A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3

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. (c) 2013 Movement Disorder Society