Dystonia in Machado-Joseph Disease (MJD/SCA3) is Associated with Thalamic and Brainstem Atrophy (P7.079)

OBJECTIVE: to compare MRI-based subcortical volumetry in MJD/SCA3 patients with (dMJD/SCA3) and without (c MJD/SCA3) dystonia. BACKGROUND:MJD/SCA3 is the most frequent spinocerebellar ataxia and has remarkable clinical heterogeneity, including movement disorders.Dystonia is frequent and sometimes disabling in MJD/SCA3, but its anatomical substrate is not yet known. DESIGN/METHODS:Demografic data (age, age at onset, gender), SARA (Scale for the Assessment and Rating of Ataxia) scores and (CAG) expansions were obtained for both groups. The Marsden-Fahn rating scale (MFR-S) was applied to quantify dystonia severity in dMJD/SCA3. 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. FreeSurfer software v.5.3 was used to measure subcortical volumes (brainstem, cerebellum, thalami and basal ganglia). We performed ANCOVAtest using subject´s age, gender and intracranial volume (eTIV) as covariates to compare groups. Next, we used a general linear model regression (corrected for head size through eTIV covariation) between MRI parameters and MFR-S. RESULTS:We included 33 cMJD/SCA3 (mean age 52.7±9.2y, 16men) and 19 dMJD/SCA3 (mean age 38.7±14.1y, 11men). dMJD/SCA3 patients had longer (CAG) expansions (75±3.9 vs 70±2.9, p<0.001) and earlier onset (29.6±13.3vs42.8±9.2 years, 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, 2blepharospasm and 7 focal limb dystonia; mean MFR-S score was 16.5±12.6. Comparison between cMJD/SCA3 and dMJD/SCA3 patients showed significant volumetric reduction of the left cerebellum white matter (p=0.037), left thalamus (p=0.035) and brainstem (p=0.027) in the later group. Left cerebellum white matter volume was associated with MFR-S scores in dMJD/SCA3 group (r=0.601, p=0.043). CONCLUSIONS:Dystonia in MJD is associated with large (CAG) expansions, early onset as well as thalamic and brainstem atrophy. These results give insights into potential therapeutic targets for MJD-related dystonia. Study Supported by: Disclosure: Dr. Martinez has nothing to disclose. Dr. Nunes has nothing to disclose. Dr. Rezende has nothing to disclose. Dr. Guimaraes has nothing to disclose. Dr. D9Abreu has received personal compensation for activities with Roche Diagnostics Corp., Novartis, and EMS. Dr. Lopes-Cendes has nothing to disclose. Dr. Franca, Jr. has nothing to disclose.