Structural signature of classical versus late-onset friedreich's ataxia by Multimodality brain MRI.

INTRODUCTION: Friedreich's ataxia (FRDA) is the most common autosomal-recessive ataxia worldwide. It is characterized by early onset, sensory abnormalities, and slowly progressive ataxia. However, some individuals manifest the disease after the age of 25 years and are classified as late-onset FRDA (LOFA). Therefore, we propose a transversal multimodal MRI-based study to investigate which anatomical substrates are involved in classical (cFRDA) and LOFA. METHODS: We enrolled 36 patients (13 with LOFA) and 29 healthy controls. All subjects underwent magnetic resonance imaging in a 3 T device; three-dimensional high-resolution T1-weighted images and diffusion tensor images were used to assess gray and white matter, respectively. We used T1 multiatlas approach to assess deep gray matter and cortical thickness measures to evaluate cerebral cortex and DTI multiatlas approach to assess white matter. All analyses were corrected for multiple comparisons. RESULTS: Group comparison showed that both groups presented gray matter atrophy mostly in the motor cortex. Regarding white matter, we found abnormalities in the cerebellar peduncles, pyramidal tracts, midbrain, pons, and medulla oblongata for both groups, but the microstructural abnormalities in the cFRDA group were more widespread. In addition, we found that the corticospinal tract presented more severe microstructural damage in the LOFA group. Finally, the midbrain volume of the cFRDA, but not of the LOFA group, correlated with disease duration (R = -0.552, P = 0.012) and severity (R = -0.783, P < 0.001). CONCLUSION: The cFRDA and LOFA groups have similar, but not identical neuroimaging damage pattern. These structural differences might help to explain the phenotypic variability observed in FRDA. Hum Brain Mapp 38:4157-4168, 2017. © 2017 Wiley Periodicals, Inc.

Dystonia in Machado-Joseph disease: Clinical profile, therapy and anatomical basis.

INTRODUCTION: Dystonia is frequent in Machado-Joseph disease, but several important aspects are not yet defined, such as the detailed clinical profile, response to treatment and anatomical substrate. METHODS: We screened 75 consecutive patients and identified those with dystonia. The Burke-Marsden-Fahn Dystonia Rating Scale was employed to quantify dystonia severity. Patients with dystonia received levodopa 600 mg/day for 2 months and were videotaped before and after treatment. A blinded evaluator rated dystonia in the videos. Patients with disabling dystonia who failed to respond to levodopa treatment received botulinum toxin. Finally, volumetric T1 and diffusion tensor imaging sequences were obtained in the dystonic group using a 3T-MRI scanner to identify areas of gray and white matter that were selectively damaged. RESULTS: There were 21 patients with dystonia (28%): 9 classified as generalized and 12 as focal/segmental. Patients with dystonia had earlier onset and larger (CAG) expansions (28.9 ± 11.7 vs 40.6 ± 11.4; p < 0.001 and 75 vs 70; p < 0.001, respectively). Although group analyses failed to show benefit on levodopa (p = 0.07), some patients had objective improvement. In addition, ten patients received botulinum toxin resulting in a significant change in dystonia scores after 4 weeks (p = 0.03). Patients with dystonia had atrophy at pre- and paracentral cortices; whereas, non-dystonic patients had occipital atrophy. Basal ganglia volume was reduced in both groups, but atrophy at the thalami, cerebellar white matter and ventral diencephali was disproportionately higher in the dystonic group. CONCLUSION: Dystonia in Machado-Joseph disease is frequent and often disabling, but may respond to levodopa. It is associated predominantly with structural abnormalities around the motor cortices and in the thalami.