Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6

Kathrin Reetz, Ana S. Costa, Shahram Mirzazade, Anna Lehmann, Agnes Juzek, Maria Rakowicz, Romana Boguslawska, Ludger Schöls, Christoph Linnemann, Caterina Mariotti, Marina Grisoli, Alexandra Dürr, Bart P. Van De Warrenburg, Dagmar Timmann, Massimo Pandolfo, Peter Bauer, Heike Jacobi, Till Karsten Hauser, Thomas Klockgether, Jörg B. Schulz

Research output: Contribution to journalArticle

Abstract

Spinocerebellar ataxias are dominantly inherited disorders that are associated with progressive brain degeneration, mainly affecting the cerebellum and brainstem. As part of the multicentre European integrated project on spinocerebellar ataxias study, 37 patients with spinocerebellar ataxia-1, 19 with spinocerebellar ataxia-3 and seven with spinocerebellar ataxia-6 were clinically examined and underwent magnetic resonance imaging at baseline and after a 2-year follow-up. All patients were compared with age-matched and gender-matched healthy control subjects. Magnetic resonance imaging analysis included three-dimensional volumetry and observer-independent longitudinal voxel-based morphometry. Volumetry revealed loss of brainstem, cerebellar and basal ganglia volume in all genotypes. Most sensitive to change was the pontine volume in spinocerebellar ataxia-1, striatal volume in spinocerebellar ataxia-3 and caudate volume in spinocerebellar ataxia-6. Sensitivity to change, as measured by standard response mean, of the respective MRI measures was greater than that of the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia. Longitudinal voxel-based morphometry revealed greatest grey matter loss in the cerebellum and brainstem in spinocerebellar ataxia-1, in the putamen and pallidum in spinocerebellar ataxia-3 and in the cerebellum, thalamus, putamen and pallidum in spinocerebellar ataxia-6. There was a mild correlation between CAG repeat length and volume loss of the bilateral cerebellum and the pons in spinocerebellar ataxia-1. Quantitative volumetry and voxel-based morphometry imaging demonstrated genotype-specific patterns of atrophy progression in spinocerebellar ataxias-1, 3 and 6, and they showed a high sensitivity to detect change that was superior to clinical scales. These structural magnetic resonance imaging findings have the potential to serve as surrogate markers, which might help to delineate quantifiable endpoints and non-invasive methods for rapid and reliable data acquisition, encouraging their use in clinical trials.

Original languageEnglish
Pages (from-to)905-917
Number of pages13
JournalBrain
Volume136
Issue number3
DOIs
Publication statusPublished - 2013

Fingerprint

Spinocerebellar Ataxias
Atrophy
Genotype
Machado-Joseph Disease
Cerebellum
Brain Stem
Globus Pallidus
Putamen
Magnetic Resonance Imaging
Corpus Striatum
Pons
Ataxia
Basal Ganglia
Thalamus
Healthy Volunteers
Biomarkers

Keywords

  • atrophy
  • neurodegeneration
  • spinocerebellar ataxia
  • volumetry
  • voxel-based morphometry

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Reetz, K., Costa, A. S., Mirzazade, S., Lehmann, A., Juzek, A., Rakowicz, M., ... Schulz, J. B. (2013). Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6. Brain, 136(3), 905-917. https://doi.org/10.1093/brain/aws369

Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6. / Reetz, Kathrin; Costa, Ana S.; Mirzazade, Shahram; Lehmann, Anna; Juzek, Agnes; Rakowicz, Maria; Boguslawska, Romana; Schöls, Ludger; Linnemann, Christoph; Mariotti, Caterina; Grisoli, Marina; Dürr, Alexandra; Van De Warrenburg, Bart P.; Timmann, Dagmar; Pandolfo, Massimo; Bauer, Peter; Jacobi, Heike; Hauser, Till Karsten; Klockgether, Thomas; Schulz, Jörg B.

In: Brain, Vol. 136, No. 3, 2013, p. 905-917.

Research output: Contribution to journalArticle

Reetz, K, Costa, AS, Mirzazade, S, Lehmann, A, Juzek, A, Rakowicz, M, Boguslawska, R, Schöls, L, Linnemann, C, Mariotti, C, Grisoli, M, Dürr, A, Van De Warrenburg, BP, Timmann, D, Pandolfo, M, Bauer, P, Jacobi, H, Hauser, TK, Klockgether, T & Schulz, JB 2013, 'Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6', Brain, vol. 136, no. 3, pp. 905-917. https://doi.org/10.1093/brain/aws369
Reetz, Kathrin ; Costa, Ana S. ; Mirzazade, Shahram ; Lehmann, Anna ; Juzek, Agnes ; Rakowicz, Maria ; Boguslawska, Romana ; Schöls, Ludger ; Linnemann, Christoph ; Mariotti, Caterina ; Grisoli, Marina ; Dürr, Alexandra ; Van De Warrenburg, Bart P. ; Timmann, Dagmar ; Pandolfo, Massimo ; Bauer, Peter ; Jacobi, Heike ; Hauser, Till Karsten ; Klockgether, Thomas ; Schulz, Jörg B. / Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6. In: Brain. 2013 ; Vol. 136, No. 3. pp. 905-917.
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