Dystonia is Associated with Macro and Microstructural Abnormalities of the Cerebellum: Analysis of Volumetric and Diffusion-Weighted MRI Data in the UK Biobank (P11-11.004)

Abstract

<h3>Objective:</h3> To determine whether subjects with dystonia in the UK Biobank exhibit MRI-based cerebellar pathology. <h3>Background:</h3> Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures. Although classically considered a basal-ganglia disorder, neuroimaging studies of dystonia have revealed physiologic, structural, and functional changes in both the (1) pallido-thalamic and (2) cerebello-thalamic networks. Diffusion-weighted-MRI (DWI) analyses of both networks in dystonia have revealed differences in non-specific Diffusion-Tensor metrics such as Fractional Anisotropy. However newer DWI models, such as Neurite Orientation Dispersion and Density Imaging (NODDI), assess more specific and biologically relevant white-matter properties. <h3>Design/Methods:</h3> Using the UK Biobank, 23 subjects with isolated dystonia and diffusion-MRI data were identified, along with 69 control subjects without neurologic (ICD10 G-coded) diagnoses, matched (1:3) on age, sex, imaging site, and medical comorbidities relevant to white-matter integrity (hypertension, hyperlipidemia, and diabetes). Two DTI metrics (mean diffusivity and fractional anisotropy) and three NODDI metrics (intracellular volume fraction, isotropic volume fraction, and orientation dispersion) were extracted from each of four tracts (inferior, middle, and superior cerebellar peduncles, and superior thalamic radiations). Volumetric data consisted of cerebellar (15 regions), basal ganglia (3 regions), and whole-brain grey and white-matter volumes. <h3>Results:</h3> After correcting for multiple-comparisons (40 volumetric and 35 diffusion-related) using the Benjamini-Hochberg procedure (FDR = 0.05), intracellular-volume-fraction (ICVF) of the middle- and superior-cerebellar peduncles was significantly lower in subjects with dystonia, suggesting reduced axon density; volumetric analysis showed significantly reduced volumes of the motor cerebellum (lobules VI and VIII). There were no differences in basal ganglia, cortical, or whole-brain volumes. <h3>Conclusions:</h3> These findings support the hypothesis that abnormalities of cerebellar networks contribute to the pathogenesis of dystonia. <b>Disclosure:</b> Dr. Mason has nothing to disclose. Miss Haddad has nothing to disclose. The institution of Neda Jahanshad has received research support from Biogen Inc.