Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6

Christoph Globas, Sophie Tezenas du Montcel, Laslo Baliko, Syliva Boesch, Chantal Depondt, Stefano DiDonato, Alexandra Durr, Alessandro Filla, Thomas Klockgether, Caterina Mariotti, Bela Melegh, Maryla Rakowicz, Pascale Ribai, Rafal Rola, Tanja Schmitz-Hubsch, Sandra Szymanski, Dagmar Timmann, Bart P. Van de Warrenburg, Peter Bauer, Ludger Schols

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Abstract

Onset of genetically determined neurodegenerative diseases is difficult to specify because of their insidious and slowly progressive nature. This is especially true for spinocerebellar ataxia (SCA) because of varying affection of many parts of the nervous system and huge variability of symptoms. We investigated early symptoms in 287 patients with SCA1, SCA2, SCA3, or SCA6 and calculated the influence of CAG repeat length on age of onset depending on (1) the definition of disease onset, (2) people defining onset, and (3) duration of symptoms. Gait difficulty was the initial symptom in two-thirds of patients. Double vision, dysarthria, impaired hand writing, and episodic vertigo preceded ataxia in 4% of patients, respectively. Frequency of other early symptoms did not differ from controls and was regarded unspecific. Data about disease onset varied between patients and relatives for 1 year or more in 44% of cases. Influence of repeat length on age of onset was maximum when onset was defined as beginning of permanent gait disturbance and cases with symptoms for more than 10 years were excluded. Under these conditions, CAG repeat length determined 64% of onset variability in SCA1, 67% in SCA2, 46% in SCA3, and 41% in SCA6 demonstrating substantial influence of nonrepeat factors on disease onset in all SCA subtypes. Identification of these factors is of interest as potential targets for disease modifying compounds. In this respect, recognition of early symptoms that develop before onset of ataxia is mandatory to determine the shift from presymptomatic to affected status in SCA.

Original languageEnglish
Pages (from-to)2232-2238
Number of pages7
JournalMovement Disorders
Volume23
Issue number15
DOIs
Publication statusPublished - nov. 15 2008

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ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Globas, C., du Montcel, S. T., Baliko, L., Boesch, S., Depondt, C., DiDonato, S., Durr, A., Filla, A., Klockgether, T., Mariotti, C., Melegh, B., Rakowicz, M., Ribai, P., Rola, R., Schmitz-Hubsch, T., Szymanski, S., Timmann, D., Van de Warrenburg, B. P., Bauer, P., & Schols, L. (2008). Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. Movement Disorders, 23(15), 2232-2238. https://doi.org/10.1002/mds.22288