patterns in extent of WM alterations associated with HS.
