Bilateral Caudate Atrophy Distinguishes Dystonic Vs Non-Dystonic Patients With Machado-Joseph Disease (P2.133)

OBJECTIVE: to compare the patterns of cerebral atrophy in patients with Machado-Joseph disease with (dMJD/SCA3) and without (cMJD/SCA3) dystonia using VBM analyses. BACKGROUND: Dystonia is frequent in MJD/SCA3, but little is known about its anatomical substrate. DESIGN/METHODS: We recruited 52 patients with MJD/SCA3 and 52 matched controls. We used SARA (Scale for the Assessment and Rating of Ataxia) and Marsden-Fahn rating scale (MFR-S) to quantify severity of ataxia and dystonia respectively. Volumetric T1W images were acquired on a 3T device using 1mm slices, TE=3.2ms, TR=7.1ms, flip angle 8°, isotropic voxels of 1mm³, FOV=240x240. We used SPM software with VBM toolbox to assess differences in gray matter volume between controls and cMJD/SCA3 and, also, controls and dMJD/SCA3. We performed a general linear model using age and gender as covariates to assess the groups. We employed a t-test to performed the group analyses and the final statistical maps for two groups were overlaid on MNI152 template to compare the different atrophy patterns in cMJD/SCA3 and dMJD/SCA3. RESULTS: We included 33 cMJD/SCA3 (mean age 52.7±9.2y, 16 men) and 19 dMJD/SCA3 (mean age 38.7±14.1y, 11 men). dMJD/SCA3 patients had longer (CAG) expansions (75±3.9 vs 70±2.9, p<0.001) and earlier onset (29.6±13.3 vs 42.8±9.2y, p=0.001) in comparison to patients in the cMJD/SCA3 group. Dystonic patients also had higher SARA scores (18.2±6.9 vs 12.9±6.9, p=0.017). Ten out of 19 dMJD/SCA3 had generalized dystonia, 2 blepharospasm and 7 focal limb dystonia; mean MFR-S score was 16.5±12.6. VBM analyses demonstrated significant volumetric reduction for both groups in the cerebellum and occipital lobes when compared to controls. However, bilateral caudate nuclei and left precentral gyri atrophy were only found in the dMJD/SCA3 group. CONCLUSIONS: Caudate nuclei and precentral damage underlie dystonia in MJD/SCA3. These structures are potential therapeutic targets to relieve dystonia through neuromodulation. Study Supported by: FAPESP and Capes Disclosure: Dr. Rezende has nothing to disclose. Dr. Martinez has nothing to disclose. Dr. Nunes has nothing to disclose. Dr. Guimaraes has nothing to disclose. Dr. D9Abreu has nothing to disclose. Dr. Lopes-Cendes has nothing to disclose. Dr. Franca, Jr. has nothing to disclose.