Display options
Cite
Maas RP, van Gaalen J, Klockgether T, et al. The preclinical stage of spinocerebellar ataxias. Neurology. 2015;85(1):96-103doi: 10.1212/WNL.0000000000001711.
Maas, R. P., van Gaalen, J., Klockgether, T., & van de Warrenburg, B. P. (2015). The preclinical stage of spinocerebellar ataxias. Neurology, 85(1), 96-103. https://doi.org/10.1212/WNL.0000000000001711
Maas, Roderick P P W M, et al. "The preclinical stage of spinocerebellar ataxias." Neurology vol. 85,1 (2015): 96-103. doi: https://doi.org/10.1212/WNL.0000000000001711
Maas RP, van Gaalen J, Klockgether T, van de Warrenburg BP. The preclinical stage of spinocerebellar ataxias. Neurology. 2015 Jul 07;85(1):96-103. doi: 10.1212/WNL.0000000000001711. Epub 2015 Jun 10. PMID: 26062625.
Copy Download .nbib Format: NLM
Share it on

Neurology. 2015 Jul 07;85(1):96-103. doi: 10.1212/WNL.0000000000001711. Epub 2015 Jun 10.

The preclinical stage of spinocerebellar ataxias.

Neurology

Roderick P P W M Maas, Judith van Gaalen, Thomas Klockgether, Bart P C van de Warrenburg

Affiliations

  1. From the Department of Neurology & Donders Institute for Brain, Cognition, and Behaviour (R.P.P.W.M.M., J.v.G., B.P.C.v.d.W.), Radboud University Medical Center, Nijmegen, the Netherlands; and the Department of Neurology & German Center for Neurodegenerative Diseases (T.K.), University Hospital Bonn, Germany.
  2. From the Department of Neurology & Donders Institute for Brain, Cognition, and Behaviour (R.P.P.W.M.M., J.v.G., B.P.C.v.d.W.), Radboud University Medical Center, Nijmegen, the Netherlands; and the Department of Neurology & German Center for Neurodegenerative Diseases (T.K.), University Hospital Bonn, Germany. [email protected].

PMID: 26062625 DOI: 10.1212/WNL.0000000000001711

Abstract

The autosomal dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of degenerative diseases of the cerebellum and connected regions. The discovery of various SCA genes and the subsequent possibility of predictive testing currently allow a genetic diagnosis to be established years or even decades before the actual appearance of ataxia symptoms. A growing body of evidence, however, indicates that this preclinical stage is subject to the earliest pathophysiologic changes. This review article comprehensively summarizes the studies conducted in preclinical carriers of a mutation in one of the SCA genes. From these data, it can indeed be concluded that the preclinical phase in SCA is already characterized by detectable central and peripheral nervous system changes, which are reflected by subtle abnormalities during a careful clinical examination, changes in structural and functional brain imaging, abnormal neurophysiologic measurements, and/or altered motor learning paradigms. As these may be compensated for a long time, ataxia symptoms probably only appear after a certain threshold of dysfunction or degeneration has been exceeded. Detailed knowledge of this disease stage is of particular relevance for a better understanding of the pathogenesis of SCAs, will allow us to determine the optimal point in time for interventions in future therapeutic trials, and points to objective, valid biomarkers to assess disease progression. Further studies will benefit from a consensus-based definition of the preclinical stage, from using one and the same validated ataxia rating scale with one fixed cutoff value, and from applying similar mathematical models to calculate time to predicted disease onset.

© 2015 American Academy of Neurology.

MeSH terms

Publication Types