title: A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3.
abstract: Although white matter damage may play a major role in the pathogenesis of spinocerebellar ataxia 3 (SCA3), available data rely exclusively upon macrostructural analyses. In this setting we designed a study to investigate white matter integrity. We evaluated 38 genetically-confirmed SCA3 patients (mean age, 52.76 ± 12.70 years; 21 males) with clinical scales and brain magnetic resonance imaging (MRI) and 38 healthy subjects as a control group (mean age, 48.86 ± 12.07 years, 20 male). All individuals underwent the same protocol for high-resolution T1 and T2 images and diffusion tensor imaging acquisition (32 directions) in a 3-T scanner. We used Tract-Based Spatial Statistics (FSL 4.1.4) to analyze diffusion data and SPM8/DARTEL for voxel-based morphometry of infratentorial structures. T2-relaxometry of cerebellum was performed with in-house-developed software Aftervoxel and Interactive Volume Segmentation (IVS). Patients' mean age at onset was 40.02 ± 11.48 years and mean duration of disease was 9.3 ± 2.7 years. Mean International Cooperative Ataxia Rating Scale (ICARS) and Scale for Assessment and Rating of Ataxia (SARA) scores were 32.08 ± 4.01 and 14.65 ± 7.33, respectively. Voxel-based morphometry demonstrated a volumetric reduction of gray and white matter in cerebellum and brainstem (P <.001). We found reduced fractional anisotropy (P <.05) in the cerebellum and brainstem. There were also areas of increased radial diffusivity (P <.05) in the cerebellum, brainstem, thalamus, frontal lobes, and temporal lobes. In addition, we found decreased T2-relaxation values in the white matter of the right cerebellar hemisphere. Microstructural white matter dysfunction, not previously reported, occurs in the cerebellum and brainstem of SCA3 patients.
authors.affiliation: Department of Neurology and Neuroimaging Laboratory, Faculty of Medicine, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Guimarães
authors.forename: Anelyssa
authors.initials: A
authors.lastname: D'Abreu
authors.forename: Clarissa L
authors.initials: CL
authors.lastname: Yasuda
authors.forename: Marcondes C
authors.initials: MC
authors.lastname: França
authors.forename: Beatriz H B
authors.initials: BH
authors.lastname: Silva
authors.forename: Fabio A M
authors.initials: FA
authors.lastname: Cappabianco
authors.forename: Felipe P G
authors.initials: FP
authors.lastname: Bergo
authors.forename: Iscia T
authors.initials: IT
authors.lastname: Lopes-Cendes
authors.forename: Fernando
authors.initials: F
authors.lastname: Cendes
mesh_terms: D000328:Adult; D000368:Aged; D016880:Anisotropy; D001931:Brain Mapping; D016022:Case-Control Studies; D016000:Cluster Analysis; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D056784:Leukoencephalopathies / Q000150:complications* / Q000473:pathology*; D017827:Machado-Joseph Disease / Q000150:complications* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D012720:Severity of Illness Index
keywords: DTI; MRI; Machado-Joseph disease; VBM