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.